WorldWideScience

Sample records for high-dose insulin therapy

  1. Lipid Rescue Therapy and High-Dose insulin Euglycemic Therapy are Effective for Severe Refractory Calcium Channel Blocker Overdose: Case Report and Review of Literature

    Directory of Open Access Journals (Sweden)

    Niko Bekjarovski

    2013-09-01

    How to cite this article: Bekjarovski NG. Lipid Rescue Therapy and High-Dose insulin Euglycemic Therapy are Effective for Severe Refractory Calcium Channel Blocker Overdose: Case Report and Review of Literature. Asia Pac J Med Toxicol 2013;2:114-6.

  2. Multifocal Electroretinography after High Dose Chloroquine Therapy for Malaria

    Directory of Open Access Journals (Sweden)

    Aline Correa de Carvalho

    2013-01-01

    Full Text Available Purpose: To investigate changes in multifocal electroretinography (mfERG parameters associated with high dose chloroquine therapy for treatment of malaria in the Amazonia region of Brazil. Methods: Forty-eight subjects who had received chloroquine treatment for single or multiple malaria infections with a cumulative dose ranging from 1,050 to 27,000mg were included. The control group consisted of 37 healthy aged-matched subjects. Data was collected on amplitude and implicit time of the N1, P1 and N2 waves in the central macular hexagon (R1 and in five concentric rings at different retinal eccentricities (R2-R6. Results: No significant difference was observed in any mfERG parameter between chloroquine treated patients and control subjects. A comparison with previous data obtained from patients with rheumatologic disorders in the same region of Brazil who had received larger cumulative doses of chloroquine and had displayed mfERG changes, indicated that retinal toxicity seems to be dependent on cumulative dose. Conclusion: Lack of mfERG changes in the current study suggests that intensive high dose chloroquine therapy for treatment of malaria is not associated with retinal toxicity.

  3. High-dose radioiodine therapy of Graves disease

    International Nuclear Information System (INIS)

    Solodky, V.; Fomin, D.; Pestritskaya, E.

    2015-01-01

    Full text of publication follows. Objectives: to estimate the effectiveness and safety of the disease treatment under different modes of applying RIT. Materials and methods: 67 patients with the thyrotoxicosis condition associated with Graves disease were researched. The patients were divided into 2 groups: a control group with 25 people (18 women and 7 men), who underwent a low-dose therapy of 150-500 MBq; and a main group of 42 people (32 women and 10 men), who underwent a high-dose therapy of 550 and 800 MBq. The volume of thyroid prior to the treatment made up 23.8 ± 20 ml in the main group and 30.2 ± 23 ml in the control one. The average age in the high-dose group was 44.6 ±23 years old and in the low-dose -47.2 ± 24 years old. In terms of the hormone level before the RIT, 52% of the main group patients experienced euthyroidism, while 48% - thyrotoxicosis. The corresponding indices in the control group were 42% and 58% respectively. The cessation of the thyreostatic therapy came on 5. to 21. day prior to the treatment, with the average of 14 ±7 days in both groups. The diagnosis of the disease was based on ultrasonography, planar scintigraphy, the hormone level and antibody titer. The performance was assessed through the attainment of hypo-thyrosis and the transition to a substitutive hormonal therapy with L-thyroxine in 6 months or more. The attainment of euthyroidism was seen as a partial effect due to a possibility of relapse. Results: in 6 months a positive result in the form of hypo-thyrosis was achieved for 39 patients in the main group, which accounted for 93%, and 3 patients (7%) experienced euthyroidism. No symptomatic thyrotoxicosis relapses were revealed. In the control group, hypo-thyrosis was achieved by 18 patients, which accounted for 72%; euthyroidism came up to 12%; 4 patients needed a refresher course of RIT, which made up 16% of the group. 93% of the main group patients tolerated the treatment favourably. 3 patients complained of the

  4. Assessments for high dose radionuclide therapy treatment planning

    International Nuclear Information System (INIS)

    Fisher, D.R.

    2003-01-01

    Advances in the biotechnology of cell specific targeting of cancer and the increased number of clinical trials involving treatment of cancer patients with radiolabelled antibodies, peptides, and similar delivery vehicles have led to an increase in the number of high dose radionuclide therapy procedures. Optimised 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 the 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 timepoints using a planar gamma camera. Time-activity curves are developed from the imaging data for the major organ tissues of concern, for the whole body and sometimes for selected tumours. Patient specific factors often require that dose estimates be customised for each patient. In the United States, 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 the methods prescribed by the Medical Internal Radiation Dose (MIRD) Committee of the Society of Nuclear Medicine. Review of high dose studies shows that some are conducted with minimal dosimetry, that the marrow dose is difficult to establish and is subject to large uncertainties. Despite the general availability of software, internal dosimetry methods often seem to be inconsistent from one clinical centre to another. (author)

  5. The Role of High Dose Interleukin-2 in the Era of Targeted Therapy.

    Science.gov (United States)

    Gills, Jessie; Parker, William P; Pate, Scott; Niu, Sida; Van Veldhuizen, Peter; Mirza, Moben; Holzbeierlein, Jeffery M; Lee, Eugene K

    2017-09-01

    We assessed survival outcomes following high dose interleukin-2 in a contemporary cohort of patients during the era of targeted agents. We retrospectively reviewed the records of patients with metastatic renal cell carcinoma treated with high dose interleukin-2 between July 2007 and September 2014. Clinicopathological data were abstracted and patient response to therapy was based on RECIST (Response Evaluation Criteria In Solid Tumors), version 1.1 criteria. The Kaplan-Meier method was used to estimate progression-free and overall survival in the entire cohort, the response to high dose interleukin-2 in regard to previous targeted agent therapy and the response to the targeted agent in relation to the response to high dose interleukin-2. We identified 92 patients, of whom 87 had documentation of a response to high dose interleukin-2. Median overall survival was 34.4 months from the initiation of high dose interleukin-2 therapy in the entire cohort. Patients who received targeted therapy before high dose interleukin-2 had overall survival (median 34.4 and 30.0 months, p = 0.88) and progression-free survival (median 1.5 and 1.7 months, p = 0.8) similar to those in patients who received no prior therapy, respectively. Additionally, patients with a complete or partial response to high dose interleukin-2 had similar outcomes for subsequent targeted agents compared to patients whose best response was stable or progressive disease (median overall survival 30.1 vs 25.4 months, p = 0.4). Our data demonstrate that patient responses to high dose interleukin-2 and to targeted agents before and after receiving high dose interleukin-2 are independent. As such, carefully selected patients should be offered high dose interleukin-2 for the possibility of a complete and durable response without the fear of limiting the treatment benefit of targeted agents. Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  6. Split high-dose oral levothyroxine treatment as a successful therapy option in myxedema coma.

    Science.gov (United States)

    Charoensri, Suranut; Sriphrapradang, Chutintorn; Nimitphong, Hataikarn

    2017-10-01

    High-dose intravenous thyroxine (T4) is the preferable treatment for myxedema coma. We describe the clinical course of a 69-year-old man who presented with myxedema coma and received oral levothyroxine (LT4) therapy (1 mg) in a split dose. This suggests split high-dose oral LT4 as a therapeutic option in myxedema coma.

  7. Transperineal high-dose-rate interstitial radiation therapy in the management of gynecologic malignancies

    Energy Technology Data Exchange (ETDEWEB)

    Itami, Jun; Hara, Ryuseke; Kozuka, Takuyou; Yamashita, Hideomi; Nakajima, Kaori; Shibata, Kouji; Abe, Yoshihisa; Fuse, Masashi; Ito, Masashi [International Medical Center of Japan, Tokyo (Japan). Dept. of Radiation Therapy and Oncology

    2003-11-01

    Background: High-dose-rate interstitial radiation therapy is a newly introduced modality, and its role in the management of gynecologic malignancies remains to be studied. Clinical experience in high-dose-rate interstitial radiation therapy was retrospectively investigated. Patients and Methods: Eight patients with primary and nine with recurrent gynecologic malignancies underwent high-dose-rate interstitial radiation therapy with/without external-beam irradiation. Fractional dose of the high-dose-rate interstitial radiation therapy ranged between 4 and 6 Gy with total doses of 15-54 Gy. Interstitial irradiation was performed twice daily with an interval of > 6 h. Results: 2-year local control rate was 75% for primary treatment and 47% for treatment of recurrence (p = 0.46). Maximum tumor size had a statistically significant impact on local control (p < 0.002). Grade 2 and 4 late complications were seen in five patients, and the incidence was significantly higher in patients with a larger volume enclosed by the prescribed fractional dose of high-dose-rate interstitial radiation therapy. The incidence of grade 2 and 4 complications at 18 months was 78% and 0% with a volume > 100 cm{sup 3} and {<=} 100 cm{sup 3}, respectively (p < 0.04). Conclusion: Although high-dose-rate interstitial radiation therapy is a promising modality, it must be applied cautiously to patients with bulky tumors because of the high incidence of serious complications. (orig.)

  8. Weight loss in obese men by caloric restriction and high-dose diazoxide-mediated insulin suppression.

    NARCIS (Netherlands)

    Boekel, G.A.J van; Loves, S.; Sorge, A.A. van; Ruinemans-Koerts, J.; Rijnders, T.; Boer, H. de

    2008-01-01

    OBJECTIVE: To examine the concept whether high-dose diazoxide (DZX)-mediated insulin suppression, in combination with moderate caloric restriction and increased physical activity, can establish a weight loss of at least 15% in obese hyperinsulinaemic men. DESIGN: Open, uncontrolled, 6-month pilot

  9. High dose therapy with autologous stem cell support in malignant disorders

    International Nuclear Information System (INIS)

    Holte, H.; Kvaloey, S.O.; Engan, T.

    1996-01-01

    New biomedical knowledge may improve the diagnostic procedures and treatment provided by the Health Services, but at additional cost. In a social democratic health care system, the hospital budgets have no room for expensive, new procedures or treatments, unless these are funded through extra allocation from the central authorities. High dose therapy with autologous stem cell support in malignant disorders is an example of a new and promising, but rather expensive treatment, but its role in cancer therapy has yet to be established. The indications for testing high dose therapy with autologous stem cell support in various malignancies are discussed, with emphasis on the principles for deciding which categories of disease should have priority. The authors suggest some malignant disorder for which high dose therapy with stem cell support should be explored versus conventional treatment in randomized prospective trials. 8 refs., 1 tab

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

    Directory of Open Access Journals (Sweden)

    F. A. Zeiler

    2015-01-01

    Full Text Available 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.

  11. High-dose therapy followed by bone marrow transplantation for relapsed follicular non-Hodgkin's lymphoma

    NARCIS (Netherlands)

    Schouten, IC; Raemaekers, JJM; Kluin-Nelemans, HC; vanKamp, H; Mellink, WAM; vantVeer, MB

    1996-01-01

    Purpose: To analyze whether, in addition to survival, and disease-free survival progression-free interval after transplantation would be longer than the last progression-free interval before transplantation, supporting the argument that high-dose therapy may change the biologic behavior of the

  12. In type 1 diabetics, high-dose biotin may compensate for low hepatic insulin exposure, promoting a more normal expression of glycolytic and gluconeogenic enyzymes and thereby aiding glycemic control.

    Science.gov (United States)

    McCarty, Mark F

    2016-10-01

    In type 1 diabetics, hepatic exposure to insulin is chronically subnormal even in the context of insulin therapy; as a result, expression of glycolytic enzymes is decreased, and that of gluconeogenic enzymes is enhanced, resulting in a physiologically inappropriate elevation of hepatic glucose output. Subnormal expression of glucokinase (GK) is of particular importance in this regard. Possible strategies for correcting this perturbation of hepatic enzyme expression include administration of small molecule allosteric activators of GK, as well as a procedure known as chronic intermittent intravenous insulin therapy (CIIIT); however, side effects accompany the use of GK activators, and CIIIT is time and labor intensive. Alternatively, administration of high-dose biotin has potential for modulating hepatic enzyme expression in a favorable way. Studies in rodents and in cultured hepatocytes demonstrate that, in the context of low insulin exposure, supra-physiological levels of biotin induce increased expression of GK while suppressing that of the key gluconeogenic enzyme phosphoenolpyruvate carboxykinase. These effects may be a downstream consequence of the fact that biotin down-regulates mRNA expression of FOXO1; insulin's antagonism of the activity of this transcription factor is largely responsible for its modulatory impact on hepatic glycolysis and gluconeogenesis. Hence, high-dose biotin may compensate for subnormal insulin exposure by suppressing FOXO1 levels. High-dose biotin also has the potential to oppose hepatic steatosis by down-regulating SREBP-1 expression. Two pilot trials of high-dose biotin (16 or 2mg per day) in type 1 diabetics have yielded promising results. There is also some reason to suspect that high-dose biotin could aid control of diabetic neuropathy and nephropathy via its stimulatory effect on cGMP production. Owing to the safety, good tolerance, moderate expense, and current availability of high-dose biotin, this strategy merits more

  13. Calcification of human vascular smooth muscle cells: associations with osteoprotegerin expression and acceleration by high-dose insulin

    DEFF Research Database (Denmark)

    Olesen, Ping; Knudsen, Kirsten Quyen Nguyen; Wogensen, Lise

    2007-01-01

    Arterial medial calcifications occur often in diabetic individuals as part of the diabetic macroangiopathy. The pathogenesis is unknown, but the presence of calcifications predicts risk of cardiovascular events. We examined the effects of insulin on calcifying smooth muscle cells in vitro...... and measured the expression of the bone-related molecule osteoprotegerin (OPG). Human vascular smooth muscle cells (VSMCs) were grown from aorta from kidney donors. Induction of calcification was performed with beta-glycerophosphate. The influence of insulin (200 microU/ml or 1,000 microU/ml) on calcification...... calcification in human smooth muscle cells from a series of donors after variable time in culture. Decreased OPG amounts were observed from the cells during the accelerated calcification phase. High dose of insulin (1,000 microU/ml) accelerated the calcification, whereas lower concentrations (200 microU/ml) did...

  14. [High-dosed gestagen therapy of the metastatic mammary carcinoma (author's transl)].

    Science.gov (United States)

    Firusian, N; Becher, R

    1981-12-01

    Thirty patients with histologically proven metastatic mammary carcinoma were treated, after exhaustion of hormonal and cytostatic therapeutic means, with high-dosed medroxyprogesterone acetate (MPA) during a ten-day induction phase with 1000 mg MPAi.m. per day and then with 600 mg oral MPA per day. In eleven patients a complete or partial remission was achieved. The median period of remission comprised ten months. A positive relationship was found between the response to high-dosed MPA therapy and the length of free intervals. Side effects were tolerable.

  15. High-dose thiamine therapy counters dyslipidemia and advanced glycation of plasma protein in streptozotocin-induced diabetic rats.

    Science.gov (United States)

    Karachalias, Nikolaos; Babaei-Jadidi, Roya; Kupich, Christian; Ahmed, Naila; Thornalley, Paul J

    2005-06-01

    The streptozotocin-induced (STZ) diabetic rat experimental model of diabetes on insulin maintenance therapy exhibits dyslipidemia, mild thiamine deficiency, and increased plasma protein advanced glycation end products (AGEs). The reversal of thiamine deficiency by high-dose thiamine and S-benzoylthiamine monophosphate (benfotiamine) prevented the development of incipient nephropathy. Recently, we reported that high-dose thiamine (but not benfotiamine) countered diabetic dyslipidemia. To understand further the differences between the effects of thiamine and benfotiamine therapy, we quantified the levels of the AGEs in plasma protein. We found hydroimidazolone AGE residues derived from glyoxal and methylglyoxal, G-H1 and MG-H1, were increased 115% and 68% in STZ diabetic rats, with respect to normal controls, and were normalized by both thiamine and benfotiamine; whereas N-carboxymethyl-lysine (CML) and N-carboxyethyl-lysine (CEL) residues were increased 74% and 118% in STZ diabetic rats and were normalized by thiamine only. The lack of effect of benfotiamine on plasma CML and CEL residue concentrations suggests there may be important precursors of plasma protein CML and CEL residues other than glyoxal and methylglyoxal. These are probably lipid-derived aldehydes.

  16. High-dose Resveratrol Inhibits Insulin Signaling Pathway in 3T3-L1 Adipocytes

    OpenAIRE

    Lee, Haemi; Kim, Jae-woo

    2013-01-01

    Background Insulin resistance is a major factor in the development of metabolic syndrome and is associated with central obesity and glucose intolerance. Resveratrol, a polyphenol found in fruits, has been shown to improve metabolic conditions. Although it has been widely studied how resveratrol affects metabolism, little is known about how resveratrol regulates lipogenesis with insulin signaling in 3T3-L1 adipocytes. Methods: We treated differentiated 3T3-L1 adipocytes with resveratrol to obs...

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

    Directory of Open Access Journals (Sweden)

    Tülay Kaçar Güvel

    2014-10-01

    Full Text Available 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.

  18. High-dose therapy improved the bone remodelling compartment canopy and bone formation in multiple myeloma

    DEFF Research Database (Denmark)

    Hinge, Maja; Delaissé, Jean-Marie; Plesner, Torben

    2015-01-01

    transplantation, and from 20 control patients with monoclonal gammopathy of undetermined significance were histomorphometrically investigated. This investigation confirmed that MM patients exhibited uncoupled bone formation to resorption and reduced canopy coverage. More importantly, this study revealed......Bone loss in multiple myeloma (MM) is caused by an uncoupling of bone formation to resorption trigged by malignant plasma cells. Increasing evidence indicates that the bone remodelling compartment (BRC) canopy, which normally covers the remodelling sites, is important for coupled bone remodelling....... Loss of this canopy has been associated with bone loss. This study addresses whether the bone remodelling in MM is improved by high-dose therapy. Bone marrow biopsies obtained from 20 MM patients, before and after first-line treatment with high-dose melphalan followed by autologous stem cell...

  19. High-dose steroid therapy for idiopathic optic perineuritis: a case series

    Directory of Open Access Journals (Sweden)

    Mimura Tatsuya

    2010-12-01

    Full Text Available Abstract Introduction It has been reported that the prognosis of optic perineuritis may be poor when initiation of treatment is delayed. Here we report the successful treatment of three patients with idiopathic optic perineuritis, including two in whom initiation of therapy was delayed. Case presentation Three Japanese patients (two women aged 73 and 66 years, and one man aged 27 years presented with loss of vision (for five months, several months, and two months respectively and pain on eye movement in the third case only, and were diagnosed as having idiopathic optic perineuritis. Fat-suppressed T2-weighted magnetic resonance images showed high signal intensity areas around the affected optic nerves, suggesting the presence of optic perineuritis. Two patients received steroid pulse therapy and the third was given high-dose steroid therapy. The visual acuity improved in all three cases. Conclusion High-dose steroid therapy may be effective for idiopathic perineuritis in patients without optic nerve atrophy, even if initial treatment (including moderate-dose steroids has failed.

  20. Total skin high-dose-rate electron therapy dosimetry using TG-51

    International Nuclear Information System (INIS)

    Gossman, Michael S.; Sharma, Subhash C.

    2004-01-01

    An approach to dosimetry for total skin electron therapy (TSET) is discussed using the currently accepted TG-51 high-energy calibration protocol. The methodology incorporates water phantom data for absolute calibration and plastic phantom data for efficient reference dosimetry. The scheme is simplified to include the high-dose-rate mode conversion and provides support for its use, as it becomes more available on newer linear accelerators. Using a 6-field, modified Stanford technique, one may follow the process for accurate determination of absorbed dose

  1. Occurrence of chronic esophageal ulcer after high dose rate intraluminal radiation therapy for esophageal cancer

    International Nuclear Information System (INIS)

    Soejima, Toshinori; Hirota, Saeko; Okamoto, Yoshiaki; Obayashi, Kayoko; Takada, Yoshiki

    1995-01-01

    Ninety-eight patients with esophageal cancer were treated by high dose rate intraluminal radiation therapy at the Department of Radiology of the Hyogo Medical Center for Adults between January 1982 and December 1993. Twenty patients with complete response after intraluminal radiation therapy, who were followed up with esophageal fiberscopy in our institute, were reviewed. The one-year cumulative rate of occurrence of esophageal ulcers was 81%, and in 69% of the cases the ulcers occurred from 4 to 8 months after completion of intraluminal radiation therapy. We graded esophageal ulcer by fiberscopic findings. Grade 0 was defined as no ulcer, grade 1 as superficial ulcer, grade 2 as deep ulcer, grade 3 as circumferencial ulcer, and severe stenosis. Factors related to grade were studied, and shorter distances from the source to the surface of the mucosa and lower surface doses of intraluminal radiation therapy appear to reduce the severity as graded on the above scale, of the esophageal ulcer. Four of the five 2-year recurrence-free patients suffered esophageal ulcers, which were cured from 15 to 22 months after intraluminal radiation therapy. However ulcers recurred in two patients, ong term care was thought to be necessary. (author)

  2. High-dose proton beam therapy for sinonasal mucosal malignant melanoma

    International Nuclear Information System (INIS)

    Fuji, Hiroshi; Yoshikawa, Shusuke; Kasami, Masako; Murayama, Shigeyuki; Onitsuka, Tetsuro; Kashiwagi, Hiroya; Kiyohara, Yoshio

    2014-01-01

    The significance of definitive radiotherapy for sinonasal mucosal melanoma (SMM) is sill controvertial. This study was to evaluate the role of high-dose proton beam therapy (PBT) in patients with SMM. The cases of 20 patients with SMM localized to the primary site who were treated by PBT between 2006 and 2012 were retrospectively analyzed. The patterns of overall survival and morbidity were assessed. The median follow-up time was 35 months (range, 6–77 months). The 5-year overall and disease-free survival rates were 51% and 38%, respectively. Four patients showed local failure, 2 showed regrowth of the primary tumor, and 2 showed new sinonasal tumors beyond the primary site. The 5-year local control rate after PBT was 62%. Nodal and distant failure was seen in 7 patients. Three grade 4 late toxicities were observed in tumor-involved optic nerve. Our findings suggested that high-dose PBT is an effective local treatment that is less invasive than surgery but with comparable outcomes

  3. High-dose-rate intraoperative radiation therapy: the nuts and bolts of starting a program

    Science.gov (United States)

    Moningi, Shalini; Armour, Elwood P.; Terezakis, Stephanie A.; Efron, Jonathan E.; Gearhart, Susan L.; Bivalacqua, Trinity J.; Kumar, Rachit; Le, Yi; Kien Ng, Sook; Wolfgang, Christopher L.; Zellars, Richard C.; Ellsworth, Susannah G.; Ahuja, Nita

    2014-01-01

    High-dose-rate intraoperative radiation therapy (HDR-IORT) has historically provided effective local control (LC) for patients with unresectable and recurrent tumors. However, IORT is limited to only a few specialized institutions and it can be difficult to initiate an HDR-IORT program. Herein, we provide a brief overview on how to initiate and implement an HDR-IORT program for a selected group of patients with gastrointestinal and pelvic solid tumors using a multidisciplinary approach. Proper administration of HDR-IORT requires institutional support and a joint effort among physics staff, oncologists, surgeons, anesthesiologists, and nurses. In order to determine the true efficacy of IORT for various malignancies, collaboration among institutions with established IORT programs is needed. PMID:24790628

  4. CD34-positive cells as stem cell support after high dose therapy

    International Nuclear Information System (INIS)

    Kvalheim, G.; Pharo, A.; Holte, H.

    1996-01-01

    Six patients, five with breast cancer and one with non-Hodgkin's lymphoma, were mobilized by chemotherapy and G-CSF. CD34-positive cells were isolated by means of immunomagnetic beads and Isolex 300 Cell Separator. Mean purity of isolated CD34-positive cells was 97% and mean yield was 54%. Three patients were treated with high dose therapy followed by reinfusion of CD34-positive cells as stem cell support. Recovery of neutrophils occurred at day 8, 11 and 13 and of platelets at day 9, 14 and 32. It is concluded that immunomagnetic isolated CD34-positive cells give high purity and yield. Although use of CD34-positive cells reduces the content of contaminating tumours cells in the graft, breast cancer cells were still detectable in two out of five CD34-positive cell products. 20 refs., 2 figs., 1 tab

  5. Radiation exposure for 'caregivers' during high-dose outpatient radioiodine therapy

    International Nuclear Information System (INIS)

    Marriott, C. J.; Webber, C. E.; Gulenchyn, K. Y.

    2007-01-01

    On 27 occasions, radiation doses were measured for a family member designated as the 'caregiver' for a patient receiving high-dose radioiodine outpatient therapy for differentiated thyroid carcinoma. For 25 of the administrations, patients received 3.7 GBq of 131 I. Radiation doses for the designated caregivers were monitored on an hourly basis for 1 week using electronic personal dosemeters. The average penetrating dose was 98±64 μSv. The maximum penetrating dose was 283 μSv. Measured dose rate profiles showed that, on average, one-third of the caregiver dose was received during the journey home from hospital. The mean dose rate profile showed rapid clearance of 131 I with three distinct phases. The corresponding clearance half-times were 131 I contaminating the home. (authors)

  6. Gafchromic EBT-XD film: Dosimetry characterization in high-dose, volumetric-modulated arc therapy.

    Science.gov (United States)

    Miura, Hideharu; Ozawa, Shuichi; Hosono, Fumika; Sumida, Naoki; Okazue, Toshiya; Yamada, Kiyoshi; Nagata, Yasushi

    2016-11-08

    Radiochromic films are important tools for assessing complex dose distributions. Gafchromic EBT-XD films have been designed for optimal performance in the 40-4,000 cGy dose range. We investigated the dosimetric characteristics of these films, including their dose-response, postexposure density growth, and dependence on scanner orientation, beam energy, and dose rate with applications to high-dose volumetric-modulated arc therapy (VMAT) verification. A 10 MV beam from a TrueBeam STx linear accelerator was used to irradiate the films with doses in the 0-4,000 cGy range. Postexposure coloration was analyzed at postirradiation times ranging from several minutes to 48 h. The films were also irradiated with 6 MV (dose rate (DR): 600 MU/min), 6 MV flattening filter-free (FFF) (DR: 1,400 MU/ min), and 10 MV FFF (DR: 2,400 MU/min) beams to determine the energy and dose-rate dependence. For clinical examinations, we compared the dose distribu-tion measured with EBT-XD films and calculated by the planning system for four VMAT cases. The red channel of the EBT-XD film exhibited a wider dynamic range than the green and blue channels. Scanner orientation yielded a variation of ~ 3% in the net optical density (OD). The difference between the film front and back scan orientations was negligible, with variation of ~ 1.3% in the net OD. The net OD increased sharply within the first 6 hrs after irradiation and gradually afterwards. No significant difference was observed for the beam energy and dose rate, with a variation of ~ 1.5% in the net OD. The gamma passing rates (at 3%, 3 mm) between the film- measured and treatment planning system (TPS)-calculated dose distributions under a high dose VMAT plan in the absolute dose mode were more than 98.9%. © 2016 The Authors.

  7. Changes in pulmonary function and influencing factors after high-dose intrathoracic radio(chemo)therapy

    Energy Technology Data Exchange (ETDEWEB)

    Schroeder, Christina [University Clinic Giessen and Marburg, Clinic for Radiotherapy and Radiation Oncology, Marburg (Germany); Ruppiner Kliniken GmbH, Clinic for Radiotherapy and Radiation Oncology, Neuruppin (Germany); Engenhart-Cabillic, Rita; Vorwerk, Hilke [University Clinic Giessen and Marburg, Clinic for Radiotherapy and Radiation Oncology, Marburg (Germany); Schmidt, Michael; Huhnt, Winfried; Blank, Eyck; Sidow, Dietrich; Buchali, Andre [Ruppiner Kliniken GmbH, Clinic for Radiotherapy and Radiation Oncology, Neuruppin (Germany)

    2017-02-15

    Using prospectively collected patient-related, dose-related, and pulmonary function test (PFT) data before radiotherapy (RT) and at several follow-up visits after RT, the time course of PFT changes after high-dose radio(chemo)therapy and influencing factors were analyzed. From April 2012 to October 2015, 81 patients with non-small-cell lung carcinoma (NSCLC), small cell lung carcinoma (SCLC), or esophageal carcinoma where treated with high-dose radio(chemo)therapy. PFT data were collected before treatment and 6 weeks, 12 weeks, and 6 months after RT. The influence of patient- and treatment-related factors on PFT was analyzed. Mean forced expiratory volume in 1 s (FEV1) constantly declined during follow-up (p = 0.001). In total, 68% of patients had a reduced FEV1 at 6 months. Mean vital capacity (VC) didn't change during follow-up (p > 0.05). Mean total lung capacity (TLC) showed a constant decline after RT (p = 0.026). At 6 months, 60% of patients showed a decline in VC and 73% in TLC. The mean diffusion capacity for carbon monoxide (DLCO) declined at 6 and 12 weeks, but recovered slightly at 6 months (p < 0.0005). At 6 months, 86% of patients had a reduced DLCO. After treatment, the partial pressure of CO{sub 2} in the blood (pCO{sub 2}) was increased and pO{sub 2} was decreased (p > 0.05). Only the pretreatment PFT classification had a significant influence on the post-RT FEV1. DLCO seems to be the most reliable indicator for lung tissue damage after thoracic RT. Ventilation parameters appear to be less reliable. Concerning patient- or treatment-related factors, no reliable conclusion can be drawn regarding which factors may be relevant. (orig.) [German] Patientenbezogene, therapiebezogene und Lungenfunktionsdaten (''pulmonary function test'', PFT) wurden vor Radiotherapie (RT) und an verschiedenen Nachsorgeterminen nach RT prospektiv gesammelt, um PFT-Veraenderungen sowie Einflussfaktoren nach Hochdosis-Radio(chemo)therapie zu

  8. Intranasal insulin therapy: the clinical realities

    DEFF Research Database (Denmark)

    Hilsted, J; Madsbad, Sten; Hvidberg, A

    1995-01-01

    To evaluate metabolic control and safety parameters (hypoglycaemia frequency and nasal mucosa physiology), 31 insulin-dependent diabetic patients were treated with intranasal insulin at mealtimes for 1 month and with subcutaneous fast-acting insulin at meals for another month in an open, crossover...... randomized trial. During both treatment periods the patients were treated with intermediate-acting insulin at bedtime. Six of the patients were withdrawn from the study during intranasal insulin therapy due to metabolic dysregulation. Serum insulin concentrations increased more rapidly and decreased more...... quickly during intranasal as compared with subcutaneous insulin administration. Metabolic control deteriorated, as assessed by haemoglobin A1c concentrations, slightly but significantly after intranasal as compared with subcutaneous insulin therapy. The bioavailability of intranasally applied insulin...

  9. High-dose ibuprofen therapy associated with esophageal ulceration after pneumonectomy in a patient with cystic fibrosis: a case report

    Directory of Open Access Journals (Sweden)

    Anbar Ran D

    2004-09-01

    Full Text Available Abstract Background Lung disease in patients with cystic fibrosis is thought to develop as a result of airway inflammation, infection, and obstruction. Pulmonary therapies for cystic fibrosis that reduce airway inflammation include corticosteroids, rhDNase, antibiotics, and high-dose ibuprofen. Despite evidence that high-dose ibuprofen slows the progression of lung disease in patients with cystic fibrosis, many clinicians have chosen not to use this therapy because of concerns regarding potential side effects, especially gastrointestinal bleeding. However, studies have shown a low incidence of gastrointestinal ulceration and bleeding in patients with cystic fibrosis who have been treated with high-dose ibuprofen. Case presentation The described case illustrates a life-threatening upper gastrointestinal bleed that may have resulted from high-dose ibuprofen therapy in a patient with CF who had undergone a pneumonectomy. Mediastinal shift post-pneumonectomy distorted the patient's esophageal anatomy and may have caused decreased esophageal motility, which led to prolonged contact of the ibuprofen with the esophagus. The concentrated effect of the ibuprofen, as well as its systemic effects, probably contributed to the occurrence of the bleed in this patient. Conclusions This report demonstrates that gastrointestinal tract anatomical abnormalities or dysmotility may be contraindications for therapy with high-dose ibuprofen in patients with cystic fibrosis.

  10. Influence of low- and high-dose radioiodine therapy on oxidative modification of fibrinogen

    International Nuclear Information System (INIS)

    Schweeger-Exeli, I.J.

    2001-10-01

    levels were significantly elevated above 300 mg/dl (p 0.05) and did not change to a significant extent after treatment in both subgroups. Conclusion: Purification of fibrinogen out of small volumes of plasma is feasible in a short period of time and requires only little technical effort. High - dose radioiodine therapy, applied in differentiated thyroid cancer, leads to significantly increased incorporation of carbonyl groups into the fibrinogen molecule. It remains to be elucidated, whether thyroid hormone status itself influences oxidative damage of fibrinogen. Key words: fibrinogen; radioiodine therapy; oxidative modification; isolation techniques; 2,4-dinitrophenylhydrazine. (author)

  11. The role of insulin pump therapy for type 2 diabetes mellitus.

    Science.gov (United States)

    Landau, Zohar; Raz, Itamar; Wainstein, Julio; Bar-Dayan, Yosefa; Cahn, Avivit

    2017-01-01

    Many patients with type 2 diabetes fail to achieve adequate glucose control despite escalation of treatment and combinations of multiple therapies including insulin. Patients with long-standing type 2 diabetes often suffer from the combination of severe insulin deficiency in addition to insulin resistance, thereby requiring high doses of insulin delivered in multiple injections to attain adequate glycemic control. Insulin-pump therapy was first introduced in the 1970s as an approach to mimic physiological insulin delivery and attain normal glucose in patients with type 1 diabetes. The recent years have seen an increase in the use of this technology for patients with type 2 diabetes. This article summarizes the clinical studies evaluating insulin pump use in patients with type 2 diabetes and discusses the benefits and shortcomings of pump therapy in this population. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  12. A blinded, randomized, controlled trial of three doses of high-dose insulin in poison-induced cardiogenic shock.

    Science.gov (United States)

    Cole, J B; Stellpflug, S J; Ellsworth, H; Anderson, C P; Adams, A B; Engebretsen, K M; Holger, J S

    2013-05-01

    High dose insulin (HDI) has proven superior to glucagon and catecholamines in the treatment of poison-induced cardiogenic shock (PICS) in previous animal studies. Standard recommendations for dosing of insulin vary and the optimal dose of HDI in PICS has not been established. Our hypothesis was a dose of 10 U/kg/hr of HDI would be superior to 1 U/kg/hr with cardiac output (CO) as our primary outcome measure in pigs with propranolol-induced PICS. This was a blinded, prospective, randomized trial with 4 arms consisting of 4 pigs in each arm. The arms were as follows: placebo (P), 1 U/kg/hr (HDI-1), 5 U/kg/hr (HDI-5), and 10 U/kg/hr (HDI-10). Cardiogenic shock was induced with a bolus of 0.5 mg/kg of propranolol followed by an infusion of 0.25 mg/kg/min until the point of toxicity, defined as 0.75 x (HR x MAP) was reached. At this point the propranolol infusion was decreased to 0.125 mg/kg/min and a 20 mL/kg bolus of normal saline (NS) was administered. The protocol was continued for 6 hours or until the animals died. 2 pigs died in the P arm, 1 pig died each in the HDI-1 and HDI-5 arms, and all pigs lived in the HDI-10 arm. There was a statistically significant difference in dose by time interaction on CO of 1.13 L/min over the 6 hr study period (p = < 0.001). There was also a statistically significant difference in dose by time interaction on MAP, HR, and systemic vascular resistance (SVR). No statistically significant difference was found between any of the arms regarding glucose utilization. HDI was statistically and clinically significantly superior to placebo in this propranolol model of PICS. Furthermore a dose response over time was found where CO increased corresponding to increases in doses of HDI.

  13. Neuropsychological function in adults after high dose fractionated radiation therapy of skull base tumors

    International Nuclear Information System (INIS)

    Glosser, Guila; McManus, Pat; Munzenrider, John; Austin-Seymour, Mary; Fullerton, Barbara; Adams, Judy; Urie, Marcia M.

    1997-01-01

    Purpose: To evaluate the long term effects of high dose fractionated radiation therapy on brain functioning prospectively in adults without primary brain tumors. Methods and Materials: Seventeen patients with histologically confirmed chordomas and low grade chondrosarcomas of the skull base were evaluated with neuropsychological measures of intelligence, language, memory, attention, motor function and mood following surgical resection/biopsy of the tumor prior to irradiation, and then at about 6 months, 2 years and 4 years following completion of treatment. None received chemotherapy. Results: In the patients without tumor recurrence or radiation necrosis, there were no indications of adverse effects on cognitive functioning in the post-acute through the late stages after brain irradiation. Even in patients who received doses of radiation up to 66 Cobalt Gy equivalent through nondiseased (temporal lobe) brain tissue, memory and cognitive functioning remained stable for up to 5 years after treatment. A mild decline in psycho-motor speed was seen in more than half of the patients, and motor slowing was related to higher radiation doses in midline and temporal lobe brain structures. Conclusion: Results suggest that in adults, tolerance for focused radiation is relatively high in cortical brain structures

  14. Results of radiation therapy for uterine cervical cancer using high dose rate remote after loading system

    International Nuclear Information System (INIS)

    Ogawa, Yoshihiro; Nemoto, Kenji

    2003-01-01

    In Japan, radiotherapy with high dose rate remote after loading system (HDR-RALS) for intracavitary brachytherapy is the standard treatment for more than 30 years. This report showed the usefulness of HDR-RALS for uterine cervical cancer. From 1980 through 1999, 442 patients with uterine cervical cancers (stage I: 66, stage II: 161, stage III: 165, stage IV: 50) were treated. Radiotherapy was performed both external teletherapy and HDR-RALS. Overall survival rate at 5 years was 60.2%. The 5-year actuarial incidence of all complications was 16.4%. The 5-year actuarial incidence of all complications in cases treated with the sum doses of whole pelvic irradiation (without central shield) and RALS up to 49 Gy, 50 to 59 Gy or larger doses were 7.5%, 11.0% and 25.2%, respectively. Radiation therapy using HDR-RALS was very effective. While the dose of whole pelvic irradiation was increased, the actuarial incidence of all complications was increased. (author)

  15. High-dose rate intra-operative radiation therapy for local advanced and recurrent colorectal cancer

    International Nuclear Information System (INIS)

    Harrison, L.B.; Mychalczak, B.; Enker, W.; Anderson, L.; Cohen, A.E.; Minsky, B.

    1996-01-01

    In an effort to improve the local control for advanced and recurrent cancers of the rectum, we have integrated high-dose rate intra-operative radiation therapy (HDR-IORT) into the treatment program. Between 11/92 and 10/95, 47 patients (pts) were treated. There were 26 males and 21 females whose ages ranged from 30-80 (median = 62) years. There were 19 pts with primary unresectable rectal cancer, and 28 pts who were treated for recurrent rectal cancer. Histology was adenocarcinoma - 45 pts, squamous cancer - 2 pts. The range of follow-up is 1-34 months (median = 14 months). The majority of primary unresectable pts received pre-operative radiation therapy (4500-5040 cGy) with chemotherapy (5-FU with Leucovorin) 4-6 weeks later, they underwent resection + HDR-IORT (1200 cGy). For the 28 pts with recurrent cancer, the majority received surgery and HDR-IORT alone because they had received prior RT. For the pts with primary unresectable disease, actuarial 2-year local control was 77%, actuarial distant metastasis-free survival was 71%, disease free survival was 66%, and overall survival was 84%. For those pts with recurrent disease, actuarial 2-year local control rate was 65%, distant metastasis-free survival was 65%, disease free survival was 47%, and overall survival was 61%. Complications occurred in 36%. There were no cases where the anatomical distribution of disease, or technical limitations prevented the adequate delivery of HDR-IORT. We conclude that this technique was most versatile, and enabled all appropriate pts to receive IORT. The preliminary data in terms of local control are encouraging, even for the poor prognostic sub-group of pts with recurrent cancer

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

    DEFF Research Database (Denmark)

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

    2015-01-01

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

  17. Resveratrol prevents endothelial cells injury in high-dose interleukin-2 therapy against melanoma.

    Directory of Open Access Journals (Sweden)

    Hongbing Guan

    Full Text Available Immunotherapy with high-dose interleukin-2 (HDIL-2 is an effective treatment for patients with metastatic melanoma and renal cell carcinoma. However, it is accompanied by severe toxicity involving endothelial cell injury and induction of vascular leak syndrome (VLS. In this study, we found that resveratrol, a plant polyphenol with anti-inflammatory and anti-cancer properties, was able to prevent the endothelial cell injury and inhibit the development of VLS while improving the efficacy of HDIL-2 therapy in the killing of metastasized melanoma. Specifically, C57BL/6 mice were injected with B16F10 cells followed by resveratrol by gavage the next day and continued treatment with resveratrol once a day. On day 9, mice received HDIL-2. On day 12, mice were evaluated for VLS and tumor metastasis. We found that resveratrol significantly inhibited the development of VLS in lung and liver by protecting endothelial cell integrity and preventing endothelial cells from undergoing apoptosis. The metastasis and growth of the tumor in lung were significantly inhibited by HDIL-2 and HDIL-2 + resveratrol treatment. Notably, HDIL-2 + resveratrol co-treatment was more effective in inhibiting tumor metastasis and growth than HDIL-2 treatment alone. We also analyzed the immune status of Gr-1(+CD11b(+ myeloid-derived suppressor cells (MDSC and FoxP3(+CD4(+ regulatory T cells (Treg. We found that resveratrol induced expansion and suppressive function of MDSC which inhibited the development of VLS after adoptive transfer. However, resveratrol suppressed the HDIL-2-induced expansion of Treg cells. We also found that resveratrol enhanced the susceptibility of melanoma to the cytotoxicity of IL-2-activated killer cells, and induced the expression of the tumor suppressor gene FoxO1. Our results suggested the potential use of resveratrol in HDIL-2 treatment against melanoma. We also demonstrated, for the first time, that MDSC is the dominant suppressor cell than regulatory

  18. On the genetic risk after high dose radioiodine therapy with regard to the gonadal dose

    International Nuclear Information System (INIS)

    Ehrenheim, C.; Hauswirth, C.; Fitschen, J.; Martin, E.; Oetting, G.; Hundeshagen, H.

    1997-01-01

    Aim: The genetic risk for the offspring of patients treated with high doses of radioiodine was to be assessed with special regard to the gonadal dose caused by diagnostic and therapeutic procedures. Methods: 41 young females (aged between 19 and 39 years) and four young males (aged 26 to 36 years) treated with radioiodine because of a thyroid carcinoma were interviewed by use of a questionnaire. The course of pregnancy and birth history could be documented as well as the congenital and developmental conditions of 56 children. Results: The amount of radioactivity applied for therapy and whole body scans ranged over 4,144 and 35,15 GBq I-131; the individual gonadal dose was calculated based on the MIRD model and ranged over 0,2 and 2,2 Sv (0,51 Sv at a mean). The period of time between the last radioiodine application and confinement was at least 9 months, not exceeding 14 years. As to the course of pregnancy and birth two early abortions, one extrauterine gravidity and one premature birth due to an insufficiency of the placenta were stated. In one case a chromosomal translocation 7/14 occured as a genetic defect which lead to an interruption. The children's development was unconspicuous except of two cases of neurodermatitis as well as multiple allergies and an early closure of the anterior fontanelle in one child each. Conclusion: Although the genetic risk is supposed to increase with the gonadal dose achieved (doubling dose 1 Sv) and the increased risk of any congenital anomaly was calculated as about 13% at a mean in our patients, the rate of genetic determined diseases was not elevated (1,8% or 1/57). Thus, no increase of genetic defects or congenital malformations was reported in a total of 408 children described in the literature and in our group. (orig.) [de

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

    Directory of Open Access Journals (Sweden)

    A. M. Strizhevskaya

    2015-01-01

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

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

    International Nuclear Information System (INIS)

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

    2012-01-01

    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.

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

    Directory of Open Access Journals (Sweden)

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

    2011-01-01

    Full Text Available 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.

  2. High-Dose Mannose-Binding Lectin Therapy for Ebola Virus Infection

    Science.gov (United States)

    2010-06-01

    host defense against a wide range of viral and other pathogens. MBL is a C-type lectin that recognizes hexose sugars including man- nose, glucose...should be evaluatedmore broadly as an immunotherapeutic agent for a wide spectrum of glycosylated pathogens. MATERIALS AND METHODS Production and... coagulation mod- ulators, antisense technologies, therapeutic antibodies and Table 1. Pharmacokinetic Parameters of Low- vs High-Dose Recombinant Human

  3. Rapid Onset of Retinal Toxicity From High-Dose Hydroxychloroquine Given for Cancer Therapy.

    Science.gov (United States)

    Leung, Loh-Shan B; Neal, Joel W; Wakelee, Heather A; Sequist, Lecia V; Marmor, Michael F

    2015-10-01

    To report rapid onset of retinal toxicity in a series of patients followed on high-dose (1000 mg daily) hydroxychloroquine during an oncologic clinical trial studying hydroxychloroquine with erlotinib for non-small cell lung cancer. Retrospective observational case series. Ophthalmic surveillance was performed on patients in a multicenter clinical trial testing high-dose (1000 mg daily) hydroxychloroquine for advanced non-small cell lung cancer. The US Food & Drug Administration-recommended screening protocol included only visual acuity testing, dilated fundus examination, Amsler grid testing, and color vision testing. In patients seen at Stanford, additional sensitive screening procedures were added at the discretion of the retinal physician: high-resolution spectral-domain optical coherence tomography (OCT), fundus autofluorescence (FAF) imaging, Humphrey visual field (HVF) testing, and multifocal electroretinography (mfERG). Out of the 7 patients having exposure of at least 6 months, 2 developed retinal toxicity (at 11 and 17 months of exposure). Damage was identified by OCT imaging, mfERG testing, and, in 1 case, visual field testing. Fundus autofluorescence imaging remained normal. Neither patient had symptomatic visual acuity loss. These cases show that high doses of hydroxychloroquine can initiate the development of retinal toxicity within 1-2 years. Although synergy with erlotinib is theoretically possible, there are no prior reports of erlotinib-associated retinal toxicity despite over a decade of use in oncology. These results also suggest that sensitive retinal screening tests should be added to ongoing and future clinical trials involving high-dose hydroxychloroquine to improve safety monitoring and preservation of vision. Published by Elsevier Inc.

  4. Pentobarbital quantitation using EMIT serum barbiturate assay reagents: application to monitoring of high-dose pentobarbital therapy.

    Science.gov (United States)

    Pape, B E; Cary, P L; Clay, L C; Godolphin, W

    1983-01-01

    Pentobarbital serum concentrations associated with a high-dose therapeutic regimen were determined using EMIT immunoassay reagents. Replicate analyses of serum controls resulted in a within-assay coefficient of variation of 5.0% and a between-assay coefficient of variation of 10%. Regression analysis of 44 serum samples analyzed by this technique (y) and a reference procedure (x) were y = 0.98x + 3.6 (r = 0.98; x = ultraviolet spectroscopy) and y = 1.04x + 2.4 (r = 0.96; x = high-performance liquid chromatography). Clinical evaluation of the results indicates the immunoassay is sufficiently sensitive and selective for pentobarbital to allow accurate quantitation within the therapeutic range associated with high-dose therapy.

  5. Prospective study in the management of high-dose radioactive iodine therapy induced gastritis

    International Nuclear Information System (INIS)

    Carbonell, C.; Ogbac, R.V.

    2007-01-01

    Full text: Gastritis is simply defined as inflammation of the gastric mucosa. In post-RAI patients, this is one of the most common complications that are encountered. Some patients may even require repetitive administration of high doses of radioactive iodine (I-131). Small doses of radiation (up to 1500 R) cause reversible mucosal damage, whereas higher radiation doses cause irreversible damage with atrophy and ischemic-related ulceration. Reversible changes consist of degenerative changes in epithelial cells and nonspecific chronic inflammatory infiltrate in the lamina propria. Higher amounts of radiation cause permanent mucosal damage, with atrophy of fundic glands, mucosal erosions, and capillary hemorrhage. Associated submucosal endarteritis results in mucosal ischemia and secondary ulcer development. Recurrent gastritis, if left untreated, may be a predisposing factor for gastric malignancy. Methods:A total of thirty post-RAI subjects were evaluated for signs and symptoms of gastritis and were divided into 3 groups which were given drugs for gastritis (H2-receptor antagonist, proton pump inhibitor, and sucralfate). Survey forms were distributed to evaluate the presence of nausea, vomiting, epigastric pain (graded according to severity of pain), and gastrointestinal bleeding. Results were tallied accordingly. Results and Discussion: In a total of 3 subjects who were given sucralfate, all of them did not experience any nausea and vomiting. One subject experienced mild epigastric discomfort and another subject was able to experience a non-specific symptom of abdominal bloatedness. (Note: Subjects are still for completion) In theory, radiation irritates the mucosa causing inflammation and mucosal damage which is further irritated by gastric acid secretion. The administration of H2-receptor blockers and proton pump inhibitors only inhibit gastric acid secretion while existing inflammation of mucosa due to high doses of radiation is left untreated. However

  6. High-dose superselective intra-arterial cisplatin and concomitant radiation therapy for carcinoma of the oral cavity

    International Nuclear Information System (INIS)

    Suzuki, Gen; Tanaka, Norimitsu; Ogo, Etuyo

    2007-01-01

    The purpose of this study was to evaluate the effect of high-dose superselective intra-arterial cisplatin and concomitant radiation therapy for carcinoma of the oral cavities. The subjects consisted of 18 patients with carcinoma of the oral, and cavity treated with superselective intra-arterial infusion of high dose cisplatin (100 mg/body) concomitant with delivery of external beam radiotherapy (median total dose, 60.8 Gy) between 2001 and 2004. Sodium thiosulfate was administered intravenously to provide effective cisplatin neutlization. They were International Union Against Cancer (UICC)1997 stage II-IV (stage II: 4 patients, stage III: 4 patients, stage IV: 10 patients). Patients ranged from 43-81 years of age, with a median of 60 years, and included 14 men and 4 women. A follow-up period was 6 months minimum from the atart of the radiation therapy, the median follow up period at 28 months. The three-year overall survival rate was 71%. The three-year disease free rate and local control rate were 60% and 65%, respectively. Three-year local control rate of the T2-3 was achieved at 83%, and that for T4 at 50%. There was borderline significant difference in local control rate between T2-3 and T4 (p=0.05). We conclude that the high-dose superselective intra-arterial cisplatin and concomitant radiation therapy provides effective results in organ preservation for cancer of oral cavities. Further studies are also required to determine the validity of this method. (author)

  7. SU-F-J-45: Sparing Normal Tissue with Ultra-High Dose Rate in Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Feng, Y [DCH Reg. Medical Center, Tuscaloosa, AL (United States)

    2016-06-15

    Purpose: To spare normal tissue by reducing the location uncertainty of a moving target, we proposed an ultra-high dose rate system and evaluated. Methods: High energy electrons generated with a linear accelerator were injected into a storage ring to be accumulated. The number of the electrons in the ring was determined based on the prescribed radiation dose. The dose was delivered within a millisecond, when an online imaging system found that the target was in the position that was consistent with that in a treatment plan. In such a short time period, the displacement of the target was negligible. The margin added to the clinical target volume (CTV) could be reduced that was evaluated by comparing of volumes between CTV and ITV in 14 cases of lung stereotactic body radiation therapy (SBRT) treatments. A design of the ultra-high dose rate system was evaluated based clinical needs and the recent developments of low energy (a few MeV) electron storage ring. Results: This design of ultra-high dose rate system was feasible based on the techniques currently available. The reduction of a target volume was significant by reducing the margin that accounted the motion of the target. ∼50% volume reduction of the internal target volume (ITV) could be achieved in lung SBRT treatments. Conclusion: With this innovation of ultra-high dose rate system, the margin of target is able to be significantly reduced. It will reduce treatment time of gating and allow precisely specified gating window to improve the accuracy of dose delivering.

  8. High-dose statin therapy in patients with stable coronary artery disease: treating the right patients based on individualized prediction of treatment effect

    NARCIS (Netherlands)

    Dorresteijn, Johannes A. N.; Boekholdt, S. Matthijs; van der Graaf, Yolanda; Kastelein, John J. P.; LaRosa, John C.; Pedersen, Terje R.; Demicco, David A.; Ridker, Paul M.; Cook, Nancy R.; Visseren, Frank L. J.

    2013-01-01

    Clinicians need to identify coronary artery disease patients for whom the benefits of high-dose versus usual-dose statin therapy outweigh potential harm. We therefore aimed to develop and validate a model for prediction of the incremental treatment effect of high-dose statins for individual patients

  9. Mechanisms of Fatal Cardiotoxicity following High-Dose Cyclophosphamide Therapy and a Method for Its Prevention.

    Directory of Open Access Journals (Sweden)

    Takuro Nishikawa

    Full Text Available Observed only after administration of high doses, cardiotoxicity is the dose-limiting effect of cyclophosphamide (CY. We investigated the poorly understood cardiotoxic mechanisms of high-dose CY. A rat cardiac myocardial cell line, H9c2, was exposed to CY metabolized by S9 fraction of rat liver homogenate mixed with co-factors (CYS9. Cytotoxicity was then evaluated by 3-(4,5-dimethyl-2-thiazolyl¬2,5-diphenyl¬2H-tetrazolium bromide (MTT assay, lactate dehydrogenase release, production of reactive oxygen species (ROS, and incidence of apoptosis. We also investigated how the myocardial cellular effects of CYS9 were modified by acrolein scavenger N-acetylcysteine (NAC, antioxidant isorhamnetin (ISO, and CYP inhibitor β-ionone (BIO. Quantifying CY and CY metabolites by means of liquid chromatography coupled with electrospray tandem mass spectrometry, we assayed culture supernatants of CYS9 with and without candidate cardioprotectant agents. Assay results for MTT showed that treatment with CY (125-500 μM did not induce cytotoxicity. CYS9, however, exhibited myocardial cytotoxicity when CY concentration was 250 μM or more. After 250 μM of CY was metabolized in S9 mix for 2 h, the concentration of CY was 73.6 ± 8.0 μM, 4-hydroxy-cyclophosphamide (HCY 17.6 ± 4.3, o-carboxyethyl-phosphoramide (CEPM 26.6 ± 5.3 μM, and acrolein 26.7 ± 2.5 μM. Inhibition of CYS9-induced cytotoxicity occurred with NAC, ISO, and BIO. When treated with ISO or BIO, metabolism of CY was significantly inhibited. Pre-treatment with NAC, however, did not inhibit the metabolism of CY: compared to control samples, we observed no difference in HCY, a significant increase of CEPM, and a significant decrease of acrolein. Furthermore, NAC pre-treatment did not affect intracellular amounts of ROS produced by CYS9. Since acrolein seems to be heavily implicated in the onset of cardiotoxicity, any competitive metabolic processing of CY that reduces its transformation to acrolein

  10. Low- and high-dose radioiodine therapy for low-/intermediate-risk differentiated thyroid cancer. A preliminary clinical trial

    International Nuclear Information System (INIS)

    Qu Yuan; Huang Rui; Li Lin

    2017-01-01

    To compare the ablation results, therapeutic responses and adverse reactions between a low dose (1.1 GBq) or high dose (3.7 GBq) of 131 I in low-/intermediate-risk differentiated thyroid cancer (DTC) patients. The factors influencing the ablation result and therapeutic response were also analyzed. The researchers used a random number table to randomly assign the enrolled patients to the low-dose group or high-dose group at a 1:1 ratio, and assessment of ablation result, therapeutic response, and adverse reactions evaluated 6 ± 3 months after therapy. A total of 140 patients were enrolled in the study through October 2014-June 2015. Until February 2016, 132 patients completed the trial. 99 patients were re-examined under thyroid-stimulating hormone (TSH) stimulation 3-9 months after 131 I therapy. For the low-dose and high-dose groups, the success rates of ablation were 52.7% (29/55) and 59.1% (26/44), respectively. The ablation results did not differ significantly between the two groups (P = 0.548). One hundred and thirty two patients were re-examined 2-9 months after 131 I therapy. The low-dose group had an excellent response rate of ∼80% (53/66), an indeterminate response rate of ∼ 20% (13/66), and no cases with a biochemical incomplete response. The high-dose group had an excellent response rate of ∼85% (36/66), an indeterminate response rate of ∼11% (7/66), and a biochemical incomplete response rate of ∼4% (3/66). No significant differences in the therapeutic response were observed between the two groups (P = 0.087). Patients in stage N1b had a significantly lower success rate of ablation than those in stage N0 (P = 0.000). The success rate of ablation increased significantly with lower thyroglobulin (Tg) levels (P = 0.000). A pre-treatment Tg level was significantly associated with a higher excellent response rate (P = 0.002). Pre-treatment-stimulated Tg of 0.47 and 3.09 μg/L were identified as cut-off values for predicting the ablation result and

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

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

    International Nuclear Information System (INIS)

    Slater, J.D.; Austin-Seymour, M.; Munzenrider, J.

    1988-01-01

    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

  13. Functional impairment of the salivary gland after high dose radioiodine therapy

    Energy Technology Data Exchange (ETDEWEB)

    Spiegel, W.; Reiners, C.; Boerner, W.

    1986-06-01

    Radiation induced impairements of salivation, which are rather related to the more radio-sensitive parotides than to the submandibular glands according to our experience, occur in about 1/3 of the patients treated with 7,4-11,1 GBq (200-300 mCi) of I-131. Based on our results and experiences after percutaneous radiation therapy of the head and neck region, a total xerostomy (Sicca's syndrome) must already be expected at a focal dose of 40 Gy to the salivary gland parenchyma. Experience has shown that this cumulative radiation dose is reached at about 18,5 GBq (500 mCi) of I-131. The acute sialadenitis occuring a few days after therapeutic administration of radioiodine is mostly associated with minor complaints and therefore often escapes the patient's notice. During the onset of xerostomy, which is associated with a moderate reduction of salivation, the patients are surprisingly indolent. However, specific examinations including patient's history, palpation and functional scintigraphy enable early detection of radiation induced functional depression of the salivary glands, which should be accounted for in the assessment of indication for further radioiodine therapy. To prevent the severe consequences of xerostomy such as ageusia, dysphagia, epithelial lesion of the oral mucosa and loss of teeth, the patients under radioiodine therapy should be urged to see to sufficient fluid supply and to steadily stimulate salivation e.g. by sour drops, chewing gum or Emser pastilles.

  14. Will long acting insulin analogs influence the use of insulin pump therapy in type 1 diabetes?

    NARCIS (Netherlands)

    DeVries, J. Hans

    2005-01-01

    Insulin pump therapy enjoys a steadily growing number of users and is associated with an approximately 0.5% lower A1c as compared to flexible insulin injection therapy in type 1 diabetes patients. An important question is whether superiority of insulin pump therapy persists in the era of rapid

  15. Intensive Insulin Therapy: Tight Blood Sugar Control

    Science.gov (United States)

    ... specific situation. McCulloch DK. General principles of insulin therapy in diabetes mellitus. http://www.uptodate.com/home. Accessed Dec. ... Diabetes Association. http://www.diabetes.org/living-with-diabetes/treatment-and-care/blood-glucose-control/checking-your-blood- ...

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

    Science.gov (United States)

    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. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. High-dose biotin therapy leading to false biochemical endocrine profiles: validation of a simple method to overcome biotin interference.

    Science.gov (United States)

    Piketty, Marie-Liesse; Prie, Dominique; Sedel, Frederic; Bernard, Delphine; Hercend, Claude; Chanson, Philippe; Souberbielle, Jean-Claude

    2017-05-01

    High-dose biotin therapy is beneficial in progressive multiple sclerosis (MS) and is expected to be adopted by a large number of patients. Biotin therapy leads to analytical interference in many immunoassays that utilize streptavidin-biotin capture techniques, yielding skewed results that can mimic various endocrine disorders. We aimed at exploring this interference, to be able to remove biotin and avoid misleading results. We measured free triiodothyronine (fT3), free thyroxine (fT4), thyroid-stimulating hormone (TSH), parathyroid homrone (PTH), 25-hydroxyvitamin D (25OHD), follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin, C-peptide, cortisol (Roche Diagnostics assays), biotin and its main metabolites (liquid chromatography tandem mass spectrometry) in 23 plasmas from MS patients and healthy volunteers receiving high-dose biotin, and in 39 biotin-unsupplemented patients, before and after a simple procedure (designated N5) designed to remove biotin by means of streptavidin-coated microparticles. We also assayed fT4, TSH and PTH in the 23 high-biotin plasmas using assays not employing streptavidin-biotin binding. The biotin concentration ranged from 31.7 to 1160 µg/L in the 23 high-biotin plasmas samples. After the N5 protocol, the biotin concentration was below the detection limit in all but two samples (8.3 and 27.6 μg/L). Most hormones results were abnormal, but normalized after N5. All results with the alternative methods were normal except two slight PTH elevations. In the 39 biotin-unsupplemented patients, the N5 protocol did not affect the results for any of the hormones, apart from an 8.4% decrease in PTH. We confirm that most streptavidin-biotin hormone immunoassays are affected by high biotin concentrations, leading to a risk of misdiagnosis. Our simple neutralization method efficiently suppresses biotin interference.

  18. Effect of Insulin Therapy using Hyper-insulinemic Normoglycemic Clamp on Inflammatory Response in Brain Dead Organ Donors.

    Science.gov (United States)

    Aljiffry, M; Hassanain, M; Schricker, T; Shaheen, M; Nouh, T; Lattermann, R; Salman, A; Wykes, L; Metrakos, P

    2016-05-01

    Brain death is a major stress that is associated with a massive inflammatory response and systemic hyperglycemia. Severe inflammation leads to increased graft immunogenicity and risk of graft dysfunction; while acute hyperglycemia aggravates the inflammatory response and increases the risk of morbidity and mortality. Insulin therapy not only controls hyperglycemia but also suppresses inflammation. The present study is to investigate the anti-inflammatory properties and the normoglycemia maintenance of high dose insulin on brain dead organ donors. 15 brain dead organ donors were divided into 2 groups, insulin treated (n=6) and controls (n=9). Insulin was provided for a minimum of 6 h using the hyperinsulinemic normoglycemic clamp technique. The changes of serum cytokines, including IL-6, IL-10, IL-1β, IL-8, TNFα, TGFα and MCP-1, were measured by suspension bead array immunoassay and glucose by a glucose monitor. Compared to controls, insulin treated donors had a significant lower blood glucose 4.8 (4-6.9) vs. 9 (5.6-11.7) mmol/L, pinsulin treated donors compared with those in controls. High dose insulin therapy decreases the concentrations of inflammatory cytokines in brain dead donors and preserves normoglycemia. High dose of insulin may have anti-inflammatory effects in brain dead organ donors and therefore, improve the quality of donor organs and potentially improve outcomes. © Georg Thieme Verlag KG Stuttgart · New York.

  19. Insulin Therapy in Diabetic Hyperglycemic Emergencies

    Directory of Open Access Journals (Sweden)

    Diana Machado Ramírez

    2014-09-01

    Full Text Available Background: diabetic ketoacidosis and hyperglycemic hyperosmolar nonketotic state are two of the most serious metabolic emergencies in diabetic patients. Objective: to identify the type of metabolic complications (diabetic ketoacidosis and hyperglycemic hyperosmolar nonketotic state in order to analyze the patients’ outcome considering the plasma pH levels, as well as the mode of insulin administration. Method: a cross-sectional descriptive study was conducted in 52 patients admitted to the intensive care unit of the Enrique Cabrera Hospital from 2000 to 2007. The variables analyzed included: type of diabetes mellitus, type of acute complication, mode of insulin administration, blood gas analysis and outcome. Results: diabetic ketoacidosis occurred in 57.5 % of the type 1 diabetic patients and in the 42.5 % of the type 2 diabetics. None of the type 1 diabetics developed hyperglycemic hyperosmolar nonketotic state and this complication was observed in 23.0 % of the patients with diabetes type 2. Microdosing was the mode of insulin administration that predominated in both ketoacidosis and hyperglycemic state cases. Mortality was higher in the hyperglycemic state (67 % and using microdoses in the insulin therapy. Conclusions: diabetic ketoacidosis was the major complication. Mortality from diabetic ketoacidosis and hyperglycemic hyperosmolar nonketotic state was high and the mode of insulin administration was inadequate in some patients.

  20. Characterization of a microDiamond detector in high-dose-per-pulse electron beams for intra operative radiation therapy.

    Science.gov (United States)

    Di Venanzio, C; Marinelli, Marco; Tonnetti, A; Verona-Rinati, G; Falco, M D; Pimpinella, M; Ciccotelli, A; De Stefano, S; Felici, G; Marangoni, F

    2015-12-01

    To characterize a synthetic diamond dosimeter (PTW Freiburg microDiamond 60019) in high dose-per-pulse electron beams produced by an Intra Operative Radiation Therapy (IORT) dedicated accelerator. The dosimetric properties of the microDiamond were assessed under 6, 8 and 9 MeV electron beams by a NOVAC11 mobile accelerator (Sordina IORT Technologies S.p.A.). The characterization was carried out with dose-per-pulse ranging from 26 to 105 mGy per pulse. The microDiamond performance was compared with an Advanced Markus ionization chamber and a PTW silicon diode E in terms of dose linearity, percentage depth dose (PDD) curves, beam profiles and output factors. A good linearity of the microDiamond response was verified in the dose range from 0.2 Gy to 28 Gy. A sensitivity of 1.29 nC/Gy was measured under IORT electron beams, resulting within 1% with respect to the one obtained in reference condition under (60)Co gamma irradiation. PDD measurements were found in agreement with the ones by the reference dosimeters, with differences in R50 values below 0.3 mm. Profile measurements evidenced a high spatial resolution of the microDiamond, slightly worse than the one of the silicon diode. The penumbra widths measured by the microDiamond resulted approximately 0.5 mm larger than the ones by the Silicon diode. Output factors measured by the microDiamond were found within 2% with those obtained by the Advanced Markus down to 3 cm diameter field sizes. The microDiamond dosimeter was demonstrated to be suitable for precise dosimetry in IORT applications under high dose-per-pulse conditions. Copyright © 2015 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

  1. Short-Term Therapy with High Dose Atorvastatin in Patients with Coronary Artery Disease Can Reduce Inflammatory Process

    Directory of Open Access Journals (Sweden)

    Vida Nesar Hossein

    2010-08-01

    Full Text Available Coronary heart disease is the leading cause of death and disability in adults. The association between acute coronary syndrom (ACS and elevated serum high sensitivity c-reactive protein (hsCRP suggests that chronic inflammation of the coronary arterial wall may play an important role. A number of drugs used in the treatment of cardiovascular disease reduce serum CRP. It* is therefore possible that reduced inflammation contributes to the beneficial effects of these medications. This was a double blind randomized clinical trial on 52 patients were admitted because of ACS at the Mazandaran Heart Center, Iran in 2007. The patients were divided to three randomized groups which received 20, 40, 80* mg Atorvastatin daily for 6 months. At the time of study enrollment and 1, 3 and 6 months after initiation hsCRP were measured. 1 and 3 month after 20mg atorvastatin therapy the median serum concentration of hsCRP did not decrease significantly, but at the end of 6th month it was* significant difference. At 40mg dosage from 3th month to 6th month versus 1st month to 3th month it was significant decrease, at the end of 1th month and 3rd month it was not significant. At 80mg dose at the end of 1th month it was not significant but at the* end of 3th month and end of 6th month it was significant. Intensive lipid-lowering therapy with high-dose atorvastatin therapy relative to moderate lipid-lowering therapy with low-dose atorvastatin reduces hsCRP better. We found that treatment with greater dose of atorvastatin might decrease greater in plasma level of hsCRP.

  2. Small bowel toxicity after high dose spot scanning-based proton beam therapy for paraspinal/retroperitoneal neoplasms

    Energy Technology Data Exchange (ETDEWEB)

    Schneider, R.A.; Albertini, F.; Koch, T.; Ares, C.; Lomax, A.; Goitein, G. [Paul Scherrer Institute PSI, Villigen (Switzerland). Center for Proton Therapy; Vitolo, V. [Fondazione CNAO, Pavia (Italy); Hug, E.B. [Paul Scherrer Institute PSI, Villigen (Switzerland). Center for Proton Therapy; ProCure Proton Therapy Centers, New York, NY (United States)

    2013-12-15

    Purpose: Mesenchymal tumours require high-dose radiation therapy (RT). Small bowel (SB) dose constraints have historically limited dose delivery to paraspinal and retroperitoneal targets. This retrospective study correlated SB dose-volume histograms with side-effects after proton radiation therapy (PT). Patients and methods: Between 1997 and 2008, 31 patients (mean age 52.1 years) underwent spot scanning-based PT for paraspinal/retroperitoneal chordomas (81 %), sarcomas (16 %) and meningiom (3 %). Mean total prescribed dose was 72.3 Gy (relative biologic effectiveness, RBE) delivered in 1.8-2 Gy (RBE) fractions. Mean follow-up was 3.8 years. Based on the pretreatment planning CT, SB dose distributions were reanalysed. Results: Planning target volume (PTV) was defined as gross tumour volume (GTV) plus 5-7 mm margins. Mean PTV was 560.22 cm{sup 3}. A mean of 93.2 % of the PTV was covered by at least 90 % of the prescribed dose. SB volumes (cm{sup 3}) receiving doses of 5, 20, 30, 40, 50, 60, 70, 75 and 80 Gy (RBE) were calculated to give V5, V20, V30, V40, V50, V60, V70, V75 and V80 respectively. In 7/31 patients, PT was accomplished without any significant SB irradiation (V5 = 0). In 24/31 patients, mean maximum dose (Dmax) to SB was 64.1 Gy (RBE). Despite target doses of > 70 Gy (RBE), SB received > 50 and > 60 Gy (RBE) in only 61 and 54 % of patients, respectively. Mean SB volumes (cm{sup 3}) covered by different dose levels (Gy, RBE) were: V20 (n = 24): 45.1, V50 (n = 19): 17.7, V60 (n = 17): 7.6 and V70 (n = 12): 2.4. No acute toxicity {>=} grade 2 or late SB sequelae were observed. Conclusion: Small noncircumferential volumes of SB tolerated doses in excess of 60 Gy (RBE) without any clinically-significant late adverse effects. This small retrospective study has limited statistical power but encourages further efforts with higher patient numbers to define and establish high-dose threshold models for SB toxicity in modern radiation oncology. (orig.)

  3. Conventional external beam radiation therapy and high dose rate afterloading brachytherapy as a boost for patients older than 70 years

    International Nuclear Information System (INIS)

    Pellizzon, Antonio Cassio Assis; Salvajoli, Joao Vitor; Fogaroli, Ricardo Cesar; Novaes, Paulo Eduardo R.S.; Maia, Maria Aparecida Conte; Ferrigno, Robson

    2005-01-01

    The treatment options for patients with non metastatic prostate cancer range from observation, radical prostatectomy, radiation therapy, hormonal therapy to various combination of some to all of them. Objective: we evaluated the impact on biochemical control of disease (bNED), acute and late intestinal (GI) and urological (GU) morbidity for a group of patients older than 70 years presenting initial or locally advanced prostate cancer treated with fractionated high dose rate brachytherapy (HDRB) as a boost to conventional external beam radiation therapy (RT) at the Department of Radiation Oncology from Hospital do Cancer A. C. Camargo, Sao Paulo, Brazil. Methods: a total of 56 patients older than 70 were treated from March, 1997 to June, 2002. All patients had prior to HDRB a course of RT to a median dose of 45 Gy. HDRB doses ranged from 16 Gy to 20 Gy, given in 4 fractions. Results: the median age of the patients was 74.4 years (range 70-83) and the median follow-up 33 months (range 24 to 60). The 5-year actuarial bNED rate was 77%. Acute GU and GI morbidity G1-2 were seen in 17.8% and 7.1% of patients, respectively. Late G1 or G2 GU morbidity was seen in 10.7% of the patients, while late G3 morbidity was observed in 7.1% of the patients, represented by urethral strictures. Conclusion: this group of patients had similar bNED rates when compared to literature, with acceptable morbidity rates. (author)

  4. High-dose therapy and autologous transplantation for lymphoma: the Peter MacCallum Cancer institute experience

    International Nuclear Information System (INIS)

    Dowling, A.J.; Prince, H.M.; Wolf, M.; Januszewicz, H.; Seymour, J.F.; Gates, P.; Wirth, A.; Juneja, S.; Smith, J.G.

    2001-01-01

    High-dose therapy (HDT) with autologous bone marrow or blood cell transplantation for the treatment of lymphoma commenced at Peter MacCallum Cancer Institute in 1986. To examine the patient characteristics and outcomes of patients with non-Hodgkin's lymphoma (NHL) and Hodgkin's disease (HD) treated with HDT and autologous transplantation at our Institute in the first 10 years of the service (1986-95). A retrospective analysis was performed examining patient characteristics, prior chemotherapy regimens, pretransplant disease status, HDT regimen, source of stem cells, time for haematopoietic recovery, complications of transplantation, response rates, overall survival (OS) and progression-free survival (PFS). Sixty-seven patients with NHL were treated with an estimated 5-year OS rate of 44% (95% confidence interval (CI) 32-56%) and PFS rate of 34% (95% CI 21-44%). Factors independently predictive of an unfavourable PFS on multivariate analyses were presence of constitutional symptoms at transplant (P < 0.002) and chemotherapy-resistant disease at transplant (P= 0.02). Twenty-three patients with HD were treated with a 5-year predicted OS rate of 74% (95% CI 56-92%) and PFS rate of 57% (95% CI 36-77%).There was no difference in PFS for HD patients who relapsed either within 12 months of completion of front-line therapy or after this time (P =0.5). The transplant-related mortality for the entire cohort was 17%, with a progressive decrease over time. HDT with autologous transplantation achieves durable PFS and OS in patients with lymphoma. Improved patient selection, therapy modifications according to prognostic factors and ongoing improvements in supportive care should improve outcomes further

  5. ORIGINAL ARTICLES Barriers to initiating insulin therapy in patients ...

    African Journals Online (AJOL)

    Nicky

    opportunities for continuing medical education (CME) and poor patient ... related to insulin therapy, language barriers between doctor and patients, and fear of ..... of primary health care professionals regarding initiation of insulin in primary ...

  6. Perioperative single high dose ATG-Fresenius S administration as induction immunosuppressive therapy in cadaveric renal transplantation--preliminary results.

    Science.gov (United States)

    Samsel, R; Chmura, A; Włodarczyk, Z; Wyzgał, J; Cieciura, T; Lagiewska, B; Pliszczyński, J; Korczak, G; Lazowski, T; Paczek, L; Wałaszewski, J; Lao, M; Rowiński, W

    1999-01-01

    Monoclonal and polyclonal antilymphocyte antibodies have been used successfully in organ transplantation as induction therapy and in the treatment of acute graft rejection. Used for induction the medication is generally given for the first 7-10 days. The aim of this study was to assess the safety and efficacy of single high dose (9 mg/kg) ATG Fresenius S given perioperatively, before revascularization, to kidney allograft recipients. During last twelve months seventy six, first cadaveric kidney adult recipients were included into the study in two centers (center A-64, center B-12). All patients received triple drug immunosuppression (Neoral, steroids and Cellcept which was replaced by azathioprine after 4 months), and were randomized to receive ATG or not. The follow-up period ranged from 1 month up to 1 year. The preliminary results are very promising, the rejection rate in bolus group was significantly lower than in control. No significant side effects or serious adverse events in both groups were observed.

  7. Fluorouracil and high-dose leucovorin with radiotherapy as adjuvant therapy for rectal cancer. Results of a phase II study

    Energy Technology Data Exchange (ETDEWEB)

    Giralt, J. [Radiation Oncology Service, Hospital General Universitari Vall d`Hebron, Barcelona (Spain); Rubio, D. [Medical Oncology Service, Hospital General Universitari Vall d`Hebron, Barcelona (Spain); Maldonado, X. [Radiation Oncology Service, Hospital General Universitari Vall d`Hebron, Barcelona (Spain); Naval, J. [Dept. of Surgery, Hospital General Universitari Vall d`Hebron, Barcelona (Spain); Casado, S. [Medical Oncology Service, Hospital General Universitari Vall d`Hebron, Barcelona (Spain); Lara, F. [Dept. of Surgery, Hospital General Universitari Vall d`Hebron, Barcelona (Spain); Rosello, J.M. [Dept. of Preventive Medicine, Hospital General Universitari Vall d`Hebron, Barcelona (Spain); Armengol, M. [Dept. of Surgery, Hospital General Universitari Vall d`Hebron, Barcelona (Spain)

    1997-07-01

    The purpose of this phase II study was to evaluate the efficacy and toxicity of fluorouracil and high-dose leucovorin (5-FU/LV) with pelvic irradiation as adjuvant therapy for patients with macroscopical resected rectal or recto-sigmoid cancer. Following surgery for stages II-III primary (52) or recurrent rectal cancer (4), 56 patients received 8 cycles of 5-FU/LV and pelvic irradiation. 5-FU doses were 200 mgr/m{sup 2} for cycles 2-3 and 300 mgr/m{sup 2} for cycles 1 and 4-8. LV doses remained fixed at 200 mgr/m{sup 2}. Pelvic radiation was started in the third week, between the first and second cycle. The total dose was 50.4 Gy. No serve complications had been recorded. The incidence of grade 3 diarrhea was 19%. Three patients presented leukopenia grade 3 (5%). In 44 patients (78%) the planned treatment could be administered. The median follow-up was 40 months (range 22-66). Seven patients had a local relapse (13%) and 6 developed distant metastasis (10%). The 3-year disease-free survival was 72% and the overall survival was 76%. These preliminary results show that combined post-operative 5-FU/LV and pelvic radiotherapy are well tolerated and present a reasonable local control and survival rates. This adjuvant treatment should be evaluated in randomized trials. (orig.).

  8. Prostate-specific antigen bounce after high-dose rate brachytherapy with external beam radiation therapy for prostate cancer patients

    International Nuclear Information System (INIS)

    Sakamoto, Naotaka; Kakinoki, Hiroaki; Tsutsui, Akio; Yoshikawa, Masahiro; Iguchi, Atsushi; Matsunobu, Toru; Uehara, Satoru

    2008-01-01

    Prostate-specific antigen (PSA) bounce after high-dose rate (HDR) brachytherapy with external beam radiation therapy (EBRT) for prostate cancer patients was evaluated. Sixty-one patients treated with HDR-brachytherapy followed by EBRT had a minimum follow-up of 12 months (median, 24 months) in our institute. A PSA bounce was defined as a rise of at least 0.1 ng/ml greater than a previous PSA level, with a subsequent decline equal to, or less than, the initial nadir. A PSA bounce was noted in 16 (26.2%) of 61 patients (one patient had a PSA bounce twice). Median time to develop a PSA bounce was 18 months, but 23.5% developed a PSA bounce after 24 months. Median duration of PSA bounce was 6 months and 11.8% had increased PSA within a period of 12 months. Median bounce height was 0.2 ng/ml (range, 0.1 to 3.39 ng/ml). A bounce height of gerater than 2 ng/ml was seen in 11.8%. Clinical characteristics (age, prostate volume, neoadjuvant endocrine therapy, risk classification, stage, pretreatment PSA, Gleason score) do not predict whether or not there will be a PSA bounce. In patients treated with HDR-brachytherapy followed by EBRT, the incidence and characteristics of PSA bounce were similar to those in patients treated with low-dose rate brachytherapy. Physicians should be aware of the possibility of PSA bounce following HDR-brachytherapy with EBRT. (author)

  9. High-dose radiation therapy alone for inoperable non-small cell lung cancer. Experience with prolonged overall treatment times

    International Nuclear Information System (INIS)

    Willers, H.; Wuerschmidt, F.; Buenemann, H.; Heilmann, H.P.

    1998-01-01

    The purpose of this study was to determine the impact of overall treatment time on long-term survival after high-dose radiation therapy alone for inoperable non-small cell lung cancer (NSCLC). Between 1978 and 1990, 229 patients with stage I-III disease and Karnofsky Performance Scores of 80-100 received a conventionally fractionated total dose of 70 Gy through a split-course technique. After a first treatment course of 40 or 50 Gy, a rest aging was performed and only patients without any contraindications, such as newly diagnosed distant metastases or serious deterioration of performance status, were given a second course. In 83% of patients this break lasted for 4-6 weeks. Overall treatment time ranged between 7 and 24 weeks (median 12 weeks). Median follow-up time was 6.6 years (range 4.0-9.3 years). Actuarial overall survival rates at 2 and 5 years were 28% and 7% respectively. Complete radiological tumor response was observed in 31% of patients, and was found to be the strongest positive predictor of survival with 2- and 5-year rates of 50% and 12% respectively compared with 17% and 4% for patients without complete response. Treatment duration was not found to be a significant prognostic factor in univariate or multivariate analysis. For overall treatment times of 7-11 weeks (n=50), 12 weeks (n=79) and >12 weeks (n=100), 5-year survival was 4%, 6%, and 8%, respectively (p=0.6). To conclude, in our experience and in contrast to other studies, prolonged overall treatment times in radiation therapy alone for inoperable NSCLC had no negative impact on long-term survival. It is hypothesized that accelerated tumor cell repopulation is absent in a significant number of these patients with the time-factor playing no apparent role for outcome of treatment. (orig.)

  10. High-dose intensity modulated radiation therapy for prostate cancer: early toxicity and biochemical outcome in 772 patients

    International Nuclear Information System (INIS)

    Zelefsky, Michael J.; Fuks, Zvi; Hunt, Margie; Yamada, Yoshiya; Marion, Christine; Ling, C. Clifton; Amols, Howard; Venkatraman, E.S.; Leibel, Steven A.

    2002-01-01

    Purpose: To report the acute and late toxicity and preliminary biochemical outcomes in 772 patients with clinically localized prostate cancer treated with high-dose intensity-modulated radiotherapy (IMRT). Methods and Materials: Between April 1996 and January 2001, 772 patients with clinically localized prostate cancer were treated with IMRT. Treatment was planned using an inverse-planning approach, and the desired beam intensity profiles were delivered by dynamic multileaf collimation. A total of 698 patients (90%) were treated to 81.0 Gy, and 74 patients (10%) were treated to 86.4 Gy. Acute and late toxicities were scored by the Radiation Therapy Oncology Group morbidity grading scales. PSA relapse was defined according to The American Society of Therapeutic Radiation Oncology Consensus Statement. The median follow-up time was 24 months (range: 6-60 months). Results: Thirty-five patients (4.5%) developed acute Grade 2 rectal toxicity, and no patient experienced acute Grade 3 or higher rectal symptoms. Two hundred seventeen patients (28%) developed acute Grade 2 urinary symptoms, and one experienced urinary retention (Grade 3). Eleven patients (1.5%) developed late Grade 2 rectal bleeding. Four patients (0.1%) experienced Grade 3 rectal toxicity requiring either one or more transfusions or a laser cauterization procedure. No Grade 4 rectal complications have been observed. The 3-year actuarial likelihood of ≥ late Grade 2 rectal toxicity was 4%. Seventy-two patients (9%) experienced late Grade 2 urinary toxicity, and five (0.5%) developed Grade 3 urinary toxicity (urethral stricture). The 3-year actuarial likelihood of ≥ late Grade 2 urinary toxicity was 15%. The 3-year actuarial PSA relapse-free survival rates for favorable, intermediate, and unfavorable risk group patients were 92%, 86%, and 81%, respectively. Conclusions: These data demonstrate the feasibility of high-dose IMRT in a large number of patients. Acute and late rectal toxicities seem to be

  11. Radical surgical resection and high-dose intraoperative radiation therapy (HDR-IORT) in patients with recurrent gynecologic cancers

    International Nuclear Information System (INIS)

    Gemignani, Mary L.; Alektiar, Kaled M.; Leitao, Mario; Mychalczak, Boris; Chi, Dennis; Venkatraman, Ennapadam; Barakat, Richard R.; Curtin, John P.

    2001-01-01

    Objective: To determine the outcome for patients with recurrent gynecologic tumors treated with radical resection and combined high-dose intraoperative radiation therapy (HDR-IORT). Methods and Materials: Between November 1993 and June 1998, 17 patients with recurrent gynecologic malignancies underwent radical surgical resection and high-dose-rate brachytherapy. The mean age of the study group was 49 years (range 28-72 years). The site of the primary tumor was the cervix in 9 (53%) patients, the uterus in 7 (41%) patients, and the vagina in 1 (6%) patient. The treatment for the primary disease was surgery with or without adjuvant radiation in 14 (82%) patients and definitive radiation in 3 (18%) patients. The current surgery consisted of exenterative surgery in 10 (59%) patients and tumor resection in 7 (41%) patients. Complete gross resection was achieved in 13 (76%) patients. The mean HDR-IORT dose was 14 Gy (range 12-15). Additional radiation in the form of permanent Iodine-125 implant was given to 3 of 4 patients with gross residual disease. The median peripheral dose was 140 Gy. Results: With a median follow-up of 20 months (range 3-65 months), the 3-year actuarial local control (LC) rate was 67%. In patients with complete gross resection, the 3-year LC rate was 83%, compared to 25% in patients with gross residual disease, p<0.01. The 3-year distant metastasis disease-free and overall survival rates were 54% and 54%, respectively. The complications were as follows: gastrointestinal obstruction, 4 (24%); wound complications, 4 (24%); abscesses, 3 (18%); peripheral neuropathy, 3 (18%); rectovaginal fistula, 2 (12%); and ureteral obstruction, 2 (12%). Conclusion: Radical surgical resection and combined IORT for patients with recurrent gynecologic tumors seems to provide a reasonable local-control rate in patients who have failed prior surgery and/or definitive radiation. Patient selection is very important, however, as only those patients with complete gross

  12. High-dose estrogen as salvage hormonal therapy for highly refractory metastatic breast cancer: a retrospective chart review.

    Science.gov (United States)

    Mahtani, Reshma L; Stein, Alisha; Vogel, Charles L

    2009-01-01

    High-dose estrogens (HDEs) are an efficacious but widely overlooked treatment option for patients with metastatic breast cancer (MBC). This is due in part to the introduction of tamoxifen in the 1970s, which was proven to be equivalent in efficacy and associated with fewer adverse events (AEs). The aim of this study was to report our experience with the use of HDE in postmenopausal women with advanced breast cancer. Local institutional review board approval was obtained to conduct a retrospective chart review of patients with MBC treated with HDEs at the Boca Raton Comprehensive Cancer Center, Boca Raton, Florida, from 2001 through March 2009. Demographic information, response rates, and tolerability profiles were collected. Of the 426 patients with MBC identified, we found 26 patients with MBC who were prescribed HDEs as a treatment in any line of therapy for advanced breast cancer. The median age at the start of HDE therapy was 59 years (range, 42-92 years). Three of the 26 patients (11.5%) were human epidermal growth factor receptor 2-positive determined via fluorescent in situ hybridization analysis. With the exception of 1 patient who had received no prior systemic treatment for metastatic disease, all patients received multiple lines of treatment (both chemotherapy and hormonal treatments) in the advanced setting (median, 7 lines; range, 0-12) prior to the initiation of HDE. Five of 20 patients (25%) with measurable metastatic disease (visceral and/or soft tissue metastases) had objective antitumor responses defined as either a partial response (PR) or a complete response (CR). Four additional patients (20%) had prolonged stable disease (SD) for > or =6 months. Three of 6 patients (50%) with nonmeasurable metastatic disease (bone-only) had prolonged SD for > or =6 months. Clinical benefit rate (defined as CR + PR + SD > or =6 months) for all patients was 46% (12/26), with a median duration of 10 months. Overall median progression-free survival for the 26

  13. Intensive insulin therapy improves insulin sensitivity and mitochondrial function in severely burned children.

    Science.gov (United States)

    Fram, Ricki Y; Cree, Melanie G; Wolfe, Robert R; Mlcak, Ronald P; Qian, Ting; Chinkes, David L; Herndon, David N

    2010-06-01

    To institute intensive insulin therapy protocol in an acute pediatric burn unit and study the mechanisms underlying its benefits. Prospective, randomized study. An acute pediatric burn unit in a tertiary teaching hospital. Children, 4-18 yrs old, with total body surface area burned > or =40% and who arrived within 1 wk after injury were enrolled in the study. Patients were randomized to one of two groups. Intensive insulin therapy maintained blood glucose levels between 80 and 110 mg/dL. Conventional insulin therapy maintained blood glucose patients were included in the data analysis consisting of resting energy expenditure, whole body and liver insulin sensitivity, and skeletal muscle mitochondrial function. Studies were performed at 7 days postburn (pretreatment) and at 21 days postburn (posttreatment). Resting energy expenditure significantly increased posttreatment (1476 +/- 124 to 1925 +/- 291 kcal/m(2) x day; p = .02) in conventional insulin therapy as compared with a decline in intensive insulin therapy. Glucose infusion rate was identical between groups before treatment (6.0 +/- 0.8 conventional insulin therapy vs. 6.8 +/- 0.9 mg/kg x min intensive insulin therapy; p = .5). Intensive insulin therapy displayed a significantly higher glucose clamp infusion rate posttreatment (9.1 +/- 1.3 intensive insulin therapy versus 4.8 +/- 0.6 mg/kg x min conventional insulin therapy, p = .005). Suppression of hepatic glucose release was significantly greater in the intensive insulin therapy after treatment compared with conventional insulin therapy (5.0 +/- 0.9 vs. 2.5 +/- 0.6 mg/kg x min; intensive insulin therapy vs. conventional insulin therapy; p = .03). States 3 and 4 mitochondrial oxidation of palmitate significantly improved in intensive insulin therapy (0.9 +/- 0.1 to 1.7 +/- 0.1 microm O(2)/CS/mg protein/min for state 3, p = .004; and 0.7 +/- 0.1 to 1.3 +/- 0.1 microm O(2)/CS/mg protein/min for state 4, p protocol improves insulin sensitivity and mitochondrial

  14. Preliminary results of concurrent chemotherapy and radiation therapy using high-dose-rate brachytherapy for cervical cancer

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Kyung Ja; Lee, Ji Hye; Lee, Re Na; Suh, Hyun Suk [Ewha Womans University College of Medicine, Seoul (Korea, Republic of)

    2006-09-15

    To determine the efficacy and safety of concurrent chemotherapy and radiation therapy with high-dose-rate brachytherapy for cervical cancer. From January 2001 to December 2002, 30 patients with cervical cancer were treated with concurrent chemotherapy (cisplatin and 5-FU) and definitive radiation therapy. The median age was 58 (range 34 {approx} 74) year old. The pathology of the biopsy sections was squamous cell carcinoma in 29 patients and one was adenocarcinoma. The distribution to FIGO staging system was as follow: stage IB, 7 (23%); IIA, 3 (10%); IIB, 12 (40%); IIIA, 3 (10%); IIIB, 5 (17%). All patients received pelvic external beam irradiation (EBRT) to a total dose of 45 {approx} 50.4 Gy (median: 50.4 Gy) over 5 {approx} 5.5 weeks. Ir-192 HDR intracavity brachytherapy (ICBT) was given after a total dose of 41.1 Gy. HDR-ICBT was performed twice a week, with a fraction point. A dose of 4 Gy and median dose to point A was 28 Gy (range: 16 {approx} 32 Gy) in 7 fractions. The median cumulative biologic effective dose (BED) at point A (EBRT + ICBT) was 88 Gy{sub 10} (range:77 {approx} 94 Gy{sub 10}). The median cumulative BED at ICRU 38 reference point (EBRT + ICBT) was 131 Gy{sub 3} (range: 122 {approx} 140 Gy{sub 3}) at point A, 109 Gy{sub 3} (range:88{approx} 125 Gy{sub 3}) at the rectum and 111 Gy{sub 3} (range: 91 {approx} 123 Gy{sub 3}) at the urinary bladder. Cisplatin (60 mg/m{sup 2}) and 5-FU (1,000 mg/m{sup 2}) was administered intravenously at 2 weeks interval from the first day of radiation for median 5 (range:2 {approx} 6) cycles. The assessment was performed at 1 month after completion of radiation therapy by clinical examination and CT scan. The median follow-up time was 36 months (range:8{approx} 50 months). The complete response rate after concurrent chemo radiation therapy was 93.3%. The 3-yr actuarial pelvic control rate was 87% and 3-yr actuarial overall survival and disease-free survival rate was 93% and 87%, respectively. The local failure

  15. Preliminary results of concurrent chemotherapy and radiation therapy using high-dose-rate brachytherapy for cervical cancer

    International Nuclear Information System (INIS)

    Lee, Kyung Ja; Lee, Ji Hye; Lee, Re Na; Suh, Hyun Suk

    2006-01-01

    To determine the efficacy and safety of concurrent chemotherapy and radiation therapy with high-dose-rate brachytherapy for cervical cancer. From January 2001 to December 2002, 30 patients with cervical cancer were treated with concurrent chemotherapy (cisplatin and 5-FU) and definitive radiation therapy. The median age was 58 (range 34 ∼ 74) year old. The pathology of the biopsy sections was squamous cell carcinoma in 29 patients and one was adenocarcinoma. The distribution to FIGO staging system was as follow: stage IB, 7 (23%); IIA, 3 (10%); IIB, 12 (40%); IIIA, 3 (10%); IIIB, 5 (17%). All patients received pelvic external beam irradiation (EBRT) to a total dose of 45 ∼ 50.4 Gy (median: 50.4 Gy) over 5 ∼ 5.5 weeks. Ir-192 HDR intracavity brachytherapy (ICBT) was given after a total dose of 41.1 Gy. HDR-ICBT was performed twice a week, with a fraction point. A dose of 4 Gy and median dose to point A was 28 Gy (range: 16 ∼ 32 Gy) in 7 fractions. The median cumulative biologic effective dose (BED) at point A (EBRT + ICBT) was 88 Gy 10 (range:77 ∼ 94 Gy 10 ). The median cumulative BED at ICRU 38 reference point (EBRT + ICBT) was 131 Gy 3 (range: 122 ∼ 140 Gy 3 ) at point A, 109 Gy 3 (range:88∼ 125 Gy 3 ) at the rectum and 111 Gy 3 (range: 91 ∼ 123 Gy 3 ) at the urinary bladder. Cisplatin (60 mg/m 2 ) and 5-FU (1,000 mg/m 2 ) was administered intravenously at 2 weeks interval from the first day of radiation for median 5 (range:2 ∼ 6) cycles. The assessment was performed at 1 month after completion of radiation therapy by clinical examination and CT scan. The median follow-up time was 36 months (range:8∼ 50 months). The complete response rate after concurrent chemo radiation therapy was 93.3%. The 3-yr actuarial pelvic control rate was 87% and 3-yr actuarial overall survival and disease-free survival rate was 93% and 87%, respectively. The local failure rate was 13% and distant metastatic rate was 3.3%. The crude rate of minor hematologic

  16. Clinical Usefulness between High Dose Radioiodine Therapy and Helicobacter Pylori Infection after Total Thyroidectomy due to Well Differentiated Thyroid Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Yun, Kuk No; Lim, Seok Tae; Moon, Eun Ha; Kim, Jin Suk; Jeong, Young Jin; Kim, Dong Wook; Jeong, Hwan Jeong; Sohn, Myung Hee [Chonbuk National University Medical School and Hospital, Jeonju (Korea, Republic of)

    2009-12-15

    Helicobacter (H) pylori infection has been considered the most important cause of gastritis, dyspepsia, and gastroduodenal ulcer. Radioiodine can be accumulated in the remaining thyroid tissue, salivary gland, and stomach. We investigated if the high radiation induced by radioiodine in the stomach after high dose radioiodine therapy (HD-RIT) is effective in the eradication of H. pylori infection. One hundred ninety nine patients (M:F=33:166, age 46.7{+-}12.3 years) who had HD-RIT (dose 159.1{+-}25.9 mCi, range 120-250 mCi) after thyroidectomy due to well differentiated thyroid cancer were enrolled. To detect H. pylori infection, the urea breath tests (UBT) were performed at 1 hour before HD-RIT and at 4 weeks after HD-RIT. The results of UBT were classified as positive ({>=}50 dpm) or negative (<50 dpm), and analyzed its values. Of 199 patients, 103 (51.8%) patients had positive UBT before HD-RIT. Of these, 80 patients had follow-up UBT after HD-RIT. Among them, 76 (95.0%) patients had persistent positive UBT and only 4 (5.0%) patients were changed negative UBT. Among 76 patients with persistent positive UBT, 26 (34.2%) patients had increased the values of follow-up UBT, 49 (64.5%) had decreased them, and 1 (1.3%) had shown the same value. The different values of UBT between before and after HD-RIT were 62{+-}66.1 dpm in increased one of follow-up UBT, and 153.3{+-}157.1 dpm in decreased one of follow-up UBT. We conclude that the radiation induced by HD-RIT is ineffective in the eradication of H. pylori infection. However, it could be influential the degree or distribution of H. pylori infection.

  17. Clinical Usefulness between High Dose Radioiodine Therapy and Helicobacter Pylori Infection after Total Thyroidectomy due to Well Differentiated Thyroid Cancer

    International Nuclear Information System (INIS)

    Yun, Kuk No; Lim, Seok Tae; Moon, Eun Ha; Kim, Jin Suk; Jeong, Young Jin; Kim, Dong Wook; Jeong, Hwan Jeong; Sohn, Myung Hee

    2009-01-01

    Helicobacter (H) pylori infection has been considered the most important cause of gastritis, dyspepsia, and gastroduodenal ulcer. Radioiodine can be accumulated in the remaining thyroid tissue, salivary gland, and stomach. We investigated if the high radiation induced by radioiodine in the stomach after high dose radioiodine therapy (HD-RIT) is effective in the eradication of H. pylori infection. One hundred ninety nine patients (M:F=33:166, age 46.7±12.3 years) who had HD-RIT (dose 159.1±25.9 mCi, range 120-250 mCi) after thyroidectomy due to well differentiated thyroid cancer were enrolled. To detect H. pylori infection, the urea breath tests (UBT) were performed at 1 hour before HD-RIT and at 4 weeks after HD-RIT. The results of UBT were classified as positive (≥50 dpm) or negative (<50 dpm), and analyzed its values. Of 199 patients, 103 (51.8%) patients had positive UBT before HD-RIT. Of these, 80 patients had follow-up UBT after HD-RIT. Among them, 76 (95.0%) patients had persistent positive UBT and only 4 (5.0%) patients were changed negative UBT. Among 76 patients with persistent positive UBT, 26 (34.2%) patients had increased the values of follow-up UBT, 49 (64.5%) had decreased them, and 1 (1.3%) had shown the same value. The different values of UBT between before and after HD-RIT were 62±66.1 dpm in increased one of follow-up UBT, and 153.3±157.1 dpm in decreased one of follow-up UBT. We conclude that the radiation induced by HD-RIT is ineffective in the eradication of H. pylori infection. However, it could be influential the degree or distribution of H. pylori infection

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

    Science.gov (United States)

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

    2013-12-01

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

  19. Design of insulin analogues for meal-related therapy.

    Science.gov (United States)

    Brange, J

    1993-01-01

    The human insulin in replacement therapy has a hexameric structure. Hexamerization of the insulin molecule facilitates biosynthesis and beta-cell storage of insulin, but is unnecessary for biologic activity and appears to contribute to delayed absorption of exogenous insulin from the subcutis. Insulin analogues with reduced self-association that are produced through recombinant DNA techniques have been shown to have in vivo activity comparable to that of human insulin and absorption kinetics characterized by higher and more constant rates of disappearance from the subcutaneous injection site. In preliminary studies in patients receiving insulin therapy, monomeric insulin analogues have been found to provide glycemic control in the postprandial period that is at least equivalent to that of human insulin. Findings in these studies suggest that the use of such analogues may provide meal-related insulin effects closer to those observed in the physiologic state by limiting excessive postprandial glucose excursions and decreasing the risk of late hypoglycemia. Banting and Best revolutionized diabetes therapy 70 years ago with the extraction of insulin from animal pancreas glands (J Lab Clin Med 7:464-472, 1922). Since that time, many refinements of the therapeutic properties of pharmaceutical preparations of the hormone have been introduced. Until recently, however, such advances have been limited to improvements in insulin purity, insulin species, and adjustment of the composition of the vehicle with respect to auxiliary substances and other additives. With the advent of recombinant DNA techniques, it has become possible to optimize the insulin molecule itself for purposes of replacement therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

  20. [Continuous insulin therapy versus multiple insulin injections in the management of type 1 diabetes: a longitutinal study].

    Science.gov (United States)

    Ribeiro, Maria Estela Bellini; Del Roio Liberatore Junior, Raphael; Custodio, Rodrigo; Martinelli Junior, Carlos Eduardo

    2016-01-01

    To compare multiple doses of insulin and continuous insulin infusion therapy as treatment for type 1 diabetes melito. 40 patients with type 1 diabetes melito (21 female) with ages between 10 and 20 years (mean=14.2) and mean duration of diabetes of 7 years used multiple doses of insulin for at least 6 months and after that, continuous insulin infusion therapy for at least 6 months. Each one of the patients has used multiple doses of insulin and continuous insulin infusion therapy. For analysis of HbA1c, mean glycated hemoglobin levels (mHbA1c) were obtained during each treatment period (multiple doses of insulin and continuous insulin infusion therapy period). Although mHbA1c levels were lower during continuous insulin infusion therapy the difference was not statistically significant. During multiple doses of insulin, 14.2% had mHbA1c values below 7.5% vs. 35.71% while on continuous insulin infusion therapy; demonstrating better glycemic control with the use of continuous insulin infusion therapy. During multiple doses of insulin, 15-40 patients have severe hypoglycemic events versus 5-40 continuous insulin infusion therapy. No episodes of ketoacidosis events were recorded. This is the first study with this design comparing multiple doses of insulin and continuous insulin infusion therapy in Brazil showing no significant difference in HbA1c; hypoglycemic events were less frequent during continuous insulin infusion therapy than during multiple doses of insulin and the percentage of patients who achieved a HbA1c less than 7.5% was greater during continuous insulin infusion therapy than multiple doses of insulin therapy. Copyright © 2015 Sociedade de Pediatria de São Paulo. Publicado por Elsevier Editora Ltda. All rights reserved.

  1. Effects of medical therapy on insulin resistance and the cardiovascular system in polycystic ovary syndrome.

    Science.gov (United States)

    Meyer, Caroline; McGrath, Barry P; Teede, Helena Jane

    2007-03-01

    We aimed to determine the impact of medical therapy for symptom management on insulin resistance, metabolic profiles, and surrogate markers of cardiovascular disease in polycystic ovary syndrome (PCOS), an insulin-resistant pre-diabetes condition. One hundred overweight women (BMI >27 kg/m2), average age 31 years, who were nonsmokers, were not pregnant, did not have diabetes, and were off relevant medications for 3 months completed this 6-month open-label controlled trial. Randomization was to a control group (higher-dose oral contraceptive [OCP] 35 microg ethinyl estradiol [EE]/2 mg cyproterone acetate, metformin [1 g b.d.] or low-dose OCP [20 microg EE/100 microg levonorgestrel + aldactone 50 mg b.d.]). Primary outcome measures were insulin resistance (area under curve on oral glucose tolerance test) and surrogate markers of cardiovascular disease including arterial stiffness (pulse wave velocity [PWV]) and endothelial function. All treatments similarly and significantly improved symptoms including hirsutism and menstrual cycle length. Insulin resistance was improved by metformin and worsened by the high-dose OCP. Arterial stiffness worsened in the higher-dose OCP group (PWV 7.46 vs. 8.03 m/s, P insulin resistance. In overweight women with PCOS, metformin and low- and high-dose OCP preparations have similar efficacy but differential effects on insulin resistance and arterial function. These findings suggest that a low-dose OCP preparation may be preferable if contraception is needed and that metformin should be considered for symptomatic management, particularly in women with additional metabolic and cardiovascular risk factors.

  2. Insulin and insulin-like growth factor-1 increased in preterm neonates following massage therapy.

    Science.gov (United States)

    Field, Tiffany; Diego, Miguel; Hernandez-Reif, Maria; Dieter, John N I; Kumar, Adarsh M; Schanberg, Saul; Kuhn, Cynthia

    2008-12-01

    To determine if massage therapy increased serum insulin and insulin-like growth factor-1 (IGF-1) in preterm neonates. Forty-two preterm neonates who averaged 34.6 weeks (M = 29.5 wk gestational age; M birth weight = 1237 g) and were in the "grower" (step-down) nursery were randomly assigned to a massage therapy group (body stroking and passive limb movements for three, 15-minute periods per day for 5 days) or a control group that received the standard nursery care without massage therapy. On Days 1 and 5, the serum collected by clinical heelsticks was also assayed for insulin and IGF-1, and weight gain and kilocalories consumed were recorded daily. Despite similar formula intake, the massaged preterm neonates showed greater increases during the 5-day period in (1) weight gain; (2) serum levels of insulin; and (3) IGF-1. Increased weight gain was significantly correlated with insulin and IGF-1. Previous data suggested that preterm infant weight gain following massage therapy related to increased vagal activity, which suggests decreased stress and gastric motility, which may contribute to more efficient food absorption. The data from this study suggest for the first time that weight gain was also related to increased serum insulin and IGF-1 levels following massage therapy. Preterm infants who received massage therapy not only showed greater weight gain but also a greater increase in serum insulin and IGF-1 levels, suggesting that massage therapy might be prescribed for all growing neonates.

  3. Chapter 10: Glucose control: insulin therapy*

    African Journals Online (AJOL)

    Insulin and its analogues lower blood glucose by stimulating peripheral glucose uptake, especially by skeletal muscle and fat, and by inhibiting hepatic glucose production. Insulin inhibits ... control on 2 or 3 oral glucose lowering drugs.

  4. [Comparison between basal insulin glargine and NPH insulin in patients with diabetes type 1 on conventional intensive insulin therapy].

    Science.gov (United States)

    Pesić, Milica; Zivić, Sasa; Radenković, Sasa; Velojić, Milena; Dimić, Dragan; Antić, Slobodan

    2007-04-01

    Insulin glargine is a long-acting insulin analog that mimics normal basal insulin secretion without pronounced peaks. The aim of this study was to compare insulin glargine with isophane insulin (NPH insulin) for basal insulin supply in patients with type 1 diabetes. A total of 48 type 1 diabetics on long term conventional intensive insulin therapy (IT) were randomized to three different regimens of basal insulin substitution: 1. continuation of NPH insulin once daily at bedtime with more intensive selfmonitoring (n = 15); 2. NPH insulin twice daily (n = 15); 3. insulin glargine once daily (n = 18). Meal time insulin aspart was continued in all groups. Fasting blood glucose (FBG) was lower in the glargine group (7.30+/-0.98 mmol/1) than in the twice daily NPH group (7.47+/-1.06 mmol/1), but without significant difference. FBG was significantly higher in the once daily NPH group (8.44+/-0.85 mmol/l; p < 0.05). HbAlc after 3 months did not change in the once daily NPH group, but decreased in the glargine group (from 7.72+/-0.86% to 6.87+/-0.50%), as well as in the twice daily NPH group (from 7.80+/-0.83% to 7.01+/-0.63%). Total daily insulin doses were similar in all groups but only in the glargine group there was an increase of basal and decrease of meal related insulin doses. The frequency of mild hypoglycemia was significantly lower in the glargine group (6.56+/-2.09) than in both NPH groups (9.0+/-1.65 in twice daily NPH group and 8.13+/-1.30 in other NPH group) (episodes/patients-month, p < 0.05). Basal insulin supplementation in type 1 diabetes mellitus with either twice daily NPH insulin or glargine can result in similar glycemic control when combined with meal time insulin aspart. However, with glargine regimen FBG, HbAlc and frequency of hypoglycemic event are lower. These facts contribute to better patients satisfaction with insulin glargine versus NPH insulin in IIT in type 1 diabetics.

  5. Comparison between basal insulin glargine and NPH insulin in patients with diabetes type 1 on conventional intensive insulin therapy

    Directory of Open Access Journals (Sweden)

    Pešić Milica

    2007-01-01

    Full Text Available Background/Aim. Insulin glargine is a long-acting insulin analog that mimics normal basal insulin secretion without pronounced peaks. The aim of this study was to compare insulin glargine with isophane insulin (NPH insulin for basal insulin supply in patients with type 1 diabetes. Methods. A total of 48 type 1 diabetics on long term conventional intensive insulin therapy (IIT were randomized to three different regimens of basal insulin substitution: 1. continuation of NPH insulin once daily at bedtime with more intensive selfmonitoring (n = 15; 2. NPH insulin twice daily (n = 15; 3. insulin glargine once daily (n = 18. Meal time insulin aspart was continued in all groups. Results. Fasting blood glucose (FBG was lower in the glargine group (7.30±0.98 mmol/l than in the twice daily NPH group (7.47±1.06 mmol/l, but without significant difference. FBG was significantly higher in the once daily NPH group (8.44±0.85 mmol/l; p < 0.05. HbA1c after 3 months did not change in the once daily NPH group, but decreased in the glargine group (from 7.72±0.86% to 6.87±0.50%, as well as in the twice daily NPH group (from 7.80±0.83% to 7.01±0.63%. Total daily insulin doses were similar in all groups but only in the glargine group there was an increase of basal and decrease of meal related insulin doses. The frequency of mild hypoglycemia was significantly lower in the glargine group (6.56±2.09 than in both NPH groups (9.0±1.65 in twice daily NPH group and 8.13±1.30 in other NPH group (episodes/patients-month, p < 0.05. Conclusion. Basal insulin supplementation in type 1 diabetes mellitus with either twice daily NPH insulin or glargine can result in similar glycemic control when combined with meal time insulin aspart. However, with glargine regimen FBG, HbA1c and frequency of hypoglycemic event are lower. These facts contribute to better patients satisfaction with insulin glargine versus NPH insulin in IIT in type 1 diabetics.

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

    Directory of Open Access Journals (Sweden)

    Tahereh Safari

    2015-01-01

    Full Text Available 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.

  7. Low dose versus high dose anti-snake venom therapy in the treatment of haematotoxic snake bite in South India.

    Science.gov (United States)

    Joseph, Imanto M; Kuriakose, Cijoy K; Dev, Anand Vimal; Philip, George A

    2017-10-01

    Most of the studies on the appropriate dose of anti-snake venom (ASV) are from tertiary hospitals and the guidelines are unclear. Our observational study compared the outcomes of two prevalent treatment regimes for haematotoxic snake bite in a secondary care hospital in South India. The time to normalisation of whole blood clotting time, mortality and complications were not different between the groups. The average dose of ASV required in the low and high dose groups were 106 mL and 246 mL, respectively. Consequently, patients who received low dose ASV incurred approximately 50% less expense. Urticarial rashes were also significantly fewer in the low dose group.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1982-12-01

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

  9. Comparison of fixed low dose versus high dose radioactive iodine for the treatment of hyperthyroidism: retrospective multifactorial analysis impacting the outcome of therapy

    International Nuclear Information System (INIS)

    Suresh Kumar, A.C.; Malhotra, G.; Basu, S.; Asopa, R.V.

    2010-01-01

    Full text: Radioactive iodine ( 131 I) as a fixed dose protocol is widely used for treatment of hyperthyroidism. However, there is no consensus on the best optimum dose for an individual patient. The objectives of this study were to observe the outcome of 131 I therapy in patients of primary hyperthyroidism in relation to fixed low dose versus high dose regimen, impact of antithyroid drugs and influence of thyroid gland size on therapy outcome. Materials and Methods: Study design: Retrospective analysis. Study group included 287 diagnosed patients of primary hyperthyroidism who had undergone 131 I therapy for the first time (68 M, 219 F; Mean age ± S.D.: 43.84 ± 12.53). All patients with low RAIU, thyrocardiac disease were excluded. Details of antithyroid (ATD) drug treatment were recorded. Analysis was done from 2002 till patients became euthyroid/hypothyroid or until January 2010. Each patient's response was evaluated initially at 6 weeks and thereafter every three months. Appropriate statistical tests were applied to compare treatment response between the groups. A P value<0.05 was considered significant. Results: Of 287 patients, 209 patients had been administered low dose (Mean ± S.D.: 4.68 ± 0.62 mCi) while 78 patients had received high dose (Mean ± S.D.: 9.15 ± 1.05 mCi) of radioiodine. 57.9% (121/ 209) patients in the low dose group responded as compared to 75.6% (59/78) in high dose group after a follow up of more than 36 months. Similarly, among patients with and without antithyroid drug treatment, grade II and above goiters the response rates were significantly higher for high dose group as compared to low dose group. Conclusion: We suggest that high dose radioiodine treatment with 8 to 10 mCi is effective in treating hyperthyroidism in patients with a better success rate than the low dose treatment with 3 to 5 mCi. This is also likely to be helpful in patients who have not received antithyroid drugs. It appears that clinically relevant

  10. Effect of high-dose oral multivitamins and minerals in participants not treated with statins in the randomized Trial to Assess Chelation Therapy (TACT).

    Science.gov (United States)

    Issa, Omar M; Roberts, Rhonda; Mark, Daniel B; Boineau, Robin; Goertz, Christine; Rosenberg, Yves; Lewis, Eldrin F; Guarneri, Erminia; Drisko, Jeanne; Magaziner, Allan; Lee, Kerry L; Lamas, Gervasio A

    2018-01-01

    In a prespecified subgroup analysis of participants not on statin therapy at baseline in the TACT, a high-dose complex oral multivitamins and multimineral regimen was found to have a large unexpected benefit compared with placebo. The regimen tested was substantially different from any vitamin regimen tested in prior clinical trials. To explore these results, we performed detailed additional analyses of participants not on statins at enrollment in TACT. TACT was a factorial trial testing chelation treatments and a 28-component high-dose oral multivitamins and multiminerals regimen versus placebo in post-myocardial infarction (MI) patients 50 years or older. There were 460 (27%) of 1,708 TACT participants not taking statins at baseline, 224 (49%) were in the active vitamin group and 236 (51%) were in the placebo group. Patients were enrolled at 134 sites around the United States and Canada. Daily high-dose oral multivitamins and multiminerals (6 tablets, active or placebo). The primary end point of TACT was time to the first occurrence of any component of the composite end point: all-cause mortality, MI, stroke, coronary revascularization, or hospitalization for angina. The primary end point occurred in 137 nonstatin participants (30%), of which 51 (23%) of 224 were in the active group and 86 (36%) of 236 were taking placebo (hazard ratio, 0.62; 95% confidence interval, 0.44-0.87; P=.006). Results in the key TACT secondary end point, a combination of cardiovascular mortality, stroke, or recurrent MI, was consistent in favoring the active vitamin group (hazard ratio, 0.46; 95% confidence interval, 0.28-0.75; P=.002). Multiple end point analyses were consistent with these results. High-dose oral multivitamin and multimineral supplementation seem to decrease combined cardiac events in a stable, post-MI population not taking statin therapy at baseline. These unexpected findings are being retested in the ongoing TACT2. Copyright © 2017 The Authors. Published by Elsevier

  11. An overview of insulin pump therapy: appropriate use of an ...

    African Journals Online (AJOL)

    2012-06-13

    Jun 13, 2012 ... Careful assessment of patients is vital, as pump therapy is an expensive treatment option and can be ... Intensive education of patients who meet the criteria is essential. .... to keep a food, blood glucose and insulin dose diary,.

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

    International Nuclear Information System (INIS)

    Hata, Masaharu; Tokuuye, Koichi; Kagei, Kenji; Sugahara, Shinji; Nakayama, Hidetsugu; Fukumitsu, Nobuyoshi; Hashimoto, Takayuki; Mizumoto, Masashi; Ohara, Kiyoshi; Akine, Yasuyuki

    2007-01-01

    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

  13. High-dose-rate stereotactic body radiation therapy for postradiation therapy locally recurrent prostatic carcinoma: Preliminary prostate-specific antigen response, disease-free survival, and toxicity assessment.

    Science.gov (United States)

    Fuller, Donald B; Wurzer, James; Shirazi, Reza; Bridge, Stephen S; Law, Jonathan; Mardirossian, George

    2015-01-01

    Patients with locally recurrent adenocarcinoma of the prostate following radiation therapy (RT) present a challenging problem. We prospectively evaluated the use of "high-dose-rate-like" prostate stereotactic body RT (SBRT) salvage for this circumstance, evaluating prostate-specific antigen response, disease-free survival, and toxicity. Between February 2009 and March 2014, 29 patients with biopsy-proven recurrent locally prostate cancer >2 years post-RT were treated. Median prior RT dose was 73.8 Gy and median interval to SBRT salvage was 88 months. Median recurrence Gleason score was 7 (79% was ≥7). Pre-existing RT toxicity >grade 1 was a reason for exclusion. Magnetic resonance imaging-defined prostate volume including any suspected extraprostatic extension, comprising the planning target volume. A total of 34 Gy/5 fractions was given, delivering a heterogeneous, high-dose-rate-like dose-escalation pattern. Toxicities were assessed using Common Terminology Criteria for Adverse Events, version 3.0, criteria. Twenty-nine treated patients had a median 24-month follow-up (range, 3-60 months). A median pre-SBRT salvage baseline prostate-specific antigen level of 3.1 ng/mL decreased to 0.65 ng/mL and 0.16 ng/mL at 1 and 2 years, respectively. Actuarial 2-year biochemical disease-free survival measured 82%, with no local failures. Toxicity >grade 1 was limited to the genitourinary domain, with 18% grade 2 or higher and 7% grade 3 or higher. No gastrointestinal toxicity >grade 1 occurred. Two-year disease-free survival is encouraging, and the prostate-specific antigen response kinetic appears comparable with that seen in de novo patients treated with SBRT, albeit still a preliminary finding. Grade ≥2 genitourinary toxicity was occasionally seen with no obvious predictive factor. Noting that our only brachytherapy case was 1 of the 2 cases with ≥grade 3 genitourinary toxicity, caution is recommended treating these patients. SBRT salvage of post-RT local recurrence

  14. Insulin gene therapy for type 1 diabetes mellitus.

    Science.gov (United States)

    Handorf, Andrew M; Sollinger, Hans W; Alam, Tausif

    2015-04-01

    Type 1 diabetes mellitus is an autoimmune disease resulting from the destruction of pancreatic β cells. Current treatments for patients with type 1 diabetes mellitus include daily insulin injections or whole pancreas transplant, each of which are associated with profound drawbacks. Insulin gene therapy, which has shown great efficacy in correcting hyperglycemia in animal models, holds great promise as an alternative strategy to treat type 1 diabetes mellitus in humans. Insulin gene therapy refers to the targeted expression of insulin in non-β cells, with hepatocytes emerging as the primary therapeutic target. In this review, we present an overview of the current state of insulin gene therapy to treat type 1 diabetes mellitus, including the need for an alternative therapy, important features dictating the success of the therapy, and current obstacles preventing the translation of this treatment option to a clinical setting. In so doing, we hope to shed light on insulin gene therapy as a viable option to treat type 1 diabetes mellitus.

  15. A consideration of distributions and treatment schedules in high dose rate intracavitary therapy of carcinoma of the uterine cervix

    International Nuclear Information System (INIS)

    Sakata, Suoh; Sato, Sigehiro; Nakano, Masao; Iida, Koyo; Yui, Nobuharu

    1979-01-01

    A remotely controlled afterloading device for high dose rate intracavitary radiation, the remote afterloader Shimadzu Ralstron MTSW-20, was installed at Chiba Cancer Center Hospital in 1973 and put into clinical use for the treatment of carcinoma of the uterine cervix. Before the clinical use, isodose distributions and treatment schedules were investigated, compared with the low dose rate intracavitary radiation by linear sources of 137 Cs used hitherto. The isodose distributions, calculated by using an electronic computer, for various combinations of the length of uterine canal and the separation of vaginal applicators, were the same as those obtained with linear sources. As for the treatment schedules, by using PT (partial tolerance) which was derived from NSD concept of Ellis, a number of fractional radiation regimes with high dose rate, equivalent to continuous low dose rate radiation, was calculated. From these, a dose of 600 rad per fraction to point A every week has been chosen as the standard radiation schedule. The number of fractions has been varied with the clinical stages. Furthermore, some changes of total dose or small modification of dose distribution have been made for individual lesions. According to the preliminary results, three-year cumulative survival rate was 68.7% and complication rate was 15.2%. Comparing these results with those of the treatment at low dose rate, the former is nearly equal, while the latter is lower. The reduction of complication rate is probably due to the improvement of therapeutic techniques such as continuous observation by fractionated intracavitary radiation, variety of isodose distributions and accuracy of source placement by a short treatment time. (author)

  16. High dose Gd-DTPA-BMA (gadodiamide) for diagnostic imaging and therapy monitoring of malignant bone tumors

    International Nuclear Information System (INIS)

    Haeussler, M.D.; Rummeny, E.J.; Raufhake, C.; Blasius, S.; Lindner, N.; Daldrup, H.E.; Reimer, P.; Peters, P.E.

    1996-01-01

    Purpose: To evaluate the efficacy of high-dose Gd-DTPA-BMA (gadodiamide, Omniscan) as a contrast for magnetic resonance imaging of malignant bone tumors and the use of high-dose dynamic studies for predicting the response to preoperative chemotherapy. Materials and methods: Examinations were performed in 22 patients with suspected malignant bone tumor on a 1.5 T system. In 8 cases a follow-up examination was done after preoperative chemotherapy. Static studies included Pd- and T2-weighted spin-echo sequences as well as T1-weighted spin-echo sequences, obtained pre- and post-contrast. Dynamic studies were performed using a FLASH 2D-gradient-echo sequence (TR 40 ms/TE 10 ms, 90 flip angle) every 20 s after intravenous bolus injection of Gd-DTPA-BMA (0.3 mmol/kg body weight). MR images were evaluated qualitatively by visual assessment of conspicuity size, extraosseous delineation and structure of the lesion and quantitatively by measurement of the signal intensities and calculation of the relative increase in signal intensity. Results: Qualitative image analysis showed best demonstration of the lesions on contrast-enhanced T1-weighted images. Comparison of T1-weighted pre- and postcontrast spin-echo sequences revealed significantly better assessment of tumor structure after administration of contrast media. After preoperative chemotherapy, all responders showed a markedly stronger reduction in relative increase in signal intensity in dynamic studies compared to nonresponders. Conclusion: Gd-DTPA-BMA is effective for magnetic resonance imaging of musculoskeletal lesions and improves assessment of the tumor structure. Dynamic studies may help to predict the response to preoperative chemotherapy. (orig.) [de

  17. Long-term reversibility of renal dysfunction associated to light chain deposition disease with bortezomib and dexamethasone and high dose therapy and autologous stem cell transplantation

    Directory of Open Access Journals (Sweden)

    Tomás J. González-López

    2011-11-01

    Full Text Available A 63-year-old woman presented with progressive renal insufficiency, until a glomerular filtration rate (GFR of 12 mL/min. A renal biopsy demonstrated glomerular deposition of immunoglobulin k light chain. The presence of a small population of monoclonal plasmacytes producing an only light k monoclonal component was demonstrated and Bortezomib and Dexamethasone (BD was provided as initial therapy. After seven courses of therapy, renal function improved without dialysis requirements up to a GFR 31 mL/min. Under hematological complete response (HCR the patient underwent high dose of melphalan (HDM and autologous peripheral blood stem cell transplant. Fifty-four months later the patient remains in HCR and the GFR has progressively improved up to 48 mL/min. This report describes a notably renal function improvement in a patient with Light Chain Deposition Disease after therapy with BD followed by HDM, which can support this treatment as a future option for these patients.

  18. Tolerability in the elderly population of high-dose alpha lipoic acid: a potential antioxidant therapy for the eye

    Directory of Open Access Journals (Sweden)

    Sarezky D

    2016-09-01

    Full Text Available Daniel Sarezky, Aaishah R Raquib, Joshua L Dunaief, Benjamin J Kim Scheie Eye Institute, Department of Ophthalmology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA Purpose: Alpha lipoic acid (ALA is an antioxidant and iron-chelating supplement that has potential benefits for geographic atrophy in dry age-related macular degeneration as well as other eye diseases. The purpose of this study was to determine the tolerability of ALA in the elderly population. Patients and methods: Fifteen subjects, age ≥65 years, took sequential ALA doses of 600, 800, and 1,200 mg. Each dose was taken once daily with a meal for 5 days. After each dose was taken by the subjects for 5 days, the subjects were contacted by phone, a review of systems was performed, and they were asked if they thought they could tolerate taking that dose of ALA for an extended period of time. Results: The 600 mg dose was well tolerated. At the 800 mg dose, one subject had an intolerable flushing sensation. At the 1,200 mg dose, two subjects had intolerable upper gastrointestinal side effects and one subject had an intolerable flushing sensation. Subjects taking gastrointestinal prophylaxis medications had no upper gastrointestinal side effects. Conclusion: High-dose ALA is not completely tolerated by the elderly. These preliminary data suggest that gastrointestinal prophylaxis may improve tolerability. (ClinicalTrials.gov, NCT02613572. Keywords: age-related macular degeneration, geographic atrophy, antioxidant, gastrointestinal, dietary supplements, lipoic acid

  19. High-dose methylprednisolone pulse therapy for treatment of refractory intestinal involvement caused by Henoch-Schönlein purpura: a case report.

    Science.gov (United States)

    Kang, Hyun Sik; Chung, Hee Sup; Kang, Ki-Soo; Han, Kyoung Hee

    2015-03-24

    Henoch-Schönlein purpura is an immunoglobulin A-mediated, small vascular inflammatory disease that can be associated with palpable purpura, arthralgia, abdominal pain, or nephritis. The presence of purpura facilitates the diagnosis of Henoch-Schönlein purpura at the onset of associated symptoms, whereas the absence of purpura makes the diagnosis challenging. It is important to diagnose Henoch-Schönlein purpura with delayed-onset skin purpura to avoid unnecessary surgery for acute abdomen. Most cases of Henoch-Schönlein purpura with severe abdominal pain are treated with low-dose steroids and intravenous immunoglobulin. A 15-year-old Korean girl complained of severe abdominal pain and delayed-onset purpura on admission. Henoch-Schönlein purpura was diagnosed based on endoscopic findings of hemorrhagic duodenitis and duodenal vasculitis and abdominal computed tomography findings of edematous bowels. Two common initial treatments, a low-dose steroid and intravenous immunoglobulin, were administered, but there was no improvement for 1 month. Subsequently, we used high-dose intravenous methylprednisolone pulse therapy (30 mg/kg/day, with a maximum of 1g/day), which dramatically alleviated her abdominal symptoms. High-dose intravenous methylprednisolone pulse therapy can be used as the ultimate treatment for delayed-onset Henoch-Schönlein purpura with severe abdominal pain when symptoms do not improve after low-dose steroid and intravenous immunoglobulin treatments.

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

    International Nuclear Information System (INIS)

    Berk, Lawrence; Berkey, Brian; Rich, Tyvin; Hrushesky, William; Blask, David; Gallagher, Michael; Kudrimoti, Mahesh; McGarry, Ronald C.; Suh, John; Mehta, Minesh

    2007-01-01

    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

  1. Duration of high-dose aspirin therapy does not affect long-term coronary artery outcomes in Kawasaki disease.

    Science.gov (United States)

    Migally, Karl; Braunlin, Elizabeth A; Zhang, Lei; Binstadt, Bryce A

    2018-05-02

    BackgroundHigh-dose aspirin (HDA) is used with intravenous immunoglobulin (IVIg) in Kawasaki disease (KD). Practice regarding HDA varies, and it is unclear whether HDA duration affects the long-term course.MethodsWe retrospectively studied KD patients at our hospital for over 10 years. Patients were categorized as having received HDA for 0, 1-7, or >7 days. Primary outcome was the maximum coronary Z-score at diagnosis and follow-up; secondary outcomes included inflammatory markers.ResultsOne hundred and three patients had HDA duration documented, of which 35 patients had coronary artery abnormalities (CAAs) at diagnosis. There was no difference in demographics or inflammatory markers between the HDA groups, and no difference in HDA duration between patients with or without CAAs. Seventeen patients received no HDA; they had longer illness and defervescence duration before diagnosis, and were less likely to receive IVIg. For CAAs, multivariate regression revealed that HDA duration did not predict the coronary Z-score at 9-15 months. Higher Z-score at diagnosis was associated with higher Z-score at 9-15 months.ConclusionThe only factor associated with coronary Z-score at 9-15 months was the Z-score at diagnosis. At our institution, longer illness and defervescence duration and the lack of IVIg administration were associated with not administering HDA. HDA duration did not affect the clinically relevant outcomes, particularly CAA persistence.Pediatric Research advance online publication, 2 May 2018; doi:10.1038/pr.2018.44.

  2. Concentrated insulins: the new basal insulins

    Directory of Open Access Journals (Sweden)

    Lamos EM

    2016-03-01

    Full Text Available Elizabeth M Lamos,1 Lisa M Younk,2 Stephen N Davis3 1Division of Endocrinology, Diabetes and Nutrition, 2Department of Medicine, University of Maryland School of Medicine, 3Department of Medicine, University of Maryland Medical Center, Baltimore, MD, USA Introduction: Insulin therapy plays a critical role in the treatment of type 1 and type 2 diabetes mellitus. However, there is still a need to find basal insulins with 24-hour coverage and reduced risk of hypoglycemia. Additionally, with increasing obesity and insulin resistance, the ability to provide clinically necessary high doses of insulin at low volume is also needed. Areas covered: This review highlights the published reports of the pharmacokinetic (PK and glucodynamic properties of concentrated insulins: Humulin-R U500, insulin degludec U200, and insulin glargine U300, describes the clinical efficacy, risk of hypoglycemic, and metabolic changes observed, and finally, discusses observations about the complexity of introducing a new generation of concentrated insulins to the therapeutic market. Conclusion: Humulin-R U500 has a similar onset but longer duration of action compared with U100 regular insulin. Insulin glargine U300 has differential PK/pharmacodynamic effects when compared with insulin glargine U100. In noninferiority studies, glycemic control with degludec U200 and glargine U300 is similar to insulin glargine U100 and nocturnal hypoglycemia is reduced. Concentrated formulations appear to behave as separate molecular entities when compared with earlier U100 insulin analog compounds. In the review of available published data, newer concentrated basal insulins may offer an advantage in terms of reduced intraindividual variability as well as reducing the injection burden in individuals requiring high-dose and large volume insulin therapy. Understanding the PK and pharmacodynamic properties of this new generation of insulins is critical to safe dosing, dispensing, and administration

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

    International Nuclear Information System (INIS)

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

    2012-01-01

    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.

  4. Prolonged high-dose intravenous magnesium therapy for severe tetanus in the intensive care unit: a case series

    Directory of Open Access Journals (Sweden)

    Fligou Fotini

    2010-03-01

    Full Text Available Abstract Introduction Tetanus rarely occurs in developed countries, but it can result in fatal complications including respiratory failure due to generalized muscle spasms. Magnesium infusion has been used to treat spasticity in tetanus, and its effectiveness is supported by several case reports and a recent randomized controlled trial. Case presentations Three Caucasian Greek men aged 30, 50 and 77 years old were diagnosed with tetanus and admitted to a general 12-bed intensive care unit in 2006 and 2007 for respiratory failure due to generalized spasticity. Intensive care unit treatment included antibiotics, hydration, enteral nutrition, early tracheostomy and mechanical ventilation. Intravenous magnesium therapy controlled spasticity without the need for additional muscle relaxants. Their medications were continued for up to 26 days, and adjusted as needed to control spasticity. Plasma magnesium levels, which were measured twice a day, remained in the 3 to 4.5 mmol/L range. We did not observe hemodynamic instability, arrhythmias or other complications related to magnesium therapy in these patients. All patients improved, came off mechanical ventilation, and were discharged from the intensive care unit in a stable condition. Conclusion In comparison with previous reports, our case series contributes the following meaningful additional information: intravenous magnesium therapy was used on patients already requiring mechanical ventilation and remained effective for up to 26 days (significantly longer than in previous reports without significant toxicity in two patients. The overall outcome was good in all our patients. However, the optimal dose, optimal duration and maximum safe duration of intravenous magnesium therapy are unknown. Therefore, until more data on the safety and efficacy of magnesium therapy are available, its use should be limited to carefully selected tetanus cases.

  5. Bitemporal v. high-dose right unilateral electroconvulsive therapy for depression: a systematic review and meta-analysis of randomized controlled trials.

    Science.gov (United States)

    Kolshus, E; Jelovac, A; McLoughlin, D M

    2017-02-01

    Brief-pulse electroconvulsive therapy (ECT) is the most acutely effective treatment for severe depression though concerns persist about cognitive side-effects. While bitemporal electrode placement is the most commonly used form worldwide, right unilateral ECT causes less cognitive side-effects though historically it has been deemed less effective. Several randomized trials have now compared high-dose (>5× seizure threshold) unilateral ECT with moderate-dose (1.0-2.5× seizure threshold) bitemporal ECT to investigate if it is as effective as bitemporal ECT but still has less cognitive side-effects. We aimed to systematically review these trials and meta-analyse clinical and cognitive outcomes where appropriate. We searched PubMed, PsycINFO, Web of Science, Cochrane Library and EMBASE for randomized trials comparing these forms of ECT using the terms 'electroconvulsive' OR 'electroshock' AND 'trial'. Seven trials (n = 792) met inclusion criteria. Bitemporal ECT did not differ from high-dose unilateral ECT on depression rating change scores [Hedges's g = -0.03, 95% confidence interval (CI) -0.17 to 0.11], remission (RR 1.06, 95% CI 0.93-1.20), or relapse at 12 months (RR 1.42, 95% CI 0.90-2.23). There was an advantage for unilateral ECT on reorientation time after individual ECT sessions (mean difference in minutes = -8.28, 95% CI -12.86 to -3.70) and retrograde autobiographical memory (Hedges's g = -0.46, 95% CI -0.87 to -0.04) after completing an ECT course. There were no differences for general cognition, category fluency and delayed visual and verbal memory. High-dose unilateral ECT does not differ from moderate-dose bitemporal ECT in antidepressant efficacy but has some cognitive advantages.

  6. Fractionated stereotactic radiation therapy and single high-dose radiosurgery for acoustic neuroma: early results of a prospective clinical study

    International Nuclear Information System (INIS)

    Meijer, O.W.M.; Wolbers, J.G.; Baayen, J.C.; Slotman, B.J.

    2000-01-01

    Purpose: To prospectively assess the local control and toxicity rate in acoustic neuroma patients treated with linear accelerator-based radiosurgery and fractionated stereotactic radiation therapy. Methods and Materials: We evaluated 37 consecutive patients treated with stereotactic radiation therapy for acoustic neuroma. All patients had progressive tumors, progressive symptoms, or both. Mean tumor diameter was 2.3 cm (range 0.8-3.3) on magnetic resonance (MR) scan. Dentate patients were given a dose of 5 x 4 Gy or 5 x 5 Gy and edentate patients were given a dose of 1 x 10 Gy or 1 x 12.50 Gy prescribed to the 80% isodose. All patients were treated with a single isocenter. Results: With a mean follow-up period of 25 months (range 12-61), the actuarial local control rate at 5 years was 91% (only 1 patient failed). The actuarial rate of hearing preservation at 5 years was 66% in previously-hearing patients. The actuarial rate of freedom from trigeminal nerve toxicity was 97% at 5 years. No patient developed facial nerve toxicity or other complications. Conclusion: In this unselected series, fractionated stereotactic radiation therapy and linear accelerator-based radiosurgery give excellent local control in acoustic neuroma. It combines a high rate of preservation of hearing with a very low rate of other toxicity, although follow-up is relatively short

  7. Sacral chordomas: Impact of high-dose proton/photon-beam radiation therapy combined with or without surgery for primary versus recurrent tumor

    International Nuclear Information System (INIS)

    Park, Lily; De Laney, Thomas F.; Liebsch, Norbert J.; Hornicek, Francis J.; Goldberg, Saveli; Mankin, Henry; Rosenberg, Andrew E.; Rosenthal, Daniel I.; Suit, Herman D.

    2006-01-01

    Purpose: To assess the efficacy of definitive treatment of sacral chordoma by high-dose proton/photon-beam radiation therapy alone or combined with surgery. Methods and Materials: The records of 16 primary and 11 recurrent sacral chordoma patients treated from November 1982 to November 2002 by proton/photon radiation therapy alone (6 patients) or combined with surgery (21 patients) have been analyzed for local control, survival, and treatment-related morbidity. The outcome analysis is based on follow-up information as of 2005. Results: Outcome results show a large difference in local failure rate between patients treated for primary and recurrent chordomas. Local control results by surgery and radiation were 12/14 vs. 1/7 for primary and recurrent lesions. For margin-positive patients, local control results were 10 of 11 and 0 of 5 in the primary and recurrent groups, respectively; the mean follow-up on these locally controlled patients was 8.8 years (4 at 10.3, 12.8, 17, and 21 years). Radiation alone was used in 6 patients, 4 of whom received ≥73.0 Gy (E); local control was observed in 3 of these 4 patients for 2.9, 4.9, and 7.6 years. Conclusion: These data indicate a high local control rate for surgical and radiation treatment of primary (12 of 14) as distinct from recurrent (1 of 7) sacral chordomas. Three of 4 chordomas treated by ≥73.0 Gy (E) of radiation alone had local control; 1 is at 91 months. This indicates that high-dose proton/photon therapy offers an effective treatment option

  8. [Experience with high-dose immunosuppressive therapy followed by transplantation of autologous stem hematopoietic cells in patients with multiple sclerosis].

    Science.gov (United States)

    Rossiev, V A; Makarov, S V; Aleksandrova, I Ia; Dolgikh, G T; Lipshina, S R; Stukalova, T A; Trushina, O A; Fedorova, E Iu; Lipina, L N; Sivak, V F; Korenev, P P; Murashov, B F

    2002-01-01

    To assess efficiency of immunosuppressive therapy and subsequent autologous transplantation of stem blood cells (SBC) in patients with multiple sclerosis. The trial enrolled 23 patients (4 men and 19 women) with multiple sclerosis (MS) lasting for 3 to 12 years. The age of the patients ranged from 18 to 44 years. The index of the progression was above 1 in all the patients. A remitting, primary-progredient, secondary-progredient course was diagnosed in 3, 3 and 17 patients, respectively. Posttransplantation follow-up was 1 to 1.5 years. The degree of the neurological deficiency (0-6 scores) was estimated by the scale of functional systems damage. Lymphocyte subpopulations were evaluated by enzyme immunoassay according to expression of membrane antigens CD3, CD4, CD8, CD16, CD20, CD25, CD56, CD95 using monoclonal antibodies ICO (Biomedspectr), humoral immunity--by serum levels of IgA, IgM and IgG. SBC mobilization was conducted for 5 days by subcutaneous introduction of neipogen (Roche) in a dose 8.7-10 mcg/kg. Preparation of SBC was made on Haemonetics blood separator on mobilization day 4-5. Cryopreservation was carried out in programmed freezer (Cryomed) with 7% dimethylsulphoxide as a cryoprotector. Pretransplantation conditioning was conducted according to the schemes BEAM + antilymphocytic globulin (protocol N 1) and fludar + melfalan + ALG (protocol N 2). In posttransplantation period most of the patients achieved a fall in intensity of motor and coordination disorders. No recovery of cranial nerve function was observed. The protocols of pretransplantation preparation were compared by efficiency and organic toxicity. Indications to immunosuppressive therapy in MS patients were defined, pathogenetic validation of the immunosuppressive therapy was attempted.

  9. Safety and tolerability of high doses of glucocorticoides

    Directory of Open Access Journals (Sweden)

    Rakić Branislava D.

    2016-01-01

    Full Text Available Introduction: Treatment of acute lymphoblastic leukemia includes the use of high doses of glucocorticoides (prednisone and dexamethasone, which significantly increase the success of therapy due to lymphocytolitic effect. The aim: The aim of the study was to determine tolerability of high doses of prednisone and dexamethasone in children with acute lymphoblastic leukemia and the structure and the intensity of adverse effects, occurred after application of these medicines. Subjects and methods: In a prospective study, we analyzed adverse effects of high doses of glucocorticoides in children suffering acute lymphoblastic leukemia treated in the Institute for Child and Youth Health Care of Vojvodina, since December 2010. until October 2014, were analyzed. This study included 18 patients, aged from 2 to 15 years. Results: Hyperglycemia appeared in 89% of patients treated with prednisone and in 61% of patients treated with dexamethasone. In order to control the high blood glucose level (above 10 mmol /L, in 11% of patients insulin was used. Hypertension appeared in 28% patients treated with prednisone and dexamethasone. Antihypertensives were needed for regulation in 17% patients. Hypopotassemia and hypocalcaemia were significantly more expressed after the use of prednisone in comparison to dexamethasone. In 11% of patients, the treatment with dexamethasone caused depressive behavior, followed by agitation. Conclusion: Adverse effects of dexamethasone and prednisone, administered in high doses in children with ALL were known, expected and reversible. Adverse reactions usually disappeared spontaneously or after short-term symptomatic therapy.

  10. High-dose antibiotic therapy is superior to a 3-drug combination of prostanoids and lipid A derivative in protecting irradiated canines

    International Nuclear Information System (INIS)

    Kumar, K.S.; Srinivasan, V.; Toles, R.E.; Miner, V.L.; Jackson, W.E.; Seed, T.M.

    2002-01-01

    There is an urgent need to develop non-toxic radioprotectors. We tested the efficacy of a 3-drug combination (3-DC) of iloprost, misoprostol, and 3D-MPL (3-deacylated monophosphoryl lipid A) and the effects of postirradiation clinical support with high doses of antibiotics and blood transfusion. Canines were given 3-DC or the vehicle and exposed to 3.4 Gy or 4.1 Gy of 60 Co radiation. Canines irradiated at 4.1 Gy were also given clinical support, which consisted of blood transfusion and antibiotics (gentamicin, and cefoxitin or cephalexin). Peripheral blood cell profile and 60-day survival were used as indices of protection. At 3.4 Gy, 3-DC- or vehicle-treated canines without postirradiation clinical support survived only for 10 to 12 days. Fifty percent of the canines treated with 3-DC or vehicle and provided postirradiation clinical support survived 4.1-Gy irradiation. Survival of canines treated with vehicle before irradiation significantly correlated with postirradiation antibiotic treatments, but not with blood transfusion. The recovery profile of peripheral blood cells in 4.1 Gy-irradiated canines treated with vehicle and antibiotics was better than drug-treated canines. These results indicate that therapy with high doses of intramuscular aminoglycoside antibiotic (gentamicin) and an oral cephalosporin (cephalexin) enhanced survival of irradiated canines. Although blood transfusion correlated with survival of 3-DC treated canines, there were no additional survivors with 3-DC treated canines than the controls. (author)

  11. High-Dose Hypofractionated Radiation Therapy for Noncompressive Vertebral Metastases in Combination With Zoledronate: A Phase 1 Study

    Energy Technology Data Exchange (ETDEWEB)

    Pichon, Baptiste [Department of Radiation Oncology, ICO Cancer Center, Saint-Herblain (France); Campion, Loïc [Department of Biostatistics, ICO Cancer Center, Saint-Herblain (France); Delpon, Grégory [Department of Medical Physics, ICO Cancer Center, Saint-Herblain (France); CRCNA, Inserm U892, CNRS UMR 6299, Nantes (France); Thillays, François [Department of Radiation Oncology, ICO Cancer Center, Saint-Herblain (France); Carrie, Christian [Department of Radiation Oncology, Léon Bérard Center, Lyon (France); Cellier, Patrice [Department of Radiation Oncology, ICO Cancer Center, Angers (France); Pommier, Pascal; Laude, Cécile [Department of Radiation Oncology, Léon Bérard Center, Lyon (France); Mervoyer, Augustin [Department of Radiation Oncology, ICO Cancer Center, Saint-Herblain (France); Hamidou, Hadji [Department of Radiation Oncology, ICO Cancer Center, Angers (France); Mahé, Marc-André [Department of Radiation Oncology, ICO Cancer Center, Saint-Herblain (France); Supiot, Stéphane, E-mail: stephane.supiot@ico.unicancer.fr [Department of Radiation Oncology, ICO Cancer Center, Saint-Herblain (France); CRCNA, Inserm U892, CNRS UMR 6299, Nantes (France)

    2016-11-15

    Introduction: Hypofractionated stereotactic radiation therapy (HSRT) for vertebral metastases gives good results in terms of local control but increases the risk of fracture in the treated volume. Preclinical and clinical studies have shown that zoledronate not only reduces the risk of fracture and stimulates osteoclastic remodeling but also increases the immune response and radiosensitivity. This study aimed to evaluate the tolerability and effectiveness of zoledronate in association with radiation therapy. Patients and Methods: We conducted a multicenter phase 1 study that combined HSRT (3 × 9 Gy) and zoledronate in patients with vertebral metastasis ( (NCT01219790)). The principal objective was the absence of spinal cord adverse reactions at 1 year. The secondary objectives were acute tolerability, the presentation of a bone event, local tumor control, pain control, progression-free survival, and overall survival. Results: Thirty patients (25 male, 5 female), median age 66 years, who were followed up for a median period of 19.2 months, received treatment for 49 vertebral metastases. A grade 3 acute mucosal adverse event occurred in 1 patient during the treatment and in 2 more at 1 month. No late neurologic adverse events were reported at 1 year. The mean pain scores diminished significantly at 1 month (1.35; P=.0125) and 3 months (0.77; P<.0001) compared with pain scores at study entry (2.49). Vertebral collapse in the irradiated zone occurred in 1 (2%) treated vertebra. Control of local disease was achieved in 94% of irradiated patients (3 local recurrences). Conclusion: The combination of zoledronate and HSRT in the treatment of vertebral metastasis is well tolerated and seems to reduce the rate of vertebral collapse, effectively relieve pain, and achieve good local tumor control with no late neurologic adverse effects.

  12. Reversible, PET-positive, generalized lymphadenopathy and splenomegaly during high-dose interferon-alpha-2b adjuvant therapy for melanoma.

    Science.gov (United States)

    Ridolfi, Laura; Cangini, Delia; Galassi, Riccardo; Passardi, Alessandro; Marzullo, Annamaria; Moretti, Andrea; Framarini, Massimo; Tauceri, Francesca; Serra, Luigi; Chiarion-Sileni, Vanna; Ridolfi, Ruggero

    2008-09-01

    A patient with resected stage III nodular melanoma treated with high-dose interferon-alpha-b2 adjuvant therapy went on to develop generalized lymphadenopathy and splenomegaly. The total body positron emission tomography showed a high F-fluorodeoxyglucose uptake (standardized uptake values >9), indicating possible lymph node and spleen malignancies. Histologic examinations of an axillary lymph node biopsy and an osteomedullar biopsy were negative, excluding both melanoma metastases and hematopoietic tumors. The symptoms completely regressed after suspension of treatment and a follow-up positron emission tomography was negative. It remains to be seen whether this unusual event can be ascribed to an autoimmune phenomenon linked to potential treatment efficacy and survival.

  13. A reviewed technique for total body electron therapy using a Varian Clinac 2100C/D high dose rate treatment beam facility

    International Nuclear Information System (INIS)

    Oliver, L.D.; Xuereb, E.M.A.; Last, V.; Hunt, P.B.; Wilfert, A.

    1996-01-01

    Our (Royal North Shore Hospital) most recent linear accelerator acquisition is a Varian Clinac 2100C/D which has a high dose rate (approximately 25Gy per minute at 1 metre) total body electron option. We investigated the physical characteristics of the electron beam to develop a suitable method of treatment for total body electron therapy. The useful electron beam width is defined as 80cm above and below the reference height. Measurements of the electron dose received from the two angled electron beams showed a critical dependence on the gantry angles. The treatment protocol uses ten different patient angles, fractionated into directly opposing fields and treated seuqentially each day. A full cycle of treatment is completed in five days. (author)

  14. The fluctuation of blood glucose, insulin and glucagon concentrations before and after insulin therapy in type 1 diabetes

    Science.gov (United States)

    Arif, Idam; Nasir, Zulfa

    2015-09-01

    A dynamical-systems model of plasma glucose, insulin and glucagon concentrations has been developed to investigate the effects of insulin therapy on blood glucose, insulin and glucagon regulations in type 1 diabetic patients. Simulation results show that the normal regulation of blood glucose concentration depends on insulin and glucagon concentrations. On type 1 diabetic case, the role of insulin on regulating blood glucose is not optimal because of the destruction of β cells in pancreas. These β cells destructions cause hyperglycemic episode affecting the whole body metabolism. To get over this, type 1 diabetic patients need insulin therapy to control the blood glucose level. This research has been done by using rapid acting insulin (lispro), long-acting insulin (glargine) and the combination between them to know the effects of insulin therapy on blood glucose, insulin and glucagon concentrations. Simulation results show that these different types of insulin have different effects on blood glucose concentration. Insulin therapy using lispro shows better blood glucose control after consumption of meals. Glargin gives better blood glucose control between meals and during sleep. Combination between lispro and glargine shows better glycemic control for whole day blood glucose level.

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

    Energy Technology Data Exchange (ETDEWEB)

    Fonteyne, Valerie, E-mail: valerie.fonteyne@uzgent.be [Department of Radiotherapy, Ghent University Hospital, Ghent (Belgium); Soete, Guy [Department of Radiotherapy, Universitair Ziekenhuis Brussels, Jette (Belgium); Arcangeli, Stefano [Department of Radiotherapy, Regina Elena National Cancer Institute, Rome (Italy); De Neve, Wilfried [Department of Radiotherapy, Ghent University Hospital, Ghent (Belgium); Rappe, Bernard [Department of Urology, Algemeen Stedelijk Ziekenhuis, Aalst (Belgium); Storme, Guy [Department of Radiotherapy, Universitair Ziekenhuis Brussels, Jette (Belgium); Strigari, Lidia [Laboratory of Medical Physics and Expert Systems, Regina Elena National Cancer Institute, Rome (Italy); Arcangeli, Giorgio [Department of Radiotherapy, Regina Elena National Cancer Institute, Rome (Italy); De Meerleer, Gert [Department of Radiotherapy, Ghent University Hospital, Ghent (Belgium)

    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.

  16. Glucemia, insulinemia y secreción de insulina en ratas prepúberes hiperandrogenizadas e hiperestrogenizadas Glycemia, insulinemia and insulin secretion in prepubescent rats receiving high doses of androgens and strogens

    Directory of Open Access Journals (Sweden)

    Aimée Álvarez Álvarez

    2001-04-01

    Full Text Available Se estudió el efecto de una sobredosis de enantato de testosterona y de benzoato de estradiol en ratas machos prepúberes, sobre el comportamiento de la glucemia y la insulinemia in vivo, durante una prueba de tolerancia a la glucosa. Adicionalmente se exploró, in vitro, la capacidad de secreción de insulina estimulada por glucosa de los islotes de Langerhans de estas ratas hiperandrogenizadas e hiperestrogenizadas. Se encontró que la hiperandrogenización se acompañaba de un deterioro de la sensibilidad a la insulina, con hiperinsulinemia, que no se corresponde con un aumento de la capacidad de secreción de insulina de los islotes de Langerhans. Sin embargo, se comprobó que la hiperestrogenización no indujo cambios en los perfiles de glucemia, ni de insulinemia, ni en la capacidad de secreción de insulina de los islotes de Langerhans de este grupo de ratas hiperestrogenizadas.The effect of an overdose of testosterone heptanoate and estradiol in male prepubescent rats on the behavior of glycemia and insulinemia was studied in vivo during a glucose tolerance test. The capacity of insulin secretion stimulated by glucose from the islets of Langerhans of these rats that were administered a high dose of androgens and estrogens was explored in vitro. It was found that the high level of circulating androgens was accompanied by a deterioration of sensitivity to insulin with hyperinsulinemia that does not correspond to an increase of the insulin secreting capacity of the islets of Langerhans. However, it was demonstrated that the high level of circulating estrogens did not produce changes either in the glycemia and insulinemia profiles or in the insulin secreting capacity of the islets of Langerhans in this group of rats that received an elevated dose of estrogens.

  17. Insulin monotherapy compared with the addition of oral glucose-lowering agents to insulin for people with type 2 diabetes already on insulin therapy and inadequate glycaemic control

    NARCIS (Netherlands)

    Vos, Rimke C; van Avendonk, Mariëlle JP; Jansen, Hanneke; Goudswaard, Alexander N; van den Donk, Maureen; Gorter, Kees; Kerssen, Anneloes; Rutten, Guy EHM

    2016-01-01

    BACKGROUND: It is unclear whether people with type 2 diabetes mellitus on insulin monotherapy who do not achieve adequate glycaemic control should continue insulin as monotherapy or can benefit from adding oral glucose-lowering agents to the insulin therapy. OBJECTIVES: To assess the effects of

  18. Combination of nitric oxide stimulation with high-dose 18F-FDG promotes apoptosis and enhances radiation therapy of endothelial cells

    International Nuclear Information System (INIS)

    Paik, Jin-Young; Park, Jin-Won; Jung, Kyung-Ho; Lee, Eun Jeong; Lee, Kyung-Han

    2012-01-01

    Introduction: High-dose 18 F-FDG can provide targeted nuclear therapy of cancer. Endothelial cell injury is a key determinant of tumor response to radiotherapy. Here, we tested the hypothesis that activation of endothelial cell glycolytic metabolism with nitric oxide can enhance the therapeutic effect of high-dose 18 F-FDG. Methods: Calf pulmonary artery endothelial (CPAE) cells were treated with graded doses of 18 F-FDG. Glycolysis was stimulated by 24 h of exposure to the nitric oxide donor, sodium nitroprusside (SNP). Cell viability was assessed by MTT and clonogenic assays. Apoptosis was evaluated by ELISA of cytosolic DNA fragments and Western blots of cleaved caspase-3. Results: SNP stimulation (0.1 and 1 mM) augmented CPAE cell 18 F-FDG uptake to 2.6- and 4.6-fold of controls without adverse effects. Treatment with 333 μCi/ml 18 F-FDG alone reduced viable cell number to 35.4% of controls by Day 3. Combining 0.1 mM SNP stimulation significantly enhanced the killing effect, reducing cell numbers to 19.2% and 39.2% of controls by 333 and 167 μCi/ml of 18 F-FDG, respectively. 18 F-FDG also suppressed clonogenic survival to 80.8% and 43.2% of controls by 83 and 167 μCi/ml, which was again intensified by SNP to 59.7% and 21.1% of controls. The cytotoxic effect of 18 F-FDG was attributed to induction of apoptosis as shown by increased cytosolic fragmented DNA and cleaved caspase-3 levels (26.4% and 30.7% increases by 167 μCi/ml). Combining SNP stimulation significantly increased both of these levels to 1.8-fold of control cells. Conclusion: High-dose 18 F-FDG combined with nitric oxide-stimulated glycolysis is an effective method to inhibit endothelial cell survival and promote apoptosis. These results suggest a potential role of this strategy for targeted radiotherapy of angiogenic vasculature.

  19. A Review of Basal-Bolus Therapy Using Insulin Glargine and Insulin Lispro in the Management of Diabetes Mellitus.

    Science.gov (United States)

    Candido, Riccardo; Wyne, Kathleen; Romoli, Ester

    2018-04-13

    Basal-bolus therapy (BBT) refers to the combination of a long-acting basal insulin with a rapid-acting insulin at mealtimes. Basal insulin glargine 100 U/mL and prandial insulin lispro have been available for many years and there is a substantial evidence base to support the efficacy and safety of these agents when they are used in BBT or basal-plus therapy for patients with type 1 or type 2 diabetes mellitus (T1DM, T2DM). With the growing availability of alternative insulins for use in such regimens, it seems timely to review the data regarding BBT with insulin glargine 100 U/mL and insulin lispro. In patients with T1DM, BBT with insulin glargine plus insulin lispro provides similar or better glycemic control and leads to less nocturnal hypoglycemia compared to BBT using human insulin as the basal and/or prandial component, and generally provides similar glycemic control and rates of severe hypoglycemia to those achieved with insulin lispro administered by continuous subcutaneous insulin infusion (CSII). Studies evaluating BBT with insulin glargine plus insulin lispro in patients with T2DM also demonstrate the efficacy and safety of these insulins. Available data suggest that BBT with insulin glargine and insulin lispro provides similar levels of efficacy and safety in pediatric and adult populations with T1DM and in adult patients and those aged more than 65 years with T2DM. These insulin preparations also appear to be safe and effective for controlling T2DM in people of different ethnicities and in patients with T1DM or T2DM and comorbidities. Eli Lilly and Company.

  20. Myostatin inhibition therapy for insulin-deficient type 1 diabetes.

    Science.gov (United States)

    Coleman, Samantha K; Rebalka, Irena A; D'Souza, Donna M; Deodhare, Namita; Desjardins, Eric M; Hawke, Thomas J

    2016-09-01

    While Type 1 Diabetes Mellitus (T1DM) is characterized by hypoinsulinemia and hyperglycemia, persons with T1DM also develop insulin resistance. Recent studies have demonstrated that insulin resistance in T1DM is a primary mediator of the micro and macrovascular complications that invariably develop in this chronic disease. Myostatin acts to attenuate muscle growth and has been demonstrated to be elevated in streptozotocin-induced diabetic models. We hypothesized that a reduction in mRNA expression of myostatin within a genetic T1DM mouse model would improve skeletal muscle health, resulting in a larger, more insulin sensitive muscle mass. To that end, Akita diabetic mice were crossed with Myostatin(Ln/Ln) mice to ultimately generate a novel mouse line. Our data support the hypothesis that decreased skeletal muscle expression of myostatin mRNA prevented the loss of muscle mass observed in T1DM. Furthermore, reductions in myostatin mRNA increased Glut1 and Glut4 protein expression and glucose uptake in response to an insulin tolerance test (ITT). These positive changes lead to significant reductions in resting blood glucose levels as well as pronounced reductions in associated diabetic symptoms, even in the absence of exogenous insulin. Taken together, this study provides a foundation for considering myostatin inhibition as an adjuvant therapy in T1DM as a means to improve insulin sensitivity and blood glucose management.

  1. Superselective intra-arterial infusion of high-dose cisplatin combined with radiation therapy for head and neck carcinoma. Experience of Yamagata University Hospital

    International Nuclear Information System (INIS)

    Hamamoto, Yasushi; Niino, Keiji; Ishiyama, Hiromichi; Koike, Shuji; Hosoya, Takaaki; Aoyagi, Masaru

    2003-01-01

    Local effectiveness and complication of superselective intra-arterial infusion of high-dose cisdiamminedichloroplatinum (CDDP) (SIC) combined with radiation therapy (RT) were investigated. Between 1998 and 2000, 18 head and neck carcinomas including 10 maxillary carcinomas (T3; 1, T4; 9), 3 oral cavity carcinomas (T2; 1, T4; 2), and 5 oropharyngeal carcinomas (T2; 2, T4; 3) were treated with SIC and RT with or without surgery. CDDP of 100-150 mg/body was administered weekly in principle for 2-9 weeks (mean: 4.9) with the simultaneous administration of sodium thiosulfate. Radiation doses ranged from 40 Gy to 70 Gy (mean: 56.8 Gy). Complete response was obtained in 7 of 10 maxillary carcinomas, 2 of 3 oral-cavity carcinomas, and 2 of 5 oropharyngeal carcinomas, respectively. When surgical intervention was performed if necessary, 2-year local control rates for maxillary carcinoma, and other carcinoma including oral-cavity carcinoma and oropharyngeal carcinoma were 80% and 63% respectively. Two-year local control rates for T4 maxillary carcinoma, and other T4 carcinoma including oral-cavity carcinoma and oropharyngeal carcinoma were 78% and 40% respectively. Two-year overall survival rates for all cases, maxillary carcinoma, and oral-cavity/oropharyngeal carcinoma were 88%, 90% and 86% respectively. All local recurrences occurred within 6 months from the initiation of treatment. The systemic toxicity of weekly SIC was comparatively mild; however, a total CDDP dose of 1,000 mg or more and/or RT of 70 Gy induced complications of local soft tissue such as mucosal ulcer and fistula. SIC combined with RT is useful to improve the local control/survival rates and to avoid the aggressive surgery for locally advanced head and neck carcinoma. A high total dose of CDDP and/or RT of a comparatively high dose may be risk factors for local soft tissue complications. (author)

  2. Multi-Institutional Phase II Study of High-Dose Hypofractionated Proton Beam Therapy in Patients With Localized, Unresectable Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma.

    Science.gov (United States)

    Hong, Theodore S; Wo, Jennifer Y; Yeap, Beow Y; Ben-Josef, Edgar; McDonnell, Erin I; Blaszkowsky, Lawrence S; Kwak, Eunice L; Allen, Jill N; Clark, Jeffrey W; Goyal, Lipika; Murphy, Janet E; Javle, Milind M; Wolfgang, John A; Drapek, Lorraine C; Arellano, Ronald S; Mamon, Harvey J; Mullen, John T; Yoon, Sam S; Tanabe, Kenneth K; Ferrone, Cristina R; Ryan, David P; DeLaney, Thomas F; Crane, Christopher H; Zhu, Andrew X

    2016-02-10

    To evaluate the efficacy and safety of high-dose, hypofractionated proton beam therapy for hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). In this single-arm, phase II, multi-institutional study, 92 patients with biopsy-confirmed HCC or ICC, determined to be unresectable by multidisciplinary review, with a Child-Turcotte-Pugh score (CTP) of A or B, ECOG performance status of 0 to 2, no extrahepatic disease, and no prior radiation received 15 fractions of proton therapy to a maximum total dose of 67.5 Gy equivalent. Sample size was calculated to demonstrate > 80% local control (LC) defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.0 criteria at 2 years for HCC patients, with the parallel goal of obtaining acceptable precision for estimating outcomes for ICC. Eighty-three patients were evaluable: 44 with HCC, 37 with ICC, and two with mixed HCC/ICC. The CTP score was A for 79.5% of patients and B for 15.7%; 4.8% of patients had no cirrhosis. Prior treatment had been given to 31.8% of HCC patients and 61.5% of ICC patients. The median maximum dimension was 5.0 cm (range, 1.9 to 12.0 cm) for HCC patients and 6.0 cm (range, 2.2 to 10.9 cm) for ICC patients. Multiple tumors were present in 27.3% of HCC patients and in 12.8% of ICC patients. Tumor vascular thrombosis was present in 29.5% of HCC patients and in 28.2% of ICC patients. The median dose delivered to both HCC and ICC patients was 58.0 Gy. With a median follow-up among survivors of 19.5 months, the LC rate at 2 years was 94.8% for HCC and 94.1% for ICC. The overall survival rate at 2 years was 63.2% for HCC and 46.5% ICC. High-dose hypofractionated proton therapy demonstrated high LC rates for HCC and ICC safely, supporting ongoing phase III trials of radiation in HCC and ICC. © 2015 by American Society of Clinical Oncology.

  3. High-Dose Barium Impaction Therapy Is Useful for the Initial Hemostasis and for Preventing the Recurrence of Colonic Diverticular Bleeding Unresponsive to Endoscopic Clipping

    Directory of Open Access Journals (Sweden)

    Ryota Niikura

    2013-01-01

    Full Text Available Most cases of colonic diverticular bleeding stop spontaneously, but some patients experience massive bleeding that requires emergency treatment. Endoscopy can be useful when the bleeding source is identified. However, bleeding sometimes recurs within a short period despite the successful endoscopic treatment. Under such conditions, more invasive therapy such as interventional angiography or surgery is required and can prolong hospitalization and involve frequent blood transfusions. We report the case of a 68-year-old woman who presented with massive hematochezia. The patient was in hemorrhagic shock and required 16 units of blood transfusion to recover to general condition. We performed multidetector row computed tomography, but it showed no sites of bleeding. We conducted colonoscopy and identified the source of bleeding as colonic diverticula. We treated the bleeding with endoscopic hemoclips and achieved hemostasis, but bleeding recurred the next day. Four units of blood transfusion were required. We tried high-dose barium impaction therapy to avoid further blood transfusion and surgery. No complications or recurrent bleeding was observed for an 18-month period. Therapeutic barium enema is an option for colonic diverticular bleeding unresponsive to endoscopic clipping and may be effective for preventing recurrent bleeding.

  4. Evaluation of current trends and recent development in insulin therapy for management of diabetes mellitus.

    Science.gov (United States)

    Nawaz, Muhammad Sarfraz; Shah, Kifayat Ullah; Khan, Tahir Mehmood; Rehman, Asim Ur; Rashid, Haroon Ur; Mahmood, Sajid; Khan, Shahzeb; Farrukh, Muhammad Junaid

    2017-12-01

    Diabetes mellitus is a major health problem in developing countries. There are various insulin therapies to manage diabetes mellitus. This systematic review evaluates various insulin therapies for management of diabetes mellitus worldwide. This review also focuses on recent developments being explored for better management of diabetes mellitus. We reviewed a number of published articles from 2002 to 2016 to find out the appropriate management of diabetes mellitus. The paramount parameters of the selected studies include the insulin type & its dose, type of diabetes, duration and comparison of different insulin protocols. In addition, various newly developed approaches for insulin delivery with potential output have also been evaluated. A great variability was observed in managing diabetes mellitus through insulin therapy and the important controlling factors found for this therapy include; dose titration, duration of insulin use, type of insulin used and combination therapy of different insulin. A range of research articles on current trends and recent advances in insulin has been summarized, which led us to the conclusion that multiple daily insulin injections or continuous subcutaneous insulin infusion (insulin pump) is the best method to manage diabetes mellitus. In future perspectives, development of the oral and inhalant insulin would be a tremendous breakthrough in Insulin therapy. Copyright © 2017 Diabetes India. Published by Elsevier Ltd. All rights reserved.

  5. Updated Outcome and Analysis of Tumor Response in Mobile Spine and Sacral Chordoma Treated With Definitive High-Dose Photon/Proton Radiation Therapy

    International Nuclear Information System (INIS)

    Kabolizadeh, Peyman; Chen, Yen-Lin; Liebsch, Norbert; Hornicek, Francis J.; Schwab, Joseph H.; Choy, Edwin; Rosenthal, Daniel I.; Niemierko, Andrzej; DeLaney, Thomas F.

    2017-01-01

    Purpose: Treatment of spine and sacral chordoma generally involves surgical resection, usually in conjunction with radiation therapy. In certain circumstances where resection may result in significant neurologic or organ dysfunction, patients can be treated definitively with radiation therapy alone. Herein, we report the outcome and the assessment of tumor response to definitive radiation therapy. Methods and Materials: A retrospective analysis was performed on 40 patients with unresected chordoma treated with photon/proton radiation therapy. Nineteen patients had complete sets of imaging scans. The soft tissue and bone compartments of the tumor were defined separately. Tumor response was evaluated by the modified Response Evaluation Criteria in Solid Tumors (RECIST) and volumetric analysis. Results: With a median follow-up time of 50.3 months, the rates of 5-year local control, overall survival, disease-specific survival, and distant failure were 85.4%, 81.9%, 89.4%, and 20.2%, respectively. Eighty-four computed tomographic and magnetic resonance imaging scans were reviewed. Among the 19 patients, only 4 local failures occurred, and the median tumor dose was 77.4 GyRBE. Analysis at a median follow-up time of 18 months showed significant volumetric reduction of the total target volume (TTV) and the soft tissue target volume (STTV) within the first 24 months after treatment initiation, followed by further gradual reduction throughout the rest of the follow-up period. The median maximum percentage volumetric regressions of TTV and STTV were 43.2% and 70.4%, respectively. There was only a small reduction in bone target volume over time. In comparison with the modified RECIST, volumetric analysis was more reliable, more reproducible, and could help in measuring minimal changes in the tumor volume. Conclusion: These results continue to support the use of high-dose definitive radiation therapy for selected patients with unresected spine and sacral chordomas

  6. Updated Outcome and Analysis of Tumor Response in Mobile Spine and Sacral Chordoma Treated With Definitive High-Dose Photon/Proton Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Kabolizadeh, Peyman, E-mail: peyman.kabolizadeh@beaumont.org [Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (United States); Chen, Yen-Lin; Liebsch, Norbert [Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (United States); Hornicek, Francis J.; Schwab, Joseph H. [Department of Orthopedic Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (United States); Choy, Edwin [Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (United States); Rosenthal, Daniel I. [Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (United States); Niemierko, Andrzej; DeLaney, Thomas F. [Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (United States)

    2017-02-01

    Purpose: Treatment of spine and sacral chordoma generally involves surgical resection, usually in conjunction with radiation therapy. In certain circumstances where resection may result in significant neurologic or organ dysfunction, patients can be treated definitively with radiation therapy alone. Herein, we report the outcome and the assessment of tumor response to definitive radiation therapy. Methods and Materials: A retrospective analysis was performed on 40 patients with unresected chordoma treated with photon/proton radiation therapy. Nineteen patients had complete sets of imaging scans. The soft tissue and bone compartments of the tumor were defined separately. Tumor response was evaluated by the modified Response Evaluation Criteria in Solid Tumors (RECIST) and volumetric analysis. Results: With a median follow-up time of 50.3 months, the rates of 5-year local control, overall survival, disease-specific survival, and distant failure were 85.4%, 81.9%, 89.4%, and 20.2%, respectively. Eighty-four computed tomographic and magnetic resonance imaging scans were reviewed. Among the 19 patients, only 4 local failures occurred, and the median tumor dose was 77.4 GyRBE. Analysis at a median follow-up time of 18 months showed significant volumetric reduction of the total target volume (TTV) and the soft tissue target volume (STTV) within the first 24 months after treatment initiation, followed by further gradual reduction throughout the rest of the follow-up period. The median maximum percentage volumetric regressions of TTV and STTV were 43.2% and 70.4%, respectively. There was only a small reduction in bone target volume over time. In comparison with the modified RECIST, volumetric analysis was more reliable, more reproducible, and could help in measuring minimal changes in the tumor volume. Conclusion: These results continue to support the use of high-dose definitive radiation therapy for selected patients with unresected spine and sacral chordomas

  7. Early observed transient prostate-specific antigen elevations on a pilot study of external beam radiation therapy and fractionated MRI guided High Dose Rate brachytherapy boost

    International Nuclear Information System (INIS)

    Singh, Anurag K; Godette, Denise J; Stall, Bronwyn R; Coleman, C Norman; Camphausen, Kevin; Ménard, Cynthia; Guion, Peter; Susil, Robert C; Citrin, Deborah E; Ning, Holly; Miller, Robert W; Ullman, Karen; Smith, Sharon; Crouse, Nancy Sears

    2006-01-01

    To report early observation of transient PSA elevations on this pilot study of external beam radiation therapy and magnetic resonance imaging (MRI) guided high dose rate (HDR) brachytherapy boost. Eleven patients with intermediate-risk and high-risk localized prostate cancer received MRI guided HDR brachytherapy (10.5 Gy each fraction) before and after a course of external beam radiotherapy (46 Gy). Two patients continued on hormones during follow-up and were censored for this analysis. Four patients discontinued hormone therapy after RT. Five patients did not receive hormones. PSA bounce is defined as a rise in PSA values with a subsequent fall below the nadir value or to below 20% of the maximum PSA level. Six previously published definitions of biochemical failure to distinguish true failure from were tested: definition 1, rise >0.2 ng/mL; definition 2, rise >0.4 ng/mL; definition 3, rise >35% of previous value; definition 4, ASTRO defined guidelines, definition 5 nadir + 2 ng/ml, and definition 6, nadir + 3 ng/ml. Median follow-up was 24 months (range 18–36 mo). During follow-up, the incidence of transient PSA elevation was: 55% for definition 1, 44% for definition 2, 55% for definition 3, 33% for definition 4, 11% for definition 5, and 11% for definition 6. We observed a substantial incidence of transient elevations in PSA following combined external beam radiation and HDR brachytherapy for prostate cancer. Such elevations seem to be self-limited and should not trigger initiation of salvage therapies. No definition of failure was completely predictive

  8. UK service level audit of insulin pump therapy in paediatrics.

    Science.gov (United States)

    Ghatak, A; Paul, P; Hawcutt, D B; White, H D; Furlong, N J; Saunders, S; Morrison, G; Langridge, P; Weston, P J

    2015-12-01

    To conduct an audit of insulin pump therapy in the UK after the issue of guidelines for the use of continuous subcutaneous insulin infusion by NICE in 2008 (Technology Appraisal 151). All centres in the UK, providing pump services to children and young people were invited to participate in an online audit. Audit metrics were aligned to NICE Technology Appraisal 151 and an electronic data collection tool was used. Of the 176 UK centres identified as providing pump services, 166 (94.3%) participated in the study. A total of 5094 children and young people were identified as using continuous subcutaneous insulin infusion (19% of all paediatric patients with Type 1 diabetes), with a median (range) of 16.9 (0.67-69.4)% per centre. Units had a median of 0.58 consultant sessions, 0.43 full-time equivalent diabetic specialist nurses, and 0.1 full-time equivalent dieticians delivering the pump service. The majority of this time was not formally funded. Families could access 24-h clinical and technical support (83% units), although the delivery varied between consultant, diabetic specialist nurse and company representatives. Only 53% of units ran, or accessed, structured education programmes for continuous subcutaneous insulin infusion use. Most units (86%) allowed continuous subcutaneous insulin infusion use for paediatric inpatients, but only 56% had written guidelines for this scenario. Nine percent of units had encountered funding refusal for a patient fulfilling NICE (Technology Appraisal 151) criteria. The number of children and young people on continuous subcutaneous insulin infusion therapy is consistent with numbers estimated by NICE. There is a worrying lack of funded healthcare professional time. The audit also identified gaps in the provision of structured education and absence of written inpatient guidelines. © 2015 The Authors. Diabetic Medicine © 2015 Diabetes UK.

  9. Ultra-rapid high dose irradiation schedules for the palliation of brain metastases: final results of the first two studies by the radiation therapy oncology group

    International Nuclear Information System (INIS)

    Borgelt, B.; Gelber, R.; Larson, M.; Hendrickson, F.; Griffin, T.; Rother, R.

    1981-01-01

    Between January, 1971, and February, 1976, the Radiation Therapy Oncology Group entered 1902 evaluable patients into two sequential Phase III national cooperative trials to study the effectiveness of different time dose radiotherapy schemes on the palliation of patients with brain metastases. Each trial included an optional arm into which patients were randomized to receive 1000 rad/1 fraction (26 patients, First study) or 1200 rad/2 fractions (33 patients, Second study). Comparisons were made with 143 control patients randomized by the same participating institutions to receive a more protracted course of irradiation (2000, 3000 or 4000 rad/1-4wks). Response of patients receiving ultra-rapid treatment, as assessed by the percent who had improvement in neurologic function, was comparable to that of patients receiving the more protracted schedules. Promptness of neurologic function improvement, treatment morbidity and median survival were also comparable to those of patients receiving 2000 to 4000 rad. However, the duration of improvement, time to progression of neurologic status and rate of complete disappearance of neurologic symptoms were generally less for those patients who received 1000 or 1200 rad. These results suggest that ultra-rapid, high dose irradiation schedules may not be so effective as higher dose schedules in the palliation of patients with brain metastases

  10. The use of high-dose-rate brachytherapy alone after lumpectomy in patients with early-stage breast cancer treated with breast-conserving therapy

    International Nuclear Information System (INIS)

    Baglan, Kathy L.; Martinez, Alvaro A.; Frazier, Robert C.; Kini, Vijay R.; Kestin, Larry L.; Chen, Peter Y.; Edmundson, Greg; Mele, Elizabeth; Jaffray, David; Vicini, Frank A.

    2001-01-01

    Purpose: We present the preliminary results of our in-house protocol using outpatient high-dose-rate (HDR) brachytherapy as the sole radiation modality following lumpectomy in patients with early-stage breast cancer. Methods and Materials: Thirty-seven patients with 38 Stage I-II breast cancers received radiation to the lumpectomy cavity alone using an HDR interstitial implant with 192 Ir. A minimum dose of 32 Gy was delivered on an outpatient basis in 8 fractions of 4 Gy to the lumpectomy cavity plus a 1- to 2-cm margin over consecutive 4 days. Results: Median follow-up is 31 months. There has been one ipsilateral breast recurrence for a crude failure rate of 2.6% and no regional or distant failures. Wound healing was not impaired in patients undergoing an open-cavity implant. Three minor breast infections occurred, and all resolved with oral antibiotics. The cosmetic outcome was good to excellent in all patients. Conclusion: In selected patients with early-stage breast cancer, treatment of the lumpectomy cavity alone with outpatient HDR brachytherapy is both technically feasible and well tolerated. Early results are encouraging, however, longer follow-up is necessary before equivalence to standard whole-breast irradiation can be established and to determine the most optimal radiation therapy technique to be employed

  11. Our experience of high dose I-131 therapy in 75 patients with well differentiated carcinoma thyroid followed up over 5 years

    International Nuclear Information System (INIS)

    Dougall, P.; Kumar, A.; Ashok, P.; Chinwan, B.P.; Khan, B.; Pandey, D.; Joshi, N.D.

    2005-01-01

    Thyroid cancer is the most common endocrine malignancy. The epidemiology of thyroid cancer is variable, depending on the geographic location of the patient population. Well differentiated thyroid cancer (WTC), is responsive to high dose I-131 treatment, and is the most accepted form of therapy, even though the dose administered for ablation of residual thyroid tissue maybe controversial. At our centre, 75 patients of WTC, mean age 42.4 years, 22 males and 53 females (M:F 1:2.4), were treated with high dose oral I-131 therapy with a Total Mean Dose (TMD) of 263.6 mCi, 4 - 6 weeks post thyroidectomy. They were followed up over a period of 6 years. Twenty ( 26.7%) patients had follicular cancer (FC), 47 (62.7%) papillary cancer (PC) and 8 (10.7%) were mixed (MC), on histopathology, at presentation. 38 (50.7%) patients had only residual thyroid tissue (RTT) on I-131 whole body bone scan (WBS) and 37 (49.3%) presented with metastatic disease (MD) at the time of therapy. Of the 37 patients with MD, 21 (56.8%) had metastases to the lymph nodes, 6 (16.2%) to the lungs, 4 (10.8%) to bone, 3 (8.1%) to bone and lung, and 4 (10.8%) to lung plus lymph nodes. Twenty-three patients (7 FC , 13 - PC and 3 MC; 6 RTT, 17 - MD) , received more than one dose of I-131 with a TMD of 422.7 mCi (Range 88 1590 mCi ). 52 patients (13 FC, 34 PC, 5 MC; 20 MD and 32 RTT) received a single TMD of 104.4 (Range 39.5 219 mCi). On follow-up, 3 patients of FC with MD (2 lung metastasis and 1 with extensive lymph node metastasis), died within 3 months 2 years of therapy. 3 patients of MD (2 FC, 1-MC; 2 bone metastasis and 1 bone with lung metastasis) died after 5 .5 years, Of the 6 patients who died, 5 were FC and only 1 was MC. 2 patients with MD to lungs and bone had received a single dose and were lost to follow up. All patients with PC and FC with only RTT, were surviving at the end of 5 years. None of the patients with MD to lymph nodes died at the end of 5 years, either receiving single or

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

    Science.gov (United States)

    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.

  13. High dose teriparatide (rPTH1-34) therapy increases callus volume and enhances radiographic healing at 8-weeks in a massive canine femoral allograft model.

    Science.gov (United States)

    Nishitani, Kohei; Mietus, Zachary; Beck, Christopher A; Ito, Hiromu; Matsuda, Shuichi; Awad, Hani A; Ehrhart, Nicole; Schwarz, Edward M

    2017-01-01

    Small animal studies have demonstrated significant high-dose recombinant parathyroid hormone1-34 (rPTH1-34) effects on intercalary allograft healing. Towards a human adjuvant therapy to decrease non-unions, we evaluated rPTH1-34 safety and efficacy in a clinically relevant canine femoral allograft model. Adult female mongrel hounds (n = 20) received a 5cm mid-diaphyseal osteotomy reconstructed with a plated allograft, and were randomized to: 1) Placebo (n = 5; daily saline), 2) Continuous rPTH1-34 (n = 7; 5 μg/kg/day s.c. from day 1-55 post-op), or 3) Delayed rPTH1-34 (n = 8; 5 μg/kg/day s.c. from day 14-28 post-op). Safety was assessed by physical behavior and blood calcium monitoring. Cone beam CT (CB-CT) was performed on days 14, 28 and 56 post-op to assess 2D cortical healing, 3D bone volume, and Union Ratio. Biomechanical testing and dynamic histomorphometry were also performed. The high drug dose was poorly tolerated, as most dogs receiving rPTH1-34 had to be given intravenous saline, and one dog died from hypercalcemia. Continuous rPTH1-34 significantly increased 2D healing and callus volumes at 4-weeks versus Placebo, and sustained the significant increase in cortical union at 8-week (p<0.05). These rPTH1-34 effects were confirmed by histomorphometry, revealing significant increases in mineral apposition rates (MAR) on host bone and graft-host junctions (p<0.05). Delayed rPTH1-34 significantly increased callus volume and MAR at 8 weeks (p<0.05). Although no biomechanical differences were observed, as expected for early healing, the results demonstrated that 2D RUST scoring significantly correlated with torsional biomechanics (p<0.01). In conclusion, 8-weeks of intermittent high-dose rPTH1-34 treatment significantly increases callus formation and accelerates bony union of intercalary massive allografts in a clinically relevant canine model, but with serious side-effects from hypercalcemia.

  14. High dose teriparatide (rPTH1-34 therapy increases callus volume and enhances radiographic healing at 8-weeks in a massive canine femoral allograft model.

    Directory of Open Access Journals (Sweden)

    Kohei Nishitani

    Full Text Available Small animal studies have demonstrated significant high-dose recombinant parathyroid hormone1-34 (rPTH1-34 effects on intercalary allograft healing. Towards a human adjuvant therapy to decrease non-unions, we evaluated rPTH1-34 safety and efficacy in a clinically relevant canine femoral allograft model. Adult female mongrel hounds (n = 20 received a 5cm mid-diaphyseal osteotomy reconstructed with a plated allograft, and were randomized to: 1 Placebo (n = 5; daily saline, 2 Continuous rPTH1-34 (n = 7; 5 μg/kg/day s.c. from day 1-55 post-op, or 3 Delayed rPTH1-34 (n = 8; 5 μg/kg/day s.c. from day 14-28 post-op. Safety was assessed by physical behavior and blood calcium monitoring. Cone beam CT (CB-CT was performed on days 14, 28 and 56 post-op to assess 2D cortical healing, 3D bone volume, and Union Ratio. Biomechanical testing and dynamic histomorphometry were also performed. The high drug dose was poorly tolerated, as most dogs receiving rPTH1-34 had to be given intravenous saline, and one dog died from hypercalcemia. Continuous rPTH1-34 significantly increased 2D healing and callus volumes at 4-weeks versus Placebo, and sustained the significant increase in cortical union at 8-week (p<0.05. These rPTH1-34 effects were confirmed by histomorphometry, revealing significant increases in mineral apposition rates (MAR on host bone and graft-host junctions (p<0.05. Delayed rPTH1-34 significantly increased callus volume and MAR at 8 weeks (p<0.05. Although no biomechanical differences were observed, as expected for early healing, the results demonstrated that 2D RUST scoring significantly correlated with torsional biomechanics (p<0.01. In conclusion, 8-weeks of intermittent high-dose rPTH1-34 treatment significantly increases callus formation and accelerates bony union of intercalary massive allografts in a clinically relevant canine model, but with serious side-effects from hypercalcemia.

  15. Influence of Comorbidity on the Risk of Mortality in Men With Unfavorable-Risk Prostate Cancer Undergoing High-Dose Radiation Therapy Alone

    Energy Technology Data Exchange (ETDEWEB)

    Huynh, Mai Anh, E-mail: mahuynh@lroc.harvard.edu [Harvard Radiation Oncology Program, Brigham and Women' s Hospital, Boston, Massachusetts (United States); Chen, Ming-Hui; Wu, Jing [Department of Statistics, University of Connecticut, Storrs, Connecticut (United States); Braccioforte, Michelle H.; Moran, Brian J. [Prostate Cancer Foundation of Chicago, Westmont, Illinois (United States); D' Amico, Anthony V. [Department of Radiation Oncology, Brigham and Women' s Hospital–Dana-Farber Cancer Institute, Boston, Massachusetts (United States)

    2016-07-15

    Purpose: To explore whether a subgroup of men with unfavorable-risk prostate cancer (PC) exists in whom high-dose radiation therapy (RT) alone is sufficient to avoid excess PC death due to competing risk from cardiometabolic comorbidity. Methods and Materials: This was a cohort study of 7399 men in whom comorbidity (including congestive heart failure, diabetes mellitus, or myocardial infarction) was assessed and recorded with T1-3NxM0 PC treated with brachytherapy with or without neoadjuvant RT, October 1997 to May 2013 at a single providing institution. Cox and competing risks regression analyses were used to assess whether men with unfavorable–intermediate/high-risk versus favorable–intermediate/low-risk PC were at increased risk of PC-specific, all-cause, or other-cause mortality (PCSM, ACM, OCM), adjusting for number of comorbidities, age at and year of brachytherapy, RT use, and an RT treatment propensity score. Results: After a median follow-up of 7.7 years, 935 men died: 80 of PC and 855 of other causes. Among men with no comorbidity, PCSM risk (adjusted hazard ratio [AHR] 2.74 [95% confidence interval (CI) 1.49-5.06], P=.001) and ACM risk (AHR 1.30 [95% CI 1.07-1.58], P=.007) were significantly increased in men with unfavorable–intermediate/high-risk PC versus favorable–intermediate/low-risk PC, with no difference in OCM (P=.07). Although PCSM risk was increased in men with 1 comorbidity (AHR 2.87 [95% CI 1.11-7.40], P=.029), ACM risk was not (AHR 1.03 [95% CI 0.78-1.36], P=.84). Neither PCSM risk (AHR 4.39 [95% CI 0.37-51.98], P=.24) or ACM risk (AHR 1.43 [95% CI 0.83-2.45], P=.20) was increased in men with 2 comorbidities. Conclusions: To minimize death from PC, high-dose RT alone may be sufficient treatment in men with 2 or more cardiometabolic comorbidities and unfavorable–intermediate- and high-risk PC.

  16. Insulin adherence behaviours and barriers in the multinational Global Attitudes of Patients and Physicians in Insulin Therapy study.

    Science.gov (United States)

    Peyrot, M; Barnett, A H; Meneghini, L F; Schumm-Draeger, P-M

    2012-05-01

    To examine patient and physician beliefs regarding insulin therapy and the degree to which patients adhere to their insulin regimens. Internet survey of 1250 physicians (600 specialists, 650 primary care physicians) who treat patients with diabetes and telephone survey of 1530 insulin-treated patients (180 with Type 1 diabetes, 1350 with Type 2 diabetes) in China, France, Japan, Germany, Spain, Turkey, the UK or the USA. One third (33.2%) of patients reported insulin omission/non-adherence at least 1 day in the last month, with an average of 3.3 days. Three quarters (72.5%) of physicians report that their typical patient does not take their insulin as prescribed, with a mean of 4.3 days per month of basal insulin omission/non-adherence and 5.7 days per month of prandial insulin omission/non-adherence. Patients and providers indicated the same five most common reasons for insulin omission/non-adherence: too busy; travelling; skipped meals; stress/emotional problems; public embarrassment. Physicians reported low patient success at initiating insulin in a timely fashion and adjusting insulin doses. Most physicians report that many insulin-treated patients do not have adequate glucose control (87.6%) and that they would treat more aggressively if not for concern about hypoglycaemia (75.5%). Although a majority of patients (and physicians) regard insulin treatment as restrictive, more patients see insulin treatment as having positive than negative impacts on their lives. Glucose control is inadequate among insulin-treated patients, in part attributable to insulin omission/non-adherence and lack of dose adjustment. There is a need for insulin regimens that are less restrictive and burdensome with lower risk of hypoglycaemia. © 2012 The Authors. Diabetic Medicine © 2012 Diabetes UK.

  17. Novel Simple Insulin Delivery Device Reduces Barriers to Insulin Therapy in Type 2 Diabetes

    Science.gov (United States)

    Hermanns, Norbert; Lilly, Leslie C.; Mader, Julia K.; Aberer, Felix; Ribitsch, Anja; Kojzar, Harald; Warner, Jay; Pieber, Thomas R.

    2015-01-01

    Background: The PaQ® insulin delivery system is a simple-to-use patch-on device that provides preset basal rates and bolus insulin on demand. In addition to feasibility of use, safety, and efficacy (reported elsewhere), this study analyzed the impact of PaQ on patient-reported outcomes, including barriers to insulin treatment, diabetes-related distress, and attitudes toward insulin therapy in patients with type 2 diabetes on a stable multiple daily injection (MDI) regimen. Methods: This single-center, open-label, single-arm study comprised three 2-week periods: baseline (MDI), transition from MDI to PaQ, and PaQ treatment. Validated questionnaires were administered during the baseline and PaQ treatment periods: Barriers to Insulin Treatment questionnaire (BIT), Insulin Treatment Appraisal Scale (ITAS), and Problem Areas in Diabetes scale (PAID). Results: Eighteen patients (age 59 ± 5 years, diabetes duration 15 ± 7 years, 21% female, HbA1c 7.7 ± 0.7%) completed the questionnaires. There was a strong, significant effect of PaQ use in mean BIT total scores (difference [D] = −5.4 ± 0.7.7, P = .01, effect size [d] = 0.70). Patients perceived less stigmatization by insulin injection (D = −2.2 ± 6.2, P = .18, d = 0.35), increased positive outcome (D = 1.9 ± 6.6, P = .17, d = 0.29), and less fear of injections (1.3 ± 4.8, P = .55, d = 0.28). Mean change in ITAS scores after PaQ device use showed a nonsignificant improvement of 1.71 ± 5.63 but moderate effect size (d = 0.30, P = .14). No increase in PAID scores was seen. Conclusions: The results and moderate to large effects sizes suggest that PaQ device use has beneficial and clinically relevant effects to overcoming barriers to and negative appraisal of insulin treatment, without increasing other diabetes-related distress. PMID:25670847

  18. Lixisenatide as add-on therapy to basal insulin

    Directory of Open Access Journals (Sweden)

    Brown DX

    2013-12-01

    Full Text Available Dominique Xavier Brown, Emma Louise Butler, Marc Evans Diabetes Department, University Hospital Llandough, Cardiff, UK Abstract: Many patients with type 2 diabetes mellitus do not achieve target glycosylated hemoglobin A1c levels despite optimally titrated basal insulin and satisfactory fasting plasma glucose levels. Current evidence suggests that HbA1c levels are dictated by both basal glucose and postprandial glucose levels. This has led to a consensus that postprandial glucose excursions contribute to poor glycemic control in these patients. Lixisenatide is a once-daily, prandial glucagon-like peptide 1 (GLP-1 receptor agonist with a four-fold affinity for the GLP-1 receptor compared with native GLP-1. Importantly, lixisenatide causes a significant delay in gastric emptying time, an important determinant of the once-daily dosing regimen. An exendin-4 mimetic with six lysine residues removed at the C-terminal, lixisenatide has pronounced postprandial glucose-lowering effects, making it a novel incretin agent for use in combination with optimally titrated basal insulin. Lixisenatide exerts profound effects on postprandial glucose through established mechanisms of glucose-dependent insulin secretion and glucagon suppression in combination with delayed gastric emptying. This review discusses the likely place that lixisenatide will occupy in clinical practice, given its profound effects on postprandial glucose and potential to reduce glycemic variability. Keywords: lixisenatide, add-on therapy, insulin, GLP-1 receptor agonist, postprandial glucose, pharmacodynamics

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

    Energy Technology Data Exchange (ETDEWEB)

    Cury, Fabio L., E-mail: fabio.cury@muhc.mcgill.ca [Department of Radiation Oncology, McGill University Health Centre, Montreal, QC (Canada); Duclos, Marie [Department of Radiation Oncology, McGill University Health Centre, Montreal, QC (Canada); Aprikian, Armen [Department of Urology, McGill University Health Centre, Montreal, QC (Canada); Patrocinio, Horacio [Department of Medical Physics, McGill University Health Centre, Montreal, QC (Canada); Kassouf, Wassim [Department of Urology, McGill University Health Centre, Montreal, QC (Canada); Shenouda, George; Faria, Sergio; David, Marc; Souhami, Luis [Department of Radiation Oncology, McGill University Health Centre, Montreal, QC (Canada)

    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.

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

    International Nuclear Information System (INIS)

    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 5 mm. Rectum, bladder, urethra, and femoral heads were considered as organs at risk. A 78 Gy in 39 fractions were prescribed for PTV. For HDR and LDR plans, the dose prescription was D 90 of 34 Gy in 8.5 Gy per fraction, and 145 Gy 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 2 Gy per fraction, EQD 2 ) for comparison of 3 techniques. HDR and LDR significantly reduced the dose to rectum and bladder compared with VMAT. The D mean (EQD 2 ) of rectum decreased 22.36 Gy in HDR and 17.01 Gy in LDR from 30.24 Gy in VMAT, respectively. The D mean (EQD 2 ) of bladder decreased 6.91 Gy in HDR and 2.53 Gy in LDR from 13.46 Gy 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 (EQD 2 ) was 80.26, 70.23, and 104.91 Gy 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.

  1. Phase I/II trial of single-fraction high-dose-rate brachytherapy-boosted hypofractionated intensity-modulated radiation therapy for localized adenocarcinoma of the prostate.

    Science.gov (United States)

    Myers, Michael A; Hagan, Michael P; Todor, Dorin; Gilbert, Lynn; Mukhopadhyay, Nitai; Randolf, Jessica; Heimiller, Jeffrey; Anscher, Mitchell S

    2012-01-01

    A Phase I/II protocol was conducted to examine the toxicity and efficacy of the combination of intensity-modulated radiation therapy (IMRT) with a single-fraction high-dose-rate (HDR) brachytherapy implant. From 2001 through 2006, 26 consecutive patients were treated on the trial. The primary objective was to demonstrate a high rate of completion without experiencing a treatment-limiting toxicity. Eligibility was limited to patients with T stage ≤2b, prostate-specific antigen (PSA) ≤20, and Gleason score ≤7. Treatment began with a single HDR fraction of 6Gy to the entire prostate and 9Gy to the peripheral zone, followed by IMRT optimized to deliver in 28 fractions with a normalized total dose of 70Gy. Patients received 50.4Gy to the pelvic lymph node. The prostate dose (IMRT and HDR) resulted in an average biologic equivalent dose >128Gy (α/β=3). Patients whose pretreatment PSA was ≥10ng/mL, Gleason score 7, or stage ≥T2b received short-term androgen ablation. Median followup was 53 months (9-68 months). There were no biochemical failures by either the American Society of Therapeutic Radiology and Oncology or the Phoenix definitions. The median nadir PSA was 0.32ng/mL. All the 26 patients completed the treatment as prescribed. The rate of Grade 3 late genitourinary toxicity was 3.8% consisting of a urethral stricture. There was no other Grade 3 or 4 genitourinary or gastrointestinal toxicities. Single-fraction HDR-boosted IMRT is a safe effective method of dose escalation for localized prostate cancer. Copyright © 2012 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

  2. Safety and efficacy of high-dose daptomycin as salvage therapy for severe gram-positive bacterial sepsis in hospitalized adult patients

    Directory of Open Access Journals (Sweden)

    Lai Chung-Chih

    2013-02-01

    Full Text Available Abstract Background Increasing the dosage of daptomycin may be advantageous in severe infection by enhancing bactericidal activity and pharmacodynamics. However, clinical data on using daptomycin at doses above 6 mg/kg in Asian population are limited. Methods A retrospective observational cohort study of all hospitalized adult patients treated with daptomycin (> 6 mg/kg for at least 72 hours was performed in Taiwan. Results A total of 67 patients (40 males with a median age of 57 years received a median dose of 7.61 mg/kg (range, 6.03-11.53 mg/kg of daptomycin for a median duration of 14 days (range, 3–53 days. Forty-one patients (61.2% were in intensive care units (ICU. Sites of infections included complicated skin and soft tissue infections (n = 16, catheter-related bacteremia (n = 16, endocarditis (n = 11, primary bacteremia (n = 10, osteomyelitis and septic arthritis (n = 9, and miscellaneous (n = 5. The median Pitt bacteremia score among the 54 (80.6% patients with bacteremia was 4. The most common pathogen was methicillin-resistant Staphylococcus aureus (n = 38. Fifty-nine patients (88.1% were treated with daptomycin after glycopepetide use. Overall, 52 (77.6% patients achieved clinical success. The all-cause mortality rate at 28 day was 35.8%. In multivariate analysis, the significant predictors of in-hospital mortality in 54 bacteremic patients were malignancies (P = 0.01 and ICU stay (P = 0.02. Adverse effects of daptomycin were generally well-tolerated, leading to discontinuation in 3 patients. Daptomycin-related creatine phosphokinase (CPK elevations were observed in 4 patients, and all received doses > 8 mg/kg. Conclusions Treatment with high dose daptomycin as salvage therapy was generally effective and safe in Taiwan. CPK level elevations were more frequent in patients with dose > 8 mg/kg.

  3. Insulin Therapy for the Management of Hyperglycemia in Hospitalized Patients

    Science.gov (United States)

    McDonnell, Marie E.; Umpierrez, Guillermo E.

    2013-01-01

    It has long been established that hyperglycemia with or without a prior diagnosis of diabetes increases both mortality and disease-specific morbidity in hospitalized patients1–4 and that goal-directed insulin therapy can improve outcomes.5–9 During the past decade, since the widespread institutional adoption of intensified insulin protocols after the publication of a landmark trial,5,10 the pendulum in the inpatient diabetes literature has swung away from achieving intensive glucose control and toward more moderate and individualized glycemic targets.11,12 This change in clinical practice is the result of several factors, including challenges faced by hospitals to coordinate glycemic control across all levels of care,13,14 publication of negative prospective trials,15,16 revised recommendations from professional organizations,17,18 and increasing evidence on the deleterious effect of hypoglycemia.19–22 This article reviews the pathophysiology of hyperglycemia during illness, the mechanisms for increased complications and mortality due to hyperglycemia and hypoglycemia, beneficial mechanistic effects of insulin therapy and provides updated recommendations for the inpatient management of diabetes in the critical care setting and in the general medicine and surgical settings.23,24 PMID:22575413

  4. Managing insulin therapy during exercise in type 1 diabetes mellitus.

    Science.gov (United States)

    Toni, Sonia; Reali, Maria Francesca; Barni, Federica; Lenzi, Lorenzo; Festini, Filippo

    2006-01-01

    Exercise is integral to the life of T1DM subjects. Several factors influence the metabolic response to exercise in these patients. Despite physical and psychological benefits of exercise, its hypo- and hyperglycemic effects may cause discouragement from participation in sports and games. To use existing evidence from literature to provide practical indications for the management of insulin therapy in subjects with T1DM who practice sports or physical activities. Bibliographic research was performed on PubMed and the main Systematic Review and Guidelines database were also searched. Existing guidelines are useful but the exact adjustments of insulin dose must be made on an individual basis and these adjustments can be made only by "trial and error" approach. These clinical indications may be a starting point from which health care providers can find practical advices for each patient.

  5. A Novel Form of Breast Intraoperative Radiation Therapy With CT-Guided High-Dose-Rate Brachytherapy: Results of a Prospective Phase 1 Clinical Trial

    International Nuclear Information System (INIS)

    Showalter, Shayna L.; Petroni, Gina; Trifiletti, Daniel M.; Libby, Bruce; Schroen, Anneke T.; Brenin, David R.; Dalal, Parchayi; Smolkin, Mark; Reardon, Kelli A.; Showalter, Timothy N.

    2016-01-01

    Purpose: Existing intraoperative radiation therapy (IORT) techniques are criticized for the lack of image guided treatment planning and energy deposition with, at times, poor resultant dosimetry and low radiation dose. We pioneered a novel method of IORT that incorporates customized, computed tomography (CT)-based treatment planning and high-dose-rate (HDR) brachytherapy to overcome these drawbacks: CT-HDR-IORT. Methods and Materials: A phase 1 study was conducted to demonstrate the feasibility and safety of CT-HDR-IORT. Eligibility criteria included age ≥50 years, invasive or in situ breast cancer, tumor size <3 cm, and N0 disease. Patients were eligible before or within 30 days of breast-conserving surgery (BCS). BCS was performed, and a multilumen balloon catheter was placed. CT images were obtained, a customized HDR brachytherapy plan was created, and a dose of 12.5 Gy was delivered to 1-cm depth from the balloon surface. The catheter was removed, and the skin was closed. The primary endpoints were feasibility and acute toxicity. Feasibility was defined as IORT treatment interval (time from CT acquisition until IORT completion) ≤90 minutes. The secondary endpoints included dosimetry, cosmetic outcome, quality of life, and late toxicity. Results: Twenty-eight patients were enrolled. The 6-month follow-up assessments were completed by 93% of enrollees. The median IORT treatment interval was 67.2 minutes (range, 50-108 minutes). The treatment met feasibility criteria in 26 women (93%). The dosimetric goals were met in 22 patients (79%). There were no Radiation Therapy Oncology Group grade 3+ toxicities; 6 patients (21%) experienced grade 2 events. Most patients (93%) had good/excellent cosmetic outcomes at the last follow-up visit. Conclusions: CT-HDR-IORT is feasible and safe. This promising approach for a conformal, image-based, higher-dose breast IORT is being evaluated in a phase 2 trial.

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

    Energy Technology Data Exchange (ETDEWEB)

    Ghadjar, Pirus; Zelefsky, Michael J.; Spratt, Daniel E. [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Munck af Rosenschöld, Per; Oh, Jung Hun; Hunt, Margie [Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Kollmeier, Marisa [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Happersett, Laura; Yorke, Ellen; Deasy, Joseph O. [Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Jackson, Andrew, E-mail: jacksona@mskcc.org [Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, New York (United States)

    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

  7. Early and late toxicity of involved-field radiation therapy in conjunction with high-dose chemotherapy and stem cell rescue

    International Nuclear Information System (INIS)

    Lubich, L.; Mundt, A.; Sibley, G.; Hallahan, D.; Nautiyal, J.; Weichselbaum, R.

    1995-01-01

    Purpose: Recent reports have demonstrated a benefit to involved-field radiation therapy (IFRT) in patients with relapsed/metastatic disease undergoing high-dose chemotherapy (HDCT) and stem cell rescue (SCR). We evaluate here the early and late toxicity of this approach. Methods: Eighty-five patients with either metastatic breast cancer (MBC) (31) or relapsed/refractory Hodgkin's disease (HD) (54) underwent HDCT/SCR. HDCT in the MBC patients consisted of cytoxan, thiotepa +/- carmustine and VP-16, cytoxan, BCNU +/- thiotepa in the HD patients. Thirty-four patients (40%) received IFRT either prior to (14) or following (20) HDCT to sites of disease involvement. A total of 18 patients received chest wall/mediastinal (CWMED) RT. Median followup for the MBC and HD patients were 21.3 months and 41 months, respectively. Results: Acute sequelae were similar in the 2 groups. Only one patient (5%) treated with IFRT (HD with 5 nodal sites) required a break from therapy due to low blood counts. Seven patients (0 MBC, 7 HD) (8.2%) suffered a toxic death (TD). No difference in was seen in the rate of TD in the patients as a whole ((1(14)) vs. (6(71))) (p =0.87) nor in the HD patients alone ((1(7)) vs. (6(47))) (p =0.91) with the use of IFRT prior to HDCT. Eleven patients (12.9%) developed late toxicity: 3 myelodysplasia/acute leukemia (MAL), 2 persistent low blood counts (requiring transfusions), 4 pulmonary toxicity (PT) and 2 hypothyroidism. All 4 cases of PT occurred in the HD group of which 3 received CWMED RT. The Table below shows the 5-yr actuarial risk of PT with and without CWMED RT as well as the 5-yr actuarial risk of MAL and any hematologic sequelae with and without RT. Multivariate analysis in the HD patients demonstrated that CWMED RT was the most significant factor for PT (p =0.09). All 3 cases of MAL and the 2 cases of persistent low blood counts occurred in the HD group. The use of IFRT did not increase the incidence of MAL or of any hematologic sequelae

  8. A Novel Form of Breast Intraoperative Radiation Therapy With CT-Guided High-Dose-Rate Brachytherapy: Results of a Prospective Phase 1 Clinical Trial

    Energy Technology Data Exchange (ETDEWEB)

    Showalter, Shayna L., E-mail: snl2t@virginia.edu [Division of Surgical Oncology, Department of Surgery, University of Virginia School of Medicine, Charlottesville, Virginia (United States); Petroni, Gina [Division of Translation Research and Applied Statistics, Department of Public Health Sciences, University of Virginia School of Medicine, Charlottesville, Virginia (United States); Trifiletti, Daniel M.; Libby, Bruce [Department of Radiation Oncology, University of Virginia School of Medicine, Charlottesville, Virginia (United States); Schroen, Anneke T.; Brenin, David R. [Division of Surgical Oncology, Department of Surgery, University of Virginia School of Medicine, Charlottesville, Virginia (United States); Dalal, Parchayi [Department of Radiation Oncology, University of Virginia School of Medicine, Charlottesville, Virginia (United States); Smolkin, Mark [Division of Translation Research and Applied Statistics, Department of Public Health Sciences, University of Virginia School of Medicine, Charlottesville, Virginia (United States); Reardon, Kelli A.; Showalter, Timothy N. [Department of Radiation Oncology, University of Virginia School of Medicine, Charlottesville, Virginia (United States)

    2016-09-01

    Purpose: Existing intraoperative radiation therapy (IORT) techniques are criticized for the lack of image guided treatment planning and energy deposition with, at times, poor resultant dosimetry and low radiation dose. We pioneered a novel method of IORT that incorporates customized, computed tomography (CT)-based treatment planning and high-dose-rate (HDR) brachytherapy to overcome these drawbacks: CT-HDR-IORT. Methods and Materials: A phase 1 study was conducted to demonstrate the feasibility and safety of CT-HDR-IORT. Eligibility criteria included age ≥50 years, invasive or in situ breast cancer, tumor size <3 cm, and N0 disease. Patients were eligible before or within 30 days of breast-conserving surgery (BCS). BCS was performed, and a multilumen balloon catheter was placed. CT images were obtained, a customized HDR brachytherapy plan was created, and a dose of 12.5 Gy was delivered to 1-cm depth from the balloon surface. The catheter was removed, and the skin was closed. The primary endpoints were feasibility and acute toxicity. Feasibility was defined as IORT treatment interval (time from CT acquisition until IORT completion) ≤90 minutes. The secondary endpoints included dosimetry, cosmetic outcome, quality of life, and late toxicity. Results: Twenty-eight patients were enrolled. The 6-month follow-up assessments were completed by 93% of enrollees. The median IORT treatment interval was 67.2 minutes (range, 50-108 minutes). The treatment met feasibility criteria in 26 women (93%). The dosimetric goals were met in 22 patients (79%). There were no Radiation Therapy Oncology Group grade 3+ toxicities; 6 patients (21%) experienced grade 2 events. Most patients (93%) had good/excellent cosmetic outcomes at the last follow-up visit. Conclusions: CT-HDR-IORT is feasible and safe. This promising approach for a conformal, image-based, higher-dose breast IORT is being evaluated in a phase 2 trial.

  9. High-dose "1"3"1I-MIBG therapies in children: feasibility, patient dosimetry and radiation exposure to workers and family caregivers

    International Nuclear Information System (INIS)

    Cougnenc, Olivier; Defachelles, Anne-Sophie; Lervat, Cyril; Carpentier, Philippe; Oudoux, Aurore; Kolesnikov-Gauthier, Helene; Clisant, Stephanie

    2017-01-01

    The objective of the present multi-centric phase II study (MIITOP) was to determine the response rate, survival and toxicity of tandem infusions of "1"3"1I-meta-iodobenzylguanidine (mIBG) and topotecan in children with relapsed/refractory neuroblastoma. High-dose "1"3"1I-mIBG therapy programme requires a deal of planning, availability of hospital resources and the commitment of individuals with training and expertise in multiple disciplines. Here in the present study, procedures and the results of patient's dosimetry, as well as family and worker's exposures, were reported for the patients treated in Lille. A total of 15 children were treated with "1"3"1I-mIBG between 2009 and 2011 according to the MIITOP protocol. High activity of "1"3"1I-mIBG (444 MBq kg"-"1) was administered on Day 0. In vivo dosimetry was used to calculate a second activity, to be given on Day 21, to obtain a total whole body absorbed dose of 4 Gy. Family and worker's exposures were performed too. The injected activity by treatment was from 703 to 11470 MBq. Total whole body absorbed dose by patient ranged from 2.74 to 5.2 Gy. Concerning relatives, whole body exposure ranged from 0.018 to 2.8 mSv. The mean whole body exposure of the radio-pharmacist was 4.4 nSv MBq"-"1, and the mean exposure of fingers ranged from 0.18 to 0.24 μSv MBq"-"1 according to each finger. The mean whole body exposure was 33.6 and 20.2 μSv d"-"1 per person, for night nurses and day nurses, respectively. Exposure of doctors was less than 5 μSv d"-"1. Under strict radiation protection precautions, this study shows the feasibility of high-activity "1"3"1I-mIBG therapy in France. (authors)

  10. Novel Simple Insulin Delivery Device Reduces Barriers to Insulin Therapy in Type 2 Diabetes: Results From a Pilot Study

    OpenAIRE

    Hermanns, Norbert; Lilly, Leslie C.; Mader, Julia K.; Aberer, Felix; Ribitsch, Anja; Kojzar, Harald; Warner, Jay; Pieber, Thomas R.

    2015-01-01

    Background: The PaQ® insulin delivery system is a simple-to-use patch-on device that provides preset basal rates and bolus insulin on demand. In addition to feasibility of use, safety, and efficacy (reported elsewhere), this study analyzed the impact of PaQ on patient-reported outcomes, including barriers to insulin treatment, diabetes-related distress, and attitudes toward insulin therapy in patients with type 2 diabetes on a stable multiple daily injection (MDI) regimen. Methods: This singl...

  11. Early intranasal insulin therapy halts progression of neurodegeneration: progress in Alzheimer's disease therapeutics.

    Science.gov (United States)

    de la Monte, Suzanne M

    Evaluation of Craft S, Baker LD, Montine TJ, Minoshima S, Watson GS, Claxton A, et al. Intranasal Insulin Therapy for Alzheimer Disease and Amnestic Mild Cognitive Impairment: A Pilot Clinical Trial. Arch Neurol . 2011 Sep 12. Alzheimer's disease is associated with brain insulin deficiency and insulin resistance, similar to the problems in diabetes. If insulin could be supplied to the brain in the early stages of Alzheimer's, subsequent neurodegeneration might be prevented. Administering systemic insulin to elderly non-diabetics poses unacceptable risks of inadvertant hypoglycemia. However, intranasal delivery directs the insulin into the brain, avoiding systemic side-effects. This pilot study demonstrates both efficacy and safety of using intranasal insulin to treat early Alzheimer's and mild cognitive impairment, i.e. the precursor to Alzheimer's. Significant improvements in learning, memory, and cognition occured within a few months, but without intranasal insulin, brain function continued to deteriorate in measurable degrees. Intranasal insulin therapy holds promise for halting progression of Alzheimer's disease.

  12. High-dose therapy and autologous bone marrow transplantation for Hodgkin's disease patients with relapses potentially treatable by radical radiation therapy

    International Nuclear Information System (INIS)

    Pezner, Richard D.; Nademanee, Auayporn; Forman, Stephen J.

    1995-01-01

    Purpose: A retrospective review evaluated the results of autologous bone marrow transplantation (A-BMT) for patients with relapsed Hodgkin's disease (HD) who were potentially treatable by radical radiation therapy (RRT). Methods and Materials: Evaluated patient cases met the following criteria: initial treatment with chemotherapy (with or without involved field radiation therapy 20 Gy to spinal cord); HD at time of salvage therapy limited to lymph nodes, Waldeyer's ring, liver, spleen, direct extension sites, and/or one lung. Results: There were 23 A-BMT patients treated between 1986 and 1991 who fulfilled the criteria. Three (13%) patients died from treatment-related complications and eight (35%) developed nonfatal Grade 3-4 complications. The 3-year actuarial disease-free survival rate was 61%. The 3-year disease-free survival rate was 55% for the nine patients with at least one prior disease-free interval (DFI) > 12 months, 67% for nine patients with DFI 0.10). These results are comparable to retrospective studies of RRT results in selected relapsed HD patients. Conclusions: Long-term disease-free survival is frequently possible with either A-BMT or RRT appropriately selected relapsed HD patients. In considering treatment options, important prognostic factors include initial stage of disease, number of prior relapses, DFI, and extent of relapsed disease

  13. Comparison of high dose rate (HDR) and low dose rate (LDR) brachytherapy in the treatment of stage IIIB cervix cancer with radiation therapy alone. The preliminary results

    International Nuclear Information System (INIS)

    Trippe, Nivaldo; Novaes, P.E.; Ferrigno, R.; Pellizzon, A.C.; Salvajoli, J.V.; Fogaroli, R.C.; Maia, M.A.C.; Baraldi, H.E.

    1996-01-01

    Purpose/Objective: To compare the results between HDR and LDR brachytherapy in the treatment of stage IIIB cervix cancer with radiation therapy alone through a prospective and randomized trial. Materials and Methods: From September 1992 to December 1993, 65 patients with stage IIIB cervical cancer were randomized to one of the following treatment schedule according to the brachytherapy used to complement the dose of external beam radiotherapy (EBRT): 1 - High dose rate (HDR) - 36 patients - 4 weekly insertions of 6,0 Gy at point A 2 - Low dose rate (LDR) - 29 patients - 2 insertions two weeks apart of 17,5 Gy at point A The External Beam radiotherapy was performed through a Linac 4MV, in box arrangement for whole pelvis and in AP-PA fields for parametrial complementation of dose. The dose at the whole pelvis was 45 Gy in 25 fractions of 1,8 Gy and the parametrial dose was 16 Gy. The brachytherapy was realized with Fletcher colpostats and intrauterine tandem, in both arms. The HDR brachytherapy was realized through a Micro-Selectron device, working with Iridium-192 with initial activity of 10 Ci and started ten days after the beginning of EBRT. The total treatment time was shortened in two weeks for this group. The LDR brachytherapy started only after the end of EBRT. Results: With the minimum follow up of 24 months and medium of 31 months, the disease free survival was 50% among the 36 patients in HDR group and 47,8% among the 29 patients in LDR group. Local failures occurred in 50% and 52,8% respectively. Grade I and II complications were restricted to rectites and cistites and the incidence of them was 8,3% for HDR group and 13% for LDR group. Until the time of evaluation there were no grade III complications in any group. Conclusions: Although the number of patients is small and the time of follow up still short, these preliminary results suggest that the HDR brachytherapy has an equivalent efficiency in local control as the LDR in the treatment of stage IIIB

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

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Ruijie, E-mail: ruijyang@yahoo.com; Zhao, Nan; Liao, Anyan; Wang, Hao; Qu, Ang

    2016-10-01

    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 5 mm. Rectum, bladder, urethra, and femoral heads were considered as organs at risk. A 78 Gy in 39 fractions were prescribed for PTV. For HDR and LDR plans, the dose prescription was D{sub 90} of 34 Gy in 8.5 Gy per fraction, and 145 Gy 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 2 Gy per fraction, EQD{sub 2}) for comparison of 3 techniques. HDR and LDR significantly reduced the dose to rectum and bladder compared with VMAT. The D{sub mean} (EQD{sub 2}) of rectum decreased 22.36 Gy in HDR and 17.01 Gy in LDR from 30.24 Gy in VMAT, respectively. The D{sub mean} (EQD{sub 2}) of bladder decreased 6.91 Gy in HDR and 2.53 Gy in LDR from 13.46 Gy 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 (EQD{sub 2}) was 80.26, 70.23, and 104.91 Gy 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.

  15. High dose rate intraoperative radiation therapy (HDR-IORT) as part of the management strategy for locally advanced primary and recurrent rectal cancer

    International Nuclear Information System (INIS)

    Harrison, Louis B.; Minsky, Bruce D.; Enker, Warren E.; Mychalczak, Borys; Guillem, Jose; Paty, Philip B.; Anderson, Lowell; White, Carol; Cohen, Alfred M.

    1998-01-01

    Purpose: Primary unresectable and locally advanced recurrent rectal cancer presents a significant clinical challenge. Local failure rates are high in both situations. Under such circumstances, there is a significant need to safely deliver tumoricidal doses of radiation in an attempt to improve local control. For this reason, we have incorporated a new approach utilizing high dose rate intraoperative radiation therapy (HDR-IORT). Methods and Materials: Between 11/92-12/96, a total of 112 patients were explored, of which 68 patients were treated with HDR-IORT, and 66 are evaluable. The majority of the 44 patients were excluded for unresectable disease or for distant metastases which eluded preoperative imaging. There were 22 patients with primary unresectable disease, and 46 patients who presented with recurrent disease. The histology was adenocarcinoma in 64 patients, and squamous cell carcinoma in four patients. In general, the patients with primary unresectable disease received preoperative chemotherapy with 5-fluorouracil (5-FU) and leucovorin, and external beam irradiation to 4500-5040 cGy, followed by surgical resection and HDR-IORT (1000-2000 cGy). In general , the patients with recurrent disease were treated with surgical resection and HDR-IORT (1000-2000 cGy) alone. All surgical procedures were done in a dedicated operating room in the brachytherapy suite, so that HDR-IORT could be delivered using the Harrison-Anderson-Mick (HAM) applicator. The median follow-up is 17.5 months (1-48 mo). Results: In primary cases, the actuarial 2-year local control is 81%. For patients with negative margins, the local control was 92% vs. 38% for those with positive margins (p = 0.002). The 2-year actuarial disease-free survival was 69%; 77% for patients with negative margins vs. 38% for patients with positive margins (p = 0.03). For patients with recurrent disease, the 2-year actuarial local control rate was 63%. For patients with negative margins, it was 82%, while it was

  16. Is insulin the most effective injectable antihyperglycaemic therapy?

    Science.gov (United States)

    Buse, J B; Peters, A; Russell-Jones, D; Furber, S; Donsmark, M; Han, J; MacConell, L; Maggs, D; Diamant, M

    2015-02-01

    The recent type 2 diabetes American Diabetes Association/European Association for the Study of Diabetes (ADA/EASD) position statement suggested insulin is the most effective glucose-lowering therapy, especially when glycated haemoglobin (HbA1c) is very high. However, randomized studies comparing glucagon-like peptide-1 receptor agonists (GLP-1RAs) exenatide once-weekly [OW; DURATION-3 (Diabetes therapy Utilization: Researching changes in A1c, weight, and other factors Through Intervention with exenatide ONce-Weekly)] and liraglutide once-daily [OD; LEAD-5 (Liraglutide Effect and Action in Diabetes)] with insulin glargine documented greater HbA1c reduction with GLP-1RAs, from baseline HbA1c ∼8.3% (67 mmol/mol). This post hoc analysis of DURATION-3 and LEAD-5 examined changes in HbA1c, fasting glucose and weight with exenatide OW or liraglutide and glargine, by baseline HbA1c quartile. Descriptive statistics were provided for change in HbA1c, fasting glucose, weight, and insulin dose, and subjects (%) achieving HbA1c <7.0%, by baseline HbA1c quartile. Inferential statistical analysis on the effect of baseline HbA1c quartile was performed for change in HbA1c. An analysis of covariance (ANCOVA) model was used to evaluate similarity in change in HbA1c across HbA1c quartiles. At 26 weeks, in both studies, HbA1c reduction, and proportion of subjects reaching HbA1c <7.0%, were similar or numerically greater with the GLP-1RAs than glargine for all baseline HbA1c quartiles. Fasting glucose reduction was similar or numerically greater with glargine. Weight decreased with both GLP-1RAs across all quartiles; subjects taking glargine gained weight, more at higher baseline HbA1c. Adverse events were uncommon although gastrointestinal events occurred more frequently with GLP-1RAs. HbA1c reduction with the GLP-1RAs appears at least equivalent to that with basal insulin, irrespective of baseline HbA1c. This suggests that liraglutide and exenatide OW may be appropriate

  17. Bortezomib before and after high-dose therapy in myeloma : Long-term results from the phase III HOVON-65/GMMGHD-4 trial

    NARCIS (Netherlands)

    Goldschmidt, H.; Lokhorst, H. M.; Mai, E. K.; van der Holt, B.; Blau, I. W.; Zweegman, S.; Weisel, K. C.; Vellenga, E.; Pfreundschuh, M.; Kersten, M. J.; Scheid, C.; Croockewit, S.; Raymakers, R.; Hose, D.; Potamianou, A.; Jauch, A.; Hillengass, J.; Stevens-Kroef, M.; Raab, M. S.; Broijl, A.; Lindemann, H. W.; Bos, G. M. J.; Brossart, P.; Kooy, M. van Marwijk; Ypma, P.; Duehrsen, U.; Schaafsma, R. M.; Bertsch, U.; Hielscher, T.; Jarari, Le; Salwender, H. J.; Sonneveld, P.

    The Dutch-Belgian Cooperative Trial Group for Hematology Oncology Group-65/German-speaking Myeloma Multicenter Group-HD4 (HOVON-65/GMMG-HD4) phase III trial compared bortezomib (BTZ) before and after high-dose melphalan and autologous stem cell transplantation (HDM, PAD arm) compared with classical

  18. Bortezomib before and after high-dose therapy in myeloma: long-term results from the phase III HOVON-65/GMMGHD-4 trial

    NARCIS (Netherlands)

    Goldschmidt, H.; Lokhorst, H. M.; Mai, E. K.; van der Holt, B.; Blau, I. W.; Zweegman, S.; Weisel, K. C.; Vellenga, E.; Pfreundschuh, M.; Kersten, M. J.; Scheid, C.; Croockewit, S.; Raymakers, R.; Hose, D.; Potamianou, A.; Jauch, A.; Hillengass, J.; Stevens-Kroef, M.; Raab, M. S.; Broijl, A.; Lindemann, H. W.; Bos, G. M. J.; Brossart, P.; van Marwijk Kooy, M.; Ypma, P.; Duehrsen, U.; Schaafsma, R. M.; Bertsch, U.; Hielscher, T.; Jarari, Le; Salwender, H. J.; Sonneveld, P.

    2018-01-01

    The Dutch-Belgian Cooperative Trial Group for Hematology Oncology Group-65/German-speaking Myeloma Multicenter Group-HD4 (HOVON-65/GMMG-HD4) phase III trial compared bortezomib (BTZ) before and after high-dose melphalan and autologous stem cell transplantation (HDM, PAD arm) compared with classical

  19. Daptomycin in the treatment of prosthetic joint infection by Enterococcus faecalis: safety and efficacy of high-dose and prolonged therapy

    OpenAIRE

    José Ramón Yuste; Milena Quesada; Pablo Díaz-Rada; José Luis Del Pozo

    2014-01-01

    Enterococci are implicated in less than 2.3% of prosthetic joint infections. These infections can be difficult to treat and therapeutic failures are not uncommon. In these situations, daptomycin is a safe and effective alternative. We present a clinical case with a successful response to the prolonged use of high-dose daptomycin.

  20. Daptomycin in the treatment of prosthetic joint infection by Enterococcus faecalis: safety and efficacy of high-dose and prolonged therapy

    Directory of Open Access Journals (Sweden)

    José Ramón Yuste

    2014-10-01

    Full Text Available Enterococci are implicated in less than 2.3% of prosthetic joint infections. These infections can be difficult to treat and therapeutic failures are not uncommon. In these situations, daptomycin is a safe and effective alternative. We present a clinical case with a successful response to the prolonged use of high-dose daptomycin.

  1. Management of insulin pump therapy in children with type 1 diabetes.

    Science.gov (United States)

    Abdullah, Nadeem; Pesterfield, Claire; Elleri, Daniela; Dunger, David B

    2014-12-01

    Insulin pump therapy is a current treatment option for children and adolescents with type 1 diabetes. Insulin pumps can provide a greater flexibility in insulin administration and meal planning, as compared with multiple insulin injections, and they may be particularly suitable for the paediatric age group. Many young people with diabetes have integrated insulin pumps into their daily practice. The use of insulin pumps can also be supplemented by the information retrieved from continuous glucose monitoring in the sensor-augmented pump therapy, which may improve glycaemic control. In this review, we describe the principles of pump therapy and summarise features of commercially available insulin pumps, with focus on practical management and the advantages and disadvantages of this technology. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  2. Skull base chordomas: treatment outcome and prognostic factors in adult patients following conformal treatment with 3D planning and high dose fractionated combined proton and photon radiation therapy

    Energy Technology Data Exchange (ETDEWEB)

    Munzenrider, J E; Hug, E; McManus, P; Adams, J; Efird, J; Liebsch, N J

    1995-07-01

    Purpose: To report treatment outcome and prognostic factors for local recurrence-free survival and overall survival in adult patients with skull base chordomas treated with 3D planning and high dose fractionated combined proton and photon radiation therapy. Methods and Materials: From 1975 through 1993, 132 adult patients with skull base chordomas were treated with fractionated combined proton and photon radiation therapy. Seventy five patients (57%) were male and 57 (43%) female. Age ranged from 19 to 80 years (median 45.5 years). All pathology was verified at MGH by a single pathologist. Ninety six had non-chondroid (NCC) and 36 chondroid chordomas (CC), respectively. Median prescribed dose was 68.7 CGE (CGE, Cobalt Gray-equivalent: proton Gy X RBE 1.1 + photon Gy), ranging from 36 to 79.2 CGE; 95% received {>=} 66.6 CGE. Between 70 and 100% of the dose was given with the 160 MeV proton beam at the Harvard Cyclotron. 3D CT-based treatment planning has been employed in all patients treated since 1980. Median follow-up was 46 months (range 2-158 months). Results: Treatment outcome was evaluated in terms of local recurrence-free survival (LRFS) and disease specific survival (DSS), as well as treatment-related morbidity. Local failure (LF), defined as progressive neurological deficit with definite increase in tumor volume on CT or MRI scan, occurred in 39 patients (29.5%). LF was more common among women than among men:(26(57)) (46%) vs (13(75)) (17%), respectively. Thirty three of the 39 LF were seen in non-chondroid chordoma patients, with 6 occurring in patients with the chondroid variant (34% of NCC and 17% of CC), respectively. Distant metastasis was documented in 8 patients. LRFS was 81 {+-} 5.8%, 59 {+-} 8.3%, and 43 {+-} 10.4%, and DSS was 94 {+-} 3.6%, 80 {+-} 6.7%, and 50 {+-} 10.7% at 36, 60, and 96 months, respectively, for the total group. LRFS and DSS were not significantly different for patients with NCC than those with CC (p > .05). Gender was

  3. Early intranasal insulin therapy halts progression of neurodegeneration: progress in Alzheimer’s disease therapeutics

    OpenAIRE

    de la Monte, Suzanne M.

    2012-01-01

    Evaluation of Craft S, Baker LD, Montine TJ, Minoshima S, Watson GS, Claxton A, et al. Intranasal Insulin Therapy for Alzheimer Disease and Amnestic Mild Cognitive Impairment: A Pilot Clinical Trial. Arch Neurol. 2011 Sep 12. Alzheimer’s disease is associated with brain insulin deficiency and insulin resistance, similar to the problems in diabetes. If insulin could be supplied to the brain in the early stages of Alzheimer’s, subsequent neurodegeneration might be prevented. ...

  4. Association of Insulin Pump Therapy vs Insulin Injection Therapy With Severe Hypoglycemia, Ketoacidosis, and Glycemic Control Among Children, Adolescents, and Young Adults With Type 1 Diabetes.

    Science.gov (United States)

    Karges, Beate; Schwandt, Anke; Heidtmann, Bettina; Kordonouri, Olga; Binder, Elisabeth; Schierloh, Ulrike; Boettcher, Claudia; Kapellen, Thomas; Rosenbauer, Joachim; Holl, Reinhard W

    2017-10-10

    Insulin pump therapy may improve metabolic control in young patients with type 1 diabetes, but the association with short-term diabetes complications is unclear. To determine whether rates of severe hypoglycemia and diabetic ketoacidosis are lower with insulin pump therapy compared with insulin injection therapy in children, adolescents, and young adults with type 1 diabetes. Population-based cohort study conducted between January 2011 and December 2015 in 446 diabetes centers participating in the Diabetes Prospective Follow-up Initiative in Germany, Austria, and Luxembourg. Patients with type 1 diabetes younger than 20 years and diabetes duration of more than 1 year were identified. Propensity score matching and inverse probability of treatment weighting analyses with age, sex, diabetes duration, migration background (defined as place of birth outside of Germany or Austria), body mass index, and glycated hemoglobin as covariates were used to account for relevant confounders. Type 1 diabetes treated with insulin pump therapy or with multiple (≥4) daily insulin injections. Primary outcomes were rates of severe hypoglycemia and diabetic ketoacidosis during the most recent treatment year. Secondary outcomes included glycated hemoglobin levels, insulin dose, and body mass index. Of 30 579 patients (mean age, 14.1 years [SD, 4.0]; 53% male), 14 119 used pump therapy (median duration, 3.7 years) and 16 460 used insulin injections (median duration, 3.6 years). Patients using pump therapy (n = 9814) were matched with 9814 patients using injection therapy. Pump therapy, compared with injection therapy, was associated with lower rates of severe hypoglycemia (9.55 vs 13.97 per 100 patient-years; difference, -4.42 [95% CI, -6.15 to -2.69]; P young patients with type 1 diabetes, insulin pump therapy, compared with insulin injection therapy, was associated with lower risks of severe hypoglycemia and diabetic ketoacidosis and with better glycemic control during the

  5. Insulin therapy for type 2 diabetes - are we there yet? The d-Nav® story.

    Science.gov (United States)

    Hodish, I

    2018-01-01

    Insulin replacement therapy is mostly used by patients with type 2 diabetes who become insulin deficient and have failed other therapeutic options. They comprise about a quarter of those with diabetes, endures the majority of the complications and consumes the majority of the resources. Adequate insulin replacement therapy can prevent complications and reduce expenses, as long as therapy goals are achieved and maintained. Sadly, these therapy goals are seldom achieved and outcomes have not improved for decades despite advances in pharmacotherapy and technology. There is a growing recognition that the low success rate of insulin therapy results from intra-individual and inter-individual variations in insulin requirements. Total insulin requirements per day vary considerably between patients and constantly change without achieving a steady state. Thus, the key element in effective insulin therapy is unremitting and frequent dosage adjustments that can overcome those dynamics. In practice, insulin adjustments are done sporadically during outpatient clinic. Due to time constraints, providers are not able to deliver appropriate insulin dosage optimization. The d-Nav® Insulin Guidance Service has been developed to provide appropriate insulinization in insulin users without increasing the burden on healthcare systems. It relies on dedicated clinicians and a spectrum of technological solutions. Patients are provided with a handheld device called d-Nav® which advises them what dose of insulin to administer during each injection and automatically adjust insulin dosage when needed. The d-Nav care specialists periodically follow-up with users through telephone calls and in-person consultations to bestow user confidence, correct usage errors, triage, and identify uncharacteristic clinical courses. The following review provide details about the service and its clinical outcomes.

  6. 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

    Energy Technology Data Exchange (ETDEWEB)

    Michalski, Jeff M., E-mail: jmichalski@radonc.wustl.edu [Department of Radiation Oncology Washington University Medical Center, St. Louis, Missouri (United States); Yan, Yan [Radiation Therapy Oncology Group Statistical Center, Philadelphia, Pennsylvania (United States); Watkins-Bruner, Deborah [Emory University School of Nursing, Atlanta, Georgia (United States); Bosch, Walter R. [Department of Radiation Oncology Washington University Medical Center, St. Louis, Missouri (United States); Winter, Kathryn [Radiation Therapy Oncology Group Statistical Center, Philadelphia, Pennsylvania (United States); Galvin, James M. [Department of Radiation Oncology Thomas Jefferson University Hospital, Philadelphia, Pennsylvania (United States); Bahary, Jean-Paul [Department of Radiation Oncology Centre Hospitalier de l' Université de Montréal-Notre Dame, Montreal, QC (Canada); Morton, Gerard C. [Department of Radiation Oncology Toronto-Sunnybrook Regional Cancer Centre, Toronto, ON (Canada); Parliament, Matthew B. [Department of Oncology Cross Cancer Institute, Edmonton, AB (Canada); Sandler, Howard M. [Department of Radiation Oncology Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California (United States)

    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

  7. Lipid profiles, inflammatory markers, and insulin therapy in youth with type 2 diabetes

    Science.gov (United States)

    Data regarding atherogenic dyslipidemia and the inflammation profile in youth with type 2 diabetes is limited and the effect of insulin therapy on these variables has not previously been studied in youth. We determined the impact of insulin therapy on lipid and inflammatory markers in youth with poo...

  8. How efficient is sliding-scale insulin therapy? Problems with a 'cookbook' approach in hospitalized patients.

    Science.gov (United States)

    Katz, C M

    1991-04-01

    Sliding-scale insulin therapy is seldom the best way to treat hospitalized diabetic patients. In the few clinical situations in which it is appropriate, close attention to details and solidly based scientific principles is absolutely necessary. Well-organized alternative approaches to insulin therapy usually offer greater efficiency and effectiveness.

  9. The SWITCH study (sensing with insulin pump therapy to control HbA(1c))

    DEFF Research Database (Denmark)

    Conget, Ignacio; Battelino, Tadej; Giménez, Marga

    2011-01-01

    studies investigating the effect of real-time continuous glucose monitoring (CGM) combined with pump therapy on glycemic outcomes in type 1 diabetes are increasing. Pump therapy is well established as a "gold standard" for insulin delivery, offering improvements over multiple daily insulin...

  10. Continuous glucose monitoring-enabled insulin-pump therapy in diabetic pregnancy

    DEFF Research Database (Denmark)

    Secher, Anna L; Schmidt, Signe; Nørgaard, Kirsten

    2010-01-01

    We describe the feasibility of continuous glucose monitoring (CGM)-enabled insulin-pump therapy during pregnancy in a woman with type 1 diabetes, who was treated with CGM-enabled insulin-pump therapy in her third pregnancy. During her first pregnancy, the woman was treated with multiple daily inj...

  11. Use of metformin earlier in pregnancy predicts supplemental insulin therapy in women with gestational diabetes.

    Science.gov (United States)

    McGrath, Rachel T; Glastras, Sarah J; Hocking, Samantha; Fulcher, Gregory R

    2016-06-01

    The use of metformin in gestational diabetes is safe and effective, yet some women require additional insulin therapy to achieve glycaemic targets. We found a significant association between earlier gestational age at initiation of metformin therapy and the necessity for supplemental insulin in women treated with metformin during pregnancy. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  12. Androgen Deprivation Therapy Use in the Setting of High-dose Radiation Therapy and the Risk of Prostate Cancer–Specific Mortality Stratified by the Extent of Competing Mortality

    Energy Technology Data Exchange (ETDEWEB)

    Rose, Brent S., E-mail: brose44@gmail.com [Harvard Radiation Oncology Program, Brigham and Women' s Hospital/Dana-Farber Cancer Institute, Boston, Massachusetts (United States); Chen, Ming-Hui; Wu, Jing [Department of Statistics, University of Connecticut, Storrs, Connecticut (United States); Braccioforte, Michelle H.; Moran, Brian J. [Prostate Cancer Foundation of Chicago, Westmont, Illinois (United States); Doseretz, Daniel E.; Katin, Michael J.; Ross, Rudolf H.; Salenius, Sharon A. [21st Century Oncology, Inc, Fort Myers, Florida (United States); D' Amico, Anthony V. [Department of Radiation Oncology, Brigham and Women' s Hospital/Dana-Farber Cancer Institute, Boston, Massachusetts (United States)

    2016-11-15

    Purpose: The addition of androgen deprivation therapy (ADT) to radiation therapy (RT) is the standard of care for men with intermediate- and high-risk prostate cancer (PC). However, whether competing mortality (CM) affects the ability of ADT to improve, survival remains unanswered. Methods and Materials: We calculated a CM risk score using a Fine-Gray semiparametric model that included age and cardiometabolic comorbidities from a cohort of 17,669 men treated with high-dose RT with or without supplemental ADT for nonmetastatic PC. Fine and Gray competing risk regression analysis was used to assess whether ADT reduced the risk of PC-specific mortality for men with a low versus a high risk of CM among the 4550 patients within the intermediate- and high-risk cohort after adjustment for established PC prognostic factors, year of treatment, site, and ADT propensity score. Results: After a median follow-up of 8.4 years, 1065 men had died, 89 (8.36%) of PC. Among the men with a low CM score, ADT use was associated with a significant reduction in the risk of PC-specific mortality (adjusted hazard ratio 0.35, 95% confidence interval 0.14-0.87, P=.02) but was not for men with high CM (adjusted hazard ratio 1.33, 95% confidence interval 0.77-2.30, P=.30). Conclusions: Adding ADT to high-dose RT appears to be associated with decreased PC-specific mortality risk in men with a low but not a high CM score. These data should serve to heighten awareness about the importance of considering competing risks when determining whether to add ADT to RT for older men with intermediate- or high-risk PC.

  13. Androgen Deprivation Therapy Use in the Setting of High-dose Radiation Therapy and the Risk of Prostate Cancer–Specific Mortality Stratified by the Extent of Competing Mortality

    International Nuclear Information System (INIS)

    Rose, Brent S.; Chen, Ming-Hui; Wu, Jing; Braccioforte, Michelle H.; Moran, Brian J.; Doseretz, Daniel E.; Katin, Michael J.; Ross, Rudolf H.; Salenius, Sharon A.; D'Amico, Anthony V.

    2016-01-01

    Purpose: The addition of androgen deprivation therapy (ADT) to radiation therapy (RT) is the standard of care for men with intermediate- and high-risk prostate cancer (PC). However, whether competing mortality (CM) affects the ability of ADT to improve, survival remains unanswered. Methods and Materials: We calculated a CM risk score using a Fine-Gray semiparametric model that included age and cardiometabolic comorbidities from a cohort of 17,669 men treated with high-dose RT with or without supplemental ADT for nonmetastatic PC. Fine and Gray competing risk regression analysis was used to assess whether ADT reduced the risk of PC-specific mortality for men with a low versus a high risk of CM among the 4550 patients within the intermediate- and high-risk cohort after adjustment for established PC prognostic factors, year of treatment, site, and ADT propensity score. Results: After a median follow-up of 8.4 years, 1065 men had died, 89 (8.36%) of PC. Among the men with a low CM score, ADT use was associated with a significant reduction in the risk of PC-specific mortality (adjusted hazard ratio 0.35, 95% confidence interval 0.14-0.87, P=.02) but was not for men with high CM (adjusted hazard ratio 1.33, 95% confidence interval 0.77-2.30, P=.30). Conclusions: Adding ADT to high-dose RT appears to be associated with decreased PC-specific mortality risk in men with a low but not a high CM score. These data should serve to heighten awareness about the importance of considering competing risks when determining whether to add ADT to RT for older men with intermediate- or high-risk PC.

  14. EDTA chelation therapy alone and in combination with oral high-dose multivitamins and minerals for coronary disease: The factorial group results of the Trial to Assess Chelation Therapy.

    Science.gov (United States)

    Lamas, Gervasio A; Boineau, Robin; Goertz, Christine; Mark, Daniel B; Rosenberg, Yves; Stylianou, Mario; Rozema, Theodore; Nahin, Richard L; Terry Chappell, L; Lindblad, Lauren; Lewis, Eldrin F; Drisko, Jeanne; Lee, Kerry L

    2014-07-01

    Disodium ethylenediaminetetraacetic acid (EDTA) reduced adverse cardiac outcomes in a factorial trial also testing oral vitamins. This report describes the intent-to-treat comparison of the 4 factorial groups overall and in patients with diabetes. This was a double-blind, placebo-controlled, 2 × 2 factorial multicenter randomized trial of 1,708 post-myocardial infarction (MI) patients ≥50 years of age and with creatinine ≤2.0 mg/dL randomized to receive 40 EDTA chelation or placebo infusions plus 6 caplets daily of a 28-component multivitamin-multimineral mixture or placebo. The primary end point was a composite of total mortality, MI, stroke, coronary revascularization, or hospitalization for angina. Median age was 65 years, 18% were female, 94% were Caucasian, 37% were diabetic, 83% had prior coronary revascularization, and 73% were on statins. Five-year Kaplan-Meier estimates for the primary end point was 31.9% in the chelation + high-dose vitamin group, 33.7% in the chelation + placebo vitamin group, 36.6% in the placebo infusion + active vitamin group, and 40.2% in the placebo infusions + placebo vitamin group. The reduction in primary end point by double active treatment compared with double placebo was significant (hazard ratio 0.74, 95% CI 0.57-0.95, P = .016). In patients with diabetes, the primary end point reduction of double active compared with double placebo was more pronounced (hazard ratio 0.49, 95% CI 0.33-0.75, P < .001). In stable post-MI patients on evidence-based medical therapy, the combination of oral high-dose vitamins and chelation therapy compared with double placebo reduced clinically important cardiovascular events to an extent that was both statistically significant and of potential clinical relevance. Copyright © 2014 The Authors. Published by Mosby, Inc. All rights reserved.

  15. The Rationale for Insulin Therapy in Alzheimer’s Disease

    Directory of Open Access Journals (Sweden)

    Samo Ribarič

    2016-05-01

    Full Text Available Alzheimer’s disease (AD is the most common form of dementia, with a prevalence that increases with age. By 2050, the worldwide number of patients with AD is projected to reach more than 140 million. The prominent signs of AD are progressive memory loss, accompanied by a gradual decline in cognitive function and premature death. AD is the clinical manifestation of altered proteostasis. The initiating step of altered proteostasis in most AD patients is not known. The progression of AD is accelerated by several chronic disorders, among which the contribution of diabetes to AD is well understood at the cell biology level. The pathological mechanisms of AD and diabetes interact and tend to reinforce each other, thus accelerating cognitive impairment. At present, only symptomatic interventions are available for treating AD. To optimise symptomatic treatment, a personalised therapy approach has been suggested. Intranasal insulin administration seems to open the possibility for a safe, and at least in the short term, effective symptomatic intervention that delays loss of cognition in AD patients. This review summarizes the interactions of AD and diabetes from the cell biology to the patient level and the clinical results of intranasal insulin treatment of cognitive decline in AD.

  16. Insulin initiation status of primary care physicians in Turkey, barriers to insulin initiation and knowledge levels about insulin therapy: A multicenter cross-sectional study.

    Science.gov (United States)

    Ates, Elif; Set, Turan; Saglam, Zuhal; Tekin, Nil; Karatas Eray, Irep; Yavuz, Erdinc; Sahin, Mustafa Kursat; Selcuk, Engin Burak; Cadirci, Dursun; Cubukcu, Mahcube

    2017-10-01

    Our aim was to evaluate the insulin initiation status, barriers to insulin initiation and knowledge levels about treatment administered by primary care physicians (PCP). We conducted our study in accordance with a multicenter, cross-sectional design in Turkey, between July 2015 and July 2016. A questionnaire inquiring demographic features, status of insulin initiation, obstacles to insulin initiation and knowledge about therapy of the PCPs was administered during face-to-face interviews. 84 PCPs (19%) (n=446, mean age=41.5±8.4years, 62.9% male and 90.0% ministry certified family physicians) initiated insulin therapy in the past. Most of the stated primary barriers (51.9%, n=230) were due to the physicians. The most relevant barrier was "lack of clinical experience" with a rate of 19% (n=84 of the total). The average total knowledge score was 5.7±2.0 for the family medicine specialist, and 3.8±2.1 for the ministry certified family physicians (p=0.000, maximum knowledge score could be 10). The status of insulin initiation in Turkey by the primary care physicians is inadequate. Medical education programs and health care systems may require restructuring to facilitate insulin initiation in primary care. Copyright © 2017 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.

  17. Modern approach to basal-bolus therapy with glargine and glulisine insulin analoguesin various age groups

    Directory of Open Access Journals (Sweden)

    Natalya Nikitichna Volevodz

    2013-03-01

    Full Text Available DCCT (Diabetes Control and Complications Trial study established that intensified insulin therapy in multiple daily injections (MDI or continuous insulin infusion (CSII regimens substantially reduce both development and progression of complications in patients with type 1 diabetes mellitus (T1DM as compared to conventional insulin therapy. Insulin analogues possess better pharmacokinetic and pharmacodynamic characteristics than unmodified human insulin agents. These characteristics are beneficial for management of diabetes mellitus, allowing better glycemic outcomes with lower incidence of hypoglycemia.Current review discusses specifics of therapy with glargine (Lantus? and glulisine (Apidra? insulin analogues. Authors analyzed available to date results from corresponding clinical trials in children, adolescents and adults. Pharmacoeconomic aspects and matters of dosage of glargine and glulisine are further addressed.

  18. Phase II trial of combined surgical resection, high dose rate intraoperative radiation therapy, and external beam radiotherapy for malignant pleural mesothelioma

    International Nuclear Information System (INIS)

    Raben, A.; Rusch, V.; Mychalczak, B.; Ginsberg, R.; Burt, M.; Bains, M.; Francois, Damien; Harrison, L.B.

    1997-01-01

    Purpose: To determine the feasibility of combining extrapleural pneumonectomy (EPP) or pleurectomy / decortication (PD), high dose rate intraoperative radiation therapy (HDR-IORT) and postoperative external beam radiation hemithoracic radiation (EBHRT) to treat malignant pleural mesothelioma (MPM). Materials and Methods: From 3/94 through 9/94, 15 patients (pts) were enrolled on this trial. This included 3 females and 12 males with a median age of 59 (Range: 45-75). Eligibility criteria included biopsy proven MPM, no evidence of T4 or N3 disease by exam/CT/MRI, no evidence of metastatic disease, no previous treatment, and a Karnofsky performance status of ≥ 80%. Pts with pulmonary function tests permitting EPP, underwent EPP and HDR-IORT (N=7). The rest underwent PD/HDR-IORT (N=4). An intraoperative dose of 15 Gy was prescribed to a depth of 5 mm in tissue to the ipsilateral mediastinum, diaphragm, and chest wall. Postoperatively, 54 Gy of EBHRT was prescribed to the hemithorax, surgical scar and surgical drain site. The median surgical procedure time, median IORT time and median overall operating time was 554 minutes, 240 minutes, and 649 minutes respectively. The median dose of EBHRT was 50.4 Gy (Range 50-54 Gy). The median follow-up time is 8 months (Range: 3.5 to 28 months). Four of 15 pts had unresectable disease at the time of surgery and were taken off study. Results are presented in crude and actuarial analysis. Results: A complete resection of all visible gross disease was accomplished in 10 pts. One pt had a single focus of gross residual disease (less than 5 mm in size) left behind in the chest wall. The overall complication rate was 54%. Treatment related mortality occurred in 2 pts (18%) at 1 and 7 months respectively. This was attributed to ARDS in 1 pt (EPP/HDR-IORT) and radiation pneumonitis combined with a tracheoesophageal fistula in 1 pt (PD/HDR-IORT). Of the 6 remaining pts undergoing EPP/HDR-IORT, 2 pts developed a postoperative empyema with

  19. 18F-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

    International Nuclear Information System (INIS)

    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

    2014-01-01

    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 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, 18 F-choline PET/CT-driven high-dose salvage radiation therapy seems to be feasible and well tolerated, with a low rate of toxicity

  20. Gamma dosimetry of high doses

    International Nuclear Information System (INIS)

    Martinez C, T.; Galvan G, A.; Canizal, G.

    1991-01-01

    The gamma dosimetry of high doses is problematic in almost all the classic dosemeters either based on the thermoluminescence, electric, chemical properties, etc., because they are saturated to very high dose and they are no longer useful. This work carries out an investigation in the interval of high doses. The solid system of heptahydrate ferrous sulfate, can be used as solid dosemeter of routine for high doses of radiation. The proposed method is simple, cheap and it doesn't require sophisticated spectrophotometers or spectrometers but expensive and not common in some laboratories

  1. Is reducing variability of blood glucose the real but hidden target of intensive insulin therapy?

    Science.gov (United States)

    Egi, Moritoki; Bellomo, Rinaldo; Reade, Michael C

    2009-01-01

    Since the first report that intensive insulin therapy reduced mortality in selected surgical critically ill patients, lowering of blood glucose levels has been recommended as a means of improving patient outcomes. In this initial Leuven trial, blood glucose control by protocol using insulin was applied to 98.7% of patients in the intensive group but to only 39.2% (P dimension of glucose management, a possible mechanism by which an intensive insulin protocol exerts its putative beneficial effects, and an important goal of glucose management in the intensive care unit. Clinicians need to be aware of this controversy when considering the application of intensive insulin therapy and interpreting future trials.

  2. Acceptance of insulin therapy: a long shot? Psychological insulin resistance in primary care

    NARCIS (Netherlands)

    Woudenberg, Y. J. C.; Lucas, C.; Latour, C.; Scholte Op Reimer, W. J. M.

    2012-01-01

    Diabet. Med. 29, 796802 (2012) Abstract Aim To explore which factors are associated with psychological insulin resistance in insulin-naive patients with Type 2 diabetes in primary care. Methods A sample of 101 insulin-naive patients with Type 2 diabetes completed self-administered questionnaires

  3. 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

    International Nuclear Information System (INIS)

    Georg, Dietmar; Hopfgartner, Johannes; Gòra, Joanna; Kuess, Peter; Kragl, Gabriele; Berger, Daniel; Hegazy, Neamat; Goldner, Gregor; Georg, Petra

    2014-01-01

    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 ( 192 Ir) and LDR-BT ( 125 I) were D 90% ≥34 Gy in 8.5 Gy per fraction and D 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 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 were clearly superior in

  4. 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

    Energy Technology Data Exchange (ETDEWEB)

    Georg, Dietmar, E-mail: Dietmar.Georg@akhwien.at [Department of Radiation Oncology, Medical University of Vienna/Allgemeines Krankenhaus der Stadt Wien, Vienna (Austria); Christian Doppler Laboratory for Medical Radiation Research for Radiation Oncology, Medical University of Vienna/Allgemeines Krankenhaus der Stadt Wien, Vienna (Austria); Hopfgartner, Johannes [Department of Radiation Oncology, Medical University of Vienna/Allgemeines Krankenhaus der Stadt Wien, Vienna (Austria); Christian Doppler Laboratory for Medical Radiation Research for Radiation Oncology, Medical University of Vienna/Allgemeines Krankenhaus der Stadt Wien, Vienna (Austria); Gòra, Joanna [Department of Radiation Oncology, Medical University of Vienna/Allgemeines Krankenhaus der Stadt Wien, Vienna (Austria); Kuess, Peter [Department of Radiation Oncology, Medical University of Vienna/Allgemeines Krankenhaus der Stadt Wien, Vienna (Austria); Christian Doppler Laboratory for Medical Radiation Research for Radiation Oncology, Medical University of Vienna/Allgemeines Krankenhaus der Stadt Wien, Vienna (Austria); Kragl, Gabriele [Department of Radiation Oncology, Medical University of Vienna/Allgemeines Krankenhaus der Stadt Wien, Vienna (Austria); Berger, Daniel [Department of Radiation Oncology, Medical University of Vienna/Allgemeines Krankenhaus der Stadt Wien, Vienna (Austria); Christian Doppler Laboratory for Medical Radiation Research for Radiation Oncology, Medical University of Vienna/Allgemeines Krankenhaus der Stadt Wien, Vienna (Austria); Hegazy, Neamat [Department of Radiation Oncology, Medical University of Vienna/Allgemeines Krankenhaus der Stadt Wien, Vienna (Austria); Goldner, Gregor; Georg, Petra [Department of Radiation Oncology, Medical University of Vienna/Allgemeines Krankenhaus der Stadt Wien, Vienna (Austria); Christian Doppler Laboratory for Medical Radiation Research for Radiation Oncology, Medical University of Vienna/Allgemeines Krankenhaus der Stadt Wien, Vienna (Austria)

    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

  5. Insulin therapy refusal among type II diabetes mellitus patients in Kubang Pasu district, Kedah, Malaysia

    Science.gov (United States)

    Tan, Wei Leong; Asahar, Siti Fairus; Harun, Noor Liani

    2015-01-01

    INTRODUCTION Diabetes mellitus is a rising non-communicable disease in Malaysia. Insulin therapy refusal is a challenge for healthcare providers, as it results in delayed insulin initiation. This study was conducted to determine the prevalence of insulin therapy refusal and its associated factors. METHODS This cross-sectional study was conducted at seven public health clinics in Kubang Pasu district of Kedah, Malaysia, from March to October 2012. A newly developed and validated questionnaire was used and participants were selected via systematic random sampling. Only patients diagnosed with type II diabetes mellitus (T2DM) and under the public health clinic care in Kubang Pasu were included in the study. Multiple logistic regression was used to study the association between insulin therapy refusal and its associated factors. RESULTS There were 461 respondents and the response rate was 100%. Among these 461 patients with T2DM, 74.2% refused insulin therapy. The most common reason given for refusal was a lack of confidence in insulin injection (85.4%). Multiple logistic regression revealed that respondents who had secondary education were 55.0% less likely to refuse insulin therapy than those who had primary education or no formal education (adjusted odds ratio [OR] 0.45, 95% confidence interval [CI] 0.25–0.82, p = 0.009). There was also a significant inverse association between glycated haemoglobin (HbA1c) level and insulin therapy refusal (adjusted OR 0.87, 95% CI 0.76–1.00, p = 0.047). CONCLUSION Insulin therapy refusal is common in Kubang Pasu. Educational status and HbA1c level should be taken into consideration when counselling patients on insulin therapy initiation. PMID:25532511

  6. Intranasal Insulin Therapy for Cognitive Impairment and Neurodegeneration: Current State of the Art

    Science.gov (United States)

    de la Monte, Suzanne M.

    2015-01-01

    Introduction Growing evidence supports the concept that insulin resistance plays an important role in the pathogenesis of cognitive impairment and neurodegeneration, including in Alzheimer's disease (AD). The metabolic hypothesis has led to the development and utilization of insulin- and insulin agonist-based treatments. Therapeutic challenges faced include the ability to provide effective treatments that do not require repeated injections and also minimize potentially hazardous off-target effects. Areas covered This review covers the role of intra-nasal insulin therapy for cognitive impairment and neurodegeneration, particularly Alzheimer's disease. The literature reviewed focuses on data published within the past 5 years as this field is evolving rapidly. The author provides evidence that brain insulin resistance is an important and early abnormality in Alzheimer's disease, and that increasing brain supply and utilization of insulin improves cognition and memory. Emphasis was placed on discussing outcomes of clinical trials and interpreting discordant results to clarify the benefits and limitations of intranasal insulin therapy. Expert Opinion Intranasal insulin therapy can efficiently and directly target the brain to support energy metabolism, myelin maintenance, cell survival, and neuronal plasticity, which begin to fail in the early stages of neurodegeneration. Efforts must continue toward increasing the safety, efficacy, and specificity of intranasal insulin therapy. PMID:24215447

  7. High-dose erythropoietin for tissue protection

    DEFF Research Database (Denmark)

    Lund, Anton; Lundby, Carsten; Olsen, Niels Vidiendal

    2014-01-01

    BACKGROUND: The discovery of potential anti-apoptotic and cytoprotective effects of recombinant human erythropoietin (rHuEPO) has led to clinical trials investigating the use of high-dose, short-term rHuEPO therapy for tissue protection in conditions such as stroke and myocardial infarction....... Experimental studies have been favourable, but the clinical efficacy has yet to be validated. MATERIALS AND METHODS: We have reviewed clinical studies regarding the use of high-dose, short-term rHuEPO therapy for tissue protection in humans with the purpose to detail the safety and efficacy of r...... no effect of rHuEPO therapy on measures of tissue protection. Five trials including 1025 patients reported safety concerns in the form of increased mortality or adverse event rates. No studies reported reduced mortality. CONCLUSIONS: Evidence is sparse to support a tissue-protective benefit of r...

  8. Real-time Tumor Oxygenation Changes After Single High-dose Radiation Therapy in Orthotopic and Subcutaneous Lung Cancer in Mice: Clinical Implication for Stereotactic Ablative Radiation Therapy Schedule Optimization

    Energy Technology Data Exchange (ETDEWEB)

    Song, Changhoon [Department of Radiation Oncology, Seoul National University College of Medicine, Seoul (Korea, Republic of); Hong, Beom-Ju; Bok, Seoyeon; Lee, Chan-Ju; Kim, Young-Eun [Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang, Gyeongbuk (Korea, Republic of); Jeon, Sang-Rok [Department of Radiation Oncology, Seoul National University College of Medicine, Seoul (Korea, Republic of); Cancer Research Institute, Seoul National University College of Medicine, Seoul (Korea, Republic of); Wu, Hong-Gyun [Department of Radiation Oncology, Seoul National University College of Medicine, Seoul (Korea, Republic of); Cancer Research Institute, Seoul National University College of Medicine, Seoul (Korea, Republic of); Institute of Radiation Medicine, Medical Research Center, Seoul National University College of Medicine, Seoul (Korea, Republic of); Lee, Yun-Sang [Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul (Korea, Republic of); Department of Molecular Medicine and Biopharmaceutical Sciences, Seoul National University College of Medicine, Seoul (Korea, Republic of); Cheon, Gi Jeong; Paeng, Jin Chul [Cancer Research Institute, Seoul National University College of Medicine, Seoul (Korea, Republic of); Institute of Radiation Medicine, Medical Research Center, Seoul National University College of Medicine, Seoul (Korea, Republic of); Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul (Korea, Republic of); Carlson, David J. [Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, Connecticut (United States); and others

    2016-07-01

    Purpose: To investigate the serial changes of tumor hypoxia in response to single high-dose irradiation by various clinical and preclinical methods to propose an optimal fractionation schedule for stereotactic ablative radiation therapy. Methods and Materials: Syngeneic Lewis lung carcinomas were grown either orthotopically or subcutaneously in C57BL/6 mice and irradiated with a single dose of 15 Gy to mimic stereotactic ablative radiation therapy used in the clinic. Serial [{sup 18}F]-misonidazole (F-MISO) positron emission tomography (PET) imaging, pimonidazole fluorescence-activated cell sorting analyses, hypoxia-responsive element-driven bioluminescence, and Hoechst 33342 perfusion were performed before irradiation (day −1), at 6 hours (day 0), and 2 (day 2) and 6 (day 6) days after irradiation for both subcutaneous and orthotopic lung tumors. For F-MISO, the tumor/brain ratio was analyzed. Results: Hypoxic signals were too low to quantitate for orthotopic tumors using F-MISO PET or hypoxia-responsive element-driven bioluminescence imaging. In subcutaneous tumors, the maximum tumor/brain ratio was 2.87 ± 0.483 at day −1, 1.67 ± 0.116 at day 0, 2.92 ± 0.334 at day 2, and 2.13 ± 0.385 at day 6, indicating that tumor hypoxia was decreased immediately after irradiation and had returned to the pretreatment levels at day 2, followed by a slight decrease by day 6 after radiation. Pimonidazole analysis also revealed similar patterns. Using Hoechst 33342 vascular perfusion dye, CD31, and cleaved caspase 3 co-immunostaining, we found a rapid and transient vascular collapse, which might have resulted in poor intratumor perfusion of F-MISO PET tracer or pimonidazole delivered at day 0, leading to decreased hypoxic signals at day 0 by PET or pimonidazole analyses. Conclusions: We found tumor hypoxia levels decreased immediately after delivery of a single dose of 15 Gy and had returned to the pretreatment levels 2 days after irradiation and had decreased

  9. Negative appraisals of insulin therapy are common among adults with Type 2 diabetes using insulin: Results from Diabetes MILES - Australia cross-sectional survey

    DEFF Research Database (Denmark)

    Holmes-Truscott, E.; Holmes-Truscott, E.; Skinner, T. C.

    2015-01-01

    Aim: To identify insulin therapy appraisals among adults with Type 2 diabetes using insulin and how negative appraisals relate to clinical, self-care and psychosocial outcomes. Methods: Diabetes MILES - Australia 2011 was a national survey of adults with diabetes, focused on behavioural...... and psychosocial issues. Subgroup analyses were conducted on the responses of 273 adults with Type 2 diabetes using insulin (46% women; mean ± sd age: 59 ± 9 years; diabetes duration: 12 ± 7 years; years using insulin: 4 ± 4). They completed validated measures of insulin therapy appraisals (ITAS), depression (PHQ......; 51% that insulin causes weight gain; 39% that they have 'failed to manage' their diabetes. Those with the greatest and least 'ITAS negative' scores did not differ by diabetes duration or years using insulin, or by average number of insulin injections or blood glucose checks per day. Those with more...

  10. Effectiveness of insulin therapy in people with Type 2 diabetes in the Hoorn Diabetes Care System

    NARCIS (Netherlands)

    Mast, M.R.; Walraven, I.; Hoekstra, T.; Jansen, A P D; van der Heijden, A.A.W.A.; Elders, Petra J M; Heine, Robert J; Dekker, J M; Nijpels, G.; Hugtenburg, J.G.

    AIMS: To identify HbA1c trajectories after the start of insulin treatment and to identify clinically applicable predictors of the response to insulin therapy. METHODS: The study population comprised 1203 people with Type 2 diabetes included in the Hoorn Diabetes Care System (n = 9849). Inclusion

  11. Effectiveness of insulin therapy in people with Type 2 diabetes in the Hoorn Diabetes Care System.

    NARCIS (Netherlands)

    Mast, M.R.; Walraven, L.; Hoekstra, T.; Jansen, A.P.D.; Heijden, A.A.W.A. van der; Elders, P.J.M.; Heine, R.J.; Dekker, J.M.; Nijpels, G.; Hugtenburg, J.G.

    2016-01-01

    Aims To identify HbA1c trajectories after the start of insulin treatment and to identify clinically applicable predictors of the response to insulin therapy. Methods The study population comprised 1203 people with Type 2 diabetes included in the Hoorn Diabetes Care System (n = 9849). Inclusion

  12. Glucose Control: non-insulin therapies* 9.1: Drug Summary ...

    African Journals Online (AJOL)

    Glucose Control: non-insulin therapies in 2017 SEMDSA Guideline for the Management of Type 2 Diabetes. Guideline ... Weight neutral or causes modest weight loss (-1.2kg). No weight ..... Older patients with multiple comorbidities. • Patients ...

  13. Intracranial meningiomas after high-dose irradiation

    International Nuclear Information System (INIS)

    Soffer, D.; Gomori, J.M.; Siegal, T.; Shalit, M.N.

    1989-01-01

    Three patients who presented with intracranial meningiomas 12, 15, and 20 years, respectively, after therapeutic high-dose irradiation of a primary brain tumor are described. Analysis of these cases and similar documented cases suggests that meningiomas after high-dose irradiation constitute a recognizable entity. Patients with such tumors received radiation therapy at a young age (mean age, 9.4 years). After a latent period of 2 to 47 years (mean, 19.8 years) they developed meningiomas at the site of irradiation, at a much younger age than patients with ''spontaneous'' meningiomas. Similar to the situation with meningiomas after low-dose irradiation, a relatively high proportion of meningiomas induced by high-dose irradiation tend to be malignant and biologically aggressive. A very young age at the time of irradiation seems to predispose to the induction of malignant meningiomas, rather than benign tumors. These unusual features provide indirect evidence that high-dose radiation may play a role in the pathogenesis of meningiomas.41 references

  14. Initiating insulin therapy in children and adolescents with type 1 diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Subhash Kumar Wangnoo

    2015-01-01

    Full Text Available The primary clinical goals to be achieved with insulin initiation are elimination of ketosis and hyperglycemia with prevention of chronic complications. Insulin therapy is the mainstay in management of type 1 diabetes, which should be aimed at achieving good glycemic control, with achievement of hemoglobin A1c (HbA1c <7.5%, pre-meal self-monitored blood glucose (SMBG of 90-130 mg/dL, bed time SMBG of 100-140 mg/dL, mean blood glucose level of 120-160 mg/dL and no ketonuria. Two classes of insulin are available for use in T1DM viz. bolus/prandial insulins (rapid-acting insulins and short-acting insulins and basal insulins (intermediate-acting insulin and long-acting insulin. Insulin glargine and glulisine can be used in children above 6 years, lispro in children above 3 years and detemir and aspart in children above 2 years. The caution for hypoglycemia should be exercised while prescribing them. Degludec is currently not approved for pediatric use. The initial insulin regimen should comprise of ≥2 daily bolus and ≥1 basal insulin injections. Insulin intensification would be required if the initial regimen fails, which can be achieved by increasing frequency of long and rapid acting insulin analogues. The American Diabetes Association guidelines recommend HbA1c targets of <8.0% for children <6 years of age, ≤7.5% for children 6 to 12 years of age, and ≤7.0% for adolescents, 12-18 years of age. However, the evidence is now in favor of a single target HbA1c of ≤7.5% for all children and adolescents <19 years of age.

  15. Early insulin therapy in patients with type 2 diabetes mellitus

    African Journals Online (AJOL)

    Type 2 diabetes mellitus (T2DM) is an insulin-insufficient disease characterised ... complications.1–4 Early in the onset of T2DM there is development of relative insulin ..... position statement of the American Diabetes Association (ADA) and.

  16. Treatment duration (persistence) of basal insulin supported oral therapy (BOT) in Type-2 diabetic patients: comparison of insulin glargine with NPH insulin.

    Science.gov (United States)

    Quinzler, Renate; Ude, Miriam; Franzmann, Alexandra; Feldt, Sandra; Schüssel, Katrin; Leuner, Kristina; Müller, Walter E; Dippel, Franz-Werner; Schulz, Martin

    2012-01-01

    To compare the persistence (treatment duration) of basal insulin supported oral therapy (BOT) using insulin glargine (GLA) or NPH insulin (NPH) in Type-2 diabetic patients. This retrospective cohort study reports results from an analysis of claims data from prescriptions for ambulatory patients within the German Statutory Health Insurance scheme. The study is based on claims data from more than 80% of German community pharmacies. Treatment duration until switching to a basal bolus treatment regimen (intensified conventional insulin therapy: ICT) was determined in insulin-naïve patients who began treatment with BOT using GLA or NPH between 01/2003 and 12/2006. A total of 97,998 patients (61,070 GLA and 36,928 NPH) were included. Within the observation period, 23.5% of GLA patients and 28.0% of NPH patients switched from BOT to ICT. The upper quartile of probability of continuation of therapy (the 75th percentile) was reached after 769 days in GLA patients and after 517 days in NPH patients. Therefore, the risk of switching to ICT was significantly higher with NPH compared to GLA: hazard ratios were 1.34 (99% CI: 1.29-1.38; unadjusted) and 1.22 (99% CI: 1.18-1.27) after adjustment for predefined covariates. Various sensitivity analyses using modified inclusion criteria and endpoint definitions were applied and these confirmed the initial results. Type-2 diabetic patients under BOT with GLA stayed significantly longer on the initial therapy before switching to ICT than patients on BOT using NPH.

  17. Two-week, high-dose proton pump inhibitor, moxifloxacin triple Helicobacter pylori therapy after failure of standard triple or non-bismuth quadruple treatments.

    Science.gov (United States)

    Gisbert, Javier P; Romano, Marco; Molina-Infante, Javier; Lucendo, Alfredo J; Medina, Enrique; Modolell, Inés; Rodríguez-Tellez, Manuel; Gomez, Blas; Barrio, Jesús; Perona, Monica; Ortuño, Juan; Ariño, Inés; Domínguez-Muñoz, Juan Enrique; Perez-Aisa, Ángeles; Bermejo, Fernando; Domínguez, Jose Luis; Almela, Pedro; Gomez-Camarero, Judith; Millastre, Judith; Martin-Noguerol, Elisa; Gravina, Antonietta G; Martorano, Marco; Miranda, Agnese; Federico, Alessandro; Fernandez-Bermejo, Miguel; Angueira, Teresa; Ferrer-Barcelo, Luis; Fernández, Nuria; Marín, Alicia C; McNicholl, Adrián G

    2015-02-01

    Aim was to evaluate the efficacy and tolerability of a moxifloxacin-containing second-line triple regimen in patients whose previous Helicobacter pylori eradication treatment failed. Prospective multicentre study including patients in whom a triple therapy or a non-bismuth-quadruple-therapy failed. Moxifloxacin (400mg qd), amoxicillin (1g bid), and esomeprazole (40 mg bid) were prescribed for 14 days. Eradication was confirmed by (13)C-urea-breath-test. Compliance was determined through questioning and recovery of empty medication envelopes. 250 patients were consecutively included (mean age 48 ± 15 years, 11% with ulcer). Previous (failed) therapy included: standard triple (n = 179), sequential (n = 27), and concomitant (n = 44); 97% of patients took all medications, 4 were lost to follow-up. Intention-to-treat and per-protocol eradication rates were 82.4% (95% CI, 77-87%) and 85.7% (95% CI, 81-90%). Cure rates were similar independently of diagnosis (ulcer, 77%; dyspepsia, 82%) and previous treatment (standard triple, 83%; sequential, 89%; concomitant, 77%). At multivariate analysis, only age was associated with eradication (OR = 0.957; 95% CI, 0.933-0.981). Adverse events were reported in 25.2% of patients: diarrhoea (9.6%), abdominal pain (9.6%), and nausea (9.2%). 14-day moxifloxacin-containing triple therapy is an effective and safe second-line strategy in patients whose previous standard triple therapy or non-bismuth quadruple (sequential or concomitant) therapy has failed, providing a simple alternative to bismuth quadruple regimen. Copyright © 2014 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

  18. Identifying and meeting the challenges of insulin therapy in type 2 diabetes

    Directory of Open Access Journals (Sweden)

    Sorli C

    2014-07-01

    Full Text Available Christopher Sorli,1,* Michael K Heile2,*1Billings Clinic Research Center, Billings, MT, USA; 2The Family Medical Group Glenway, Cincinnati, OH, USA*Both authors contributed equally to this workAbstract: Type 2 diabetes mellitus (T2DM is a chronic illness that requires clinical recognition and treatment of the dual pathophysiologic entities of altered glycemic control and insulin resistance to reduce the risk of long-term micro- and macrovascular complications. Although insulin is one of the most effective and widely used therapeutic options in the management of diabetes, it is used by less than one-half of patients for whom it is recommended. Clinician-, patient-, and health care system-related challenges present numerous obstacles to insulin use in T2DM. Clinicians must remain informed about new insulin products, emerging technologies, and treatment options that have the potential to improve adherence to insulin therapy while optimizing glycemic control and mitigating the risks of therapy. Patient-related challenges may be overcome by actively listening to the patient's fears and concerns regarding insulin therapy and by educating patients about the importance, rationale, and evolving role of insulin in individualized self-treatment regimens. Enlisting the services of Certified Diabetes Educators and office personnel can help in addressing patient-related challenges. Self-management of diabetes requires improved patient awareness regarding the importance of lifestyle modifications, self-monitoring, and/or continuous glucose monitoring, improved methods of insulin delivery (eg, insulin pens, and the enhanced convenience and safety provided by insulin analogs. Health care system-related challenges may be improved through control of the rising cost of insulin therapy while making it available to patients. To increase the success rate of treatment of T2DM, the 2012 position statement from the American Diabetes Association and the European

  19. Initial results of a phase II trial of high dose radiation therapy, 5-fluorouracil, and cisplatin for patients with anal cancer (E4292): an eastern cooperative oncology group study

    International Nuclear Information System (INIS)

    Martenson, James A.; Lipsitz, Stuart R.; Wagner, Henry; Kaplan, Edward H.; Otteman, Larry A.; Schuchter, Lynn M.; Mansour, Edward G.; Talamonti, Mark S.; Benson, Al Bowen

    1996-01-01

    Purpose: A prospective clinical trial was performed to assess the response and toxicity associated with the use of high dose radiation therapy, 5-fluorouracil, and cisplatin in patients with anal cancer. Methods and Materials: Patients with anal cancer without distant metastasis were eligible for this study. Radiation therapy consisted of 59.4 Gy in 33 fractions; a 2 week break in treatment was taken after 36 Gy had been given. A treatment of 5-fluorouracil, 1,000 mg/m 2 per day intravenously, was given for the first 4 days of radiation therapy, and cisplatin, 75 mg/m 2 intravenously, was given on day 1 of radiation therapy. A second course of 5-fluorouracil and cisplatin was given after 36 Gy of radiation, when the radiation therapy was resumed. Results: Nineteen patients entered this study and received treatment. Thirteen (68%) had a complete response, 5 (26%) had a partial response, and 1 (5%) had stable disease. The patient with stable disease and one of the patients with a partial response had complete disappearance of tumor more than 8 weeks after completion of radiation therapy. Fifteen patients had toxicity of Grade 3 or higher: the worst toxicity was Grade 3 in eight patients, Grade 4 in six patients, and Grade 5 in one patient. The most common form of toxicity of Grade 3 or higher was hematologic. The one lethal toxicity was due to pseudomembranous colitis, which was a complication of antibiotic therapy for a urinary tract infection. Conclusion: Radiation therapy, cisplatin, and 5-fluorouracil resulted in an overall response rate of 95%. Significant toxicity occurred, an indication that this regimen is near the maximal tolerated dose. A Phase III clinical trial is planned in which radiation therapy, cisplatin, and 5-fluorouracil will be used as an experimental arm

  20. Comparison of absorbed dose in the cervix carcinoma therapy by brachytherapy of high dose rate using the conventional planning and Monte Carlo simulation

    International Nuclear Information System (INIS)

    Silva, Aneli Oliveira da

    2010-01-01

    This study aims to compare the doses received for patients submitted to brachytherapy High Dose Rate (HDR) brachytherapy, a method of treatment of the cervix carcinoma, performed in the planning system PLATO BPS with the doses obtained by Monte Carlo simulation using the radiation transport code MCNP 5 and one female anthropomorphic phantom based on voxel, the FAX. The implementation of HDR brachytherapy treatment for the cervix carcinoma consists of the insertion of an intrauterine probe and an intravaginal probe (ring or ovoid) and then two radiographs are obtained, anteroposterior (AP) and lateral (LAT) to confirm the position of the applicators in the patient and to allow the treatment planning and the determination of the absorbed dose at points of interest: rectum, bladder, sigmoid and point A, which corresponds anatomically to the crossings of the uterine arteries with ureters The absorbed doses obtained with the code MCNP 5, with the exception of the absorbed dose in the rectum and sigmoid for the simulation considering a point source of 192 Ir, are lower than the absorbed doses from PLATO BPS calculations because the MCNP 5 considers the chemical compositions and densities of FAX body, not considering the medium as water. When considering the Monte Carlo simulation for a source with dimensions equal to that used in the brachytherapy irradiator used in this study, the values of calculated absorbed dose to the bladder, to the rectum, to the right point A and to the left point A were respectively lower than those determined by the treatment planning system in 33.29, 5.01, 22.93 and 19.04%. These values are almost all larger than the maximum acceptable deviation between patient planned and administered doses (5 %). With regard to the rectum and bladder, which are organs that must be protected, the present results are in favor of the radiological protection of patients. The point A, that is on the isodose of 100%, used to tumor treatment, the results indicate

  1. Continuous subcutaneous insulin infusion therapy for Type 1 diabetes mellitus in children.

    Science.gov (United States)

    Mavinkurve, M; Quinn, A; O'Gorman, C S

    2016-05-01

    Continuous subcutaneous insulin pump therapy (CSII or pump therapy) is a well-recognised treatment option for Type 1 diabetes mellitus (T1DM) in paediatrics. It is especially suited to children because it optimises control by improving flexibility across age-specific lifestyles. The NICE guidelines (2008) recognise that pump therapy is advantageous and that it should be utilised to deliver best practice. In Ireland, the National Clinical Program for Diabetes will increase the availability and uptake of CSII in children and thus more clinicians are likely to encounter children using CSII therapy. This is a narrative review which discusses the basic principles of pump therapy and focuses on aspects of practical management. Insulin pump management involves some basic yet important principles which optimise the care of diabetes in children. This review addresses the principles of insulin pump management in children which all health care professionals involved in caring for the child with diabetes, shoud be familiar with.

  2. Prospective randomized study for optimal insulin therapy in type 2 diabetic patients with secondary failure

    Directory of Open Access Journals (Sweden)

    Tojo Katsuyoshi

    2008-05-01

    Full Text Available Abstract Background The large clinical trials proved that Basal-Bolus (BB insulin therapy was effective in the prevention of diabetic complications and their progression. However, BB therapy needs multiple insulin injections per a day. In this regard, a biphasic insulin analogue needs only twice-daily injections, and is able to correct postprandial hyperglycemia. Therefore it may achieve the blood glucose control as same as that of BB therapy and prevent the diabetic complications including macroangiopathy. Methods In PROBE (Prospective, Randomized, Open, Blinded-Endpoint design, forty-two type 2 diabetic patients (male: 73.8%, median(inter quartile range age: 64.5(56.8~71.0years with secondary failure of sulfonylurea (SU were randomly assigned to BB therapy with a thrice-daily insulin aspart and once-daily basal insulin (BB group or to conventional therapy with a twice-daily biphasic insulin analogue (30 Mix group, and were followed up for 6 months to compare changes in HbA1c, daily glycemic profile, intima-media thickness (IMT of carotid artery, adiponectin levels, amounts of insulin used, and QOL between the two groups. Results After 6 months, HbA1c was significantly reduced in both groups compared to baseline (30 Mix; 9.3(8.1~11.3 → 7.4(6.9~8.7%, p Conclusion Both BB and 30 mix group produced comparable reductions in HbA1c in type 2 diabetic patients with secondary failure. There was no significant change in IMT as an indicator of early atherosclerotic changes between the two groups. The basal-bolus insulin therapy may not be necessarily needed if the type 2 diabetic patients have become secondary failure. Trial registration Current Controlled Trials number, NCT00348231

  3. Combination therapy in type 2 diabetes mellitus: adding empagliflozin to basal insulin

    Directory of Open Access Journals (Sweden)

    Andrew Ahmann

    2015-11-01

    Full Text Available Type 2 diabetes mellitus (T2DM management is complex, with few patients successfully achieving recommended glycemic targets with monotherapy, most progressing to combination therapy, and many eventually requiring insulin. Sodium glucose cotransporter 2 (SGLT2 inhibitors are an emerging class of antidiabetes agents with an insulin-independent mechanism of action, making them suitable for use in combination with any other class of antidiabetes agents, including insulin. This review evaluates a 78-week, randomized, double-blind, placebo-controlled trial investigating the impact of empagliflozin, an SGLT2 inhibitor, as add-on to basal insulin in patients with inadequate glycemic control on basal insulin, with or without metformin and/or a sulfonylurea. Empagliflozin added on to basal insulin resulted in significant and sustained reductions in glycated hemoglobin (HbA1c levels compared with placebo. Empagliflozin has previously been shown to induce weight loss, and was associated with sustained weight loss in this study. This combination therapy was well tolerated, with similar levels of hypoglycemic adverse events in the empagliflozin and placebo groups over the 78-week treatment period. Urinary tract infections and genital infections, side effects associated with SGLT2 inhibitors, were reported more commonly in the empagliflozin group; however, such events led to treatment discontinuation in very few patients. These findings suggest that, with their complementary mechanisms of action, empagliflozin added on to basal insulin may be a useful treatment option in patients on basal insulin who need additional glycemic control without weight gain.

  4. R-hyper-CVAD versus R-CHOP/cytarabine with high-dose therapy and autologous haematopoietic stem cell support in fit patients with mantle cell lymphoma: 20 years of single-center experience.

    Science.gov (United States)

    Widmer, Fabienne; Balabanov, Stefan; Soldini, Davide; Samaras, Panagiotis; Gerber, Bernhard; Manz, Markus G; Goede, Jeroen S

    2018-02-01

    Standard of care for untreated mantle cell lymphoma (MCL) is still debated. At the University Hospital Zurich, advanced MCL in physically fit patients is treated either with rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone induction followed by consolidating high-dose chemotherapy and autologous stem cell support (R-CHOP/HD-ASCT), or with rituximab plus fractionated cyclophosphamide, vincristine, doxorubicin and dexamethasone alternating with high-dose methotrexate-cytarabine (R-hyper-CVAD/MTX-AraC) without consolidating HD-ASCT upon physicians' and patients' choice. We retrospectively analysed the outcome and therapy tolerance in patients with MCL treated with R-CHOP/HD-ASCT or R-hyper-CVAD/MTX-AraC at the University Hospital Zurich between January 1996 and January 2016. Forty-three patients were included; 29 patients received R-CHOP/HD-ASCT and 14 patients R-hyper-CVAD/MTX-AraC. Mean age at diagnosis was 54.4 years (range 38-68 years). Thirty-five patients (81.4%) completed the entire first-line therapy (n = 24 in the R-CHOP/HD-ASCT group, n = 11 in the R-hyper-CVAD group). Of those, all patients responded and 97% achieved a complete remission (CR). With a mean follow-up of 5.7 years 10-year progression-free survival (PFS) for all patients was 32% and overall survival (OS) was 76%, with no difference between the two therapy groups. Complication-induced hospitalisation rate, haematological toxicity and economic burden were significantly higher in the R-hyper-CVAD therapy group. In contrast, quality of life and global health state were better in the R-hyper-CVAD therapy group. Both first-line therapies showed similar outcome with a median OS longer than 10 years. Due to significantly lower haematological toxicity and lower economic burden, we recommend R-CHOP/HD-ASCT as first-line therapy in fit adult patients with advanced MCL.

  5. Comparison of the Influence on the Liver Function Between Thyroid Hormone Withdrawal and rh-TSH Before High-Dose Radioiodine Therapy in Patients with Well-Differentiated Thyroid Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Han, Yeon-Hee; Lim, Seok Tae; Yun, Kuk-No; Yim, Sung Kyun; Kim, Dong Wook; Jeong, Hwan-Jeong; Sohn, Myung-Hee [Chonbuk National Univ. Medical School and Hospital, Jeonju (Korea, Republic of)

    2012-06-15

    An elevated thyroid stimulating hormone level (TSH) is essential to stimulate the uptake of radioiodine into thyroid remnants and metastases and metastases of thyroid cancer when a patient under-goes high-dose radioiodine therapy. Nowadays, recombinant human thyroid stimulating hormone (rh-TSH) is increasingly used instead of the classic method of thyroid hormone withdrawal (THW). However, beyond the therapeutic effects, clinical differences between the two methods have not yet been clearly demonstrated. The aim of this work was to investigate the effects of the two methods, especially on liver function. We identified 143 evaluable patients who were further divided into two groups: THW and rh-TSH. We first reviewed the aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels, which were measured during the admission period for total thyroidectomy. We called these liver enzyme levels 'base AST' and 'base ALT.' We also assessed other chemistry profiles, including AST, ALT, total cholesterol, LDL cholesterol, alkaline phosphatase (ALP), total bilirubin (TB), and triglyceride (TG), which were measured on admission day for high-dose radioiodine therapy. We called these liver enzyme levels 'follow-up AST'and 'follow-up ALT.' We compared the changes in base and follow-up liver enzyme levels and the other chemistry profiles between the two groups. The base AST and base ALT levels of the two groups were within normal range, and there was no significant difference between the two groups. In contrast to these base liver enzyme levels, follow-up AST and ALT levels than did the rh-TSH group. Patients in the THW group. Patients in the THW group also had higher levels of total cholesterol and LDL cholesterol than did the patients in the rh-TSH group. However there were no statistically significant differences in ALP, total bilirubin, and triglyceride levels between the two groups. In this retrospective analysis of liver

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

    Directory of Open Access Journals (Sweden)

    Beth A. Taylor

    2014-01-01

    Full Text Available 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.

  7. Patient's quality of life after high-dose radiation therapy for thoracic carcinomas. Changes over time and influence on clinical outcome

    Energy Technology Data Exchange (ETDEWEB)

    Schroeder, Christina [University Clinic Giessen and Marburg, Clinic for Radiotherapy and Radiation Oncology, Marburg (Germany); Ruppiner Kliniken GmbH, Clinic for Radiotherapy and Radiation Oncology, Neuruppin (Germany); Engenhart-Cabillic, Rita; Vorwerk, Hilke [University Clinic Giessen and Marburg, Clinic for Radiotherapy and Radiation Oncology, Marburg (Germany); Schmidt, Michael; Huhnt, Winfried; Blank, Eyck; Sidow, Dietrich; Buchali, Andre [Ruppiner Kliniken GmbH, Clinic for Radiotherapy and Radiation Oncology, Neuruppin (Germany)

    2017-02-15

    Quality of life (QoL) is an important factor in patient care. This analysis is focused on QoL before and after radio(chemo)therapy in patients with thoracic carcinomas, as well as on its influence on clinical follow-up and survival, and the correlation with treatment-related toxicities. The analysis included 81 patients with intrathoracic carcinoma receiving radio(chemo)therapy. For analysis of QoL, the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and the lung cancer-specific supplement (EORTC QLQ-LC13) were used. QoL data were collected before radiation treatment (RT), and 6 weeks, 12 weeks, 6 months, and 12 months after RT. Other factors were additionally analyzed, including clinical outcome, survival, and side effects. The functional scales showed maximum values or at least a recovery 12 weeks after RT. Symptoms with a high mean symptom score (> 40) at all appointments were fatigue, dyspnea, and coughing. Insomnia, peripheral neuropathy, appetite loss, dyspnea (from QLQ-LC13), and all pain parameters had an intermediate mean score (10-40). There were low mean scores of < 10 for nausea and vomiting, diarrhea, sore mouth, and hemoptysis. There was a significant correlation between clinical dysphagia and radiation pneumonitis with the associated symptom scales. None of the QoL scores had a significant influence on local and distant control or survival. 12 weeks after RT the QLQ-C30 functional scales show the highest scores or at least a temporary recovery. The symptom scales accurately reflect the common symptoms and treatment-related toxicities. QoL did not prove to be a significant predictor for local and distant control or survival. (orig.) [German] Die Lebensqualitaet (QoL) ist ein entscheidender Faktor in der Patientenversorgung. In der vorliegenden Untersuchung lag der Fokus auf der QoL vor und nach Radio(chemo)therapie von Patienten mit thorakalen Tumoren sowie deren Einfluss auf das klinische

  8. A prospective randomized study concerning the point a dose in high-dose rate intracavitary therapy for carcinoma of the uterine cervix. The final results

    International Nuclear Information System (INIS)

    Chatani, M.; Matayoshi, Y.; Masaki, N.; Teshima, T.; Inoue, T.

    1994-01-01

    Between January 1983 and February 1989, a total of 165 patients with carcinoma of the unterine cervix was entered in a prospective randomized study concerning the point A dose of HDR therapy (6 Gy/fraktion vs 7.5 Gy/fraction) and external irradiation dose at Department of Radiation Therapy, The Center for Adult Diseases, Osaka. UICC stage distribution of patients was as follows: Stage IA=4, stage IB=33, stage IIA=18, stage IIB=38, stage III=57, stage IV=15. Overall 5-year cause specific survivals were as follows: Stage IA=100%, stage IB=96%, stage IIA=92%, stage IIB=79%, stage III=57%, stage IV=27%. In each stage, 5-year survival rates in groups A and B were 100%, 93% in stage I, 82% and 85% in stage II, 62% and 52% in stage II and 22% and 31% in stage IV, respectively. There were no statistically significant differences among these survival curves in each stage. Five-year local failure rates were 16% in group A and 16% in group B (p=0.9096), and corresponding distant failure rates were 23% in group A and 19% in group B (p=0.2955). Moderate-to-severe complications requiring treatment (Kottmeier's grade 2 or more) were noted in 6 patients (7%) in group A and 6 patients (7%) in group B. All of the bladder and rectal complications needed medical treatment (Kottmeier's grade 2). Severe complications receiving surgery were noted in 4 patients (A: 1; B: 3), i.e., small intestine 3 and sigmoid colon 1 patient. Another 1 patient (A) was dead of ileus. There were no statistically significant differences between 2 treatment schedules in survival rates, failure patterns and complications rates. This fact suggests that small number of fractions (7.5 Gy/fraction) may be advantageous because of short duration and a low load of treatment. (orig.) [de

  9. Patient's quality of life after high-dose radiation therapy for thoracic carcinomas. Changes over time and influence on clinical outcome

    International Nuclear Information System (INIS)

    Schroeder, Christina; Engenhart-Cabillic, Rita; Vorwerk, Hilke; Schmidt, Michael; Huhnt, Winfried; Blank, Eyck; Sidow, Dietrich; Buchali, Andre

    2017-01-01

    Quality of life (QoL) is an important factor in patient care. This analysis is focused on QoL before and after radio(chemo)therapy in patients with thoracic carcinomas, as well as on its influence on clinical follow-up and survival, and the correlation with treatment-related toxicities. The analysis included 81 patients with intrathoracic carcinoma receiving radio(chemo)therapy. For analysis of QoL, the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and the lung cancer-specific supplement (EORTC QLQ-LC13) were used. QoL data were collected before radiation treatment (RT), and 6 weeks, 12 weeks, 6 months, and 12 months after RT. Other factors were additionally analyzed, including clinical outcome, survival, and side effects. The functional scales showed maximum values or at least a recovery 12 weeks after RT. Symptoms with a high mean symptom score (> 40) at all appointments were fatigue, dyspnea, and coughing. Insomnia, peripheral neuropathy, appetite loss, dyspnea (from QLQ-LC13), and all pain parameters had an intermediate mean score (10-40). There were low mean scores of < 10 for nausea and vomiting, diarrhea, sore mouth, and hemoptysis. There was a significant correlation between clinical dysphagia and radiation pneumonitis with the associated symptom scales. None of the QoL scores had a significant influence on local and distant control or survival. 12 weeks after RT the QLQ-C30 functional scales show the highest scores or at least a temporary recovery. The symptom scales accurately reflect the common symptoms and treatment-related toxicities. QoL did not prove to be a significant predictor for local and distant control or survival. (orig.) [de

  10. Insulin

    Science.gov (United States)

    ... For Consumers Home For Consumers Consumer Information by Audience For Women Women's Health Topics Insulin Share Tweet ... I start having side effects? What is my target blood sugar level? How often should I check ...

  11. Novel simple insulin delivery device reduces barriers to insulin therapy in type 2 diabetes: results from a pilot study.

    Science.gov (United States)

    Hermanns, Norbert; Lilly, Leslie C; Mader, Julia K; Aberer, Felix; Ribitsch, Anja; Kojzar, Harald; Warner, Jay; Pieber, Thomas R

    2015-05-01

    The PaQ® insulin delivery system is a simple-to-use patch-on device that provides preset basal rates and bolus insulin on demand. In addition to feasibility of use, safety, and efficacy (reported elsewhere), this study analyzed the impact of PaQ on patient-reported outcomes, including barriers to insulin treatment, diabetes-related distress, and attitudes toward insulin therapy in patients with type 2 diabetes on a stable multiple daily injection (MDI) regimen. This single-center, open-label, single-arm study comprised three 2-week periods: baseline (MDI), transition from MDI to PaQ, and PaQ treatment. Validated questionnaires were administered during the baseline and PaQ treatment periods: Barriers to Insulin Treatment questionnaire (BIT), Insulin Treatment Appraisal Scale (ITAS), and Problem Areas in Diabetes scale (PAID). Eighteen patients (age 59 ± 5 years, diabetes duration 15 ± 7 years, 21% female, HbA1c 7.7 ± 0.7%) completed the questionnaires. There was a strong, significant effect of PaQ use in mean BIT total scores (difference [D] = -5.4 ± 0.7.7, P = .01, effect size [d] = 0.70). Patients perceived less stigmatization by insulin injection (D = -2.2 ± 6.2, P = .18, d = 0.35), increased positive outcome (D = 1.9 ± 6.6, P = .17, d = 0.29), and less fear of injections (1.3 ± 4.8, P = .55, d = 0.28). Mean change in ITAS scores after PaQ device use showed a nonsignificant improvement of 1.71 ± 5.63 but moderate effect size (d = 0.30, P = .14). No increase in PAID scores was seen. The results and moderate to large effects sizes suggest that PaQ device use has beneficial and clinically relevant effects to overcoming barriers to and negative appraisal of insulin treatment, without increasing other diabetes-related distress. © 2015 Diabetes Technology Society.

  12. Folliculitis et perifolliculitis capitis abscedens et suffodiens controlled with a combination therapy: Systemic antibiosis (Metronidazole Plus Clindamycin, dermatosurgical approach, and high-dose isotretinoin

    Directory of Open Access Journals (Sweden)

    Georgi Tchernev

    2011-01-01

    Full Text Available Folliculitis et perifolliculitis capitis abscedens et suffodiens is a rare disease of unknown etiology. It is a suppurative process that involves the scalp, eventually resulting in extensive scarring and irreversible alopecia. The condition is also known as ′acne necrotica miliaris′ or ′Proprionibacterium′ folliculitis. Most often the disease affects men of African-American or African-Caribbean descent between 20 and 40 years of age. The clinical picture is determined by fluctuating painful fistule-forming conglomerates of abscesses in the region of the occipital scalp. The cause of scalp folliculitis is not well understood. It is generally considered to be an inflammatory reaction to components of the hair follicle, particularly the micro-organisms. These include: bacteria (especially Propionibacterium acnes, but in severe cases, also Staphylococcus aureus, Yeasts (Malassezia species and mites (Demodex folliculorum. The initial histopathologic finding is an exclusively neutrophilic infiltration followed by a granulomatous infiltrate. The treatment of the disease is usually difficult and often disappointing. Successful treatment with isotretinoin 1 mg/kg body mass could be achieved only after regular systematic administration in the course of 3-4 months. Here we describe a patient with eruptive purulent form of the disease, which has been controlled with combination therapy: systemic antibiosis with metronidazole and clindamycin, dermatosurgical removal of single nodular formations, and isotretinoin 1 mg/kg body mass for 3-5 months.

  13. [Perception of insulin therapy in uncontrolled patients with type 2 diabetes mellitus].

    Science.gov (United States)

    Leyva Jiménez, Rafael; Hernández Zambrano, Gustavo; Ibarra Maldonado, Silvia; Ibarra Ramírez, Carlos Tomás

    2016-10-01

    To determine the perception of insulin therapy by patients with uncontrolled type2 diabetes mellitus, who have been treated with oral hypoglycaemic agents or insulin. Prospective comparative cross-sectional study. Family Medicine Unit No. 53 León, Guanajuato of Mexican Institute of Social Security. Patients between 40 and 80years old with uncontrolled type2 mellitus diabetes, treated with insulin or oral hypoglycaemic agents. Perception was assessed using the insulin treatment appraisal scale (ITAS). The rating of the survey is from 20 to 100 points, as such that when score increases the greater is the negative opinion. A sample of 459 diabetes patients were interviewed and split into 2 groups of patients according to their treatment. The OH group were patients treated with oral hypoglycaemic drugs only (56.9%), and the IN group were patients treated with insulin alone or combined with an oral hypoglycaemic (43.1%). Perception score was significantly higher in OH group (56.95±7.78 versus 49.55±8.89 points) than in the IN group (P1). The perception of insulin therapy was worse in patients treated with only oral hypoglycaemic agents than in patients using insulin. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

  14. Insulin pump therapy in children with type 1 diabetes

    DEFF Research Database (Denmark)

    Szypowska, Agnieszka; Schwandt, Anke; Svensson, Jannet

    2016-01-01

    BACKGROUND: Intensified insulin delivery using multiple daily injections (MDI) or continuous subcutaneous insulin infusion (CSII) is recommended in children with type 1 diabetes (T1D) to achieve good metabolic control. OBJECTIVE: To examine the frequency of pump usage in T1D children treated...... in SWEET (Better control in Paediatric and Adolescent diabeteS: Working to crEate CEnTers of Reference) centers and to compare metabolic control between patients treated with CSII vs MDI. METHODS: This study included 16 570 T1D children participating in the SWEET prospective, multicenter, standardized...... is offered by most Sweet centers. The differences between centers affect the frequency of use of modern technology. Despite the heterogeneity of centers, T1D children achieve relatively good metabolic control, especially those treated with insulin pumps and those of younger age....

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

    Energy Technology Data Exchange (ETDEWEB)

    Song, Chang W., E-mail: songx001@umn.edu [Department of Therapeutic Radiology-Radiation Oncology, University of Minnesota Medical School, Minneapolis, Minnesota (United States); Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Lee, Yoon-Jin [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Griffin, Robert J. [Department of Radiation Oncology, University of Arkansas for Medical Sciences, Little Rock, Arkansas (United States); Park, Inhwan [Department of Therapeutic Radiology-Radiation Oncology, University of Minnesota Medical School, Minneapolis, Minnesota (United States); Koonce, Nathan A. [Department of Radiation Oncology, University of Arkansas for Medical Sciences, Little Rock, Arkansas (United States); Hui, Susanta [Department of Therapeutic Radiology-Radiation Oncology, University of Minnesota Medical School, Minneapolis, Minnesota (United States); Kim, Mi-Sook [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Dusenbery, Kathryn E. [Department of Therapeutic Radiology-Radiation Oncology, University of Minnesota Medical School, Minneapolis, Minnesota (United States); Sperduto, Paul W. [Minneapolis Radiation Oncology and Gamma Knife Center, University of Minnesota, Minneapolis, Minnesota (United States); Cho, L. Chinsoo [Department of Therapeutic Radiology-Radiation Oncology, University of Minnesota Medical School, Minneapolis, Minnesota (United States)

    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.

  16. Barriers towards insulin therapy in type 2 diabetic patients: results of an observational longitudinal study

    Directory of Open Access Journals (Sweden)

    Kulzer Bernd

    2010-10-01

    Full Text Available Abstract Background The course of barriers towards insulin therapy was analysed in three different groups of type 2 diabetic patients. This observational longitudinal study surveyed a three-month follow-up. Methods Participants in this study totalled 130 type 2 diabetic patients. The first subgroup was on insulin therapy at baseline (group 1: n = 57, age 55.6 ± 8.7 yrs, disease duration 12.7 ± 7.2 yrs, HbA1c 8.5 ± 1.6% and remained on insulin at follow-up. Of an initial 73 insulin-naïve patients, 44 were switched to insulin therapy (group 2: age 58.1 ± 6.8 yrs, disease duration 7.7 ± 5.0 yrs, HbA1c 9.1 ± 1.7% and 29 patients remained on an oral regimen (group 3: age 52.7 ± 10.7 yrs, disease duration 5.3 ± 4.6 yrs, HbA1c 8.3 ± 1.4%. Barriers towards insulin therapy were measured using the Insulin Treatment Appraisal Scale (ITAS. As generic instruments of health related quality of life patients completed also the Problem Areas of Diabetes Questionnaire (PAID, the WHO-5 Well-Being Scale (WHO-5, the Centre for Epidemiologic Studies Depression Scale (CES-D and the Trait Version of the State Trait Anxiety Inventory (STAI at baseline and at three-month follow-up. Results At the three-month follow-up, HbA1c had improved in all three groups (7.7 ± 1.2% vs. 7.1 ± 1.1% vs. 6.7 ± 0.8%. The course of negative appraisal of insulin therapy was significantly different in the three groups (p > .003: the ITAS score increased in patients remained on oral antidiabetic drugs (51.2 ± 12.2 to 53.6 ± 12.3, whereas it decreased in patients switched to insulin therapy (49.2 ± 9.8 to 46.2 ± 9.9 or remained on insulin treatment (45.8 ± 8.3 to 44.5 ± 8.0. Diabetes-related distress, trait anxiety, and well-being, showed a similar course in all three groups. The depression score improved significantly in patients switched to insulin treatment compared with patients remaining on insulin therapy. Conclusions In summary, this study suggests that a negative

  17. SU-F-T-506: Development and Commissioning of the Effective and Efficient Grid Therapy Using High Dose Rate Flattening Filter Free Beam and Multileaf Collimator

    Energy Technology Data Exchange (ETDEWEB)

    Liu, M; Wen, N; Beyer, C; Siddiqui, F; Chetty, I; Zhao, B [Henry Ford Health System, Detroit, MI (United States)

    2016-06-15

    Purpose: Treating bulky tumors with grid therapy (GT) has demonstrated high response rates. Long delivery time (∼15min), with consequent increased risk of intrafraction motion, is a major disadvantage of conventional MLC-based GT (MLC-GT). The goal of this study was to develop and commission a MLC-GT technique with similar dosimetric characteristics, but more efficient delivery. Methods: Grid plan was designed with 10X-FFF (2400MU/min) beam and MLC in a commercial treatment planning system (TPS). Grid size was 1cm by 1cm and grid-to-grid distance was 2cm. Field-in-field technique was used to flatten the dose profile at depth of 10cm. Prescription was 15Gy at 1.5cm depth. Doses were verified at depths of 1.5cm, 5cm and 10cm. Point dose was measured with a plastic scintillator detector (PSD) while the planar dose was measured with calibrated Gafchromic EBT3 films in a 20cm think, 30cmx30cm solid water phantom. The measured doses were compared to the doses calculated in the treatment planning system. Percent depth dose (PDD) within the grid was also measured using EBT3 film. Five clinical cases were planned to compare beam-on time. Results: The valley-to-peak dose ratio at the 3 depths was approximately 10–15%, which is very similar to published result. The average point dose difference between the PSD measurements and TPS calculation is 2.1±0.6%. Film dosimetry revealed good agreement between the delivered and calculated dose. The average gamma passing rates at the 3 depths were 95% (3%, 1mm). The average percent difference between the measured PDD and calculated PDD was 2.1% within the depth of 20cm. The phantom plan delivery time was 3.6 min. Average beam-on time was reduced by 66.1±5.6% for the 5 clinical cases. Conclusion: An effective and efficient GT technique was developed and commissioned for the treatment of bulky tumors using FFF beam combined with MLC and automation. The Department of Radiation Oncology at Henry Ford Health System receives research

  18. Phase II trial of combined surgical resection, intraoperative high dose rate brachytherapy (IORT), and external beam radiation therapy (EBRT) for malignant pleural mesothelioma (MPM)

    International Nuclear Information System (INIS)

    Raben, A.; Rusch, V.; Mychalczak, B.; Schupak, K.; Ginsburg, R.; Burt, M.; Bains, M.; Harrison, L.B.

    1996-01-01

    respiratory distress and expired. Two pts developed a postoperative empyema with bronchial stump leak; with 1 pt developing bleeding from mediastinal vessels at 7 months. This was felt to be related to late radiation toxicity. Wound dehiscence of the thoracotomy incision occurred in 1 pt. Of the 4 pts undergoing PD, 1 pt developed a tracheoesophageal fistula, and 1 developed a postoperative chest tube leak. IORT in conjunction with EPP led to prohibitive local complications and has been discontinued. Although follow-up is short, IORT with PD shows no improvement in local control compared to our historical experience. Local control with EPP/EBRT has thus far been excellent with most patients relapsing outside of the EBRT field, in distinct contrast to the reported pattern of disease progression in MPM, emphasizing the need for improved systemic therapy

  19. Lateral rectal shielding reduces late rectal morbidity after high dose three-dimensional conformal radiation therapy for clinically localized prostate cancer: further evidence for a dose effect

    Energy Technology Data Exchange (ETDEWEB)

    Lee, W Robert; Hanks, Gerald E; Hanlon, Alexandra; Schultheiss, Timothy E

    1995-07-01

    Purpose: Using conventional treatment methods for the treatment of clinically localized prostate cancer central axis doses must be limited to 65-70 Gy to prevent significant damage to nearby normal tissues. A fundamental hypothesis of three-dimensional conformal radiation therapy (3DCRT) is that, by defining the target organ(s) accurately in three dimensions, it is possible to deliver higher doses to the target without a significant increase in normal tissue complications. This study examines whether this hypothesis holds true and whether a simple modification of treatment technique can reduce the incidence of late rectal morbidity in patients with prostate cancer treated with 3DCRT to minimum planning target volume (PTV) doses of 71-75 Gy. Materials and Methods: 257 patients with clinically localized prostate cancer completed 3DCRT by December 31, 1993 and received a minimum PTV dose of 71-75 Gy. The median follow-up time was 22 months (range 4-67 months) and 98% of patients had followup of longer than 12 months. The calculated dose at the center of the prostate was <74 Gy in 19 patients, 74-76 Gy in 206 patients and >76 Gy in 32 patients. Late rectal morbidity was graded according to the LENT scoring system. Eighty-eight consecutive patients were treated with a rectal block added to the lateral fields. In these patients the posterior margin from the prostate to the block edge was reduced from the standard 15 mm to 7.5 mm for the final 10 Gy which reduced the dose to portions of the anterior rectal wall by approximately 4-5 Gy. Estimates of rates for rectal morbidity were determined by Kaplan-Meier actuarial analyses. Differences in morbidity percentages were evaluated by the Pearson chi square test. Results: Grade 2-3 rectal morbidity developed in 46 of 257 patients (18%) and in the majority of cases consisted of rectal bleeding. No patient has developed grade 4 or 5 rectal morbidity. The actuarial rate of grade 2-3 morbidity is 22% at 24 months and the median

  20. Early insulin therapy in patients with type 2 diabetes mellitus ...

    African Journals Online (AJOL)

    Type 2 diabetes mellitus (T2DM) is a progressive disease characterised by beta cell dysfunction and insulin resistance. Beta cell dysfunction progresses to beta cell failure. Many patients with T2DM are managed with oral agents until complications develop. 'Clinical inertia' in T2DM, defined as lack of initiation or ...

  1. Insulin therapy and quality of life. A review

    DEFF Research Database (Denmark)

    Pouwer, Francois; Hermanns, Norbert

    2009-01-01

    Three central goals in the treatment of diabetes mellitus are (1) the avoidance of hyperglycaemia to prevent the development or progression of diabetes complications over time, (2) the avoidance of hypoglycaemia and (3) the maintenance or achievement of good quality of life. Insulin is the most...

  2. Glucose-Responsive Implantable Polymeric Microdevices for "Smart" Insulin Therapy of Diabetes

    Science.gov (United States)

    Chu, Michael Kok Loon

    Diabetes mellitus is a chronic illness manifested by improper blood glucose management, affecting over 350 million worldwide. As a result, all type 1 patients and roughly 20% of type 2 patients require exogenous insulin therapy to survive. Typically, daily multiple injections are taken to maintain normal glucose levels in response glucose spikes from meals. However, patient compliance and dosing accuracy can fluctuate with variation in meals, exercise, glucose metabolism or stress, leading to poor clinical outcomes. A 'smart', closed-loop insulin delivery system providing on-demand release kinetics responding to circulating glucose levels would be a boon for diabetes patients, replacing constant self monitoring and insulin. This thesis focuses on the development of a novel, 'smart' insulin microdevice that can provide on-demand insulin release in response to blood glucose levels. In the early stage, the feasibility of integrating a composite membrane with pH-responsive nanoparticles embedded in ethylcellulose membrane to provide pH-responsive in vitro release was examined and confirmed using a model drug, vitamin B12. In the second microdevice, glucose oxidase for generating pH signals from glucose oxidation, catalase and manganese dioxide nanoparticles, as peroxide scavengers, were used in a bioinorganic, albumin-based membrane cross-linked with a polydimethylsiloxane (PDMS) grid-microdevice system. This prototype device demonstrated insulin release in response to glucose levels in vitro and regulating plasma glucose in type 1 diabetic rats when implanted intraperitoneally. Advancement allowing for subcutaneous implantation and improved biocompatibility was achieved with surface modification of PDMS microdevices grafted with activated 20 kDa polyethylene glycol (PEG) chains, dramatically reducing immune response and local inflammation. When implanted subcutaneously in diabetic rats, glucose-responsive insulin delivery microdevices showed short and long

  3. Overweight, insulin resistance and type II diabetes in type I Gaucher disease patients in relation to enzyme replacement therapy

    NARCIS (Netherlands)

    Langeveld, M.; de Fost, M.; Aerts, J. M. F. G.; Sauerwein, H. P.; Hollak, C. E. M.

    2008-01-01

    Type I Gaucher disease, a lysosomal storage disorder is associated with metabolic abnormalities such as high resting energy expenditure, low circulating adiponectin and peripheral insulin resistance. Treatment with enzyme replacement therapy (enzyme therapy) leads to a decrease in resting energy

  4. Short-term oestrogen replacement therapy improves insulin resistance, lipids and fibrinolysis in postmenopausal women with NIDDM

    NARCIS (Netherlands)

    Brussaard, H.E.; Gevers Leuven, J.A.; Frölich, M.; Kluft, C.; Krans, H.M.J.

    1997-01-01

    Oestrogen replacement therapy is associated with a decreased risk of cardiovascular disease in postmenopausal women. Patients with non-insulin- dependent diabetes mellitus (NIDDM) have an increased cardiovascular risk. However, oestrogen replacement therapy is only reluctantly prescribed for

  5. Clearance of Hepatitis C Virus Improves Insulin Resistance During and After Peginterferon and Ribavirin Therapy.

    Science.gov (United States)

    Chien, Cheng-Hung; Lin, Chih-Lang; Hu, Ching-Chih; Chang, Jia-Jang; Chien, Rong-Nan

    2015-12-01

    Patients with chronic hepatitis C virus (HCV) infection are at a greater risk of developing insulin resistance (IR). However, little is known about when insulin sensitivity may improve during or after treatment for hepatitis C. In this study, we examined the effect of combination therapy with pegylated interferon-α and ribavirin on IR in patients with chronic HCV infection. We also analyzed factors associated with changes in insulin sensitivity. IR was estimated by homeostasis model assessment (HOMA-IR). HOMA-IR was measured before therapy, during therapy (12 and 24 weeks), and at the end of therapy (EOT; 24 or 48 weeks). We analyzed 78 HCV patients receiving combination therapy. Twenty-two patients (28.2%) exhibited pretreatment IR (HOMA-IR >2.5). In all patients, HOMA-IR was not significantly different from baseline values at 12 weeks (P = 0.823), 24 weeks (P = 0.417), or at EOT (P = 0.158). In patients with pretreatment IR, a significant decrease in HOMA-IR was observed at 12 weeks (P = 0.023), 24 weeks (P = 0.008), and at EOT (P = 0.002). Multivariate analysis using a logistic regression model showed that baseline HOMA-IR is the only factor associated with the decline in HOMA-IR during and after therapy. The eradication of HCV infection was associated with improved insulin sensitivity among patients with pretreatment IR. This significant improvement in insulin sensitivity may occur as early as 12 weeks after the initiation of antiviral therapy.

  6. Insulin therapy in patients with cystic fibrosis in the pre-diabetes stage: a systematic review.

    Science.gov (United States)

    Pu, Mariana Zorrón Mei Hsia; Christensen-Adad, Flávia Corrêa; Gonçalves, Aline Cristina; Minicucci, Walter José; Ribeiro, José Dirceu; Ribeiro, Antonio Fernando

    2016-09-01

    To elucidate whether insulin is effective or not in patients with cystic fibrosis before the diabetes mellitus phase. The study was performed according to the Prisma method between August and September 2014, using the PubMed, Embase, Lilacs and SciELO databases. Prospective studies published in English, Portuguese and Spanish from 2002 to 2014, evaluating the effect of insulin on weight parameters, body mass index and pulmonary function in patients with cystic fibrosis, with a mean age of 17.37 years before the diabetes mellitus phase were included. Eight articles were identified that included 180 patients undergoing insulin use. Sample size ranged from 4 to 54 patients, with a mean age ranging from 12.4 to 28 years. The type of follow-up, time of insulin use, the dose and implementation schedule were very heterogeneous between studies. There are theoretical reasons to believe that insulin has a beneficial effect in the studied population. The different methods and populations assessed in the studies do not allow us to state whether early insulin therapy should or should not be carried out in patients with cystic fibrosis prior to the diagnosis of diabetes. Therefore, studies with larger samples and insulin use standardization are required. Copyright © 2016 Sociedade de Pediatria de São Paulo. Publicado por Elsevier Editora Ltda. All rights reserved.

  7. Insulin therapy in patients with cystic fibrosis in the pre-diabetes stage: a systematic review

    Directory of Open Access Journals (Sweden)

    Mariana Zorrón Mei Hsia Pu

    Full Text Available Abstract Objective: To elucidate whether insulin is effective or not in patients with cystic fibrosis before the diabetes mellitus phase. Data source: The study was performed according to the Prisma method between August and September 2014, using the PubMed, Embase, Lilacs and SciELO databases. Prospective studies published in English, Portuguese and Spanish from 2002 to 2014, evaluating the effect of insulin on weight parameters, body mass index and pulmonary function in patients with cystic fibrosis, with a mean age of 17.37 years before the diabetes mellitus phase were included. Data synthesis: Eight articles were identified that included 180 patients undergoing insulin use. Sample size ranged from 4 to 54 patients, with a mean age ranging from 12.4 to 28 years. The type of follow-up, time of insulin use, the dose and implementation schedule were very heterogeneous between studies. Conclusions: There are theoretical reasons to believe that insulin has a beneficial effect in the studied population. The different methods and populations assessed in the studies do not allow us to state whether early insulin therapy should or should not be carried out in patients with cystic fibrosis prior to the diagnosis of diabetes. Therefore, studies with larger samples and insulin use standardization are required.

  8. Long-term interdisciplinary therapy reduces endotoxin level and insulin resistance in obese adolescents.

    Science.gov (United States)

    Lira, Fábio S; Rosa, Jose C; Pimentel, Gustavo D; Santos, Ronaldo V; Carnier, June; Sanches, Priscila L; de Piano, Aline; de Souza, Claudio T; Tock, Lian; Tufik, Sergio; de Mello, Marco T; Seelaender, Marília; Oller do Nascimento, Claudia M; Oyama, Lila M; Dâmaso, Ana R

    2012-09-18

    The purpose of the present study was to assess the dietary fat intake, glucose, insulin, Homeostasis model assessment for insulin resistance HOMA-IR, and endotoxin levels and correlate them with adipokine serum concentrations in obese adolescents who had been admitted to long-term interdisciplinary weight-loss therapy. The present study was a longitudinal clinical intervention of interdisciplinary therapy. Adolescents (n = 18, aged 15-19 y) with a body mass index > 95th percentile were admitted and evaluated at baseline and again after 1 year of interdisciplinary therapy. We collected blood samples, and IL-6, adiponectin, and endotoxin concentrations were measured by ELISA. Food intake was measured using 3-day diet records. In addition, we assessed glucose and insulin levels as well as the homeostasis model assessment for insulin resistance (HOMA-IR). The most important finding from the present investigation was that the long-term interdisciplinary lifestyle therapy decreased dietary fat intake and endotoxin levels and improved HOMA-IR. We observed positive correlations between dietary fat intake and endotoxin levels, insulin levels, and the HOMA-IR. In addition, endotoxin levels showed positive correlations with IL-6 levels, insulin levels and the HOMA-IR. Interestingly, we observed a negative correlation between serum adiponectin and both dietary fat intake and endotoxin levels. The present results indicate an association between dietary fat intake and endotoxin level, which was highly correlated with a decreased pro-inflammatory state and an improvement in HOMA-IR. In addition, this benefits effect may be associated with an increased adiponectin level, which suggests that the interdisciplinary therapy was effective in improving inflammatory pathways.

  9. Long-term interdisciplinary therapy reduces endotoxin level and insulin resistance in obese adolescents

    Directory of Open Access Journals (Sweden)

    Lira Fábio S

    2012-09-01

    Full Text Available Abstract Aim The purpose of the present study was to assess the dietary fat intake, glucose, insulin, Homeostasis model assessment for insulin resistance HOMA-IR, and endotoxin levels and correlate them with adipokine serum concentrations in obese adolescents who had been admitted to long-term interdisciplinary weight-loss therapy. Design The present study was a longitudinal clinical intervention of interdisciplinary therapy. Adolescents (n = 18, aged 15–19 y with a body mass index > 95th percentile were admitted and evaluated at baseline and again after 1 year of interdisciplinary therapy. We collected blood samples, and IL-6, adiponectin, and endotoxin concentrations were measured by ELISA. Food intake was measured using 3-day diet records. In addition, we assessed glucose and insulin levels as well as the homeostasis model assessment for insulin resistance (HOMA-IR. Results The most important finding from the present investigation was that the long-term interdisciplinary lifestyle therapy decreased dietary fat intake and endotoxin levels and improved HOMA-IR. We observed positive correlations between dietary fat intake and endotoxin levels, insulin levels, and the HOMA-IR. In addition, endotoxin levels showed positive correlations with IL-6 levels, insulin levels and the HOMA-IR. Interestingly, we observed a negative correlation between serum adiponectin and both dietary fat intake and endotoxin levels. Conclusions The present results indicate an association between dietary fat intake and endotoxin level, which was highly correlated with a decreased pro-inflammatory state and an improvement in HOMA-IR. In addition, this benefits effect may be associated with an increased adiponectin level, which suggests that the interdisciplinary therapy was effective in improving inflammatory pathways.

  10. The use and efficacy of continuous glucose monitoring in type 1 diabetes treated with insulin pump therapy

    DEFF Research Database (Denmark)

    Battelino, T; Conget, I; Olsen, B

    2012-01-01

    The aim of this multicentre, randomised, controlled crossover study was to determine the efficacy of adding continuous glucose monitoring (CGM) to insulin pump therapy (CSII) in type 1 diabetes.......The aim of this multicentre, randomised, controlled crossover study was to determine the efficacy of adding continuous glucose monitoring (CGM) to insulin pump therapy (CSII) in type 1 diabetes....

  11. A pilot study of factors associated with glycaemic control in adults with Type 1 diabetes mellitus on insulin pump therapy.

    Science.gov (United States)

    Wen, W; Frampton, R; Wright, K; Fattore, S; Shadbolt, B; Perampalam, S

    2016-02-01

    To identify the knowledge and management factors associated with glycaemic control among adults with Type 1 diabetes mellitus treated with insulin pump therapy. A cross-sectional study of adults with Type 1 diabetes mellitus on insulin pump therapy for at least 12 months (n = 50, 18-70 years old) was undertaken between December 2013 and May 2014. A new questionnaire was developed to evaluate participants' knowledge and management related to insulin pump therapy, and were correlated with insulin pump data, HbA1c and frequency of hypoglycaemia. Participants who changed their insulin pump settings when indicated had significantly better glycaemic control than those who did not (P = 0.04). Multivariate logistic regression analysis found that better overall insulin pump therapy management was a significant predictor of better glycaemic control (odds ratio 4.45, 95% confidence interval 1.61-12.3; P = 0.004) after adjusting for potential confounders including age, gender, duration of diabetes and insulin pump therapy. However, overall insulin pump therapy knowledge was not a significant predictor of glycaemic control (P = 0.058). There was no significant association between frequency of hypoglycaemia and insulin pump therapy knowledge or management. We identified some key knowledge and management factors associated with glycaemic control in adults with Type 1 diabetes mellitus on insulin pump therapy using a newly designed questionnaire. The pilot study assessed the clinical utility of this evaluation tool, which may facilitate provision of targeted education to insulin pump therapy users to achieve optimal glycaemic control. © 2015 The Authors. Diabetic Medicine © 2015 Diabetes UK.

  12. Impact of Sequencing Targeted Therapies With High-dose Interleukin-2 Immunotherapy: An Analysis of Outcome and Survival of Patients With Metastatic Renal Cell Carcinoma From an On-going Observational IL-2 Clinical Trial: PROCLAIMSM.

    Science.gov (United States)

    Clark, Joseph I; Wong, Michael K K; Kaufman, Howard L; Daniels, Gregory A; Morse, Michael A; McDermott, David F; Agarwala, Sanjiv S; Lewis, Lionel D; Stewart, John H; Vaishampayan, Ulka; Curti, Brendan; Gonzalez, René; Lutzky, Jose; Rudraptna, Venkatesh; Cranmer, Lee D; Jeter, Joanne M; Hauke, Ralph J; Miletello, Gerald; Milhem, Mohammed M; Amin, Asim; Richart, John M; Fishman, Mayer; Hallmeyer, Sigrun; Patel, Sapna P; Van Veldhuizen, Peter; Agarwal, Neeraj; Taback, Bret; Treisman, Jonathan S; Ernstoff, Marc S; Perritt, Jessica C; Hua, Hong; Rao, Tharak B; Dutcher, Janice P; Aung, Sandra

    2017-02-01

    This analysis describes the outcome for patients who received targeted therapy (TT) prior to or following high-dose interleukin-2 (HD IL-2). Patients with renal cell carcinoma (n = 352) receiving HD IL-2 were enrolled in Proleukin R Observational Study to Evaluate the Treatment Patterns and Clinical Response in Malignancy (PROCLAIM SM ) beginning in 2011. Statistical analyses were performed using datasets as of September 24, 2015. Overall, there were 4% complete response (CR), 13% partial response (PR), 39% stable disease (SD), and 43% progressive disease (PD) with HD IL-2. The median overall survival (mOS) was not reached in patients with CR, PR, or SD, and was 15.5 months in patients with PD (median follow-up, 21 months). Sixty-one patients had prior TT before HD IL-2 with an overall response rate (ORR) to HD IL-2 of 19% (1 CR, 9 PR) and an mOS of 22.1 months. One hundred forty-nine patients received TT only after HD IL-2 with an mOS of 35.5 months. One hundred forty-two patients had no TT before or after HD IL-2, and mOS was not reached. The mOS was 8.5 months in PD patients who received HD IL-2 without follow-on TT and 29.7 months in PD patients who received follow-on TT after HD IL-2. HD IL-2 as sole front-line therapy, in the absence of added TT, shows extended clinical benefit (CR, PR, and SD). Patients with PD after HD IL-2 appear to benefit from follow-on TT. Patients who progressed on TT and received follow-on HD IL-2 experienced major clinical benefit. HD IL-2 therapy should be considered in eligible patients. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  13. Effect of metformin on plasma metabolite profile in the Copenhagen Insulin and Metformin Therapy (CIMT) trial

    DEFF Research Database (Denmark)

    Safai, N; Suvitaival, T; A, Ali

    2018-01-01

    of the Copenhagen Insulin and Metformin Therapy (CMIT) trial, a multicentre study from May 2008 to December 2012, was carried out. We used a non-target method to analyse 87 plasma metabolites in participants with Type 2 diabetes (n = 370) who were randomized in a 1 : 1 ratio to 18 months of metformin or placebo...

  14. Maternal insulin therapy does not restore foetoplacental endothelial dysfunction in gestational diabetes mellitus

    NARCIS (Netherlands)

    Subiabre, Mario; Silva, Luis; Villalobos-Labra, Roberto; Toledo, Fernando; Paublo, Mario; López, Marcia A.; Salsoso, Rocío; Pardo, Fabián; Leiva, Andrea; Sobrevia, Luis

    Pregnant women diagnosed with gestational diabetes mellitus subjected to diet (GDMd) that do not reach normal glycaemia are passed to insulin therapy (GDMi). GDMd associates with increased human cationic amino acid transporter 1 (hCAT-1)-mediated transport of L-arginine and nitric oxide synthase

  15. Determination of attitude and knowledge of type 2 diabetic patients towards insulin therapy in Northern Cyprus

    International Nuclear Information System (INIS)

    Yilmaz, U.D.; Tarhan, S.

    2017-01-01

    To determine the attitude and knowledge of type-2 diabetics related to insulin therapy. Methods: The descriptive cross-sectional study was conducted from January to March 2014 at the Dr. Burhan Nalbantoglu Public Hospital, Nicosia in the Turkish Republic of Northern Cyprus, and comprised patients with type-2 diabetes. The Likert scale was used to score participants' response to questions using the following scoring system: 0 (disagree), 1 (neutral) and 2 (agree). The minimum scoring value for all the questions combined was 0 whereas the maximum scoring value was 50. Patients' attitudes were classified as either high, medium or low based on scores between 0-16, 17-33 and 34-50, respectively. SPSS 16 was used for data analysis. Results: Of the 271 participants, 165(60.9%) were female and 106(39.1%) male. The overall mean age was 60.3+-32.4 years. Moreover, 136(50.3%) participants had a medium attitude and knowledge score towards insulin therapy. men scored significantly better than females (p<0.05). Only 25(9.2%) participants had a high score towards insulin therapy. Conclusion: The participants were found to have an inadequate attitude and knowledge response to insulin therapy. (author)

  16. Four-year evolution of insulin regimens, glycaemic control, hypoglycaemia and body weight after starting insulin therapy in type 2 diabetes across three continents.

    Science.gov (United States)

    Home, Philip D; Dain, Marie-Paule; Freemantle, Nick; Kawamori, Ryuzo; Pfohl, Martin; Brette, Sandrine; Pilorget, Valérie; Scherbaum, Werner A; Vespasiani, Giacomo; Vincent, Maya; Balkau, Beverley

    2015-05-01

    It is of interest to understand how insulin therapy currently evolves in clinical practice, in the years after starting insulin in people with type 2 diabetes. We aimed to describe this evolution prospectively over 4 years, to assist health care planning. People who had started any insulin were identified from 12 countries on three continents. Baseline, then yearly follow-up, data were extracted from clinical records over 4 years. Of the 2999 eligible people, 2272 were followed over 4 years. When starting insulin, mean (SD) duration of diabetes was 10.6 (7.8) years, HbA1c 9.5 (2.0)% (80 [22]mmol/mol) and BMI 29.3 (6.3)kg/m(2). Initial insulin therapy was basal 52%, premix 23%, mealtime+basal 14%, mealtime 8% and other 3%; at 4 years, 30%, 25%, 33%, 2% and 5%, respectively, with 5% not on insulin. Insulin dose was 20.2U/day at the start and 45.8U/day at year 4. There were 1258 people (55%) on their original regimen at 4 years, and this percentage differed according to baseline insulin regimen. HbA1c change was -2.0 (2.2)% (-22 [24]mmol/mol) and was similar by final insulin regimen. Hypoglycaemia prevalence was <20% in years 1-4. Body weight change was mostly in year 1, and was very variable, mean +2.7 (7.5)kg at year 4. Different insulin regimens were started in people with differing characteristics, and they evolved differently; insulin dose, hypoglycaemia and body weight change were diverse and largely independent of regimen. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  17. Exploring patients’ perceptions for insulin therapy in type 2 diabetes: a Brazilian and Canadian qualitative study

    Directory of Open Access Journals (Sweden)

    Camila Guimarães

    2010-06-01

    Full Text Available Camila Guimarães2, Carlo A Marra1, Sabrina Gill1, Graydon Meneilly1, Scot Simpson3, Ana LPC Godoy2, Maria Cristina Foss de Freitas2, Regina HC Queiroz2, Larry Lynd11The University of British Columbia, Canada; 2University of São Paulo, Brazil; 3The University of Alberta, CanadaObjective: To explore which attributes of insulin therapy drive patients’ preferences for management in Canada and Brazil.Methods: A qualitative design was implemented in which a total of 32 patients with type 2 diabetes from Canada and Brazil, were interviewed in one of the 4 focus groups, or 16 individual interviews. Eighteen participants (56% were women and fourteen participants (44% were men (15 insulin nonusers and 17 insulin users. Two focus groups of 4 participants each and 9 individual interviews were conducted in Brazil. In Canada, 2 focus groups of 4 participants each and 7 individual interviews were conducted. A framework analysis was used to analyse all data.Results: Brazilian participants, when considering two insulin treatments, would prefer the one that had fewer side-effects (specially hypoglycemia events, was noninjectable, had the lowest cost and was most effective. Meanwhile, Canadian participants would prefer a treatment that had fewer side-effects (specially weight gain, was less invasive, was more convenient and was most effective.Conclusions: Finding the insulin-delivery system and the attributes of insulin therapy that best meet patients’ preferences may lead to improved control, through improved compliance, which may ultimately reduce the financial burden of the disease and improve quality of life.Keywords: type 2 diabetes, insulin administration, glycemic control, weight gain, hypoglycemia, qualitative study, patients’ preferences

  18. SGLT2 inhibitors as adjunct therapy to insulin in type 1 diabetes: Meta analysis

    Directory of Open Access Journals (Sweden)

    Jiao CHEN

    2017-02-01

    Full Text Available Objective To evaluate the efficacy and safety of sodium glucose co-transporter-2 (SGLT-2 inhibitors as adjunct therapy to insulin in type 1 diabetes (T1DM. Methods The PubMed, The Cochrane Library, EMbase, CENTRRAI, CBM, CNKI, VIP and WangFang database were searched from inception to April 5, 2016 for systematic reviews, references screen was performed manually. The trials of SGLT2 inhibitors versus placebo add to insulin carried out in patients with T1DM were collected, and their bias risk was assessed and meta-analysis was conducted by using RevMan 5.3 software. Results Four randomized control trials (RCTs were yielded for meta-analysis, including 529 patients. Compared with control group, SGLT2 inhibitors as adjunct therapy to insulin significantly reduced fasting plasma glucose (FPG [weighted mean difference (WMD=–0.65mmol/L, 95% confidence interval (CI=–1.30 to –0.08, P<0.05], glycated hemoglobin A1C (HbA1c (WMD=–0.37%, 95%CI=–0.54 to –0.20, P<0.00001, body weight (WMD=–2.54kg, 95%CI=–3.48 to –1.60, P<0.0001 and total daily insulin dose (WMD=–6.23IU, 95% CI=–8.05 to –4.40, P<0.0001, but the total adverse events (AEs, hypoglycemia, genital and urinary infections showed no significant difference. Conclusions Based on current studies, SGLT-2 inhibitors are effective as adjunct therapy to insulin in T1DM, may improve glycemic control, reduce body weight and total daily insulin dose without increase of total AEs, hypoglycemia, and genital and urinary infections. DOI: 10.11855/j.issn.0577-7402.2016.12.15

  19. Insulin therapy refusal among type II diabetes mellitus patients in Kubang Pasu district, the state of Kedah, Malaysia.

    Science.gov (United States)

    Tan, Wei Leong; Asahar, Siti Fairus; Harun, Noor Liani

    2015-04-01

    Diabetes mellitus is a rising non-communicable disease in Malaysia. Insulin therapy refusal is a great challenge for healthcare providers, as it results in delayed insulin initiation. This study was conducted to determine the prevalence of insulin therapy refusal and its associated factors. This cross sectional study was conducted at seven public health clinics in Kubang Pasu district, Malaysia, from March to October 2012. A newly developed and validated questionnaire was used and participants were selected via systematic random sampling. Only patients diagnosed with type II diabetes mellitus (T2DM) and under the public health clinic care in Kubang Pasu were included in the study. Multiple logistic regressions were used to study the association between insulin therapy refusal and its associated factors. There were 461 respondents and the response rate was 100%. Among these 461 patients with T2DM, 74.2% refused insulin therapy. The most common reason given for refusal was a lack of confidence in insulin injection (85.4%). Multiple logistic regression revealed that respondents who had secondary education were 55.0% less likely to refuse insulin therapy than those who had primary or no formal education (p = 0.009, adjusted odds ratio [OR] = 0.45, 95% confidence interval [CI] = 0.25-0.82). There was also a significant inverse association between glycated haemoglobin (HbA1c) and insulin therapy refusal (p = 0.047, adjusted OR = 0.87, 95% CI = 0.76-1.00). Insulin therapy refusal is common in Kubang Pasu. Education status and HbA1c should be taken into consideration when counselling patients on insulin therapy initiation.

  20. Comparison of acute and subacute genitourinary and gastrointestinal adverse events of radiotherapy for prostate cancer using intensity-modulated radiation therapy, three-dimensional conformal radiation therapy, permanent implant brachytherapy and high-dose-rate brachytherapy

    NARCIS (Netherlands)

    Morimoto, Masahiro; Yoshioka, Yasuo; Konishi, Koji; Isohashi, Fumiaki; Takahashi, Yutaka; Ogata, Toshiyuki; Koizumi, Masahiko; Teshima, Teruki; Bijl, Henk P; van der Schaaf, Arjen; Langendijk, Johannes A; Ogawa, Kazuhiko

    2014-01-01

    AIMS AND BACKGROUND: To examine acute and subacute urinary and rectal toxicity in patients with localized prostate cancer monotherapeutically treated with the following four radiotherapeutic techniques: intensity-modulated radiation therapy, three-dimensional conformal radiation therapy,

  1. 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.

    Science.gov (United States)

    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.

  2. Cortical thinning in type 2 diabetes mellitus and recovering effects of insulin therapy.

    Science.gov (United States)

    Chen, Zhiye; Sun, Jie; Yang, Yang; Lou, Xin; Wang, Yulin; Wang, Yan; Ma, Lin

    2015-02-01

    The purpose of this study was to explore the brain structural changes in type 2 diabetes and the effect of insulin on the brain using a surface-based cortical thickness analysis. High-resolution three-dimensional T1-weighted fast spoiled gradient recalled echo MRI were obtained from 11 patients with type 2 diabetes before and after insulin therapy. The cortical thickness over the entire brain was calculated, and cross-sectional and longitudinal surface-based cortical thickness analyses were also performed. Regional cortical thinning was demonstrated in the middle temporal gyrus, posterior cingulate gyrus, precuneus, right lateral occipital gyrus and entorhinal cortex bilaterally for patients with type 2 diabetes mellitus compared with normal controls. Cortical thickening was seen in the middle temporal gyrus, entorhinal cortex and left inferior temporal gyrus bilaterally after patients underwent 1 year of insulin therapy. These findings suggest that insulin therapy may have recovering effects on the brain cortex in type 2 diabetes mellitus. The precise mechanism should be investigated further. Copyright © 2014 Elsevier Ltd. All rights reserved.

  3. Insulin therapy waste produced in the households of people with diabetes monitored in Primary Care

    Directory of Open Access Journals (Sweden)

    Gilmara Holanda da Cunha

    Full Text Available ABSTRACT Objective: To analyze the insulin therapy waste disposal produced in the households of people with diabetes mellitus (DM. Method: Cross-sectional study with 105 Primary Care patients. Socio-demographic and clinical variables and insulin therapy practice were analyzed through the absolute and relative frequencies, Fisher's exact test and prevalence ratio (PR. Results: The association between types of insulin (60.0%, administered with a disposable syringe attached to a needle (80.9%, and a high percentage of reuse and disposal in normal household waste (57.1% stood out. The professionals who most frequently provided guidance to people with diabetes were the nurses. Patients who had received instructions about disposal were 21 times more likely to dispose of waste properly than those who had not (PR 21.5; P 0.05. Conclusion: People with diabetes served in Primary Health Care require guidance and material resources to carry out the appropriate disposal of insulin therapy waste.

  4. The efficacy of pharmaceutical combination of glucose, insulin, potassium, and magnesium along with thrombolytic therapy on the mortality of patients with acute myocardial infarction

    Directory of Open Access Journals (Sweden)

    Mohammad Garakyaraghi

    2012-03-01

    Full Text Available BACKGROUND: Despite conventional treatment methods of acute myocardial infarction, its complications and mortality rates are still very high. Finding new cost-effective treatments like regulation of ischemic muscle metabolism at the time of thrombolytic therapy can meet this requirement to some extent. This study investigated the efficacy of the pharmaceutical combination of glucose, insulin, potassium (GIK and magnesium along with thrombolytic therapy.METHODS: In a double-blind, controlled clinical trial, 200 patients with acute myocardial infarction who had the indication for thrombolytic treatment were selected and divided to 6 groups of almost 30 people. A specific treatment protocol was designed for each group. The patients in the first 5 groups were compared with the ones in the sixth group as the control group in terms of frequency of complications and in-hospital mortality and also mortality during 3 and 6 months after the treatment.RESULTS: Mean age of the patients was 58.77 ± 2.6 years. Males constituted 77% of the study population. Heart failure, in-hospital arrhythmia and ejection fraction (EF at discharge showed favorable results in the five groups which received metabolic regulations as compared to the control group. In-hospital mortality of no groups was different from that of the control group (P > 0.05. Three months after the treatment, mortality of the group that received GIK and magnesium was lower than that of the control group (P < 0.05. After 6 months, none of the patients who received high-dose GIK and magnesium along with thrombolytic therapy died while the mortality rate of the control group was 44.4% (P < 0.05.CONCLUSION: The infusion of GIK and magnesium solution along with thrombolytic therapy can lead to a decrease in the long-term mortality and complications in patients with acute myocardial infarction.Keywords: Acute Myocardial Infarction, Glucose, Insulin, Potassium, Magnesium, Thrombolytic Therapy

  5. Retinal characteristics during 1 year of insulin pump therapy in type 1 diabetes

    DEFF Research Database (Denmark)

    Klefter, Oliver Niels; Hommel, Eva; Munch, Inger Christine

    2016-01-01

    of CSII led to an HbA1c reduction relative to continued MDI and a small increase in retinal thickness but not to early retinopathy worsening or to changes in retinal vascular, structural or functional characteristics. Longer duration of type 1 diabetes appears to be associated with lower macular venous......PURPOSE: To investigate changes in retinal metabolism, function, structure and morphology in relation to initiation of insulin pump therapy (continuous subcutaneous insulin infusion, CSII). METHODS: Visual acuity, retinopathy level, dark adaptation kinetics, retinal and subfoveal choroidal...... thickness, macular perfusion velocities, retinal vessel diameters and blood oxygen saturations were measured at baseline and after 1, 4, 16, 32 and 52 weeks in 31 patients with type 1 diabetes who started CSII and 20 patients who continued multiple daily insulin injections (MDI). RESULTS: One year of CSII...

  6. Attenuation measurements show that the presence of a TachoSil surgical patch will not compromise target irradiation in intra-operative electron radiation therapy or high-dose-rate brachytherapy.

    Science.gov (United States)

    Sarmento, Sandra; Costa, Filipa; Pereira, Alexandre; Lencart, Joana; Dias, Anabela; Cunha, Luís; Sousa, Olga; Silva, José Pedro; Santos, Lúcio

    2015-01-09

    Surgery of locally advanced and/or recurrent rectal cancer can be complemented with intra-operative electron radiation therapy (IOERT) to deliver a single dose of radiation directly to the unresectable margins, while sparing nearby sensitive organs/structures. Haemorrhages may occur and can affect the dose distribution, leading to an incorrect target irradiation. The TachoSil (TS) surgical patch, when activated, creates a fibrin clot at the surgical site to achieve haemostasis. The aim of this work was to determine the effect of TS on the dose distribution, and ascertain whether it could be used in combination with IOERT. This characterization was extended to include high dose rate (HDR) intraoperative brachytherapy, which is sometimes used at other institutions instead of IOERT. CT images of the TS patch were acquired for initial characterization. Dosimetric measurements were performed in a water tank phantom, using a conventional LINAC with a hard-docking system of cylindrical applicators. Percentage Depth Dose (PDD) curves were obtained, and measurements made at the depth of dose maximum for the three clinically used electron energies (6, 9 and 12MeV), first without any attenuator and then with the activated patch of TS completely covering the tip of the IOERT applicator. For HDR brachytherapy, a measurement setup was improvised using a solid water phantom and a Farmer ionization chamber. Our measurements show that the attenuation of a TachoSil patch is negligible, both for high energy electron beams (6 to 12MeV), and for a HDR (192)Ir brachytherapy source. Our results cannot be extrapolated to lower beam energies such as 50 kVp X-rays, which are sometimes used for breast IORT. The TachoSil surgical patch can be used in IORT procedures using 6MeV electron energies or higher, or HDR (192)Ir brachytherapy.

  7. 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

    Energy Technology Data Exchange (ETDEWEB)

    Bi, Xi-Wen; Li, Ye-Xiong, E-mail: yexiong@yahoo.com; 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.

  8. Acute and late vaginal toxicity after adjuvant high-dose-rate vaginal brachytherapy in patients with intermediate risk endometrial cancer: is local therapy with hyaluronic acid of clinical benefit?

    Science.gov (United States)

    Delishaj, Durim; Fabrini, Maria Grazia; Gonnelli, Alessandra; Morganti, Riccardo; Perrone, Franco; Tana, Roberta; Paiar, Fabiola; Gadducci, Angiolo

    2016-01-01

    Purpose The aim of the present study was to evaluate the effectiveness of hyaluronic acid (HA) in the prevention of acute and late vaginal toxicities after high-dose-rate (HDR) vaginal brachytherapy (BT). Material and methods Between January 2011 and January 2015, we retrospectively analyzed 126 patients with endometrial cancer who underwent extrafascial hysterectomy with or without lymphadenectomy and adjuvant HDR-vaginal BT +/– adjuvant chemotherapy. The total dose prescription was 21 Gy in 3 fractions (one fraction for week). Vaginal ovules containing 5 mg of HA were given for whole duration of vaginal BT and for the two following weeks. Acute and late toxicities were evaluated according to CTCAE vs 4.02. Results According to the revised FIGO 2009 classification, most tumors were in stage IA (30.9%) and in stage IB (57.9%). Thirty-three patients (26.2%) received adjuvant chemotherapy before vaginal BT. Five-year disease-free survival (DFS) and five-year overall survival (OS) were 88% and 93%, respectively. The most common grade 1-2 acute toxicities were vaginal inflammation (18 patients, 14.3%) and dyspareunia (7 patients, 5.5%). Two patients (1.6%) had more than one toxicity. Late toxicity occurred in 20 patients (15.9%). Grade 1-2 late toxicities were fibrosis (14 patients, 11.1%) and telangiectasias (7 patients, 5.5%). Six patients (4.8%) had more than one late toxicity. No grade 3 or higher acute or late toxicities were observed. Conclusions These results appear to suggest that the local therapy with HA is of clinical benefit for intermediate risk endometrial cancer patients who receive adjuvant HDR-vaginal BT after surgery. A randomized trial comparing HA treatment vs. no local treatment in this clinical setting is warranted to further evaluate the efficacy of HA in preventing vaginal BT-related vaginal toxicity. PMID:28115957

  9. Attenuation measurements show that the presence of a TachoSil surgical patch will not compromise target irradiation in intra-operative electron radiation therapy or high-dose-rate brachytherapy

    International Nuclear Information System (INIS)

    Sarmento, Sandra; Costa, Filipa; Pereira, Alexandre; Lencart, Joana; Dias, Anabela; Cunha, Luís; Sousa, Olga; Silva, José Pedro; Santos, Lúcio

    2015-01-01

    Surgery of locally advanced and/or recurrent rectal cancer can be complemented with intra-operative electron radiation therapy (IOERT) to deliver a single dose of radiation directly to the unresectable margins, while sparing nearby sensitive organs/structures. Haemorrhages may occur and can affect the dose distribution, leading to an incorrect target irradiation. The TachoSil (TS) surgical patch, when activated, creates a fibrin clot at the surgical site to achieve haemostasis. The aim of this work was to determine the effect of TS on the dose distribution, and ascertain whether it could be used in combination with IOERT. This characterization was extended to include high dose rate (HDR) intraoperative brachytherapy, which is sometimes used at other institutions instead of IOERT. CT images of the TS patch were acquired for initial characterization. Dosimetric measurements were performed in a water tank phantom, using a conventional LINAC with a hard-docking system of cylindrical applicators. Percentage Depth Dose (PDD) curves were obtained, and measurements made at the depth of dose maximum for the three clinically used electron energies (6, 9 and 12MeV), first without any attenuator and then with the activated patch of TS completely covering the tip of the IOERT applicator. For HDR brachytherapy, a measurement setup was improvised using a solid water phantom and a Farmer ionization chamber. Our measurements show that the attenuation of a TachoSil patch is negligible, both for high energy electron beams (6 to 12MeV), and for a HDR 192 Ir brachytherapy source. Our results cannot be extrapolated to lower beam energies such as 50 kVp X-rays, which are sometimes used for breast IORT. The TachoSil surgical patch can be used in IORT procedures using 6MeV electron energies or higher, or HDR 192 Ir brachytherapy

  10. 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

    Energy Technology Data Exchange (ETDEWEB)

    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 [Department of Oncology, Affiliated Hospital of Luzhou Medical College, Luzhou (China); Chen, Yue, E-mail: chenyue5523@126.com [Department of Nuclear Medicine, Affiliated Hospital of Luzhou Medical College, Luzhou (China); Wu, Jing-Bo, E-mail: wjb6147@163.com [Department of Oncology, Affiliated Hospital of Luzhou Medical College, Luzhou (China)

    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.

  11. Personality variables and compliance with insulin therapy in Type 2 diabetic subjects.

    Science.gov (United States)

    Gentili, P; Maldonato, A; Bloise, D; Burla, F; Coronel, G; Di Paolantonio, T

    2000-02-01

    Forty-five diabetic patients were studied to evaluate adaptation and coping strategies. The authors have also analysed personality traits mainly to study different behaviour in compliance conduct. The results revealed an important psychological dimension made up of difficulties in accepting insulin immediately, in fear of addiction and doubts about the therapy. On the basis of these results the sample was then divided into two subgroups, which were then tested and compared with the Adjective Check List. The subgroup that showed more fear, insecurity and initial resistance towards insulin therapy appeared to be more rigid and seemingly conforming. These people also revealed personality aspects compatible with the presence of passive-aggressive and avoidant traits.

  12. Bortezomib or high-dose dexamethasone for relapsed multiple myeloma

    NARCIS (Netherlands)

    P.G. Richardson (Paul Gerard); P. Sonneveld (Pieter); M.W. Schuster (Michael); D. Irwin (David); E.A. Stadtmauer (Edward); T. Facon (Thierry); J-L. Harousseau (Jean-Luc); D. Ben-Yehuda (Dina); S. Lonial (Sagar); H. Goldschmidt (Hartmut); D. Reece (Donna); J.F. San Miguel (Jesús Fernando); J. Bladé (Joan); M. Boccadoro (Mario); J. Cavenagh (Jamie); W. Dalton (William); A.L. Boral (Anthony); D.-L. Esseltine (Dixie-Lee); J.B. Porter (Jane); D. Schenkein (David); K.C. Anderson (Kenneth)

    2005-01-01

    textabstractBACKGROUND: This study compared bortezomib with high-dose dexamethasone in patients with relapsed multiple myeloma who had received one to three previous therapies. METHODS: We randomly assigned 669 patients with relapsed myeloma to receive either an intravenous bolus of bortezomib (1.3

  13. Late Radiation and Cardiovascular Adverse Effects After Androgen Deprivation and High-Dose Radiation Therapy in Prostate Cancer: Results From the DART 01/05 Randomized Phase 3 Trial

    Energy Technology Data Exchange (ETDEWEB)

    Zapatero, Almudena, E-mail: almudena.zapatero@salud.madrid.org [Hospital Universitario de la Princesa, Madrid (Spain); Guerrero, Araceli [Hospital Son Espases, Palma de Mallorca (Spain); Maldonado, Xavier [Hospital Universitari Vall d' Hebron, Barcelona (Spain); Álvarez, Ana; González-San Segundo, Carmen [Hospital General Universitario Gregorio Marañón, Madrid (Spain); Cabeza Rodriguez, Maria Angeles [Hospital Universitario 12 de Octubre, Madrid (Spain); Macías, Victor [Hospital General de Catalunya, Sant Cugat del Vallès and Hospital Universitario de Salamanca, Salamanca (Spain); Pedro Olive, Agustí [Hospital Plató, Barcelona (Spain); Casas, Francesc [Hospital Clinic, Barcelona (Spain); Boladeras, Ana [Institut Català d' Oncologia, Barcelona (Spain); Martín de Vidales, Carmen [Hospital Universitario de la Princesa, Madrid (Spain); Vázquez de la Torre, Maria Luisa [Hospital Do Meixoeiro, Vigo (Spain); Calvo, Felipe A. [Hospital General Universitario Gregorio Marañón, Madrid (Spain)

    2016-10-01

    Purpose: To present data on the late toxicity endpoints of a randomized trial (DART 01/05) conducted to determine whether long-term androgen deprivation (LTAD) was superior to short-term AD (STAD) when combined with high-dose radiation therapy (HDRT) in patients with prostate cancer (PCa). Patients and Methods: Between November 2005 and December 2010, 355 eligible men with cT1c-T3aN0M0 PCa and intermediate-risk and high-risk factors (2005 National Comprehensive Cancer Network criteria) were randomized to 4 months of AD combined with HDRT (median dose, 78 Gy) (STAD) or the same treatment followed by 24 months of AD (LTAD). Treatment-related complications were assessed using European Organization for Research and Treatment of Cancer–Radiation Therapy Oncology Group and Common Terminology Criteria for Adverse Events v3.0 scoring schemes. Multivariate analyses for late toxicity were done using the Fine-Gray method. Results: The 5-year incidence of grade ≥2 rectal and urinary toxicity was 11.1% and 8.2% for LTAD and 7.6% and 7.3% for STAD, respectively. Compared with STAD, LTAD was not significantly associated with a higher risk of late grade ≥2 rectal toxicity (hazard ratio [HR] 1.360, 95% confidence interval [CI] 0.660-2.790, P=.410) or urinary toxicity (HR 1.028, 95% CI 0.495-2.130, P=.940). The multivariate analysis showed that a baseline history of intestinal comorbidity (HR 3.510, 95% CI 1.560-7.930, P=.025) and the rectal volume receiving >60 Gy (Vr60) (HR 1.030, 95% CI 1.001-1.060, P=.043) were the only factors significantly correlated with the risk of late grade ≥2 rectal complications. A history of previous surgical prostate manipulations was significantly associated with a higher risk of grade ≥2 urinary complications (HR 2.427, 95% CI 1.051-5.600, P=.038). Long-term AD (HR 2.090; 95% CI 1.170-3.720, P=.012) and a history of myocardial infarction (HR 2.080; 95% CI 1.130-3.810, P=.018) were significantly correlated with a higher probability of

  14. Prostate Specific Antigen (PSA) as Predicting Marker for Clinical Outcome and Evaluation of Early Toxicity Rate after High-Dose Rate Brachytherapy (HDR-BT) in Combination with Additional External Beam Radiation Therapy (EBRT) for High Risk Prostate Cancer.

    Science.gov (United States)

    Ecke, Thorsten H; Huang-Tiel, Hui-Juan; Golka, Klaus; Selinski, Silvia; Geis, Berit Christine; Koswig, Stephan; Bathe, Katrin; Hallmann, Steffen; Gerullis, Holger

    2016-11-10

    High-dose-rate brachytherapy (HDR-BT) with external beam radiation therapy (EBRT) is a common treatment option for locally advanced prostate cancer (PCa). Seventy-nine male patients (median age 71 years, range 50 to 79) with high-risk PCa underwent HDR-BT following EBRT between December 2009 and January 2016 with a median follow-up of 21 months. HDR-BT was administered in two treatment sessions (one week interval) with 9 Gy per fraction using a planning system and the Ir192 treatment unit GammaMed Plus iX. EBRT was performed with CT-based 3D-conformal treatment planning with a total dose administration of 50.4 Gy with 1.8 Gy per fraction and five fractions per week. Follow-up for all patients was organized one, three, and five years after radiation therapy to evaluate early and late toxicity side effects, metastases, local recurrence, and prostate-specific antigen (PSA) value measured in ng/mL. The evaluated data included age, PSA at time of diagnosis, PSA density, BMI (body mass index), Gleason score, D'Amico risk classification for PCa, digital rectal examination (DRE), PSA value after one/three/five year(s) follow-up (FU), time of follow-up, TNM classification, prostate volume, and early toxicity rates. Early toxicity rates were 8.86% for gastrointestinal, and 6.33% for genitourinary side effects. Of all treated patients, 84.81% had no side effects. All reported complications in early toxicity were grade 1. PSA density at time of diagnosis ( p = 0.009), PSA on date of first HDR-BT ( p = 0.033), and PSA on date of first follow-up after one year ( p = 0.025) have statistical significance on a higher risk to get a local recurrence during follow-up. HDR-BT in combination with additional EBRT in the presented design for high-risk PCa results in high biochemical control rates with minimal side-effects. PSA is a negative predictive biomarker for local recurrence during follow-up. A longer follow-up is needed to assess long-term outcome and toxicities.

  15. Will the next generation of basal insulins offer clinical advantages?

    Science.gov (United States)

    Garber, A J

    2014-06-01

    The 21st century has seen the arrival of several insulin analogue products and the refinement of insulin regimens, with widespread advocacy of continuous titration algorithms and earlier initiation of supplementary insulin therapy (predominantly using basal insulins) in type 2 diabetes. Nevertheless, many insulin-treated diabetes patients remain in poor glycaemic control. This might reflect insufficient titration effort or lax adherence, but these issues could in some cases result from concerns about hypoglycaemia. Certainly there is scope for improving the pharmacokinetic/pharmacodynamic (PK/PD) profile of basal insulin, and three new products offer this prospect. Insulin degludec, now in clinical use, and PEGylated insulin lispro, in development, have greatly extended action profiles that result from two very different, but unique, mechanisms. With once-daily dosing, these insulins produce stable PK/PD profiles at steady state, associated with a low incidence of hypoglycaemia. The feasibility of varied daily dose timing has also been confirmed with insulin degludec. High strength formulations of insulin glargine and insulin degludec offer the prospect of a reduced injection number/volume in high dose users, and in the case of glargine, the PK/PD profile might also be favourably modified. This review considers critically the clinical evidence and expectations we should have for these new basal insulins. © 2013 John Wiley & Sons Ltd.

  16. The Role of Insulin Therapy in Correcting Hepcidin Levels in Patients with Type 2 Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    Driton Vela

    2017-05-01

    Full Text Available Objectives: Iron overload can cause or contribute to the pathogenesis of type 2 diabetes mellitus (T2DM, but how the major parameters of iron metabolism change in different settings of diabetes are still unclear. The aim of this study was to determine the relationship between iron, ferritin, and hepcidin levels in diabetic patients and the effect of insulin treatment. Methods: The study included 80 subjects, 60 with T2DM and 20 without (control group. Serum hepcidin, insulin, ferritin, and iron levels were determined as well as other clinical parameters. The associations between these parameters were analyzed between both groups. Results: Hepcidin levels expressed as mean± standard deviation between groups showed no significant changes (14.4±6.7 ng/mL for the control group, and 18.4±7.9 ng/mL for patients with diabetes, p = 0.069. Parameters of iron metabolism showed modest correlation with the parameters of glucose metabolism. However, the correlation between ferritin and insulin in both groups was statistically significant (p = 0.032; ρ = 0.480 vs. p = 0.011; ρ = 0.328. Conclusions: Our study showed that hepcidin levels in patients with T2DM on insulin therapy do not change, which might be a result of treatment with insulin. In this context, insulin treatment can be used as a novel method for correction of hepcidin levels. By correcting hepcidin levels, we can prevent cellular iron overload and reduce the risk of diabetes.

  17. Brain expansion in patients with type II diabetes following insulin therapy: a preliminary study with longitudinal voxel-based morphometry.

    Science.gov (United States)

    Chen, Zhiye; Li, Jinfeng; Sun, Jie; Ma, Lin

    2014-01-01

    We performed a longitudinal analysis based on magnetic resonance (MR) imaging to investigate the brain structural and perfusion changes caused by insulin therapy in patients with type II diabetes. High resolution three-dimensional T1-weighted fast spoiled gradient recalled echo images and flow-sensitive alternating inversion recovery (FAIR) images were obtained from 11 patients with type II diabetes before and 1 year after initiation of insulin therapy and 11 normal controls. Brain volume changes were investigated by a longitudinal voxel-based morphometry (VBM), and perfusion changes were evaluated by FAIR imaging between baseline and follow-up data. Significant regional gray matter (GM) expansion located in bilateral frontal, parietal, and left occipital lobes, and regional white matter (WM) expansion was shown in left precentral subcortical WM and right angular subcortical WM after insulin therapy (P Brain hyperperfusion was detected in bilateral frontal cortex, left occipital cortex, and right temporal cortex after insulin therapy (P brain expansion and hyperperfusion were demonstrated 1 year after initiation of insulin therapy, and insulin therapy could contribute to the brain volume gainment in the patients with type II diabetes. Copyright © 2013 by the American Society of Neuroimaging.

  18. Influence of insulin therapy on circulating ghrelin and insulin-like ghrelinowth factor-1(IGF-1) levels in children with type-1 diabetes mellitus

    International Nuclear Information System (INIS)

    Moawad, A.T.; Nassar, E.M.; Mostafa, A.M.; Mohammed, S.K.

    2009-01-01

    Diabetes mellitus type 1 (IDDM)is a chronic disease associated with alterations in the growth hormone/insulin -like growth factor (GH-IGF) system and ghrelin level which may lead to changes in metabolic control. This study aimed to evaluate the circulating levels of the gut-derived peptides (ghrelin and insulin-like growth factors (IGF s ) in children with IDDM and to link these two peptides with the glucose level in diabetic children at diagnoses and after insulin therapy. Design and methods: the studied group consisted of 30 newly diagnosed diabetic children (17 females and 13 males) diagnosed in paediatric diabetes unit, children's hospital, Ain shams university. Their age ranged from (6.2-11.8) years with mean of 10.10± 1.74 years. Twenty non diabetic healthy children matching in age and sex served as controls. Serum ghrelin was determined by enzyme linked immuno absorbanet assay (ELISA), while IGF-1 and insulin-like growth factors binding proteins -1 and 3 (IGFBP s ) were assessed by radioimmunoassay(RIA). Results: body mass index (BMI) in patients was significantly decreased in the diabetic group as compared to the healthy group at diagnosis. After insulin therapy BMI was significantly increase as compared to its value at diagnosis (p< 0.05) such increase was not significant on comparing to controls. Regarding blood glucose level there was very highly significant decrease in the level of HBAI (glycolated HB) in diabetic patients after insulin therapy (p<0.0001) than at diagnosis . The mean ghrelin level was highly significantly decreased in diabetic children at diagnosis and after insulin therapy as compared to controls (p<0.0001). No differences were found in the mean ghrelin levels in diabetic children at diagnosis or after insulin therapy.conclusions : the decrease in mean gherlin levels in this study at diagnosis and after therapy could reflect an attempt by the body to decrease the glucose level and thus may prevent hyperglycemia in diabetic patients

  19. Improvement of insulin secretion in rat models of diabetes after ACEI/ARB therapy

    International Nuclear Information System (INIS)

    Tian Jingyan; Li Fengying; Liu Yun; Long Hongmei; Li Weiyi; Wang Xiao; Zhang Hongli; Li Guo; Luo Min

    2009-01-01

    Objective To study the effect of ACEI/ARB therapy on the secretion of insulin and glucagon as well as serum lipid peroxidation marker 8-iso PGF-2α levels in streptozoticin (STZ) induced diabetic rat models.Methods Twenty-four rat models of STZ induced diabetes were prepared (random blood sugar>16.7 mmol/L). Of which, 8 models were fed enalaprial 5mg/kg/d, 8 models were fed losartan 10μg/kg/d and 8 models left unterated. Fasting serum insulin,glucagon (with RIA) and 8-iso PGF-2α (with ELISA) levels were measured in these models and 8 control rats three weeks later. Intravenous glucose tolerance test (IVGTT) were performed in 12 rats (3 animals in each group) six weeks later. Results: Serum levels of insulin in the treated models were higher than those in the non-treated models but without significance (P>0.05). Serum levels of glucagon and 8-iso PGF-2α levels in the treated models were significantly lower than those in the non-treated models (P 6 x ) in the treated models. Conclusion: ACEI/ARB treatment could improve the secretion of insulin in rat models of diabetes, which might be beneficial for controlling the progression of the disease. This phenomenon is consistent with the result of clinical study. (authors)

  20. 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

    Energy Technology Data Exchange (ETDEWEB)

    Dyk, Pawel; Jiang, Naomi; Sun, Baozhou; DeWees, Todd A. [Department of Radiation Oncology, Washington University School of Medicine, St Louis, Missouri (United States); Fowler, Kathryn J.; Narra, Vamsi [Department of Diagnostic Radiology, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St Louis, Missouri (United States); Garcia-Ramirez, Jose L.; Schwarz, Julie K. [Department of Radiation Oncology, Washington University School of Medicine, St Louis, Missouri (United States); Grigsby, Perry W., E-mail: pgrigsby@wustl.edu [Department of Radiation Oncology, Washington University School of Medicine, St Louis, Missouri (United States); Division of Nuclear Medicine, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St Louis, Missouri (United States); Division of Gynecologic Oncology, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St Louis, Missouri (United States); Alvin J. Siteman Cancer Center, Washington University School of Medicine, St Louis, Missouri (United States)

    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.

  1. Adherence to Basal Insulin Therapy Among People with Type 2 Diabetes: A Retrospective Cohort Study of Costs and Patient Outcomes.

    Science.gov (United States)

    Perez-Nieves, Magaly; Boye, Kristina S; Kiljanski, Jacek; Cao, Dachung; Lage, Maureen J

    2018-04-11

    This research compares costs, resource utilization, and complications between adherent and nonadherent patients over the 3-year period post initiation on basal insulin therapy. The study utilized the US-based Truven Health MarketScan ® Research Databases from 2011 through 2015. Adults aged 18 years or older and identified with type 2 diabetes (T2D) who initiated therapy on basal insulin in 2012 were included. Patients were excluded if they were pregnant, filled their index basal insulin prescription via mail order, or were not continuously insured from 1 year before through 3 years following initiation of treatment with basal insulin. Instrumental variables were used to control for selection bias, and multivariable analyses were used to examine the associations between adherence to basal insulin therapy and costs, resource utilization, and acute complications. A total of 21,363 individuals were included in the study. Three years after initiating therapy on basal insulin, patients who were adherent over time to basal insulin treatment therapy (33.8% of patients) had significantly higher diabetes-related drug costs. However, patients' adherence was associated with significantly lower diabetes-related outpatient, acute care, and total costs. Results for all-cause costs were similar. Adherent patients also had significantly fewer all-cause and diabetes-related hospitalizations and emergency room visits and were significantly less likely to be diagnosed with an acute complication. Results of this study illustrate that despite higher drug costs, there are disease-specific and all-cause cost offsets and improved patient outcomes associated with adherence to basal insulin therapy for people with T2D. Eli Lilly and Company.

  2. Consolidation therapy with autologous stem cell transplantation in plasma cell leukemia after VAD, high-dose cyclophosphamide and EDAP courses : a report of three cases and a review of the literature

    NARCIS (Netherlands)

    Hovenga, S; deWolf, JTM; Klip, H; Vellenga, E

    1997-01-01

    Plasma cell leukemia (PCL) is a rare lymphoproliferative disorder characterized by a malignant proliferation of plasma cells in blood and bone marrow, Treatment of primary PCL has been mostly disappointing, Three patients with primary PCL are described who received high-dose melphalan with

  3. Development of a booklet on insulin therapy for children with diabetes mellitus type 1.

    Science.gov (United States)

    Moura, Denizielle de Jesus Moreira; Moura, Nádya Dos Santos; Menezes, Luciana Catunda Gomes de; Barros, Ariane Alves; Guedes, Maria Vilani Cavalcante

    2017-01-01

    to describe the process of developing of an educational booklet on insulin therapy for children with diabetes mellitus type 1. methodological approach, in which the following steps were carried out: selecting of the content and type of technology to be developed (for this step, an integrative review, an analysis of the comments of blogs about Diabetes Mellitus type 1 and interviews with the children were performed), creation of images, formatting and layout composition. the work resulted in the production of the final version of the educational booklet, which was titled Aplicando a insulina: a aventura de Beto [Applying insulin: Beto's adventure]. The process of developing of the booklet was based on the active participation of the children and guided by the theoretical framework of Piagetian Constructivism. the resource is a facilitator for the improvement of the knowledge and practices of self care of children with Diabetes Mellitus type 1.

  4. [The optimal blood glucose target in critically ill patient: comparison of two intensive insulin therapy protocols].

    Science.gov (United States)

    Raurell Torredà, Marta; del Llano Serrano, César; Almirall Solsona, Dolors; Catalan Ibars, Rosa María; Nicolás Arfelis, José María

    2014-03-04

    Recent studies in critically ill patients receiving insulin intravenous therapy (IIT) have shown an increased incidence of severe hypoglycemia, while intermittent subcutaneous insulin «sliding scales» (conventional insulin therapy [CIT]) is associated with hyperglycemia. The objective of this study is to assess whether glycemic control range IIT can affect glucose levels and their variability and to compare it with CIT. Prospective comparative cohort study in intensive care unit, with 2 study periods: Period 1, IIT with glycemic target range 110-140 mg/dL, and Period 2, IIT of 140-180 mg/dL. In both periods CIT glycemic target was 110-180 mg/dL. We assessed severe hypoglycemia ( 216 mg/L) and the variability of blood glucose. We studied 221 patients with 12.825 blood glucose determinations. Twenty-six and 17% of patients required IIT for glycemic control in Period 1 and 2, respectively. Hypoglycemia was associated with a discontinuous nutritional intake, glycemic target 110-140 mg/dL and low body mass index (BMI) (P = .002). Hyperglycemia was exclusively associated with a history of diabetes mellitus (OR 2.6 [95% CI 1.6 to 4.5]). Glycemic variability was associated with a discontinuous nutritional intake, low BMI, CIT insulinization, diabetes mellitus, elderly and high APACHE II (P < .001). The use of IIT is useful to reduce the variability of blood glucose. Although the 140-180 mg/dL range would be more secure as to presenting greater variability and hyperglycemia, the 110-140 mg/dL range is most suitable. Copyright © 2012 Elsevier España, S.L. All rights reserved.

  5. Performing a cure for schizophrenia: insulin coma therapy on the wards.

    Science.gov (United States)

    Doroshow, Deborah Blythe

    2007-04-01

    Most historians of psychiatry regard insulin coma therapy (ICT) either as an embarrassing stumble on the path to modern biological psychiatry or as one member of a long line of somatic therapies used to treat mental illness in the mid-twentieth century. This article explores the ICT era, roughly 1933-60, as a key moment in the development of American psychiatry. Developed only ten years after insulin had been embraced as a "miracle drug" for the treatment of diabetes, ICT was perceived by psychiatrists as a means of bringing their field closer to mainstream medicine, particularly to neurology. In addition, the story of ICT reveals how a treatment never quite proven on paper was unquestionably efficacious in the local world in which it was performed. An institutionally-based treatment, ICT was administered in a specific area of the mental hospital deemed the insulin unit, a room with its own staff, practices, and attitudes toward mental illness. There, psychiatrists often experienced wondrous recoveries of individual, formerly intractable patients. These intense personal experiences allowed psychiatrists to feel truly efficacious, enabling them to reinvent themselves as medical doctors rather than behavioral and disciplinary supervisors. The confidence they derived from this capacity, along with the operating room-like setting of the insulin unit, the unit's specialized staffing and group bond, and the availability of both risk-assessment tests and a medley of treatments that countered side effects and complications, allowed ICT to be understood as an efficacious treatment for schizophrenia within the local world in which it was administered.

  6. Brachytherapy treatment with high dose rate

    International Nuclear Information System (INIS)

    Santana Rodriguez, Sergio Marcelino; Rodriguez Rodriguez, Lissi Lisbet; Ciscal Chiclana, Onelio Alberto

    2009-01-01

    Retrospectively analyze results and prognostic factors of cervical cancer patients treated with radio concomitant cisplatin-based chemotherapy, radiation therapy combined modality. Methods: From January 2003 to December 2007, 198 patients with invasive cervical cancer were treated at the Oncology Department of Hospital Robau Celestino Hernandez (brachytherapy performed at INOR). The most common age group was 31 to 40 years. The histology in squamous cell carcinoma accounted for 84.3% of cases. The treatment consisted of external pelvic irradiation and vaginal brachytherapy, high dose rate. Concomitant chemotherapy consisted of cisplatin 40 mg/m2 weekly with a maximum of 70 mg for 5 weeks. Results: 66.2% of patients completed 5 cycles of chemotherapy. The median overall survival was 39 months, overall survival, disease-free survival and survival free of locoregional recurrence at 5 years of 78%, 76% and 78.6% respectively .. We found that clinical stage, histological type (adenocarcinoma worst outcome) were statistically related to level of response. Conclusions: Treatment with external pelvic radiation, brachytherapy and concurrent weekly cisplatin in patients with stage IIIB cervical cancer is feasible in the Chilean public health system, well tolerated and results comparable to international literature. (Author)

  7. High dose rate brachytherapy for oral cancer

    International Nuclear Information System (INIS)

    Yamazaki, Hideya; Yoshida, Ken; Yoshioka, Yasuo; Shimizutani, Kimishige; Koizumi, Masahiko; Ogawa, Kazuhiko; Furukawa, Souhei

    2013-01-01

    Brachytherapy results in better dose distribution compared with other treatments because of steep dose reduction in the surrounding normal tissues. Excellent local control rates and acceptable side effects have been demonstrated with brachytherapy as a sole treatment modality, a postoperative method, and a method of reirradiation. Low-dose-rate (LDR) brachytherapy has been employed worldwide for its superior outcome. With the advent of technology, high-dose-rate (HDR) brachytherapy has enabled health care providers to avoid radiation exposure. This therapy has been used for treating many types of cancer such as gynecological cancer, breast cancer, and prostate cancer. However, LDR and pulsed-dose-rate interstitial brachytherapies have been mainstays for head and neck cancer. HDR brachytherapy has not become widely used in the radiotherapy community for treating head and neck cancer because of lack of experience and biological concerns. On the other hand, because HDR brachytherapy is less time-consuming, treatment can occasionally be administered on an outpatient basis. For the convenience and safety of patients and medical staff, HDR brachytherapy should be explored. To enhance the role of this therapy in treatment of head and neck lesions, we have reviewed its outcomes with oral cancer, including Phase I/II to Phase III studies, evaluating this technique in terms of safety and efficacy. In particular, our studies have shown that superficial tumors can be treated using a non-invasive mold technique on an outpatient basis without adverse reactions. The next generation of image-guided brachytherapy using HDR has been discussed. In conclusion, although concrete evidence is yet to be produced with a sophisticated study in a reproducible manner, HDR brachytherapy remains an important option for treatment of oral cancer. (author)

  8. High dose rate brachytherapy for oral cancer.

    Science.gov (United States)

    Yamazaki, Hideya; Yoshida, Ken; Yoshioka, Yasuo; Shimizutani, Kimishige; Furukawa, Souhei; Koizumi, Masahiko; Ogawa, Kazuhiko

    2013-01-01

    Brachytherapy results in better dose distribution compared with other treatments because of steep dose reduction in the surrounding normal tissues. Excellent local control rates and acceptable side effects have been demonstrated with brachytherapy as a sole treatment modality, a postoperative method, and a method of reirradiation. Low-dose-rate (LDR) brachytherapy has been employed worldwide for its superior outcome. With the advent of technology, high-dose-rate (HDR) brachytherapy has enabled health care providers to avoid radiation exposure. This therapy has been used for treating many types of cancer such as gynecological cancer, breast cancer, and prostate cancer. However, LDR and pulsed-dose-rate interstitial brachytherapies have been mainstays for head and neck cancer. HDR brachytherapy has not become widely used in the radiotherapy community for treating head and neck cancer because of lack of experience and biological concerns. On the other hand, because HDR brachytherapy is less time-consuming, treatment can occasionally be administered on an outpatient basis. For the convenience and safety of patients and medical staff, HDR brachytherapy should be explored. To enhance the role of this therapy in treatment of head and neck lesions, we have reviewed its outcomes with oral cancer, including Phase I/II to Phase III studies, evaluating this technique in terms of safety and efficacy. In particular, our studies have shown that superficial tumors can be treated using a non-invasive mold technique on an outpatient basis without adverse reactions. The next generation of image-guided brachytherapy using HDR has been discussed. In conclusion, although concrete evidence is yet to be produced with a sophisticated study in a reproducible manner, HDR brachytherapy remains an important option for treatment of oral cancer.

  9. Novas opções na terapia insulínica New options in insulin therapy

    Directory of Open Access Journals (Sweden)

    Helena Schmid

    2007-11-01

    Full Text Available OBJETIVO: Revisar as novas opções nas terapêuticas insulínicas para controlar o diabetes melito de crianças e adolescentes. FONTES DOS DADOS: Foram revisados artigos indexados no PubMed buscados conforme as palavras insulin analogs in children and adolescents e incluídas informações contidas nos consensos da American Diabetes Association e Sociedade Brasileira de Diabetes. SÍNTESE DOS DADOS: São apresentadas informações sobre os novos análogos da insulina e, para comparação, são também revisadas as outras diferentes modalidades de insulina que estão atualmente disponíveis, focalizando nas terapias insulínicas que tentam fornecer uma aproximação mais fisiológica das estratégias basal-bolos no tratamento. Com o objetivo de obter melhor controle metabólico, mais e mais crianças estão em regimes de múltiplas injeções diárias ou usando infusões subcutâneas contínuas de insulina. Atingir controle glicêmico ótimo nas crianças é difícil devido ao maior risco de hipoglicemia decorrente da grande variabilidade em hábitos de ingerir alimentos e em níveis de atividade física. Se aplicados em bolos, subcutâneos, no diabetes tipo 1, os análogos de ação rápida, comparados com insulina humana regular, geralmente reduzem os episódios de hipoglicemia e glicemia pós-prandial, enquanto os análogos basais tendem a reduzir particularmente a hipoglicemia noturna. CONCLUSÃO: Embora os benefícios nos desfechos individuais metabólicos e clínicos pareçam modestos, a maioria dos estudos demonstra benefícios quando são usados análogos de insulina no tratamento do diabetes tipo 1 ou 2.OBJECTIVE:To review the new options in insulin therapy for controlling diabetes mellitus in children and adolescents. SOURCES: Articles indexed in PubMed were located using the search terms insulin analogs in children and adolescents and reviewed. Information was also obtained from American Diabetes Association and Sociedade Brasileira

  10. Insulin Therapy

    Science.gov (United States)

    ... insert the strip into a machine called an electronic glucose meter. The results will tell you whether ... Article >>Allergy Shots: Could They Help Your Allergies?Plasma Viral Load TestingRead Article >>Plasma Viral Load TestingHow ...

  11. Identification of barriers to insulin therapy and approaches to overcoming them

    DEFF Research Database (Denmark)

    Russell-Jones, D; Pouwer, F; Khunti, K

    2018-01-01

    Poor glycaemic control in type 2 diabetes (T2D) is a global problem despite the availability of numerous glucose-lowering therapies and clear guidelines for T2D management. Tackling clinical or therapeutic inertia, where the person with diabetes and/or their healthcare providers do not intensify...... delayed for several years. Patient- and physician-related factors both contribute to this resistance at the stages of insulin initiation, titration and intensification, impeding achievement of optimal glycaemic control. This review evaluates the evidence and reasons for this delay, together with available...

  12. Acute genitourinary toxicity after high-dose-rate (HDR) brachytherapy combined with hypofractionated external-beam radiation therapy for localized prostate cancer: Correlation between the urethral dose in HDR brachytherapy and the severity of acute genitourinary toxicity

    International Nuclear Information System (INIS)

    Akimoto, Tetsuo; Ito, Kazuto; Saitoh, Jun-ichi; Noda, Shin-ei; Harashima, Koichi; Sakurai, Hideyuki; Nakayama, Yuko; Yamamoto, Takumi; Suzuki, Kazuhiro; Nakano, Takashi; Niibe, Hideo

    2005-01-01

    Purpose: Several investigations have revealed that the α/β ratio for prostate cancer is atypically low, and that hypofractionation or high-dose-rate (HDR) brachytherapy regimens using appropriate radiation doses may be expected to yield tumor control and late sequelae rates that are better or at least as favorable as those achieved with conventional radiation therapy. In this setting, we attempted treating localized prostate cancer patients with HDR brachytherapy combined with hypofractionated external beam radiation therapy (EBRT). The purpose of this study was to evaluate the feasibility of using this approach, with special emphasis on the relationship between the severity of acute genitourinary (GU) toxicity and the urethral dose calculated from the dose-volume histogram (DVH) of HDR brachytherapy. Methods and Materials: Between September 2000 and December 2003, 70 patients with localized prostate cancer were treated by iridium-192 HDR brachytherapy combined with hypofractionated EBRT at the Gunma University Hospital. Hypofractionated EBRT was administered in fraction doses of 3 Gy, three times per week; a total dose of 51 Gy was delivered to the prostate gland and the seminal vesicles using the four-field technique. No elective pelvic irradiation was performed. After the completion of EBRT, all the patients additionally received transrectal ultrasonography (TRUS)-guided HDR brachytherapy. The fraction size and the number of fractions in HDR brachytherapy were prospectively changed, whereas the total radiation dose for EBRT was fixed at 51 Gy. The fractionation in HDR brachytherapy was as follows: 5 Gy x 5, 7 Gy x 3, 9 Gy x 2, administered twice per day, although the biologic effective dose (BED) for HDR brachytherapy combined with EBRT, assuming that the α/β ratio is 3, was almost equal to 138 in each fractionation group. The planning target volume was defined as the prostate gland with 5-mm margin all around, and the planning was conducted based on

  13. Determination of Therapeutic Dose of I-131 for First High Dose Radioiodine Therapy in Patients with Differentiated Thyroid Cancer: Comparison of Usefulness between Pathological Staging, Serum Thyroglobulin Level and Finding of I-123 Whole Body Scan

    International Nuclear Information System (INIS)

    Jeong, Hwan Jeong; Lim, Seok Tae; Youn, Hyun Jo; Sohn, Myung-Hee

    2008-01-01

    Recently, a number of patients needed total thyroidectomy and high dose radioiodine therapy (HD-RAI) get increased more. The aim of this study is to evaluate whether pathological staging (PS) and serum thyroglobulin (sTG) level could replace the diagnostic I-123 scan for the determination of therapeutic dose of HD-RAI in patients with differentiated thyroid cancer. Fifty eight patients (M:F=13;45, age 44.5±11.5 yrs) who underwent total thyroidectomy and central or regional lymph node dissection due to differentiated thyroid cancer were enrolled. Diagnostic scan of I-123 and sTG assay were also performed on off state of thyroid hormone. The therapeutic doses of I-131 (TD) were determined by the extent of uptakes on diagnostic I-123 scan as a gold standard. PS was graded by the criteria recommended in 6th edition of AJCC cancer staging manual except consideration of age. For comparison of the determination of therapeutic doses, PS and sTG were compared with the results of I-123 scan. All patients were underwent HD-RAI. Among them, five patients (8.6%) were treated with 100 mCi of I-131, forty three (74.1%) with 150 mCi, six (10.3%) with 180 mCi, three (5.2%) with 200 mCi, and one (1.7%) with 250 mCi, respectively. On the assessment of PS, average TDs were 154±25 mCi in stage I (n=9), 175±50 mCi in stage II (n=4), 149±21 mCi in stage III (n=38), and 161±20 mCi in stage IV (n=7). The statistical significance was not shown between PS and TD (p=0.169). Among fifty two patients who had available sTG, 25 patients (48.1%) having below 2 ng/mL of sTG were treated with 149±26 mCi of I-131, 9 patients (17.3%) having 2≤ sTG <5 ng/mL with 156±17 mCi, 5 patients (9.6%) having 5≤ sTG <10 ng/mL with 156±13 mCi, 7 patients (13.5%) having 10≤ sTG <50 ng/mL with 147±24 mCi, and 6 patients (11.5%) having above 50 ng/mL with 175±42 mCi. The statistical significance between sTG level and TD (p=0.252) was not shown. In conclusion, PS and sTG could not replace the

  14. Simulation and qualitative analysis of glucose variability, mean glucose, and hypoglycemia after subcutaneous insulin therapy for stress hyperglycemia.

    Science.gov (United States)

    Strilka, Richard J; Stull, Mamie C; Clemens, Michael S; McCaver, Stewart C; Armen, Scott B

    2016-01-27

    The critically ill can have persistent dysglycemia during the "subacute" recovery phase of their illness because of altered gene expression; it is also not uncommon for these patients to receive continuous enteral nutrition during this time. The optimal short-acting subcutaneous insulin therapy that should be used in this clinical scenario, however, is unknown. Our aim was to conduct a qualitative numerical study of the glucose-insulin dynamics within this patient population to answer the above question. This analysis may help clinicians design a relevant clinical trial. Eight virtual patients with stress hyperglycemia were simulated by means of a mathematical model. Each virtual patient had a different combination of insulin resistance and insulin deficiency that defined their unique stress hyperglycemia state; the rate of gluconeogenesis was also doubled. The patients received 25 injections of subcutaneous regular or Lispro insulin (0-6 U) with 3 rates of continuous nutrition. The main outcome measurements were the change in mean glucose concentration, the change in glucose variability, and hypoglycemic episodes. These end points were interpreted by how the ultradian oscillations of glucose concentration were affected by each insulin preparation. Subcutaneous regular insulin lowered both mean glucose concentrations and glucose variability in a linear fashion. No hypoglycemic episodes were noted. Although subcutaneous Lispro insulin lowered mean glucose concentrations, glucose variability increased in a nonlinear fashion. In patients with high insulin resistance and nutrition at goal, "rebound hyperglycemia" was noted after the insulin analog was rapidly metabolized. When the nutritional source was removed, hypoglycemia tended to occur at higher Lispro insulin doses. Finally, patients with severe insulin resistance seemed the most sensitive to insulin concentration changes. Subcutaneous regular insulin consistently lowered mean glucose concentrations and glucose

  15. The effect of functional insulin therapy on glycaemic parameters in children with diabetes mellitus type 1.

    Science.gov (United States)

    Štimjanin-Koldžo, Diana; Alajbegović, Salem; Štimjanin, Ena; Mehinagić, Jasmina

    2017-08-01

    Aim The aim of the study is to evaluate the effect of a prospectively conducted interactive 5-day education programme based on Düsseldorf model on glycated haemoglobin (A1C), and total daily dose of insulin in type 1 diabetes patients. Methods A total of 67 type 1 diabetes patients was analysed; mean age of 11±0.68 years, 43 females and 24 males. The programme was led by a trained team of diabetes specialist doctors and nurses. All subjects and their parents completed a knowledge test about diabetes at beginning, and at the end of education, and after 12 months (30 questions). Subjects were evaluated for total daily insulin, and HbA1c at baseline, as well as 3, 6, 9 and 12 months after the end of the education programme. Results Results of the knowledge test after the education have shown higher knowledge at baseline. At the end of the education programme an average of total daily insulin dose was significantly lower. There was a 3.17% reduction in HbA1c values over 9 months, and 1.8% over 12 months in the comparison to the baseline values (p1). Conclusions Structured education programme of functional insulin therapy was associated with improved glycaemic control in type 1 diabetes patients and their parents. It motivated patients and parents to improve glycaemic control. One year after the follow up, glycaemic control was worsening, due to lack of patients' motivation, therefore, there is a need for yearly re-education. Copyright© by the Medical Assotiation of Zenica-Doboj Canton.

  16. Effectiveness of basal-supported oral therapy (BOT) using insulin glargine in patients with poorly controlled type 2 diabetes.

    Science.gov (United States)

    Suzuki, Daisuke; Umezono, Tomoya; Miyauchi, Masaaki; Kimura, Moritsugu; Yamamoto, Naoyuki; Tanaka, Eitaro; Kuriyama, Yusuke; Sato, Hiroki; Miyatake, Han; Kondo, Masumi; Toyoda, Masao; Fukagawa, Masafumi

    2012-07-20

    To determine the clinical usefulness of basal-supported oral therapy (BOT) using insulin glargine in Japanese patients with type 2 diabetes. We compared HbA1c levels, body weight, and insulin doses before the introduction of BOT and in the final month of the observation period in 122 patients with type 2 diabetes who received BOT with insulin glargine between October 2007 and July 2009. To exclude the possible effects of seasonal changes in glycemic control, 57 of the 122 patients were followed-up for one year and examined for changes in HbA1c levels, body weight, and insulin dose. Examination of all cases (n=122) showed a significant decrease in HbA1c (before BOT: 8.7±1.8, after: 7.1±1.1%), but no significant change in body weight (before: 63.1±16.1, after: 63.8±17.0 kg). The mean observation period was 10.5±6.4 months. Insulin doses were significantly increased during the study. HbA1c levels improved significantly in patients on non-insulin-secreting drugs (biguanide, α-glucosidase inhibitor and thiazolidine derivatives) than those on insulin-secreting drugs (SU agents and glinides). BOT with insulin glargine is a useful strategy that can achieve good glycemic control in clinical practice without causing serious hypoglycemia. The introduction of BOT before exhaustion of pancreatic β cells may increase its effectiveness.

  17. Concomitant chemoradiotherapy with high dose rate brachytherapy ...

    African Journals Online (AJOL)

    Concomitant chemoradiotherapy with high dose rate brachytherapy as a definitive treatment modality for locally advanced cervical cancer. T Refaat, A Elsaid, N Lotfy, K Kiel, W Small Jr, P Nickers, E Lartigau ...

  18. Fiber optics in high dose radiation fields

    International Nuclear Information System (INIS)

    Partin, J.K.

    1985-01-01

    A review of the behavior of state-of-the-art optical fiber waveguides in high dose (greater than or equal to 10 5 rad), steady state radiation fields is presented. The influence on radiation-induced transmission loss due to experimental parameters such as dose rate, total dose, irradiation history, temperature, wavelength, and light intensity, for future work in high dose environments are given

  19. Radiotherapy and high-dose chemotherapy in advanced Ewing's tumors

    International Nuclear Information System (INIS)

    Pape, H.; Glag, M.; Gripp, S.; Wittkamp, M.; Schmitt, G.; Laws, H.J.; Kaik, B. van; Goebel, U.; Burdach, S.; Juergens, H.

    1999-01-01

    Background: Ewing's tumors are sensitive to radio- and chemotherapy. Patients with multifocal disease suffer a poor prognosis. Patients presenting primary bone marrow involvement or bone metastases at diagnosis herald a 3-year disease-free survival below 15%. The European Intergroup Cooperative Ewing's Sarcoma Study (EICESS) has established the following indications for high-dose therapy in advanced Ewing's tumors: Patients with primary multifocal bone disease, patients with early ( [de

  20. Glycemic control and adherence to basal insulin therapy in Taiwanese patients with type 2 diabetes mellitus.

    Science.gov (United States)

    Chien, Ming-Nan; Chen, Yen-Ling; Hung, Yi-Jen; Wang, Shu-Yi; Lu, Wen-Tsung; Chen, Chih-Hung; Lin, Ching-Ling; Huang, Tze-Pao; Tsai, Ming-Han; Tseng, Wei-Kung; Wu, Ta-Jen; Ho, Cheng; Lin, Wen-Yu; Chen, Bill; Chuang, Lee-Ming

    2016-11-01

    The aim of the present study was to assess the glycemic control, adherence and treatment satisfaction in a real-world setting with basal insulin therapy in type 2 diabetes patients in Taiwan. This was a multicenter, prospective, observational registry. A total of 836 patients with type 2 diabetes taking oral antidiabetic drugs with glycated hemoglobin (HbA1c) >7% entered the study. Basal insulin was given for 24 weeks. All treatment choices and medical instructions were at the physician's discretion to reflect real-life practice. After 24-week treatment, 11.7% of patients reached set HbA1c goals without severe hypoglycemia (primary effectiveness end-point). HbA1c and fasting blood glucose were significantly decreased from (mean ± SD) 10.1 ± 1.9% to 8.7 ± 1.7% (-1.4 ± 2.1%, P 1) and from 230.6 ± 68.8 mg/dL to 159.1 ± 55.6 mg/dL (-67.4 ± 72.3 mg/dL, P 1), respectively. Patients received insulin therapy at a frequency of nearly one shot per day on average, whereas self-monitoring of blood glucose was carried out approximately four times a week. Hypoglycemia was reported by 11.4% of patients, and only 0.7% of patients experienced severe hypoglycemia. Slight changes in weight (0.7 ± 2.4 kg) and a low incidence of adverse drug reactions (0.4%) were also noted. The score of 7-point treatment satisfaction rated by patients was significantly improved by 1.9 ± 1.7 (P 1). Basal insulin therapy was associated with a decrease in HbA1c and fasting blood glucose, and an improved treatment satisfaction. Most patients complied with physicians' instructions. The treatment was generally well tolerated by patients with type 2 diabetes, but findings pointed out the need to reinforce the early and appropriate uptitration to achieve treatment targets. © 2016 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.

  1. Determinants of renal potassium excretion in critically ill patients : The role of insulin therapy

    NARCIS (Netherlands)

    Hoekstra, Miriam; Yeh, Lu; Oude Lansink, Annemieke; Vogelzang, Mathijs; Stegeman, Coen A.; Rodgers, Michael G. G.; van der Horst, Iwan C. C.; Wietasch, Gotz; Zijlstra, Felix; Nijsten, Maarten W. N.

    Objectives: Insulin administration lowers plasma potassium concentration by augmenting intracellular uptake of potassium. The effect of insulin administration on renal potassium excretion is unclear. Some studies suggest that insulin has an antikaliuretic effect although plasma potassium levels were

  2. From the Cover: Cell-replacement therapy for diabetes: Generating functional insulin-producing tissue from adult human liver cells

    Science.gov (United States)

    Sapir, Tamar; Shternhall, Keren; Meivar-Levy, Irit; Blumenfeld, Tamar; Cohen, Hamutal; Skutelsky, Ehud; Eventov-Friedman, Smadar; Barshack, Iris; Goldberg, Iris; Pri-Chen, Sarah; Ben-Dor, Lya; Polak-Charcon, Sylvie; Karasik, Avraham; Shimon, Ilan; Mor, Eytan; Ferber, Sarah

    2005-05-01

    Shortage in tissue availability from cadaver donors and the need for life-long immunosuppression severely restrict the large-scale application of cell-replacement therapy for diabetic patients. This study suggests the potential use of adult human liver as alternate tissue for autologous beta-cell-replacement therapy. By using pancreatic and duodenal homeobox gene 1 (PDX-1) and soluble factors, we induced a comprehensive developmental shift of adult human liver cells into functional insulin-producing cells. PDX-1-treated human liver cells express insulin, store it in defined granules, and secrete the hormone in a glucose-regulated manner. When transplanted under the renal capsule of diabetic, immunodeficient mice, the cells ameliorated hyperglycemia for prolonged periods of time. Inducing developmental redirection of adult liver offers the potential of a cell-replacement therapy for diabetics by allowing the patient to be the donor of his own insulin-producing tissue. pancreas | transdifferentiation

  3. NASH Therapy: omega 3 supplementation, vitamin E, insulin sensitizers and statin drugs

    Directory of Open Access Journals (Sweden)

    Stephen Caldwell

    2017-06-01

    Full Text Available Non-alcoholic steatohepatitis (NASH is the more aggressive form of non-alcoholic fatty liver disease (NAFLD. NASH can progress to hepatic fibrosis, cirrhosis, portal hypertension and primary liver cancer. Therapy is evolving with a substantial number of trials of promising new agents now in progress. In this article however, we will examine data for several older forms of therapy which have been fairly extensively studied over the years: Polyunsaturated Fatty Acid (PUFA supplements, vitamin E, insulin sensitizing agents with a focus on pioglitazone and statin agents. Early interest in PUFA derived from their potential benefit in cardio-metabolic disease and the close association of NAFLD/NASH with Metabolic Syndrome. Results have been variable although most studies show reduction of liver fat without other major effects and their effects are influenced by concomitant weight loss and underlying genetic factors. Vitamin E has had some efficacy in pediatric NASH but questionable efficacy in even mild NASH among adults. Pioglitazone has shown significant histological benefit in a number of trials but concern over side-effects (especially weight gain have dampened enthusiasm. A newer insulin sensitizer, liraglutide, has also shown promise in a small randomized, controlled trial. Very limited data exists regarding the histological effects of the statins in NASH and these agents appear to be fairly neutral with neither clear cut benefit nor detriment. Their use is best guided by cardiovascular risks rather than liver histology.

  4. Heterogeneity of change in state affect following insulin therapy initiation in type 2 diabetic patients

    Directory of Open Access Journals (Sweden)

    Gruszczyńska Ewa

    2017-09-01

    Full Text Available The aim of the study was to explore heterogeneity of change in state affect following the introduction of insulin therapy in patients with type 2 diabetes. State affect was assessed twice among 305 patients: just before the introduction of insulin therapy and at 1-month follow-up. Latent class growth modeling showed that negative affect (NA increased in 78% of the sample, whereas positive affect (PA improved in only 17% of the participants. On the basis of cross-tabulation of these changes a 4-class model of emotional response to the new treatment was obtained. The largest subgroup of participants (57% manifested “threat response”, i.e. moderate-stable PA with increase in NA. Participants in the “challenge response” subgroup (11.8% showed increases in both NA and PA. The third class (10.2% characterized by “no response”, had low-stable NA and moderate-stable PA. The smallest “stress response” subgroup (9.8% showed increase in NA and high-stable PA. Gender, age and education level were significant covariates of group membership. Thus, the findings revealed heterogeneous emotional response to the new treatment, which may be of clinical relevance for improving diabetic patients’ adjustment through a more individual, person-centered approach.

  5. High-dose buprenorphine: perioperative precautions and management strategies.

    Science.gov (United States)

    Roberts, D M; Meyer-Witting, M

    2005-02-01

    Buprenorphine has been in clinical use in anaesthesia for several decades. Recently, the high-dose sublingual formulation (Subutex, Reckitt Benckiser, Slough, U.K.) has been increasingly used as maintenance therapy in opioid dependence, as an alternative to methadone and other pharmacological therapies. Buprenorphine has unique pharmacological properties making it well suited for use as a maintenance therapy in opioid dependence. However, these same properties may cause difficulty in the perioperative management of pain. Buprenorphine is a partial opioid agonist, attenuating the effects of supplemental illicit or therapeutic opioid agonists. As a result of its high receptor affinity, supplemental opioids do not readily displace buprenorphine from the opioid receptor in standard doses. High-dose buprenorphine has an extended duration of action that prolongs both of these effects. The perioperative management of patients stabilized on high-dose buprenorphine and undergoing surgery requires consideration of the likely analgesic requirements. Where possible the buprenorphine should be continued. Pain management should focus on maximizing non-opioid analgesia, local anaesthesia and non-pharmacological techniques. Where pain may not be adequately relieved by these methods, the addition of a full opioid agonist such as fentanyl or morphine at appropriate doses should be considered, accompanied by close monitoring in a high dependency unit. In situations where this regimen is unlikely to be effective, preoperative conversion to morphine or methadone may be an option. Where available, liaison with a hospital-based alcohol and drug service should always be considered.

  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).

    Science.gov (United States)

    Kokame, Gregg T

    2014-07-01

    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? 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. 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. 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.

  7. Effect of intensive vs conventional insulin therapy on perioperative nutritional substrates metabolism in patients undergoing gastrectomy

    Institute of Scientific and Technical Information of China (English)

    Han-Cheng Liu; Yan-Bing Zhou; Dong Chen; Zhao-Jian Niu; Yang Yu

    2012-01-01

    AIM:To investigate the effect of intensive vs conventional insulin therapy on perioperative nutritional substrates metabolism in patients undergoing radical distal gastrectomy.METHODS:Within 24 h of intensive care unit management,patients with gastric cancer were enrolled after written informed consent and randomized to the intensive insulin therapy (IIT) group to keep glucose levels from 4.4 to 6.1 mmol/L or the conventional insulin therapy (CIT) group to keep levels less than 10 mmol/L.Resting energy expenditure (REE),respiratory quotient (RQ),resting energy expenditure per kilogram (REE/kg),and the lipid oxidation rate were monitored by the indirect calorimeter of calcium citrate malate nutrition metabolism investigation system.The changes in body composition were analyzed by multi-frequency bioimpedance analysis.Blood fasting glucose and insulin concentration were measured for assessment of Homeostasis model assessment of insulin resistance.RESULTS:Sixty patients were enrolled.Compared with preoperative baseline,postoperative REE increased by over 22.15% and 11.07%; REE/kg rose up to 27.22 ± 1.33 kcal/kg and 24.72 ± 1.43 kcal/kg; RQ decreased to 0.759 ± 0.034 and 0.791 ± 0.037; the lipid oxidation ratio was up to 78.25% ± 17.74% and 67.13% ± 12.76% supported by parenteral nutrition solutions from 37.56% ± 11.64% at the baseline; the level of Ln-HOMA-IR went up dramatically (P < 0.05,respectively) on postoperative days 1 and 3 in the IIT group.Meanwhile the concentration of total protein,albumin and triglyceride declined significantly on postoperative days 1 and 3 compared with pre-operative levels (P < 0.05,respectively).Compared with the CIT group,IIT reduced the REE/kg level (27.22 ± 1.33 kcal/kg vs 29.97 ± 1.47 kcal/kg,P =0.008; 24.72 ± 1.43 kcal/kg vs 25.66 ± 1.63 kcal/kg,P =0.013); and decreased the Ln-HOMA-IR score (P =0.019,0.028) on postoperative days 1 and 3; IIT decreased the level of CRP on postoperative days 1 and 3 (P

  8. [Prospective observational study of insulin detemir in patients with poorly controlled type 2 diabetes mellitus initiating insulin therapy for the first time (SOLVE Study)].

    Science.gov (United States)

    Orozco-Beltrán, Domingo; Artola-Menéndez, Sara

    2016-02-01

    Describe the experience in the primary care setting with insulin detemir in patients with poorly controlled type2 diabetes mellitus that need to add-on insulin to their oral antidiabetic drug therapy. Prospective observational study of 6 months of follow up, performed in 10 countries. In Spain, participating sites were only from the primary care setting. Eligible patients were those with poorly controlled type2 diabetes mellitus adding-on once-daily insulin detemir to their existing oral antidiabetic therapy in the month prior to their enrollment. The change of Hb1Ac and of weight at the end of the study and the incidence of hypoglycemia and adverse reactions, were analyzed. We report the results obtained in the Spanish cohort. Overall 17,374 patients were included, 973 in Spain [mean age 64.8 years (SE 12); duration of diabetes 9.4 years (SE 6.2); Hb1Ac 8.9% (DE 1.4)]. In the sample analyzed for efficacy (n=474) the mean change of Hb1Ac was -1.6% (95%CI: -1.75 to -1.42; P<.001), mean change of weight was -2.9 kg (95%CI: -3.72 to -2.08; P<.001). Only one episode of severe hypoglycemia was reported, which was also the only serious adverse reaction reported in the study. The incidence rate of non-severe hypoglycemia was 2.44 events/patient-year. In this cohort of patients with type 2 diabetes mellitus receiving newly initiated insulin therapy, once-daily detemir improved the glycemic control, with low incidence of hypoglycemia and a significant reduction of the weight. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

  9. Insulin Therapy for Adult Patients with Type 2 Diabetes Mellitus: A Position Statement of the Korean Diabetes Association, 2017.

    Science.gov (United States)

    Lee, Byung Wan; Kim, Jin Hwa; Ko, Seung Hyun; Hur, Kyu Yeon; Kim, Nan Hee; Rhee, Sang Youl; Kim, Hyun Jin; Moon, Min Kyong; Park, Seok O; Choi, Kyung Mook

    2017-10-01

    The Korean Diabetes Association (KDA) has regularly updated its Clinical Practice Guidelines. In 2017, the KDA published a position statement on the use of antihyperglycemic agents for patients with type 2 diabetes mellitus (T2DM). Growing evidence from new multinational clinical trials using novel and traditional insulin analogues has also been accumulated. Following global trends, many results of clinical trials, especially concerning the clinical efficacy and safety of insulin therapy, have been published about Korean patients with T2DM. After a systematic search of recent evidence, the KDA updated and modified its clinical practice recommendations regarding the initiation, choice, and intensification of insulin and created an insulin treatment algorithm for the first time to guide physicians caring for adult Korean patients with T2DM. Copyright © 2017 Korean Diabetes Association.

  10. Insulin Therapy for Adult Patients with Type 2 Diabetes Mellitus: A Position Statement of the Korean Diabetes Association, 2017

    Directory of Open Access Journals (Sweden)

    Byung-Wan Lee

    2017-10-01

    Full Text Available The Korean Diabetes Association (KDA has regularly updated its Clinical Practice Guidelines. In 2017, the KDA published a position statement on the use of antihyperglycemic agents for patients with type 2 diabetes mellitus (T2DM. Growing evidence from new multinational clinical trials using novel and traditional insulin analogues has also been accumulated. Following global trends, many results of clinical trials, especially concerning the clinical efficacy and safety of insulin therapy, have been published about Korean patients with T2DM. After a systematic search of recent evidence, the KDA updated and modified its clinical practice recommendations regarding the initiation, choice, and intensification of insulin and created an insulin treatment algorithm for the first time to guide physicians caring for adult Korean patients with T2DM.

  11. [Increasing cost of insulin therapy in Belgium. From a critical analysis of the situation to a search for practical solutions].

    Science.gov (United States)

    Scheen, A J

    2006-09-01

    Cost related to insulin therapy is markedly increasing in Belgium, as in other Eucopean countries. In the present paper, we will briefly analyze the main reasons for such aa increase, integrate such observation withIn the global context of diabetes management and suggest some solutions to provide best care to insulin-treated diabetic patients at a reasonable cost. The rise of the cost of insulin therapy has a multifactorial origin. It mainly results from an increase in the number of diabetic patients, a more intensive management, In both type 1 and type 2 diabetes, and a greater use of more expansive insulin analogues. It is important to analyze the increase of the cost of insulin therapy within the global burden of diabetes melitus. Only a better responsibility of all health care partners, patients, physicians, pharmaceutical companies, public health authorities, could provide solutions allowing diabetic people to profit from best treatments they should receive in order to prevent diabetic complications, by far the main cause of expenses.

  12. Progress in high-dose radiation dosimetry

    International Nuclear Information System (INIS)

    Ettinger, K.V.; Nam, J.W.; McLaughlin, W.L.; Chadwick, K.H.

    1981-01-01

    The last decade has witnessed a deluge of new high-dose dosimetry techniques and expanded applications of methods developed earlier. Many of the principal systems are calibrated by means of calorimetry, although production of heat is not always the final radiation effect of interest. Reference systems also include a number of chemical dose meters: ferrous sulphate, ferrous-cupric sulphate, and ceric sulphate acidic aqueous solutions. Requirements for stable and reliable transfer dose meters have led to further developments of several important high-dose systems: amino acids and saccharides analysed by ESR or lyoluminescence, thermoluminescent materials, radiochromic dyes and plastics, ceric-cerous solutions analysed by potentiometry, and ethanol-chlorobenzene solutions analysed by high-frequency oscillometry. A number of other prospective dose meters are also treated in this review. In addition, an IAEA programme of high-dose standardization and intercomparison for industrial radiation processing is described. (author)

  13. Use of case-based reasoning to enhance intensive management of patients on insulin pump therapy.

    Science.gov (United States)

    Schwartz, Frank L; Shubrook, Jay H; Marling, Cynthia R

    2008-07-01

    This study was conducted to develop case-based decision support software to improve glucose control in patients with type 1 diabetes mellitus (T1DM) on insulin pump therapy. While the benefits of good glucose control are well known, achieving and maintaining good glucose control remains a difficult task. Case-based decision support software may assist by recalling past problems in glucose control and their associated therapeutic adjustments. Twenty patients with T1DM on insulin pumps were enrolled in a 6-week study. Subjects performed self-glucose monitoring and provided daily logs via the Internet, tracking insulin dosages, work, sleep, exercise, meals, stress, illness, menstrual cycles, infusion set changes, pump problems, hypoglycemic episodes, and other events. Subjects wore a continuous glucose monitoring system at weeks 1, 3, and 6. Clinical data were interpreted by physicians, who explained the relationship between life events and observed glucose patterns as well as treatment rationales to knowledge engineers. Knowledge engineers built a prototypical system that contained cases of problems in glucose control together with their associated solutions. Twelve patients completed the study. Fifty cases of clinical problems and solutions were developed and stored in a case base. The prototypical system detected 12 distinct types of clinical problems. It displayed the stored problems that are most similar to the problems detected, and offered learned solutions as decision support to the physician. This software can screen large volumes of clinical data and glucose levels from patients with T1DM, identify clinical problems, and offer solutions. It has potential application in managing all forms of diabetes.

  14. The Barbados Insulin Matters (BIM study: Barriers to insulin therapy among a population-based sample of people with type 2 diabetes in the Caribbean island of Barbados

    Directory of Open Access Journals (Sweden)

    Charles G. Taylor, Jr.

    2017-06-01

    Conclusions: Multiple factors related to patient beliefs and attitudes need to be considered and addressed when initiating insulin in order to minimise psychological insulin resistance and delay. Patients using insulin had less negative perceptions than those not on insulin.

  15. Failure to initiate early insulin therapy - A risk factor for diabetic retinopathy in insulin users with Type 2 diabetes mellitus: Sankara Nethralaya-Diabetic Retinopathy Epidemiology and Molecular Genetics Study (SN-DREAMS, Report number 35).

    Science.gov (United States)

    Gupta, Aditi; Delhiwala, Kushal S; Raman, Rajiv P G; Sharma, Tarun; Srinivasan, Sangeetha; Kulothungan, Vaitheeswaran

    2016-06-01

    Insulin users have been reported to have a higher incidence of diabetic retinopathy (DR). The aim was to elucidate the factors associated with DR among insulin users, especially association between duration, prior to initiating insulin for Type 2 diabetes mellitus (DM) and developing DR. Retrospective cross-sectional observational study included 1414 subjects having Type 2 DM. Insulin users were defined as subjects using insulin for glycemic control, and insulin nonusers as those either not using any antidiabetic treatment or using diet control or oral medications. The duration before initiating insulin after diagnosis was calculated by subtracting the duration of insulin usage from the duration of DM. DR was clinically graded using Klein's classification. SPSS (version 9.0) was used for statistical analysis. Insulin users had more incidence of DR (52.9% vs. 16.3%, P 1) and sight threatening DR (19.1% vs. 2.4%, P 1) in comparison to insulin nonusers. Among insulin users, longer duration of DM (odds ratio [OR] 1.12, 95% confidence interval [CI] 1.00-1.25, P = 0.044) and abdominal obesity (OR 1.15, 95% CI 1.02-1.29, P = 0.021) was associated with DR. The presence of DR was significantly associated with longer duration (≥5 years) prior to initiating insulin therapy, overall (38.0% vs. 62.0%, P = 0.013), and in subjects with suboptimal glycemic control (32.5% vs. 67.5%, P = 0.022). The presence of DR is significantly associated with longer duration of diabetes (>5 years) and sub-optimal glycemic control (glycosylated hemoglobin insulin users, abdominal obesity was found to be a significant predictor of DR; DR is associated with longer duration prior to initiating insulin therapy in Type 2 DM subjects with suboptimal glycemic control.

  16. Remission without insulin therapy on gluten-free diet in a 6-year old boy with type 1 diabetes mellitus

    DEFF Research Database (Denmark)

    Sildorf, Stine Møller; Fredheim, Siri; Svensson, Jannet

    2012-01-01

    A 5-year and 10-month old boy was diagnosed with classical type 1 diabetes mellitus (T1DM) without celiac disease. He started on a gluten-free diet after 2–3 week without need of insulin treatment. At the initiation of gluten-free diet, HbA1c was 7.8% and was stabilised at 5.8%–6.0% without insulin...... therapy. Fasting blood glucose was maintained at 4.0–5.0 mmol/l. At 16 months after diagnosis the fasting blood glucose was 4.1 mmol/l and after 20 months he is still without daily insulin therapy. There was no alteration in glutamic acid decarboxylase positivity. The gluten-free diet was safe and without...... side effects. The authors propose that the gluten-free diet has prolonged remission in this patient with T1DM and that further trials are indicated....

  17. Continuous subcutaneous insulin infusion therapy and multiple daily insulin injections in type 1 diabetes mellitus: a comparative overview and future horizons.

    Science.gov (United States)

    Thabit, Hood; Hovorka, Roman

    2016-01-01

    Continuous subcutaneous insulin infusion (CSII) therapy is currently accepted as a treatment strategy for type 1 diabetes. Transition from multiple daily injection therapy (MDI; including basal-bolus regimens) to CSII is based on expectations of better metabolic control and fewer hypoglycaemic events. Evidence to date has not been always conclusive. Evidence for CSII and MDI in terms of glycaemic control, hypoglycaemia and psychosocial outcomes is reviewed in the adult and paediatric population with type 1 diabetes. Findings from studies on threshold-based insulin pump suspension and predictive low glucose management (PLGM) are outlined. Limitations of current CSII application and future technological developments are discussed. Glycaemic control and quality of life (QOL) may be improved by CSII compared to MDI depending on baseline HbA1c and hypoglycaemia rates. Future studies are expected to provide evidence on clinical and cost effectiveness in those who will benefit the most. Training, structured education and support are important to benefit from CSII. Novel technological approaches linking continuous glucose monitoring (CGM) and CSII may help mitigate against frequent hypoglycaemia in those at risk. Development of glucose-responsive automated closed-loop insulin delivery systems may reduce the burden of disease management and improve outcomes in type 1 diabetes.

  18. Insulin pump therapy in children with diabetes mellitus: practice of Krasnoyarsk Krai

    Directory of Open Access Journals (Sweden)

    Tatiana Evgen'evna Taranushenko

    2012-12-01

    Full Text Available Aim. To summarize practical experience of insulin pump therapy (IPT in child population of Krasnoyarsk and to assess its efficacy for treatment of type 1 diabetes mellitus (T1DM in paediatrics. Materials and Methods. We performed a comparative analysis of clinical and laboratory data from 48 children with T1DM prior to and after 6-12 months of IPT. Results. IPT yielded fourfold decrease in complaints of hyperglycemia and labile glycemia without concurrent increase in reports of severe hypoglycemia.  We observed a trend for lowering of mean HbA1c levels, where 65% of patients showed positive dynamics in comparison with the period of multiple daily injection regimen. Interestingly, after 6-12 months of IPT, insulin requirement dropped in most patients. Conclusion. Our data support clinical efficiency and safety of IPT, as well as superiority of this treatment over multiple daily injection regimen. We conclude that IPT is a treatment of choice for children with T1DM.

  19. Continuous subcutaneous insulin infusion (CSII) therapy at Derby Teaching Hospitals: sustained benefits in glucose control.

    Science.gov (United States)

    Anyanwagu, U; Olaoye, H; Jennings, P; Ashton-Cleary, S; Sugunendran, S; Hughes, D; Idris, I; Wilmot, E G

    2017-08-01

    In the short term, continuous subcutaneous insulin infusion (CSII) has been associated with improved glycaemic control, reduced hypoglycaemia and improved quality of life (QOL). However, limited data are available on its long-term benefits, particularly in the UK. We aimed to assess the impact of CSII on longer term outcomes. Patient-level data were obtained for CSII users at Derby Teaching Hospitals, UK. Patient confidence and satisfaction questionnaires using the Likert scale were used to assess confidence in self-management. Comparative statistics were conducted using Pearson's chi-square and Student's t-tests. Some 258 CSII users were identified (60.1% female, mean age 43.9 ± 13.4 years). Overall, there was significant decrease in HbA 1c from 78 mmol/mol (9.3 ± 2.0%) at baseline, to 69 mmol/mol (8.5 ± 1.3%) at 6 months [mean difference (md): -0.64; 95% confidence interval (95% CI): -0.91 to -0.37; P quality of care received in the insulin pump service. CSII therapy led to a sustained long-term improvement in glycaemic control in addition to a reduction in self-reported hypoglycaemia. © 2017 Diabetes UK.

  20. Effects of switching from prandial premixed insulin therapy to basal plus two times bolus insulin therapy on glycemic control and quality of life in patients with type 2 diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Ito H

    2014-04-01

    Full Text Available Hiroyuki Ito, Mariko Abe, Shinichi Antoku, Takashi Omoto, Masahiro Shinozaki, Shinya Nishio, Mizuo Mifune, Michiko ToganeDepartment of Diabetes, Metabolism and Kidney Disease, Edogawa Hospital, Tokyo, JapanBackground: The effects of switching from prandial premixed insulin therapy (PPT injected three times a day to basal plus two times bolus insulin therapy (B2B on glycemic control and quality of life were investigated in patients with type 2 diabetes mellitus.Methods: The clinical course was prospectively observed during the first 16 weeks after switching to B2B (insulin glargine plus insulin glulisine before breakfast and dinner in 27 subjects previously treated with PPT using 50/50 premixed insulin. The Diabetes Treatment Satisfaction Questionnaire (DTSQ was administered at the start and end of the study.Results: The glycated hemoglobin (HbA1c level (8.3%±1.8% to 8.2%±1.1% and the DTSQ score did not change between the start and end of the study. An improvement in HbA1c level was found in nine (33% subjects. The change in HbA1c showed a significant negative correlation with baseline HbA1c, and was significantly better in patients with a baseline HbA1c >8.0% than in those with an HbA1c ≤8.0% (−0.9±2.0 versus 0.3±0.6, respectively, P=0.02. The change in DTSQ score representing treatment satisfaction was significantly greater in patients whose HbA1c level was improved than in those in whom it was not (2.7±3.6 versus −0.8±3.5, P=0.04.Conclusion: B2B was noninferior to PPT with regard to HbA1c levels in patients with type 2 diabetes mellitus. B2B should be considered particularly for subjects whose glycemic control is poor despite PPT.Keywords: type 2 diabetes mellitus, insulin therapy, basal plus two times bolus insulin therapy, prandial premixed insulin therapy, Diabetes Treatment Satisfaction Questionnaire

  1. 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

    International Nuclear Information System (INIS)

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

    2011-01-01

    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∗ (reddish) and reduction in L∗ (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∗ values, and EBRT did not, demonstrating that the reduction in b∗ 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.

  2. Effect of Cardiac Resynchronization Therapy in Patients With Insulin-Treated Diabetes Mellitus

    DEFF Research Database (Denmark)

    Szepietowska, Barbara; Kutyifa, Valentina; Ruwald, Martin H

    2015-01-01

    Diabetes mellitus (DM) modify outcome in patients with heart failure (HF). We aimed to analyze the risk for death, HF alone, combined end point HF/death, and ventricular tachycardia/ventricular fibrillation (VT/VF) in patients with mild HF without DM and in those with DM, further stratified...... branch block in the Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy trial. Treatment with CRT-D versus implantable cardioverter defibrillator was associated with 76% risk reduction in all-cause mortality (hazard ratio 0.24; 95% confidence interval 0.08 to 0.......74, p = 0.012) in subgroup of diabetic patients treated with insulin only (interaction p = 0.043). Significant risk reduction in HF alone, HF/death, and the VT/VF after CRT-D was observed across investigated groups and similar left ventricular reverse remodeling to CRT-D. In conclusion, patients...

  3. Comparison of liraglutide plus basal insulin and basal-bolus insulin therapy (BBIT) for glycemic control, body weight stability, and treatment satisfaction in patients treated using BBIT for type 2 diabetes without severe insulin deficiency: A randomized prospective pilot study.

    Science.gov (United States)

    Yamamoto, Saki; Hayashi, Toshiyuki; Ohara, Makoto; Goto, Satoshi; Sato, Jun; Nagaike, Hiroe; Fukase, Ayako; Sato, Nobuko; Hiromura, Munenori; Tomoyasu, Masako; Nakanishi, Noriko; Lee, Soushou; Osamura, Anna; Yamamoto, Takeshi; Fukui, Tomoyasu; Hirano, Tsutomu

    2018-03-26

    We examined whether 0.9 mg/day liraglutide plus basal insulin (Lira-basal) is superior to basal-bolus insulin therapy (BBIT) for type 2 diabetes (T2DM) without severe insulin deficiency as determined by glucagon stimulation. Fifty patients receiving BBIT were enrolled in this 24-week, prospective, randomized, open-labeled study. After excluding subjects with fasting C-peptide immunoreactivity (CPR) basal (n = 12) or continued BBIT (n = 13). Primary endpoint was change in HbA1c. Secondary endpoints were changes in body weight (BW), 7-point self-monitored blood glucose (SMBG), and Diabetes Treatment Satisfaction Questionnaire status (DTSQs) scores. The Lira-basal group demonstrated reduced HbA1c, whereas the BBIT group showed no change. BW was reduced in the Lira-basal group but increased in the BBIT group. The Lira-basal group also exhibited significantly reduced pre-breakfast and pre-lunch SMBG. DTSQs scores improved in the Lira-basal group but not the BBIT group. Plasma lipids, liver function, and kidney function were not significantly changed in either group. Lira-basal therapy is superior to BBIT for T2DM without severe insulin deficiency. This study was registered with UMIN Clinical Trials Registry (UMIN000028313). Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

  4. Insulin glargine 300 U/mL for basal insulin therapy in type 1 and type 2 diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Lau IT

    2017-06-01

    Full Text Available Ip Tim Lau,1 Ka Fai Lee,2 Wing Yee So,3 Kathryn Tan,4 Vincent Tok Fai Yeung5 1Department of Medicine, Tseung Kwan O Hospital, 2Department of Medicine and Geriatrics, Kwong Wah Hospital, 3Department of Medicine and Therapeutics, Chinese University of Hong Kong, Prince of Wales Hospital, 4Department of Medicine, Queen Mary Hospital, University of Hong Kong, 5Department of Medicine and Geriatrics, Our Lady of Maryknoll Hospital, Hong Kong, China Objective: To review published clinical studies on the efficacy and safety of new insulin glargine 300 units/mL (Gla-300, a new long-acting insulin analog, for the treatment of type 1 and type 2 diabetes mellitus (T1DM, T2DMMaterials and methods: Data sources comprised primary research articles on Gla-300, including pharmacodynamic, pharmacokinetic, and clinical studies.Results: In pharmacodynamic and pharmacokinetic studies, Gla-300 showed a flatter time–action profile and longer duration of action than Gla-100. Noninferiority of Gla-300 versus Gla-100 for lowering of glycated hemoglobin was demonstrated in Phase III clinical studies covering a range of T1DM and T2DM patient populations. Over 6–12 months of follow-up, Gla-300 consistently showed comparable glycemic efficacy with less hypoglycemia vs Gla-100, even during the first 8 weeks of treatment. Although titrated insulin doses were 11%–17% higher with Gla-300 vs Gla-100, changes in body weight were similar or favored Gla-300.Conclusion: Clinical studies provide evidence that the pharmacodynamic and pharmacokinetic properties of Gla-300 may translate into clinical benefits in both T1DM and T2DM. Gla-300 may provide a new option for people initiating basal insulin, those requiring higher basal insulin doses, those with T1DM, and those who may be at increased risk for hypoglycemia, such as people with chronic kidney disease, the elderly, and those with cardiovascular comorbidities. Keywords: diabetes mellitus, long-acting insulin, insulin glargine

  5. Insulin requirement profiles of short-term intensive insulin therapy in patients with newly diagnosed type 2 diabetes and its association with long-term glycemic remission.

    Science.gov (United States)

    Liu, Liehua; Ke, Weijian; Wan, Xuesi; Zhang, Pengyuan; Cao, Xiaopei; Deng, Wanping; Li, Yanbing

    2015-05-01

    To investigate the insulin requirement profiles during short-term intensive continuous subcutaneous insulin infusion (CSII) in patients with newly diagnosed type 2 diabetes and its relationship with long-term glycemic remission. CSII was applied in 104 patients with newly diagnosed type 2 diabetes. Daily insulin doses were titrated and recorded to achieve and maintain euglycemia for 2 weeks. Measurements of blood glucose, lipid profiles as well as intravenous glucose tolerance tests were performed before and after the therapy. Afterwards, patients were followed up for 1 year. Total daily insulin dose (TDD) was 56.6±16.1IU at the first day when euglycemia was achieved (TDD-1). Thereafter, TDD progressively decreased at a rate of 1.4±1.0IU/day to 36.2±16.5IU at the end of the therapy. TDD-1 could be estimated with body weight, FPG, triglyceride and waist circumference in a multiple linear regression model. Decrement of TDD after euglycemia was achieved (ΔTDD) was associated with reduction of HOMA-IR (r=0.27, P=0.008) but not with improvement in β cell function. Patients in the lower tertile of ΔTDD had a significantly higher risk of hyperglycemia relapse than those in the upper tertile within 1 year (HR 3.4, 95%CI [1.4, 8.4], P=0.008). There is a steady decline of TDD after euglycemia is achieved in patients with newly diagnosed type 2 diabetes treated with CSII, and ΔTDD is associated with a better long-term glycemic outcome. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  6. Endorectal high dose rate brachytherapy quality assurance

    International Nuclear Information System (INIS)

    Devic, S.; Vuong, T.; Evans, M.; Podgorsak, E.

    2008-01-01

    We describe our quality assurance method for preoperative high dose rate (HDR) brachytherapy of endorectal tumours. Reproduction of the treatment planning dose distribution on a daily basis is crucial for treatment success. Due to the cylindrical symmetry, two types of adjustments are necessary: applicator rotation and dose distribution shift along the applicator axis. (author)

  7. Short-term intensive insulin therapy in type 2 diabetes mellitus: a systematic review and meta-analysis.

    Science.gov (United States)

    Kramer, Caroline Kaercher; Zinman, Bernard; Retnakaran, Ravi

    2013-09-01

    Studies have shown that, when implemented early in the course of type 2 diabetes mellitus, treatment with intensive insulin therapy for 2-3 weeks can induce a glycaemic remission, wherein patients are able to maintain normoglycaemia without any anti-diabetic medication. We thus did a systematic review and meta-analysis of interventional studies to assess the effect of short-term intensive insulin therapy on the pathophysiological defects underlying type 2 diabetes mellitus (pancreatic β-cell dysfunction and insulin resistance) and identify clinical predictors of remission. We identified studies published between 1950 and Nov 19, 2012, which assessed the effect of intensive insulin therapy on β-cell function or insulin resistance, or both, or assessed long-term drug-free glycaemic remission in adults aged 18 years or older with newly diagnosed type 2 diabetes mellitus. We calculated pooled estimates by random-effects model. This study is registered with International Prospective Register of Systematic Reviews, number CRD42012002829. We identified 1645 studies of which seven fulfilled inclusion criteria (n=839 participants). Five studies were non-randomised. A pooled analysis of the seven studies showed a post-intensive insulin therapy increase in Homeostasis Model Assessment of β-cell function as compared with baseline (1·13, 95% CI 1·02 to 1·25) and a decrease in Homeostasis Model Assessment of Insulin Resistance (-0·57, -0·84 to -0·29). In the four studies that assessed glycaemic remission (n=559 participants), the proportion of participants in drug-free remission was about 66·2% (292 of 441 patients) after 3 months of follow-up, about 58·9% (222 of 377 patients) after 6 months, about 46·3% (229 of 495 patients) after 12 months, and about 42·1% (53 of 126 patients) after 24 months. Patients who achieved remission had higher body-mass index than those who did not achieve remission (1·06 kg/m(2), 95% CI 0·55 to 1·58) and lower fasting plasma glucose

  8. Effects of Vildagliptin Add-on Insulin Therapy on Nocturnal Glycemic Variations in Uncontrolled Type 2 Diabetes.

    Science.gov (United States)

    Li, Feng-Fei; Shen, Yun; Sun, Rui; Zhang, Dan-Feng; Jin, Xing; Zhai, Xiao-Fang; Chen, Mao-Yuan; Su, Xiao-Fei; Wu, Jin-Dan; Ye, Lei; Ma, Jian-Hua

    2017-10-01

    To investigate whether vildagliptin add-on insulin therapy improves glycemic variations in patients with uncontrolled type 2 diabetes (T2D) compared to patients with placebo therapy. This was a 24-week, single-center, double-blind, placebo-controlled trial. Inadequately controlled T2D patients treated with insulin therapy were recruited between June 2012 and April 2013. The trial included a 2-week screening period and a 24-week randomized period. Subjects were randomly assigned to a vildagliptin add-on insulin therapy group (n = 17) or a matched placebo group (n = 16). Scheduled visits occurred at weeks 4, 8, 12, 16, 20, and 24. Continuous glucose monitoring (CGM) was performed before and at the endpoint of the study. A total of 33 subjects were admitted, with 1 patient withdrawing from the placebo group. After 24 weeks of therapy, HbA1c values were significantly reduced at the endpoint in the vildagliptin add-on group. CGM data showed that patients with vildagliptin add-on therapy had a significantly lower 24-h mean glucose concentration and mean amplitude of glycemic excursion (MAGE). At the endpoint of the study, patients in the vildagliptin add-on group had a significantly lower MAGE and standard deviation compared to the control patients during the nocturnal period (0000-0600). A severe hypoglycemic episode was not observed in either group. Vildagliptin add-on therapy to insulin has the ability to improve glycemic variations, especially during the nocturnal time period, in patients with uncontrolled T2D.

  9. Severe hypoglycemia rates and associated costs among type 2 diabetics starting basal insulin therapy in the United States.

    Science.gov (United States)

    Ganz, Michael L; Wintfeld, Neil S; Li, Qian; Lee, Yuan-Chi; Gatt, Elyse; Huang, Joanna C

    2014-10-01

    To derive current real-world data on the rates and costs of severe hypoglycemia (SH) for people with type 2 diabetes mellitus (T2D) who have initiated basal insulin therapy and to examine differences in SH rates and costs stratified by history of prior SH events. We used a nation-wide electronic health records database that included encounter and laboratory data, as well as clinical notes, to estimate the rates and costs of SH events among adults with T2D who initiated basal insulin between 2008 and 2011. Unadjusted and regression-adjusted rates and quarterly costs were calculated for all patients as well as stratified by history of a SH event before starting basal insulin and history of a SH event during the basal insulin titration period. We identified 7235 incident cases of basal insulin use among patients with T2D who did not use insulin during the previous 12 months. Regression-adjusted incidence and total event rates were 10.36 and 11.21 per 100 patient-years, respectively. A history of SH events during the pre-index baseline and post-index titration periods were statistically significantly associated with both the incidence and total event rates (p history of previous SH or SH events during the titration period were not statistically significantly associated with costs. These results suggest that the real-world burden of SH is high among people with T2D who start using basal insulin and that history of previous SH events, both before starting insulin and during the insulin titration period, influences future SH. These results can also provide insights into interventions that can prevent or delay SH. These results should, however, be interpreted in light of the key limitations of our study: not all SH events may have been captured or coded in the database, data on filled prescriptions were not available, and the post-titration follow-up period could have been divided into time units other than quarters (3 month blocks) resulting in potentially different

  10. Effects of Hormone Replacement Therapy on Insulin Resistance in Postmenopausal Diabetic Women

    Directory of Open Access Journals (Sweden)

    Iskra Bitoska

    2016-02-01

    CONCLUSION: HRT was associated with statistically signifficant increase of insulin sensitivity. Larger clinical trials will be necessary to understand whether HRT may improve insulin resistance and glucose homeostasis in women with diabetes, especially when given shortly after entering menopause.

  11. Skeletal Muscle Sorbitol Levels in Diabetic Rats with and without Insulin Therapy and Endurance Exercise Training

    Science.gov (United States)

    Sánchez, O. A.; Walseth, T. F.; Snow, L. M.; Serfass, R. C.; Thompson, L. V.

    2009-01-01

    Sorbitol accumulation is postulated to play a role in skeletal muscle dysfunction associated with diabetes. The purpose of this study was to determine the effects of insulin and of endurance exercise on skeletal muscle sorbitol levels in streptozotocin-induced diabetic rats. Rats were assigned to one experimental group (control sedentary, control exercise, diabetic sedentary, diabetic exercise, diabetic sedentary no-insulin). Diabetic rats received daily subcutaneous insulin. The exercise-trained rats ran on a treadmill (1 hour, 5X/wk, for 12 weeks). Skeletal muscle sorbitol levels were the highest in the diabetic sedentary no-insulin group. Diabetic sedentary rats receiving insulin had similar sorbitol levels to control sedentary rats. Endurance exercise did not significantly affect sorbitol levels. These results indicate that insulin treatment lowers sorbitol in skeletal muscle; therefore sorbitol accumulation is probably not related to muscle dysfunction in insulin-treated diabetic individuals. Endurance exercise did not influence intramuscular sorbitol values as strongly as insulin. PMID:20016800

  12. Efficacy and safety comparison between liraglutide as add-on therapy to insulin and insulin dose-increase in Chinese subjects with poorly controlled type 2 diabetes and abdominal obesity

    Directory of Open Access Journals (Sweden)

    Li Chun-jun

    2012-11-01

    Full Text Available Abstract Objective To assess the efficacy and safety of adding liraglutide to established insulin therapy in poorly controlled Chinese subjects with type 2 diabetes and abdominal obesity compared with increasing insulin dose. Methods A 12-week, randomized, parallel-group study was carried out. A total of 84 patients completed the trial who had been randomly assigned to either the liraglutide-added group or the insulin-increasing group while continuing current insulin based treatment. Insulin dose was reduced by 0-30% upon the initiation of liraglutide. Insulin doses were subsequently adjusted to optimized glycemic control. Glycosylated hemoglobin (HbA1c values, blood glucose, total daily insulin dose, body weight, waist circumference, and the number of hypoglycemic events and adverse events were evaluated. Results At the end of study, the mean reduction in HbA1c between the liraglutide-added group and the insulin-increasing group was not significantly different (1.9% vs. 1.77%, p>0.05. However, the percentage of subjects reaching the composite endpoint of HbA1c ≤ 7.0% with no weight gain and no hypoglycemia, was significantly higher in the liraglutide-added group than in the insulin-increasing group (67% vs. 19%, p2, p Conclusions Addition of liraglutide to abdominally obese, insulin-treated patients led to improvement in glycemic control similar to that achieved by increasing insulin dosage, but with a lower daily dose of insulin and fewer hypoglycemic events. Adding liraglutide to insulin also induced a significant reduction in body weight and waist circumference. Liraglutide combined with insulin may be the best treatment option for poorly controlled type 2 diabetes and abdominal obesity.

  13. Endurance training improves insulin sensitivity and body composition in prostate cancer patients treated with androgen deprivation therapy

    DEFF Research Database (Denmark)

    Hvid, Thine; Winding, Kamilla; Rinnov, Anders

    2013-01-01

    Insulin resistance and changes in body composition are side effects of androgen deprivation therapy (ADT) given to prostate cancer patients. The present study investigated whether endurance training improves insulin sensitivity and body composition in ADT-treated prostate cancer patients. Nine me...... and magnetic resonance imaging). The secondary endpoint was systemic inflammation. Statistical analysis was carried out using two-way ANOVA. Endurance training increased VO2max (ml(O2)/min per kg) by 11 and 13% in the patients and controls respectively (P...

  14. Sub-acute insulin therapy does not affect long-term visiospatial ...

    African Journals Online (AJOL)

    Insulin is a common hypoglycaemic agent used to treat diabetes, but it has also been reported to exert other effects on the body including modulation cognition. Reported findings on insulin effect on learning and memory are scanty and often conflicting. This study was aimed at evaluating the effect of sub-acute insulin ...

  15. Clinical evidence and mechanistic basis for vildagliptin's effect in combination with insulin

    Directory of Open Access Journals (Sweden)

    Schweizer A

    2013-02-01

    Full Text Available Anja Schweizer,1 James E Foley,2 Wolfgang Kothny,2 Bo Ahrén31Novartis Pharma AG, Basel, Switzerland; 2Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA; 3Department of Clinical Sciences, Lund University, Lund, SwedenAbstract: Due to the progressive nature of type 2 diabetes, many patients need insulin as add-on to oral antidiabetic drugs (OADs in order to maintain adequate glycemic control. Insulin therapy primarily targets elevated fasting glycemia but is less effective to reduce postprandial hyperglycemia. In addition, the risk of hypoglycemia limits its effectiveness and there is a concern of weight gain. These drawbacks may be overcome by combining insulin with incretin-based therapies as these increase glucose sensitivity of both the α- and β-cells, resulting in improved postprandial glycemia without the hypoglycemia and weight gain associated with increasing the dose of insulin. The dipeptidyl peptidase-IV (DPP-4 inhibitor vildagliptin has also been shown to protect from hypoglycemia by enhancing glucagon counterregulation. The effectiveness of combining vildagliptin with insulin was demonstrated in three different studies in which vildagliptin decreased A1C levels when added to insulin therapy without increasing hypoglycemia. This was established with and without concomitant metformin therapy. Furthermore, the effectiveness of vildagliptin appears to be greater when insulin is used as a basal regimen as opposed to being used to reduce postprandial hyperglycemia, since improvement in insulin secretion likely plays a minor role when relatively high doses of insulin are administered before meals. This article reviews the clinical experience with the combination of vildagliptin and insulin and discusses the mechanistic basis for the beneficial effects of the combination. The data support the use of vildagliptin in combination with insulin in general and, in line with emerging clinical practice, suggest that treating patients with

  16. High-dose irradiation of food

    International Nuclear Information System (INIS)

    Diehl, J.F.

    1999-01-01

    Studies performed on behalf of the International Project on Food Irradiation in the period from 1971 until 1980 resulted in the concluding statement that ''.the irradiation of any food commodity up to an overall average dose of 10 kGy presents no toxicological hazard; hence, toxicological testing of foods so treated is no longer required.'' Since then, licenses for food irradiation have been restricted to this maximum dose in any country applying this technology. Further testing programmes have been carried out investigating the wholesomeness or hazards of high-dose irradiation, but there has been little demand so far by the food industry for licensing of high-dose irradiation, as there is only a small range of products whose irradiation at higher doses offers advantages for given, intended use. These include eg. spices, dried herbs, meat products in flexible pouch packagings for astronauts, or patients with immune deficiencies. (orig./CB) [de

  17. Sleep architecture, insulin resistance and the nasal cycle: Implications for positive airway pressure therapy

    Directory of Open Access Journals (Sweden)

    Catherine A.P. Crofts

    2018-03-01

    Full Text Available Background: The global pandemic of metabolic disease is worsening. The metabolic theory of obesity proposes that hormonal changes, especially hyperinsulinaemia, precede metabolic disease development. Although quality sleep is recognised as a key factor for good health, less is known about disrupted sleep as a risk factor for hyperinsulinaemia.   Aim: To explore the relationship between sleep, especially sleep architecture and the nasal cycle, on insulin secretion in obstructive sleep apnoea (OSA with comorbid metabolic disease. This review includes a discussion of the potential role of Rest-Activity-Cycler positive airway pressure (RACer-PAP, a novel non-pharmacological OSA treatment strategy.   Methods: A narrative review of all the relevant papers known to the authors was conducted. This review also included results from a polysomnographic sleep clinic pilot study (n = 3 comparing sleep efficiency of RACer-PAP to nasal continuous positive airways pressure (n-CPAP in OSA patients.   Results: Metabolic disease is strongly associated with disturbed sleep. Sleep architecture influences cerebral hormonal secretion, lateral shifts in the autonomic nervous system and nasal airflow dominance. Disturbed sleep shortens short-wave sleep periods, decreasing insulin sensitivity and glucose tolerance. Improvements to metabolic function during n-CPAP treatment are inconsistent. If RACer-PAP demonstrates superior effects on sleep architecture and autonomic function, it may offer advantages in OSA patients with comorbid metabolic disease.   Conclusion: Improving sleep architecture by maintaining the nasal cycle proposes a novel non-pharmacological treatment paradigm for treating OSA with comorbid metabolic disease. Research is required to demonstrate if RACer-PAP therapy influences whole night sleep architecture, sympathovagal balance and markers of metabolic disease.

  18. Use and Effectiveness of Continuous Subcutaneous Insulin Infusion (CSII) and Multiple Daily Insulin Injection Therapy (MIT) in Children, Adolescents and Young Adults with Type 1 Diabetes Mellitus.

    Science.gov (United States)

    Schiel, R; Burgard, D; Perenthaler, T; Stein, G; Kramer, G; Steveling, A

    2016-02-01

    Today continuous subcutaneous insulin infusion (CSII) is frequently used in children and adolescents with type 1 diabetes mellitus. The present cross-sectional trial aimed to document current practice, quality of diabetes control and incidence of acute complications in different age-groups under CSII vs. multiple daily insulin injection therapy (MIT). Moreover the survey analyzed socio-demographic backgrounds of the patients. A total of 901 patients (age 11.5±4.0, diabetes duration 4.0±3.6 years) was entered in the database. Clinical data, laboratory parameters and, using a standardized questionnaire, socio-demographic data were assessed. For age-related analyses patients were allocated to 4 groups: pre-school children (MIT. Patients with CSII vs. MIT had a longer diabetes duration, they used more frequently insulin analogues, performed more frequently blood-glucose self-tests and had a lower insulin dosage per kilogram body weight. In respect of HbA1c, the mean amplitude of blood-glucose excursions, but also of lipids, creatinine, microalbuminuria and blood pressure, there were no differences in neither age-group between patients with CSII and MIT. In patients with CSII and MIT, there was a tendency (pMIT there is an increase of HbA1c towards adolescence. It must also highlighted that CSII seems to be expansive and that CSII is more frequently used in patients with better educational levels and deriving from higher social classes. © Georg Thieme Verlag KG Stuttgart · New York.

  19. Analysis of Biochemical Control and Prognostic Factors in Patients Treated With Either Low-Dose Three-Dimensional Conformal Radiation Therapy or High-Dose Intensity-Modulated Radiotherapy for Localized Prostate Cancer

    International Nuclear Information System (INIS)

    Vora, Sujay A.; Wong, William W.; Schild, Steven E.; Ezzell, Gary A.; Halyard, Michele Y.

    2007-01-01

    Purpose: To identify prognostic factors and evaluate biochemical control rates for patients with localized prostate cancer treated with either high-dose intensity-modulated radiotherapy (IMRT) or conventional-dose three-dimensional conformal radiotherapy 3D-CRT. Methods: Four hundred sixteen patients with a minimum follow-up of 3 years (median, 5 years) were included. Two hundred seventy-one patients received 3D-CRT with a median dose of 68.4 Gy (range, 66-71 Gy). The next 145 patients received IMRT with a median dose of 75.6 Gy (range, 70.2-77.4 Gy). Biochemical control rates were calculated according to both American Society for Therapeutic Radiology and Oncology (ASTRO) consensus definitions. Prognostic factors were identified using both univariate and multivariate analyses. Results: The 5-year biochemical control rate was 60.4% for 3D-CRT and 74.1% for IMRT (p < 0.0001, first ASTRO Consensus definition). Using the ASTRO Phoenix definition, the 5-year biochemical control rate was 74.4% and 84.6% with 3D-RT and IMRT, respectively (p = 0.0326). Univariate analyses determined that PSA level, T stage, Gleason score, perineural invasion, and radiation dose were predictive of biochemical control. On multivariate analysis, dose, Gleason score, and perineural invasion remained significant. Conclusion: On the basis of both ASTRO definitions, dose, Gleason score, and perineural invasion were predictive of biochemical control. Intensity-modulated radiotherapy allowed delivery of higher doses of radiation with very low toxicity, resulting in improved biochemical control

  20. WE-DE-201-01: BEST IN PHYSICS (THERAPY): A Fast Multi-Target Inverse Treatment Planning Strategy Optimizing Dosimetric Measures for High-Dose-Rate (HDR) Brachytherapy

    Energy Technology Data Exchange (ETDEWEB)

    Guthier, C [Brigham and Women’s Hospital, Boston, MA (United States); University Medical Center Mannheim, Mannheim (Germany); Harvard Medical School, Boston, MA (United States); Damato, A; Viswanathan, A; Cormack, R [Dana Farber Cancer Institut/Brigham and Women’s Hospital, Boston, MA (United States); Harvard Medical School, Boston, MA (United States); Hesser, J [University Medical Center Mannheim, Mannheim (Germany)

    2016-06-15

    Purpose: Inverse treatment planning (ITP) for interstitial HDR brachytherapy of gynecologic cancers seeks to maximize coverage of the clinical target volumes (tumor and vagina) while respecting dose-volume-histogram related dosimetric measures (DMs) for organs at risk (OARs). Commercially available ITP tools do not support DM-based planning because it is computationally too expensive to solve. In this study we present a novel approach that allows fast ITP for gynecologic cancers based on DMs for the first time. Methods: This novel strategy is an optimization model based on a smooth DM-based objective function. The smooth approximation is achieved by utilizing a logistic function for the evaluation of DMs. The resulting nonconvex and constrained optimization problem is then optimized with a BFGS algorithm. The model was evaluated using the implant geometry extracted from 20 patient treatment plans under an IRB-approved retrospective study. For each plan, the final DMs were evaluated and compared to the original clinical plans. The CTVs were the contoured tumor volume and the contoured surface of the vagina. Statistical significance was evaluated with a one-sided paired Wilcoxon signed-rank test. Results: As did the clinical plans, all generated plans fulfilled the defined DMs for OARs. The proposed strategy showed a statistically significant improvement (p<0.001) in coverage of the tumor and vagina, with absolute improvements of related DMs of (6.9 +/− 7.9)% and (28.2 +/− 12.0)%, respectively. This was achieved with a statistically significant (p<0.01) decrease of the high-dose-related DM for the tumor. The runtime of the optimization was (2.3 +/− 2.0) seconds. Conclusion: We demonstrated using clinical data that our novel approach allows rapid DM-based optimization with improved coverage of CTVs with fewer hot spots. Being up to three orders of magnitude faster than the current clinical practice, the method dramatically shortens planning time.

  1. WE-DE-201-01: BEST IN PHYSICS (THERAPY): A Fast Multi-Target Inverse Treatment Planning Strategy Optimizing Dosimetric Measures for High-Dose-Rate (HDR) Brachytherapy

    International Nuclear Information System (INIS)

    Guthier, C; Damato, A; Viswanathan, A; Cormack, R; Hesser, J

    2016-01-01

    Purpose: Inverse treatment planning (ITP) for interstitial HDR brachytherapy of gynecologic cancers seeks to maximize coverage of the clinical target volumes (tumor and vagina) while respecting dose-volume-histogram related dosimetric measures (DMs) for organs at risk (OARs). Commercially available ITP tools do not support DM-based planning because it is computationally too expensive to solve. In this study we present a novel approach that allows fast ITP for gynecologic cancers based on DMs for the first time. Methods: This novel strategy is an optimization model based on a smooth DM-based objective function. The smooth approximation is achieved by utilizing a logistic function for the evaluation of DMs. The resulting nonconvex and constrained optimization problem is then optimized with a BFGS algorithm. The model was evaluated using the implant geometry extracted from 20 patient treatment plans under an IRB-approved retrospective study. For each plan, the final DMs were evaluated and compared to the original clinical plans. The CTVs were the contoured tumor volume and the contoured surface of the vagina. Statistical significance was evaluated with a one-sided paired Wilcoxon signed-rank test. Results: As did the clinical plans, all generated plans fulfilled the defined DMs for OARs. The proposed strategy showed a statistically significant improvement (p<0.001) in coverage of the tumor and vagina, with absolute improvements of related DMs of (6.9 +/− 7.9)% and (28.2 +/− 12.0)%, respectively. This was achieved with a statistically significant (p<0.01) decrease of the high-dose-related DM for the tumor. The runtime of the optimization was (2.3 +/− 2.0) seconds. Conclusion: We demonstrated using clinical data that our novel approach allows rapid DM-based optimization with improved coverage of CTVs with fewer hot spots. Being up to three orders of magnitude faster than the current clinical practice, the method dramatically shortens planning time.

  2. [Attitudes toward insulin prescription in type 2 diabetic patients non-compliant with diet therapy].

    Science.gov (United States)

    Mordenti, F; D'Angiolini, G; Murgia, F

    2000-01-01

    Investigate the compliance of type 2 diabetic patients with the prescription of insulin according to pre-existing ideas on insulin, and to personality traits. Twenty insulin-treated type 2 diabetic patients were selected on the basis of previous scarce compliance with diet and exercise and BMI > 28 kg/m2. The patients' attitudes toward insulin prescription were evaluated with a semi-structured interview and personality traits were evaluated with the ACL test(Adjective Check List). When insulin was first prescribed to these patients, 65% accepted immediately. However, 45% answered that their acquiescence to insulin treatment was accompanied by doubts or apprehension. The fear of insulin dependence was shared by 50%, with a much greater prevalence among those who resisted to insulin treatment (86% vs 31%) and those who recalled doubts and fears about insulin (73% vs 22%). Patients with a fear of dependence differed significantly from the others in five personality scales: greater opposition and ambiguity, less self-confidence, more inflexible, less demanding of others and more inclined to bargain. The irrational fear of dependence may, therefore, play a role in both the manifest acceptance/rejection of insulin and non-expressed doubts, and may in turn be influenced by personality traits. Specific patient education on insulin treatment in type 2 diabetes is necessary, and should be planned according to the personality factors that may influence the perception of facts and the patients' motivation.

  3. Sustained trilineage recovery and disappearance of abnormal chromosome clone in a patient with myelodysplastic syndrome following combination therapy with cytokines (granulocyte colony-stimulating factor and erythropoietin) and high-dose methylprednisolone.

    Science.gov (United States)

    Imai, Y; Fukuoka, T; Nakatani, A; Ohsaka, A; Takahashi, A

    1996-04-01

    We report a case of hypoplastic myelodyplastic syndrome (MDS) (refractory anemia (RA)) in which sustained trilineage haematological response and persistent disappearance of an abnormal chromosome clone were achieved after treatment with combination therapy of cytokines (granulocyte colony-stimulating factor (G-CSF) and erythropoietin (Epo)) and methylprednisolone (mPSL) pulse dose. The patient's haematological recovery was rapid and maintained even after cessation of the therapy. In addition, the predominant chromosome clone 13q- in bone marrow cells disappeared in the fourth week. The patient's improved bone marrow haemopoiesis and disappearance of the abnormal chromosome has continued to the present, 13 months after treatment. The occurrence of both trilineage response and abnormal chromosome disappearance in MDS patients treated with cytokine(s) or steroids is rare. Combination therapy might therefore be advantageous in MDS.

  4. Attenuation of Ca2+ homeostasis, oxidative stress, and mitochondrial dysfunctions in diabetic rat heart: insulin therapy or aerobic exercise?

    Science.gov (United States)

    da Silva, Márcia F; Natali, Antônio J; da Silva, Edson; Gomes, Gilton J; Teodoro, Bruno G; Cunha, Daise N Q; Drummond, Lucas R; Drummond, Filipe R; Moura, Anselmo G; Belfort, Felipe G; de Oliveira, Alessandro; Maldonado, Izabel R S C; Alberici, Luciane C

    2015-07-15

    We tested the effects of swimming training and insulin therapy, either alone or in combination, on the intracellular calcium ([Ca(2+)]i) homeostasis, oxidative stress, and mitochondrial functions in diabetic rat hearts. Male Wistar rats were separated into control, diabetic, or diabetic plus insulin groups. Type 1 diabetes mellitus was induced by streptozotocin (STZ). Insulin-treated groups received 1 to 4 UI of insulin daily for 8 wk. Each group was divided into sedentary or exercised rats. Trained groups were submitted to swimming (90 min/day, 5 days/wk, 8 wk). [Ca(2+)]i transient in left ventricular myocytes (LVM), oxidative stress in LV tissue, and mitochondrial functions in the heart were assessed. Diabetes reduced the amplitude and prolonged the times to peak and to half decay of the [Ca(2+)]i transient in LVM, increased NADPH oxidase-4 (Nox-4) expression, decreased superoxide dismutase (SOD), and increased carbonyl protein contents in LV tissue. In isolated mitochondria, diabetes increased Ca(2+) uptake, susceptibility to permeability transition pore (MPTP) opening, uncoupling protein-2 (UCP-2) expression, and oxygen consumption but reduced H2O2 release. Swimming training corrected the time course of the [Ca(2+)]i transient, UCP-2 expression, and mitochondrial Ca(2+) uptake. Insulin replacement further normalized [Ca(2+)]i transient amplitude, Nox-4 expression, and carbonyl content. Alongside these benefits, the combination of both therapies restored the LV tissue SOD and mitochondrial O2 consumption, H2O2 release, and MPTP opening. In conclusion, the combination of swimming training with insulin replacement was more effective in attenuating intracellular Ca(2+) disruptions, oxidative stress, and mitochondrial dysfunctions in STZ-induced diabetic rat hearts. Copyright © 2015 the American Physiological Society.

  5. Effects of insulin therapy on weight gain and fat distribution in the HF/HS-STZ rat model of type 2 diabetes

    DEFF Research Database (Denmark)

    Skovsø, Søs; Damgaard, J; Fels, J J

    2015-01-01

    insulin on fat distribution in the high-fat/high-sucrose fed rat treated with streptozotocin (HF/HS-STZ) rat model of type 2 diabetes. We also examined effects of insulin therapy on circulating CVD markers, including adiponectin, triglycerides (TGs), total cholesterol and high-density lipoprotein......-density lipoprotein (HDL) and adiponectin levels were elevated (Ptype 2 diabetes, we find that insulin therapy modulates fat distribution. Specifically, our data show that insulin has a relatively positive effect on CVD-associated parameters......BACKGROUND/OBJECTIVES: Insulin therapy is required for many patients with the obesity-related disorder type 2 diabetes, but is also associated with weight gain. The specific location of adipose tissue location matters to cardiovascular disease (CVD) risk. We investigated effects of exogenous...

  6. Long-term efficacy and safety of vildagliptin add-on therapy in type 2 diabetes mellitus with insulin treatment.

    Science.gov (United States)

    Kanazawa, Ippei; Tanaka, Ken-Ichiro; Notsu, Masakazu; Tanaka, Sayuri; Kiyohara, Nobuaki; Koike, Sayo; Yamane, Yuko; Tada, Yuko; Sasaki, Motofumi; Yamauchi, Mika; Sugimoto, Toshitsugu

    2017-01-01

    The use of dipeptidyl peptidase (DPP)-4 inhibitors in patients with type 2 diabetes treated with insulin may be beneficial. However, the long-term efficacy and safety of vildagliptin add-on therapy in these patients remains unclear. A total of 73 patients with type 2 diabetes treated with insulin were randomly assigned to receive either add-on therapy of vildagliptin (n=37) or conventional therapy without DPP-4 inhibitors (n=36) for glucose control. Hemoglobin A1c (HbA1c) levels, dose and number of insulin injections, number of hypoglycemia episodes, and liver and renal function were monitored for 2years. The baseline characteristics of subjects, including age, dose of insulin injections, or HbA1c levels, did not differ between the two groups. In the vildagliptin group, HbA1c levels significantly decreased and the significance of HbA1c reduction was maintained for 24months (from 8.0±1.2% to 7.4±1.0%, pinsulin injections significantly reduced (-5.6units, p1, and -0.9 times, p1). However, these parameters were unchanged in the control group. The number of patients who experienced three or more episodes of hypoglycemia per year was significantly lower in the vildagliptin group (n=4) than in the control group (n=11) (odds ratio, 0.28; 95% confidence interval, 0.08-0.97; pinsulin treatment for 24months was well tolerated and led to sustained reductions in HbA1c, the dose and number of insulin injections, and the risk of hypoglycemia. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  7. The effect of 30 months of low-dose replacement therapy with recombinant human growth hormone (rhGH) on insulin and C-peptide kinetics, insulin secretion, insulin sensitivity, glucose effectiveness, and body composition in GH-deficient adults

    DEFF Research Database (Denmark)

    Rosenfalck, A M; Maghsoudi, S; Fisker, S

    2000-01-01

    The aim of the present study was to evaluate the long-term (30 months) metabolic effects of recombinant human GH (rhGH) given in a mean dose of 6.7 microg/kg x day (= 1.6 IU/day), in 11 patients with adult GH deficiency. Glucose metabolism was evaluated by an oral glucose tolerance test and an iv...... (frequently sampled iv glucose tolerance test) glucose tolerance test, and body composition was estimated by dual-energy x-ray absorptiometry. Treatment with rhGH induced persistent favorable changes in body composition, with a 10% increase in lean body mass (P ... in glucose tolerance, beta-cell response was still inappropriate. Our conclusion is that long-term rhGH-replacement therapy in GH deficiency adults induced a significant deterioration in glucose tolerance, profound changes in kinetics of C-peptide, and insulin and prehepatic insulin secretion, despite...

  8. Prospective Study Delivering Simultaneous Integrated High-dose Tumor Boost (≤70 Gy) With Image Guided Adaptive Radiation Therapy for Radical Treatment of Localized Muscle-Invasive Bladder Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Hafeez, Shaista, E-mail: Shaista.Hafeez@icr.ac.uk [The Institute of Cancer Research, London (United Kingdom); The Royal Marsden National Health Service Foundation Trust, London (United Kingdom); Warren-Oseni, Karole [The Royal Marsden National Health Service Foundation Trust, London (United Kingdom); McNair, Helen A.; Hansen, Vibeke N.; Jones, Kelly; Tan, Melissa; Khan, Attia [The Institute of Cancer Research, London (United Kingdom); The Royal Marsden National Health Service Foundation Trust, London (United Kingdom); Harris, Victoria; McDonald, Fiona; Lalondrelle, Susan; Mohammed, Kabir; Thomas, Karen; Thompson, Alan; Kumar, Pardeep [The Royal Marsden National Health Service Foundation Trust, London (United Kingdom); Dearnaley, David; Horwich, Alan; Huddart, Robert [The Institute of Cancer Research, London (United Kingdom); The Royal Marsden National Health Service Foundation Trust, London (United Kingdom)

    2016-04-01

    Purpose: Image guided adaptive radiation therapy offers individualized solutions to improve target coverage and reduce normal tissue irradiation, allowing the opportunity to increase the radiation tumor dose and spare normal bladder tissue. Methods and Materials: A library of 3 intensity modulated radiation therapy plans were created (small, medium, and large) from planning computed tomography (CT) scans performed at 30 and 60 minutes; treating the whole bladder to 52 Gy and the tumor to 70 Gy in 32 fractions. A “plan of the day” approach was used for treatment delivery. A post-treatment cone beam CT (CBCT) scan was acquired weekly to assess intrafraction filling and coverage. Results: A total of 18 patients completed treatment to 70 Gy. The plan and treatment for 1 patient was to 68 Gy. Also, 1 patient's plan was to 70 Gy but the patient was treated to a total dose of 65.6 Gy because dose-limiting toxicity occurred before dose escalation. A total of 734 CBCT scans were evaluated. Small, medium, and large plans were used in 36%, 48%, and 16% of cases, respectively. The mean ± standard deviation rate of intrafraction filling at the start of treatment (ie, week 1) was 4.0 ± 4.8 mL/min (range 0.1-19.4) and at end of radiation therapy (ie, week 5 or 6) was 1.1 ± 1.6 mL/min (range 0.01-7.5; P=.002). The mean D{sub 98} (dose received by 98% volume) of the tumor boost and bladder as assessed on the post-treatment CBCT scan was 97.07% ± 2.10% (range 89.0%-104%) and 99.97% ± 2.62% (range 96.4%-112.0%). At a median follow-up period of 19 months (range 4-33), no muscle-invasive recurrences had developed. Two patients experienced late toxicity (both grade 3 cystitis) at 5.3 months (now resolved) and 18 months after radiation therapy. Conclusions: Image guided adaptive radiation therapy using intensity modulated radiation therapy to deliver a simultaneous integrated tumor boost to 70 Gy is feasible, with acceptable toxicity, and will be

  9. Prostate cancer treated with image-guided helical TomoTherapy {sup registered} and image-guided LINAC-IMRT. Correlation between high-dose bladder volume, margin reduction, and genitourinary toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Drozdz, Sonia; Wendt, Thomas G. [University Hospital Jena, Friedrich-Schiller-University Jena, Department of Radiation Oncology, Jena (Germany); Schwedas, Michael; Salz, Henning [University Hospital Jena, Friedrich-Schiller-University Jena, Department of Radiation Oncology, Section of Medical Physics, Jena (Germany); Foller, Susan [University Hospital Jena, Friedrich-Schiller-University Jena, Department of Urology, Jena (Germany)

    2016-04-15

    We compared different image-guidance (IG) strategies for prostate cancer with high-precision IG intensity-modulated radiation therapy (IMRT) using TomoTherapy {sup registered} (Accuray Inc., Madison, WI, USA) and linear accelerator (LINAC)-IMRT and their impact on planning target volume (PTV) margin reduction. Follow-up data showed reduced bladder toxicity in TomoTherapy patients compared to LINAC-IMRT. The purpose of this study was to quantify whether the treatment delivery technique and decreased margins affect reductions in bladder toxicity. Setup corrections from 30 patients treated with helical TomoTherapy and 30 treated with a LINAC were analyzed. These data were used to simulate three IG protocols based on setup error correction and a limited number of imaging sessions. For all patients, gastrointestinal (GI) and genitourinary (GU) toxicity was documented and correlated with the treatment delivery technique. For fiducial marker (FM)-based RT, a margin reduction of up to 3.1, 3.0, and 4.8 mm in the left-right (LR), superior-inferior (SI), and anterior-posterior (AP) directions, respectively, could be achieved with calculation of a setup correction from the first three fractions and IG every second day. Although the bladder volume was treated with mean doses of 35 Gy in the TomoTherapy group vs. 22 Gy in the LINAC group, we observed less GU toxicity after TomoTherapy. Intraprostate FMs allow for small safety margins, help decrease imaging frequency after setup correction, and minimize the dose to bladder and rectum, resulting in lower GU toxicity. In addition, IMRT delivered with TomoTherapy helps to avoid hotspots in the bladder neck, a critical anatomic structure associated with post-RT urinary toxicity. (orig.) [German] Wir haben im Rahmen der Prostatakarzinombehandlung verschiedene bildgefuehrte (IG) Strategien der hochpraezisen intensitaetsmodulierten Radiotherapie (IMRT) unter Einsatz der Tomotherapie (TomoTherapy {sup registered}, Accuray Inc., Madison

  10. Effects of switching from prandial premixed insulin therapy to basal plus two times bolus insulin therapy on glycemic control and quality of life in patients with type 2 diabetes mellitus.

    Science.gov (United States)

    Ito, Hiroyuki; Abe, Mariko; Antoku, Shinichi; Omoto, Takashi; Shinozaki, Masahiro; Nishio, Shinya; Mifune, Mizuo; Togane, Michiko

    2014-01-01

    The effects of switching from prandial premixed insulin therapy (PPT) injected three times a day to basal plus two times bolus insulin therapy (B2B) on glycemic control and quality of life were investigated in patients with type 2 diabetes mellitus. The clinical course was prospectively observed during the first 16 weeks after switching to B2B (insulin glargine plus insulin glulisine before breakfast and dinner) in 27 subjects previously treated with PPT using 50/50 premixed insulin. The Diabetes Treatment Satisfaction Questionnaire (DTSQ) was administered at the start and end of the study. The glycated hemoglobin (HbA1c) level (8.3% ± 1.8% to 8.2% ± 1.1%) and the DTSQ score did not change between the start and end of the study. An improvement in HbA1c level was found in nine (33%) subjects. The change in HbA1c showed a significant negative correlation with baseline HbA1c, and was significantly better in patients with a baseline HbA1c >8.0% than in those with an HbA1c ≤ 8.0% (-0.9 ± 2.0 versus 0.3 ± 0.6, respectively, P = 0.02). The change in DTSQ score representing treatment satisfaction was significantly greater in patients whose HbA1c level was improved than in those in whom it was not (2.7 ± 3.6 versus -0.8 ± 3.5, P = 0.04). B2B was noninferior to PPT with regard to HbA1c levels in patients with type 2 diabetes mellitus. B2B should be considered particularly for subjects whose glycemic control is poor despite PPT.

  11. High dose rate endobronchial brachytherapy - treatment technique

    International Nuclear Information System (INIS)

    Carvalho, Heloisa de Andrade; Aisen, Salim; Haddad, Cecilia Maria Kalil; Nadalin, Wladimir; Pedreira Junior, Wilson Leite; Chavantes, Maria Cristina

    1998-01-01

    High dose rate endobronchial brachytherapy is efficient in symptom relief due to obstructive endobronchial malignancies. However, it's role in survival improvement for patients with lung cancer is not yet established. The use of this treatment in increasing, specially in the developing countries. The purpose of this paper is to present the treatment technique used in the Radiotherapy Department of the Hospital da Clinicas, University of Sao Paulo, based on an experience of 60 cases treated with 180 procedures. Some practical suggestions and rules adopted in the Department are described. The severe complications rate is 6.7%, demonstrating an adequate patient selection associated with the technique utilized. (author)

  12. Neuroprotective potential of high-dose biotin.

    Science.gov (United States)

    McCarty, Mark F; DiNicolantonio, James J

    2017-11-01

    A recent controlled trial has established that high-dose biotin supplementation - 100 mg, three times daily - has a stabilizing effect on progression of multiple sclerosis (MS). Although this effect has been attributed to an optimization of biotin's essential cofactor role in the brain, a case can be made that direct stimulation of soluble guanylate cyclase (sGC) by pharmacological concentrations of biotin plays a key role in this regard. The utility of high-dose biotin in MS might reflect an anti-inflammatory effect of cGMP on the cerebral microvasculature, as well on oligodendrocyte differentiation and on Schwann cell production of neurotrophic factors thought to have potential for managing MS. But biotin's ability to boost cGMP synthesis in the brain may have broader neuroprotective potential. In many types of neurons and neural cells, cGMP exerts neurotrophic-mimetic effects - entailing activation of the PI3K-Akt and Ras-ERK pathways - that promote neuron survival and plasticity. Hippocampal long term potentiation requires nitric oxide synthesis, which in turn promotes an activating phosphorylation of CREB via a pathway involving cGMP and protein kinase G (PKG). In Alzheimer's disease (AD), amyloid beta suppresses this mechanism by inhibiting sGC activity; agents which exert a countervailing effect by boosting cGMP levels tend to restore effective long-term potentiation in rodent models of AD. Moreover, NO/cGMP suppresses amyloid beta production within the brain by inhibiting expression of amyloid precursor protein and BACE1. In conjunction with cGMP's ability to oppose neuron apoptosis, these effects suggest that high-dose biotin might have potential for the prevention and management of AD. cGMP also promotes neurogenesis, and may lessen stroke risk by impeding atherogenesis and hypertrophic remodeling in the cerebral vasculature. The neuroprotective potential of high-dose biotin likely could be boosted by concurrent administration of brain

  13. Safety handling manual for high dose rate remote afterloading system

    International Nuclear Information System (INIS)

    1999-01-01

    This manual is mainly for safety handling of 192 Ir-RALS (remote afterloading system) of high dose rate and followings were presented: Procedure and document format for the RALS therapy and for handling of its radiation source with the purpose of prevention of human errors and unexpected accidents, Procedure for preventing errors occurring in the treatment schedule and operation, and Procedure and format necessary for newly introducing the system into a facility. Consistency was intended in the description with the quality assurance guideline for therapy with small sealed radiation sources made by JASTRO (Japan Society for Therapeutic Radiology and Oncology). Use of the old type 60 Co-RALS was pointed out to be a serious problem remained and its safety handling procedure was also presented. (K.H.)

  14. Immune reactivity after high-dose irradiation

    International Nuclear Information System (INIS)

    Gassmann, W.; Wottge, H.U.; von Kolzynski, M.; Mueller-Ruchholtz, W.

    1986-01-01

    Immune reactivity after total-body irradiation was investigated in rats using skin graft rejection as the indicator system. After sublethal irradiation with 10.5 Gy (approximately 50% lethality/6 weeks) the rejection of major histocompatibility complex allogeneic skin grafts was delayed significantly compared with nonirradiated control animals (28 versus 6.5 days). In contrast, skin grafts were rejected after 7.5 days in sublethally irradiated animals and 7 days in lethally irradiated animals if additional skin donor type alloantigens--namely, irradiated bone marrow cells--were given i.v. either simultaneously or with a delay of not more than 24 hr after the above conditioning regimen. These reactions were alloantigen-specific. They were observed in six different strain combinations with varying donors and recipients. Starting on day 2 after irradiation, i.v. injection of bone marrow gradually lost its effectivity and skin grafts were no longer rejected with uniform rapidity; skin donor marrow given on days 4 or 8 did not accelerate skin graft rejection at all. These data show that for approximately 1-2 days after high-dose total-body irradiation rats are still capable of starting a vigorous immune reaction against i.v.-injected alloantigens. The phenomenon of impaired rejection of skin grafted immediately after high-dose irradiation appears to result from the poor accessibility of skin graft alloantigens during the early postirradiation phase when vascularization of the grafted skin is insufficient

  15. High-dose vitamin C and cancer

    Directory of Open Access Journals (Sweden)

    Ahmet Unlu, M.D.

    2016-01-01

    Full Text Available Vitamin C (ascorbic acid, ascorbate is a basic compound that is of great importance with its role in various enzymatic reactions including the synthesis of collagen, as well as with its redox functions. Vitamin C has become the center of interest in cancer studies, in consequence of the facts that connective tissue changes and vitamin C deficiency were first alleged to be associated with cancer in the 1950s; and that high doses of vitamin C was asserted to be cytotoxic for cancer cells, later on. The results of the first study carried out in the 1970s were promising; but afterwards, the studies were ascertained to be faulty. Despite the positive results achieved from some laboratory and animal experiments, randomized clinical trials did not verify those findings, and no clear benefit of vitamin C for cancer treatment could be demonstrated. As for studies, where its use in combination with other cancer treatment regimens was assessed, conflicting results were obtained. Although intake of high doses of vitamin C is alleged to be harmless, based on that it is in the group of water soluble vitamins and is not stored in the body, there are many side effects and drug interactions reported in the literature. For now, it is better to abstain from this treatment, until the benefit of the treatment (if any is clearly demonstrated, considering the potential side effects and interactions.

  16. Reliability and Validity of Modified Service Quality Instrument (SERVQUAL) in Patients' Motivation to Adhere to Insulin Therapy.

    Science.gov (United States)

    Jakupovic, Vedran; Solakovic, Suajb; Celebic, Nedim; Kulovic, Dzenan

    2018-03-01

    Diabetes is progressive condition which requires various ways of treatment. Adequate therapy prescribed in the right time helps patient to postpone development of complications. Adherence to complicated therapy is challenge for both patients and HCPs and is subject of research in many disciplines. Improvement in communication between HCP and patients is very important in patient's adherence to therapy. Aim of this research was to explore validity and reliability of modified SERVQUAL instrument in attempt to explore ways of motivating diabetic patient to accept prescribed insulin therapy. We used modified SERVQUAL questionnaire as instrument in the research. It was necessary to check validity and reliability of the new modified instrument. Results show that modified Servqual instrument has excellent reliability (α=0.908), so we could say that it measures precisely Expectations, Perceptions and Motivation at patients. Factor analysis (EFA method) with Varimax rotation extracted 4 factors which together explain 52.902% variance of the results on this subscale. Bifactorial solution could be seen on Scree-plot diagram (break at second factor). Results in this research show that modified Servqual instrument which is created in order to measure expectations and perceptions of the patients is valid and reliable. Reliability and validity are proven indeed in additional dimension which was created originally for this research - motivation to accept insulin therapy.

  17. Reliability and Validity of Modified Service Quality Instrument (SERVQUAL) in Patients’ Motivation to Adhere to Insulin Therapy

    Science.gov (United States)

    Jakupovic, Vedran; Solakovic, Suajb; Celebic, Nedim; Kulovic, Dzenan

    2018-01-01

    Introduction: Diabetes is progressive condition which requires various ways of treatment. Adequate therapy prescribed in the right time helps patient to postpone development of complications. Adherence to complicated therapy is challenge for both patients and HCPs and is subject of research in many disciplines. Improvement in communication between HCP and patients is very important in patient’s adherence to therapy. Aim: Aim of this research was to explore validity and reliability of modified SERVQUAL instrument in attempt to explore ways of motivating diabetic patient to accept prescribed insulin therapy. Material and Methods: We used modified SERVQUAL questionnaire as instrument in the research. It was necessary to check validity and reliability of the new modified instrument. Results: Results show that modified Servqual instrument has excellent reliability (α=0.908), so we could say that it measures precisely Expectations, Perceptions and Motivation at patients. Factor analysis (EFA method) with Varimax rotation extracted 4 factors which together explain 52.902% variance of the results on this subscale. Bifactorial solution could be seen on Scree-plot diagram (break at second factor). Conclusion: Results in this research show that modified Servqual instrument which is created in order to measure expectations and perceptions of the patients is valid and reliable. Reliability and validity are proven indeed in additional dimension which was created originally for this research - motivation to accept insulin therapy. PMID:29670478

  18. Terapia com inibidor da ECA com dosagens relativamente altas e risco de agravamento renal na insuficiência cardíaca crônica ACE-inhibitor therapy at relatively high doses and risk of renal worsening in chronic heart failure

    Directory of Open Access Journals (Sweden)

    Renato De Vecchis

    2011-12-01

    : ACE-inhibitors "high" dose, age, basal LVEF, history of repeated intensive intravenous loop diuretic therapies (IV diur, diabetes, basal Cr, history of hypertension, systolic blood pressure < 100 mm Hg. RESULTS: 57 patients were recruited, of whom 15 were treated with ACE-inhibitor "high" dose. During a mean follow-up of 718 days, ARD occurred in 17 (29.8% patients. Only ACE-inhibitor "high" dose (HR: 12.4681 C.I.: 2.1614-71.9239 p=0.0050 and basal Cr (HR: 1.2344 C.I.: 1.0414-1.4632 p=0.0157 were shown to predict ARD. Moreover, ACE-inhibitor "high" doses were shown to fail to predict ARD in both CHF without IV diur and CHF with diabetes. CONCLUSION: In III NYHA class CHF, ACE-inhibitor "high" doses and a higher basal Cr predicted ARD. Nephrotoxicity related to ACE-inhibitor "high" doses was increased by IV diur, whereas it was not detected in CHF patients with diabetes.

  19. Influence of ezetimibe in addition to high-dose atorvastatin therapy on plaque composition in patients with ST-segment elevation myocardial infarction assessed by serial Intravascular ultrasound with iMap: the OCTIVUS trial*

    DEFF Research Database (Denmark)

    Hougaard, Mikkel; Hansen, Henrik Steen; Thayssen, Per

    2017-01-01

    Background: The aim of this study was to examine the influence of ezetimibe in addition to atorvastatin on plaque composition in patients with first-time ST-segment Elevation Myocardial Infarction treated with primary percutaneous intervention. Methods: Eighty-seven patients were randomized ( 1: 1......) to ezetimibe 10mg or placebo in addition to Atorvastatin 80 mg. Intravascular ultrasound with iMap was performed at baseline and after 12 months in a non-infarctrelated artery. Primary endpoint was change in necrotic core (NC). Secondary endpoints were total atheroma volume (TAV) and percentage atheroma volume.......3 +/- 9.4% to 42.2 +/- 10.7 p - 0.07),p - 0.91 between groups. Conclusions: Ezetimibe in addition to atorvastatin therapy did not influence NC content, but was associated with regression of coronary atherosclerosis. (C) 2016 Elsevier Inc. All rights reserved....

  20. Social, Organizational, and Contextual Characteristics of Clinical Decision Support Systems for Intensive Insulin Therapy: A Literature Review and Case Study

    Science.gov (United States)

    Campion, Thomas R.; Waitman, Lemuel R.; May, Addison K.; Ozdas, Asli; Lorenzi, Nancy M.; Gadd, Cynthia S.

    2009-01-01

    Introduction: Evaluations of computerized clinical decision support systems (CDSS) typically focus on clinical performance changes and do not include social, organizational, and contextual characteristics explaining use and effectiveness. Studies of CDSS for intensive insulin therapy (IIT) are no exception, and the literature lacks an understanding of effective computer-based IIT implementation and operation. Results: This paper presents (1) a literature review of computer-based IIT evaluations through the lens of institutional theory, a discipline from sociology and organization studies, to demonstrate the inconsistent reporting of workflow and care process execution and (2) a single-site case study to illustrate how computer-based IIT requires substantial organizational change and creates additional complexity with unintended consequences including error. Discussion: Computer-based IIT requires organizational commitment and attention to site-specific technology, workflow, and care processes to achieve intensive insulin therapy goals. The complex interaction between clinicians, blood glucose testing devices, and CDSS may contribute to workflow inefficiency and error. Evaluations rarely focus on the perspective of nurses, the primary users of computer-based IIT whose knowledge can potentially lead to process and care improvements. Conclusion: This paper addresses a gap in the literature concerning the social, organizational, and contextual characteristics of CDSS in general and for intensive insulin therapy specifically. Additionally, this paper identifies areas for future research to define optimal computer-based IIT process execution: the frequency and effect of manual data entry error of blood glucose values, the frequency and effect of nurse overrides of CDSS insulin dosing recommendations, and comprehensive ethnographic study of CDSS for IIT. PMID:19815452

  1. Social, organizational, and contextual characteristics of clinical decision support systems for intensive insulin therapy: a literature review and case study.

    Science.gov (United States)

    Campion, Thomas R; Waitman, Lemuel R; May, Addison K; Ozdas, Asli; Lorenzi, Nancy M; Gadd, Cynthia S

    2010-01-01

    Evaluations of computerized clinical decision support systems (CDSS) typically focus on clinical performance changes and do not include social, organizational, and contextual characteristics explaining use and effectiveness. Studies of CDSS for intensive insulin therapy (IIT) are no exception, and the literature lacks an understanding of effective computer-based IIT implementation and operation. This paper presents (1) a literature review of computer-based IIT evaluations through the lens of institutional theory, a discipline from sociology and organization studies, to demonstrate the inconsistent reporting of workflow and care process execution and (2) a single-site case study to illustrate how computer-based IIT requires substantial organizational change and creates additional complexity with unintended consequences including error. Computer-based IIT requires organizational commitment and attention to site-specific technology, workflow, and care processes to achieve intensive insulin therapy goals. The complex interaction between clinicians, blood glucose testing devices, and CDSS may contribute to workflow inefficiency and error. Evaluations rarely focus on the perspective of nurses, the primary users of computer-based IIT whose knowledge can potentially lead to process and care improvements. This paper addresses a gap in the literature concerning the social, organizational, and contextual characteristics of CDSS in general and for intensive insulin therapy specifically. Additionally, this paper identifies areas for future research to define optimal computer-based IIT process execution: the frequency and effect of manual data entry error of blood glucose values, the frequency and effect of nurse overrides of CDSS insulin dosing recommendations, and comprehensive ethnographic study of CDSS for IIT. Copyright (c) 2009. Published by Elsevier Ireland Ltd.

  2. The efficacy of therapy with DPP-4 inhibitors combined with insulin in patients with type 2 diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Alexander Sergeevich Ametov

    2011-12-01

    Full Text Available Recently, researchers started to pay increasingly more attention to the role of gastrointestinal hormones in regulation of insulin secretion, i.e. glucosehomeostasis. To-day, there are two approaches to the treatment of DM based on the use of GLP-1 effects. One takes advantage of DPP-4 inhibitorsthe other is combination of these agents with various drugs necessitated by heterogeneity of pathophysiological factors responsible for the developmentof DM2. The latter approach ensures multiple therapeutic effects on DM2 and its complications. Many on-going studies are focused on the use ofcombination of DPP-4 inhibitors and insulin. Vildagliptin (Galvus, Novartis Pharma, Switzerland is presently the sole DPP-4 inhibitor approvedfor application with insulin in Russia.Aim. To estimate the efficacy and safety of DPP-4 inhibitor combined with long-acting insulin in the treatment of DM2. Materials and methods. The study group included 18 patients (2 men and 16 women with DM2 treated with long-acting insulin (glargine, humulinNPH for at least 3 months at a mean daily dose of 31.96?4.95 U. The age of the patients averaged 59.9?2.84 years (46-75, DM2 duration8.9?1.18 years (2-15. Parameters of comprehensive glycemic control (FG, PPG, HbA1c, LMWH - low-molecular weight heparins CGM-continuousglucose monitoring were measured using a CGMS system in the beginning and end of the study. Functional activity of pancreatic betbeta-cells and insulinresistance (HOMA-IR, lipid metabolism, and anthropometric characteristics were estimated. Results. Combined therapy resulted in positive dynamics of carbohydrate metabolism within 12 weeks after onset. The functional activity of pancreaticbetbeta-cells significantly (by 157.96 U improved by the end of the study. Changes of HOMA-IR were insignificant. CGM showed that prescription ofvildagliptin to the patients who failed to reach compensation of DM2 with long-acting insulin alone significantly improved glycemic control

  3. Efficacy and tolerability of high-dose phenobarbital in children with focal seizures.

    Science.gov (United States)

    Okumura, Akihisa; Nakahara, Eri; Ikeno, Mitsuru; Abe, Shinpei; Igarashi, Ayuko; Nakazawa, Mika; Takasu, Michihiko; Shimizu, Toshiaki

    2016-04-01

    We retrospectively reviewed the outcomes of children with focal epilepsy treated with oral high-dose phenobarbital. We reviewed data on children (agedphenobarbital (>5 mg/kg/day to maintain a target serum level >40 μg/mL) for at least 6 months. Seizure frequency was evaluated after phenobarbital titration, and 1 and 2 years after high-dose phenobarbital treatment commenced. Treatment was judged effective when seizure frequencies fell by ⩾75%. Seven boys and eight girls were treated. The median age at commencement of high-dose phenobarbital therapy was 30 months. The maximal serum phenobarbital level ranged from 36.5 to 62.9 μg/mL. High-dose PB was effective in seven. In two patients, treatment was transiently effective, but seizure frequency later returned to the baseline. High-dose PB was ineffective in six. No significant association between effectiveness and any clinical variable was evident. Drowsiness was recorded in nine patients, but no patient developed a behavioral problem or hypersensitivity. Oral high-dose phenobarbital was effective in 7 of 15 patients with focal epilepsy and well tolerated. High-dose PB may be useful when surgical treatment is difficult. Copyright © 2015 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  4. Endurance training improves insulin sensitivity and body composition in prostate cancer patients treated with androgen deprivation therapy.

    Science.gov (United States)

    Hvid, Thine; Winding, Kamilla; Rinnov, Anders; Dejgaard, Thomas; Thomsen, Carsten; Iversen, Peter; Brasso, Klaus; Mikines, Kari J; van Hall, Gerrit; Lindegaard, Birgitte; Solomon, Thomas P J; Pedersen, Bente K

    2013-10-01

    Insulin resistance and changes in body composition are side effects of androgen deprivation therapy (ADT) given to prostate cancer patients. The present study investigated whether endurance training improves insulin sensitivity and body composition in ADT-treated prostate cancer patients. Nine men undergoing ADT for prostate cancer and ten healthy men with normal testosterone levels underwent 12 weeks of endurance training. Primary endpoints were insulin sensitivity (euglycemic-hyperinsulinemic clamps with concomitant glucose-tracer infusion) and body composition (dual-energy X-ray absorptiometry and magnetic resonance imaging). The secondary endpoint was systemic inflammation. Statistical analysis was carried out using two-way ANOVA. Endurance training increased VO2max (ml(O2)/min per kg) by 11 and 13% in the patients and controls respectively (PBody weight (Pbody fat mass (FM) (Pbody mass (P=0.99) was unchanged. Additionally, reductions were observed in abdominal (Pcancer patients exhibited improved insulin sensitivity and body composition to a similar degree as eugonadal men.

  5. Clinical evidence and mechanistic basis for vildagliptin’s effect in combination with insulin

    Science.gov (United States)

    Schweizer, Anja; Foley, James E; Kothny, Wolfgang; Ahrén, Bo

    2013-01-01

    Due to the progressive nature of type 2 diabetes, many patients need insulin as add-on to oral antidiabetic drugs (OADs) in order to maintain adequate glycemic control. Insulin therapy primarily targets elevated fasting glycemia but is less effective to reduce postprandial hyperglycemia. In addition, the risk of hypoglycemia limits its effectiveness and there is a concern of weight gain. These drawbacks may be overcome by combining insulin with incretin-based therapies as these increase glucose sensitivity of both the α- and β-cells, resulting in improved postprandial glycemia without the hypoglycemia and weight gain associated with increasing the dose of insulin. The dipeptidyl peptidase-IV (DPP-4) inhibitor vildagliptin has also been shown to protect from hypoglycemia by enhancing glucagon counterregulation. The effectiveness of combining vildagliptin with insulin was demonstrated in three different studies in which vildagliptin decreased A1C levels when added to insulin therapy without increasing hypoglycemia. This was established with and without concomitant metformin therapy. Furthermore, the effectiveness of vildagliptin appears to be greater when insulin is used as a basal regimen as opposed to being used to reduce postprandial hyperglycemia, since improvement in insulin secretion likely plays a minor role when relatively high doses of insulin are administered before meals. This article reviews the clinical experience with the combination of vildagliptin and insulin and discusses the mechanistic basis for the beneficial effects of the combination. The data support the use of vildagliptin in combination with insulin in general and, in line with emerging clinical practice, suggest that treating patients with vildagliptin, metformin, and basal insulin could be an attractive therapeutic option. PMID:23431062

  6. NIST high-dose calibration services

    International Nuclear Information System (INIS)

    Humphreys, J.C.

    1989-01-01

    There is a need for the standardization of high-dose measurements used in the radiation-processing industry in order to provide assured traceability to national standards. NIST provides dosimetry calibration services to this industry. One of these services involves administration of known absorbed doses of gamma rays to customer-supplied dosimeters. The dosimeters are packaged to provide electron equilibrium conditions and are irradiated in a standard 60 Co calibration facility; this provides a calibration of that batch of dosimeters. Another service consists of supplying to a customer calibrated transfer dosimeters for irradiation with the customer's radiation source. The irradiated transfer dosimeters are then returned to NIST for analysis; the results are reported to the customer, providing a calibration of the dose rate of the customer's source. (orig.)

  7. Onyx as radiation detector for high doses

    International Nuclear Information System (INIS)

    Teixeira, Maria Inês; Souza, Divanizia N.; Caldas, Linda V.E.

    2011-01-01

    A study of the thermoluminescent (TL) characteristics of white, black and stripped onyx samples is reported in this work. Onyx is a variety of chalcedony, a form of quartz. The onyx stone is considered nobler than marble. The irradiations were performed using a Gamma-Cell 220 system ( 60 Co). The TL emission curves presented two peaks around 150 °C and 210 °C for all samples. The dose–response curves showed a sublinear behavior between 0.5 Gy and 5 kGy, and the lower detection limit for the white onyx pellets was 1.5 mGy. The main dosimetric characteristics were studied, and the material showed good performance for high dose dosimetry.

  8. High-dose calcium stimulation test in a case of insulinoma masquerading as hysteria.

    Science.gov (United States)

    Nakamura, Yoshio; Doi, Ryuichiro; Kohno, Yasuhiro; Shimono, Dai; Kuwamura, Naomitsu; Inoue, Koichi; Koshiyama, Hiroyuki; Imamura, Masayuki

    2002-11-01

    It is reported that some cases with insulinoma present with neuropsychiatric symptoms and are often misdiagnosed as psychosis. Here we report a case of insulinoma masquerading as hysteria, whose final diagnosis could be made using high-dose calcium stimulation test. A 28-yr-old woman was referred presenting with substupor, mutism, mannerism, restlessness, and incoherence. Laboratory examinations revealed hypoglycemia (33 mg/dL) and detectable insulin levels (9.7 microU/mL), suggesting the diagnosis of insulinoma. However, neither imaging studies nor selective arterial calcium injection (SACI) test with a conventional dose of calcium (0.025 mEq/kg) indicated the tumor. High-dose calcium injection (0.05 mEq/kg) evoked insulin secretion when injected into superior mesenteric artery. A solitary tumor in the head of the pancreas was resected, and her plasma glucose returned to normal. Postoperatively, iv injection of secretin resulted in a normal response of insulin, which was not found preoperatively. This case suggests the usefulness of the SACI test with high-dose of calcium in the case of insulinoma when the standard dose fails to detect such a tumor.

  9. Nonlinear model of high-dose implantation

    International Nuclear Information System (INIS)

    Danilyuk, A.

    2001-01-01

    The models of high-dose implantation, using the distribution functions, are relatively simple. However, they must take into account the variation of the function of distribution of the implanted ions with increasing dose [1-4]. This variation takes place owing to the fact that the increase of the concentration of the implanted ions results in a change of the properties of the target. High-dose implantation is accompanied by sputtering, volume growth, diffusion, generation of defects, formation of new phases, etc. The variation of the distribution function is determined by many factors and is not known in advance. The variation within the framework of these models [1-4] is taken into account in advance by the introduction of intuitive assumptions on the basis of implicit considerations. Therefore, these attempts should be regarded as incorrect. The model prepared here makes it possible to take into account the sputtering of the target, volume growth and additional declaration on the implanted ions. Without any assumptions in relation to the variation of the distribution function with increasing dose. In our model it is assumed that the type of distribution function for small doses in a pure target substance is the same as in substances with implanted ions. A second assumption relates to the type of the distribution function valid for small doses in the given substances. These functions are determined as a result of a large number of theoretical and experimental investigations and are well-known at the present time. They include the symmetric and nonsymmetric Gauss distribution, the Pearson distribution, and others. We examine implantation with small doses of up to 10 14 - 10 15 cm -2 when the accurately known distribution is valid

  10. 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

    Energy Technology Data Exchange (ETDEWEB)

    Vahedi, Shahrzad; Okada, Go; Morrell, Brian; Muzar, Edward; Koughia, Cyril; Kasap, Safa [Department of Electrical and Computer Engineering, University of Saskatchewan, Saskatoon, Saskatchewan S7N 5A9 (Canada); Edgar, Andy; Varoy, Chris [School of Chemical and Physical Sciences and MacDiarmid Institute, Victoria University of Wellington, Kelburn Parade (New Zealand); Belev, George; Wysokinski, Tomasz [Canadian Light Source, Inc., University of Saskatchewan, Saskatoon, Saskatchewan S7N 0X4 (Canada); Chapman, Dean [Department of Anatomy and Cell Biology, University of Saskatchewan, Saskatoon, Saskatchewan S7N 5E5 (Canada)

    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+}.

  11. Insulin and the Brain

    Directory of Open Access Journals (Sweden)

    Grosu Cristina

    2017-12-01

    Full Text Available The brain represents an important site for the action of insulin. Besides the traditionally known importance in glucoregulation, insulin has significant neurotrophic properties and influences the brain activity: insulin influences eating behavior, regulates the storage of energy and several aspects concerning memory and knowledge. Insulin resistance and hyperinsulinism could be associated with brain aging, vascular and metabolic pathologies. Elucidating the pathways and metabolism of brain insulin could have a major impact on future targeted therapies.

  12. High-dose Sulbactam Treatment for Ventilator-Associated Pneumonia Caused by Carbapenem-Resistant

    Directory of Open Access Journals (Sweden)

    In Beom Jeong

    2016-11-01

    Full Text Available Background Several antibiotics can be used to treat ventilator-associated pneumonia caused by carbapenem-resistant A. baumannii (CRAB-VAP including high-dose sulbactam. However, the effectiveness of high-dose sulbactam therapy is not well known. We report our experience with high-dose sulbactam for treatment of CRAB-VAP. Methods Medical records of patients with CRAB-VAP who were given high-dose sulbactam between May 2013 and June 2015 were reviewed. Results Fifty-eight patients with CRAB-VAP were treated with high-dose sulbactam. The mean age was 72.0 ± 15.2 years, and the acute physiology and chronic health evaluation II (APACHE II score was 15.1 ± 5.10 at the time of CRAB-VAP diagnosis. Early clinical improvement was observed in 65.5% of patients, and 30-day mortality was 29.3%. Early clinical failure (odds ratio [OR]: 8.720, confidence interval [CI]: 1.346-56.484; p = 0.023 and APACHE II score ≥ 14 at CRAB-VAP diagnosis (OR: 10.934, CI: 1.047-114.148; p = 0.046 were associated with 30-day mortality. Conclusions High-dose sulbactam therapy may be effective for the treatment of CRAB-VAP. However, early clinical failure was observed in 35% of patients and was associated with poor outcome.

  13. Audits in high dose rate brachytherapy in Brazil

    International Nuclear Information System (INIS)

    Marechal, M.H.; Rosa, L.A.; Velasco, A.; Paiva, E. de; Goncalves, M.; Castelo, L.C.

    2002-01-01

    The lack of well established dosimetry protocols for HDR sources is a point of great concern regarding the uniformity of procedures within a particular country. The main objective of this paper is to report the results of an implementation of the audit program in dosimetry of high dose rate brachytherapy sources used by the radiation therapy centers in Brazil. In Brazil, among 169 radiotherapy centers, 35 have HDR brachytherapy systems. This program started in August 2001 and until now eight radiotherapy services were audited. The audit program consists of the visit in loco to each center and the evaluation of the intensity of the source with a well type chamber specially design for HDR 192 Ir sources. The measurements was carried out with a HDR1000PLUS Brachytherapy Well Type Chamber and a MAX 4000 Electrometer, both manufactured by Standard Imaging Inc. The chamber was calibrated in air kerma strength by the Accredited Dosimetry Calibration Laboratory, Department of Medical Physics, University of Wisconsin in the USA. The same chamber was calibrated in Brazil using a 192 lr high dose rate source whose intensity was determined by 60 Co gamma rays and 250 kV x rays interpolation methodology. The Nk of 60 Co and 250 kV x rays were provided by the Brazilian National Standard Laboratory for Ionizing Radiation (LMNRI)

  14. Pharmacoeconomic analysis of clinical efficiency of combined metformin (Siofor - insulin therapy in patients with type 2 diabetes mellitus

    Directory of Open Access Journals (Sweden)

    I Yu Demidova

    2009-06-01

    Full Text Available Aim. To assess expedience of metformin combination with long-acting insulin, determine optimal doses of metformin for patients with type 2 diabetesmellitus (DM2, and accomplish pharmacoeconomic analysis of clinical efficiency of various therapeutic modalities. Materials and methods. Patients with decompensated DM2 (n=126 were under observation for 1 year during which they received rational hypoglycemictherapy with metformin and long-acting insulin (LAI at bedtime, with the dose being titrated until the desired level of glycemic control wasachieved. The patients were randomly allocated to the following 3 groups: group 1 (sulponylurea derivatives (SUD, LAI, and metformin at a doseof 1000 mg b.i.d., group 2 (SUD, LAI, and metformin at 500 mg b.i.d., group 3 (SUD and LAI. In case of postprandial glycemia >9 mmol/l at amaximum dose of SUD, it was replaced by short-acting insulin. Cost-effectiveness analysis of different therapeutic regimes was performed. Results. The cost of examination and treatment of patients given SUD and LAI in combination with metformin at a daily dose of 2000 mg to achievethe desired quality of glycemic control was lower compared with two other groups. Moreover, this therapy was most efficacious and ensured the desiredlevel of glycemic control in a greater number of patients. Cost-effectiveness analysis confirmed advantages of this treatment. Conclusion. Combined hypoglycemic therapy with SUD, LAI, and metformin (200 mg daily has the advantage of lowest cost and maximum efficiencycompared with other modalities.

  15. Successful Management of Insulin Allergy and Autoimmune Polyendocrine Syndrome Type 4 with Desensitization Therapy and Glucocorticoid Treatment: A Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Joselyn Rojas

    2014-01-01

    Full Text Available Introduction. Insulin allergy is a rare complication of insulin therapy, especially in type 1 diabetes mellitus (T1DM. Key manifestations are hypersensitivity-related symptoms and poor metabolic control. T1DM, as well as insulin allergy, may develop in the context of autoimmune polyendocrine syndrome (APS, further complicating management. Case Report. A 17-year-old male patient, diagnosed with T1DM, was treated with various insulin therapy schemes over several months, which resulted in recurrent anaphylactoid reactions and poor glycemic control, after which he was referred to our Endocrinology and Immunology Department. A prick test was carried out for all commercially available insulin presentations and another insulin scheme was designed but proved unsuccessful. A desensitization protocol was started with Glargine alongside administration of Prednisone, which successfully induced tolerance. Observation of skin lesions typical of vitiligo prompted laboratory workup for other autoimmune disorders, which returned positive for autoimmune gastritis/pernicious anemia. These findings are compatible with APS type 4. Discussion. To our knowledge, this is the first documented case of insulin allergy in type 4 APS, as well as this particular combination in APS. Etiopathogenic components shared by insulin allergy and APS beg for further research in immunogenetics to further comprehend pathophysiologic aspects of these diseases.

  16. High Prevalence of Dyslipidemia and Insulin Resistance in HIV-infected Prepubertal African Children on Antiretroviral Therapy.

    Science.gov (United States)

    Innes, Steve; Abdullah, Kameelah L; Haubrich, Richard; Cotton, Mark F; Browne, Sara H

    2016-01-01

    Data describing the true extent of antiretroviral therapy (ART)-induced dyslipidemia and insulin resistance in perinatally infected children on ART in Africa are sparse. Fasting total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides, insulin and glucose were performed on the first 100 of 190 pediatric ART clinic attendees. Diet assessment was performed by a trained dietician. Lipoatrophy was formally graded by consensus between 2 expert HIV pediatricians. Durations of previous ART exposures, clinical stage, pre-ART viral load, nadir and current CD4 were recorded. Dual-energy X-ray absorptiometry was performed on a subset of 42 patients selected semi-randomly. Prevalences of insulin resistance, abnormal total cholesterol, LDL, HDL and triglyceride were 10%, 13%, 12%, 13% and 9%, respectively. Overall, 40% had at least 1 lipid abnormality or insulin resistance. Adjusted mean LDL cholesterol increased by 0.24 mmol/L for each additional year of cumulative lopinavir/r exposure (P = 0.03) after correcting for age, gender, body mass index, previous stavudine exposure, age at ART initiation, dietary fat and refined carbohydrate, whereas adjusted mean LDL cholesterol was 0.9 mmol/L higher in children exposed to efavirenz within the previous 6 months (P = 0.02). Adjusting for age, gender and ethnicity, dual-energy X-ray absorptiometry revealed that greater trunk fat and lower peripheral subcutaneous fat were associated with elevated triglycerides but not with total cholesterol, LDL, HDL or homeostatic model assessment. Similarly, the presence of visually obvious lipoatrophy was associated with elevated triglycerides but not with total cholesterol, LDL, HDL, homeostatic model assessment or lactate. Prevalences of insulin resistance and dyslipidemia were high. Cumulative lopinavir is an independent risk factor for dyslipidemia, with efavirenz exposure having only transitory effect.

  17. Prospective hormone study of hypothalamic-pituitary function in patients with nasopharyngeal carcinoma after high dose irradiation

    International Nuclear Information System (INIS)

    Chen, Ming-Shen; Lin, Fang-Jen; Huang, Miau-Ju; Wang, Pei-Wan; Tang, Simon; Leung, Wei-Man; Leung, Wan

    1989-01-01

    With the aim of evaluating the effect of high dose irradiation (6,500 cGy/36 fractions or higher) to pituitary fossa, a prospective study was carried out in patients with nasopharyngeal cancer by a serial determination of several hormones in the serum, before and after the course of radiation therapy (RT). The radiation treatment field was at least 1 cm above the skull base with bilateral parallel opposing fields. Hormone assays were performed three times on each patient: (1)prior to, (2)one month after, (3)15-18 months after radiation therapy. The study included determination of serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), thyroid-stimulating hormone (TSH), cortisol, growth hormone (GH) and prolactin concentrations and LH-releasing hormone, thyrotrophin-releasing hormone stimulation and insulin tolerance tests were also carried out. Complete profiles were obtained in 24 patients (16 males and 8 females), aged 16-67 years. The results showed a significant decrease in the level of serum peak value of LH in males 18 months after therapy, and also in GH both one month and 18 months after therapy. A significant increase in the peak value of serum TSH was observed after therapy. Decreased serum FSH, cortisol and prolactin levels were noted, but these did not reach statistical significance. The decrease in GH level appeared earlier and was more sensitive than that found for the other hormones, and could prove to be a useful parameter for clinical evaluation. None of the patients showed any clinically recognizable symptoms or signs of hormone deficiency in the 18-33 months following completion of the radiation therapy. (author)

  18. Influence of dietary protein on postprandial blood glucose levels in individuals with Type 1 diabetes mellitus using intensive insulin therapy.

    Science.gov (United States)

    Paterson, M A; Smart, C E M; Lopez, P E; McElduff, P; Attia, J; Morbey, C; King, B R

    2016-05-01

    To determine the effects of protein alone (independent of fat and carbohydrate) on postprandial glycaemia in individuals with Type 1 diabetes mellitus using intensive insulin therapy. Participants with Type 1 diabetes mellitus aged 7-40 years consumed six 150 ml whey isolate protein drinks [0 g (control), 12.5, 25, 50, 75 and 100] and two 150 ml glucose drinks (10 and 20 g) without insulin, in randomized order over 8 days, 4 h after the evening meal. Continuous glucose monitoring was used to assess postprandial glycaemia. Data were collected from 27 participants. Protein loads of 12.5 and 50 g did not result in significant postprandial glycaemic excursions compared with control (water) throughout the 300 min study period (P > 0.05). Protein loads of 75 and 100 g resulted in lower glycaemic excursions than control in the 60-120 min postprandial interval, but higher excursions in the 180-300 min interval. In comparison with 20 g glucose, the large protein loads resulted in significantly delayed and sustained glucose excursions, commencing at 180 min and continuing to 5 h. Seventy-five grams or more of protein alone significantly increases postprandial glycaemia from 3 to 5 h in people with Type 1 diabetes mellitus using intensive insulin therapy. The glycaemic profiles resulting from high protein loads differ significantly from the excursion from glucose in terms of time to peak glucose and duration of the glycaemic excursion. This research supports recommendations for insulin dosing for large amounts of protein. © 2015 The Authors. Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.

  19. Insulin therapy does not interfere with venous endothelial function evaluation in patients with type 2 diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Antônio Marcos Vargas da Silva

    2010-01-01

    Full Text Available INTRODUCTION: Endothelium-dependent dilation is improved in insulin-treated diabetic patients, but this effect is probably due to improved glycemic control. The objective of the present study was to compare endothelium-dependent dilation in patients with well-controlled type 2 diabetes who are or are not using insulin as part of their therapy. METHODS: We studied 27 patients with type 2 diabetes (11 women, 60.3 years ± 6 years, with HbA1c < 7% and no nephropathy, including 16 patients treated with anti-diabetic agents (No-Ins, 8 women and 11 patients treated with insulin alone or in combination with anti-diabetic agents (Ins, 3 women. Endothelial function was evaluated by the dorsal hand vein technique, which measures changes in vein diameter in response to phenylephrine, acetylcholine (endothelium-dependent vasodilation and sodium nitroprusside (endothelium-independent vasodilation. RESULTS: Age, systolic blood pressure (No-Ins: 129.4 mmHg ± 11.8 mmHg, Ins: 134.8 mmHg ± 12.0 mmHg; P= 0.257, HbA1c, lipids and urinary albumin excretion rate [No-Ins: 9 mg/24 h (0-14.1 mg/24 h vs. Ins: 10.6 mg/24 h (7.5-14.4 mg/24 h, P=0.398] were similar between groups. There was no difference between endothelium-dependent vasodilation of the No-Ins group (59.3% ± 26.5% vs. the Ins group (54.0% ± 16.3%; P=0.526. Endothelium-independent vasodilation was also similar between the No-Ins (113.7% ± 35.3% and Ins groups (111.9% ± 28.5%; P=0.888. CONCLUSIONS: Subcutaneous insulin therapy does not interfere with venous endothelial function in type 2 diabetes when glycemic and blood pressure control are stable.

  20. Insulin therapy does not interfere with venous endothelial function evaluation in patients with type 2 diabetes mellitus.

    Science.gov (United States)

    Silva, Antônio Marcos Vargas da; Penno, Luciana de Moraes; Bertoluci, Marcello Casaccia; Irigoyen, Maria Cláudia; Schaan, Beatriz D'Agord

    2010-01-01

    Endothelium-dependent dilation is improved in insulin-treated diabetic patients, but this effect is probably due to improved glycemic control. The objective of the present study was to compare endothelium-dependent dilation in patients with well-controlled type 2 diabetes who are or are not using insulin as part of their therapy. We studied 27 patients with type 2 diabetes (11 women, 60.3 years ± 6 years, with HbA1c < 7% and no nephropathy), including 16 patients treated with anti-diabetic agents (No-Ins, 8 women) and 11 patients treated with insulin alone or in combination with anti-diabetic agents (Ins, 3 women). Endothelial function was evaluated by the dorsal hand vein technique, which measures changes in vein diameter in response to phenylephrine, acetylcholine (endothelium-dependent vasodilation) and sodium nitroprusside (endothelium-independent vasodilation). Age, systolic blood pressure (No-Ins: 129.4 mmHg ± 11.8 mmHg, Ins: 134.8 mmHg ± 12.0 mmHg; P= 0.257), HbA1c, lipids and urinary albumin excretion rate [No-Ins: 9 mg/24 h (0-14.1 mg/24 h) vs. Ins: 10.6 mg/24 h (7.5-14.4 mg/24 h), P=0.398] were similar between groups. There was no difference between endothelium-dependent vasodilation of the No-Ins group (59.3% ± 26.5%) vs. the Ins group (54.0% ± 16.3%; P=0.526). Endothelium-independent vasodilation was also similar between the No-Ins (113.7% ± 35.3%) and Ins groups (111.9% ± 28.5%; P=0.888). Subcutaneous insulin therapy does not interfere with venous endothelial function in type 2 diabetes when glycemic and blood pressure control are stable.

  1. Ionization chamber for high dose measurements

    International Nuclear Information System (INIS)

    Rodrigues Junior, Ary de Araujo

    2005-01-01

    Industrial gamma irradiators facilities are designed for processing large amounts of products, which are exposed to large doses of gamma radiation. The irradiation, in industrial scale, is usually carried out in a dynamic form, where the products go through a 60 Co gamma source with activity of TBq to P Bq (k Ci to MCi). The dose is estimated as being directly proportional to the time that the products spend to go through the source. However, in some situations, mainly for research purposes or for validation of customer process following the ISO 11137 requirements, it is required to irradiate small samples in a static position with fractional deliver doses. The samples are put inside the irradiation room at a fixed distance from the source and the dose is usually determined using dosimeters. The dose is only known after the irradiation, by reading the dosimeter. Nevertheless, in the industrial irradiators, usually different kinds of products with different densities go through between the source and the static position samples. So, the dose rate varies in function of the product density. A suitable methodology would be to monitor the samples dose in real time, measuring the dose on line with a radiation detector, which would improve the dose accuracy and avoid the overdose. A cylindrical ionization chamber of 0.9 cm 3 has been developed for high-doses real-time monitoring, during the sample irradiation at a static position in a 60 Co gamma industrial plant. Nitrogen and argon gas at pressure of 10 exp 5 Pa (1 bar) was utilized to fill the ionization chamber, for which an appropriate configuration was determined to be used as a detector for high-dose measurements. To transmit the signal generated in the ionization chamber to the associated electronic and processing unit, a 20 m mineral insulated cable was welded to the ionization chamber. The signal to noise ratio produced by the detector was about 100. The dosimeter system was tested at a category I gamma

  2. Insulin biosimilars: the impact on rapid-acting analogue-based therapy.

    Science.gov (United States)

    Franzè, S; Cilurzo, F; Minghetti, P

    2015-04-01

    The impending expiration of patent protection for recombinant insulins provides the opportunity to introduce cost-saving copies, named biosimilars, onto the market. Although there is broad experience in the production and characterisation of insulins, the development of copies is still a challenge. In this paper, the main features of insulins and the EU regulatory framework for their biosimilar products are reviewed. The main focus is on rapid-acting insulin analogues (Humalog(®); Novolog(®)/NovoRapid(®); Apidra(®)). Since they differ by one or two amino acids in chain B, production of one biosimilar for all three drug products is not feasible. However, from post-marketing-collected clinical data, rapid-acting insulin analogues seem to have similar therapeutic efficacy. It is reasonable to suppose that, for prescription to treatment-naïve patients, the cheaper biosimilar would be the preferred choice of physicians, either spontaneously or induced by health insurance. Therefore, its introduction will affect the market share of all the other rapid-acting insulin analogues.

  3. Race, socioeconomic status, and treatment center are associated with insulin pump therapy in youth in the first year following diagnosis of type 1 diabetes

    Science.gov (United States)

    Increasing numbers of children and adolescents with type 1 diabetes (T1D) have been placed on insulin pump therapy. Nevertheless, data are limited regarding patterns of pump use during the first year of treatment and the clinical and socioeconomic factors associated with early use of pump therapy. T...

  4. Relationship between irreversible alopecia and exposure to cyclophosphamide, thiotepa and carboplatin (CTC) in high-dose chemotherapy

    NARCIS (Netherlands)

    de Jonge, M. E.; Mathôt, R. A. A.; Dalesio, O.; Huitema, A. D. R.; Rodenhuis, S.; Beijnen, J. H.

    2002-01-01

    Reversible alopecia is a commonly observed, important and distressing complication of chemotherapy. Permanent alopecia, however, is rare after standard-dose therapy, but has occasionally been observed after high-dose chemotherapy with cyclophosphamide, thiotepa and carboplatin (CTC). We evaluated

  5. Professional continuous glucose monitoring for the identification of type 1 diabetes mellitus among subjects with insulin therapy.

    Science.gov (United States)

    Chen, Yin-Chun; Huang, Yu-Yao; Li, Hung-Yuan; Liu, Shih-Wei; Hsieh, Sheng-Hwu; Lin, Chia-Hung

    2015-01-01

    The identification of type 1 diabetes in diabetic subjects receiving insulin therapy is sometimes difficult. The purpose of this study is to evaluate whether results of professional continuous glucose monitoring can improve the identification of type 1 diabetes.From 2007 to 2012, 119 adults receiving at least twice-daily insulin therapy and professional continuous glucose monitoring were recruited. Type 1 diabetes was diagnosed by endocrinologists according to American Diabetes Association standards, including a very low C-peptide level (diabetic ketoacidosis. Continuous glucose monitoring was applied for 3 days.Among 119 subjects, 86 were diagnosed with type 1 diabetes. Subjects with type 1 diabetes were younger (33.8 vs 52.3 years old, P 1), had lower body mass index (BMI, 21.95 vs 24.42, P = 0.003), lower serum creatinine (61.77  vs 84.65 μmol/L, P = 0.001), and higher estimated glomerular filtration rate (108.71 vs 76.48 mg/mL/min/1.73m2, P 1) than subjects with type 2 diabetes. Predictive scores for identification of type 1 diabetes were constructed, including age, BMI, average mean amplitude of glucose excursion in days 2 and 3, and the area under the curve of nocturnal hyperglycemic and hypoglycemic states. The area under the receiver operating characteristic curve was 0.90. With the cutoff of 0.58, the sensitivity was 86.7% and the specificity was 80.8%. The good performance was validated by the leave-one-out method (sensitivity 83.3%, specificity 73.1%).Professional continuous glucose monitoring is a useful tool that improves identification of type 1 diabetes among diabetic patients receiving insulin therapy.

  6. Endothelial function and insulin resistance in polycystic ovary syndrome: the effects of medical therapy.

    Science.gov (United States)

    Teede, Helena J; Meyer, Caroline; Hutchison, Samantha K; Zoungas, Sophia; McGrath, Barry P; Moran, Lisa J

    2010-01-01

    To assess the interaction between insulin resistance and endothelial function and the optimal treatment strategy addressing cardiovascular risk in polycystic ovary syndrome. Randomized controlled trial. Controlled clinical study. Overweight age- and body mass index-matched women with polycystic ovary syndrome. Six months metformin (1 g two times per day, n = 36) or oral contraceptive pill (OCP) (35 microg ethinyl E(2)-2 mg cytoproterone acetate, n = 30). Fasting and oral glucose tolerance test glucose and insulin levels, endothelial function (flow-mediated dilation, asymmetric dimethylarginine, plasminogen activator inhibitor-1, von Willebrand factor), inflammatory markers (high-sensitivity C-reactive protein), lipids, and hyperandrogenism. The OCP increased levels of glucose and insulin on oral glucose tolerance test, high-sensitivity C-reactive protein, triglycerides, and sex-hormone binding globulin and decreased levels of low-density lipoprotein cholesterol and T. Metformin decreased levels of fasting insulin, oral glucose tolerance test insulin, high-density lipoprotein cholesterol, and high-sensitivity C-reactive protein. Flow-mediated dilation increased only with metformin (+2.2% +/- 4.8%), whereas asymmetric dimethylarginine decreased equivalently for OCP and metformin (-0.3 +/- 0.1 vs. -0.1 +/- 0.1 mmol/L). Greater decreases in plasminogen activator inhibitor-1 occurred for the OCP than for metformin (-1.8 +/- 1.6 vs. -0.7 +/- 1.7 U/mL). In polycystic ovary syndrome, metformin improves insulin resistance, inflammatory markers, and endothelial function. The OCP worsens insulin resistance and glucose homeostasis, inflammatory markers, and triglycerides and has neutral or positive endothelial effects. The effect of the OCP on cardiovascular risk in polycystic ovary syndrome is unclear. Copyright 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  7. Variability of Basal Rate Profiles in Insulin Pump Therapy and Association with Complications in Type 1 Diabetes Mellitus.

    Science.gov (United States)

    Laimer, Markus; Melmer, Andreas; Mader, Julia K; Schütz-Fuhrmann, Ingrid; Engels, Heide-Rose; Götz, Gabriele; Pfeifer, Martin; Hermann, Julia M; Stettler, Christoph; Holl, Reinhard W

    2016-01-01

    Traditionally, basal rate profiles in continuous subcutaneous insulin infusion therapy are individually adapted to cover expected insulin requirements. However, whether this approach is indeed superior to a more constant BR profile has not been assessed so far. This study analysed the associations between variability of BR profiles and acute and chronic complications in adult type 1 diabetes mellitus. BR profiles of 3118 female and 2427 male patients from the "Diabetes-Patienten-Verlaufsdokumentation" registry from Germany and Austria were analysed. Acute and chronic complications were recorded 6 months prior and after the most recently documented basal rate. The "variability index" was calculated as variation of basal rate intervals in percent and describes the excursions of the basal rate intervals from the median basal rate. The variability Index correlated positively with severe hypoglycemia (r = .06; p1), hypoglycemic coma (r = .05; p = 0.002), and microalbuminuria (r = 0.05; p = 0.006). In addition, a higher variability index was associated with higher frequency of diabetic ketoacidosis (r = .04; p = 0.029) in male adult patients. Logistic regression analysis adjusted for age, gender, duration of disease and total basal insulin confirmed significant correlations of the variability index with severe hypoglycemia (β = 0.013; p1) and diabetic ketoacidosis (β = 0.012; p = 0.017). Basal rate profiles with higher variability are associated with an increased frequency of acute complications in adults with type 1 diabetes.

  8. High dose gamma-ray standard

    International Nuclear Information System (INIS)

    Macrin, R.; Moraru, R.

    1999-01-01

    The high gamma-ray doses produced in a gamma irradiator are used, mainly, for radiation processing, i.e. sterilization of medical products, processing of food, modifications of polymers, irradiation of electronic devices, a.s.o. The used absorbed doses depend on the application and cover the range 10 Gy to 100 MGy. The regulations in our country require that the response of the dosimetry systems, used for the irradiation of food and medical products, be calibrated and traceable to the national standards. In order to be sure that the products receive the desired absorbed dose, appropriate dosimetric measurements must be performed, including the calibration of the dosemeters and their traceability to the national standards. The high dose gamma-ray measurements are predominantly based on the use of reference radiochemical dosemeters. Among them the ferrous sulfate can be used as reference dosemeter for low doses (up to 400 Gy) but due to its characteristics it deserves to be considered a standard dosemeter and to be used for transferring the conventional absorbed dose to other chemical dosemeters used for absorbed doses up to 100 MGy. The study of the ferrous sulfate dosemeter consisted in preparing many batches of solution by different operators in quality assurance conditions and in determining for all batches the linearity, the relative intrinsic error, the repeatability and the reproducibility. The principal results are the following: the linear regression coefficient: 0.999, the relative intrinsic error: max.6 %, the repeatability (for P* = 95 %): max.3 %, the reproducibility (P* = 95%): max.5 %. (authors)

  9. Short-term intensive insulin therapy could be the preferred option for new onset Type 2 diabetes mellitus patients with HbA1c > 9.

    Science.gov (United States)

    Weng, Jianping

    2017-10-01

    Type 2 diabetes mellitus (T2DM) is a heterogeneous disease. Currently, the typical clinical therapeutic pathway for the disease consists of the stepwise addition of antihyperglycemic preparations over time, followed lastly by insulin therapy when functional β-cell capacity is severely deteriorated. Recognizing the complexity of disease management, personalized (precision) medicine approaches may enable the physician to tailor diabetes treatment based on HbA1c levels, body mass index (BMI), efficacy, risk of hypoglycemia, risk of weight gain, age, safety, cost, and even genetic characteristics. Although insulin therapy has traditionally been recommended as the last option in the sequential treatment algorithm of T2DM, it is notable that several guidelines and consensus statements suggest consideration of insulin as part of a first-line regimen. In the American Association of Clinical Endocrinologists (AACE)/American College of Endocrinology (ACE) comprehensive T2DM 2017 management algorithm, insulin is recommended for T2DM patients presenting with symptoms and an HbA1c >9.0%. In addition, the American Diabetes Association (ADA)/European Association for the Study of Diabetes (EASD) consensus statement recommends initial insulin therapy as an option when HbA1c ≥9%, and definite consideration with HbA1c ≥10-12%, and mentions that it may be possible to taper off insulin once initial glucotoxicity is reversed and to consider transfer to other types of non-insulin therapies. Based on accumulating evidence, an expert group has endorsed the concept of short-term intensive insulin (STII) therapy as an option for some patients with T2DM at the time of diagnosis. Notably, the latest Israeli guidelines suggest considering immediate, sometimes short-term, insulin treatment for patients with HbA1c >9% or with symptoms. It has been reported that nearly one-quarter (23%) of newly diagnosed T2DM patients in the US had an HbA1c ≥9.0% prior to initiation of treatment. For such

  10. Efficacy of Insulin Pump Therapy on Diabetes Treatment Satisfaction and Glycemic Control Among Patients with Type 1 Diabetes Mellitus in Saudi Arabia: A Prospective Study

    OpenAIRE

    Al Hayek, Ayman A.; Robert, Asirvatham A.; Al Dawish, Mohamed A.; Braham, Rim B.; Goudeh, Hanouf S.; Al Sabaan, Fahad S.

    2015-01-01

    Introduction The aim of this study was to explore the impact of insulin pump therapy on diabetes treatment satisfaction and glycemic control among patients with type 1 diabetes mellitus (T1DM) in Saudi Arabia. Methods A 6-month, prospective study was conducted among 47 patients (aged 17?24?years) with T1DM who attended the Insulin Pump Clinic at Prince Sultan Military Medical City, Riyadh, Saudi Arabia, between April 2014 and November 2014. The respondents were purposively and conveniently se...

  11. Influence of orlistat therapy on serum insulin level and morphological and functional parameters of peripheral arterial circulation in obese patients

    Directory of Open Access Journals (Sweden)

    Hajduković Zoran

    2005-01-01

    Full Text Available Background/Aim. Insulin resistance is related to accelerated atherosclerosis, whereas weight loss is associated with the increasing insulin sensitivity, the improvement of functional and the morphological parameters of arterial circulation, and the reduction of cardiovascular morbidity and mortality. The aim of our study was to evaluate the influence of orlistat treatment on serum insulin level and functional and morphologic parameters of peripheral arterial circulation. Methods. We conducted a prospective, randomized, double − blind, placebo − controlled study. Thirty patients with body mass index over 30 kg/m2 normotensive, nonsmokers, without clinically manifested cardiovascular disease or diabetes were randomly assigned either orlistat (120 mg, 3 times daily; n = 20 or placebo (n = 10 in a double − blind manner. All of the patients were on individually calculated hypocaloric diet. The follow-up period was 24 weeks. Arterial pressure, fasting serum glucose and insulin level, triglycerides, total cholesterol and low density lipoprotein-cholesterol were determined at the beginning, following 3 and 6 months. Also, the intima − media thickness of right superficial femoral artery and the mean blood flow velocity were determined with ultrasonography. Results. Inside the period of 3 and 6 months, there were the greater reductions of body mass index, arterial pressure, fasting glucose and insulin level, total cholesterol, low density lipoproteins, as well as the greater reductions of mean velocity blood flow and peripheral pulse pressure in the orlistat group vs the placebo group (p < 0.01. Greater reductions in the waist circumference and intima − media thickness were registered following 6 months in the orlistat vs the placebo group (p < 0.01. Conclusion. In the group of obese patients orlistat therapy reduced risk factors, serum insulin level and improved early arterial functional changes as assessed with the reductions of the mean

  12. Effect of high dose thiamine therapy on activity and molecular ...

    African Journals Online (AJOL)

    Commonest form of diabetes mellitus is Type 2, treated with oral hypoglycemic agents, which often carry potential adverse effects and do not address the intracellular metabolism of glucose. Thiamine is an essential co-factor for vital subcellular enzymes and has potential to benefit Type 2 diabetics. This study was therefore ...

  13. Radiation Sialadenitis Induced by High-dose Radioactive Iodine Therapy

    International Nuclear Information System (INIS)

    Jeong, Shin Young; Lee, Jaetae

    2010-01-01

    Radioactive iodine ( 131 I) is accumulated in the thyroid tissue and plays an important role in the treatment of differentiated papillary and follicular cancers after thyroidectomy. Simultaneously, 131 I is concentrated in the salivary glands and secreted into the saliva. Dose-related damage to the salivary parenchyma results from the 131 I irradiation. Salivary gland swelling and pain, usually involving the parotid, can be seen. The symptoms may develop immediately after a therapeutic dose of 131 I and/or months later and progress in intensity with time. In conjunction with the radiation sialadenitis, secondary complications reported include xerostomia, taste alterations, infection, increases in caries, facial nerve involvement, candidiasis, and neoplasia. Prevention of 131 I sialadenitis may involve the use of sialogogic agents to hasten the transit time of the radioactive iodine through the salivary glands. However, studies are not available to delineate the efficacy of this approach. Treatment of the varied complications that may develop encompass numerous approaches and include gland massage, sialogogic agents, duct probing, antibiotics, mouthwashes, good oral hygiene, and adequate hydration. Recently interventional sialoendoscopy has been introduced an effective tool for the management of patients with 131 I-induced sialadenitis that is unresponsive to medical treatment.

  14. Radiation Sialadenitis Induced by High-dose Radioactive Iodine Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, Shin Young; Lee, Jaetae [Kyungpook National University Hospital, Daegu (Korea, Republic of)

    2010-06-15

    Radioactive iodine ({sup 131}I) is accumulated in the thyroid tissue and plays an important role in the treatment of differentiated papillary and follicular cancers after thyroidectomy. Simultaneously, {sup 131}I is concentrated in the salivary glands and secreted into the saliva. Dose-related damage to the salivary parenchyma results from the {sup 131}I irradiation. Salivary gland swelling and pain, usually involving the parotid, can be seen. The symptoms may develop immediately after a therapeutic dose of {sup 131}I and/or months later and progress in intensity with time. In conjunction with the radiation sialadenitis, secondary complications reported include xerostomia, taste alterations, infection, increases in caries, facial nerve involvement, candidiasis, and neoplasia. Prevention of {sup 131}I sialadenitis may involve the use of sialogogic agents to hasten the transit time of the radioactive iodine through the salivary glands. However, studies are not available to delineate the efficacy of this approach. Treatment of the varied complications that may develop encompass numerous approaches and include gland massage, sialogogic agents, duct probing, antibiotics, mouthwashes, good oral hygiene, and adequate hydration. Recently interventional sialoendoscopy has been introduced an effective tool for the management of patients with {sup 131}I-induced sialadenitis that is unresponsive to medical treatment.

  15. Symptoms of depression and diabetes-specific emotional distress are associated with a negative appraisal of insulin therapy in insulin-naive patients with Type 2 diabetes mellitus. A study from the European Depression in Diabetes [EDID] Research Consortium

    NARCIS (Netherlands)

    Makine, C.; Karsidag, C.; Kadioglu, P.; Ilkova, H.; Karsidag, K.; Skovlund, S.E.; Snoek, F.J.; Pouwer, F.

    2009-01-01

    Aims: A meta-analysis concluded that depression is associated with poor glycaemic control in Type 2 diabetes (DM2). In DM2 patients with deteriorating glycaemic control, the initiation of insulin therapy is often postponed. The aim of the present study was to determine whether symptoms of depression

  16. Insulin-like growth factor family and combined antisense approach in therapy of lung carcinoma.

    OpenAIRE

    Pavelić, Jasminka; Pavelić, Ljubomir; Karadza, Jerolim; Krizanac, Simun; Unesić, Josip; Spaventi, Sime; Pavelić, Kresimir

    2002-01-01

    BACKGROUND: Perturbation in a level of any peptide from insulin-like growth factor (IGF) family (ligands, receptors, and binding proteins) seems to be implicated in lung cancer formation; IGF ligands and IGF-I receptor through their mitogenic and anti-apoptotic action, and the mannose 6-phosphate/insulin-like growth factor II receptor (M6-P/IGF-IIR) possibly as a tumor suppressor. MATERIALS AND METHODS: To determine the identity, role, and mutual relationship of IGFs in lung cancer growth and...

  17. INSULIN AND INSULIN RESISTANCE: NEW MOLECULE MARKERS AND TARGET MOLECULE FOR THE DIAGNOSIS AND THERAPY OF DISEASES OF THE CENTRAL NERVOUS SYSTEM

    Directory of Open Access Journals (Sweden)

    A. B. Salmina

    2013-01-01

    Full Text Available The review summarizes current data on the role of insulin in the regulation of t glucose metabolism in the central nervous system at physiologic and pathologic conditions. For many years, the brain has been considered as an insulin-independent organ which utilizes glucose without insulin activity. However, it is become clear now that insulin not only regulates glucose transport and metabolism, but also has modulatory efftects in impact on excitability, proliferation and differentiation of brain progenitor cells, synaptic plasticity and memory formation, secretion of neurotransmitters, apoptosis. We have critically reviewed literature information and our own data on the role of insulin and insulin resistance in neuron-glia metabolic coupling, regulation of NAD+ metabolism and action of NAdependent enzymes, neurogenesis, brain development in (pathophysiological conditions. The paper clarifies interrelations between alterations in glucose homeostasis, development of insulin resistance and development of neurodegeneration (Alzheimer's disease and Parkinson's disease, autism, stroke, and depression. We discuss the application of novel molecular markers of insulin resistance (adipokines, α-hydroxybutyrate, BDNF, insulin-regulated aminopeptidase, provasopressin and molecular targets for diagnostics and treatment of brain disorders associated with insulin resistance.

  18. Perioperative Interstitial High-Dose-Rate Brachytherapy for the Treatment of Recurrent Keloids

    DEFF Research Database (Denmark)

    Jiang, Ping; Baumann, René; Dunst, Jürgen

    2016-01-01

    PURPOSE: To prospectively evaluate high-dose-rate brachytherapy in the treatment of therapy-resistant keloids and report first results, with emphasis on feasibility and early treatment outcome. METHODS AND MATERIALS: From 2009 to 2014, 24 patients with 32 recurrent keloids were treated with immed...

  19. Occlusion-amblyopia following high dose oral levodopa combined with part time patching

    OpenAIRE

    Mihir Kothari

    2014-01-01

    Part time occlusion therapy is not reported to cause occlusion (reverse) amblyopia. However, when combined with high dose oral levodopa, an increase in the plasticity of the visual cortex can lead to occlusion amblyopia. In this case report, we describe a six year old child who developed occlusion amblyopia following part time patching combined with oral levodopa.

  20. Occlusion-amblyopia following high dose oral levodopa combined with part time patching.

    Science.gov (United States)

    Kothari, Mihir

    2014-12-01

    Part time occlusion therapy is not reported to cause occlusion (reverse) amblyopia. However, when combined with high dose oral levodopa, an increase in the plasticity of the visual cortex can lead to occlusion amblyopia. In this case report, we describe a six year old child who developed occlusion amblyopia following part time patching combined with oral levodopa.

  1. Occlusion-amblyopia following high dose oral levodopa combined with part time patching

    Directory of Open Access Journals (Sweden)

    Mihir Kothari

    2014-01-01

    Full Text Available Part time occlusion therapy is not reported to cause occlusion (reverse amblyopia. However, when combined with high dose oral levodopa, an increase in the plasticity of the visual cortex can lead to occlusion amblyopia. In this case report, we describe a six year old child who developed occlusion amblyopia following part time patching combined with oral levodopa.

  2. Effect of intensive insulin therapy on macular biometrics, plasma VEGF and its soluble receptor in newly diagnosed diabetic patients.

    Science.gov (United States)

    Hernández, Cristina; Zapata, Miguel A; Losada, Eladio; Villarroel, Marta; García-Ramírez, Marta; García-Arumí, José; Simó, Rafael

    2010-07-01

    To evaluate whether intensive insulin therapy leads to changes in macular biometrics (volume and thickness) in newly diagnosed diabetic patients with acute hyperglycaemia and its relationship with serum levels of vascular endothelial growth factor (VEGF) and its soluble receptor (sFlt-1). Twenty-six newly diagnosed diabetic patients admitted to our hospital to initiate intensive insulin treatment were prospectively recruited. Examinations were performed on admission (day 1) and during follow-up (days 3, 10 and 21) and included a questionnaire regarding the presence of blurred vision, standardized refraction measurements and optical coherence tomography. Plasma VEGF and sFlt-1 were assessed by ELISA at baseline and during follow-up. At study entry seven patients (26.9%) complained of blurred vision and five (19.2%) developed burred vision during follow-up. Macular volume and thickness increased significantly (p = 0.008 and p = 0.04, respectively) in the group with blurred vision at day 3 and returned to the baseline value at 10 days. This pattern was present in 18 out of the 24 eyes from patients with blurred vision. By contrast, macular biometrics remained unchanged in the group without blurred vision. We did not detect any significant changes in VEGF levels during follow-up. By contrast, a significant reduction of sFlt-1 was observed in those patients with blurred vision at day 3 (p = 0.03) with normalization by day 10. Diabetic patients with blurred vision after starting insulin therapy present a significant transient increase in macular biometrics which is associated with a decrease in circulating sFlt-1. Copyright (c) 2010 John Wiley & Sons, Ltd.

  3. Diamel Therapy in Polycystic Ovary Syndrome Reduces Hyperinsulinaemia, Insulin Resistance, and Hyperandrogenaemia

    Directory of Open Access Journals (Sweden)

    Arturo Hernández-Yero

    2012-01-01

    Full Text Available For to determine the effect of Diamel on the insulin resistance, insulin sensitivity, and sexual hormones results in women with polycystic ovary syndrome (PCOS. A study was carried out on 37 patients with this disorder. A triple-blind clinical trial was designed in which the Diamel food supplement was compared with a placebo. The women with reproductive ages were randomly distributed in two groups, with 18 and 19 women respectively, and they took Diamel or placebo and were followed up during 6 months with clinical and biochemical evaluation. A significant decrease in the HOMA-IR from the initial value at six months was observed in the group with Diamel. The insulin sensitivity improved considerably in this group. The rate of menstrual recovery was higher in the group with Diamel, and two patients from this group obtained pregnancy. The hormone levels shows a significant decrease in testosterone at 3 months in the group with Diamel compared with the control group. The LH also decreases in the same group when comparing the start with 6 months.We concluded that the Diamel decreases insulin resistance and improves sensitivity to this hormone in women with PCOS, with improvement in the levels of LH and testosterone.

  4. Insulin resistance, role of metformin and other noninsulin therapies in pediatric type 1 diabetes

    Science.gov (United States)

    Type 1 diabetes mellitus (T1DM) in youth is a challenging chronic medical condition. Its management should address not only the glycemic control but also insulin resistance and cardiovascular disease risk factors which are increasingly recognized to be present in youth with TID. Current knowledge on...

  5. Refining basal insulin therapy: what have we learned in the age of analogues?

    NARCIS (Netherlands)

    DeVries, J. H.; Nattrass, M.; Pieber, T. R.

    2007-01-01

    BACKGROUND: The basal insulin analogues glargine and detemir have been subject to a series of trials comparing their clinical profiles to the conventional preparation, neutral protamine Hagedorn (NPH). Careful review of these trials provides opportunities to learn clinically useful lessons about

  6. Switching to multiple daily injection therapy with glulisine improves glycaemic control, vascular damage and treatment satisfaction in basal insulin glargine-injected diabetic patients.

    Science.gov (United States)

    Yanagisawa, Katsuyuki; Ashihara, Junya; Obara, Shinji; Wada, Norio; Takeuchi, Masayoshi; Nishino, Yuri; Maeda, Sayaka; Ishibashi, Yuji; Yamagishi, Sho-ichi

    2014-11-01

    Basal and bolus insulin therapy is required for strict blood control in diabetic patients, which could lead to prevention of vascular complications in diabetes. However, the optimal combination regimen is not well established. Fifty-nine diabetic patients (49 type 1 and 10 type 2; 52.9 ± 13.3 years old) whose blood glucose levels were uncontrolled (HbA1c  > 6.2%) by combination treatment of basal insulin glargine with multiple daily pre-meal injections of bolus short-acting insulin [aspart (n = 19), lispro (n = 37) and regular human insulin (n = 3)] for at least 8 weeks were enrolled in this study. We examined whether glycaemic control and vascular injury were improved by replacement of short-acting insulin with glulisine. Patient satisfaction was assessed with Diabetes Treatment Satisfaction Questionnaire. Although bolus and basal insulin doses were almost unchanged before and after replacement therapy, switching to glulisine insulin for 24 weeks significantly decreased level of HbA1c , advanced glycation end products (AGEs), soluble receptor for AGEs (sRAGE), monocyte chemoattractant protein-1 (MCP-1) and urinary albumin excretion. In multiple stepwise regression analysis, change in MCP-1 values from baseline (ΔMCP-1) was a sole determinant of log urinary albumin excretion. ΔAGEs and ΔsRAGE were independently correlated with each other. The relationship between ΔMCP-1 and ΔsRAGE was marginally significant (p = 0.05). Replacement of short-acting insulin by glulisine significantly increased Diabetes Treatment Satisfaction Questionnaire scores. Our present study suggests that combination therapy of glargine with multiple daily pre-meal injections of glulisine might show superior efficacy in controlling blood glucose, preventing vascular damage and improving treatment satisfaction in diabetic patients. Copyright © 2014 John Wiley & Sons, Ltd.

  7. Salvage high-dose-rate brachytherapy for local prostate cancer recurrence after radical radiotherapy

    Directory of Open Access Journals (Sweden)

    V. A. Solodkiy

    2016-01-01

    Full Text Available Studies salvage interstitial radiation therapy for recurrent prostate cancer, launched at the end of the XX century. In recent years, more and more attention is paid to high-dose-rate brachytherapy (HDR-BT as a method of treating local recurrence.The purpose of research – preliminary clinical results of salvage high-dose-rate brachytherapy applied in cases of suspected local recurrence or of residual tumour after radiotherapy.Preliminary findings indicate the possibility of using HDR-BT, achieving local tumor control with low genitourinary toxicity.

  8. Evaluation of Total Daily Dose and Glycemic Control for Patients Taking U-500 Insulin Admitted to the Hospital

    Science.gov (United States)

    2016-04-27

    mail:jack.e.lewi.mil@mail.mil Key Words: U-500 regular insulin , inpatient diabetes mellitus, insulin resistance Conflict of Interest Statements...500 regular insulin are severely insulin resistant requiring high doses of insulin . It has been observed that a patient’s insulin requirements may...concentrated than U-100 regular insulin and is generally used in patients with severe insulin resistance requiring greater than 200 units of insulin

  9. Performance of thermoluminescent materials for high dose dosimetry

    International Nuclear Information System (INIS)

    Texeira, Maria I.; Cecatti, Sonia G.P.; Caldas, Linda V.E.

    2008-01-01

    Cases involving high-doses of ionizing radiation are becoming increasingly common.The objective of this work was to characterize thermoluminescent materials for the dosimetry of workers exposed to high doses. Samples of TLD-200, TLD-400 and TLD-800 pellets from Thermo Electron Corporation were studied in gamma high-doses. Dose-response curves were obtained for doses between 100 mGy and 100 Gy. The reproducibility, the lower detection limits and dose-response curves were obtained for all three materials. The different kinds of detectors show usefulness for dosimetry of workers exposed accidentally to high doses. (author)

  10. Insulin resistance in multiple tissues in patients with type 1 diabetes mellitus on long-term continuous subcutaneous insulin infusion therapy

    NARCIS (Netherlands)

    Donga, Esther; van Dijk, Marieke [Leiden Univ., LUMC; Hoogma, Roel P. L. M.; Corssmit, Eleonora P. M.; Romijn, Johannes A.

    2013-01-01

    The aim of this study was to determine whether insulin resistance is present in lean patients with uncomplicated type 1 diabetes mellitus on long-term continuous subcutaneous insulin infusion (CSII), compared with matched healthy controls. We studied eight patients (four men and four women) with

  11. Adipose tissue NAD+ biology in obesity and insulin resistance: From mechanism to therapy.

    Science.gov (United States)

    Yamaguchi, Shintaro; Yoshino, Jun

    2017-05-01

    Nicotinamide adenine dinucleotide (NAD + ) biosynthetic pathway, mediated by nicotinamide phosphoribosyltransferase (NAMPT), a key NAD + biosynthetic enzyme, plays a pivotal role in controlling many biological processes, such as metabolism, circadian rhythm, inflammation, and aging. Over the past decade, NAMPT-mediated NAD + biosynthesis, together with its key downstream mediator, namely the NAD + -dependent protein deacetylase SIRT1, has been demonstrated to regulate glucose and lipid metabolism in a tissue-dependent manner. These discoveries have provided novel mechanistic and therapeutic insights into obesity and its metabolic complications, such as insulin resistance, an important risk factor for developing type 2 diabetes and cardiovascular disease. This review will focus on the importance of adipose tissue NAMPT-mediated NAD + biosynthesis and SIRT1 in the pathophysiology of obesity and insulin resistance. We will also critically explore translational and clinical aspects of adipose tissue NAD + biology. © 2017 WILEY Periodicals, Inc.

  12. "Time sequential high dose of Cytarabine in acute myelocytic leukemia "

    Directory of Open Access Journals (Sweden)

    Ghavamzadeh A

    2003-05-01

    Full Text Available Given preliminary evidence of timed, sequential chemotherapy of high dose cytosine arabinoside the current study was initiated to assess the side effects and efficacy of this regimen in patients with newly acute myelocytic leukemia (AML. Nineteen adults who referred to Hematology-Oncology and Bone Marrow Transplantation (BMT research center of Tehran University of Medical Sciences were enrolled in a trial from Aug 1999 to Nov 2000. All patients had a Karnofski classification above 60%. At this time induction therapy consisted of daunorubicin or idarubicin given at a dose of 60 mg/m² and 12 mg/m² IV respectively on days 1-3, and cytarabine (Ara-C 100 mg/m² intravenously by continuous infusion on days 1-7, followed by Ara-C 1000 mg/m² given on day 8-10 every 12 hours by IV infusion. Consolidation therapy started after 35th day. Of 19 fully evaluable patients, 10 patients achieved a complete remission, whereas 36.6% patients succumbed to death due to regeneration failure. The clinical data show that the overall survival rate from diagnosis 55.5% (95% CI, 30.8-78.5 at 6 months for the entire cohort of the patients. Disease free survival is also 50% (95% CI, 26-74. Mean duration of death due to treatment was 20 days (range 17-29 after beginning the regimen. Presenting WBC counts, French-American-British (FAB classification, sex and age were not useful prognostic variables. Fever, diarrhea, nausea and vomiting and GI hemorrhage were seen in 19, 6, 4, 7 patients respectively. It seems the 3+7+3 regimen is a promising approach for the AML patients regarding to high complete remission rate, but more supportive care should be considered. Furthermore any, benefit in long-term outcome can’t be determined regardless to the choice of post remission therapy (e.g., GCSF, appropriate antibiotics and etc.

  13. Electroacupuncture and Rosiglitazone Combined Therapy as a Means of Treating Insulin Resistance and Type 2 Diabetes Mellitus: A Randomized Controlled Trial

    Directory of Open Access Journals (Sweden)

    Rong-Tsung Lin

    2013-01-01

    Full Text Available Aims. To evaluate the efficacy of rosiglitazone (TZD and electroacupuncture (EA combined therapy as a treatment for type 2 diabetes mellitus (T2DM patients by randomized single-blind placebo controlled clinical trial. Methods. A total of 31 newly diagnostic T2DM patients, who fulfilled the study's eligibility criteria, were recruited. The individuals were randomly assigned into two groups, the control group (TZD, N=15 and the experimental group (TZD + EA, N=16. Changes in their plasma free fatty acid (FFA, glucose, and insulin levels, together with their homeostasis model assessment (HOMA indices, were statistically compared before and after treatment. Hypoglycemic activity (% was also compared between these two groups. Results. There was no significant difference in hypoglycemic activity between the TZD and TZD + EA group. The effectiveness of the combined therapy seems to derive from an improvement in insulin resistance and a significant lowering of the secreted insulin rather than the effect of TZD alone on T2DM. The combined treatment had no significant adverse effects. A lower plasma FFA concentration is likely to be the mechanism that causes this effect. Conclusion. This combined therapy seems to suppress endogenous insulin secretion by improving insulin resistance via a mechanism involving a reduction in plasma FFA. This trial is registered with ClinicalTrials.gov NCT01577095.

  14. How and why do patients with Type 1 diabetes sustain their use of flexible intensive insulin therapy? A qualitative longitudinal investigation of patients' self-management practices following attendance at a Dose Adjustment for Normal Eating (DAFNE) course.

    Science.gov (United States)

    Rankin, D; Cooke, D D; Clark, M; Heller, S; Elliott, J; Lawton, J

    2011-05-01

    Conventional insulin therapy requires patients with Type 1 diabetes to adhere to rigid dietary and insulin injection practices. Recent trends towards flexible intensive insulin therapy enable patients to match insulin to dietary intake and lifestyle; however, little work has examined patients' experiences of incorporating these practices into real-life contexts. This qualitative longitudinal study explored patients' experiences of using flexible intensive insulin therapy to help inform the development of effective long-term support. Semi-structured interviews were conducted with 30 adult patients with Type 1 diabetes following participation in a structured education programme on using flexible intensive insulin therapy, and 6 and 12 months post-course. Longitudinal data analysis used an inductive, thematic approach. Patients consistently reported feeling committed to and wanting to sustain flexible intensive insulin therapy. This regimen was seen as a logical and effective method of self-management, as patients experienced improved blood glucose readings and/or reported feeling better. Implementing and sustaining flexible intensive insulin therapy was enhanced when patients had stable routines, with more challenges reported by those working irregular hours and during weekends/holidays. Some patients re-crafted their lives to make this approach work for them; for instance, by creating dietary routines or adjusting dietary choices. Clinical data have shown that flexible intensive insulin therapy can lead to improvement in glycaemic control. This study, drawing on patients' perspectives, provides further endorsement for flexible intensive insulin therapy by demonstrating patients' liking of, and their motivation to sustain, this approach over time. To help patients implement and sustain flexible intensive insulin therapy, follow-up support should encourage them to identify routines to better integrate this regimen into their lives. © 2011 The Authors. Diabetic

  15. The impact of extended release exenatide as adjuvant therapy on hemoglobin A1C, weight, and total daily dose of insulin in patients with type 2 diabetes mellitus using U-500 insulin.

    Science.gov (United States)

    Farwig, Phillip A; Zielinski, Angela J; Accursi, Mallory L; Burant, Christopher J

    2017-12-01

    To evaluate the efficacy and safety of adjuvant exenatide extended release (ER) therapy in patients treated with regular U-500 insulin. In this retrospective chart review at an ambulatory care center in the Midwest, 18 patients with type 2 diabetes being treated with regular U-500 insulin and adjuvant exenatide ER were identified. These patients were evaluated for outcomes following the addition of exenatide ER. The primary outcome was change in HbA 1C from baseline to 3, 6, and 12months. Secondary outcomes included change in weight, total daily dose (TDD) of insulin, and hypoglycemia. Repeated measures ANOVA was performed to assess the differences in mean scores over four time periods. A total of 18 of 50 patients met inclusion criteria with sufficient data to be included in analysis. HbA 1C showed non-significant findings from baseline to 12months (8.08% vs. 8.23%; p=0.75). A non-significant, modest weight loss occurred (146.4kgvs. 144.2kg; -2.2kg; p=0.31). A significant decrease in TDD of insulin was observed (378 units vs. 326 units; p1). There was a trend towards hypoglycemia from baseline to month 3 post addition of exenatide ER (0.33 events vs. 1.33 events; p=0.055). In patients treated with regular U-500 insulin, adjuvant exenatide ER therapy showed no significant improvement in HbA 1C , but did show modest weight loss as well as decreased insulin requirements to achieve a HbA 1C that was comparable to baseline. Published by Elsevier B.V.

  16. Acute renal failure in high dose carboplatin chemotherapy

    NARCIS (Netherlands)

    Frenkel, J.; Kool, G.; de Kraker, J.

    1995-01-01

    Carboplatin has been reported to cause acute renal failure when administered in high doses to adult patients. We report a 4 1/2-year-old girl who was treated with high-dose carboplatin for metastatic parameningeal embryonal rhabdomyosarcoma. Acute renal failure developed followed by a slow partial

  17. Pharmacogenetics and Pharmacokinetics in high-dose alkylating chemotherapy

    NARCIS (Netherlands)

    Ekhart, G.C. (Corine)

    2008-01-01

    High-dose chemotherapy in combination with peripheral blood progenitor cell transplantation has been developed as a possible curative treatment modality in several solid tumours. A frequently used high-dose regimen in the Netherlands is the CTC regimen, which is a 4-day course of cyclophosphamide,

  18. Keeping Up with the Diabetes Technology: 2016 Endocrine Society Guidelines of Insulin Pump Therapy and Continuous Glucose Monitor Management of Diabetes.

    Science.gov (United States)

    Galderisi, Alfonso; Schlissel, Elise; Cengiz, Eda

    2017-09-23

    Decades after the invention of insulin pump, diabetes management has encountered a technology revolution with the introduction of continuous glucose monitoring, sensor-augmented insulin pump therapy and closed-loop/artificial pancreas systems. In this review, we discuss the significance of the 2016 Endocrine Society Guidelines for insulin pump therapy and continuous glucose monitoring and summarize findings from relevant diabetes technology studies that were conducted after the publication of the 2016 Endocrine Society Guidelines. The 2016 Endocrine Society Guidelines have been a great resource for clinicians managing diabetes in this new era of diabetes technology. There is good body of evidence indicating that using diabetes technology systems safely tightens glycemic control while managing both type 1 and type 2 diabetes. The first-generation diabetes technology systems will evolve as we gain more experience and collaboratively work to improve them with an ultimate goal of keeping people with diabetes complication and burden-free until the cure for diabetes becomes a reality.

  19. Health Economic Evaluation of Home and Hospital-Based Care in T2D Patients on Insulin Therapy.

    Science.gov (United States)

    Janati, Ali; Sarabchian, Mohamad Ali; Mohaghegh, Bahram; Aghmohamadzadeh, Naser; Seyedin, Hesam; Gholizadeh, Masumeh; Hasanpoor, Edris

    2017-11-01

    Type 2 Diabetes is a main concern of public health in contemporary world with remarkable mortality, delayed complications and health costs. Governments are obliged to improve the quality of health care and consider appropriate strategies to reduce the costs. An alternative strategy for hospital services is care at home. Therefore, this study was aimed to evaluate the cost-effectiveness of home-based and hospital-based diabetes care. A quasi-experimental, pre-test and post-test design was conducted in Northwest Iran. Sixty subjects who were eligible insulin-treatment type 2 diabetes mellitus were randomly assigned into two equal groups to receive home-based or conventional hospital-based care. Data on glycosylated hemoglobin (HbA1c), hypoglycemia episodes, time needed to achieve glycemic control level, diabetes treatment satisfaction, diabetes knowledge and costs during three months were collected. The cost of home-based care in insulin therapy diabetes was 61% less compared with the hospital-based methods. The former strategy was cost-effective in terms of reduction in HbA1C and the time needed to achieve glycemic control. The patients in home care group were more satisfied and knowledgeable. The care at home approach for type 2 diabetic patients can be introduced and supported as a cost-effective care method in the country.

  20. Reported Benefits of Insulin Therapy for Better Glycemic Control in Type 2 Diabetic Patients–-Is this Applicable in Saudi Patients?

    Directory of Open Access Journals (Sweden)

    Wafaa AlSaggaf

    2016-01-01

    Full Text Available Aim To compare the effect of different treatment regimens (oral hypoglycemic agents [OHGs], insulin therapy, and combination of both on glycemic control and other cardiometabolic risk factors in type 2 diabetes mellitus (T2DM patients in Saudi. Subjects and Methods Patients with T2DM, but no serious diabetic complications, were randomly recruited from the diabetes clinics at two large hospitals in Jeddah, Saudi Arabia, during June 2013 to July 2014. Only those without change in treatment modality for the last 18 months were included. Blood pressure and anthropometric measurements were measured. Treatment plan was recorded from the patients' files. Fasting blood sample was obtained to measure glucose, HbA1c, and lipid profile. Results A total of 197 patients were recruited; 41.1% were men and 58.9% were women. The mean (±SD age was 58.5 ± 10.5 years. Most patients (60.7% were on OHGs, 11.5% on insulin therapy, and 27.7% were using a combination of insulin and OHGs. The mean HbA1c was lower in patients using OHGs only, compared with means in those using insulin, or combined therapy in patients with disease duration of #10 years ( P = 0.001 and also in those with a longer duration of the disease ( P < 0.001. A lower mean diastolic and systolic blood pressure was found among patients on insulin alone ( P < 0.01. No significant differences were found in lipid profiles among the groups. Conclusion Insulin therapy, without adequate diabetes education, fails to control hyperglycemia adequately in Saudi T2DM patients. There is a challenge to find out reasons for poor control and the ways as to how to improve glycemic control in T2DM.

  1. Comparison between SGLT2 inhibitors and DPP4 inhibitors added to insulin therapy in type 2 diabetes: a systematic review with indirect comparison meta-analysis.

    Science.gov (United States)

    Min, Se Hee; Yoon, Jeong-Hwa; Hahn, Seokyung; Cho, Young Min

    2017-01-01

    Both sodium glucose cotransporter 2 (SGLT2) inhibitors and dipeptidyl peptidase-4 (DPP4) inhibitors can be used to treat patients with type 2 diabetes mellitus (T2DM) that is inadequately controlled with insulin therapy, and yet there has been no direct comparison of these two inhibitors. We searched MEDLINE, EMBASE, LILACS, the Cochrane Central Register of Controlled Trials and ClinicalTrials.gov through June 2015. Randomized controlled trials published in English that compare SGLT2 inhibitor plus insulin (SGLT2i/INS) with placebo plus insulin or DPP4 inhibitor plus insulin (DPP4i/INS) with placebo plus insulin in patients with T2DM were selected. Data on the study characteristics, efficacy and safety outcomes were extracted. We compared the efficacy and safety between SGLT2i/INS and DPP4i/INS indirectly with covariates adjustment. Risk of potential bias was assessed. Fourteen eligible randomized controlled trials comprising 6980 patients were included (five SGLT2 inhibitor studies and nine DPP4 inhibitor studies). Covariate-adjusted indirect comparison using meta-regression analyses revealed that SGLT2i/INS achieved greater reduction in HbA 1c [weighted mean difference (WMD) -0.24%, 95% confidence interval (CI) -0.43 to -0.05%], fasting plasma glucose (WMD -18.0 mg/dL, 95% CI -28.5 to -7.6 mg/dL) and body weight (WMD -2.38 kg, 95% CI -3.18 to -1.58 kg) from baseline than DPP4i/INS without increasing the risk of hypoglycaemia (relative risks 1.19, 95% CI 0.78 to 1.82). Sodium glucose cotransporter 2 inhibitors achieved better glycaemic control and greater weight reduction than DPP4 inhibitors without increasing the risk of hypoglycaemia in patients with T2DM that is inadequately controlled with insulin. There has been no direct comparison of SGLT2 inhibitors and DPP4 inhibitors in patients with T2DM inadequately controlled with insulin therapy. In this study, we performed indirect meta-analysis comparing SGLT2 inhibitors and DPP4 inhibitors added to insulin

  2. Effect of Continuous Positive Airway Pressure Therapy on Glycemic Excursions and Insulin Sensitivity in Patients with Obstructive Sleep Apnea-hypopnea Syndrome and Type 2 Diabetes

    Directory of Open Access Journals (Sweden)

    Li-Xin Guo

    2015-01-01

    Conclusions: CPAP therapy may have a beneficial effect on improving not only blood glucose but also upon insulin sensitivity in T2DM patients with OSAHS. This suggests that CPAP may be an effective treatment for T2DM in addition to intensive diabetes management.

  3. A two year observational study of nicotinamide and intensive insulin therapy in patients with recent onset type 1 diabetes mellitus.

    Science.gov (United States)

    Crinó, A; Schiaffini, R; Ciampalini, P; Suraci, M C; Manfrini, S; Visalli, N; Matteoli, M C; Patera, P; Buzzetti, R; Guglielmi, C; Spera, S; Costanza, F; Fioriti, E; Pitocco, D; Pozzilli, P

    2005-08-01

    A number of trials have evaluated residual beta-cell function in patients with recent onset type 1 diabetes mellitus (DM1) treated with nicotinamide in addition to intensive insulin therapy (IIT). In most studies, only a slight decline of C-peptide secretion was observed 12 months after diagnosis; however, no data is available on C-peptide secretion and metabolic control in patients continuing nicotinamide and IIT for up to 2 years after diagnosis. We retrospectively analysed data from 25 patients (mean age 14.7 years +/- 5 SD) with DM1 in whom nicotinamide at a dose of 25 mg/kg b. wt. was added from diagnosis (< 4 weeks) to IIT (three injections of regular insulin at meals + one NPH at bed time) and continued for up to 2 years after diagnosis. Data were also analysed from patients (n = 27) in whom IIT was introduced at diagnosis and who were similarly followed for 2 years. Baseline C-peptide as well as insulin dose and HbA1c levels were evaluated at 12 and 24 months after diagnosis. In the course of the follow-up, patients on nicotinamide + IIT or IIT alone did not significantly differ in terms of C-peptide secretion (values at 24 months in the two groups were 0.19 +/- 0.24 nM vs 0.19 +/- 0.13 nM, respectively). Insulin requirement (0.6 +/- 0.3 U/kg/day vs 0.7 +/- 0.2 U/kg/day at 24 months, respectively) did not differ between the two groups. However, HbA1c was significantly lower 2 years after diagnosis in patients treated with nicotinamide + IIT (6.09 +/- 0.9% vs 6.98 +/- 0.9%, respectively, p < 0.01). No adverse effects were observed in patients receiving nicotinamide for 2 years. Implementation of IIT with the addition of nicotinamide at diagnosis continued for 2 years improves metabolic control as assessed by HbA1c. In both nicotinamide and control patients, no decline in C-peptide was detected 2 years after diagnosis, indicating that IIT preserves C-peptide secretion. We conclude that nicotinamide + IIT at diagnosis of DM1 prolonged for up to 2 years can be

  4. Hypertonic saline solution and high-dose furosemide infusion in cardiorenal syndrome: our experience

    Directory of Open Access Journals (Sweden)

    Francesco Ventrella

    2013-03-01

    Full Text Available Introduction Heart failure is frequently complicated by renal failure, and this association is a negative prognostic factor. These patients sometimes present oligo-/anuria and resistance to high-dose furosemide, a condition referred to as the cardiorenal syndrome (CRS. Acute or chronic reductions in left ventricular function result in decreased blood flow, with reduction of renal perfusion and activation of several neurohormonal systems, which cause resistance to diuretic therapy. This condition often requires ultrafiltration, which is an effective, but invasive and expensive procedure. Infusions of hypertonic saline solution (HSS and high-dose furosemide can be an effective alternative. Materials and methods From November 2009 through May 2010, our team treated 20 patients with CRS and resistance to iv boluses of high-dose furosemide. These patients were treated with small-volume (150-250 mL infusions of HSS (NaCl 1.57 – 4.5%, depending on serum Na values and high-dose furosemide twice a day. The aim of this treatment is to modify renal hemodynamics and the water-saline balance in the kidney by counteracting the extracellular fluid accumulation and eliminating symptoms of congestion. Results In 18 patients (90%, urine output was restored and renal function improved during the first hours of treatment. Clinical improvement was evident from the first day of therapy, and there were no adverse events. Two patients (10% did not respond to the treatment: one (who had been in critical condition since admission died; the other required regular sessions of ultrafiltration. Conclusions HSS combined with high-dose furosemide is a safe, effective, low-cost approach to the treatment of CRS that is resistant to diuretic therapy.

  5. Metformin versus placebo in combination with insulin analogues in patients with type 2 diabetes mellitus-the randomised, blinded Copenhagen Insulin and Metformin Therapy (CIMT) trial

    DEFF Research Database (Denmark)

    Lundby-Christensen, Louise; Tarnow, Lise; Boesgaard, Trine W

    2016-01-01

    OBJECTIVE: To assess the effect of metformin versus placebo both in combination with insulin analogue treatment on changes in carotid intima-media thickness (IMT) in patients with type 2 diabetes. DESIGN AND SETTING: Investigator-initiated, randomised, placebo-controlled trial with a 2×3 factorial...... design conducted at eight hospitals in Denmark. PARTICIPANTS AND INTERVENTIONS: 412 participants with type 2 diabetes (glycated haemoglobin (HbA1c) ≥7.5% (≥58 mmol/mol); body mass index >25 kg/m2) were in addition to open-labelled insulin treatment randomly assigned 1:1 to 18 months blinded metformin (1...... weight gain, and smaller insulin dose compared with placebo plus insulin. However, the trial only reached 46% of the planned sample size and lack of power may therefore have affected our results. TRIAL REGISTRATION NUMBER: NCT00657943; Results....

  6. InsuOnline, an Electronic Game for Medical Education on Insulin Therapy: A Randomized Controlled Trial With Primary Care Physicians.

    Science.gov (United States)

    Diehl, Leandro Arthur; Souza, Rodrigo Martins; Gordan, Pedro Alejandro; Esteves, Roberto Zonato; Coelho, Izabel Cristina Meister

    2017-03-09

    Most patients with diabetes mellitus (DM) are followed by primary care physicians, who often lack knowledge or confidence to prescribe insulin properly. This contributes to clinical inertia and poor glycemic control. Effectiveness of traditional continuing medical education (CME) to solve that is limited, so new approaches are required. Electronic games are a good option, as they can be very effective and easily disseminated. The objective of our study was to assess applicability, user acceptance, and educational effectiveness of InsuOnline, an electronic serious game for medical education on insulin therapy for DM, compared with a traditional CME activity. Primary care physicians (PCPs) from South of Brazil were invited by phone or email to participate in an unblinded randomized controlled trial and randomly allocated to play the game InsuOnline, installed as an app in their own computers, at the time of their choice, with minimal or no external guidance, or to participate in a traditional CME session, composed by onsite lectures and cases discussion. Both interventions had the same content and duration (~4 h). Applicability was assessed by the number of subjects who completed the assigned intervention in each group. Insulin-prescribing competence (factual knowledge, problem-solving skills, and attitudes) was self-assessed through a questionnaire applied before, immediately after, and 3 months after the interventions. Acceptance of the intervention (satisfaction and perceived importance for clinical practice) was also assessed immediately after and 3 months after the interventions, respectively. Subjects' characteristics were similar between groups (mean age 38, 51.4% [69/134] male). In the game group, 69 of 88 (78%) completed the intervention, compared with 65 of 73 (89%) in the control group, with no difference in applicability. Percentage of right answers in the competence subscale, which was 52% at the baseline in both groups, significantly improved

  7. InsuOnline, an Electronic Game for Medical Education on Insulin Therapy: A Randomized Controlled Trial With Primary Care Physicians

    Science.gov (United States)

    2017-01-01

    Background Most patients with diabetes mellitus (DM) are followed by primary care physicians, who often lack knowledge or confidence to prescribe insulin properly. This contributes to clinical inertia and poor glycemic control. Effectiveness of traditional continuing medical education (CME) to solve that is limited, so new approaches are required. Electronic games are a good option, as they can be very effective and easily disseminated. Objective The objective of our study was to assess applicability, user acceptance, and educational effectiveness of InsuOnline, an electronic serious game for medical education on insulin therapy for DM, compared with a traditional CME activity. Methods Primary care physicians (PCPs) from South of Brazil were invited by phone or email to participate in an unblinded randomized controlled trial and randomly allocated to play the game InsuOnline, installed as an app in their own computers, at the time of their choice, with minimal or no external guidance, or to participate in a traditional CME session, composed by onsite lectures and cases discussion. Both interventions had the same content and duration (~4 h). Applicability was assessed by the number of subjects who completed the assigned intervention in each group. Insulin-prescribing competence (factual knowledge, problem-solving skills, and attitudes) was self-assessed through a questionnaire applied before, immediately after, and 3 months after the interventions. Acceptance of the intervention (satisfaction and perceived importance for clinical practice) was also assessed immediately after and 3 months after the interventions, respectively. Results Subjects’ characteristics were similar between groups (mean age 38, 51.4% [69/134] male). In the game group, 69 of 88 (78%) completed the intervention, compared with 65 of 73 (89%) in the control group, with no difference in applicability. Percentage of right answers in the competence subscale, which was 52% at the baseline in both

  8. Clinical course after five years of insulin therapy in patients with type 2 diabetes in Spain: results of the EDIN study.

    Science.gov (United States)

    Rodríguez, Angel; Tofe, Santiago; Reviriego, Jesus

    2014-01-01

    The primary study objective was to assess the proportion of patients with type 2 diabetes and an HbA1c value ≤ 6.5% from the start of insulin therapy to five years later in the outpatient setting in Spain. This was an observational, multicenter, naturalistic study with retrospective collection of clinical data. Investigators were endocrinologists or internal medicine specialists from all over Spain. During standard clinical care, patients started insulin therapy, which was continued for at least 5 years. The clinical records of 405 patients were reviewed. The final analysis set included records from 346 patients. At baseline (start of insulin therapy), 51.2% of patients were female; mean (SD) age was 64.6 (9.0) years; body mass index, 29.8 (4-5) kg/m(2); time since diagnosis, 8.8 (6.8) years; HbA1c, 9.4% (1.5); fasting glucose, 223.7 (55.9) mg/dL; and mean 2-hour postprandial glucose, 293.6 (71.0) mg/dL. When insulin therapy was started, 1.0% of patients had an HbA1c value ≤ 6.5%. At 5 years, 10.3% of patients achieved the HbA1c goal of ≤ 6.5% (mean, 7.72%). All glucose parameters (HbA1c, fasting glucose, and 2-hour postprandial glucose) improved at 5 years as compared to values at the start of insulin therapy. Glucose parameters improved over time in patients with type 2 diabetes in this naturalistic study. However, blood glucose control exceeded the internationally recommended target values. These results therefore suggest that there is still some margin for improvement in outpatient care in Spain. Copyright © 2013 SEEN. Published by Elsevier Espana. All rights reserved.

  9. State of the Art Review: Emerging Therapies: The Use of Insulin Sensitizers in the Treatment of Adolescents with Polycystic Ovary Syndrome (PCOS).

    Science.gov (United States)

    Geller, David H; Pacaud, Danièle; Gordon, Catherine M; Misra, Madhusmita

    2011-08-26

    PCOS, a heterogeneous disorder characterized by cystic ovarian morphology, androgen excess, and/or irregular periods, emerges during or shortly after puberty. Peri- and post-pubertal obesity, insulin resistance and consequent hyperinsulinemia are highly prevalent co-morbidities of PCOS and promote an ongoing state of excess androgen. Given the relationship of insulin to androgen excess, reduction of insulin secretion and/or improvement of its action at target tissues offer the possibility of improving the physical stigmata of androgen excess by correction of the reproductive dysfunction and preventing metabolic derangements from becoming entrenched. While lifestyle changes that concentrate on behavioral, dietary and exercise regimens should be considered as first line therapy for weight reduction and normalization of insulin levels in adolescents with PCOS, several therapeutic options are available and in wide use, including oral contraceptives, metformin, thiazolidenediones and spironolactone. Overwhelmingly, the data on the safety and efficacy of these medications derive from the adult PCOS literature. Despite the paucity of randomized control trials to adequately evaluate these modalities in adolescents, their use, particularly that of metformin, has gained popularity in the pediatric endocrine community. In this article, we present an overview of the use of insulin sensitizing medications in PCOS and review both the adult and (where available) adolescent literature, focusing specifically on the use of metformin in both mono- and combination therapy.

  10. State of the Art Review: Emerging Therapies: The Use of Insulin Sensitizers in the Treatment of Adolescents with Polycystic Ovary Syndrome (PCOS)

    Science.gov (United States)

    2011-01-01

    PCOS, a heterogeneous disorder characterized by cystic ovarian morphology, androgen excess, and/or irregular periods, emerges during or shortly after puberty. Peri- and post-pubertal obesity, insulin resistance and consequent hyperinsulinemia are highly prevalent co-morbidities of PCOS and promote an ongoing state of excess androgen. Given the relationship of insulin to androgen excess, reduction of insulin secretion and/or improvement of its action at target tissues offer the possibility of improving the physical stigmata of androgen excess by correction of the reproductive dysfunction and preventing metabolic derangements from becoming entrenched. While lifestyle changes that concentrate on behavioral, dietary and exercise regimens should be considered as first line therapy for weight reduction and normalization of insulin levels in adolescents with PCOS, several therapeutic options are available and in wide use, including oral contraceptives, metformin, thiazolidenediones and spironolactone. Overwhelmingly, the data on the safety and efficacy of these medications derive from the adult PCOS literature. Despite the paucity of randomized control trials to adequately evaluate these modalities in adolescents, their use, particularly that of metformin, has gained popularity in the pediatric endocrine community. In this article, we present an overview of the use of insulin sensitizing medications in PCOS and review both the adult and (where available) adolescent literature, focusing specifically on the use of metformin in both mono- and combination therapy. PMID:21899727

  11. State of the Art Review: Emerging Therapies: The Use of Insulin Sensitizers in the Treatment of Adolescents with Polycystic Ovary Syndrome (PCOS

    Directory of Open Access Journals (Sweden)

    Gordon Catherine M

    2011-08-01

    Full Text Available Abstract PCOS, a heterogeneous disorder characterized by cystic ovarian morphology, androgen excess, and/or irregular periods, emerges during or shortly after puberty. Peri- and post-pubertal obesity, insulin resistance and consequent hyperinsulinemia are highly prevalent co-morbidities of PCOS and promote an ongoing state of excess androgen. Given the relationship of insulin to androgen excess, reduction of insulin secretion and/or improvement of its action at target tissues offer the possibility of improving the physical stigmata of androgen excess by correction of the reproductive dysfunction and preventing metabolic derangements from becoming entrenched. While lifestyle changes that concentrate on behavioral, dietary and exercise regimens should be considered as first line therapy for weight reduction and normalization of insulin levels in adolescents with PCOS, several therapeutic options are available and in wide use, including oral contraceptives, metformin, thiazolidenediones and spironolactone. Overwhelmingly, the data on the safety and efficacy of these medications derive from the adult PCOS literature. Despite the paucity of randomized control trials to adequately evaluate these modalities in adolescents, their use, particularly that of metformin, has gained popularity in the pediatric endocrine community. In this article, we present an overview of the use of insulin sensitizing medications in PCOS and review both the adult and (where available adolescent literature, focusing specifically on the use of metformin in both mono- and combination therapy.

  12. Efficacy and safety of teneligliptin in addition to insulin therapy in type 2 diabetes mellitus patients on hemodialysis evaluated by continuous glucose monitoring.

    Science.gov (United States)

    Yajima, Takahiro; Yajima, Kumiko; Hayashi, Makoto; Takahashi, Hiroshi; Yasuda, Keigo

    2016-12-01

    Appropriate glycemic control without hypoglycemia is important in patients with type 2 diabetes on hemodialysis. Teneligliptin, a novel dipeptidyl peptidase-4 inhibitor, can be used without dose adjustment for these patients. Using continuous glucose monitoring (CGM), we evaluated the efficacy and safety of adding teneligliptin to insulin therapy. Twenty-one type 2 diabetes mellitus patients on hemodialysis treated with insulin were enrolled. After the adjustment of insulin dose, their blood glucose level was monitored by CGM. Insulin dose was reduced after teneligliptin administration. The median total daily insulin dose significantly reduced from 18 (9-24)U to 6 (0-14)U (p1). Maximum, mean, and standard deviation of blood glucose level on the hemodialysis and non-hemodialysis days did not change after teneligliptin administration. However, minimum blood glucose level was significantly elevated on the hemodialysis day after teneligliptin administration (from 3.9±1.0mmol/L to 4.4±0.9mmol/L, p=0.040). The incidence of asymptomatic hypoglycemia on the hemodialysis day detected by CGM significantly decreased from 38.1% to 19.0% (p=0.049). Teneligliptin may contribute toward reducing the total daily insulin dose and preventing hypoglycemic events on the hemodialysis day in type 2 diabetes mellitus patients. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  13. Pregestational diabetes with extreme insulin resistance: use of U-500 insulin in pregnancy.

    Science.gov (United States)

    Zuckerwise, Lisa C; Werner, Erika F; Pettker, Christian M; McMahon-Brown, Erin K; Thung, Stephen F; Han, Christina S

    2012-08-01

    Increased insulin requirements in pregnancy can hinder attainment of glycemic control in diabetic patients. U-500 insulin is a concentrated form of regular insulin that can be a valuable tool in the treatment of patients with severe insulin resistance. A 24-year-old woman with pregestational diabetes mellitus experienced increasing insulin requirements during pregnancy, peaking at 650 units daily. The frequent, large-volume injections of standard-concentration insulin were poorly tolerated by the patient and resulted in nonadherence. She subsequently achieved glycemic control on thrice-daily U-500 insulin. Pregnancy exacerbates insulin resistance in diabetic patients, and these patients may require high doses of insulin. U-500 insulin is an effective alternative for patients with severe insulin resistance and should be considered for pregnant women with difficulty achieving glycemic control.

  14. Accelerated Irradiations for High Dose Microstructures in Fast Reactor Alloys

    Energy Technology Data Exchange (ETDEWEB)

    Jiao, Zhijie [Univ. of Michigan, Ann Arbor, MI (United States)

    2017-03-31

    The objective of this project is to determine the extent to which high dose rate, self-ion irradiation can be used as an accelerated irradiation tool to understand microstructure evolution at high doses and temperatures relevant to advanced fast reactors. We will accomplish the goal by evaluating phase stability and swelling of F-M alloys relevant to SFR systems at very high dose by combining experiment and modeling in an effort to obtain a quantitative description of the processes at high and low damage rates.

  15. Future of newer basal insulin

    OpenAIRE

    Madhu, S. V.; Velmurugan, M.

    2013-01-01

    Basal insulin have been developed over the years. In recent times newer analogues have been added to the armanentarium for diabetes therapy. This review specifically reviews the current status of different basal insulins

  16. Safety and Efficacy in Early Insulin Initiation as Comprehensive Therapy for Patients with Type 2 Diabetes in Primary Health Care Centers

    Directory of Open Access Journals (Sweden)

    Agung Pranoto

    2015-04-01

    Full Text Available Aim: to analyze the safety and efficacy of early insulin initiation therapy for patients with type 2 diabetes mellitus (T2DM in primary health care provided by general practitioners (GPs in Surabaya, East Java, Indonesia. Methods: pre-post study of ninety nine diabetic patients without previous insulin treatment with HbA1c levels >8% were involved in this study. The study was conducted in 10 primary health care centers in Surabaya between October 2011 to June 2012. Each patient received insulin therapy for 12 weeks. Laboratory examination was performed for each patient including fasting plasma glucose (FPG, 2 hours post-prandial plasma glucose (2hPPG and HbA1c examination before and after the study. Self monitoring blood glucose (SMBG examination was conducted in order to adjust the insulin dose and prevent the incidence of hypoglycemia. Data was statistically analyzed using paired-T test. Results: FPG level was decreased from baseline data (209 mg/dL to 152.07 mg/dL at the end of the study (Δ56.93 mg/dl; p=0.0001. The average of 2hPPG level was also decreased from 313.00 mg/dl to 220.72 mg/dL (Δ 92.28 mg/dL; p=0.0001. HbA1c was reduced from 11.60% at baseline to 8.95% at the end of study (Δ 2.65%; p=0.0001. Hypoglycemia was found in 6 patients (6.06% in this study, but all events were mild and did not need to be admitted to hospital. Conclusion: the safety of insulin therapy iniatiation might be provided by GPs at primary health centers with significant efficacy and minimal side effects. Key words: insulin, general practioner, primary health center.

  17. Insulin-like growth factor-I gene therapy reverses morphologic changes and reduces hyperprolactinemia in experimental rat prolactinomas

    Directory of Open Access Journals (Sweden)

    Bracamonte Maria I

    2008-01-01

    Full Text Available Abstract Background The implementation of gene therapy for the treatment of pituitary tumors emerges as a promising complement to surgery and may have distinct advantages over radiotherapy for this type of tumors. Up to now, suicide gene therapy has been the main experimental approach explored to treat experimental pituitary tumors. In the present study we assessed the effectiveness of insulin-like growth factor I (IGF-I gene therapy for the treatment of estrogen-induced prolactinomas in rats. Results Female Sprague Dawley rats were subcutaneously implanted with silastic capsules filled with 17-β estradiol (E2 in order to induce pituitary prolactinomas. Blood samples were taken at regular intervals in order to measure serum prolactin (PRL. As expected, serum PRL increased progressively and 23 days after implanting the E2 capsules (Experimental day 0, circulating PRL had undergone a 3–4 fold increase. On Experimental day 0 part of the E2-implanted animals received a bilateral intrapituitary injection of either an adenoviral vector expressing the gene for rat IGF-I (RAd-IGFI, or a vector (RAd-GFP expressing the gene for green fluorescent protein (GFP. Seven days post vector injection all animals were sacrificed and their pituitaries morphometrically analyzed to evaluate changes in the lactotroph population. RAd-IGFI but not RAd-GFP, induced a significant fall in serum PRL. Furthermore, RAd-IGFI but not RAd-GFP significantly reversed the increase in lactotroph size (CS and volume density (VD induced by E2 treatment. Conclusion We conclude that IGF-I gene therapy constitutes a potentially useful intervention for the treatment of prolactinomas and that bioactive peptide gene delivery may open novel therapeutic avenues for the treatment of pituitary tumors.

  18. Daily insulin requirement of children and adolescents with type 1 diabetes: effect of age, gender, body mass index and mode of therapy.

    Science.gov (United States)

    Wiegand, Susanna; Raile, Klemens; Reinehr, Thomas; Hofer, Sabine; Näke, Andrea; Rabl, Wolfgang; Holl, Reinhard W

    2008-04-01

    The purpose of this study was to generate insulin dose (ID) percentiles for children and adolescents with type 1 diabetes mellitus (DM1) having the opportunity to assess this important parameter in relation to age and sex. Daily IDs per weight (ID/kg) were recorded in 22,177 patients with DM1 (3-25 years of age, DM1 duration of more than 2 years, 48% female) and ID percentiles (ID-Perc) were created statistically. The ID-Perc were compared between male and female, and between multiple insulin injection therapy (MIT) and continuous s.c. insulin infusion (CSII). A multivariate regression analysis was performed for ID in the third year of DM1 with ID/kg, body weight, age, gender, and insulin delivery regimen as variables. The 50th ID-Perc (P50) varied among 0.67 IU/kg (age 3 years), 0.93 IU/kg (13 years), and 0.70 IU/kg (23 years) increasing from early childhood to adolescence and decreasing toward adulthood. Highest P50 ID was found at 12 years in females (0.94 IU/kg) and at 14 years in males (0.92 IU/kg). Using ICT, the ID was significantly higher compared with CSII (P50: 0.94 IU/kg versus 0.79 IU/kg at 13 years). In multivariate regression analysis, ID was significantly (P>0.001) associated with age, gender, and insulin delivery regime. The ID-Perc were significantly different during various periods of childhood and were influenced by gender, body weight, and insulin injection regimes. Therefore, the presented data 1) provide evidence to interpret individual ID in children and adolescents with DM1 and 2) more specifically identify children with unusually high (insulin resistance and non-compliance) or low (MODY and persistent remission) insulin requirement.

  19. High-Protein Intake during Weight Loss Therapy Eliminates the Weight-Loss-Induced Improvement in Insulin Action in Obese Postmenopausal Women

    OpenAIRE

    Gordon I. Smith; Jun Yoshino; Shannon C. Kelly; Dominic N. Reeds; Adewole Okunade; Bruce W. Patterson; Samuel Klein; Bettina Mittendorfer

    2016-01-01

    High-protein (HP) intake during weight loss (WL) therapy is often recommended because it reduces the loss of lean tissue mass. However, HP intake could have adverse effects on metabolic function, because protein ingestion reduces postprandial insulin sensitivity. In this study, we compared the effects of ∼10% WL with a hypocaloric diet containing 0.8 g protein/kg/day and a hypocaloric diet containing 1.2 g protein/kg/day on muscle insulin action in postmenopausal women with obesity. We found ...

  20. Relative safety profiles of high dose statin regimens

    Directory of Open Access Journals (Sweden)

    Carlos Escobar

    2008-06-01

    Full Text Available Carlos Escobar, Rocio Echarri, Vivencio BarriosDepartment of Cardiology, Hospital Ramón y Cajal, Madrid, SpainAbstract: 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.Keywords: statins, high doses, tolerability, liver, muscle

  1. Treatment of the prostate cancer with high dose rate brachytherapy

    International Nuclear Information System (INIS)

    Martinez, Alvaro; Torres Silva, Felipe

    2002-01-01

    The prostate cancer treatment in early stages is controversial. The high dose rate brachytherapy has been used like monotherapy or boost with external beam radiotherapy in advanced disease. This paper describes the technique and the advantages over other modalities

  2. High-dose dosimetry using natural silicate minerals

    International Nuclear Information System (INIS)

    Carmo, Lucas S. do; Mendes, Leticia; Watanabe, Shigueo; Rao, Gundu; Lucas, Natasha; Sato, Karina; Barbosa, Renata F.

    2015-01-01

    In the present study, certain natural silicate minerals such as aquamarine (AB), morganite (PB), goshenite (WB), white jadeite (JW), green jadeite (JG), pink tourmaline (PT) and two varieties of jadeite-like quartz, denoted here by JQ1 and JQ2, were investigated using the thermoluminescence technique to evaluate their potential for use as very-high- and high-dose dosimeters. These minerals respond to high doses of γ-rays of up to 1000 kGy and often to very high doses of up to 3000 kGy. The TL response of these minerals may be considered to be satisfactory for applications in high-dose dosimetry. Investigations of electron paramagnetic resonance and optically stimulated luminescence dosimetry are in progress. (author)

  3. High-dose dosimetry using natural silicate minerals

    Energy Technology Data Exchange (ETDEWEB)

    Carmo, Lucas S. do; Mendes, Leticia, E-mail: isatiro@usp.br [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil); Watanabe, Shigueo; Rao, Gundu; Lucas, Natasha; Sato, Karina, E-mail: lacifid@if.usp.br [Universidade de Sao Paulo (USP), Sao Paulo, SP (Brazil). Instituto de Fisica. Departamento de Fisica Nuclear; Barbosa, Renata F., E-mail: profcelta@hotmail.com [Universidade Federal de Sao Paulo (UNIFESP), Santos, SP (Brazil). Departamento de Ciencias do Mar

    2015-07-01

    In the present study, certain natural silicate minerals such as aquamarine (AB), morganite (PB), goshenite (WB), white jadeite (JW), green jadeite (JG), pink tourmaline (PT) and two varieties of jadeite-like quartz, denoted here by JQ1 and JQ2, were investigated using the thermoluminescence technique to evaluate their potential for use as very-high- and high-dose dosimeters. These minerals respond to high doses of γ-rays of up to 1000 kGy and often to very high doses of up to 3000 kGy. The TL response of these minerals may be considered to be satisfactory for applications in high-dose dosimetry. Investigations of electron paramagnetic resonance and optically stimulated luminescence dosimetry are in progress. (author)

  4. High Dose Oral Calcium Treatment in Patients with Vitamin D-dependent Rickets Type II

    Directory of Open Access Journals (Sweden)

    R Vakili

    2017-02-01

    Full Text Available BACKGROUND AND OBJECTIVE: Vitamin D-dependent rickets type II (VDDR2 is a rare genetic disorder caused by mutations in vitamin D receptor (VDR and leads to resistance to biological effects of calcitriol. Based on the type of mutation, this disease is resistant to calcitriol even at high doses of calcitriol and successful treatment of these patients requires hypocalcemic modification through administration of high doses of calcium and bypassing the intestinal defect in VDR signaling. In addition to the need for frequent hospitalization and high costs, intravenous administration of calcium is associated with complications and problems such as arrhythmia and sepsis, venous catheter infection and hypercalciuria. This study aims to report the positive treatment effects of high doses of oral calcium in 4 patients with vitamin D-dependent rickets type II. CASE REPORT: In this study, 4 patients with vitamin D-dependent rickets type II, diagnosed based on clinical and biochemical symptoms of rickets with alopecia, underwent therapy using high doses of oral calcium (300 mg/kg/day in pediatric endocrinology and metabolism center of Imam Reza hospital. After a short period, increased growth rate in height, strength and elasticity of muscles was observed in addition to biochemical improvements without serious side effects and even one patient started walking independently within the first week of therapy for the first time. Patients were regularly followed up in terms of height and weight, growth rate and biochemical factors including calcium, phosphorus and alkaline phosphatase every 3 months for one year. CONCLUSION: Regardless of the type of mutation in vitamin D receptor, it is suggested that a 3-6 months trial of high dose oral calcium be started in each patient with vitamin D-dependent rickets type II, particularly for patients whose disease was diagnosed at lower ages.

  5. Eradicating hepatitis C virus ameliorates insulin resistance without change in adipose depots.

    Science.gov (United States)

    Milner, K-L; Jenkins, A B; Trenell, M; Tid-Ang, J; Samocha-Bonet, D; Weltman, M; Xu, A; George, J; Chisholm, D J

    2014-05-01

    Chronic hepatitis C (CHC) is associated with lipid-related changes and insulin resistance; the latter predicts response to antiviral therapy, liver disease progression and the risk of diabetes. We sought to determine whether insulin sensitivity improves following CHC viral eradication after antiviral therapy and whether this is accompanied by changes in fat depots or adipokine levels. We compared 8 normoglycaemic men with CHC (genotype 1 or 3) before and at least 6 months post viral eradication and 15 hepatitis C antibody negative controls using an intravenous glucose tolerance test and two-step hyperinsulinaemic-euglycaemic clamp with [6,6-(2) H2 ] glucose to assess peripheral and hepatic insulin sensitivity. Magnetic resonance imaging and spectroscopy quantified abdominal fat compartments, liver and intramyocellular lipid. Peripheral insulin sensitivity improved (glucose infusion rate during high-dose insulin increased from 10.1 ± 1.6 to 12 ± 2.1 mg/kg/min/, P = 0.025), with no change in hepatic insulin response following successful viral eradication, without any accompanying change in muscle, liver or abdominal fat depots. There was corresponding improvement in incremental glycaemic response to intravenous glucose (pretreatment: 62.1 ± 8.3 vs post-treatment: 56.1 ± 8.5 mm, P = 0.008). Insulin sensitivity after viral clearance was comparable to matched controls without CHC. Post therapy, liver enzyme levels decreased but, interestingly, levels of glucagon, fatty acid-binding protein and lipocalin-2 remained elevated. Eradication of the hepatitis C virus improves insulin sensitivity without alteration in fat depots, adipokine or glucagon levels, consistent with a direct link of the virus with insulin resistance. © 2013 John Wiley & Sons Ltd.

  6. Effects of insulin therapy on porosity, non-enzymatic glycation and mechanical competence in the bone of rats with type 2 diabetes mellitus.

    Science.gov (United States)

    Campbell, G M; Tiwari, S; Picke, A-K; Hofbauer, C; Rauner, M; Morlock, M M; Hofbauer, L C; Glüer, C-C

    2016-10-01

    Type 2 diabetes mellitus increases skeletal fragility; however, the contributing mechanisms and optimal treatment strategies remain unclear. We studied the effects of diabetes and insulin therapy on non-enzymatic glycation (NEG), cortical porosity (Ct.Po) and biomechanics of the bone tissue in Zucker Diabetic Fatty (ZDF) rats. Eleven-week old ZDF diabetic and non-diabetic rats were given insulin to achieve glycaemic control or vehicle seven days per week over twelve weeks (insulin dose adapted individually 0.5 international units (IU) at week 1 to 13.0IU at week 12). The right femora were excised, micro-CT scanned, and tested in 3-point bending to measure biomechanics. NEG of the midshaft was determined from bulk fluorescence. Diabetes led to increased NEG (+50.1%, p=0.001) and Ct.Po (+22.9%, p=0.004), as well as to reduced mechanical competence (max. stress: -14.2%, p=0.041, toughness: -29.7%, p=0.016) in the bone tissue. NEG and Ct.Po both correlated positively to serum glucose (NEG: R(2)=0.41, p1, Ct.Po: R(2)=0.34, p=0.003) and HbA1c (NEG: R(2)=0.42, p1, Ct.Po: R(2)=0.28, p=0.008) levels, while NEG correlated negatively with bone biomechanics (elastic modulus: R(2)=0.21, p=0.023, yield stress: R(2)=0.17, p=0.047). Twelve weeks of insulin therapy had no significant effect on NEG or Ct.Po, and was unable to improve the mechanical competence of the bone tissue. A reduction of mechanical competence was observed in the bone tissue of the diabetic rats, which was explained in part by increased collagen NEG. Twelve weeks of insulin therapy did not alter NEG, Ct.Po or bone biomechanics. However, significant correlations between NEG and serum glucose and HbA1c were observed, both of which were reduced with insulin therapy. This suggests that a longer duration of insulin therapy may be required to reduce the NEG of the bone collagen and restore the mechanical competence of diabetic bone. Copyright © 2016 Elsevier Inc. All rights reserved.

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

    Energy Technology Data Exchange (ETDEWEB)

    Pellizzon, Antonio Cassio Assis, E-mail: acapellizzon@hcancer.org.br [A.C. Camargo Cancer Center, Sao Paulo, SP (Brazil). Departamento de Radioterapia

    2016-05-15

    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. (author)

  8. Antiretroviral therapy-induced insulin resistance and oxidative deoxy nucleic acid damage in human immunodeficiency virus-1 patients

    Directory of Open Access Journals (Sweden)

    Vaishali Kolgiri Honnapurmath

    2017-01-01

    Full Text Available Background and Objectives: Insulin resistance (IR is frequent in human immunodeficiency virus (HIV infection and may be related to antiretroviral therapy (ART. Increased oxidative stress parameters and carbonyl protein are linked to insulin sensitivity. The present study is aimed to determine IR, its association with oxidative deoxy nucleic acid (DNA damage in HIV-1-infected patients with different ART status. Materials and Methods: In this case–control study, a total 600 subjects were included. We used plasma levels of the oxidized base, 8-hydroxy-2-deoxyguanosine (8-OHdG, as our biomarker of oxidative DNA damage. 8-OHdG was measured with the highly sensitive 8-OHdG check enzyme-linked immunosorbent assay kit. IR was determined using homeostasis model assessment. Results: All subjects were randomly selected and grouped as HIV-negative (control group (n = 300, HIV-positive without ART (n = 100, HIV-positive with ART first line (n = 100, and HIV-positive with ART second line (n = 100. IR and oxidative DNA damage were significantly higher in HIV-positive patients with second-line ART and HIV-positive patients with first-line ART than ART-naive patients. In a linear regression analysis, increased IR was positively associated with the increased DNA damage (odds ratio: 3.052, 95% confidence interval: 2.595–3.509 P < 0.001. Interpretation and Conclusions: In this study, we observed that ART plays a significant role in the development of IR and oxidative DNA damage in HIV-positive patients taking ART. Awareness and knowledge of these biomarkers may prove helpful to clinicians while prescribing ART to HIV/AIDS patients. Larger studies are warranted to determine the exact role of ART in the induction of IR and DNA damage.

  9. Urethral stricture following high dose rate brachytherapy for prostate cancer

    International Nuclear Information System (INIS)

    Sullivan, Lisa; Williams, Scott G.; Tai, Keen Hun; Foroudi, Farshad; Cleeve, L.; Duchesne, Gillian M.

    2009-01-01

    Purpose: To evaluate the incidence, timing, nature and outcome of urethral strictures following high dose rate brachytherapy (HDRB) for prostate carcinoma. Methods and materials: Data from 474 patients with clinically localised prostate cancer treated with HDRB were analysed. Ninety percent received HDRB as a boost to external beam radiotherapy (HDRBB) and the remainder as monotherapy (HDRBM). Urethral strictures were graded according to the Common Terminology Criteria for Adverse Events v3.0. Results: At a median follow-up of 41 months, 38 patients (8%) were diagnosed with a urethral stricture (6-year actuarial risk 12%). Stricture location was bulbo-membranous (BM) urethra in 92.1%. The overall actuarial rate of grade 2 or more BM urethral stricture was estimated at 10.8% (95% CI 7.0-14.9%), with a median time to diagnosis of 22 months (range 10-68 months). All strictures were initially managed with either dilatation (n = 15) or optical urethrotomy (n = 20). Second line therapy was required in 17 cases (49%), third line in three cases (9%) and 1 patient open urethroplasty (grade 3 toxicity). Predictive factors on multivariate analysis were prior trans-urethral resection of prostate (hazard ratio (HR) 2.81, 95% CI 1.15-6.85, p = 0.023); hypertension (HR 2.83, 95% CI 1.37-5.85, p = 0.005); and dose per fraction used in HDR (HR for 1 Gy increase per fraction 1.33, 95% CI 1.08-1.64, p = 0.008). Conclusions: BM urethral strictures are the most common late grade 2 or more urinary toxicity following HDR brachytherapy for prostate cancer. Most are manageable with minimally invasive procedures. Both clinical and dosimetric factors appear to influence the risk of stricture formation.

  10. Tolerance of the Brachial Plexus to High-Dose Reirradiation

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Allen M., E-mail: achen5@kumc.edu; Yoshizaki, Taeko; Velez, Maria A.; Mikaeilian, Argin G.; Hsu, Sophia; Cao, Minsong

    2017-05-01

    Purpose: To study the tolerance of the brachial plexus to high doses of radiation exceeding historically accepted limits by analyzing human subjects treated with reirradiation for recurrent tumors of the head and neck. Methods and Materials: Data from 43 patients who were confirmed to have received overlapping dose to the brachial plexus after review of radiation treatment plans from the initial and reirradiation courses were used to model the tolerance of this normal tissue structure. A standardized instrument for symptoms of neuropathy believed to be related to brachial plexus injury was utilized to screen for toxicity. Cumulative dose was calculated by fusing the initial dose distributions onto the reirradiation plan, thereby creating a composite plan via deformable image registration. The median elapsed time from the initial course of radiation therapy to reirradiation was 24 months (range, 3-144 months). Results: The dominant complaints among patients with symptoms were ipsilateral pain (54%), numbness/tingling (31%), and motor weakness and/or difficulty with manual dexterity (15%). The cumulative maximum dose (Dmax) received by the brachial plexus ranged from 60.5 Gy to 150.1 Gy (median, 95.0 Gy). The cumulative mean (Dmean) dose ranged from 20.2 Gy to 111.5 Gy (median, 63.8 Gy). The 1-year freedom from brachial plexus–related neuropathy was 67% and 86% for subjects with a cumulative Dmax greater than and less than 95.0 Gy, respectively (P=.05). The 1-year complication-free rate was 66% and 87%, for those reirradiated within and after 2 years from the initial course, respectively (P=.06). Conclusion: The development of brachial plexus–related symptoms was less than expected owing to repair kinetics and to the relatively short survival of the subject population. Time-dose factors were demonstrated to be predictive of complications.

  11. Prevention of incipient diabetic nephropathy by high-dose thiamine and benfotiamine.

    Science.gov (United States)

    Babaei-Jadidi, Roya; Karachalias, Nikolaos; Ahmed, Naila; Battah, Sinan; Thornalley, Paul J

    2003-08-01

    Accumulation of triosephosphates arising from high cytosolic glucose concentrations in hyperglycemia is the trigger for biochemical dysfunction leading to the development of diabetic nephropathy-a common complication of diabetes associated with a high risk of cardiovascular disease and mortality. Here we report that stimulation of the reductive pentosephosphate pathway by high-dose therapy with thiamine and the thiamine monophosphate derivative benfotiamine countered the accumulation of triosephosphates in experimental diabetes and inhibited the development of incipient nephropathy. High-dose thiamine and benfotiamine therapy increased transketolase expression in renal glomeruli, increased the conversion of triosephosphates to ribose-5-phosphate, and strongly inhibited the development of microalbuminuria. This was associated with decreased activation of protein kinase C and decreased protein glycation and oxidative stress-three major pathways of biochemical dysfunction in hyperglycemia. Benfotiamine also inhibited diabetes-induced hyperfiltration. This was achieved without change in elevated plasma glucose concentration and glycated hemoglobin in the diabetic state. High-dose thiamine and benfotiamine therapy is a potential novel strategy for the prevention of clinical diabetic nephropathy.

  12. The effect of intensive insulin therapy on the insulin-regulatable glucose transporter (GLUT4) expression in skeletal muscle in type 1 diabetes

    DEFF Research Database (Denmark)

    Andersen, P H; Vestergaard, H; Lund, S

    1993-01-01

    h given to patients with Type 1 diabetes in poor metabolic control was associated with an adaptive regulation of GLUT4 mRNA and protein levels in vastus lateralis muscle. Nine Type 1 diabetic patients with a mean HbA1c of 10.3% were included in the protocol. After intensified treatment with soluble.......54). These results suggest, that in spite of evidence that high insulin levels affect GLUT4 expression in muscle, changes in serum insulin within the physiological range do not play a major role in the short-term regulation of GLUT4 expression in Type 1 diabetic patients....

  13. Possible applications of gliptins (dipeptidyl peptidase-4 inhibitors in patients with type 2 diabetes mellitus on the various modes of insulin therapy

    Directory of Open Access Journals (Sweden)

    Gagik Radikovich Galstyan

    2015-10-01

    Full Text Available The evidence for DPP-4 inhibitors effectiveness at the late stages of type 2 diabetes mellitus (T2DM are still growing. This is particularly important for those patients who receive insulin without adequately glycemic control. This publication provides the overview of studies which demonstrate high efficacy of Vildagliptin in reducing the blood glucose level in patients with hight duration of T2DM and insulin therapy. DPP-4 inhibitors normalize basal and postprandial glucagon secretion with pancreas α-cells that helps to provide better glycemic control and to reduce a risk of hypoglycemia. Besides, there are very interesting data for Vildagliptin to reduce insulin requirement in T2DM patients in addition to HbA1clevel decrease.

  14. Cost-effectiveness analysis of exenatide twice daily (BID) vs insulin glargine once daily (QD) as add-on therapy in Chinese patients with Type 2 diabetes mellitus inadequately controlled by oral therapies.

    Science.gov (United States)

    Deng, Jing; Gu, Shuyan; Shao, Hui; Dong, Hengjin; Zou, Dajin; Shi, Lizheng

    2015-01-01

    To estimate cost-effectiveness of exenatide twice daily (BID) vs insulin glargine once daily (QD) as add-on therapy in Chinese type 2 diabetes patients not well controlled by oral anti-diabetic (OAD) agents. The Cardiff model was populated with data synthesized from three head-to-head randomized clinical trials of up to 30 weeks in China comparing exenatide BID vs insulin glargine as add-on therapies to oral therapies in the Chinese population. The Cardiff model generated outputs including macrovascular and microvascular complications, diabetes-specific mortality, costs, and quality-adjusted life years (QALYs). Cost and QALYs were estimated with a time horizon of 40 years at a discount rate of 3% from a societal perspective. Compared with insulin glargine plus OAD treatments, patients on exenatide BID plus OAD gained 1.88 QALYs, at an incremental cost saving of Chinese Renminbi (RMB) 114,593 (i.e., cost saving of RMB 61078/QALY). The cost-effectiveness results were robust to various sensitivity analyses including probabilistic sensitivity analysis. The variables with the most impact on incremental cost-effectiveness ratio included HbA1c level at baseline, health utilities decrement, and BMI at baseline. Compared with insulin glargine QD, exenatide BID as add-on therapy to OAD is a cost-effective treatment in Chinese patients inadequately controlled by OAD treatments.

  15. High-Dose Methylprednisolone fo