Science.gov

Sample records for radioiodine therapy improves

  1. Radioactive Iodine (Radioiodine) Therapy

    MedlinePlus

    ... and Stage Thyroid Cancer Treating Thyroid Cancer Radioactive Iodine (Radioiodine) Therapy for Thyroid Cancer Your thyroid gland absorbs nearly all of the iodine in your body. When radioactive iodine (RAI), also ...

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

    PubMed

    Vogiatzi, S; Liossis, A; Lamprinakou, M

    2015-07-01

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

  3. Primary hyperthyroidism--diagnosis and treatment. Indications and contraindications for radioiodine therapy.

    PubMed

    Gurgul, Edyta; Sowinski, Jerzy

    2011-01-01

    Isotope therapy is one of the methods used in primary hyperthyroidism. The therapy is based on short-range beta radiation emitted from radioactive iodine. Radioiodine administration must always be preceded by pharmacological normalization of thyroid function. Otherwise, post-radiation thyrocyte destruction and thyroid hormones release may lead to hyperthyroidism exacerbation. Indications for radioiodine therapy in Graves-Basedow disease include recurrent hyperthyroidism after thyrostatic treatment or thyroidectomy and side-effects observed during thyrostatic treatment. In toxic nodule, isotope therapy is the first choice therapy. Radioiodine is absorbed only in autonomous nodule. Therefore, it destroys only this area and does not damage the remaining thyroid tissue. In toxic goitre, radioiodine is used mostly in recurrent nodules. Absolute contraindications for radioiodine treatment are pregnancy and lactation. Relative contraindications are thyroid nodules suspected of malignancy and age under 15 years. In patients with thyroid nodules suspected of malignancy, radioiodine treatment may be applied as a preparation for surgery, if thyrostatic drugs are ineffective or contraindicated. In children, radioiodine therapy should be considered in recurrent toxic goitre and when thyrostatic drugs are ineffective. In patients with Graves-Basedow disease and thyroid-associated orbitopathy, radioiodine treatment may increase the inflammatory process and exacerbate the ophthalmological symptoms. However, thyroid-associated orbitopathy cannot be considered as a contraindication for isotope therapy. The potential carcinogenic properties of radioiodine, especially associated with tissues with high iodine uptake (thyroid, salivary glands, stomach, intestine, urinary tract, breast), have not been confirmed.

  4. Radioiodine therapy for thyroid cancer in the era of risk stratification and alternative targeted therapies.

    PubMed

    Pryma, Daniel A; Mandel, Susan J

    2014-09-01

    Differentiated thyroid cancers are typically iodine-avid and can be effectively treated with radioiodine. In most patients, radioiodine treatment is done for ablation of residual tissue, and in these cases the focus should be on using the minimum effective dose. Adjuvant therapy can be done to reduce the risk of recurrence, but optimal patient selection and dose are unclear. Patients with advanced disease benefit most from treatment with the maximum-tolerated dose. Recent research has focused on better patient selection and reduced radioiodine doses for remnant ablation. There are emerging targeted therapeutic approaches in patients who are appropriately shown to have iodine-refractory disease, with 1 drug approved by the Food and Drug Administration. Numerous trials are ongoing to assess targeted therapeutics alone or in combination with radioiodine.

  5. The role of radioiodine therapy in benign nodular goitre.

    PubMed

    Bonnema, Steen Joop; Fast, Søren; Hegedüs, Laszlo

    2014-08-01

    For treatment of benign nodular goitre the choice usually stands between surgery and (131)I therapy. (131)I therapy, used for 30 years for this condition, leads to a goitre volume reduction of 35-50% within 1-2 years. However, this treatment has limited efficacy if the thyroid (131)I uptake is low or if the goitre is large. Recombinant human TSH (rhTSH)-stimulated (131)I therapy significantly improves goitre reduction, as compared with conventional (131)I therapy without pre-stimulation, and adverse effects are few with rhTSH doses of 0.1 mg or lower. RhTSH-stimulated (131)I therapy reduces the need for additional therapy due to insufficient goitre reduction, but the price is a higher rate of hypothyroidism. Another approach with rhTSH-stimulation is to reduce the administered (131)I activity by a factor that equals the increase in the thyroid (131)I uptake. Using this approach, radiation exposure is considerably reduced while the goitre reduction is similar to that obtained with conventional (131)I therapy.

  6. Effectiveness of radioiodine therapy in treatment of hyperthyroidism.

    PubMed

    Alam, M N; Chakrabarty, R K; Akhter, M; Nahar, N; Swapan, M K; Alam, M M; Nahar, R; Sultana, N; Hallaz, M M; Alam, M M; Uddin, M M; Hossain, M A; Yasmin, S; Islam, M R

    2013-10-01

    The present non randomized clinical trial was conducted in the Center for Nuclear Medicine and Ultrasound, Mymensingh, Bangladesh for duration of one year. Total 30 patients with hyperthyroidism diagnosed by clinical and biochemical profile were included in the study. All patients received radioiodine treatment and regular follow up at 1st month, 3rd month, 6th month & 9th month were done to evaluate clinical and biochemical status and complications. Data were analyzed by computer with SPSS programme using 't' test and chi-square test. In the present study, out of 30 respondents more than three fourth of the respondents (76.6%) were in the age group of 31-50 years followed by less than 30 years are group (16.7%) and rest of respondents were in the age group of more than 50 years (06.7%). Mean±SD and range of age of the respondents were 39.80±10.02 years and 17-65 years respectively. Among the 30 respondents 11(36.7%) were male and 19(63.3%) were female. Male to female ratio was 1:1.73. Out of 30 patients 26(86.7%) presented with goiter and among them 21(80.8%) has diffused goiter and five (19.2%) had nodular goiter. Baseline mean±SD, median, range of serum T₃ level were 5.24±3.62, 4.34, 1.48-14.65nmol/L respectively. Base line mean±SD, median range of serum T₄ level were 192.25±99.17, 201.77, 1.75-336.25nmol/L respectively. Baseline mean±SD, median range of serum TSH level were 6.33±23.93, 0.15-0.07, 130.46nmol/L respectively. In the present study serum T₃, T₄ level among the respondents sharply decrease from baseline to 2nd follow up then gradually decrease from 2nd to 4th follow up. Serum TSH level gradually increases from baseline to 3rd follow up and then gradually decreases from 3rd to 4th follow up. The result showed radioiodine is an effective option for the treatment of thyrotoxicosis.

  7. Ablative radioiodine therapy for hyperthyroidism: long term follow up study.

    PubMed Central

    Kendall-Taylor, P; Keir, M J; Ross, W M

    1984-01-01

    A total of 225 patients were treated for hyperthyroidism with 555 MBq (15 mCi) radioiodine to ablate the thyroid and induce early hypothyroidism. The efficacy of this treatment in eradicating hyperthyroidism and problems of follow up were assessed one to six years later from case records and questionnaires. Information was received from 197 out of 219 live patients (90%) and from 160 doctors concerning 207 patients (92%). Only three patients were not traced and six had died since treatment. The modal time to hypothyroidism was three months, and 64% of patients were hypothyroid at one year; 5.6% had failed to become euthyroid within one year. Ninety five per cent of patients had been seen by the doctor and 82% had had a thyroid test done within the past two years. Most doctors preferred patients to be returned to their care once thyroxine treatment was stabilised. An ablative dose of 131I is recommended as an effective means of treatment which has clear advantages over conventional methods. Good communications and effective follow up should ensure success. PMID:6432100

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

    SciTech Connect

    Gamstedt, A.; Karlsson, A. )

    1991-07-01

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

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

    PubMed Central

    Yürekli, Yakup; Cengiz, Arzu; Güney, Engin

    2015-01-01

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

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

    SciTech Connect

    Franke, A.; Oeff, K.

    1984-01-01

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

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

    SciTech Connect

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

    2014-01-15

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

  12. Radioiodine therapy in benign thyroid diseases: effects, side effects, and factors affecting therapeutic outcome.

    PubMed

    Bonnema, Steen Joop; Hegedüs, Laszlo

    2012-12-01

    Radioiodine ((131)I) therapy of benign thyroid diseases was introduced 70 yr ago, and the patients treated since then are probably numbered in the millions. Fifty to 90% of hyperthyroid patients are cured within 1 yr after (131)I therapy. With longer follow-up, permanent hypothyroidism seems inevitable in Graves' disease, whereas this risk is much lower when treating toxic nodular goiter. The side effect causing most concern is the potential induction of ophthalmopathy in predisposed individuals. The response to (131)I therapy is to some extent related to the radiation dose. However, calculation of an exact thyroid dose is error-prone due to imprecise measurement of the (131)I biokinetics, and the importance of internal dosimetric factors, such as the thyroid follicle size, is probably underestimated. Besides these obstacles, several potential confounders interfere with the efficacy of (131)I therapy, and they may even interact mutually and counteract each other. Numerous studies have evaluated the effect of (131)I therapy, but results have been conflicting due to differences in design, sample size, patient selection, and dose calculation. It seems clear that no single factor reliably predicts the outcome from (131)I therapy. The individual radiosensitivity, still poorly defined and impossible to quantify, may be a major determinant of the outcome from (131)I therapy. Above all, the impact of (131)I therapy relies on the iodine-concentrating ability of the thyroid gland. The thyroid (131)I uptake (or retention) can be stimulated in several ways, including dietary iodine restriction and use of lithium. In particular, recombinant human thyrotropin has gained interest because this compound significantly amplifies the effect of (131)I therapy in patients with nontoxic nodular goiter.

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

    PubMed

    Shahbazi-Gahrouei, Daryoush; Ayat, Saba

    2015-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2016-03-01

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

  15. Improved therapeutic outcomes of thermal ablation on rat orthotopic liver allograft sarcoma models by radioiodinated hypericin induced necrosis targeted radiotherapy

    PubMed Central

    Gao, Long; Zhang, Jian; Ma, Tengchuang; Yao, Nan; Gao, Meng; Shan, Xin; Ni, Yicheng; Shao, Haibo; Xu, Ke

    2016-01-01

    Residual tumor resulting in tumor recurrence after various anticancer therapies is an unmet challenge in current clinical oncology. This study aimed to investigate the hypothesis that radioiodinated hypericin (131I-Hyp) may inhibit residual tumor recurrence after microwave ablation (MWA) on rat orthotopic liver allograft sarcoma models. Thirty Sprague-Dawley (SD) rats with hepatic tumors were divided into three groups: Group A received laparotomy MWA and sequential intravenous injection (i.v.) of 131I labelled hypericin (131I-Hyp) in a time interval of 24 h; Group B received only laparotomy MWA; Group C was a blank control. Tumor inhibitory effects were monitored with in vivo magnetic resonance imaging (MRI) and these findings were compared to histopathology data before (baseline, day 0) and 1, 4, and 8 days after MWA. In addition, biodistribution of 131I-Hyp was assessed with in vivo single-photon emission computed tomography-computed tomography (SPECT-CT) imaging, in vitro autoradiography, fluorescent microscopy, and gamma counting. A fast clearance of 131I-Hyp and increasing deposit in necrotic tumors appeared over time, with a significantly higher radioactivity than other organs (0.9169 ± 1.1138 % ID/g, P < 0.01) on day 9. Tumor growth was significantly slowed down in group A compared to group B and C according to MRI images and corresponding tumor doubling time (12.13 ± 1.99, 4.09 ± 0.97, 3.36 ± 0.72 days respectively). The crescent tagerability of 131I-Hyp to necrosis was visualized consistently by autoradiography and fluorescence microscopy. In conclusion, 131I-Hyp induced necrosis targeted radiotherapy improved therapeutic outcomes of MWA on rat orthotopic liver allograft sarcoma models. PMID:27285983

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

    SciTech Connect

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

    1985-06-01

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

  17. Adverse Reactions to Radioiodine 131I Therapy of Goiter in West African Tertiary Hospital

    PubMed Central

    Onimode, Yetunde A.; Ejeh, John E.; Orunmuyi, Akintunde T.

    2016-01-01

    Objective: Radioactive iodine therapy (RAIT) is established as an efficient means of treating toxic goiter (TG) globally. The field of nuclear medicine (NM) still appears novel to many Nigerian clinicians and patients. A culturally embedded dread of radiation may raise ethical and moral concerns about potential adverse effects in the wake of RAIT in our setting. An adverse drug reaction may be described as “a response to a drug which is noxious and unintended, and which occurs at doses normally used in man”. This study therefore, seeks to review adverse reactions (ARs) experienced following RAIT. We would also like to improve patient and physician education about the safety profile of RAIT. Methods: This is a retrospective analysis of all patients who had received RAIT for thyroid disease from August 2006 to June 2015. Results: Forty typical ARs were experienced following 36 therapy sessions (18.65%) with RAIT in 35 patients (21.47%) aged 17-78 years, of which three had multiple sessions for well-differentiated thyroid carcinoma (WDTC). Conclusion: RAIT remains a safe option for the treatment of benign and TG. The experienced ARs are mainly mild to moderate in severity and mostly short-lived. As larger doses of radioactive iodine for WDTC and TG were more commonly associated with ARs, our study suggests that these patients merit stronger prophylactic measures as well as closer monitoring for earlier detection and management of these reactions. PMID:27751975

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

    PubMed

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

    2016-01-01

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

  19. Persistent high TRAb values during pregnancy predict increased risk of neonatal hyperthyroidism following radioiodine therapy for refractory hyperthyroidism.

    PubMed

    Hamada, Noboru; Momotani, Naoko; Ishikawa, Naofumi; Yoshimura Noh, Jaeduk; Okamoto, Yasuyuki; Konishi, Toshiaki; Ito, Koichi; Ito, Kunihiko

    2011-01-01

    Serum levels of TSH receptor antibody (TRAb) often increase after radioiodine treatment for Graves' disease, and high-serum levels of maternal TRAb in late pregnancy indicate a risk of neonatal hyperthyroidism. The aim of this retrospective study is to investigate the characteristics of Graves' women who had a history of radioiodine treatment for intractable Graves' disease, and whose neonates suffered from hyperthyroidism. The subjects of this study were 45 patients with Graves' disease who became pregnant during the period from 1988 to 1998 after receiving radioiodine treatment at Ito Hospital. 25 of the 45 subjects had had a relapse of hyperthyroidism after surgical treatment for Graves' disease. 19 pregnancies were excluded because of artificial or spontaneous abortion. In the remaining 44 pregnancies of 35 patients, neonatal hyperthyroidism developed in 5 (11.3%) pregnancies of 4 patients. Serum levels of TRAb at delivery were higher in patients whose neonates suffered from hyperthyroidism (NH mother) than those of patients who delivered normal infants (N mother). Furthermore, serum levels of TRAb in NH mother did not change during pregnancy, although those of 4 patients of N mother, in which serum levels of TRAb before radioiodine treatment were as high as in NH mother, decreased significantly during pregnancy. In conclusion, women who delivered neonates with hyperthyroidism following radioiodine treatment seem to have very severe and intractable Graves' disease. Persistent high TRAb values during pregnancy observed in those patients may be a cause of neonatal hyperthyroidism.

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

    PubMed

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

    2016-06-01

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

  1. Serial Thyroglobulin Variation Trend Shortly after Radioiodine Therapy in Poorly to Moderately Differentiated Recurrent Thyroid Cancer.

    PubMed

    2016-06-10

    Objective To dynamically observe the early change of thyroglobulin(Tg) levels after (131)I therapy in differentiated thyroid cancer(DTC) patients. Methods The study enrolled 22 post-total-thyroidectomy DTC patients and they were stratified as low to intermediate recurrence according to the 2009 American Thyroid Association Guidelines. The clinical data including pre-ablation stimulated Tg (ps-Tg),corresponding thyroid stimulating hormone(TSH),anti-thyroglobulin (TgAb) values,and the afterwards parameters were dynamically measured each week in the first month after (131)I therapy. Values collected at the first time were defined as Tg 0 and TSH0,while Tg1 and TSH1 were collected at the first week after (131)I therapy respectively. Then the variation trend curves of Tg were drawn,and factors influencing the variation of Tg were analyzed. Two groups were divided according to Tg levels:G1 (Tg≤0.1 ng/ml,n=9) and G2(Tg>0.1 ng/ml,n=13). Results The rates of negative Tg were 4.5%,18.0%,27.0%,36.0%,and 41.0%,respectively,exactly before (131)I therapy and the 1(st),2(nd),3(rd),and 4(th) week after the therapy. One-way analysis of variance showed that the two groups statistically differed in age (F=3.182,P=0.04) and remnant thyroid (U=4.849,P=0.026). Multivariate logistic regression analysis showed that early negative Tg was related to remnant thyroid tissue (OR:2.132;95%Cl:1.418-6.532,P=0.009).Conclusions Negative Tg can be achieved in nearly half of DTC patients by the end of first month after (131)I therapy. The negative conversion is closely related with the volume of remnant thyroid tissue.

  2. Manipulation of PBF/PTTG1IP Phosphorylation Status; a Potential New Therapeutic Strategy for Improving Radioiodine Uptake in Thyroid and Other Tumors

    PubMed Central

    Smith, V. E.; Sharma, N.; Watkins, R. J.; Read, M. L.; Ryan, G. A.; Kwan, P. P.; Martin, A.; Watkinson, J. C.; Boelaert, K.; Franklyn, J. A.

    2013-01-01

    Context: The clinical effectiveness of ablative radioiodine treatment of thyroid tumors is limited by the availability of the sodium iodide symporter (NIS) at the plasma membrane (PM) for uptake of 131I. A significant proportion of well-differentiated thyroid tumors are unable to concentrate sufficient radioiodine for effective therapy, and in other tumor models such as breast tumors, where radioiodine uptake would be an attractive therapeutic option, uptake is insufficient. Objective: Pituitary tumor–transforming gene-binding factor (PBF; PTTG1IP) is overexpressed in multiple cancers and significantly decreases NIS expression at the PM. The goal of this study was to identify a method by which PBF repression of NIS may be overcome in human tumors. Results: Here, we identify PBF as a tyrosine phosphoprotein that specifically binds the proto-oncogene tyrosine protein kinase Src in mass spectrometry, glutathione S-transferase pulldown and coimmunoprecipitation assays. Src induction leads to phosphorylation at PBF residue Y174. Abrogation of this residue results in PM retention and a markedly reduced ability to bind NIS. The Src inhibitor PP1 inhibits PBF phosphorylation in multiple cell lines in vitro, including human primary thyroid cells. Of direct clinical importance to the treatment of thyroid cancer, PP1 stimulates iodide uptake by transfected NIS in TPC1 thyroid carcinoma cells and entirely overcomes PBF repression of iodide uptake in human primary thyroid cells. Conclusions: We propose that targeting PBF phosphorylation at residue Y174 via tyrosine kinase inhibitors may be a novel therapeutic strategy to enhance the efficacy of ablative radioiodine treatment in thyroid and other endocrine and endocrine-related tumors. PMID:23678037

  3. Fetus dose estimation in thyroid cancer post-surgical radioiodine therapy.

    PubMed

    Mianji, Fereidoun A; Diba, Jila Karimi; Babakhani, Asad

    2015-01-01

    Unrecognised pregnancy during radioisotope therapy of thyroid cancer results in hardly definable embryo/fetus exposures, particularly when the thyroid gland is already removed. Sources of such difficulty include uncertainty in data like pregnancy commencing time, amount and distribution of metastasized thyroid cells in body, effect of the thyroidectomy on the fetus dose coefficient etc. Despite all these uncertainties, estimation of the order of the fetus dose in most cases is enough for medical and legal decision-making purposes. A model for adapting the dose coefficients recommended by the well-known methods to the problem of fetus dose assessment in athyrotic patients is proposed. The model defines a correction factor for the problem and ensures that the fetus dose in athyrotic pregnant patients is less than the normal patients. A case of pregnant patient undergone post-surgical therapy by I-131 is then studied for quantitative comparison of the methods. The results draw a range for the fetus dose in athyrotic patients using the derived factor. This reduces the concerns on under- or over-estimation of the embryo/fetus dose and is helpful for personal and/or legal decision-making on abortion.

  4. Receptor-purified, Bolton-Hunter radioiodinated, recombinant, human epidermal growth factor: An improved radioligand for receptor studies

    SciTech Connect

    Kermode, J.C.; Tritton, T.R. )

    1990-01-01

    We report an assessment of the applicability of the Bolton-Hunter method to the radioiodination of epidermal growth factor (EGF). Recombinant human EGF (hEGF) could be radioiodinated successfully by this method, whereas murine EGF could not. Bolton-Hunter {sup 125}I-labeled hEGF was compared with commercial 125I-labeled hEGF prepared by the chloramine-T radioiodination method. Neither radioligand was sufficiently pure for a detailed characterization of the purportedly heterogeneous pattern of binding of EGF to its receptors. A procedure based on receptor adsorption was thus developed for repurification of the Bolton-Hunter 125I-labeled hEGF. This provided a much purer radioligand suitable for detailed studies of receptor-binding heterogeneity.

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

    SciTech Connect

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

    2011-10-15

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

  6. EANM Dosimetry Committee series on standard operational procedures for pre-therapeutic dosimetry II. Dosimetry prior to radioiodine therapy of benign thyroid diseases.

    PubMed

    Hänscheid, Heribert; Canzi, Cristina; Eschner, Wolfgang; Flux, Glenn; Luster, Markus; Strigari, Lidia; Lassmann, Michael

    2013-07-01

    The EANM Dosimetry Committee Series "Standard Operational Procedures for Pre-Therapeutic Dosimetry" (SOP) provides advice to scientists and clinicians on how to perform patient-specific absorbed dose assessments. This particular SOP describes how to tailor the therapeutic activity to be administered for radioiodine therapy of benign thyroid diseases such as Graves' disease or hyperthyroidism. Pretherapeutic dosimetry is based on the assessment of the individual (131)I kinetics in the target tissue after the administration of a tracer activity. The present SOP makes proposals on the equipment to be used and guides the user through the measurements. Time schedules for the measurement of the fractional (131)I uptake in the diseased tissue are recommended and it is shown how to calculate from these datasets the therapeutic activity necessary to administer a predefined target dose in the subsequent therapy. Potential sources of error are pointed out and the inherent uncertainties of the procedures depending on the number of measurements are discussed. The theoretical background and the derivation of the listed equations from compartment models of the iodine kinetics are explained in a supplementary file published online only.

  7. Thyroid peroxidase (TPO) as a tumor marker in the follow-up of differentiated thyroid carcinomas with surgical and ablative radioiodine therapy. An assessment after evaluation.

    PubMed

    Franke, W G; Zöphel, K; Wunderlich, G; Kühne, A; Schimming, C; Kropp, J; Bredow, J

    1999-01-01

    The clinical significance of serum thyroid peroxidase (TPO) for differentiated thyroid carcinomas(DTA) is estimated differently. In our preliminary studies it was found that TPO presented information extending those that from hTG. For further clarification a prospective follow-up study was performed including 66 female and 14 male total thyroidectomized patients with DTA for the time course of TPO and human thyroglobulin (hTg) in relation to the ablative radioidine therapy (ART). In 34/50 evaluable cases TPO levels showed an approximately analogous time course with hTg. In relation to the extension of residues, some cases presented increasing of TPO and hTG after radioiodine treatment. 6/7 patients suffering from extended postoperative residues with high anti hTg levels but without elevated TPO concentrations showed distinctly elevated TPO values. Therefore, TPO seems to be an indicator for the destruction of normal thyroid cells or thyroid tumor cells. The clinical value of TPO seems to be in the time being limited to DTA due to false negative hTg values. However, it should be possible that TPO can did the evaluation of thyroid specific therapy.

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

    PubMed

    Shahbazi-Gahrouei, Daryoush; Ayat, Saba

    2012-07-01

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

  9. Radioiodine and radiotherapy in the management of thyroid cancers

    SciTech Connect

    Simpson, W.J. )

    1990-06-01

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

  10. Extrathyroidal Radioiodine Accumulation in a Fibroadenoma of the Breast.

    PubMed

    Kim, Myoung Hyoun; Kim, Hun Soo; Park, Soon-Ah

    2017-02-01

    A 45-year-old woman with a differentiated thyroid carcinoma received adjuvant radioiodine therapy following total thyroidectomy and left modified radical neck dissection. A posttherapy planar radioiodine scan showed multifocal uptake in the thyroid bed and left chest. SPECT/CT revealed a fibroadenoma in the left breast. Six months later, an I scan showed no iodine avidity in the breast fibroadenoma, whereas ultrasonography showed no significant change in the size of the fibroadenoma. Altered radioiodine uptake of a breast fibroadenoma can be observed on follow-up scans after cytotoxic radioiodide treatment in patients with differentiated thyroid carcinoma.

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

    SciTech Connect

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

    1983-08-01

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

  12. Radioiodinated branched carbohydrates

    DOEpatents

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

    1989-01-01

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

  13. The added clinical value of 18F-FDG PET/CT in evaluating intratracheal recurrence of differentiated thyroid carcinoma: implications for planning surgery, assessing its completeness, and planning radioiodine therapy.

    PubMed

    Basu, Sandip; Abhyankar, Amit

    2013-12-01

    In selected patients with differentiated thyroid carcinoma, (18)F-FDG PET/CT has been shown to have added value. We present 2 clinical examples in the settings of both iodine-concentrating and non-iodine-concentrating lesions with tracheal involvement with special reference to its importance in planning of surgery or radioiodine therapy and assessing completeness of surgery. We believe that the use of PET/CT should be considered on a case-by-case basis and specifically when SPECT/CT is unavailable or has inconclusive findings.

  14. Radioiodine: the classic theranostic agent.

    PubMed

    Silberstein, Edward B

    2012-05-01

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

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

    PubMed

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

    2016-07-01

    Radiation Protection in Radiology, Nuclear Medicine and Radio Oncology is of the utmost importance. Radioiodine therapy is a frequently used and effective method for the treatment of thyroid disease. Prior to each therapy the radioactivity of the [ 131I]-capsule must be determined to prevent misadministration. This leads to a significant radiation exposure to the staff. We describe an alternative method, allowing a considerable reduction of the radiation exposure. Two [ 131I]-capsules (A01=2818.5; A02=73.55.0 MBq) were measured multiple times in their own delivery lead containers - that is to say, [ 131I]-capsules remain inside the containers during the measurements (shielded measurement) using a dose calibrator and a well-type and a thyroid uptake probe. The results of the shielded measurements were correlated linearly with the [ 131I]-capsules radioactivity to create calibration curves for the used devices. Additional radioactivity measurements of 50 [ 131I]-capsules of different radioactivities were done to validate the shielded measuring method. The personal skin dose rate (HP(0.07)) was determined using calibrated thermo luminescent dosimeters. The determination coefficients for the calibration curves were R2>0.9980 for all devices. The relative uncertainty of the shielded measurement was <6.8%. At a distance of 10 cm from the unshielded capsule the HP(0.07) was 46.18 μSv/(GBq⋅s), and on the surface of the lead container containing the [ 131I]-capsule the HP(0.07) was 2.99 and 0.27 μSv/(GBq⋅s) for the two used container sizes. The calculated reduction of the effective dose by using the shielded measuring method was, depending on the used container size, 74.0% and 97.4%, compared to the measurement of the unshielded [ 131I]-capsule using a dose calibrator. The measured reduction of the effective radiation dose in the practice was 56.6% and 94.9 for size I and size II containers. The shielded [ 131I]-capsule measurement reduces the

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

    SciTech Connect

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

    1994-08-01

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

  17. Facilities for radio-iodination.

    PubMed

    Ramsey, N W; Bhattacharyya, A K; Dunn, M J

    1980-02-01

    A fume cabinet with a sloping front, fitted with a chemical absorbing filter and extractor fan, but without exhaust ducting, appears to possess considerable advantages for radio-iodination work compared with standard fume cupboards.

  18. Quantification of absorbed doses to urine bladder depending on drinking water during radioiodine therapy to thyroid cancer patients: a clinical study using MIRDOSE3.

    PubMed

    Sabbir Ahmed, A S M; Demir, M; Yasar, D; Uslu, I

    2003-07-01

    The object of the study was to quantify the absorbed doses to urinary bladder using MIRDOSE3 (medical internal radiation dose package program) depending on drinking water after giving radioiodine dose to thyroid cancer patients. Twenty-nine female thyroid cancer patients (aged 40-60 years, mean 50 years) were selected. The therapeutic doses ranged from 3700 to 7400 MBq of 131I. The radioiodine uptake was measured at 1 cm distance from three organs (previously marked), the thyroid, thigh and stomach, by using a calibrated Eberline ESP-2 GM counter, with a special arrangement of each patient. Urine samples were collected every 12 h for first 72 h, and then every 24 h for the next 96 h. The individual biological half-life of excreted urine was calculated using individual effective half-life. Absorbed doses were calculated for an adult female phantom using the dynamic bladder model of MIRDOSE3 program in two phases: firstly, for different voiding intervals; and secondly, depending on individual drinking water. An average of 85% of the total dose passed through the urinary tract within the first 72 h, with a biological half-life of 28.5+/-0.747 h, and 9% for the next 96 h with a biological half life of 118.43+/-0.645 h. The voiding interval shows great impact on total absorbed dose to bladder and water supplementation needs to be intensified to reduce absorbed doses to bladder wall for the first 3 days.

  19. Radioiodination of chicken luteinizing hormone without affecting receptor binding potency

    SciTech Connect

    Kikuchi, M.; Ishii, S. )

    1989-12-01

    By improving the currently used lactoperoxidase method, we were able to obtain radioiodinated chicken luteinizing hormone (LH) that shows high specific binding and low nonspecific binding to a crude plasma membrane fraction of testicular cells of the domestic fowl and the Japanese quail, and to the ovarian granulosa cells of the Japanese quail. The change we made from the original method consisted of (1) using chicken LH for radioiodination that was not only highly purified but also retained a high receptor binding potency; (2) controlling the level of incorporation of radioiodine into chicken LH molecules by employing a short reaction time and low temperature; and (3) fractionating radioiodinated chicken LH further by gel filtration using high-performance liquid chromatography. Specific radioactivity of the final {sup 125}I-labeled chicken LH preparation was 14 microCi/micrograms. When specific binding was 12-16%, nonspecific binding was as low as 2-4% in the gonadal receptors. {sup 125}I-Labeled chicken LH was displaced by chicken LH and ovine LH but not by chicken follicle-stimulating hormone. The equilibrium association constant of quail testicular receptor was 3.6 x 10(9) M-1. We concluded that chicken LH radioiodinated by the present method is useful for studies of avian LH receptors.

  20. Targeted treatments of radio-iodine refractory differentiated thyroid cancer.

    PubMed

    de la Fouchardière, C

    2015-02-01

    Radio-iodine refractory metastatic thyroid cancers are rare and their management was until recently relatively complex. New therapeutic agents, kinase inhibitors, joined since the early 2000s the fight against these cancers with very promising results. These targeted agents showed for two of them (sorafenib; lenvatinib), in randomized phase III trials, a significant improvement in response rate and progressionfree survival when compared to placebo, leading to the first approval for radio-iodine refractory metastatic thyroid cancers. In parallel, patients also benefited from the development of interventional radiology techniques and organization of cares in oncology, with multidisciplinary management strengthened by the creation of a national network (TUTHYREF).

  1. Improve T Cell Therapy in Neuroblastoma

    DTIC Science & Technology

    2014-07-01

    AD_________________ Award Number: W81XWH-10-1-0425 TITLE: Improve T Cell Therapy in Neuroblastoma ...2014 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Improve T Cell Therapy in Neuroblastoma 5b. GRANT NUMBER W81XWH-10-1-0425 5c. PROGRAM...AVAILABILITY STATEMENT Approved for Public Release; Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT Neuroblastoma (NB) is

  2. Treatment of hyperthyroidism with radioiodine targeted activity: A comparison between two dosimetric methods.

    PubMed

    Amato, Ernesto; Campennì, Alfredo; Leotta, Salvatore; Ruggeri, Rosaria M; Baldari, Sergio

    2016-06-01

    Radioiodine therapy is an effective and safe treatment of hyperthyroidism due to Graves' disease, toxic adenoma, toxic multinodular goiter. We compared the outcomes of a traditional calculation method based on an analytical fit of the uptake curve and subsequent dose calculation with the MIRD approach, and an alternative computation approach based on a formulation implemented in a public-access website, searching for the best timing of radioiodine uptake measurements in pre-therapeutic dosimetry. We report about sixty-nine hyperthyroid patients that were treated after performing a pre-therapeutic dosimetry calculated by fitting a six-point uptake curve (3-168h). In order to evaluate the results of the radioiodine treatment, patients were followed up to sixty-four months after treatment (mean 47.4±16.9). Patient dosimetry was then retrospectively recalculated with the two above-mentioned methods. Several time schedules for uptake measurements were considered, with different timings and total number of points. Early time schedules, sampling uptake up to 48h, do not allow to set-up an accurate treatment plan, while schedules including the measurement at one week give significantly better results. The analytical fit procedure applied to the three-point time schedule 3(6)-24-168h gave results significantly more accurate than the website approach exploiting either the same schedule, or the single measurement at 168h. Consequently, the best strategy among the ones considered is to sample the uptake at 3(6)-24-168h, and carry out an analytical fit of the curve, while extra measurements at 48 and 72h lead only marginal improvements in the accuracy of therapeutic activity determination.

  3. Radioactive Iodine Therapy of Differentiated Thyroid Carcinoma: Redesigning the Paradigm

    PubMed Central

    Goldsmith, Stanley J.

    2017-01-01

    Radioactive iodine therapy has evolved over the past 70 years from treatment of known metastatic thyroid carcinoma to include adjuvant use to decrease the incidence of recurrent disease and to ablation of normal remnant tissue following thyroidectomy, even for minimal tumor involvement. Advances in laboratory testing, development of drugs useful in radioiodine treatment, as well as advances in radiation detection and imaging instrumentation, have progressively improved the utility of radioiodine therapy of differentiated thyroid carcinoma. Guidelines have proliferated and they have become more detailed and complex. This trend is likely to continue as the science and technology involved increases in sophistication and efficacy. PMID:28117291

  4. Radioiodine in the Savannah River Site environment

    SciTech Connect

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

    1993-01-15

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

  5. Improved exercise myocardial perfusion during lidoflazine therapy

    SciTech Connect

    Shapiro, W.; Narahara, K.A.; Park, J.

    1983-11-01

    Lidoflazine is a synthetic drug with calcium-channel blocking effects. In a study of 6 patients with severe classic angina pectoris, single-blind administration of lidoflazine was associated with improved myocardial perfusion during exercise as determined by thallium-201 stress scintigraphy. These studies demonstrate that lidoflazine therapy is associated with relief of angina, an increased physical work capacity, and improved regional myocardial perfusion during exercise.

  6. Accuracy and optimal timing of activity measurements in estimating the absorbed dose of radioiodine in the treatment of Graves' disease

    NASA Astrophysics Data System (ADS)

    Merrill, S.; Horowitz, J.; Traino, A. C.; Chipkin, S. R.; Hollot, C. V.; Chait, Y.

    2011-02-01

    Calculation of the therapeutic activity of radioiodine 131I for individualized dosimetry in the treatment of Graves' disease requires an accurate estimate of the thyroid absorbed radiation dose based on a tracer activity administration of 131I. Common approaches (Marinelli-Quimby formula, MIRD algorithm) use, respectively, the effective half-life of radioiodine in the thyroid and the time-integrated activity. Many physicians perform one, two, or at most three tracer dose activity measurements at various times and calculate the required therapeutic activity by ad hoc methods. In this paper, we study the accuracy of estimates of four 'target variables': time-integrated activity coefficient, time of maximum activity, maximum activity, and effective half-life in the gland. Clinical data from 41 patients who underwent 131I therapy for Graves' disease at the University Hospital in Pisa, Italy, are used for analysis. The radioiodine kinetics are described using a nonlinear mixed-effects model. The distributions of the target variables in the patient population are characterized. Using minimum root mean squared error as the criterion, optimal 1-, 2-, and 3-point sampling schedules are determined for estimation of the target variables, and probabilistic bounds are given for the errors under the optimal times. An algorithm is developed for computing the optimal 1-, 2-, and 3-point sampling schedules for the target variables. This algorithm is implemented in a freely available software tool. Taking into consideration 131I effective half-life in the thyroid and measurement noise, the optimal 1-point time for time-integrated activity coefficient is a measurement 1 week following the tracer dose. Additional measurements give only a slight improvement in accuracy.

  7. Interference of iohexol with radioiodine thyroid uptake in the hyperthyroid cat.

    PubMed

    Peremans, Kathelijne; Vandermeulen, Eva; van Hoek, Ingrid; Daminet, Sylvie; Vermeire, Simon; Bacher, Klaus

    2008-10-01

    Absorbed thyroid dose and effective half-life were determined in 46 hyperthyroid cats after treatment with a low dose (mean 111MBq) of radioiodine intravenously. Thirteen of these cats had received iohexol for glomerular filtration rate (GFR) measurement within 24h before treatment with radioiodine in view of another ongoing study at our institution. Pre-therapy values were obtained for total thyroxine (TT(4)) and for the thyroid to salivary gland ratio with sodium pertechnetate gamma-camera imaging. All cats underwent post-therapy scans at 24, 48 and 120 h for evaluation of radioactive iodine uptake (RAIU) and the effective half-life of radioiodine. The absorbed dose was calculated from the cumulative activity with Olinda software. Both groups were comparable in age, TT(4) and the ratio of thyroid activity to salivary gland activity. Statistical analysis revealed a significant decreased absorbed dose in the thyroid in the iohexol group. This decreased uptake was not accompanied by an decreased effective half-life of the radioiodine. The variation of inter-individual RAIU decreased in this group and more homogenous absorbed doses were obtained. No significant difference in outcome could be demonstrated. However, a tendency towards a higher number of residual hyperthyroidism in the iohexol group was noted (15 versus 6% in control group). This study demonstrates that iohexol interferes with the uptake of radioiodine in the hyperthyroid cat but does not provoke increased turnover. In this study, albeit including a small number of cats, outcome did not seem to be significantly affected.

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

    SciTech Connect

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

    2006-11-03

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

  9. Immobilization of radioiodine in synthetic boracite

    DOEpatents

    Babad, H.; Strachan, D.M.

    1982-09-23

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

  10. [Lenvatinib in radioiodine refractory thyroid carcinomas].

    PubMed

    de la Fouchardiere, Christelle

    2016-11-01

    Differentiated thyroid cancers are usually cured by an appropriate surgery and a radioiodine remnant ablation. If metastases occur, successive radioiodine administrations and/or local treatments can be provided. Nevertheless, some patients will be, or become refractory to radioiodine. In case of significant and rapid progression of metastatic lesions, they will be candidate to kinase inhibitor treatments. Two agents are now approved in this situation: sorafenib and lenvatinib. Lenvatinib (Lenvima(®)) is a tyrosine kinase inhibitor (TKI) targeting the VEGFR1-3, FGFR 1-4, PDGFR-α, RET and c-kit. It received an FDA and EMA approval in February and March 2015 for the treatment of radioiodine refractory thyroid cancers following the SELECT study's results. In this study, patients treated with lenvatinib had a significant increase in progression-free survival (18.3 months vs. 3.6 months; HR=0.21; CI=0.14-0.31, P < 0.001) and response rate (64.8% vs. 1.5% with placebo). The median overall survival was not reached in both groups at the time of data cutoff. In France, lenvatinib was first available within a compassionate use program (ATU) and is now dispended by hospitals because not yet marketed.

  11. Integrating spheres for improved skin photodynamic therapy.

    PubMed

    Glennie, Diana L; Farrell, Thomas J; Hayward, Joseph E; Patterson, Michael S

    2010-01-01

    The prescribed radiant exposures for photodynamic therapy (PDT) of superficial skin cancers are chosen empirically to maximize the success of the treatment while minimizing adverse reactions for the majority of patients. They do not take into account the wide range of tissue optical properties for human skin, contributing to relatively low treatment success rates. Additionally, treatment times can be unnecessarily long for large treatment areas if the laser power is not sufficient. Both of these concerns can be addressed by the incorporation of an integrating sphere into the irradiation apparatus. The light fluence rate can be increased by as much as 100%, depending on the tissue optical properties. This improvement can be determined in advance of treatment by measuring the reflectance from the tissue through a side port on the integrating sphere, allowing for patient-specific treatment times. The sphere is also effective at improving beam flatness, and reducing the penumbra, creating a more uniform light field. The side port reflectance measurements are also related to the tissue transport albedo, enabling an approximation of the penetration depth, which is useful for real-time light dosimetry.

  12. Differentiated Thyroid Cancer: Management of Patients with Radioiodine Nonresponsive Disease

    PubMed Central

    Busaidy, Naifa Lamki; Cabanillas, Maria E.

    2012-01-01

    Differentiated thyroid carcinoma (papillary and follicular) has a favorable prognosis with an 85% 10-year survival. The patients that recur often require surgery and further radioactive iodine to render them disease-free. Five percent of thyroid cancer patients, however, will eventually succumb to their disease. Metastatic thyroid cancer is treated with radioactive iodine if the metastases are radioiodine avid. Cytotoxic chemotherapies for advanced or metastatic noniodine avid thyroid cancers show no prolonged responses and in general have fallen out of favor. Novel targeted therapies have recently been discovered that have given rise to clinical trials for thyroid cancer. Newer aberrations in molecular pathways and oncogenic mutations in thyroid cancer together with the role of angiogenesis in tumor growth have been central to these discoveries. This paper will focus on the management and treatment of metastatic differentiated thyroid cancers that do not take up radioactive iodine. PMID:22530159

  13. Synthesis and biodistribution of radioiodinated nicotine analogs

    SciTech Connect

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

    1984-01-01

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

  14. Giving radioiodine? Think about airport security alarms.

    PubMed

    Kaniuka-Jakubowska, S; Lewczuk, A; Mizan-Gross, K; Obołończyk, L; Lass, P; Sworczak, K

    2012-01-01

    An increased sensitivity of airport detectors, a growing number of isotopic tests, and globalization of the society have raised a number of false positive radioactive alarms at airports and public places. This paper presents two new cases of patients who triggered airport security alarms after receiving 740MBq of (131)I for non-toxic goitre and attempts to compare surprisingly limited literature concerning this problem. A 57-year-old man triggered a security alarm at three different airports on the 17th, 28th, and 31st day after radioiodine exposure. Interestingly enough, in the meantime, on the 18th and 22nd day, no radiation was detected in him at the airport where he was twice detained as a source of radiation later on. The second case presents a 45-year-old woman who activated security alarm detectors while crossing a border on her coach trip 28 days after radioiodine administration.

  15. Mitochondria-targeting for improved photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Ngen, Ethel J.

    Photodynamic therapy (PDT) is an emerging cancer therapeutic modality, with great potential to selectively treat surface cancers, thus minimizing systemic side effects. In this dissertation, two approaches to deliver photosensitizers to mitochondria were investigated: 1) Reducing photosensitizer sizes to improve endocytosis and lysosomal localization. Upon irradiation the photosensitizers would then produce singlet oxygen which could rupture the lysosomal membrane releasing the lysosomally trapped photosensitizers to the cytosol, from where they could relocalize to mitochondria by passive diffusion (photochemical internalization). 2) Using delocalized lipophilic cationic dyes (DLCs) to exploit membrane potential differences between the cytoplasm and mitochondria in delivering photosensitizers to mitochondria. To investigate the effects of steric hindrance on mitochondrial localization and photodynamic response, a series of eight thiaporphyrins were studied. Two new thiaporphyrin analogues 6 and 8 with reduced steric hindrance at the 10- and 15- meso positions were studied in comparison to 5,20-diphenyl-10,15-bis[4 (carboxymethyleneoxy)-phenyl]-21,23-dithiaporphyrin 1, previously validated as a potential second generation photosensitizer. Although 6 showed an extraordinarily high uptake (7.6 times higher than 1), it was less potent than 1 (IC 50 = 0.18 muM versus 0.13 muM) even though they both showed similar sub-cellular localization patterns. This low potency was attributed to its high aggregation tendency in aqueous media (4 times higher than 1), which might have affected its ability to generate singlet oxygen in vitro . 8 on the other hand showed an even lower potency than 6 (2.28 vs 0.18 muM). However this was attributed to its low cellular uptake (20 times less than 6) and inefficient generation of singlet oxygen. Overall, although the structural modifications did improve the cellular uptake of 6, 6 was still less potent than the lead photosensitizers 1. Thus

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

    PubMed

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

    2015-05-01

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

  17. Microbial copper reduction method to scavenge anthropogenic radioiodine

    PubMed Central

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

    2016-01-01

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

  18. Microbial copper reduction method to scavenge anthropogenic radioiodine

    NASA Astrophysics Data System (ADS)

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

    2016-06-01

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

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

    MedlinePlus

    ... Physician Resources Professions Site Index A-Z Radioactive Iodine (I-131) Therapy Radioiodine therapy is a nuclear ... thyroid cancer. When a small dose of radioactive iodine I-131 (an isotope of iodine that emits ...

  20. Translating depression biomarkers for improved targeted therapies.

    PubMed

    Bredt, David S; Furey, Maura L; Chen, Guang; Lovenberg, Tim; Drevets, Wayne C; Manji, Husseini K

    2015-12-01

    Mood disorders are among the most common medical conditions and cause amongst the greatest disease burden. Currently approved antidepressants target monoamine pathways; these medicines take many weeks to relieve symptoms, and most patients do not have sustained responses. This review will highlight recent advances in translational science identifying dysfunctional biochemical processes and neuronal circuits associated with mood disorders. We will also summarize strategies for targeting these pathways and for enhancing synaptic plasticity to develop most effective and rapidly acting antidepressant therapies.

  1. Guidelines for radioiodinated MIBG scintigraphy in children.

    PubMed

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

    2003-05-01

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

  2. Effective doses to family members of patients treated with radioiodine-131

    NASA Astrophysics Data System (ADS)

    Zdraveska Kocovska, M.; Vaskova, O.; Majstorov, V.; Kuzmanovska, S.; Pop Gjorceva, D.; Spasic Jokic, V.

    2011-09-01

    The purpose of this study was to evaluate the effective dose to family members of thyroid cancer and hyperthyroid patients treated with radioiodine-131, and also to compare the results with dose constraints proposed by the International Commission of Radiological Protection (ICRP) and the Basic Safety Standards (BSS) of the International Atomic Energy Agency (IAEA). For the estimation of the effective doses, sixty family members of sixty patients, treated with radioiodine-131, and thermoluminiscent dosimeters (Model TLD 100) were used. Thyroid cancer patients were hospitalized for three days, while hyperthyroid patients were treated on out-patient basis. The family members wore TLD in front of the torso for seven days. The radiation doses to family members of thyroid cancer patients were well below the recommended dose constraint of 1 mSv. The mean value of effective dose was 0.21 mSv (min 0.02 - max 0.51 mSv). Effective doses, higher than 1 mSv, were detected for 11 family members of hyperthyroid patients. The mean value of effective dose of family members of hyperthyroid patients was 0.87 mSv (min 0.12 - max 6.79). The estimated effective doses to family members of hyperthyroid patients were higher than the effective doses to family members of thyroid carcinoma patients. These findings may be considered when establishing new national guidelines concerning radiation protection and release of patients after a treatment with radioiodine therapy.

  3. Improving upon nature's somatic mitochondrial DNA therapies.

    PubMed

    Dani, M A; Dani, S U

    2010-06-01

    Mitochondrial DNA (mtDNA) directs key metabolic functions in eukaryotic cells. While a number of mtDNA mutations are known causes of human diseases and age-related dysfunctions, some mtDNA haplotypes are associated with extreme longevity. Despite the mutagenic mitochondrial environment naturally enhancing somatic mtDNA mutation rates, mtDNA remains grossly stable along generations of plant and animal species including man. This relative stability can be accounted for by the purging of deleterious mutations by natural selection operating on growing cells, tissues, organisms and populations, as observed in gametogenesis, embryogenesis, oncogenesis and cladogenesis. In the adult multicellular organism, however, mtDNA mutations accumulate in slowly dividing cells, and, to a much higher degree, in postmitotic cells and tissues. Dynamic mitochondrial fusion and fission, by redistributing polymorphic mtDNA molecules; mitophagy, by clearing defective mitochondria and mutated mtDNA; compensatory mutations and mtDNA repair can compensate for the accumulation of mtDNA mutations only to a certain extent, thereby creating a dysfunctional threshold. Here we hypothesize that this threshold is naturally up-regulated by both vertical and horizontal transfers of mtDNA from stem cells or cell types which retain the capacity of purging deleterious mtDNA through cell division and natural selection in the adult organism. When these natural cell and tissue mtDNA reserves are exhausted, artificial mtDNA therapy may provide for additional threshold up-regulation. Replacement of mtDNA has been already successfully accomplished in early stage embryos and stem cells in a number of species including primates. It is thus simply a matter of refinement of technique that somatic mtDNA therapy, i.e., therapy of pathological conditions based on the transfer of mtDNA to somatic eukaryotic cells and tissues, becomes a medical reality.

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

    SciTech Connect

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

    2008-09-15

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

  5. Improving Cell-Based Therapies by Nanomodification

    PubMed Central

    Chen, Wei; Fu, Liwu; Chen, Xiaoyuan

    2015-01-01

    Cell-based therapies are emerging as a promising approach for various diseases. Their therapeutic efficacy depends on rational control and regulation of the functions and behaviors of cells during their treatment. Different from conventional regulatory strategy by chemical adjuvant or genetic engineering, which is restricted by limited synergistic regulatory efficiency or uncertain safety problems, a novel approach based on nanoscale artificial materials can be applied to modify living cells to endow them with novel functions and unique properties. Inspired by the natural “nano shell” and “nano compass” structures, cell nanomodification can be developed through both external and internal pathways. In this review, some novel cell surface engineering and intracellular nanoconjugation strategies are summarized. Their potential applications are also discussed, including cell protection, cell labeling, targeted delivery and in situ regulation. It is believed that these novel cell-material complexes can have great potentials for biomedical applications. PMID:26423238

  6. RADIOIODINE GEOCHEMISTRY IN THE SRS SUBSURFACE ENVIRONMENT

    SciTech Connect

    Kaplan, D.; Emerson, H.; Powell, B.; Roberts, K.; Zhang, S.; Xu, C.; Schwer, K.; Li, H.; Ho, Y.; Denham, M.; Yeager, C.; Santschi, P.

    2013-05-16

    Iodine-129 is one of the key risk drivers for several Savannah River Site (SRS) performance assessments (PA), including that for the Low-Level Waste Disposal Facility in E-Area. In an effort to reduce the uncertainty associated with the conceptual model and the input values used in PA, several studies have recently been conducted dealing with radioiodine geochemistry at the SRS. The objective of this report was to review these recent studies and evaluate their implications on SRS PA calculations. For the first time, these studies measured iodine speciation in SRS groundwater and provided technical justification for assuming the presence of more strongly sorbing species (iodate and organo-iodine), and measured greater iodine sediment sorption when experiments included these newly identified species; specifically they measured greater sorption coefficients (K{sub d} values: the concentration ratio of iodine on the solid phase divided by the concentration in the aqueous phase). Based on these recent studies, new best estimates were proposed for future PA calculations. The new K{sub d} values are greater than previous recommended values. These proposed K{sub d} values reflect a better understanding of iodine geochemistry in the SRS subsurface environment, which permits reducing the associated conservatism included in the original estimates to account for uncertainty. Among the key contributing discoveries supporting the contention that the K{sub d} values should be increased are that: 1) not only iodide (I{sup -}), but also the more strongly sorbing iodate (IO{sub 3}{sup -}) species exists in SRS groundwater (average total iodine = 15% iodide, 42% iodate, and 43% organoiodine), 2) when iodine was added as iodate, the measured K{sub d} values were 2 to 6 times greater than when the iodine was added as iodide, and perhaps most importantly, 3) higher desorption (10 to 20 mL/g) than (ad)sorption (all previous studies) K{sub d} values were measured. The implications of this

  7. Compliance therapy: an intervention to improve inpatients' attitudes toward treatment.

    PubMed

    Tay, Sim-Eng Clara

    2007-06-01

    Nonadherence to prescription medication is the leading cause of relapse or recurrence of psychotic illness. Literature has shown that compliance therapy, a brief intervention based on motivational interviewing and cognitive approaches, can lead to improved attitudes, adherence to treatment, and insight. This descriptive study aimed to examine the effectiveness of compliance therapy on treatment adherence. The 69 participants were patients of the same ward, either referred for patient education by the psychiatrist or selected from a convenience sample of patients on the clinical pathway of relapsed schizophrenia or major depression. Compliance therapy was conducted individually or in small groups of 2 to 3 patients. The shortened version of the Drug Attitude Inventory (DAI-10), along with a rating scale adapted from another study, was used to measure attitude and the rate of adherence before and after therapy. Patients in both individual and group sessions showed significant improvements in attitude. Those with six or more admissions had slightly less significant improvement, and those with personality disorder or substance abuse showed no significant improvement. Compliance therapy benefits patients and improves their attitude toward treatment. Psychiatric nurses could be trained in this clinical intervention to enable them to conduct compliance therapy in the hospital or in the community.

  8. Hyperbaric oxygen therapy improves cognitive functioning after brain injury.

    PubMed

    Liu, Su; Shen, Guangyu; Deng, Shukun; Wang, Xiubin; Wu, Qinfeng; Guo, Aisong

    2013-12-15

    Hyperbaric oxygen therapy has been widely applied and recognized in the treatment of brain injury; however, the correlation between the protective effect of hyperbaric oxygen therapy and changes of metabolites in the brain remains unclear. To investigate the effect and potential mechanism of hyperbaric oxygen therapy on cognitive functioning in rats, we established traumatic brain injury models using Feeney's free falling method. We treated rat models with hyperbaric oxygen therapy at 0.2 MPa for 60 minutes per day. The Morris water maze test for spatial navigation showed that the average escape latency was significantly prolonged and cognitive function decreased in rats with brain injury. After treatment with hyperbaric oxygen therapy for 1 and 2 weeks, the rats' spatial learning and memory abilities were improved. Hydrogen proton magnetic resonance spectroscopy analysis showed that the N-acetylaspartate/creatine ratio in the hippocampal CA3 region was significantly increased at 1 week, and the N-acetylaspartate/choline ratio was significantly increased at 2 weeks after hyperbaric oxygen therapy. Nissl staining and immunohistochemical staining showed that the number of nerve cells and Nissl bodies in the hippocampal CA3 region was significantly increased, and glial fibrillary acidic protein positive cells were decreased after a 2-week hyperbaric oxygen therapy treatment. Our findings indicate that hyperbaric oxygen therapy significantly improves cognitive functioning in rats with traumatic brain injury, and the potential mechanism is mediated by metabolic changes and nerve cell restoration in the hippocampal CA3 region.

  9. Delayed Posthypoxic Leukoencephalopathy: Improvement with Antioxidant Therapy

    PubMed Central

    King, Franklin; Morris, Nicholas A.; Schmahmann, Jeremy D.

    2015-01-01

    Introduction Delayed posthypoxic leukoencephalopathy (DPHL) may result from a variety of hypoxic insults, including respiratory depression from an opiate overdose. The underlying pathophysiological mechanism of DPHL remains uncertain. We describe a patient with a typical case of DPHL who responded clinically to antioxidant treatment. Methods Clinical, serological, and radiographic investigations were undertaken in the evaluation of the patient. Results A 63-year-old man developed altered mental status 10 days following recovery from an opiate overdose and aspiration pneumonia that required intubation. The clinical course and brain imaging were consistent with DPHL. Initiation of antioxidant therapy with vitamin E, vitamin C, B-complex vitamins, and coenzyme Q10 coincided with the prompt reversal of clinical deterioration. Conclusions The potential therapeutic effect of antioxidants on DPHL needs to be explored in future cases. If this relationship indeed holds true, it would be consistent with the hypothesis that formation of reactive oxygen species during reperfusion plays a role in the pathophysiology of this disorder. PMID:26955335

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

    SciTech Connect

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

    1989-06-01

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

  11. Proton radiography to improve proton therapy treatment

    NASA Astrophysics Data System (ADS)

    Takatsu, J.; van der Graaf, E. R.; Van Goethem, M.-J.; van Beuzekom, M.; Klaver, T.; Visser, J.; Brandenburg, S.; Biegun, A. K.

    2016-01-01

    The quality of cancer treatment with protons critically depends on an accurate prediction of the proton stopping powers for the tissues traversed by the protons. Today, treatment planning in proton radiotherapy is based on stopping power calculations from densities of X-ray Computed Tomography (CT) images. This causes systematic uncertainties in the calculated proton range in a patient of typically 3-4%, but can become even 10% in bone regions [1,2,3,4,5,6,7,8]. This may lead to no dose in parts of the tumor and too high dose in healthy tissues [1]. A direct measurement of proton stopping powers with high-energy protons will allow reducing these uncertainties and will improve the quality of the treatment. Several studies have shown that a sufficiently accurate radiograph can be obtained by tracking individual protons traversing a phantom (patient) [4,6,10]. Our studies benefit from the gas-filled time projection chambers based on GridPix technology [2], developed at Nikhef, capable of tracking a single proton. A BaF2 crystal measuring the residual energy of protons was used. Proton radiographs of phantom consisting of different tissue-like materials were measured with a 30×30 mm2 150 MeV proton beam. Measurements were simulated with the Geant4 toolkit.First experimental and simulated energy radiographs are in very good agreement [3]. In this paper we focus on simulation studies of the proton scattering angle as it affects the position resolution of the proton energy loss radiograph. By selecting protons with a small scattering angle, the image quality can be improved significantly.

  12. Molten Hydroxide Trapping Process for Radioiodine

    SciTech Connect

    Trowbridge, L.D.

    2003-01-28

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

  13. Radioiodine in kelp from western Australia

    SciTech Connect

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

    1987-03-25

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

  14. Site specific radioiodination of recombinant hirudin

    SciTech Connect

    Tuong, A.; Maftouh, M.; Picard, C.; Gachon, M. )

    1990-09-01

    Recombinant hirudin variant rHV2-Lys47 was radioiodinated using the chloramine-T method. Depending on the reaction pH, the two tyrosine residues, Tyr3 and Tyr63, responded differently to iodination but without change in total iodination yield. Of the incorporated -125 iodine 80% was located on Tyr3 at pH 7.4, but 65% was found on Tyr63 at pH 4. These distinct iodination patterns suggest the existence of a pH-dependent multimerization and/or important conformational changes in the tertiary structure with pH. Each radiotracer was purified to high specific activity by simple low-pressure chromatography including gel filtration and reverse-phase separation, both on short cartridges. The method was validated by reverse-phase and anion-exchange HPLC with on-line radioactivity detection. The iodination sites were characterized following carboxypeptidase Y cleavage coupled with radio-HPLC.

  15. Patterns of radioiodine uptake by the lactating breast.

    PubMed

    Bakheet, S M; Hammami, M M

    1994-07-01

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

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

    SciTech Connect

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

    1986-08-01

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

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

    PubMed

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

    1986-08-01

    Iodine excess is associated with a low thyroidal radioiodine uptake due to dilution of the radioisotope by the increased stable iodide pool. We studied thyroidal uptake of radioisotopes in cardiac patients with iodine excess due to amiodarone treatment. 99mTc-pertechnetate scintigraphy was performed in 13 patients receiving long term amiodarone therapy. Five patients had a clearly visible thyroid gland, and 8 patients had no or a very faint thyroid image. All patients with positive scans had an increased plasma TSH level, whereas all patients with negative scans had a normal or absent TSH response to TRH. Thyroidal uptake and discharge of 123I were studied in 30 other patients. Group I (n = 11) had normal plasma TSH responses to TRH and no iodine excess, group II (n = 7) had normal TSH responses to TRH and excess iodine from metrizoate angiography in the previous month, group III (n = 7) had normal or decreased TSH responses to TRH while receiving long term amiodarone therapy, and group IV (n = 5) had increased TSH responses to TRH while receiving long term amiodarone therapy. The mean radioiodine uptake value in group I [5.4 +/- 0.8% (+/- SE) at 60 min] was higher than those in group II (2.3 +/- 0.7%; P = 0.009) and group III (0.8 +/- 0.3%; P = 0.0005), but not different from that in group IV (5.3 +/- 1.2%; P = NS). Radioiodine discharge after perchlorate (expressed as a percentage of the 60 min uptake) in group I (10.1 +/- 2.2%) was lower than those in group II (24.9 +/- 10.6%; P = 0.05) and group III (28.8 +/- 5.3%; P less than 0.005), whereas discharge in group IV (58.0 +/- 6.1%) was greater than those in group II (P less than 0.05) and group III (P less than 0.01). In conclusion, 1) thyroid visualization by 99mTc-pertechnetate and thyroid radioiodine uptake during iodine excess are decreased in euthyroid and hyperthyroid patients, but preserved in hypothyroid patients. 2) The organification defect induced by iodine excess is greater in iodide

  18. Genomically Driven Precision Medicine to Improve Outcomes in Anaplastic Thyroid Cancer

    PubMed Central

    Patel, Krupal; Mymryk, Joe S.; Barrett, John W.; Nichols, Anthony C.

    2014-01-01

    Thyroid cancer is an endocrine malignancy with an incidence rate that has been increasing steadily over the past 30 years. While well-differentiated subtypes have a favorable prognosis when treated with surgical resection and radioiodine, undifferentiated subtypes, such as anaplastic thyroid cancer (ATC), are far more aggressive and have a poor prognosis. Conventional therapies (surgical resection, radiation, chemotherapy, and radioiodine) have been utilized for treatment of ATC, yet these treatments have not significantly improved the overall mortality rate. As cancer is a genetic disease, genetic alterations such as mutations, fusions, activation of oncogenes, and silencing of tumor suppressors contribute to its aggressiveness. With the use of next-generation sequencing and the Cancer Genome Atlas, mutation-directed therapy is recognized as the upcoming standard of care. In this review, we highlight the known genetic landscape of ATC and the need for a comprehensive genetic characterization of this disease in order to identify additional therapeutic targets to improve patient outcomes. PMID:25276134

  19. Improving translation success of cell-based therapies in orthopaedics.

    PubMed

    Bara, Jennifer J; Herrmann, Marietta; Evans, Christopher H; Miclau, Theodore; Ratcliffe, Anthony; Richards, R Geoff

    2016-01-01

    There is a clear discrepancy between the growth of cell therapy and tissue engineering research in orthopaedics over the last two decades and the number of approved clinical therapies and products available to patients. At the 2015 annual meeting of the Orthopaedic Research Society, a workshop was held to highlight important considerations from the perspectives of an academic scientist, clinical researcher, and industry representative with the aim of helping researchers to successfully translate their ideas into clinical and commercial reality. Survey data acquired from workshop participants indicated an overall positive opinion on the future potential of cell-based therapies to make a significant contribution to orthopaedic medicine. The survey also indicated an agreement on areas requiring improvement in the development of new therapies, specifically; increased support for fundamental research and education and improved transparency of regulatory processes. This perspectives article summarises the content and conclusions of the workshop and puts forward suggestions on how translational success of cell-based therapies in orthopaedics may be achieved.

  20. The effects of maitland orthopedic manual therapy on improving constipation.

    PubMed

    Koo, Ja-Pung; Choi, Jung-Hyun; Kim, Nyeon-Jun

    2016-10-01

    [Purpose] This study aimed to examine the effects of interventions on constipation and to provide basic data for physical therapy in internal medicine. [Subjects and Methods] The colon transit times of 30 subjects were measured and after the interventions. Fifteen subjects were assigned to a Maitland orthopedic manual therapy group, and 15 subjects were assigned to a dietary fiber group. [Results] The analysis of changes in colon transit time showed statistically significant differences in left colon transit time, rectosigmoid colon transit time, and total colon transit time for the Maitland orthopedic manual therapy group and statistically significant differences in rectosigmoid colon transit time and total colon transit time for the dietary fiber group. An analysis of group differences in the effects of Maitland orthopedic manual therapy and dietary fiber showed that the Maitland orthopedic manual therapy group achieved statistically significantly larger declines in rectosigmoid colon transit time and total colon transit time compared with the dietary fiber group. [Conclusion] This study confirmed that Maitland orthopedic manual therapy can be an effective treatment method for internal conditions such as functional constipation by almost normalizing the colon transit time, not only by improving the symptoms of constipation but also by facilitating intestinal movements.

  1. The effects of maitland orthopedic manual therapy on improving constipation

    PubMed Central

    Koo, Ja-Pung; Choi, Jung-Hyun; Kim, Nyeon-Jun

    2016-01-01

    [Purpose] This study aimed to examine the effects of interventions on constipation and to provide basic data for physical therapy in internal medicine. [Subjects and Methods] The colon transit times of 30 subjects were measured and after the interventions. Fifteen subjects were assigned to a Maitland orthopedic manual therapy group, and 15 subjects were assigned to a dietary fiber group. [Results] The analysis of changes in colon transit time showed statistically significant differences in left colon transit time, rectosigmoid colon transit time, and total colon transit time for the Maitland orthopedic manual therapy group and statistically significant differences in rectosigmoid colon transit time and total colon transit time for the dietary fiber group. An analysis of group differences in the effects of Maitland orthopedic manual therapy and dietary fiber showed that the Maitland orthopedic manual therapy group achieved statistically significantly larger declines in rectosigmoid colon transit time and total colon transit time compared with the dietary fiber group. [Conclusion] This study confirmed that Maitland orthopedic manual therapy can be an effective treatment method for internal conditions such as functional constipation by almost normalizing the colon transit time, not only by improving the symptoms of constipation but also by facilitating intestinal movements. PMID:27821950

  2. Radioiodine Biogeochemistry and Prevalence in Groundwater

    PubMed Central

    Kaplan, D. I.; Denham, M. E.; Zhang, S.; Yeager, C.; Xu, C.; Schwehr, K. A.; Li, H. P.; Ho, Y. F.; Wellman, D.; Santschi, P. H.

    2014-01-01

    129I is commonly either the top or among the top risk drivers, along with 99Tc, at radiological waste disposal sites and contaminated groundwater sites where nuclear material fabrication or reprocessing has occurred. The risk stems largely from 129I having a high toxicity, a high bioaccumulation factor (90% of all the body's iodine concentrates in the thyroid), a high inventory at source terms (due to its high fission yield), an extremely long half-life (16M years), and rapid mobility in the subsurface environment. Another important reason that 129I is a key risk driver is that there is uncertainty regarding its biogeochemical fate and transport in the environment. We typically can define 129I mass balance and flux at sites, but cannot predict accurately its response to changes in the environment. As a consequence of some of these characteristics, 129I has a very low drinking water standard, which is set at 1 pCi/L, the lowest of all radionuclides in the Federal Register. Recently, significant advancements have been made in detecting iodine species at ambient groundwater concentrations, defining the nature of the organic matter and iodine bond, and quantifying the role of naturally occurring sediment microbes to promote iodine oxidation and reduction. These recent studies have led to a more mechanistic understanding of radioiodine biogeochemistry. The objective of this review is to describe these advances and to provide a state of the science of radioiodine biogeochemistry relevant to its fate and transport in the terrestrial environment and provide information useful for making decisions regarding the stewardship and remediation of 129I contaminated sites. As part of this review, knowledge gaps were identified that would significantly advance the goals of basic and applied research programs for accelerating 129I environmental remediation and reducing uncertainty associated with disposal of 129I waste. Together the information gained from addressing these knowledge

  3. Radioiodine Biogeochemistry and Prevalence in Groundwater.

    PubMed

    Kaplan, D I; Denham, M E; Zhang, S; Yeager, C; Xu, C; Schwehr, K A; Li, H P; Ho, Y F; Wellman, D; Santschi, P H

    2014-10-18

    (129)I is commonly either the top or among the top risk drivers, along with (99)Tc, at radiological waste disposal sites and contaminated groundwater sites where nuclear material fabrication or reprocessing has occurred. The risk stems largely from (129)I having a high toxicity, a high bioaccumulation factor (90% of all the body's iodine concentrates in the thyroid), a high inventory at source terms (due to its high fission yield), an extremely long half-life (16M years), and rapid mobility in the subsurface environment. Another important reason that (129)I is a key risk driver is that there is uncertainty regarding its biogeochemical fate and transport in the environment. We typically can define (129)I mass balance and flux at sites, but cannot predict accurately its response to changes in the environment. As a consequence of some of these characteristics, (129)I has a very low drinking water standard, which is set at 1 pCi/L, the lowest of all radionuclides in the Federal Register. Recently, significant advancements have been made in detecting iodine species at ambient groundwater concentrations, defining the nature of the organic matter and iodine bond, and quantifying the role of naturally occurring sediment microbes to promote iodine oxidation and reduction. These recent studies have led to a more mechanistic understanding of radioiodine biogeochemistry. The objective of this review is to describe these advances and to provide a state of the science of radioiodine biogeochemistry relevant to its fate and transport in the terrestrial environment and provide information useful for making decisions regarding the stewardship and remediation of (129)I contaminated sites. As part of this review, knowledge gaps were identified that would significantly advance the goals of basic and applied research programs for accelerating (129)I environmental remediation and reducing uncertainty associated with disposal of (129)I waste. Together the information gained from

  4. Radioiodine Biogeochemistry and Prevalence in Groundwater

    SciTech Connect

    Kaplan, Daniel I.; Denham, Miles E.; Zhang, Saijin; Yeager, Chris; Xu, Chen; Schwehr, Kathy; Li, Hsiu-Ping; Ho, Yi-Fang; Wellman, Dawn M.; Santschi, Peter H.

    2014-08-03

    129I is commonly either the top or among the top risk drivers, along with 99Tc, at radiological waste disposal sites and contaminated groundwater sites where nuclear material fabrication or reprocessing has occurred. The risk stems largely from 129I having a high toxicity, a high bioaccumulation factor (90% of all the body’s iodine concentrates in the thyroid), a high inventory at source terms (due to its high fission yield), an extremely long half-life (16M yr), and rapid mobility in the subsurface environment. Another important reason that 129I is a key risk driver is that there is the uncertainty regarding its biogeochemical fate and transport in the environment. We typically can define 129I mass balance and flux at sites, but cannot predict accurately its response to changes in the environment. As a consequence of some of these characteristics, 129I has a very low Drinking Water Standard, DWS, which is set at 1 pCi/L, the lowest of all radionuclides in the Federal Register. Recently, significant advancements have been made in detecting iodine species at ambient groundwater concentrations, defining the nature of the organic matter and iodine bond, and quantifying the role of naturally occurring sediment microbes to promote iodine oxidation and reduction. These recent studies have led to a more mechanistic understanding of radioiodine biogeochemistry. The objective of this review is to describe these advances and to provide a state of the science of radioiodine biogeochemistry relevant to its fate and transport in the terrestrial environment and provide information useful for making decisions regarding the stewardship and remediation of 129I contaminated sites. As part of this review, knowledge gaps were identified that would significantly advance the goals of basic and applied research programs for accelerating 129I environmental remediation and reducing uncertainty associated with disposal of 129I waste. Together the information gained from addressing these

  5. Improvement of hepatic steatosis in cystic fibrosis with ivacaftor therapy.

    PubMed

    Hayes, Don; Warren, Patrick S; McCoy, Karen S; Sheikh, Shahid I

    2015-05-01

    Treatment of liver disease, including hepatic steatosis, in patients with cystic fibrosis (CF) is limited. With the development of ivacaftor, which corrects the gating defect of the CF transmembrane regulator channel, there is a potential new therapy available for this subgroup of the CF patient population. We present an adolescent with CF who had significant improvement in hepatic steatosis with ivacaftor treatment while hypothesizing on a mechanism of why it occurred.

  6. Therapies to improve the cosmetic symptoms of rosacea.

    PubMed

    Lanoue, Julien; Goldenberg, Gary

    2015-07-01

    Rosacea is a commonly encountered chronic inflammatory skin disease with a predilection for highly visible areas of the skin such as the face. The cosmetic symptoms of rosacea can be substantial and may greatly reduce a patient's quality of life. Although there is no definitive cure for rosacea, effective treatment of symptoms can mitigate the deleterious effects of this condition and improve quality of life. In this article, we review both existing and emerging cosmetic treatments for rosacea, including topical medications, systemic pharmacologic therapies, light-based modalities, and procedural interventions, and assess their ability to improve the cosmetic symptoms of rosacea.

  7. Mixed species radioiodine air sampling readout and dose assessment system

    DOEpatents

    Distenfeld, Carl H.; Klemish, Jr., Joseph R.

    1978-01-01

    This invention provides a simple, reliable, inexpensive and portable means and method for determining the thyroid dose rate of mixed airborne species of solid and gaseous radioiodine without requiring highly skilled personnel, such as health physicists or electronics technicians. To this end, this invention provides a means and method for sampling a gas from a source of a mixed species of solid and gaseous radioiodine for collection of the mixed species and readout and assessment of the emissions therefrom by cylindrically, concentrically and annularly molding the respective species around a cylindrical passage for receiving a conventional probe-type Geiger-Mueller radiation detector.

  8. Aggressive therapy improves cirrhosis in glycogen storage disease type IX.

    PubMed

    Tsilianidis, Laurie A; Fiske, Laurie M; Siegel, Sara; Lumpkin, Chris; Hoyt, Kate; Wasserstein, Melissa; Weinstein, David A

    2013-06-01

    Glycogen storage disease type IX (GSD IX) is described as a benign condition that often does not require treatment. Most patients with the disease are thought to outgrow the childhood manifestations, which include hepatomegaly, poor growth, and ketosis with or without hypoglycemia. Long term complications including fibrosis and cirrhosis have seldom been reported in the most common subtype, GSD IXα. We present two cases of children with GSD IXα who had fibrosis at the time of diagnosis in addition to the commonly reported disease manifestations. Structured therapy with frequent doses of uncooked cornstarch and protein supplementation was initiated, and both children responded with improved growth velocity, increased energy, decreased hepatomegaly and improved well-being. Additionally, radiographic features of fibrosis improved. We propose that GSD IXα is not a benign condition. Even in patients with a less severe presentation, consideration of a structured treatment regimen to improve quality of life appears warranted.

  9. Sleep Quality Improvement During Cognitive Behavioral Therapy for Anxiety Disorders.

    PubMed

    Ramsawh, Holly J; Bomyea, Jessica; Stein, Murray B; Cissell, Shadha H; Lang, Ariel J

    2016-01-01

    Despite the ubiquity of sleep complaints among individuals with anxiety disorders, few prior studies have examined whether sleep quality improves during anxiety treatment. The current study examined pre- to posttreatment sleep quality improvement during cognitive behavioral therapy (CBT) for panic disorder (PD; n = 26) or generalized anxiety disorder (GAD; n = 24). Among sleep quality indices, only global sleep quality and sleep latency improved significantly (but modestly) during CBT. Sleep quality improvement was greater for treatment responders, but did not vary by diagnosis. Additionally, poor baseline sleep quality was independently associated with worse anxiety treatment outcome, as measured by higher intolerance of uncertainty. Additional intervention targeting sleep prior to or during CBT for anxiety may be beneficial for poor sleepers.

  10. Cardiac Resynchronization Therapy Leads to Improvements in Handgrip Strength

    PubMed Central

    Warriner, David R.; Lawford, Patricia; Sheridan, Paul J.

    2016-01-01

    Background A reduction in skeletal muscle performance measured by handgrip strength is common in heart failure. No trial has investigated the role of cardiac resynchronization therapy, which leads to improvements in cardiac performance, on the function of skeletal muscle in patients with heart failure. Methods Nineteen patients were recruited, 18 male, age 69 ± 8 years, New York Heart Association class II-IV, QRS duration 173 ± 21 ms and left ventricular ejection fraction 26±8%. Handgrip strength was measured at baseline before, and 6 and 12 months, following cardiac resynchronization therapy. Response was assessed using quality of life questionnaire, 6-minute walk distance, left ventricular end-diastolic volume, and cardiopulmonary exercise testing at the same time points. Results Fourteen patients were identified as responders, demonstrating significant improvements in all four markers of response. There was no significant difference at baseline in left or right handgrip strength between responders and non-responders. Compared to baseline, handgrip strength significantly increased in responders during follow-up, left (34.4 ± 11.4 to 40.3 ± 11.3 kgf, P < 0.001) and right (35.7 ± 12.5 to 42.2 ± 11.5 kgf, P < 0.001) at 12 months. No such improvement was seen in non-responders. Conclusions This study demonstrates that positive response to cardiac resynchronization therapy is associated with significant gains in handgrip strength, suggesting that cardiac resynchronization therapy may indirectly lead to secondary gains in skeletal muscle function. PMID:28197275

  11. Radioiodine Remnant Ablation: A Critical Review

    PubMed Central

    Bal, Chandra Sekhar; Padhy, Ajit Kumar

    2015-01-01

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

  12. Improved cancer therapy and molecular imaging with multivalent, multispecific antibodies.

    PubMed

    Sharkey, Robert M; Rossi, Edmund A; Chang, Chien-Hsing; Goldenberg, David M

    2010-02-01

    Antibodies are highly versatile proteins with the ability to be used to target diverse compounds, such as radionuclides for imaging and therapy, or drugs and toxins for therapy, but also can be used unconjugated to elicit therapeutically beneficial responses, usually with minimal toxicity. This update describes a new procedure for forming multivalent and/or multispecific proteins, known as the dock-and-lock (DNL) technique. Developed as a procedure for preparing bispecific antibodies capable of binding divalently to a tumor antigen and monovalently to a radiolabeled hapten-peptide for pretargeted imaging and therapy, this methodology has the flexibility to create a number of other biologic agents of therapeutic interest. A variety of constructs, based on anti-CD20 and CD22 antibodies, have been made, with results showing that multispecific antibodies have very different properties from the respective parental monospecific antibodies. The technique is not restricted to antibody combination, but other biologics, such as interferon-alpha2b, have been prepared. These types of constructs not only allow small biologics to be sustained in the blood longer, but also to be selectively targeted. Thus, DNL technology is a highly flexible platform that can be used to prepare many different types of agents that could further improve cancer detection and therapy.

  13. Improved Cancer Therapy and Molecular Imaging with Multivalent, Multispecific Antibodies

    PubMed Central

    Rossi, Edmund A.; Chang, Chien-Hsing; Goldenberg, David M.

    2010-01-01

    Summation Antibodies are highly versatile proteins with the ability to be used to target diverse compounds, such as radionuclides for imaging and therapy, or drugs and toxins for therapy, but also can be used unconjugated to elicit therapeutically beneficial responses, usually with minimal toxicity. This update describes a new procedure for forming multivalent and/or multispecific proteins, known as the dock-and-lock (DNL) technique. Developed as a procedure for preparing bispecific antibodies capable of binding divalently to a tumor antigen and monovalently to a radiolabeled hapten-peptide for pretargeted imaging and therapy, this methodology has the flexibility to create a number of other biologic agents of therapeutic interest. A variety of constructs, based on anti-CD20 and CD22 antibodies, have been made, with results showing that multispecific antibodies have very different properties from the respective parental monospecific antibodies. The technique is not restricted to antibody combination, but other biologics, such as interferon-α2b, have been prepared. These types of constructs not only allow small biologics to be sustained in the blood longer, but also to be selectively targeted. Thus, DNL technology is a highly flexible platform that can be used to prepare many different types of agents that could further improve cancer detection and therapy. PMID:20187791

  14. Effect of reserpine on salivary gland radioiodine uptake in thyroid cancer

    SciTech Connect

    Levy, H.A.; Park, C.H.

    1987-04-01

    Nine patients with thyroid cancer were treated with reserpine in an attempt to reduce radiation exposure to the salivary glands from 100-150 mCi doses of I-131 therapy to thyroid remnants or metastases. Three control patients were not treated with reserpine but did receive 100-150 mCi of I-131. Parotid/background ratios of activity after radioablative doses of I-131 in patients not treated with reserpine were significantly higher than the patients treated with reserpine, and this was also true seven days after the radioablative dose. Combined therapy with reserpine, chewing gum, lemon candies, and hydration is suggested for the prevention of sialadenitis and xerostomia due to large doses of radioiodine.

  15. Improving Cell Engraftment in Cardiac Stem Cell Therapy

    PubMed Central

    Xie, Xiaoyun

    2016-01-01

    Myocardial infarction (MI) affects millions of people worldwide. MI causes massive cardiac cell death and heart function decrease. However, heart tissue cannot effectively regenerate by itself. While stem cell therapy has been considered an effective approach for regeneration, the efficacy of cardiac stem cell therapy remains low due to inferior cell engraftment in the infarcted region. This is mainly a result of low cell retention in the tissue and poor cell survival under ischemic, immune rejection and inflammatory conditions. Various approaches have been explored to improve cell engraftment: increase of cell retention using biomaterials as cell carriers; augmentation of cell survival under ischemic conditions by preconditioning cells, genetic modification of cells, and controlled release of growth factors and oxygen; and enhancement of cell survival by protecting cells from excessive inflammation and immune surveillance. In this paper, we review current progress, advantages, disadvantages, and potential solutions of these approaches. PMID:26783405

  16. A survey of owners' perceptions and experiences of radioiodine treatment of feline hyperthyroidism in the UK.

    PubMed

    Boland, Lara A; Murray, Jane K; Bovens, Catherine Pv; Hibbert, Angie

    2014-08-01

    The efficacy of radioiodine treatment of feline hyperthyroidism is well established; however, limited information is known about owners' perceptions or experiences of radioiodine. This study aimed to examine factors that influence owner treatment choices and their opinions following radioiodine. Surveys were sent to owners of cats referred for radioiodine treatment between 2002 and 2011 (radioiodine group; 264 cats) and owners of non-radioiodine-treated hyperthyroid cats seen at first-opinion practices (control group; 199 cats). The response rate was 67.0% (310 returned: 175 radioiodine, 135 control). Of 135 controls, 72 (53.3%) were unaware of radioiodine as a treatment option. Owners of cats ⩾15 years old and uninsured cats were less likely to pursue radioiodine. Cost of treatment, travel distance, potential human or animal health risks and waiting periods for radioiodine had a low impact on owners' treatment choice. Owners reported a moderate level of concern about treatment hospitalisation length, which included (158 respondents) the possibility of the cat being unhappy 130 (82.3%), owner missing the cat 102 (64.6%), inappetence 50 (31.6%), other pets missing the cat 32 (20.3%), development of co-morbid disease 28 (17.7%) and side effects 25 (15.8%). Owners assessed their cat's quality of life on a scale of 1 (very poor) to 10 (excellent), as 4 (4) (median [interquartile range]) pre-radioiodine (134 respondents) and 9 (2) post-radioiodine (131 respondents). Of 132 respondents, 121 (91.7%) were happy with their decision to choose radioiodine. The results of this questionnaire may assist veterinarians in addressing common owner concerns when discussing radioiodine as a treatment option for hyperthyroidism.

  17. Inhibition of miR-146b expression increases radioiodine-sensitivity in poorly differential thyroid carcinoma via positively regulating NIS expression

    SciTech Connect

    Li, Luchuan; Lv, Bin; Chen, Bo; Guan, Ming; Sun, Yongfeng; Li, Haipeng; Zhang, Binbin; Ding, Changyuan; He, Shan; Zeng, Qingdong

    2015-07-10

    Dedifferentiated thyroid carcinoma (DTC) with the loss of radioiodine uptake (RAIU) is often observed in clinical practice under radioiodine therapy, indicating the challenge for poor prognosis. MicroRNA (miRNA) has emerged as a promising therapeutic target in many diseases; yet, the role of miRNAs in RAIU has not been generally investigated. Based on recent studies about miRNA expression in papillary or follicular thyroid carcinomas, the expression profiles of several thyroid relative miRNAs were investigated in one DTC cell line, derived from normal DTC cells by radioiodine treatment. The top candidate miR-146b, with the most significant overexpression profiles in dedifferentiated cells, was picked up. Further research found that miR-146b could be negatively regulated by histone deacetylase 3 (HDAC3) in normal cells, indicating the correlation between miR-146b and Na{sup +}/I{sup −} symporter (NIS)-mediated RAIU. Fortunately, it was confirmed that miR-146b could regulate NIS expression/activity; what is more important, miR-146b interference would contribute to the recovery of radioiodine-sensitivity in dedifferentiated cells via positively regulating NIS. In the present study, it was concluded that NIS-mediated RAIU could be modulated by miR-146b; accordingly, miR-146b might serve as one of targets to enhance efficacy of radioactive therapy against poorly differential thyroid carcinoma (PDTC). - Highlights: • Significant upregulated miR-146b was picked up from thyroid relative miRNAs in DTC. • MiR-146b was negatively regulated by HDAC3 in normal thyroid carcinoma cells. • NIS activity and expression could be regulated by miR-146b in thyroid carcinoma. • MiR-146b inhibition could recover the decreased radioiodine-sensitivity of DTC cells.

  18. Radioiodinated glucose analogues for use as imaging agents

    DOEpatents

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

    1988-01-01

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

  19. Limits of fetal thyroid risk from radioiodine exposure

    SciTech Connect

    Lloyd, R.D.; Tripp, D.A.; Kerber, R.A.

    1996-04-01

    An incident in which a young women became pregnant soon after being treated with 444 MBq {sup 131}I for Graves disease prompted us to search local records for the occurrence of thyroid abnormalities among people exposed in utero to fallout radioiodine. The data base from the Utah Fallout Study indicated that there had been 480 cohort subjects for whom dose to thyroid from fallout radioiodine had been calculated and who could have received any thyroid dose before birth (2473 subjects had been re-examined in 1985-86 of the 4818 examined in 1965-70). Of these 480 subjects in this category, 403 of them could be located in the 1980`s and were examined for abnormalities. Although nodules, thyroiditis, hypothyroidism and goiter were seen among the 375 persons with in utero thyroid doses from fallout radioiodine below 0.42 Gy, no thyroid abnormalities of any kind occurred in the 4 persons with in utero thyroid doses of 0.5 to 2.6 Gy. In addition, no neoplasia was found in any of the 403 subjects examined about 3 decades after in utero fallout exposure. These limited data do not indicate that the fetal thyroid is more sensitive than the postnatal thyroid by more than about a factor of about 4 when thyroid dose is considered and by not much more than unity when the comparison is based on dose equivalent (x-ray vs. radioiodine). 21 refs., 1 tab.

  20. Tongguan Liqiao acupuncture therapy improves dysphagia after brainstem stroke

    PubMed Central

    Zhang, Chun-hong; Bian, Jin-ling; Meng, Zhi-hong; Meng, Li-na; Ren, Xue-song; Wang, Zhi-lin; Guo, Xiao-yan; Shi, Xue-min

    2016-01-01

    Tongguan Liqiao acupuncture therapy has been shown to effectively treat dysphagia after stroke-based pseudobulbar paralysis. We presumed that this therapy would be effective for dysphagia after bulbar paralysis in patients with brainstem infarction. Sixty-four patients with dysphagia following brainstem infarction were recruited and divided into a medulla oblongata infarction group (n = 22), a midbrain and pons infarction group (n = 16), and a multiple cerebral infarction group (n = 26) according to their magnetic resonance imaging results. All patients received Tongguan Liqiao acupuncture for 28 days. The main acupoints were Neiguan (PC6), Renzhong (DU26), Sanyinjiao (SP6), Fengchi (GB20), Wangu (GB12), and Yifeng (SJ17). Furthermore, the posterior pharyngeal wall was pricked. Before and after treatment, patient swallowing functions were evaluated with the Kubota Water Test, Fujishima Ichiro Rating Scale, and the Standard Swallowing Assessment. The Barthel Index was also used to evaluate their quality of life. Results showed that after 28 days of treatment, scores on the Kubota Water Test and Standard Swallowing Assessment had decreased, but scores on the Fujishima Ichiro Rating Scale and Barthel Index had increased in each group. The total efficacy rate was 92.2% after treatment, and was most obvious in patients with medulla oblongata infarction (95.9%). These findings suggest that Tongguan Liqiao acupuncture therapy can repair the connection of upper motor neurons to the medulla oblongata motor nucleus, promote the recovery of brainstem infarction, and improve patient's swallowing ability and quality of life. PMID:27073382

  1. Evaluation of a continuous quality improvement program in anticoagulant therapy

    PubMed Central

    Cantin, Ariane; Lahaie, Alexandre; Odobasic, Bojan; Tremblay, Marie-Philip; Wazzan, Dana; Caron, Stéphanie; Leblanc, Caroline; Martineau, Josée; Lalonde, Lyne

    2016-01-01

    Background: The ACO Program (Programme ACO), a continuous quality improvement program (CQIP) in anticoagulation therapy, was offered in community pharmacies as a pilot project. Objective: To evaluate the participants’ appreciation for the various activities of the program. Methods: Participants had access to training activities, including an audit with feedback, online training activities (OTA), clinical tools and support from facilitators. Cognitive behavioural learning determinants were evaluated before and 5 months after the beginning of the program. Participants’ satisfaction and perception were documented via online questionnaires and a semistructured interview. Results: Of the 52 pharmacists in the ACO Program, 47 participated in this evaluation. Seventy-seven percent of the participants completed at least 1 OTA and 6% published on the forum. The feeling of personal effectiveness rose from 8.01 (7.67-8.35) to 8.62 (8.24-8.99). The audit and feedback, as well as the high-quality OTA and their lecturers, were the most appreciated elements. Discussion: There was a high OTA participation rate. The facilitators seemed to play a key role in the CQIP. The low level of participation in the forum reflects the known phenomenon of social loafing. Technical difficulties affecting the platform and data collection for the audit with feedback constituted limitations. Conclusion: The CQIP in anticoagulation therapy is appreciated by community pharmacists and is associated with an improved feeling of personal effectiveness. PMID:27829859

  2. Synthesis of N-(2-diethylamino-ethyl)-4-(4-fluoro-benzamido)-2-methoxybenzamide (desiodo-MIP-1145) by coupling technique and its radioiodination: a potential melanoma imaging agent.

    PubMed

    Aglan, H; Kandil, S A; El-Kafrawy, A F; Seddik, U

    2016-07-01

    Radioiodinated MIP-1145, which specifically targets melanin, is an ideal candidate for targeted therapy of melanoma. An analogue of MIP-1145 lacking the iodo-substituent (desiodo-MIP-1145) was synthesized as a labeling precursor in three simple steps. The radioiodination of desiodo-MIP-1145 by iodine-125 was carried out via an electrophilic substitution reaction. An optimization study for the iodination reaction was carried out. The labeled compound was isolated and purified by means of electrophoresis and HPLC. The maximum radiochemical yield, 76%, was obtained with radiochemical purity greater than 99%. The log P value for [(125) I]MIP-1145 was measured as 4.5.

  3. Improvement of endothelial function following initiation of testosterone replacement therapy

    PubMed Central

    Tucky, Barbara; Polackwich, Allan S.

    2016-01-01

    Background Isolated recent studies have suggested an increased risk of heart attack as early as 3 months following testosterone replacement therapy (TRT). Such a rapid risk increase would likely require rapid deterioration of arterial endothelial function. Our goal was to assess arterial endothelial function in hypogonadal men prior to and at least 3 months after initiation of TRT. Methods Adult men were consented if they had symptoms of hypogonadism, a total testosterone <350 ng/dL, and planned to begin TRT. Endothelial function was non-invasively assessed using the EndoPAT-2000 machine. We measured the augmentation index (AI) (normal <3%), a measure of arterial stiffness and reactive hyperemia index (RHI), a measure of endothelial vasodilation (normal >1.69). Prior studies suggest that a 10% level of day-to-day test variability is expected. Endothelial function was reassessed at the next clinic visit, between 3 and 6 months if the patients were compliant with therapy. Changes in continuous variables were assessed with the paired t test. Results Twenty-three patients were consented with a mean age of 52.7 years (range, 34–68 years) and starting testosterone 196.9 ng/dL (range, 35–339 ng/dL). There was a history of diabetes in four, hypertension in ten and coronary artery disease in five. Mean RHI was 1.67±0.37 (70% were abnormal) and mean AI was 2.57%±14.0% (39% were abnormal). There were no cardiac events. At follow-up 20 patients were compliant with therapy and retested. Mean testosterone increased from 203 to 511 (P<0.0001). Mean RHI improved from 1.70 to 2.14 (P=0.01). Mean AI improved from 2.9% to −1.75% (P=0.01). In four men RHI worsened but in each case less than the 10% error of the test. No man had worsened AI. Conclusions Men with symptomatic hypogonadism often have abnormal arterial endothelial function. Following TRT, endothelial function either remains unchanged or improves. PMID:28078212

  4. Late onset radioiodine-induced hypothyroidism presenting with psychosis 14 years after treatment: a rare case

    PubMed Central

    Er, Chaozer; Sule, Ashish Anil

    2016-01-01

    Radioiodine treatment-induced hypothyroid psychosis is uncommon. Our literature search shows only three cases of hypothyroid psychosis developed within 3 months after the radioiodine treatment. Our case represents the first case of radioiodine-induced hypothyroidism presenting as psychosis much later (14 years) after the radioiodine treatment. A 60-year-old Chinese lady, with long-standing primary hypothyroidism due to the radioiodine treatment performed 14 years ago, presented with a 1-week history of hallucination, delusion and agitation. She was not on thyroid replacement. Thyroid function test done 14 years ago and again upon her admission to our facility was consistent with primary hypothyroidism. General blood tests and brain imaging were unremarkable. Her psychotic features resolved within 1 week with thyroid replacement and 9 days of antipsychotics. No further relapse of psychosis was noted. This emphasizes that radioiodine-induced hypothyroidism can go unnoticed for many years and present much later solely as psychosis. PMID:27099771

  5. Improving adherence with amlodipine/atorvastatin therapy: IMPACT study.

    PubMed

    Oliver, Saran; Jones, Jennifer; Leonard, David; Crabbe, Andrew; Delkhah, Yana; Nesbitt, Shawna

    2011-08-01

    Hypertension is prevalent in the United States and remains uncontrolled. The primary objective of the study was to determine the effect of once-daily dosing of a combination therapy for blood pressure (BP) and dyslipidemia using home BP monitoring on reaching clinical BP and the effect of daily dosing of combination therapy on reaching lipid goals. The study was conducted in middle-aged, indigent, African Americans who had high-risk, resistant hypertension and dyslipidemia. Patients were randomly assigned to either the home and clinic BP group or usual care group and were followed for 6 months. The average BPs for each group were compared and used to titrate the study drug appropriately. Both groups achieved significant declines in BP, total cholesterol, and low-density lipoprotein (LDL) (P<.0001). These findings demonstrate that BP control could be achieved at a rate of 43.5% compared with the 2004 national control rate of 35%. The LDL control rate was also improved. Cardiovascular risk reduction has been proven to be achieved through managing lipids and BP. This trial demonstrates that these goals can be achieved similar to other groups in indigent African Americans with high-risk hypertension and dyslipidemia.

  6. Nanosized ZSM-5 will improve photodynamic therapy using Methylene blue.

    PubMed

    Kariminezhad, H; Habibi, M; Mirzababayi, N

    2015-07-01

    Nowadays, nanotechnology is growing to improve Photodynamic Therapy and reduce its side effects. In this research, the synthesized co-polymeric Zeolite Secony Mobile-5 (ZSM-5) was employed to modify Methylene Blue (MB) for these reasons. UV-Visible, FTIR, XRD analysis and SEM images were used to investigate obtained nanostructure. The crystal size for these nanostructures were determined 75 nm and maximum adsorption capacity of MB in the nanostructure was estimated 111 (mg g(-1)). Also, the role of Polyethylene Glycol (PEG) was studied as a capable non-toxic polymeric coating to overcome biological barriers. Moreover, potential of singlet oxygen production of the synthesized nanostructure was compared with MB and ZSM-5 nanoparticles control samples. Synthesized nanodrugs show impressive light induced singlet oxygen production efficiency.

  7. Radioiodination of interleukin 2 to high specific activities by the vapor-phase chloramine T method

    SciTech Connect

    Siekierka, J.J.; DeGudicibus, S.

    1988-08-01

    Recombinant human interleukin 2 (IL-2) was radioiodinated utilizing the vapor phase chloramine T method of iodination. The method is rapid, reproducible, and allows the efficient radioiodination of IL-2 to specific activities higher than those previously attained with full retention of biological activity. IL-2 radioiodinated by this method binds with high affinity to receptors present on phytohemagglutinin-stimulated peripheral blood lymphocytes and should be useful for the study of receptor structure and function.

  8. Directly Observed Therapy and Improved Tuberculosis Treatment Outcomes in Thailand

    PubMed Central

    Anuwatnonthakate, Amornrat; Limsomboon, Pranom; Nateniyom, Sriprapa; Wattanaamornkiat, Wanpen; Komsakorn, Sittijate; Moolphate, Saiyud; Chiengsorn, Navarat; Kaewsa-ard, Samroui; Sombat, Potjaman; Siangphoe, Umaporn; Mock, Philip A.; Varma, Jay K.

    2008-01-01

    Background The World Health Organization (WHO) recommends that tuberculosis (TB) patients receive directly observed therapy (DOT). Randomized controlled trials have not consistently shown that this practice improves TB treatment success rates. In Thailand, one of 22 WHO-designated high burden TB countries, patients may have TB treatment observed by a health care worker (HCW), family member, or no one. We studied whether DOT improved TB treatment outcomes in a prospective, observational cohort. Methods and Findings We prospectively collected epidemiologic data about TB patients treated at public and private facilities in four provinces in Thailand and the national infectious diseases hospital from 2004–2006. Public health staff recorded the type of observed therapy that patients received during the first two months of TB treatment. We limited our analysis to pulmonary TB patients never previously treated for TB and not known to have multidrug-resistant TB. We analyzed the proportion of patients still on treatment at the end of two months and with treatment success at the end of treatment according to DOT type. We used propensity score analysis to control for factors associated with DOT and treatment outcome. Of 8,031 patients eligible for analysis, 24% received HCW DOT, 59% family DOT, and 18% self-administered therapy (SAT). Smear-positive TB was diagnosed in 63%, and 21% were HIV-infected. Of patients either on treatment or that defaulted at two months, 1601/1636 (98%) patients that received HCW DOT remained on treatment at two months compared with 1096/1268 (86%) patients that received SAT (adjusted OR [aOR] 3.8; 95% confidence interval [CI] 2.4–6.0) and 3782/3987 (95%) patients that received family DOT (aOR 2.1; CI, 1.4–3.1). Of patients that had treatment success or that defaulted at the end of treatment, 1369/1477 (93%) patients that received HCW DOT completed treatment compared with 744/1074 (69%) patients that received SAT (aOR 3.3; CI, 2.4–4.5) and

  9. Reevaluation of the newborn thyroid dose from radioiodines

    SciTech Connect

    Hedrick, W.R.; Milavickas, L.R.

    1987-07-01

    The basis for the current thyroid absorbed dose estimates for radioiodines has been examined. The values for the newborn thyroid dose were found to underestimate the dose by a factor of 3. This underestimation of the dose was caused by the assumption that the biokinetic distribution of iodine is the same for the newborn and the adult. Increased thyroid uptake by the newborn requires that higher cumulated activities be incorporated into the dose determinations for the newborn.

  10. Can Technology Improve Adherence to Long-Term Therapies?

    PubMed Central

    Reach, Gérard

    2009-01-01

    Background Therapeutic nonadherence is defined as the lack of equivalence between the behavior of the patients and their prescribed medical treatment. Consequences of nonadherence include not only health outcomes, but also cost saving. Thus, this issue gets paramount importance in contemporary medicine. Method The aim of this article is to discuss the relationships between technology and adherence by asking the following three questions. (1) How can technology be used to monitor patient adherence? (2) Considering the mechanisms of nonadherence in chronic diseases, is there room for technology in interventions aimed to improve patient adherence? (3) What about adherence to technology in diabetes care? Results and Conclusion Technology may help improve adherence to long-term therapies by (1) giving a concrete representation of adherence rewards, (2) overcoming immediate obstacles to adherence, such as the fear of hypoglycemia, and (3) providing an opportunity for patient–doctor conversations. This assumes, however, that both the patient and the doctor are convinced that technologies are useful. PMID:20144287

  11. Improving cultural diversity awareness of physical therapy educators.

    PubMed

    Lazaro, Rolando T; Umphred, Darcy A

    2007-01-01

    In a climate of increasing diversity in the population of patients requiring physical therapy (PT) services, PT educators must prepare students and future clinicians to work competently in culturally diverse environments. To be able to achieve this goal, PT educators must be culturally competent as well. The purposes of the study were to develop a valid and reliable instrument to assess cultural diversity awareness and to develop an educational workshop to improve cultural diversity awareness of PT academic and clinical educators. Phase 1 of the study involved the development of an instrument to assess cultural diversity awareness. The Cultural Diversity Awareness Questionnaire (CDAQ) was developed, validated for content, analyzed for reliability, and field and pilot tested. Results indicated that the CDAQ has favorable psychometric properties. Phase 2 of the study involved the development and implementation of the Cultural Diversity Workshop (CDW). The seminar contents and class materials were developed, validated, and implemented as a one-day cultural diversity awareness seminar. A one-group, pretest-posttest experimental design was used, with participants who completed the CDAQ before and after the workshop. Results indicated that the workshop was effective in improving cultural diversity awareness of the participants. Results of the workshop evaluation affirmed the achievement of objectives and effectiveness of the facilitator. This study provided a solid initial foundation upon which a comprehensive cultural competence program can be developed.

  12. Photodynamic therapy improves the ultraviolet-irradiated hairless mice skin

    NASA Astrophysics Data System (ADS)

    Jorge, Ana Elisa S.; Hamblin, Michael R.; Parizotto, Nivaldo A.; Kurachi, Cristina; Bagnato, Vanderlei S.

    2014-03-01

    Chronic exposure to ultraviolet (UV) sunlight causes premature skin aging. In light of this fact, photodynamic therapy (PDT) is an emerging modality for treating cancer and other skin conditions, however its response on photoaged skin has not been fully illustrated by means of histopathology. For this reason, the aim of this study was analyze whether PDT can play a role on a mouse model of photoaging. Hence, SKH-1 hairless mice were randomly allocated in two groups, UV and UV/PDT. The mice were daily exposed to an UV light source (280-400 nm: peak at 350 nm) for 8 weeks followed by a single PDT session using 20% 5-aminolevulinic acid (ALA) topically. After the proper photosensitizer accumulation within the tissue, a non-coherent red (635 nm) light was performed and, after 14 days, skin samples were excised and processed for light microscopy, and their sections were stained with hematoxylin-eosin (HE) and Masson's Trichrome. As a result, we observed a substantial epidermal thickening and an improvement in dermal collagen density by deposition of new collagen fibers on UV/PDT group. These findings strongly indicate epidermal and dermal restoration, and consequently skin restoration. In conclusion, this study provides suitable evidences that PDT improves the UV-irradiated hairless mice skin, supporting this technique as an efficient treatment for photoaged skin.

  13. Improving proton therapy by metal-containing nanoparticles: nanoscale insights

    PubMed Central

    Schlathölter, Thomas; Eustache, Pierre; Porcel, Erika; Salado, Daniela; Stefancikova, Lenka; Tillement, Olivier; Lux, Francois; Mowat, Pierre; Biegun, Aleksandra K; van Goethem, Marc-Jan; Remita, Hynd; Lacombe, Sandrine

    2016-01-01

    The use of nanoparticles to enhance the effect of radiation-based cancer treatments is a growing field of study and recently, even nanoparticle-induced improvement of proton therapy performance has been investigated. Aiming at a clinical implementation of this approach, it is essential to characterize the mechanisms underlying the synergistic effects of nanoparticles combined with proton irradiation. In this study, we investigated the effect of platinum- and gadolinium-based nanoparticles on the nanoscale damage induced by a proton beam of therapeutically relevant energy (150 MeV) using plasmid DNA molecular probe. Two conditions of irradiation (0.44 and 3.6 keV/μm) were considered to mimic the beam properties at the entrance and at the end of the proton track. We demonstrate that the two metal-containing nanoparticles amplify, in particular, the induction of nanosize damages (>2 nm) which are most lethal for cells. More importantly, this effect is even more pronounced at the end of the proton track. This work gives a new insight into the underlying mechanisms on the nanoscale and indicates that the addition of metal-based nanoparticles is a promising strategy not only to increase the cell killing action of fast protons, but also to improve tumor targeting. PMID:27143877

  14. Stokes radius determination of radioiodinated polypeptide hormones by gel filtration

    SciTech Connect

    Ribela, M.T.; Bartolini, P.

    1988-11-01

    A simple technique for determination of the molecular (Stokes) radius of radioiodinated proteins was developed using the same column and chromatographic conditions employed in routine radioimmunoassay tracer purification. The calibration curve for five radioiodinated standard proteins presented a highly significant correlation (r = -0.996; P less than 0.001) and allowed precise molecular radius determination for labeled human growth hormone (hGH), luteotropin (hLH), follicle-stimulating hormone (hFSH), thyrotropin (hTSH), prolactin (hPRL), and corticotropin (hACTH), enabling detection of differences of the order of +/- 3%. The validity of the method was verified by determining the molecular radius of hGH in both ''cold'' (unlabeled standards and unknowns) and ''hot'' (radioiodinated standards and unknowns) systems. The technique can be applied in a very simple manner, requiring just one simple additional calibration run before Sephadex G-100 tracer purification. Furthermore, it can be applied to any protein, even when only extremely limited amounts are available. Since the standards and unknowns are labeled and chromatographed under identical conditions, potential common alterations of the molecule due to oxidation, iodine incorporation, tracer-carrier interactions, etc., are automatically corrected for.

  15. In contrast to matrix metalloproteinases, serum adiponectin concentrations increase after radioiodine treatment of thyrotoxicosis

    PubMed Central

    2012-01-01

    Background Matrix metalloproteinases (MMPs), together with their tissue inhibitors (TIMPs), remodel extracellular matrix under physiological and pathological conditions and are implicated in pathogenesis of cardiovascular diseases, cancer and in chronic inflammation. We have endeavoured to assess whether concentrations of MMPs, TIMPs, and anti-inflammatory adiponectin are altered by pharmacological treatment of acute thyrotoxicosis or by radioiodine therapy (RIT). Material and methods We measured serum concentrations of MMP-2, MMP-9, TIMP-1, TIMP-2, and adiponectin, TSH, free T4 (FT4) and free T3 (FT3) in 15 patients (4 males), age (years) 51.8±15.3 (mean±SD) with hyperthyroidism treated with thiamazole (Group 1) and in 20 subjects (2 males), treated for thyrotoxicosis with radioiodine, age 52.3±12.4 (Group 2), where blood samples were taken before RIT, visit 1 (V1), seven days post RIT, visit 2 (V2), and two to three months post RIT, visit 3 (V3). Results In Group 1 there was no significant change in concentrations of MMP-2, MMP-9, TIMP-1, TIMP-2 or adiponectin, despite a fall in FT4 and FT3 (8.74±4.79 pg/ml vs 3.54±2.40 pg/ml, for FT3, and 4.48 ±2.21 ng/ml vs 1.02±1.07 ng/ml, for FT4, p<0.001). In Group 2 RIT did not cause any acute change in serum MMP-2, MMP-9, TIMP-1 and TIMP-2 or adiponectin (V1 vs V2). However, there was a significant increase in serum adiponectin [from 15201±8860 ng/ml (V1) to 19373±8657 ng/ml (at V3), p<0.05], and TIMP-2 at V3 [from 129±45 ng/ml (V1) to 149±38 ng/ml (V3), p<0.01]. There was no significant change MMP-2, MMP-9 and TIMP-1 between V1 and V3. There was a decrease in FT4 and FT3 from 24.4±15.4 pmol/l (V1) to 14.7±10.6 pmol/l (V3), and from 10.0±5.65 (V1) to 6.1±4.8 pmol/l (V2), p<0.01, for FT4 and FT3, respectively. Conclusions Radioiodine therapy of thyrotoxicosis does not alter serum MMP-2, MMP-9 or TIMP-1 concentrations either acutely or after about three months of observation. An increase in serum adiponectin

  16. Autologous bone marrow-derived cell therapy combined with physical therapy induces functional improvement in chronic spinal cord injury patients.

    PubMed

    El-Kheir, Wael Abo; Gabr, Hala; Awad, Mohamed Reda; Ghannam, Osama; Barakat, Yousef; Farghali, Haithem A M A; El Maadawi, Zeinab M; Ewes, Ibrahim; Sabaawy, Hatem E

    2014-04-01

    Spinal cord injuries (SCI) cause sensory loss and motor paralysis. They are normally treated with physical therapy, but most patients fail to recover due to limited neural regeneration. Here we describe a strategy in which treatment with autologous adherent bone marrow cells is combined with physical therapy to improve motor and sensory functions in early stage chronic SCI patients. In a phase I/II controlled single-blind clinical trial (clinicaltrials.gov identifier: NCT00816803), 70 chronic cervical and thoracic SCI patients with injury durations of at least 12 months were treated with either intrathecal injection(s) of autologous adherent bone marrow cells combined with physical therapy or with physical therapy alone. Patients were evaluated with clinical and neurological examinations using the American Spinal Injury Association (ASIA) Impairment Scale (AIS), electrophysiological somatosensory-evoked potential, magnetic resonance imaging (MRI), and functional independence measurements. Chronic cervical and thoracic SCI patients (15 AIS A and 35 AIS B) treated with autologous adherent bone marrow cells combined with physical therapy showed functional improvements over patients in the control group (10 AIS A and 10 AIS B) treated with physical therapy alone, and there were no long-term cell therapy-related side effects. At 18 months posttreatment, 23 of the 50 cell therapy-treated cases (46%) showed sustained functional improvement. Compared to those patients with cervical injuries, a higher rate of functional improvement was achieved in thoracic SCI patients with shorter durations of injury and smaller cord lesions. Therefore, when combined with physical therapy, autologous adherent bone marrow cell therapy appears to be a safe and promising therapy for patients with chronic SCI of traumatic origin. Randomized controlled multicenter trials are warranted.

  17. Targeting Nuclear EGFR: Strategies for Improving Cetuximab Therapy in Lung Cancer

    DTIC Science & Technology

    2015-12-01

    AWARD NUMBER: W81XWH-12-1-0467 TITLE: Targeting Nuclear EGFR: Strategies for Improving Cetuximab Therapy in Lung Cancer PRINCIPAL...2012-08/31/2015 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Targeting Nuclear EGFR: Strategies for Improving Cetuximab Therapy in Lung Cancer 5b. GRANT...features FY14 LCRP publicity materials; LC110082 - Targeting Nuclear EGFR: Strategies for Improving Cetuximab Therapy in Lung Cancer) was highlighted in

  18. Narrative therapy for adults with major depressive disorder: improved symptom and interpersonal outcomes.

    PubMed

    Vromans, Lynette P; Schweitzer, Robert D

    2011-01-01

    This study investigated depressive symptom and interpersonal relatedness outcomes from eight sessions of manualized narrative therapy for 47 adults with major depressive disorder. Post-therapy, depressive symptom improvement (d=1.36) and proportions of clients achieving reliable improvement (74%), movement to the functional population (61%), and clinically significant improvement (53%) were comparable to benchmark research outcomes. Post-therapy interpersonal relatedness improvement (d=.62) was less substantial than for symptoms. Three-month follow-up found maintenance of symptom, but not interpersonal gains. Benchmarking and clinical significance analyses mitigated repeated measure design limitations, providing empirical evidence to support narrative therapy for adults with major depressive disorder.

  19. Modulation of the Tumor Vasculature and Oxygenation to Improve Therapy

    PubMed Central

    Siemann, Dietmar W.; Horsman, Michael R.

    2015-01-01

    The tumor microenvironment is increasingly recognized as a major factor influencing the success of therapeutic treatments and has become a key focus for cancer research. The progressive growth of a tumor results in an inability of normal tissue blood vessels to oxygenate and provide sufficient nutritional support to tumor cells. As a consequence the expanding neoplastic cell population initiates its own vascular network which is both structurally and functionally abnormal. This aberrant vasculature impacts all aspects of the tumor microenvironment including the cells, extracellular matrix, and extracellular molecules which together are essential for the initiation, progression and spread of tumor cells. The physical conditions that arise are imposing and manifold, and include elevated interstitial pressure, localized extracellular acidity, and regions of oxygen and nutrient deprivation. No less important are the functional consequences experienced by the tumor cells residing in such environments: adaptation to hypoxia, cell quiescence, modulation of transporters and critical signaling molecules, immune escape, and enhanced metastatic potential. Together these factors lead to therapeutic barriers that create a significant hindrance to the control of cancers by conventional anticancer therapies. However, the aberrant nature of the tumor microenvironments also offers unique therapeutic opportunities. Particularly interventions that seek to improve tumor physiology and alleviate tumor hypoxia will selectively impair the neoplastic cell populations residing in these environments. Ultimately, by combining such therapeutic strategies with conventional anticancer treatments it may be possible to bring cancer growth, invasion, and metastasis to a halt. PMID:26073310

  20. Follistatin Gene Therapy Improves Ambulation in Becker Muscular Dystrophy.

    PubMed

    Al-Zaidy, Samiah A; Sahenk, Zarife; Rodino-Klapac, Louise R; Kaspar, Brian; Mendell, Jerry R

    2015-09-02

    Follistatin is a ubiquitous secretory propeptide that functions as a potent inhibitor of the myostatin pathway, resulting in an increase in skeletal muscle mass. Its ability to interact with the pituitary activin-inhibin axis and suppress the secretion of follicle-stimulating hormone (FSH) called for caution in its clinical applicability. This limitation was circumvented by the use of one of the alternatively spliced follistatin variants, FS344, undergoing post-translational modification to FS315. This follistatin isoform is serum-based, and has a 10-fold lower affinity to activin compared to FS288. Preclinical studies of intramuscular delivery of the follistatin gene demonstrated safety and efficacy in enhancing muscle mass. We herein review the evidence supporting the utility of follistatin as a genetic enhancer to improve cellular performance. In addition, we shed light on the results of the first clinical gene transfer trial using the FS344 isoform of follistatin in subjects with Becker muscular dystrophy as well as the future directions for clinical gene therapy trials using follistatin.

  1. The solid mechanics of cancer and strategies for improved therapy

    PubMed Central

    Stylianopoulos, Triantafyllos

    2016-01-01

    Tumor progression and response to treatment is determined in large part by the generation of mechanical stresses that stem from both the solid and the fluid phase of the tumor. Furthermore, elevated solid stress levels can regulate fluid stresses by compressing intratumoral blood and lymphatic vessels. Blood vessel compression reduces tumor perfusion, while compression of lymphatic vessels hinders the ability of the tumor to drain excessive fluid from its interstitial space contributing to the uniform elevation of the interstitial fluid pressure. Hypo-perfusion and interstitial hypertension pose major barriers to the systemic administration of chemotherapeutic agents and nanomedicines to tumors, reducing treatment efficacies. Hypo-perfusion can also create a hypoxic and acidic tumor microenvironment that promotes tumor progression and metastasis. Hence, alleviation of intratumoral solid stress levels can decompress tumor vessels and restore perfusion and interstitial fluid pressure. In this review, three major types of tissue level solid stresses involved in tumor growth, namely stress exerted externally on the tumor by the host tissue, swelling stress and residual stress are discussed separately and details are provided regarding their causes, magnitudes and remedies. Subsequently, evidence of how stress-alleviating drugs could be used in combination with chemotherapy to improve treatment efficacy is presented, highlighting the potential of stress-alleviation strategies to enhance cancer therapy. Finally, a continuum-level, mathematical framework to incorporate these types of solid stress is outlined. PMID:27760260

  2. Follistatin Gene Therapy Improves Ambulation in Becker Muscular Dystrophy

    PubMed Central

    Al-Zaidy, Samiah A.; Sahenk, Zarife; Rodino-Klapac, Louise R.; Kaspar, Brian; Mendell, Jerry R.

    2015-01-01

    Abstract Follistatin is a ubiquitous secretory propeptide that functions as a potent inhibitor of the myostatin pathway, resulting in an increase in skeletal muscle mass. Its ability to interact with the pituitary activin-inhibin axis and suppress the secretion of follicle-stimulating hormone (FSH) called for caution in its clinical applicability. This limitation was circumvented by the use of one of the alternatively spliced follistatin variants, FS344, undergoing post-translational modification to FS315. This follistatin isoform is serum-based, and has a 10-fold lower affinity to activin compared to FS288. Preclinical studies of intramuscular delivery of the follistatin gene demonstrated safety and efficacy in enhancing muscle mass. We herein review the evidence supporting the utility of follistatin as a genetic enhancer to improve cellular performance. In addition, we shed light on the results of the first clinical gene transfer trial using the FS344 isoform of follistatin in subjects with Becker muscular dystrophy as well as the future directions for clinical gene therapy trials using follistatin. PMID:27858738

  3. Improved animal models for testing gene therapy for atherosclerosis.

    PubMed

    Du, Liang; Zhang, Jingwan; De Meyer, Guido R Y; Flynn, Rowan; Dichek, David A

    2014-04-01

    Gene therapy delivered to the blood vessel wall could augment current therapies for atherosclerosis, including systemic drug therapy and stenting. However, identification of clinically useful vectors and effective therapeutic transgenes remains at the preclinical stage. Identification of effective vectors and transgenes would be accelerated by availability of animal models that allow practical and expeditious testing of vessel-wall-directed gene therapy. Such models would include humanlike lesions that develop rapidly in vessels that are amenable to efficient gene delivery. Moreover, because human atherosclerosis develops in normal vessels, gene therapy that prevents atherosclerosis is most logically tested in relatively normal arteries. Similarly, gene therapy that causes atherosclerosis regression requires gene delivery to an existing lesion. Here we report development of three new rabbit models for testing vessel-wall-directed gene therapy that either prevents or reverses atherosclerosis. Carotid artery intimal lesions in these new models develop within 2-7 months after initiation of a high-fat diet and are 20-80 times larger than lesions in a model we described previously. Individual models allow generation of lesions that are relatively rich in either macrophages or smooth muscle cells, permitting testing of gene therapy strategies targeted at either cell type. Two of the models include gene delivery to essentially normal arteries and will be useful for identifying strategies that prevent lesion development. The third model generates lesions rapidly in vector-naïve animals and can be used for testing gene therapy that promotes lesion regression. These models are optimized for testing helper-dependent adenovirus (HDAd)-mediated gene therapy; however, they could be easily adapted for testing of other vectors or of different types of molecular therapies, delivered directly to the blood vessel wall. Our data also supports the promise of HDAd to deliver long

  4. Radioiodinated Capsids Facilitate In Vivo Non-Invasive Tracking of Adeno-Associated Gene Transfer Vectors

    PubMed Central

    Kothari, P.; De, B. P.; He, B.; Chen, A.; Chiuchiolo, M. J.; Kim, D.; Nikolopoulou, A.; Amor-Coarasa, A.; Dyke, J. P.; Voss, H. U.; Kaminsky, S. M.; Foley, C. P.; Vallabhajosula, S.; Hu, B.; DiMagno, S. G.; Sondhi, D.; Crystal, R. G.; Babich, J. W.; Ballon, D.

    2017-01-01

    Viral vector mediated gene therapy has become commonplace in clinical trials for a wide range of inherited disorders. Successful gene transfer depends on a number of factors, of which tissue tropism is among the most important. To date, definitive mapping of the spatial and temporal distribution of viral vectors in vivo has generally required postmortem examination of tissue. Here we present two methods for radiolabeling adeno-associated virus (AAV), one of the most commonly used viral vectors for gene therapy trials, and demonstrate their potential usefulness in the development of surrogate markers for vector delivery during the first week after administration. Specifically, we labeled adeno-associated virus serotype 10 expressing the coding sequences for the CLN2 gene implicated in late infantile neuronal ceroid lipofuscinosis with iodine-124. Using direct (Iodogen) and indirect (modified Bolton-Hunter) methods, we observed the vector in the murine brain for up to one week using positron emission tomography. Capsid radioiodination of viral vectors enables non-invasive, whole body, in vivo evaluation of spatial and temporal vector distribution that should inform methods for efficacious gene therapy over a broad range of applications. PMID:28059103

  5. Novel Approaches in Anaplastic Thyroid Cancer Therapy

    PubMed Central

    Hsu, Kun-Tai; Yu, Xiao-Min; Audhya, Anjon W.; Jaume, Juan C.; Lloyd, Ricardo V.; Miyamoto, Shigeki; Prolla, Tomas A.

    2014-01-01

    Anaplastic thyroid cancer (ATC), accounting for less than 2% of all thyroid cancer, is responsible for the majority of death from all thyroid malignancies and has a median survival of 6 months. The resistance of ATC to conventional thyroid cancer therapies, including radioiodine and thyroid-stimulating hormone suppression, contributes to the very poor prognosis of this malignancy. This review will cover several cellular signaling pathways and mechanisms, including RET/PTC, RAS, BRAF, Notch, p53, and histone deacetylase, which are identified to play roles in the transformation and dedifferentiation process, and therapies that target these pathways. Lastly, novel approaches and agents involving the Notch1 pathway, nuclear factor κB, Trk-fused gene, cancer stem-like cells, mitochondrial mutation, and tumor immune microenvironment are discussed. With a better understanding of the biological process and treatment modality, the hope is to improve ATC outcome in the future. PMID:25260367

  6. Juvenile hypothyroidism among two populations exposed to radioiodine.

    PubMed Central

    Goldsmith, J R; Grossman, C M; Morton, W E; Nussbaum, R H; Kordysh, E A; Quastel, M R; Sobel, R B; Nussbaum, F D

    1999-01-01

    We found an epidemic of juvenile hypothyroidism among a population of self-defined "downwinders" living near the Hanford nuclear facility located in southeast Washington State. The episode followed massive releases of 131I. Self-reported data on 60 cases of juvenile hypothyroidism (<20 years of age) among a group of 801 Hanford downwinders are presented, as well as data concerning the thyroid status of approximately 160,000 children exposed to radioiodine before 10 years of age as a result of the 26 April 1986 Chernobyl explosion in the former Soviet Union. These children were residents of five regions near Chernobyl. They were examined by standardized screening protocols over a period of 5 years from 1991 to 1996. They are a well-defined group of 10 samples. Fifty-six cases of hypothyroidism were found among boys and 92 among girls. Body burdens of 137Cs have been correlated with hypothyroidism prevalence rates. On the other hand, the group of juvenile (<20 years of age) Hanford downwinders is not a representative sample. Most of the 77 cases of juvenile hypothyroidism in the Hanford group were diagnosed from 1945 to 1970. However, the ratio of reported cases to the county population under 20 years of age is roughly correlated with officially estimated mean levels of cumulative thyroid 131I uptake in these counties, providing evidence that juvenile hypothyroidism was associated with radioiodine exposures. Because even subtle hypothyroidism may be of clinical significance in childhood and can be treated, it may be useful to screen for the condition in populations exposed to radioiodine fallout. Although radiation exposure is associated with hypothyroidism, its excess among fallout-exposed children has not been previously quantified. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 PMID:10090710

  7. From prophylaxis to atomic cocktail: circulation of radioiodine.

    PubMed

    Santesmases, María Jesús

    2009-01-01

    This paper is a history of iodine. To trace the trajectory of this element, goiter is used as a guideline for the articulation of a historical account, as a representation of thyroid disorders and of the spaces of knowledge and practices related to iodine. Iodine's journey from goiter treatment and prophylaxis in the late interwar period took on a new course after WWII by including the element's radioactive isotopes. I intend to show how the introduction of radioiodine contributed to stabilize the epistemic role of iodine, in both its non-radioactive and radioactive form, in thyroid gland studies and in the treatment of its disorders.

  8. Savannah River Site radioiodine atmospheric releases and offsite maximum doses

    SciTech Connect

    Marter, W.L.

    1990-11-01

    Radioisotopes of iodine have been released to the atmosphere from the Savannah River Site since 1955. The releases, mostly from the 200-F and 200-H Chemical Separations areas, consist of the isotopes, I-129 and 1-131. Small amounts of 1-131 and 1-133 have also been released from reactor facilities and the Savannah River Laboratory. This reference memorandum was issued to summarize our current knowledge of releases of radioiodines and resultant maximum offsite doses. This memorandum supplements the reference memorandum by providing more detailed supporting technical information. Doses reported in this memorandum from consumption of the milk containing the highest I-131 concentration following the 1961 1-131 release incident are about 1% higher than reported in the reference memorandum. This is the result of using unrounded 1-131 concentrations of I-131 in milk in this memo. It is emphasized here that this technical report does not constitute a dose reconstruction in the same sense as the dose reconstruction effort currently underway at Hanford. This report uses existing published data for radioiodine releases and existing transport and dosimetry models.

  9. Improvement with ongoing Enzyme Replacement Therapy in advanced late-onset Pompe disease: a case study.

    PubMed

    Case, Laura E; Koeberl, Dwight D; Young, Sarah P; Bali, Deeksha; DeArmey, Stephanie M; Mackey, Joanne; Kishnani, Priya S

    2008-12-01

    Benefits of enzyme replacement therapy with Myozyme (alglucosidase alfa), anecdotally reported in late-onset Pompe disease, range from motor and pulmonary improvement in less severely affected patients, to stabilization with minimal improvement in those with advanced disease. We report a case of a 63-year-old patient with significant morbidity who made notable motor and pulmonary function gains after two years on therapy. Thus, improvements in those with advanced disease may be possible after long-term treatment.

  10. Minocycline Improves the Efficacy of EGFR Inhibitor Therapy: A Hypothesis

    PubMed Central

    Venniyoor, Ajit; Al Bahrani, Bassim

    2016-01-01

    Skin rash is a side effect of drugs that inhibit epithelial growth factor receptor (EGFR) as a part of targeted therapy of cancer. Its appearance and severity correlates with survival. Minocycline, an oral tetracycline antibiotic, is recommended as treatment (and increasingly, for prevention) of the rash, though infection is seen in only one-third of the patients. Minocycline has additional anticancer properties such as poly(ADP-ribose) polymerase inhibition. It is proposed that such properties contribute to the efficacy of EGFR inhibitors and can also explain the positive correlation between grade of rash and survival as patients with higher grades of rash are more likely to receive minocycline. Early concurrent administration of minocycline is recommended in patients planned for EGFR therapy while awaiting trials proving this hypothesis. PMID:27833902

  11. Testicular function in patients with differentiated thyroid carcinoma treated with radioiodine

    SciTech Connect

    Pacini, F.; Gasperi, M.; Fugazzola, L.

    1994-09-01

    The aim of the present study was to assess whether {sup 131}I therapy for differentiated thyroid carcinoma (DTC) can affect endocrine testicular function. Serum follicle-stimulating hormone (FSH) and testosterone (T) concentrations were measured in 103 patients periodically submitted for radioiodine therapy for residual or metastatic disease. Mean follow-up was 93.7{+-}54 mo (range 10-243 mo). Mean FSH values in {sup 131}I-treated patients tested after their last treatment were 15.3{+-}9.9 mU/ml, significantly higher than those of 19 untreated patients (6.5{+-}3.1 mU/ml). Considering the mean +3 s.d. FSH of untreated subjects as the upper limit of normal range, 36.8% of the patients had an abnormal increase in serum FSH. Longitudinal analysis performed in 21 patients showed that the behavior of FSH in response to {sup 131}I therapy was not universal. Six patients had no change or a slight increase in serum FSH after {sup 131}I administration; eleven patients had a transient increase above normal values 6-12 mo after {sup 131}I treatment, with return to normal levels in subsequent months. The administration of a second dose was followed by a similar increase in FSH levels. Finally, four patients, followed for a long period of time and treated with several {sup 131}I doses, showed a progressive increase in serum FSH, which eventually became permanent. Semen analysis, performed in a small subgroup of patients, showed a consistent reduction in the number of normokinetic sperm. No change was found in serum T levels between treated and untreated patients. The results indicate that {sup 131}I therapy for thyroid carcinoma is associated with transient impairment of testicular germinal cell function. The damage may become permanent for high-radiation activities delivered year after year and might pose a significant risk of infertility. 14 refs., 8 figs., 1 tab.

  12. Characterization and restoration of performance of {open_quotes}aged{close_quotes} radioiodine removing activated carbons

    SciTech Connect

    Freeman, W.P.

    1997-08-01

    The degradation of radioiodine removal performance for impregnated activated carbons because of ageing is well established. However, the causes for this degradation remain unclear. One theory is that this reduction in performance from the ageing process results from an oxidation of the surface of the carbon. Radioiodine removing activated carbons that failed radioiodine removal tests showed an oxidized surface that had become hydrophilic compared with new carbons. We attempted to restore the performance of these {open_quotes}failed{close_quotes} carbons with a combination of thermal and chemical treatment. The results of these investigations are presented and discussed with the view of extending the life of radioiodine removing activated carbons. 4 refs., 2 tabs.

  13. Hibernation-Based Therapy to Improve Survival of Severe Blood Loss

    DTIC Science & Technology

    2013-10-01

    AD_________________ Award Number: W81xwh-10-2-0121 TITLE: Hibernation -Based Therapy to Improve...COVERED 1 October 2012 to 30 September 2013 4. TITLE AND SUBTITLE Hibernation -Based Therapy to Improve Survival of Severe Blood 5a. CONTRACT...risk for bleeding to death. Our overall strategy in this series of studies is to capitalize on the physiologic adaptive responses seen in hibernating

  14. Hibernation-Based Therapy to Improve Survival of Severe Blood Loss

    DTIC Science & Technology

    2014-10-01

    AWARD NUMBER: W81XWH-10-2-0121 TITLE: Hibernation -Based Therapy to Improve Survival of Severe...2014 4. TITLE AND SUBTITLE Hibernation -Based Therapy to Improve Survival of Severe Blood 5a. CONTRACT NUMBER Loss 5b. GRANT...responses in hibernating mammals to aid in salvage of a patient with a potentially life-threatening blood loss, permitting survival to reach effective

  15. Hibernation-Based Therapy to Improve Survival of Severe Blood Loss

    DTIC Science & Technology

    2012-10-01

    AD_________________ Award Number: W81XWH-10-2-0121 TITLE: Hibernation -Based Therapy to Improve... Hibernation -Based Therapy to Improve Survival of Severe Blood 5a. CONTRACT NUMBER Loss 5b. GRANT NUMBER W81XWH-10-2-0121 5c. PROGRAM ELEMENT NUMBER...physiologic adaptive responses in hibernating mammals to aid in slavage of a patient with a potentially life-threatening blood loss, permitting

  16. Hibernation-Based Therapy to Improve Survival of Severe Blood Loss

    DTIC Science & Technology

    2011-10-01

    Award Number: W81XWH-10-2-0121 TITLE: Hibernation -Based Therapy to Improve Survival of Severe Blood Loss PRINCIPAL INVESTIGATOR: Gregory...SUBTITLE 5a. CONTRACT NUMBER Hibernation -Based Therapy to Improve Survival of Severe Blood Loss 5b. GRANT NUMBER W81XWH-10-2-0121 5c. PROGRAM...death. The overall strategy is to use strategies learned from study of hibernating mammals to survive a potentially life-threatening blood loss and allow

  17. Postremission therapy in acute promyelocytic leukemia: room for improvement?

    PubMed

    Lancet, Jeffrey E

    2014-11-20

    A 29-year-old white man presented to the hospital with a 3-week history of fatigue, generalized weakness, gingival swelling and bleeding, and headaches. Laboratory work revealed WBC 30.4 k/μL, hemoglobin 7.9 g/dL, and platelets 16 k/μL. The WBC differential showed 64% blasts and 24% promyelocytes. Coagulation studies revealed prothrombin time (PT) 13.5 seconds, internationalized normalized ratio (INR) 1.3, fibrinogen 199 mg/dL, D-dimer greater than 1.0 μg/mL, and fibrin split products greater than 40 μg/mL. A bone-marrow aspirate with biopsy was performed, yielding the diagnosis of acute promyelocytic leukemia (APL), with t(15;17)(q23;q21.1) in all metaphases. Induction therapy commenced with daunorubicin, cytarabine (Ara-C), and all-trans retinoic acid (ATRA), and complete remission was documented 5 weeks later. PML-RARA fusion transcripts were still detected by reverse transcription polymerase chain reaction. He is now referred to you for consideration of postremission therapy in the setting of high-risk acute promyelocytic leukemia in first remission.

  18. Harnessing the immune system to improve cancer therapy

    PubMed Central

    Papaioannou, Nikos E.; Beniata, Ourania V.; Vitsos, Panagiotis

    2016-01-01

    Cancer immunotherapy uses the immune system and its components to mount an anti-tumor response. During the last decade, it has evolved from a promising therapy option to a robust clinical reality. Many immunotherapeutic modalities are already approved by the Food and Drug Administration (FDA) for treating cancer patients and many others are in the pipeline for approval as standalone or combinatorial therapeutic interventions, several also combined with standard treatments in clinical studies. The two main axes of cancer immunotherapeutics refer to passive and active treatments. Prominent examples of passive immunotherapy include administration of monoclonal antibodies and cytokines and adoptive cell transfer of ex vivo “educated” immune cells. Active immunotherapy refers, among others, to anti-cancer vaccines [peptide, dendritic cell (DC)-based and allogeneic whole cell vaccines], immune checkpoint inhibitors and oncolytic viruses, whereas new approaches that can further enhance anti-cancer immune responses are also widely explored. Herein, we present the most popular cancer immunotherapy approaches and discuss their clinical relevance referring to data acquired from clinical trials. To date, clinical experience and efficacy suggest that combining more than one immunotherapy interventions, in conjunction with other treatment options like chemotherapy, radiotherapy and targeted or epigenetic therapy, should guide the way to cancer cure. PMID:27563648

  19. Radio-iodination of neurotrophins and their delivery in vivo: advantages of membrane filtration and the use of disposable syringes.

    PubMed

    von Bartheld, C S

    1998-02-20

    This paper reports two simple improvements for the radio-iodination of neurotrophins and their delivery in vivo. (1) Neurotrophins can be effectively separated from free iodide by using membrane filtration devices. Seven methods for the separation of free iodide are compared, including dialysis, gel filtration, and membrane filtration. Membrane filtration of the iodinated protein has several important advantages over dialysis or gel filtration. These include the precise control over the final concentration; excellent recovery of the neurotrophin; easy and inexpensive procedure; performance of the entire procedure in a fume hood; and reduced volume of radioactive waste. (2) Disposable, inexpensive syringes are suitable for the delivery of small volumes of radio-iodinated or non-radioactive neurotrophins. Plastic disposable insulin syringes are compared with Hamilton syringes. The ejection volume of the disposable syringes is surprisingly reliable in the dose range 2-15 microl. Their in vivo performance was tested by injections in the eyes of chick embryos in ovo. The amounts remaining in the eye varied significantly less with the disposable syringes. Leakage into the surrounding eye-muscles after intraocular injection was significantly more frequent with Hamilton syringes than with the disposable syringes. Thus, disposable syringes can be a reliable and cost-effective alternative for drug delivery of 2-15 microl volumes.

  20. Atorvastatin therapy associated with improvement in left ventricular remodeling in a case of idiopathic dilated cardiomyopathy.

    PubMed

    Yamada, Takahisa; Node, Koichi; Mine, Takanao; Morita, Takashi; Kioka, Hidetaka; Tamaki, Shunsuke; Tsukamoto, Yasumasa; Masuda, Masaharu; Okuda, Keiji; Fukunami, Masatake

    2006-12-01

    Statins have pleiotropic effects such as anti-inflammatory and vascular protective effects that would be beneficial for patients with chronic heart failure. This report describes a patient with idiopathic dilated cardiomyopathy and a long-standing history of heart failure that was treated with atorvastatin in addition to conventional therapy that included beta-blockers. Atorvastatin therapy for 12 months was associated with an improvement in cardiac function and improved left ventricular remodeling and peak oxygen consumption. This result suggests that statin therapy may be a potential novel treatment strategy for patients with chronic heart failure.

  1. Improving adherence to hormone replacement therapy with effective patient-physician communication.

    PubMed

    Sarrel, P M

    1999-03-01

    Surgically menopausal women are 5 times more likely to begin hormone replacement therapy than are naturally menopausal women, and they continue therapy for longer periods. The primary reasons that women refuse hormone replacement are fear of cancer and perceived side effects. In contrast, withdrawal bleeding is the major reason that women discontinue hormone replacement therapy. Physician-patient communication plays an important role in a woman's decision to use hormone replacement therapy, to fill her prescription, and to adhere to the regimen. The first visit at which hormone replacement therapy is discussed is crucial to establishing an effective patient-physician relationship. At least 15 minutes, and preferably 45 minutes, should be reserved for this visit. Patient follow-up-either by phone or in person-during the first month can help improve adherence because this is when many women may have nuisance side effects and discontinue therapy.

  2. [Postoperative radioiodine ablation in patients with low risk differentiated thyroid carcinoma].

    PubMed

    Díez, Juan J; Grande, Enrique; Iglesias, Pedro

    2015-01-06

    Most patients with newly diagnosed differentiated thyroid carcinoma have tumors with low risk of mortality and recurrence. Standard therapy has been total or near total thyroidectomy followed by postoperative radioiodine remnant ablation (RRA). Although RRA provides benefits, current clinical guidelines do not recommend it universally, since an increase in disease-free survival or a decrease in mortality in low risk patients has not been demonstrated so far. Advancements in our understanding of the biological behavior of thyroid cancer have been translated into the clinic in a personalized approach to the patients based on their individual risk of recurrence and mortality. Current evidence suggests that RRA is not indicated in most low-risk patients, especially those with papillary carcinomas smaller than 1cm, without extrathyroidal extension, unfavorable histology, lymph node involvement or distant metastases. Follow-up of these patients with serial measurements of serum thyroglobulin and neck ultrasound is adequate. Careful evaluation of all risk factors of clinical relevance will allow a more realistic assessment of each individual patient.

  3. Engineering nanomedicines for improved melanoma therapy: progress and promises

    PubMed Central

    Bei, Di; Meng, Jianing; Youan, Bi-Botti C

    2012-01-01

    Once metastatic, melanoma remains one of the most aggressive and morbid malignancies. Moreover, in past decades, the overall survival for advanced unresectable melanoma exhibited a constancy of poor prognosis. Low response rates and serious adverse effects have been characteristic of standard therapy based on a combination of chemotherapeutic agents or immunotherapy with IL-2. For example, the chemotherapy including dacarbazine, carmustin, cisplatin and tamoxifen is known as ‘Dartmouth regimen’ while the CVD regimen comprises carmustine, vinblastine and dacarbazine. Thus, there is an urgent and critical need to reformulate these bioactive agents using nanoscience and nanotechnology as alternative strategies. This article overviews current design and evaluation of nanomedicine undertaken to address this unmet medical need. The nanomedicines studied include polymeric nanoparticles, liposomes, polymersomes, dendrimers, cubosomes, niosomes and nanodiamonds. In this preclinical article, nanotechnology provides hope for effective treatment of this aggressive and largely treatment-resistant disease. PMID:21128721

  4. [Improvement of parodontitis therapy of patients with HIV-infection].

    PubMed

    Soboleva, L A; Oseeva, A O; Shul'diakov, A A; Bulkina, N V

    2010-01-01

    For the purpose to determine the clinic-pathogenetic efficacy of cycloferon liniment in the combined therapy of periodontitis of patients with subclinical stage of HIV-infection medical examination and treatment of 40 patients was carried out. It was established that use of liniment cycloferon in the combined treatment of patients with subclinical stage of HIV-infection allowed to accelerate process of normalization of lipid peroxidation parameters and antioxidant potential of blood, to decrease infection load (herpes symplex virus I, Candida albicans, Staphylococcus aureus) in parodontal recess and evidence of local inflammation with reduction of activity of the tumours necrosis factor and interleukin 1beta, what provided acceleration of recuperation processes, lowering the frequency of parodontitis relapses.

  5. Chromobacterium Violaceum Sepsis: Rethinking Conventional Therapy to Improve Outcome

    PubMed Central

    Richard, Kathleen R.; Lovvorn, Joshua J.; Oliver, Sara E.; Ross, Shannon A.; Benner, Kim W.; Kong, Michele Y.F.

    2015-01-01

    Patient: Male, 11 Final Diagnosis: Chromobacterium violaceum infection Symptoms: Abscess • fever • rash Medication: — Clinical Procedure: ECMO Specialty: Critical Care Medicine Objective: Rare disease Background: Chromobacterium violaceum (C. violaceum) is a facultative anaerobic gram-negative bacterium found in soil and water, especially in tropical and subtropical areas. Although infection in humans is rare, it is associated with significant morbidity. The bacterium is known for its resistance to multiple antimicrobials, and the possibility of relapse and reinfection. Presence of bacteremia, disseminated infection, and ineffective antimicrobial agents are predictors of mortality. Case Report: We report the case of a previously healthy 11-year-old male with C. violaceum sepsis who was exposed to stagnant water. He presented with severe septic shock and developed multi-organ system failure. Initial presumptive diagnosis was staphylococcal infection secondary to presence of skin abscesses resulting in antibiotic coverage with vancomycin, clindamycin, nafcillin and ceftriaxone. He also had multiple lung and liver abscesses. Once C. violaceum was identified, he received meropenem and ciprofloxacin, and was later discharged on ertapenem and trimethoprim-sulfamethoxazole (TMP-SMX) to complete a total of six months of antibiotics. He was diagnosed with chronic granulomatous disease (CGD) and is currently on prophylactic TMP-SMX and itraconazole. He has not had any relapses since his initial presentation. Conclusions: This case highlights the importance of considering C. violaceum as a relevant human pathogen, and considering it early in temperate regions, particularly in cases of fulminant sepsis associated with multi-organ abscesses. Once C. violaceum is identified, appropriate antimicrobial therapy should be started promptly, and sufficient duration of treatment is necessary for successful therapy. PMID:26477750

  6. Clinical potential of gene-directed enzyme prodrug therapy to improve radiation therapy in prostate cancer patients.

    PubMed

    Vajda, Alice; Marignol, Laure; Foley, Ruth; Lynch, Thomas H; Lawler, Mark; Hollywood, Donal

    2011-12-01

    Despite the advances in prostate cancer diagnosis and treatment, current therapies are not curative in a significant proportion of patients. Gene-directed enzyme prodrug therapy (GDEPT), when combined with radiation therapy, could improve the outcome of treatment for prostate cancer, the second leading cause of cancer death in the western world. GDEPT involves the introduction of a therapeutic transgene, which can be targeted to the tumour cells. A prodrug is administered systemically and is converted to its toxic form only in those cells containing the transgene, resulting in cell kill. This review will discuss the clinical trials which have investigated the potential of GDEPT at various stages of prostate cancer progression. The advantages of using GDEPT in combination with radiotherapy will be examined, as well as some of the recent advances which enhance the potential utility of GDEPT.

  7. Eye-Search: A web-based therapy that improves visual search in hemianopia

    PubMed Central

    Ong, Yean-Hoon; Jacquin-Courtois, Sophie; Gorgoraptis, Nikos; Bays, Paul M; Husain, Masud; Leff, Alexander P

    2015-01-01

    Persisting hemianopia frequently complicates lesions of the posterior cerebral hemispheres, leaving patients impaired on a range of key activities of daily living. Practice-based therapies designed to induce compensatory eye movements can improve hemianopic patients' visual function, but are not readily available. We used a web-based therapy (Eye-Search) that retrains visual search saccades into patients' blind hemifield. A group of 78 suitable hemianopic patients took part. After therapy (800 trials over 11 days), search times into their impaired hemifield improved by an average of 24%. Patients also reported improvements in a subset of visually guided everyday activities, suggesting that Eye-Search therapy affects real-world outcomes. PMID:25642437

  8. Robotic therapy for chronic stroke: general recovery of impairment or improved task-specific skill?

    PubMed Central

    Goldsmith, Jeff; Harran, Michelle; Kane, Leslie; Berard, Jessica; Huang, Sylvia; Ryan, Sophia L.; Mazzoni, Pietro; Krakauer, John W.; Huang, Vincent S.

    2015-01-01

    There is a great need to develop new approaches for rehabilitation of the upper limb after stroke. Robotic therapy is a promising form of neurorehabilitation that can be delivered in higher doses than conventional therapy. Here we sought to determine whether the reported effects of robotic therapy, which have been based on clinical measures of impairment and function, are accompanied by improved motor control. Patients with chronic hemiparesis were trained for 3 wk, 3 days a week, with titrated assistive robotic therapy in two and three dimensions. Motor control improvements (i.e., skill) in both arms were assessed with a separate untrained visually guided reaching task. We devised a novel PCA-based analysis of arm trajectories that is sensitive to changes in the quality of entire movement trajectories without needing to prespecify particular kinematic features. Robotic therapy led to skill improvements in the contralesional arm. These changes were not accompanied by changes in clinical measures of impairment or function. There are two possible interpretations of these results. One is that robotic therapy only leads to small task-specific improvements in motor control via normal skill-learning mechanisms. The other is that kinematic assays are more sensitive than clinical measures to a small general improvement in motor control. PMID:26180120

  9. Robotic therapy for chronic stroke: general recovery of impairment or improved task-specific skill?

    PubMed

    Kitago, Tomoko; Goldsmith, Jeff; Harran, Michelle; Kane, Leslie; Berard, Jessica; Huang, Sylvia; Ryan, Sophia L; Mazzoni, Pietro; Krakauer, John W; Huang, Vincent S

    2015-09-01

    There is a great need to develop new approaches for rehabilitation of the upper limb after stroke. Robotic therapy is a promising form of neurorehabilitation that can be delivered in higher doses than conventional therapy. Here we sought to determine whether the reported effects of robotic therapy, which have been based on clinical measures of impairment and function, are accompanied by improved motor control. Patients with chronic hemiparesis were trained for 3 wk, 3 days a week, with titrated assistive robotic therapy in two and three dimensions. Motor control improvements (i.e., skill) in both arms were assessed with a separate untrained visually guided reaching task. We devised a novel PCA-based analysis of arm trajectories that is sensitive to changes in the quality of entire movement trajectories without needing to prespecify particular kinematic features. Robotic therapy led to skill improvements in the contralesional arm. These changes were not accompanied by changes in clinical measures of impairment or function. There are two possible interpretations of these results. One is that robotic therapy only leads to small task-specific improvements in motor control via normal skill-learning mechanisms. The other is that kinematic assays are more sensitive than clinical measures to a small general improvement in motor control.

  10. Can anthocyanins improve maintenance therapy of Ph(+) acute lymphoblastic leukaemia?

    PubMed

    Köchling, Joachim; Schmidt, Manuel; Rott, Yvonne; Sagner, Michael; Ungefroren, Hendrik; Wittig, Burghard; Henze, Günter

    2013-04-01

    Chemotherapy and tyrosine kinase inhibitors provide high remission rates. However, prognosis of adult patients with Philadelphia chromosome-positive acute lymphoblastic leukaemia (Ph(+) ALL) still remains poor. Because most adults eventually relapse without allogeneic stem cell transplantation, which is not available for all patients, novel strategies are required for relapse prevention. As the integrity of the immune system is essential for the control of remaining leukaemia cells, we compared the efficacy of anthocyanins, imatinib and a DNA-based vaccine as non-immunosuppressant components with 6-mercaptopurine (6-MP) to control minimal residual disease in vitro and in vivo using different leukaemia cell lines and syngeneic mice. Proliferation of Ph(+) ALL was significantly better inhibited by anthocyanin-rich berry extract or imatinib compared with 6-MP. Although anthocyanins induced apoptosis in some leukaemia cell lines, the level of caspase-3, caspase-8 and caspase-9 was significantly lower compared with imatinib and 6-MP. When used as single components, anthocyanins and imatinib mesylate failed to eradicate pre-existing Ph(+) ALL in syngeneic mice, while 6-MP led to 10% and DNA vaccination to 56% survival. Intriguingly, only the combination of DNA vaccination with berry extract but not with the isolated anthocyanin, cyanidin-3-rutinoside or imatinib further increased leukaemia-free and overall survival, and 90% of lethally challenged mice survived. We suggest that induction and enhancement of a leukaemia-specific immunity by DNA vaccination and anthocyanin-rich berry extract can also decrease the relapse rate in patients with Ph(+) ALL. Furthermore, this approach may serve as strategy for maintenance therapy of other malignancies.

  11. Towards improved therapies using nanopharmaceuticals: recent patents on pharmaceutical nanoformulations.

    PubMed

    Horstkotte, Elke; Odoerfer, Kathrin I

    2012-12-01

    Pharmaceutical formulations that contain nanosized drugs are perceived as "Nanopharmaceuticals" and offer significant benefit for the patient compared to the conventional formulated drugs. There are several advantages of nanoparticular drug formulations such as enhanced solubility and dissolution rate, enhanced oral bioavailability, improved dose proportionality, reduced food effects, suitability for administration by all routes and possibility of sterile filtration due to decreased particle size range. Several nanopharmaceuticals are successfully marketed. Different patented techniques are commercialized to prepare nanopharmaceuticals such as milling, homogenization and precipitation. The focus of the underlying review is to give an overview of those technologies for nanosizing active pharmaceutical ingredients and recently published patents in the field of nanosized pharmaceutics.

  12. Improving L-dopa therapy: the development of enzyme inhibitors.

    PubMed

    Gershanik, Oscar S

    2015-01-01

    The introduction of levodopa produced a monumental change in the treatment of Parkinson's disease (PD). Limitations in its bioavailability and tolerability led to the search for drugs that could improve its pharmacokinetics and safety profile. Dopa-decarboxylase inhibitors were the first such drugs that were developed, and their use in combination with L-dopa has become standard practice. Increasing knowledge on the metabolism of L-dopa allowed the identification of additional targets for intervention in an attempt to improve the symptomatic efficacy of L-dopa. Monoamineoxidase inhibitors, enhancing the central bioavailability of dopamine by blocking its metabolism, were the next step, and despite controversies regarding their efficacy, they have remained as valuable adjuncts to l-dopa in the treatment of PD. More recently, the introduction of potent, selective catechol-O-methyl transferase inhibitors have found their place in the therapeutic armamentarium of PD and are prescribed in combination with l-dopa to prolong the duration of its action.

  13. Improvement and decline in vision with gene therapy in childhood blindness.

    PubMed

    Jacobson, Samuel G; Cideciyan, Artur V; Roman, Alejandro J; Sumaroka, Alexander; Schwartz, Sharon B; Heon, Elise; Hauswirth, William W

    2015-05-14

    Retinal gene therapy for Leber's congenital amaurosis, an autosomal recessive childhood blindness, has been widely considered to be safe and efficacious. Three years after therapy, improvement in vision was maintained, but the rate of loss of photoreceptors in the treated retina was the same as that in the untreated retina. Here we describe long-term follow-up data from three treated patients. Topographic maps of visual sensitivity in treated regions, nearly 6 years after therapy for two of the patients and 4.5 years after therapy for the third patient, indicate progressive diminution of the areas of improved vision. (Funded by the National Eye Institute; ClinicalTrials.gov number, NCT00481546.).

  14. Cancer therapy improvement with mesoporous silica nanoparticles combining photodynamic and photothermal therapy

    NASA Astrophysics Data System (ADS)

    Zhao, Z. X.; Huang, Y. Z.; Shi, S. G.; Tang, S. H.; Li, D. H.; Chen, X. L.

    2014-07-01

    In this work, we develop novel mesoporous silica composite nanoparticles (hm-SiO2(AlC4Pc)@Pd) for the co-delivery of photosensitizer (PS) tetra-substituted carboxyl aluminum phthalocyanine (AlC4Pc) and small Pd nanosheets as a potential dual carrier system to combine photodynamic therapy (PDT) with photothermal therapy (PTT). In the nanocomposite, PS AlC4Pc was covalently conjugated to a mesoporous silica network, and small Pd nanosheets were coated onto the surface of mesoporous silica by both coordination and electrostatic interaction. Since small Pd nanosheets and AlC4Pc display matched maximum absorptions in the 600-800 nm near-infrared (NIR) region, the fabricated hm-SiO2(AlC4Pc)@Pd nanocomposites can generate both singlet oxygen and heat upon 660 nm single continuous wavelength (CW) laser irradiation. In vitro results indicated that the cell-killing efficacy by simultaneous PDT/PTT treatment using hm-SiO2(AlC4Pc)@Pd was higher than PDT or PTT treatment alone after exposure to a 660 nm CW-NIR laser.

  15. Cancer therapy improvement with mesoporous silica nanoparticles combining photodynamic and photothermal therapy.

    PubMed

    Zhao, Z X; Huang, Y Z; Shi, S G; Tang, S H; Li, D H; Chen, X L

    2014-07-18

    In this work, we develop novel mesoporous silica composite nanoparticles (hm-SiO2(AlC4Pc)@Pd) for the co-delivery of photosensitizer (PS) tetra-substituted carboxyl aluminum phthalocyanine (AlC4Pc) and small Pd nanosheets as a potential dual carrier system to combine photodynamic therapy (PDT) with photothermal therapy (PTT). In the nanocomposite, PS AlC4Pc was covalently conjugated to a mesoporous silica network, and small Pd nanosheets were coated onto the surface of mesoporous silica by both coordination and electrostatic interaction. Since small Pd nanosheets and AlC4Pc display matched maximum absorptions in the 600-800 nm near-infrared (NIR) region, the fabricated hm-SiO2(AlC4Pc)@Pd nanocomposites can generate both singlet oxygen and heat upon 660 nm single continuous wavelength (CW) laser irradiation. In vitro results indicated that the cell-killing efficacy by simultaneous PDT/PTT treatment using hm-SiO2(AlC4Pc)@Pd was higher than PDT or PTT treatment alone after exposure to a 660 nm CW-NIR laser.

  16. Hibernation-Based Therapy to Improve Survival of Severe Blood Loss

    DTIC Science & Technology

    2015-10-01

    AWARD NUMBER: W81XWH-10-2-0121 TITLE: Hibernation -Based Therapy to Improve Survival of Severe Blood Loss PRINCIPAL INVESTIGATOR: Gregory...PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. 1. REPORT DATE 2. REPORT TYPE 3. DATES COVERED 4. TITLE AND SUBTITLE Hibernation -Based Therapy to... hibernating mammals to aid in salvage of a patient with a potentially life-threatening blood loss, permitting survival to reach effective medical

  17. Improvement of tumor localization of photosensitizers for photodynamic therapy and its application for tumor diagnosis.

    PubMed

    Ogura, Shun-Ichiro; Hagiya, Yuichiro; Tabata, Kenji; Kamachi, Toshiaki; Okura, Ichiro

    2012-01-01

    Photodynamic therapy (PDT) and photodynamic diagnosis of cancer are widely used in clinical fields. These are performed using photosensitizers. Many metalloporphyrin-related compounds have been developed as photosensitizers for use in PDT, and these tumor localization ability have been improved in recent research. Moreover, the precursor of porphyrin 5-aminolevulinic acid is used in fluorescence diagnosis using its tumor localization ability. In this review, these applications of photosensitizers in cancer therapy and diagnosis are summarized.

  18. Mesenchymal stem cell therapy promotes the improvement and recovery of renal function in a preclinical model

    PubMed Central

    Urt-Filho, Antônio; Oliveira, Rodrigo Juliano; Hermeto, Larissa Correa; Pesarini, João Renato; de David, Natan; Cantero, Wilson de Barros; Falcão, Gustavo; Marks, Guido; Antoniolli-Silva, Andréia Conceição Milan Brochado

    2016-01-01

    Abstract Acute renal failure (ARF) is an extremely important public health issue in need of novel therapies. The present study aimed to evaluate the capacity of mesenchymal stem cell (MSC) therapy to promote the improvement and recovery of renal function in a preclinical model. Wistar rats were used as the experimental model, and our results show that cisplatin (5mg/kg) can efficiently induce ARF, as measured by changes in biochemical (urea and creatinine) and histological parameters. MSC therapy performed 24h after the administration of chemotherapy resulted in normalized plasma urea and creatinine levels 30 and 45d after the onset of kidney disease. Furthermore, MSC therapy significantly reduced histological changes (intratubular cast formation in protein overload nephropathy and tubular hydropic degeneration) in this ARF model. Thus, considering that current therapies for ARF are merely palliative and that MSC therapy can promote the improvement and recovery of renal function in this model system, we suggest that innovative/alternative therapies involving MSCs should be considered for clinical studies in humans to treat ARF. PMID:27275667

  19. Antifungal Therapy for Systemic Mycosis and the Nanobiotechnology Era: Improving Efficacy, Biodistribution and Toxicity

    PubMed Central

    Souza, Ana C. O.; Amaral, Andre C.

    2017-01-01

    Fungal diseases have been emerging as an important public health problem worldwide with the increase in host predisposition factors due to immunological dysregulations, immunosuppressive and/or anticancer therapy. Antifungal therapy for systemic mycosis is limited, most of times expensive and causes important toxic effects. Nanotechnology has become an interesting strategy to improve efficacy of traditional antifungal drugs, which allows lower toxicity, better biodistribution, and drug targeting, with promising results in vitro and in vivo. In this review, we provide a discussion about conventional antifungal and nanoantifungal therapies for systemic mycosis. PMID:28326065

  20. Astym therapy improves function and range of motion following mastectomy

    PubMed Central

    Davies, Claire C; Brockopp, Dorothy; Moe, Krista

    2016-01-01

    Hypersensitive scar tissue formation along the incision line and drain site is a common side effect following mastectomy. If this scar tissue is not addressed, it can lead to decreased flexibility and function in the involved upper quadrant. Astym® treatment is a new approach to soft tissue injuries, and is evidenced in animal studies to promote the healing and regeneration of soft tissues. It has also been found to reduce pain and increase function in people with soft tissue dysfunction. The aim of Astym treatment is to engage the regenerative mechanisms of the body in order to resorb scar tissue, stimulate tissue turnover, and regenerate soft tissues. Handheld instrumentation is applied topically to locate and treat the underlying dysfunctional soft tissue through specific protocols for the application of particular pressures and shear forces. The purpose of this study was to examine the effects of Astym treatment on activities of daily living in women who had undergone a mastectomy following a diagnosis of breast cancer. A quasi-experiment involving 40 women, following a mastectomy, evaluated five outcome measures pre- and post-Astym treatment. All five measurement scores: Disabilities of the Arm, Shoulder, and Hand Outcome Measure; a clothing questionnaire on their ability to wear a bra; Patient-Specific Functional Scale; active range of motion of shoulder flexion; and active range of motion of abduction were also measured and all demonstrated significant changes. In this study, Astym treatment improved active range of motion in the involved quadrant and also improved function in patients following a mastectomy. PMID:27022302

  1. Exploring Theranostic Potentials of Radioiodinated Hypericin in Rodent Necrosis Models

    PubMed Central

    Li, Junjie; Cona, Marlein Miranda; Chen, Feng; Feng, Yuanbo; Zhou, Lin; Yu, Jie; Nuyts, Johan; de Witte, Peter; Zhang, Jian; Himmelreich, Uwe; Verbruggen, Alfons; Ni, Yicheng

    2012-01-01

    Objectives: The present animal experiments were conducted to evaluate radioiodinated Hypericin (Hyp) for its regional distribution as well as theranostic potentials. Materials and Methods: Rat models of reperfused liver infarction (RLI) and hepatic rhabdomyosarcoma (R1) were surgically induced. R1 models received Combretastatin A4 phosphate (CA4P) intravenously at 10 mg/kg 24 h prior to radioiodinated Hyp. Three groups of 6 rats each containing 3 RLI and 3 R1 models received iv injections of 123I-Hyp at 37, 74, and 185 MBq/kg respectively and followed by 0.1 ml of 1% Evans blue solution were sacrificed at 4, 24 and 48 hour post injection immediately after in vivo examination of MRI and planar gamma scintigraphy. Besides, two groups of 6 R1 models that received either 300 MBq/kg of 131I-Hyp or vehicle intravenously were examined using MRI to compare tumor growth for 12 days. Autoradiography, gamma counting, and histopathology were performed for postmortem verifications and quantification. Results: Necrosis as seen in vivo on contrast-enhanced MRI corresponded well with the hot spots on planar scintigraphy. Autoradiography and gamma counting revealed intense accumulation of 123I-Hyp in necrotic liver (3.94 ± 1.60, 5.38 ± 1.04, and 6.03 ± 2.09 %ID/g ± SD) and necrotic tumor (4.27 ± 0.76, 5.57 ± 0.76, and 5.68 ± 1.33 %ID/g ± SD) relative to normal liver (1.76 ± 0.54, 0.41 ± 0.18, and 0.16 ± 0.07 %ID/g ± SD), with a high necrosis-to-liver ratio of 2.3, 14.0, and 37.0 at 4, 24 and 48 h respectively. Tumor volumes in R1 models that received 131I-Hyp and vehicle changed from 0.45 ± 0.09, and 0.47 ± 0.12 cm3 (p > 0.05) on day 0 to1.32 ± 0.76 and 3.63 ± 0.72 cm3 (p < 0.001) on day 12, with the corresponding necrosis ratios from 73 ± 12 %, and 76 ± 17 % to 47 ± 18% and 17 ± 13 % (p < 0.01), and with the tumor DT of 7.3 ± 1.0 and 4.2 ± 0.7 days, respectively. Conclusions: Radioiodinated Hyp as a necrosis avid tracer appears promising for non

  2. Cardiac resynchronization therapy improves the uptake of MIBI-99mTc and cardiac function.

    PubMed

    Brandão, Simone Cristina Soares; Giorgi, Maria Clementina; Nishioka, Silvana D'Orio; Martinelli Filho, Martino; Soares, José; Meneghetti, José Cláudio

    2008-09-01

    This case shows the improvement promoted by cardiac resynchronization therapy (CRT) on myocardial perfusion and left ventricular (LV) performance assessed by gated myocardial perfusion scintigraphy. The patient had idiopathic dilated cardiomyopathy, left bundle branch block and severe heart failure despite optimized medical treatment. After CRT, clinical improvement, QRS reduction and improvement of previously hypoperfused anterior and septal walls were observed. There was also decrease in LV end-diastolic and systolic volumes and increase in LV ejection fraction.

  3. Speech and language therapies to improve pragmatics and discourse skills in patients with schizophrenia.

    PubMed

    Joyal, Marilyne; Bonneau, Audrey; Fecteau, Shirley

    2016-06-30

    Individuals with schizophrenia display speech and language impairments that greatly impact their integration to the society. The aim of this systematic review was to identify the importance of speech and language therapy (SLT) as part of rehabilitation curriculums for patients with schizophrenia emphasizing on the speech and language abilities assessed, the therapy setting and the therapeutic approach. This article reviewed 18 studies testing the effects of language therapy or training in 433 adults diagnosed with schizophrenia. Results showed that 14 studies out of 18 lead to improvements in language and/or speech abilities. Most of these studies comprised pragmatic or expressive discursive skills being the only aim of the therapy or part of it. The therapy settings vary widely ranging from twice daily individual therapy to once weekly group therapy. The therapeutic approach was mainly operant conditioning. Although the evidence tends to show that certain areas of language are treatable through therapy, it remains difficult to state the type of approach that should be favoured and implemented to treat language impairments in schizophrenia.

  4. Vocal improvement after voice therapy in the treatment of benign vocal fold lesions.

    PubMed

    Schindler, A; Mozzanica, F; Ginocchio, D; Maruzzi, P; Atac, M; Ottaviani, F

    2012-10-01

    Benign vocal fold lesions are common in the general population, and have important public health implications and impact on patient quality of life. Nowadays, phonomicrosurgery is the most common treatment of these lesions. Voice therapy is generally associated in order to minimize detrimental vocal behaviours that increase the stress at the mid-membranous vocal folds. Nonetheless, the most appropriate standard of care for treating benign vocal fold lesion has not been established. The aim of this study was to analyze voice changes in a group of dysphonic patients affected by benign vocal fold lesions, evaluated with a multidimensional protocol before and after voice therapy. Sixteen consecutive patients, 12 females and 4 males, with a mean age of 49.7 years were enrolled. Each subject had 10 voice therapy sessions with an experienced speech/language pathologist for a period of 1-2 months, and was evaluated before and at the end of voice therapy with a multidimensional protocol that included self-assessment measures and videostroboscopic, perceptual, aerodynamic and acoustic ratings. Videostroboscopic examination did not reveal resolution of the initial pathology in any case. No improvement was observed in aerodynamic and perceptual ratings. A clear and significant improvement was visible on Wilcoxon signed-rank test for the mean values of Jitt%, Noise to Harmonic Ratio (NHR) and Voice Handicap Index (VHI) scores. Even if it is possible that, for benign vocal fold lesions, only a minor improvement of voice quality can be achieved after voice therapy, rehabilitation treatment still seems useful as demonstrated by improvement in self-assessment measures. If voice therapy is provided as an initial treatment to the patients with benign vocal fold lesions, this may lead to an improvement in the perceived voice quality, making surgical intervention unnecessary. This is one of the first reports on the efficacy of voice therapy in the management of benign vocal fold

  5. Bispecific Antibody Pretargeting for Improving Cancer Imaging and Therapy

    SciTech Connect

    Sharkey, Robert M.

    2005-02-04

    The main objective of this project was to evaluate pretargeting systems that use a bispecific antibody (bsMAb) to improve the detection and treatment of cancer. A bsMAb has specificity to a tumor antigen, which is used to bind the tumor, while the other specificity is to a peptide that can be radiolabeled. Pretargeting is the process by which the unlabeled bsMAb is given first, and after a sufficient time (1-2 days) is given for it to localize in the tumor and clear from the blood, a small molecular weight radiolabeled peptide is given. According to a dynamic imaging study using a 99mTc-labeled peptide, the radiolabeled peptide localizes in the tumor in less than 1 hour, with > 80% of it clearing from the blood and body within this same time. Tumor/nontumor targeting ratios that are nearly 50 times better than that with a directly radiolabeled Fab fragment have been observed (Sharkey et al., ''Signal amplification in molecular imaging by a multivalent bispecific nanobody'' submitted). The bsMAbs used in this project have been composed of 3 antibodies that will target antigens found in colorectal and pancreatic cancers (CEA, CSAp, and MUC1). For the ''peptide binding moiety'' of the bsMAb, we initially examined an antibody directed to DOTA, but subsequently focused on another antibody directed against a novel compound, HSG (histamine-succinyl-glycine).

  6. Active Music Therapy and Physical Improvements From Rehabilitation for Neurological Conditions.

    PubMed

    Kogutek, Demian Leandro; Holmes, Jeffrey David; Grahn, Jessica Adrienne; Lutz, Sara G; Ready, Emily

    2016-01-01

    Context • A variety of rehabilitation-based interventions are currently available for individuals with physical impairments resulting from neurological conditions, including physiotherapy, occupational therapy, and speech language pathology. Many individuals find participation in those therapies to be challenging. Alternative therapies have emerged as beneficial adjunctive treatments for individuals undergoing neurological rehabilitation, including music therapy (MT). Objective • The study intended to identify and collate systematically the evidence on MT interventions that address physical improvements in a rehabilitative setting. Design • The research team performed a literature review, searching electronic databases from their inception to April 2014, including Embase, CINAHL, PubMed, Scopus, and ProQuest. The review included original studies that examined the use of active MT as an intervention that promotes physical improvements for adults >18 y of age. Articles were excluded if the studies focused primarily on psychosocial, emotional, or spiritual therapeutic goals. The review identified the studies' outcome measures for different populations and the MT approaches and interventions and obtained a general description of the clinical sessions, such as the frequency and duration of the therapy, interventions performed, sessions designs, populations, equipment used, and credentials of the therapists. Results • Eleven studies identified 2 major categories for the delivery of MT sessions: individual and group. One study included group sessions, and 10 studies included individual sessions. The studies included a total of 290 participants, 32 in the group MT, and 258 in the individual MT. The one study that used group therapy was based on active MT improvisation. For the individual therapy, 2 studies had investigated therapeutic instrument music performance and 8 used music-supported therapy. Conclusions • The findings of the review suggested that active MT

  7. Status of radioiodine control for nuclear fuel reprocessing plants

    SciTech Connect

    Burger, L.L.; Scheele, R.D.

    1983-07-01

    This report summarizes the status of radioiodine control in a nuclear fuel reprocessing plant with respect to capture, fixation, and disposal. Where possible, we refer the reader to a number of survey documents which have been published in the last four years. We provide updates where necessary. Also discussed are factors which must be considered in developing criteria for iodine control. For capture from gas streams, silver mordenite and a silver nitrate impregnated silica (AC-6120) are considered state-of-the-art and are recommended. Three aqueous scrubbing processes have been demonstrated: Caustic scrubbing is simple but probably will not give an adequate iodine retention by itself. Mercurex (mercuric nitrate-nitric acid scrubbing) has a number of disadvantages including the use of toxic mercury. Iodox (hyperazeotropic nitric acid scrubbing) is effective but employs a very corrosive and hazardous material. Other technologies have been tested but require extensive development. The waste forms recommended for long-term storage or disposal are silver iodide, the iodates of barium, strontium, or calcium, and silver loaded sorbents, all fixed in cement. Copper iodide in bitumen (asphalt) is a possibility but requires testing. The selection of a specific form will be influenced by the capture process used.

  8. Radioiodinated carnitine and acylcarnitine analogs as potential myocardial imaging agents

    SciTech Connect

    McConnell, D.S.

    1991-01-01

    R-carnitine is extremely important in mammalian energy metabolism. Gamma-butyrobetaine, the immediate biosynthetic precursor to R-carnitine, is synthesized in many organs. However, only liver can hydroxylate gamma-butyrobetaine to carnitine. Thus the transport of carnitine from its site of synthesis to the site of utilization is of utmost importance. Carnitine is found in highest concentration in cardiac and skeletal muscle, where it is required for the transport of fatty acids into the mitochondria. Before fatty acids are utilized as fuel for the myocyte by beta-oxidation, they are bound to carnitine as an acylcarnitine ester at the 3-hydroxyl, and transported across the micochondrial membranes. R,S-Carnitine has been shown to be taken up by myocytes. The author has begun a study on the use of carnitine derivatives as potential carriers for the site-specific delivery of radioiodine to bidning sites in the myocardium. Such agents labeled with a gamma-emitting nuclide such as iodine-123 would be useful for the noninvasive imaging of these tissues. The aim was to synthesize a variety of radiolabeled analogs of carnitine and acylcarnitine to address questions of transport, binding and availability for myocardial metabolism. These analogs consist of N-alkylated derivatives of carnitine, acylcarnitine esters as well as carnitine amides and ethers. One C-alkylated derivative showed interesting biodistribution, elevated myocardial uptake and competition with carnitine for binding in the myocardium.

  9. Site-specifically radioiodinated antibody for targeting tumors

    SciTech Connect

    Rea, D.W.; Ultee, M.E.; Belinka, B.A. Jr.; Coughlin, D.J.; Alvarez, V.L. )

    1990-02-01

    Labeling of an antibody site specifically through its carbohydrate regions preserves its antigen-binding activity. Previously site-specific labeling studies have conjugated antibodies with metallic radioisotopes or drugs. We now report site-specific labeling with a new radioiodinated compound, 2-hydroxy-5-iodo-3-methylbenzoyl hydrazide, whose synthesis we described earlier. The compound is reacted with aldehyde groups produced by specific oxidation of the carbohydrate portion of the antibody with sodium m-periodate. Optimized conjugation conditions give good recovery of active antibody containing 10 groups per molecule. The conjugate is stable in solution for at least several weeks at both 4 and -70 degrees C. When injected into nude mice bearing LS174T human cancer xenografts, the conjugate of B72.3 antibody localizes well to tumor tissue, with low uptake by other organs. This biodistribution is similar to that of conjugate prepared by using solid-phase chloramine-T (Iodohead). There are only two significant differences. First, the carbohydrate conjugate is much less susceptible to dehalogenation, and thus shows much less thyroid uptake. Secondly, the biological half-life of the carbohydrate conjugate was about half that of the chloramine-T one. This could be due primarily to lysis of the hydrazine bond through which the antibody is attached to the compound, which would then be excreted rapidly by itself. The new reagent will be especially useful for antibodies which either cannot be labeled by chloramine-T methods, or whose activity is impaired by them.

  10. Integrated insulin pump therapy with continuous glucose monitoring for improved adherence: technology update.

    PubMed

    Tumminia, Andrea; Sciacca, Laura; Frittitta, Lucia; Squatrito, Sebastiano; Vigneri, Riccardo; Le Moli, Rosario; Tomaselli, Letizia

    2015-01-01

    Insulin pump therapy combined with real-time continuous glucose monitoring, known as sensor-augmented pump (SAP) therapy, has been shown to improve metabolic control and to reduce the rate of hypoglycemia in adults with type 1 diabetes compared to multiple daily injections or standard continuous subcutaneous insulin infusion. Glycemic variability is also reduced in patients on SAP therapy. This approach allows patients to monitor their glucose levels being informed of glycemic concentration and trend. Trained diabetic patients, therefore, can appropriately modify insulin infusion and/or carbohydrate intake in order to prevent hypo- or hyperglycemia. For these reasons, SAP therapy is now considered the gold standard for type 1 diabetes treatment. To be clinically effective, however, devices and techniques using advanced technology should not only have the potential to theoretically ameliorate metabolic control, but also be well accepted by patients in terms of satisfaction and health-related quality of life, because these factors will improve treatment adherence and consequently overall outcome. SAP therapy is generally well tolerated by patients; however, many clinical trials have identified significant noncompliance in the use of this device, most notably in the pediatric and adolescent populations. In this review we aim to analyze the main reasons for good or poor adherence to SAP therapy and to provide useful tips in order to fully benefit from this kind of novel therapeutic approach.

  11. Combining Enriched Environment, Progesterone, and Embryonic Neural Stem Cell Therapy Improves Recovery after Brain Injury.

    PubMed

    Nudi, Evan T; Jacqmain, Justin; Dubbs, Kelsey; Geeck, Katalin; Salois, Garrick; Searles, Madeleine A; Smith, Jeffrey S

    2015-07-15

    Millions of persons every year are affected by traumatic brain injury (TBI), and currently no therapies have shown efficacy in improving outcomes clinically. Recent research has suggested that enriched environments (EE), embryonic neural stem cells (eNSC), and progesterone (PROG) improve functional outcomes after TBI, and further, several investigators have suggested that a polytherapuetic approach may have greater efficacy than a single therapy. The purpose of the current study was to determine if varying combinations of post-injury EE, progesterone therapy, or eNSC transplantation would improve functional outcomes over just a single therapy. A controlled cortical impact was performed in rats to create a lesion in the medial frontal cortex. The rats were then placed in either EE or standard environments and administered 10 mg/kg progesterone or vehicle injections 4 h post-injury and every 12 h for 72 h after the initial injection. Seven days after the surgery, rats were transplanted with either eNSCs or media. Rats were then tested on the open field test, Barnes maze, Morris water maze, and Rotor-Rod tasks. Improved functional outcomes were shown on a majority of the behavioral tasks in animals that received a combination of therapies. This effect was especially prominent with therapies that were combined with EE. Immunohistochemistry showed that the transplanted eNSCs survived, migrated, and displayed neural phenotypes. These data suggest that a poly-therapeutic approach after TBI improves functional recovery to a greater magnitude. Moreover, when polytherapies are combined with EE, the effects on recovery are enhanced, leading to greater recovery of function.

  12. Effect of CPAP Therapy in Improving Daytime Sleepiness in Indian Patients with Moderate and Severe OSA

    PubMed Central

    Battan, Gulshan; Panwar, Ajay; Atam, Virendra; Kumar, Pradeep; Gangwar, Anil; Roy, Ujjawal

    2016-01-01

    Introduction Obstructive Sleep Apnoea (OSA) is a highly prevalent disease and a major public health issue in India. Excessive daytime sleepiness is an almost ubiquitous symptom of OSA. Epworth Sleepiness Scale (ESS) score is a validated objective score to measure the degree of daytime sleepiness. Continuous Positive Airway Pressure (CPAP) therapy has been established as the gold standard treatment modality for OSA patients. A few Indian studies have reported the effectiveness of CPAP therapy in improving ESS scores after 1st month of CPAP use. Aim To observe both, short-term (one month) and long-term (three month) effects of CPAP therapy on ESS scores in moderate to severe OSA patients. Materials and Methods The patients complaining of excessive day-time sleepiness, snoring and choking episodes during sleep, consecutively presenting to medicine OPD over a period of 2 years, were subjected to Polysomnography (PSG). Seventy-three patients with apnoea-hypopnea index (AHI) ≥15 were categorised as having moderate to severe forms of OSA (moderate OSA with AHI=15-30 and severe OSA with AHI >30), and were scheduled for an initial trial of CPAP therapy. Forty-seven patients reported good tolerance to CPAP therapy after a trial period of 2 weeks and comprised the final study group. ESS scores in these patients were recorded at the baseline, and after 1st and 3rd month of CPAP therapy, and statistically analysed for significance. Results Mean ESS score at the baseline among moderate and severe OSA patients were 13.67±2.29 and 16.56 ±1.87, respectively. ESS score in both these subgroups improved significantly to 11.63±3.79, p=0.022, CI (0.3293-4.0106)} and 14.13 ±3.74, p < 0.001, CI (1.2991-4.5408), respectively after one month of CPAP therapy. Likewise, mean ESS scores among moderate and severe OSA patients improved significantly to 9.84 ±2.97, p = 0.022, CI (0.3293-4.0106) and 12.29 ±3.97, p <0.001, CI (2.9414-6.1385), respectively after three months of CPAP therapy

  13. CD25 preselective anti-HIV vectors for improved HIV gene therapy.

    PubMed

    Kalomoiris, Stefanos; Lawson, Je'tai; Chen, Rachel X; Bauer, Gerhard; Nolta, Jan A; Anderson, Joseph S

    2012-12-01

    As HIV continues to be a global public health problem with no effective vaccine available, new and innovative therapies, including HIV gene therapies, need to be developed. Due to low transduction efficiencies that lead to low in vivo gene marking, therapeutically relevant efficacy of HIV gene therapy has been difficult to achieve in a clinical setting. Methods to improve the transplantation of enriched populations of anti-HIV vector-transduced cells may greatly increase the in vivo efficacy of HIV gene therapies. Here we describe the development of preselective anti-HIV lentiviral vectors that allow for the purification of vector-transduced cells to achieve an enriched population of HIV-resistant cells. A selectable protein, human CD25, not normally found on CD34+ hematopoietic progenitor cells (HPCs), was incorporated into a triple combination anti-HIV lentiviral vector. Upon purification of cells transduced with the preselective anti-HIV vector, safety was demonstrated in CD34+ HPCs and in HPC-derived macrophages in vitro. Upon challenge with HIV-1, improved efficacy was observed in purified preselective anti-HIV vector-transduced macrophages compared to unpurified cells. These proof-of-concept results highlight the potential use of this method to improve HIV stem cell gene therapy for future clinical applications.

  14. Muscarinic cholinergic receptor binding: in vivo depiction using single photon emission computed tomography and radioiodinated quinuclidinyl benzilate

    SciTech Connect

    Drayer, B.; Jaszczak, R.; Coleman, E.; Storni, A.; Greer, K.; Petry, N.; Lischko, M.; Flanagan, S.

    1982-06-01

    An attempt was made to characterize, in vivo, specific binding to the muscarinic cholinergic receptor in the calf using the radioiodinated ligand quinuclidinyl benzilate (/sup 123/I-OH-QNB) and single photon detection emission computed tomography (SPECT). The supratentorial brain activity was significantly increased after the intravenous infusion of /sup 123/I-OH-QNB as compared to free /sup 123/I. Scopolamine, a muscarinic cholinergic receptor antagonist, decreased the measured brain activity when infused prior to /sup 123/I-OH-QNB consistent with pharmacologic blockade of specific receptor binding. Quantitative in vitro tissue distribution studies obtained following SPECT imaging were consistent with regionally distinct specific receptor binding in the striatum and cortical gray matter, nonspecific binding in the cerebellum, and pharmacologic blockade of specific binding sites with scopolamine. Although /sup 123/I-OH-QNB is not the ideal radioligand, our limited success will hopefully encourage the development of improved binding probes for SPECT imaging and quantitation.

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

    PubMed

    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.

  16. Does Nursing Facility Use of Habilitation Therapy Improve Performance on Quality Measures?

    PubMed

    Fitzler, Sandra; Raia, Paul; Buckley, Fredrick O; Wang, Mei

    2016-12-01

    The purpose of the project, Centers for Medicare & Medicaid Services (CMS) Innovation study, was to evaluate the impact on 12 quality measures including 10 Minimum Data Set (MDS) publicly reported measures and 2 nursing home process measures using habilitation therapy techniques and a behavior team to manage dementia-related behaviors. A prospective design was used to assess the changes in the measures. A total of 30 Massachusetts nursing homes participated in the project over a 12-month period. Project participation required the creation of an interdisciplinary behavior team, habilitation therapy training, facility visit by the program coordinator, attendance at bimonthly support and sharing calls, and monthly collection of process measure data. Participating facilities showed improvement in 9 of the 12 reported measures. Findings indicate potential quality improvement in having nursing homes learn habilitation therapy techniques and know how to use the interdisciplinary team to manage problem behaviors.

  17. The potential for nanotechnology to improve delivery of therapy to the acute ischemic heart.

    PubMed

    Evans, Cameron W; Iyer, K Swaminathan; Hool, Livia C

    2016-04-01

    Treatment of acute cardiac ischemia remains an area in which there are opportunities for therapeutic improvement. Despite significant advances, many patients still progress to cardiac hypertrophy and heart failure. Timely reperfusion is critical in rescuing vulnerable ischemic tissue and is directly related to patient outcome, but reperfusion of the ischemic myocardium also contributes to damage. Overproduction of reactive oxygen species, initiation of an inflammatory response and deregulation of calcium homeostasis all contribute to injury, and difficulties in delivering a sufficient quantity of drug to the affected tissue in a controlled manner is a limitation of current therapies. Nanotechnology may offer significant improvements in this respect. Here, we review recent examples of how nanoparticles can be used to improve delivery to the ischemic myocardium, and suggest some approaches that may lead to improved therapies for acute cardiac ischemia.

  18. The Hypothalamic-Pituitary-Thyroid Axis in Infants and Children: Protection from Radioiodines

    PubMed Central

    Yang, Xiaoxia; Harris, Curtis; Lumen, Annie

    2014-01-01

    Potassium iodide (KI) is recommended as an emergency treatment for exposure to radioiodines, most commonly associated with nuclear detonation or mishaps at nuclear power plants. Protecting the thyroid gland of infants and children remains a priority because of increased incidence of thyroid cancer in the young exposed to radioiodines (such as 131I and 133I). There is a lack of clinical studies for KI and radioiodines in children or infants to draw definitive conclusions about the effectiveness and safety of KI administration in the young. In this paper, we compare functional aspects of the hypothalamic-pituitary-thyroid (HPT) axis in the young and adults and review the limited studies of KI in children. The HPT axis in the infant and child is hyperactive and therefore will respond less effectively to KI treatment compared to adults. Research on the safety and efficacy of KI in infants and children is needed. PMID:24971190

  19. Development of a stable radioiodinating reagent to label monoclonal antibodies for radiotherapy of cancer

    SciTech Connect

    Wilbur, D.S.; Hadley, S.W.; Hylarides, M.D.; Abrams, P.G.; Beaumier, P.A.; Morgan, A.C.; Reno, J.M.; Fritzberg, A.R. )

    1989-02-01

    A method of radioiodinating monoclonal antibodies such that the labeled antibodies do not undergo in vivo deiodination has been studied. The method utilizes conjugation of succinimidyl para-iodobenzoate to the antibody. The iodobenzoate was radiolabeled by using an organometallic intermediate to facilitate the reaction. Thus, succinimidyl para-tri-n-butylstannylbenzoate was radiolabeled in 60-90% radiochemical yield and subsequently conjugated to the antibody in 80-90% yield. Animal biodistribution studies were carried out with two separate anti-melanoma antibodies (9.2.27 and NR-M1-05) labeled by this method, and examined in nude mice bearing human melanoma tumor xenografts. Very large differences in the localization of radioactivity were observed in the thyroids and stomachs of mice when the iodobenzoyl-labeled antibodies were compared with the same antibodies labeled using the chloramine-T method of radioiodination. Few other significant differences in the tissue distribution of the radioiodinated antibodies were seen.

  20. Development and testing of a prototype on-line radioiodine monitor for nuclear power stations

    SciTech Connect

    Tseng, T.T.; Jester, W.A.; Baratta, A.J.; McMaster, I.B.; Miller, D.W.

    1986-01-01

    A prototype on-line monitor has been developed which is capable of detecting radioiodine in the presence of as much as 1 X 10(6) higher concentration of noble gases. The system contains two identical radiation monitoring chambers through which the monitored air and a purging gas alternately cycle. Each chamber contains a silver zeolite filter which has a high retention of the various forms of airborne radioiodine but low retention of noble gases. During the purging cycle the radioactive noble gases are quickly purged from the filter and chamber and the lower levels of radioiodine accumulated on the filter are detected. This system has been successfully tested using short-lived radionuclides simulating vented reactor gases resulting from an abnormal condition.

  1. The impact of improved glycaemic control with GLP-1 receptor agonist therapy on diabetic retinopathy.

    PubMed

    Varadhan, Lakshminarayanan; Humphreys, Tracy; Walker, Adrian B; Varughese, George I

    2014-03-01

    Rapid improvement in glycaemic control with GLP-1 receptor agonist (RA) therapy has been reported to be associated with significant progression of diabetic retinopathy. This deterioration is transient, and continuing GLP-1 RA treatment is associated with reversal of this phenomenon. Pre-existent maculopathy, higher grade of retinopathy and longer duration of diabetes may be risk factors for persistent deterioration.

  2. Efficacy of Adjunct In-Home Coaching to Improve Outcomes in Parent-Child Interaction Therapy

    ERIC Educational Resources Information Center

    Timmer, Susan G.; Zebell, Nancy M.; Culver, Michelle A.; Urquiza, Anthony J.

    2010-01-01

    Objectives: The purpose of this study is to test whether increasing the exposure to coaching by adding an in-home component to clinic-delivered Parent-Child Interaction Therapy (PCIT) will increase the speed of parenting skill acquisition and show greater improvements in children's behaviors and parental stress. Methods: Seventy-three parent-child…

  3. Substance Abuse Treatment And Family Therapy. A Treatment Improvement Protocol (TIP) Series 39

    ERIC Educational Resources Information Center

    Gilbert, Jonathan Max; Oliff, Helen; Sutton, David; Bartlett, Catalina; Henderson, Randi

    2004-01-01

    This Treatment Improvement Protocol (TIP) addresses substance abuse treatment in the context of family therapy. TIPs are best-practice guidelines for the treatment of substance use disorders that make the latest research in substance abuse treatment available to counselors and educators. The content was generated by a panel of experts in the…

  4. Substance Abuse Treatment: Group Therapy. Treatment Improvement Protocol (TIP) Series 41

    ERIC Educational Resources Information Center

    Gilbert, Jonathan Max; Hills, Susan; Rife, Mary Lou

    2005-01-01

    This Treatment Improvement Protocol (TIP) presents an overview of the role and efficacy of group therapy in substance abuse treatment. TIPs are best-practice guidelines for the treatment of substance use disorders that make the latest research in substance abuse treatment available to counselors and educators. The content was generated by a panel…

  5. TSL Family Therapy Followed by Improved Marital Quality and Reduced Oxidative Stress

    ERIC Educational Resources Information Center

    Kim, Jae Yop; Kim, Dong Goo; Nam, Seok In

    2012-01-01

    Objectives: The current study evaluated the effectiveness of a form of family therapy developed in Korea. The "Thank you--Sorry--Love" (TSL) model was applied to a group of elderly retired men to improve the quality of their marriage and to reduce their stress. Methods: Thirty married retired Korean men were assigned to three groups.…

  6. Barriers to preventive therapy for breast and other major cancers and strategies to improve uptake

    PubMed Central

    DeCensi, Andrea; Thorat, Mangesh A; Bonanni, Bernardo; Smith, Samuel G; Cuzick, Jack

    2015-01-01

    The global cancer burden continues to rise and the war on cancer can only be won if improvements in treatment go hand in hand with therapeutic cancer prevention. Despite the availability of several efficacious agents, utilisation of preventive therapy has been poor due to various barriers, such as the lack of physician and patient awareness, fear of side effects, and licensing and indemnity issues. In this review, we discuss these barriers in detail and propose strategies to overcome them. These strategies include improving physician awareness and countering prejudices by highlighting the important differences between preventive therapy and cancer treatment. The importance of the agent–biomarker–cohort (ABC) paradigm to improve effectiveness of preventive therapy cannot be overemphasised. Future research to improve therapeutic cancer prevention needs to include improvements in the prediction of benefits and harms, and improvements in the safety profile of existing agents by experimentation with dose. We also highlight the role of drug repurposing for providing new agents as well as to address the current imbalance between therapeutic and preventive research. In order to move the field of therapeutic cancer prevention forwards, engagement with policymakers to correct research imbalance as well as to remove practical obstacles to implementation is also urgently needed. PMID:26635899

  7. Recommendations for improving adherence to type 2 diabetes mellitus therapy--focus on optimizing insulin-based therapy.

    PubMed

    Campbell, R Keith

    2012-04-01

    Despite its unsurpassed efficacy in the management of diabetes, insulin has been resisted and feared for its risk of side effects (ie, weight gain, hypoglycemia). Many patients and providers have perceived insulin as a last resort therapy given to patients with a poor prognosis, and some patients even as a form of punishment for poor self-management. Also, fear of needles is a constant concern. Fortunately, these challenges to insulin use may be overcome via patient education as well as new developments in insulin therapy. Insulin formulations have been developed that possess pharmacokinetic profiles better adapted to the physiologic needs of patients with type 2 diabetes mellitus (T2DM), including rapid- and long-acting insulin analogues, as well as premixed formulations. Appropriate use of these agents is associated with improved glycemic control, higher levels of adherence to treatment, and lower healthcare costs. A variety of pen delivery systems for insulin delivery are available that allow for easier, more discreet, and more accurately dosed insulin therapy. Patients generally prefer pen delivery systems, and they are associated with greater adherence and better glycemic control as compared with vial and syringe use. In addition to the ever-increasing variety of insulin formulations and delivery systems, educational initiatives are absolutely vital in order to overcome the limited knowledge about diabetes, self-management, and coping skills that can be seen in a large proportion of people with T2DM. Improved adherence to treatment, better outcomes, and reduced costs are contingent upon the appropriate use of, and full access to, appropriate treatment and patient education.

  8. Radioiodine Accumulation in a Giant Ovarian Cystadenofibroma Detected Incidentally by 131-I Whole Body Scans

    PubMed Central

    Mebarki, Mohammed; Menemani, Abdelghani; Medjahedi, Abdelkader; Boualou, Fouad; Slama, Abdelhak; Ouguirti, Sarah; Kherbouche, Fatima Zahra; Berber, Nécib

    2012-01-01

    Ovarian cystadenofibroma is a relatively rare tumor; it is usually asymptomatic and is found incidentally. We present the case of a 24-year-old female patient, who had undergone total thyroidectomy for thyroid papillary carcinoma, with an asymptomatic giant cystadenofibroma, incidentally discovered by diagnostic 131I-SPECT/CT WBSs. We summarize the clinical history, imaging data, and histopathological study on a rare case of radioiodine accumulation in cystadenofibroma, and we discuss the mechanism of uptake of radioiodine in this case. PMID:23119215

  9. Lenvatinib - A multikinase inhibitor for radioiodine-refractory differentiated thyroid cancer.

    PubMed

    Hewett, Yvonne; Ghimire, Subash; Farooqi, Bilal; Shah, Binay K

    2016-11-17

    Lenvatinib, an oral multikinase inhibitor, was approved by the US Food and Drug Administration in February 2015. In a pivotal phase III study of 392 patients with progressive radioiodine-refractory thyroid cancer, the overall response rate of patients receiving lenvatinib was 64.8%, with complete response in four patients. The median progression-free survival was 18.3 months in the lenvatinib arm versus 3.6 months in patients receiving placebo. Median overall survival was not reached in either arm. Lenvatinib is a promising new treatment for patients with radioiodine (iodine-131)-refractory differentiated thyroid cancer.

  10. Role of bismuth in improving Helicobacter pylori eradication with triple therapy.

    PubMed

    Dore, Maria Pina; Lu, Hong; Graham, David Y

    2016-05-01

    In most regions of the world, antimicrobial resistance has increased to the point where empirical standard triple therapy for Helicobacter pylorieradication is no longer recommended. The treatment outcome in a population is calculated as the sum of the treatment success in the subpopulation with susceptible infections plus treatment success in the subpopulation with resistant infections. The addition of bismuth (i.e., 14-day triple therapy plus bismuth) can improve cure rates despite a high prevalence of antimicrobial resistance. The major bismuth effect is to add an additional 30%-40% to the success with resistant infections. The overall result is therefore dependent on the prevalence of resistance and the treatment success in the subpopulation with resistant infections (eg, with proton-pump inhibitor-amoxicillin dual therapy). Here, we explore the contribution of each component and the mechanisms of how bismuth might enhance the effectiveness of triple therapy. We also discuss the limitations of this approach and provide suggestions how triple therapy plus bismuth might be further improved.

  11. Cancer Nanotheranostics: Improving Imaging and Therapy by Targeted Delivery across Biological Barriers

    PubMed Central

    Kievit, Forrest M.; Zhang, Miqin

    2012-01-01

    Cancer nanotheranostics aims to combine imaging and therapy of cancer through use of nanotechnology. The ability to engineer nanomaterials to interact with cancer cells at the molecular level can significantly improve the effectiveness and specificity of therapy to cancers that are currently difficult to treat. In particular, metastatic cancers, drug-resistant cancers, and cancer stem cells impose the greatest therapeutic challenge that requires targeted therapy to treat effectively. Targeted therapy can be achieved with appropriate designed drug delivery vehicles such as nanoparticles, adult stem cells, or T cells in immunotherapy. In this article, we first review the different types of materials commonly used to synthesize nanotheranostic particles and their use in imaging. We then discuss biological barriers that these nanoparticles encounter and must bypass to reach the target cancer cells, including the blood, liver, kidneys, spleen, and particularly the blood-brain barrier. We then review how nanotheranostics can be used to improve targeted delivery and treatment of cancer cells using nanoparticles, adult stem cells, and T cells in immunotherapy. Finally, we discuss development of nanoparticles to overcome current limitations in cancer therapy. PMID:21842473

  12. Biologic therapy improves psoriasis by decreasing the activity of monocytes and neutrophils.

    PubMed

    Yamanaka, Keiichi; Umezawa, Yoshinori; Yamagiwa, Akisa; Saeki, Hidehisa; Kondo, Makoto; Gabazza, Esteban C; Nakagawa, Hidemi; Mizutani, Hitoshi

    2014-08-01

    Therapy with monoclonal antibodies to tumor necrosis factor (TNF)-α and the interleukin (IL)-12/23 p40 subunit has significantly improved the clinical outcome of patients with psoriasis. These antibodies inhibit the effects of the target cytokines and thus the major concern during their use is the induction of excessive immunosuppression. Recent studies evaluating the long-term efficacy and safety of biologic therapy in psoriasis have shown no significant appearance of serious adverse effects including infections and malignancies. However, the immunological consequence and the mechanism by which the blockade of a single cytokine by biologics can successfully control the activity of psoriasis remain unclear. In the current study, we investigated the effect of biologic therapy on cytokine production of various lymphocytes and on the activity of monocytes and neutrophils in psoriatic patients. Neutrophils, monocytes and T cells were purified from heparinized peripheral venous blood by Ficoll density gradient centrifugation, and γ-interferon, TNF-α and IL-17 production from lymphocytes was measured by flow cytometer. The activation maker of neutrophils and the activated subsets of monocytes were also analyzed. Biologic therapy induced no significant changes in the cytokine production by lymphocytes from the skin and gut-homing T cells. However, neutrophil activity and the ratio of activated monocyte population increased in severely psoriatic patients were normalized in psoriatic patients receiving biologic therapy. The present study showed that biologic therapy ameliorates clinical symptoms and controls the immune response in patients with psoriasis.

  13. Improving Quality and Access to Radiation Therapy-An IAEA Perspective.

    PubMed

    Abdel-Wahab, May; Zubizarreta, Eduardo; Polo, Alfredo; Meghzifene, Ahmed

    2017-04-01

    The International Atomic Energy Agency (IAEA) has been involved in radiation therapy since soon after its creation in 1957. In response to the demands of Member States, the IAEA׳s activities relating to radiation therapy have focused on supporting low- and middle-income countries to set up radiation therapy facilities, expand the scope of treatments, or gradually transition to new technologies. In addition, the IAEA has been very active in providing internationally harmonized guidelines on clinical, dosimetry, medical physics, and safety aspects of radiation therapy. IAEA clinical research has provided evidence for treatment improvement as well as highly effective resource-sparing interventions. In the process, training of researchers occurs through this program. To provide this support, the IAEA works with its Member States and multiple partners worldwide through several mechanisms. In this article, we review the main activities conducted by the IAEA in support to radiation therapy. IAEA support has been crucial for achieving tangible results in many low- and middle-income countries. However, long-term sustainability of projects can present a challenge, especially when considering health budget constraints and the brain drain of skilled professionals. The need for support remains, with more than 90% of patients in low-income countries lacking access to radiotherapy. Thus, the IAEA is expected to continue its support and strengthen quality radiation therapy treatment of patients with cancer.

  14. Electrophoretic purification of radioiodinated follicle-stimulating hormone for radioligand receptor assay and radioimmunoassay

    SciTech Connect

    Schneyer, A.L.; Sluss, P.M.; Bosukonda, D.; Reichert, L.E. Jr.

    1986-10-01

    A method is described for electrophoretic purification of (/sup 125/I)human (h) FSH after radioiodination that improves radioligand binding to FSH membrane receptors. Lactoperoxidase-iodinated hFSH was separated from reaction products by electrophoresis on 7.5% polyacrylamide tube gels (PAGE). Material eluted from 3-mm gel slices was analyzed for incorporation of /sup 125/I and binding to antibody (RIA) or receptor (RRA), and by sodium dodecyl sulfate-PAGE for protein composition. Sodium dodecyl sulfate-PAGE analysis of individual PAGE fractions demonstrated that iodinated proteins, both higher and lower in apparent mol wt than intact FSH, were separated by PAGE, but not by gel filtration chromatography (Sephadex G-25). PAGE purification of radioligand resulted in significantly greater (compared to gel filtration) RRA sensitivity and specificity. Maximum binding of PAGE-purified (/sup 125/I)hFSH to excess calf tests membrane receptors was 45%, with a specific activity of approximately 26 microCi/micrograms, as determined by the method of self-displacement. Maximum binding to excess hFSH antisera (NIH anti-hFSH 4) was 80-85%. This allowed a useful final dilution of 1:120,000, thereby facilitating development of a sensitive and specific RIA with this antiserum. These data indicate that PAGE separation of intact (/sup 125/I)hFSH from other iodinated proteins results in improved radioligand binding, assay sensitivity, and assay specificity. In addition, PAGE-purified lactoperoxidase-iodinated hFSH is suitable for use in both RIA and RRA.

  15. Clinical utility of far-infrared therapy for improvement of vascular access blood flow and pain control in hemodialysis patients

    PubMed Central

    Choi, Soo Jeong; Cho, Eun Hee; Jo, Hye Min; Min, Changwook; Ji, Young Sok; Park, Moo Yong; Kim, Jin Kuk; Hwang, Seung Duk

    2015-01-01

    Background Maintenance of a well-functioning vascular access and minimal needling pain are important goals for achieving adequate dialysis and improving the quality of life in hemodialysis (HD) patients. Far-infrared (FIR) therapy may improve endothelial function and increase access blood flow (Qa) and patency in HD patients. The aim of this study was to evaluate effects of FIR therapy on Qa and patency, and needling pain in HD patients. Methods This prospective clinical trial enrolled 25 outpatients who maintained HD with arteriovenous fistula. The other 25 patients were matched as control with age, sex, and diabetes. FIR therapy was administered for 40 minutes during HD 3 times/wk and continued for 12 months. The Qa was measured by the ultrasound dilution method, whereas pain was measured by a numeric rating scale at baseline, then once per month. Results One patient was transferred to another facility, and 7 patients stopped FIR therapy because of an increased body temperature and discomfort. FIR therapy improved the needling pain score from 4 to 2 after 1 year. FIR therapy increased the Qa by 3 months and maintained this change until 1 year, whereas control patients showed the decrease in Qa. The 1-year unassisted patency with FIR therapy was not significantly different from control. Conclusion FIR therapy improved needling pain. Although FIR therapy improved Qa, the unassisted patency was not different compared with the control. A larger and multicenter study is needed to evaluate the effect of FIR therapy. PMID:27069856

  16. Manual Therapy and Exercise to Improve Outcomes in Patients With Muscle Tension Dysphonia: A Case Series

    PubMed Central

    Archer, Kristin R.

    2015-01-01

    Background and Purpose Muscle tension dysphonia (MTD), a common voice disorder that is not commonly referred for physical therapy intervention, is characterized by excessive muscle recruitment, resulting in incorrect vibratory patterns of vocal folds and an alteration in voice production. This case series was conducted to determine whether physical therapy including manual therapy, exercise, and stress management education would be beneficial to this population by reducing excess muscle tension. Case Description Nine patients with MTD completed a minimum of 9 sessions of the intervention. Patient-reported outcomes of pain, function, and quality of life were assessed at baseline and the conclusion of treatment. The outcome measures were the numeric rating scale (NRS), Patient-Specific Functional Scale (PSFS), and Voice Handicap Index (VHI). Cervical and jaw range of motion also were assessed at baseline and postintervention using standard goniometric measurements. Outcomes Eight of the patients had no pain after treatment. All 9 of the patients demonstrated an improvement in PSFS score, with 7 patients exceeding a clinically meaningful improvement at the conclusion of the intervention. Three of the patients also had a clinically meaningful change in VHI scores. All 9 of the patients demonstrated improvement in cervical flexion and lateral flexion and jaw opening, whereas 8 patients improved in cervical extension and rotation postintervention. Discussion The findings suggest that physical therapists can feasibly implement an intervention to improve outcomes in patients with MTD. However, a randomized clinical trial is needed to confirm the results of this case series and the efficacy of the intervention. A clinical implication is the expansion of physical therapy to include referrals from voice centers for the treatment of MTD. PMID:25256740

  17. Recommendations for improving adherence to type 2 diabetes mellitus therapy--focus on optimizing oral and non-insulin therapies.

    PubMed

    Nau, David P

    2012-04-01

    Adherence to therapy in patients with type 2 diabetes mellitus is contingent upon a number of variables, including variables specific to the patient, to the provider, and to the treatment. While treatment selection will involve consideration to maximize effectiveness and minimize side effects, the physician must also take into account the priorities and preferences of each individual patient. For some patients, the risk of weight gain may exert a significant influence on adherence, while for others the risk of hypoglycemia or the cost of medications may be more important factors. It is incumbent upon physicians to discuss these issues with patients and to develop a patient-centric treatment plan to achieve optimal adherence and therapeutic outcomes. The nature of the clinical setting can also influence the likelihood of patient adherence to treatment. A multidisciplinary team approach to diabetes management has been shown to improve outcomes and to have a neutral or beneficial effect on costs. The treatment plan itself plays an additional role in the likelihood of a patient adhering to treatment. Less complex treatment regimens with fewer pills are associated with higher rates of adherence, as are fixed-dose combinations for those patients requiring combination therapy. Frequency and timing of dosing are also important aspects of adherence, as once-daily dosing is associated with higher rates of adherence than twice-daily dosing for anti-hyperglycemic medications.

  18. Specific inhibition of the ABCG2 transporter could improve the efficacy of photodynamic therapy.

    PubMed

    Bebes, Attila; Nagy, Tünde; Bata-Csörgo, Zsuzsanna; Kemény, Lajos; Dobozy, Attila; Széll, Márta

    2011-11-03

    Photodynamic therapy is based on the selective accumulation of a photosensitizer in tumors, followed by destruction of the target tissue by a light source. Protoporphyrin IX, a well-known photosensitizer, was recently reported as an endogenous substrate for the multidrug transporter ABCG2. We investigated the role of ABCG2 protein in the porphyrin extrusion ability of keratinocytes, with regard to the impact of the specific inhibition of ABCG2 by a non-toxic fumitremorgin C analog, Ko-134, on photodynamic therapy efficacy. We studied the level of porphyrin accumulation in response to delta-aminolevulinic acid pretreatment in proliferating and highly differentiated HaCaT keratinocytes. An in vitro model of photodynamic therapy on HaCaT cells was established with a therapeutically approved narrow-bandwidth red-light source. The porphyrin extrusion ability of HaCaT cells proved to correlate with their ABCG2 expression which was higher in proliferating cells than in differentiated cells. Moreover, the specific inhibition of ABCG2 by Ko-134 enhanced the sensitivity of keratinocytes to photodynamic therapy in vitro. These results suggest that ABCG2 may serve as a target molecule via which to improve the photodynamic therapy of skin lesions: its inhibition by the non-toxic Ko-134 is a promising therapeutic modality.

  19. [Prognosis improvements in children with acute myelocytic leucemia after more intensive induction therapy (author's transl)].

    PubMed

    Scheer, U; Schellong, G; Riehm, H

    1979-03-01

    Between October 1974 and October 1978 23 children with acute myelocytic leucemia (AML) received intensive therapy in the Univ.-Kinderklinik Münster: 4 children were treated according to the ALGB-protocol consisting of 5-7 day courses of ARA-C-infusion and 3 DNR-injections. 19 patients received the West-Berlin-protocol: The first 7 the original ALL protocol, 11 the modified form of AML, which will be presented here as AML-therapy-study BFM 78. 4 of the 23 patients died with early acute cerebral bleeding. 2 patients were nonresponders. 17 children went into remission. One girl died in remission of septicemic aspergillosis. 4 children had a relapse. In November 1978 there were still 12 patients in continuous complete remission, 3 of them already without therapy. 13 of the 19 patients, who were treated with the West-Berlin-protocol went into remission. 1 had a relapse. At present there are 11 patients in continuous complete remission. The above results and those found in the literature could signify that the long term prognosis of children with AML will be improved. To coordinate efforts toward this goal a cooperative AML-therapy-study in the "Deutsche Arbeitsgemeinschaft für Leukämieforschung" (BFM-group) using the here presented therapy protocol was formed in November 1978.

  20. Headache improvement through TMD stabilization appliance and self-management therapies.

    PubMed

    Wright, Edward F; Clark, Elizabeth G; Paunovich, Eleonore D; Hart, Robert G

    2006-04-01

    The purpose of this study was to assess headache response of unselected neurology clinic chronic headache patients to TMD stabilization appliance and self-management therapies, and to identify features of patients whose headaches are more likely to improve from these therapies. Twenty chronic headache patients in a nontreatment control period were provided appliance and self-management therapies, evaluated five weeks after therapy, and those who chose to continue using their appliances were evaluated three months later. The mean pretreatment Headache Disability Inventory (HDI) score of 64.5 suggested the headaches were severe. After five weeks, the mean HDI score decreased by 17 percent (p<0.003), headache medication consumption dropped by 18 percent (p<0.0001), and headache symptoms decreased by 19 percent (p<0.002). Comparing the three months with pretreatment follow-up, the fourteen participants who chose to continue using their appliances had a mean HDI score decrease of 23 percent (p<0.003), headache medication consumption drop of 46 percent (p<0.001), and headache symptom decrease of 39 percent (p<0.001). There was no correlation between response and headache type (p=0.722). These results suggest appliance and self-management therapies can be beneficial for many severe headache patients, irrespective of the headache type (tension-type, migraine without aura, and migraine with aura).

  1. Survival benefit and phenotypic improvement by hamartin gene therapy in a tuberous sclerosis mouse brain model.

    PubMed

    Prabhakar, Shilpa; Zhang, Xuan; Goto, June; Han, Sangyeul; Lai, Charles; Bronson, Roderick; Sena-Esteves, Miguel; Ramesh, Vijaya; Stemmer-Rachamimov, Anat; Kwiatkowski, David J; Breakefield, Xandra O

    2015-10-01

    We examined the potential benefit of gene therapy in a mouse model of tuberous sclerosis complex (TSC) in which there is embryonic loss of Tsc1 (hamartin) in brain neurons. An adeno-associated virus (AAV) vector (serotype rh8) expressing a tagged form of hamartin was injected into the cerebral ventricles of newborn pups with the genotype Tsc1(cc) (homozygous for a conditional floxed Tsc1 allele) SynI-cre(+), in which Tsc1 is lost selectively in neurons starting at embryonic day 12. Vector-treated Tsc1(cc)SynIcre(+) mice showed a marked improvement in survival from a mean of 22 days in non-injected mice to 52 days in AAV hamartin vector-injected mice, with improved weight gain and motor behavior in the latter. Pathologic studies showed normalization of neuron size and a decrease in markers of mTOR activation in treated as compared to untreated mutant littermates. Hence, we show that gene replacement in the brain is an effective therapeutic approach in this mouse model of TSC1. Our strategy for gene therapy has the advantages that therapy can be achieved from a single application, as compared to repeated treatment with drugs, and that AAV vectors have been found to have minimal to no toxicity in clinical trials for other neurologic conditions. Although there are many additional issues to be addressed, our studies support gene therapy as a useful approach in TSC patients.

  2. Mindfulness-based cognitive therapy for depressed individuals improves suppression of irrelevant mental-sets.

    PubMed

    Greenberg, Jonathan; Shapero, Benjamin G; Mischoulon, David; Lazar, Sara W

    2017-04-01

    An impaired ability to suppress currently irrelevant mental-sets is a key cognitive deficit in depression. Mindfulness-based cognitive therapy (MBCT) was specifically designed to help depressed individuals avoid getting caught in such irrelevant mental-sets. In the current study, a group assigned to MBCT plus treatment-as-usual (n = 22) exhibited significantly lower depression scores and greater improvements in irrelevant mental-set suppression compared to a wait-list plus treatment-as-usual (n = 18) group. Improvements in mental-set-suppression were associated with improvements in depression scores. Results provide the first evidence that MBCT can improve suppression of irrelevant mental-sets and that such improvements are associated with depressive alleviation.

  3. Chinese hamster ovary cell lysosomes retain pinocytized horseradish peroxidase and in situ-radioiodinated proteins

    SciTech Connect

    Storrie, B.; Sachdeva, M.; Viers, V.S.

    1984-02-01

    We used Chinese hamster ovary cells, a cell line of fibroblastic origin, to investigate whether lysosomes are an exocytic compartment. To label lysosomal contents, Chinese hamster ovary cells were incubated with the solute marker horseradish peroxidase. After an 18-h uptake period, horseradish peroxidase was found in lysosomes by cell fractionation in Percoll gradients and by electron microscope cytochemistry. Over a 24-h period, lysosomal horseradish peroxidase was quantitatively retained by Chinese hamster ovary cells and inactivated with a t 1/2 of 6 to 8 h. Lysosomes were radioiodinated in situ by soluble lactoperoxidase internalized over an 18-h uptake period. About 70% of the radioiodine incorporation was pelleted at 100,000 X g under conditions in which greater than 80% of the lysosomal marker enzyme beta-hexosaminidase was released into the supernatant. By one-dimensional electrophoresis, about 18 protein species were present in the lysosomal membrane fraction, with radioiodine incorporation being most pronounced into species of 70,000 to 75,000 daltons. After a 30-min or 2-h chase at 37 degrees C, radioiodine that was incorporated into lysosomal membranes and contents was retained in lysosomes. These observations indicate that lysosomes labeled by fluid-phase pinocytosis are a terminal component of endocytic pathways in fibroblasts.

  4. Tinea corporis overlying the thyroid gland after radioiodine (131I) treatment of Graves' disease

    SciTech Connect

    Moreno, A.J.; Hartshorne, M.F.; Yedinak, M.A.; Crooks, L.A.; Fox, B.J.

    1986-04-01

    A case of tinea corporis involving the skin overlying the thyroid gland is described in a 36-year-old man who had received radioiodine treatment for Graves' disease. The dermatophytosis mimicked a delayed roentgen erythema. Radiation to the dermis may have locally altered the cell-mediated immunity and predisposed this patient to the dermatophytosis.

  5. Mercuric iodate precipitation from radioiodine-containing off-gas scrubber solution

    DOEpatents

    Partridge, Jerry A.; Bosuego, Gail P.

    1982-01-01

    Mercuric nitrate-nitric acid scrub solutions containing radioiodine may be reduced in volume without excessive loss of volatile iodine. The use of concentrated nitric acid during an evaporation process oxidizes the mercury-iodide complex to a less volatile mercuric iodate precipitate.

  6. Facile-radioiododemetallation reactions for the convenient preparation of radioiodinated compounds

    SciTech Connect

    Srivastava, P.C.; Knapp, F.F. Jr.; Kabalka, G.W.; Kunda, S.A.

    1985-01-01

    Several new methods for the preparation of vinyl iodides via mercuration and thallation reactions of vinylboronic acids have been explored. Chloramine-T oxidation of alkylvinylmercury iodides or iodide treatment of alkylvinylthallium trifluoroacetate substrates, prepared from the corresponding alkylvinylboronic acid and thallic trifluoroacetate, yields the corresponding alkylvinyl iodides. These methods are also efficient for the synthesis of the corresponding radioiodinated compounds. 21 references.

  7. A review of countermeasures to reduce radioiodine in milk of dairy animals

    SciTech Connect

    Howard, B.J.; Voigt, G.; Segal, M.G.

    1996-11-01

    The most effective countermeasure for radioiodine contamination of milk is to provide dairy animals with uncontaminated feed, with the added advantage that it will be effective for other radionuclides in the fallout. Another effective response is to process the milk into storable dairy products for an appropriate length of time to allow for physical decay. The use of additives given to ruminants to reduce radioiodine in milk is an alternative countermeasure which could be effective. Stable iodine administration is a practically feasible option which has the potential to reduce radioiodine levels in milk by at most a factor of three. Stable iodine supplementation should be at sufficiently high rates to be effective (and at least 1 g d{sup {minus}1} for dairy cows), particularly for ruminants already receiving high amounts of iodine in the diet. Currently available data are inadequate to recommend a suitable stable iodine administration rate for different species of ruminants. Other compounds, such as perchlorate and thiocyanate, also reduce the transfer to radioiodine to milk (and thyroid). Some of these compounds seem to be potentially equally as effective as stable iodine. However, currently there is inadequate information on their effectiveness and possible toxicity to both ruminants and humans for these compounds to be considered as suitable countermeasure additives. 85 refs., 2 figs., 3 tabs.

  8. Estrogen therapy increases BDNF expression and improves post-stroke depression in ovariectomy-treated rats

    PubMed Central

    Su, Qiaoer; Cheng, Yifan; Jin, Kunlin; Cheng, Jianhua; Lin, Yuanshao; Lin, Zhenzhen; Wang, Liuqing; Shao, Bei

    2016-01-01

    The present study investigated the effect of exogenous estrogen on post-stroke depression. Rats were exposed to chronic mild stress following middle cerebral artery occlusion. The occurrence of post-stroke depression was evaluated according to the changes in preference for sucrose and performance in a forced swimming test. Estrogen therapy significantly improved these neurological symptoms, indicating that estrogen is effective in treating post-stroke depression. Increased brain-derived neurotrophic factor (BDNF) expression was reported in the hippocampus of rats that had been treated with estrogen for two weeks, suggesting that BDNF expression may be an important contributor to the improvement of post-stroke depression that is observed following estrogen therapy. PMID:27602095

  9. Heavy Charged Particle Radiobiology: Using Enhanced Biological Effectiveness and Improved Beam Focusing to Advance Cancer Therapy

    PubMed Central

    Allen, Christopher; Borak, Thomas B.; Tsujii, Hirohiko; Nickoloff, Jac A.

    2011-01-01

    Ionizing radiation causes many types of DNA damage, including base damage and single- and double-strand breaks. Photons, including X-rays and γ-rays, are the most widely used type of ionizing radiation in radiobiology experiments, and in radiation cancer therapy. Charged particles, including protons and carbon ions, are seeing increased use as an alternative therapeutic modality. Although the facilities needed to produce high energy charged particle beams are more costly than photon facilities, particle therapy has shown improved cancer survival rates, reflecting more highly focused dose distributions and more severe DNA damage to tumor cells. Despite early successes of charged particle radiotherapy, there is room for further improvement, and much remains to be learned about normal and cancer cell responses to charged particle radiation. PMID:21376738

  10. Cognitive enhancement therapy improves emotional intelligence in early course schizophrenia: preliminary effects.

    PubMed

    Eack, Shaun M; Hogarty, Gerard E; Greenwald, Deborah P; Hogarty, Susan S; Keshavan, Matcheri S

    2007-01-01

    This research examined the preliminary effects of Cognitive Enhancement Therapy (CET) on social cognition in early course schizophrenia, using an objective, performance-based measure of emotional intelligence. Individuals in the early course of schizophrenia were randomly assigned to either CET (n=18) or Enriched Supportive Therapy (n=20), and assessed at baseline and after 1 year of treatment with the Mayer-Salovey-Caruso Emotional Intelligence Test. A series of analyses of covariance showed highly significant (p=.005) and large (Cohen's d=.96) effects favoring CET for improving emotional intelligence, with the most pronounced improvements occurring in patients' ability to understand and manage their own and others' emotions. These findings lend preliminary support to the previously documented benefits of CET on social cognition in schizophrenia, and suggest that such benefits can be extended to patients in the early course of the illness.

  11. Creative arts therapy improves quality of life for pediatric brain tumor patients receiving outpatient chemotherapy.

    PubMed

    Madden, Jennifer R; Mowry, Patricia; Gao, Dexiang; Cullen, Patsy McGuire; Foreman, Nicholas K

    2010-01-01

    This mixed methods pilot study evaluated the effects of the creative arts therapy (CAT) on the quality of life (QOL) of children receiving chemotherapy. A 2-group, repeated measures randomized design compared CAT with a volunteer's attention (n = 16). Statistical analysis of the randomized controlled phase of the study suggested an improvement in the following areas after the CAT: parent report of child's hurt (P = .03) and parent report of child's nausea (P = .0061). A nonrandomized phase, using a different instrument showed improved mood with statistical significance on the Faces Scale (P < .01), and patients were more excited (P < .05), happier (P < .02), and less nervous (P < .02). Provider focus groups revealed positive experiences. Case studies are included to exemplify the therapeutic process. With heightened interest in complementary therapy for children with cancer, future research with a larger sample size is needed to document the impact of incorporating creative arts into the healing process.

  12. Heavy charged particle radiobiology: using enhanced biological effectiveness and improved beam focusing to advance cancer therapy.

    PubMed

    Allen, Christopher; Borak, Thomas B; Tsujii, Hirohiko; Nickoloff, Jac A

    2011-06-03

    Ionizing radiation causes many types of DNA damage, including base damage and single- and double-strand breaks. Photons, including X-rays and γ-rays, are the most widely used type of ionizing radiation in radiobiology experiments, and in radiation cancer therapy. Charged particles, including protons and carbon ions, are seeing increased use as an alternative therapeutic modality. Although the facilities needed to produce high energy charged particle beams are more costly than photon facilities, particle therapy has shown improved cancer survival rates, reflecting more highly focused dose distributions and more severe DNA damage to tumor cells. Despite early successes of charged particle radiotherapy, there is room for further improvement, and much remains to be learned about normal and cancer cell responses to charged particle radiation.

  13. Interventions for improving adherence to iron chelation therapy in people with sickle cell disease or thalassaemia

    PubMed Central

    Fortin, Patricia M; Madgwick, Karen V; Trivella, Marialena; Hopewell, Sally; Doree, Carolyn; Estcourt, Lise J

    2016-01-01

    This is the protocol for a review and there is no abstract. The objectives are as follows: To identify and assess the effectiveness of interventions to improve adherence to iron chelation therapy compared to standard care in people with SCD or thalassaemia including: identifying and assessing the effectiveness of different types of interventions (psychological and psychosocial, educational, medication interventions, or multi-component interventions);identifying and assessing the effectiveness of interventions specific to different age groups (children, adolescents, adults). PMID:27713668

  14. Enzyme replacement therapy for murine mucopolysaccharidosis type VII leads to improvements in behavior and auditory function.

    PubMed Central

    O'Connor, L H; Erway, L C; Vogler, C A; Sly, W S; Nicholes, A; Grubb, J; Holmberg, S W; Levy, B; Sands, M S

    1998-01-01

    Mucopolysaccharidosis type VII (MPS VII; Sly syndrome) is one of a group of lysosomal storage diseases that share many clinical features, including mental retardation and hearing loss. Lysosomal storage in neurons of the brain and the associated behavioral abnormalities characteristic of a murine model of MPS VII have not been shown to be corrected by either bone marrow transplantation or gene therapy. However, intravenous injections of recombinant beta-glucuronidase initiated at birth reduce the pathological evidence of disease in MPS VII mice. In this study we present evidence that enzyme replacement initiated at birth improved the behavioral performance and reduced hearing loss in MPS VII mice. Enzyme-treated MPS VII mice performed similarly to normal mice and significantly better than mock- treated MPS VII mice in every phase of the Morris Water Maze test. In addition, the auditory function of treated MPS VII mice was dramatically improved, and was indistinguishable from normal mice. These data indicate that some of the learning, memory, and hearing deficits can be prevented in MPS VII mice if enzyme replacement therapy is initiated early in life. These data also provide functional correlates to the biochemical and histopathological improvements observed after enzyme replacement therapy. PMID:9525982

  15. Assessment of anti-atherogenic drugs in vivo and reconstitution of lipoproteins using radioiodinated cholesteryl iopanoate

    SciTech Connect

    DeGalan, M.R.

    1987-01-01

    A nonhydrolyzable radioiodinated cholesteryl ester, 125I-cholesteryl iopanoate (125I-Cl), was found to accumulate in high concentrations in atherosclerotic aortas of cholesterol-fed rabbits after intravenous administration. Aortas from normal chow-fed rabbits did not exhibit significant 125I-Cl accumulation. When cholesterol-fed rabbits were intravenously administered Tween-solubilized 125I-Cl and simultaneously treated with either of two anti-atherogenic compounds, estradiol 17..beta..-cypionate or colestipol, the extent of aortic atherosclerosis was found to dramatically decrease. Measurement of aortic radioactivity was found to strongly correlate with the severity of atherosclerosis. Although the specificity of 125I-Cl for atheromatous lesions was very good, gamma-camera scintigraphy of the abdomens of these rabbits 6 days after cessation of 125I-Cl administration was not able to consistently predict the severity of atherosclerosis. Tissue distribution studies suggested that high blood and spinal column bone marrow radioactivity produced aorta:nontarget radioactivity ratios unfavorable with respect to imaging. To improve this ratio so as to permit noninvasive imaging, attempts were made to incorporate 125I-Cl into serum lipoproteins. Labelling of either rabbit LDL by in vivo incorporation or human LDL by transfer of 125I-Cl from liposomes using cholesteryl ester transfer protein resulted in lipoproteins with low specific activity. Higher specific activity was achieved by reconstituting delipidated human LDL with a mixture of 125I-Cl and unlabeled cholesteryl oleate. These particles were taken up in high amounts by monolayers of human fibroblasts but not by fibroblasts deficient in LDL receptors or by normal fibroblasts during competition with unlabeled native LDL.

  16. Effects of radioiodine administration on serum concentrations of matrix metalloproteinases, adiponectin and thrombospondin-1

    PubMed Central

    2013-01-01

    Background In order to assess safety of radioactive iodine administration in the treatment of thyrotoxicosis, we measured concentrations of matrix metalloproteinase-2 (MMP-2), its main inhibitor – TIMP-2 (tissue inhibitor of MMP-2), matrix metalloproteinase-9 (MMP-9), its main inhibitor – TIMP-1, adiponectin, as well as pro-inflammatory and procancerogenic thrombospondin-1 (TSP-1). Design and patients The study involved 23 patients treated with radioiodine for thyrotoxicosis. Serum concentrations of TSH, free T4, free T3, MMP-2, MMP-9, TIMP-1, TIMP-2, total adiponectin and TSP-1 were measured by immunoassays just before radioiodine administration (visit 1), and subsequently, after 7 days (visit 2), 3 months (visit 3), 6 to 8 months (visit 4) and 15–18 months after radioiodine administration (visit 5). Results There were no acute changes in serum concentrations of MMP-2, MMP-9, TIMP-1, TIMP-2, adiponectin and TSP-1 (visit 1 vs. 2). Subsequently, there was an increase in MMP-2 (from 393±106 ng/ml to 774±424 ng/ml), TIMP-1 (from 177±76 ng/ml to 296±118 ng/ml), and adiponectin (from 16442±9490 ng/ml to 23518±9840 ng/ml), visit 1 to 5, respectively (p < 0.01). Further analysis revealed no significant change in MMP-2/TIMP-2 ratio, but there was a significant decrease in MMP-9/TIMP-1 ratio (p < 0.05), suggestive of possible decrease in free MMP-9 concentrations. Conclusions Our data reveal a significant and sustained increase in serum adiponectin, as well as possible decrease of free MMP-9 concentration after radioiodine administration. In contrast, there was no significant change of TSP-1. This might indicate overall safety of radioiodine treatment of thyrotoxicosis in terms of the risks of subsequent cardiovascular and neoplastic disease. PMID:23919647

  17. Intensity-modulated arc therapy to improve radiation dose delivery in the treatment of abdominal neuroblastoma.

    PubMed

    Gains, Jennifer E; Stacey, Christopher; Rosenberg, Ivan; Mandeville, Henry C; Chang, Yen-Ch'ing; D'Souza, Derek; Moroz, Veronica; Wheatley, Keith; Gaze, Mark N

    2013-03-01

    The standard European radiotherapy technique for children with neuroblastoma is a conventional parallel opposed pair. This frequently results in compromise on planning target volume coverage to stay within normal tissue tolerances. This study investigates the use of an intensity-modulated arc therapy (IMAT) technique to improve dose distribution and allow better protocol compliance. Among 20 previously treated patients, ten had received the full prescribed dose with conventional planning (protocol compliant) and ten had a compromise on planning target volume coverage (protocol noncompliant). All patients were replanned with IMAT. Dosimetric parameters of the conventional radiotherapy and IMAT were compared. The dose received by 98% of the planning target volume, homogeneity and conformity indices were all improved with IMAT (p < 0.001). IMAT would have enabled delivery of the full protocol dose in eight out of ten protocol-noncompliant patients. IMAT may improve outcomes through improved protocol compliance and better dose distributions.

  18. Improved outcomes associated with advances in therapy for invasive fungal infections in immunocompromised hosts.

    PubMed

    Metcalf, S C; Dockrell, D H

    2007-10-01

    Invasive fungal infections cause substantial morbidity and mortality in immunocompromised hosts. The response rate to therapy, in particular for invasive aspergillosis and invasive mould infections, has been poor. Recently a number of techniques to facilitate early diagnosis of these infections, in parallel with the development of a number of antifungals with increased potency and lower toxicity, have raised optimism that outcomes for invasive fungal infection can be improved upon. The availability of lipid formulations of amphotericin B, azoles with extended spectrum against filamentous fungi and the development of a new class of antifungal agents, the echinocandins, presents the clinician with a range of therapeutic choices. Recent clinical trials have provided important insights into how these agents should be used. In particular, voriconazole has demonstrated superior efficacy to amphotericin B in the management of invasive aspergillosis, posaconazole has been shown to have significant efficacy in the prophylaxis of invasive fungal infection in high-risk individuals and a role in salvage therapy of invasive aspergillosis, caspofungin has demonstrated efficacy in salvage therapy of invasive aspergillosis, and each of the echinocandins show activity without significant toxicity in invasive candidiasis. Nevertheless, many therapeutic areas of uncertainty remain, including the role of combination therapy, and will provide the focus for future studies.

  19. Electric stimulation and decimeter wave therapy improve the recovery of injured sciatic nerves

    PubMed Central

    Zhao, Feng; He, Wei; Zhang, Yingze; Tian, Dehu; Zhao, Hongfang; Yu, Kunlun; Bai, Jiangbo

    2013-01-01

    Drug treatment, electric stimulation and decimeter wave therapy have been shown to promote the repair and regeneration of the peripheral nerves at the injured site. This study prepared a Mackinnon's model of rat sciatic nerve compression. Electric stimulation was given immediately after neurolysis, and decimeter wave radiation was performed at 1 and 12 weeks post-operation. Histological observation revealed that intraoperative electric stimulation and decimeter wave therapy could improve the local blood circulation of repaired sites, alleviate hypoxia of compressed nerves, and lessen adhesion of compressed nerves, thereby decreasing the formation of new entrapments and enhancing compressed nerve regeneration through an improved microenvironment for regeneration. Immunohistochemical staining results revealed that intraoperative electric stimulation and decimeter wave could promote the expression of S-100 protein. Motor nerve conduction velocity and amplitude, the number and diameter of myelinated nerve fibers, and sciatic functional index were significantly increased in the treated rats. These results verified that intraoperative electric stimulation and decimeter wave therapy contributed to the regeneration and the recovery of the functions in the compressed nerves. PMID:25206506

  20. The peer review system (PRS) for quality assurance and treatment improvement in radiation therapy

    NASA Astrophysics Data System (ADS)

    Le, Anh H. T.; Kapoor, Rishabh; Palta, Jatinder R.

    2012-02-01

    Peer reviews are needed across all disciplines of medicine to address complex medical challenges in disease care, medical safety, insurance coverage handling, and public safety. Radiation therapy utilizes technologically advanced imaging for treatment planning, often with excellent efficacy. Since planning data requirements are substantial, patients are at risk for repeat diagnostic procedures or suboptimal therapeutic intervention due to a lack of knowledge regarding previous treatments. The Peer Review System (PRS) will make this critical radiation therapy information readily available on demand via Web technology. The PRS system has been developed with current Web technology, .NET framework, and in-house DICOM library. With the advantages of Web server-client architecture, including IIS web server, SOAP Web Services and Silverlight for the client side, the patient data can be visualized through web browser and distributed across multiple locations by the local area network and Internet. This PRS will significantly improve the quality, safety, and accessibility, of treatment plans in cancer therapy. Furthermore, the secure Web-based PRS with DICOM-RT compliance will provide flexible utilities for organization, sorting, and retrieval of imaging studies and treatment plans to optimize the patient treatment and ultimately improve patient safety and treatment quality.

  1. Improved growth and clinical, nutritional, and respiratory changes in response to nutritional therapy in cystic fibrosis.

    PubMed

    Shepherd, R; Cooksley, W G; Cooke, W D

    1980-09-01

    To investigate the role of nutritional factors in growth and in the clinical, nurtitional, and respiratory status in cystic fibrosis, we studied 12 problem CF patients from six months before to six months after a period of supplemental parenteral nutrition. During the initial six months' observation period on appropriate conventional therapy, the patients (aged 0.5 to 11 years) had inadequate growth and weight gain, a total of 21 active pulmonary infections, and, despite dietary supplements, inadequate ad libitum nutrient intakes. After nutritional therapy, providing a balanced consistent hypercaloric intake for 21 days, catch-up weight gain occurred by one month and continued at six months; catch-up in linear growth was observed by three months and continued at six months. In addition, significantly fewer pulmonary infections were observed in the six months' post-therapy (n = 3), sustained and significant improvements were noted in clinical score and plumonary function, and there was a marked improvement in well-being and ad libitum nutrient intake. We conclude that adequate nutritional support can favorably affect growth, clinical status, and the course of chronic pulmonary disease in problem cases of CF.

  2. Interactive rehabilitation system for improvement of balance therapies in people with cerebral palsy.

    PubMed

    Jaume-i-Capó, Antoni; Martínez-Bueso, Pau; Moyà-Alcover, Biel; Varona, Javier

    2014-03-01

    The present study covers a new experimental system, designed to improve the balance and postural control of adults with cerebral palsy. This system is based on a serious game for balance rehabilitation therapy, designed using the prototype development paradigm and features for rehabilitation with serious games: feedback, adaptability, motivational elements, and monitoring. In addition, the employed interaction technology is based on computer vision because motor rehabilitation consists of body movements that can be recorded, and because vision capture technology is noninvasive and can be used for clients who have difficulties in holding physical devices. Previous research has indicated that serious games help to motivate clients in therapy sessions; however, there remains a paucity of clinical evidence involving functionality. We rigorously evaluated the effects of physiotherapy treatment on balance and gait function of adult subjects with cerebral palsy undergoing our experimental system. A 24-week physiotherapy intervention program was conducted with nine adults from a cerebral palsy center who exercised weekly in 20-min sessions. Findings demonstrated a significant increase in balance and gait function scores resulting in indicators of greater independence for our participating adults. Scores improved from 16 to 21 points in a scale of 28, according to the Tinetti Scale for risk of falls, moving from high fall risk to moderate fall risk. Our promising results indicate that our experimental system is feasible for balance rehabilitation therapy.

  3. Successful Phenotype Improvement following Gene Therapy for Severe Hemophilia A in Privately Owned Dogs.

    PubMed

    Callan, Mary Beth; Haskins, Mark E; Wang, Ping; Zhou, Shangzhen; High, Katherine A; Arruda, Valder R

    2016-01-01

    Severe hemophilia A (HA) is an inherited bleeding disorder characterized by <1% of residual factor VIII (FVIII) clotting activity. The disease affects several mammals including dogs, and, like humans, is associated with high morbidity and mortality. In gene therapy using adeno-associated viral (AAV) vectors, the canine model has been one of the best predictors of the therapeutic dose tested in clinical trials for hemophilia B (factor IX deficiency) and other genetic diseases, such as congenital blindness. Here we report our experience with liver gene therapy with AAV-FVIII in two outbred, privately owned dogs with severe HA that resulted in sustained expression of 1-2% of normal FVIII levels and prevented 90% of expected bleeding episodes. A Thr62Met mutation in the F8 gene was identified in one dog. These data recapitulate the improvement of the disease phenotype in research animals, and in humans, with AAV liver gene therapy for hemophilia B. Our experience is a novel example of the benefits of a relevant preclinical canine model to facilitate both translational studies in humans and improved welfare of privately owned dogs.

  4. Negative symptom improvement during cognitive rehabilitation: results from a 2-year trial of Cognitive Enhancement Therapy.

    PubMed

    Eack, Shaun M; Mesholam-Gately, Raquelle I; Greenwald, Deborah P; Hogarty, Susan S; Keshavan, Matcheri S

    2013-08-30

    Cognitive rehabilitation has shown beneficial effects on cognition in patients with schizophrenia, which may also help to improve negative symptoms due to overlapping pathophysiology between these two domains. To better understand the possible relationship between these areas, we conducted an exploratory analysis of the effects of Cognitive Enhancement Therapy (CET) on negative symptoms. Early course schizophrenia outpatients (n=58) were randomized to 2 years of CET or an Enriched Supportive Therapy (EST) control condition. Results revealed significant and medium-sized (d=0.61) differential improvements favoring CET in overall negative symptoms, particularly social withdrawal, affective flattening, and motor retardation. Neurocognitive improvement was associated with reduced negative symptoms in CET, but not EST patients. No relationships were observed between improvements in emotion processing aspects of social cognition, as measured by the Mayer-Salovey-Caruso Emotional Intelligence Test, and negative symptoms. CET represents an effective cognitive rehabilitation intervention for schizophrenia that may also have benefits to negative symptoms. Future studies specifically designed to examine negative symptoms during the course of cognitive rehabilitation are needed.

  5. A cloud-based mobile system to improve respiratory therapy services at home.

    PubMed

    Risso, Nicolas A; Neyem, Andrés; Benedetto, Jose I; Carrillo, Marie J; Farías, Angélica; Gajardo, Macarena J; Loyola, Oscar

    2016-10-01

    Chronic respiratory diseases are one of the most prevalent health problems in the world. Treatment for these kind of afflictions often take place at home, where the continuous care of a medical specialist is frequently beyond the economical means of the patient, therefore having to rely on informal caregivers (family, friends, etc.). Unfortunately, these treatments require a deep involvement on their part, which results in a heavy burden on the caregivers' routine and usually end up deteriorating their quality of life. In recent years, mHealth and eHealth applications have gained a wide interest in academia due to new capabilities enabled by the latest advancements in mobile technologies and wireless communication infrastructure. These innovations have resulted in several applications that have successfully managed to improve automatic patient monitoring and treatment and to bridge the distance between patients, caregivers and medical specialists. We therefore seek to move this trend forward by now pushing these capabilities into the field of respiratory therapies in order to assist patients with chronic respiratory diseases with their treatment, and to improve both their own and their caregivers' quality of life. This paper presents a cloud-based mobile system to support and improve homecare for respiratory diseases. The platform described uses vital signs monitoring as a way of sharing data between hospitals, caregivers and patients. Using an iterative research approach and the user's direct feedback, we show how mobile technologies can improve a respiratory therapy and a family's quality of life.

  6. Adjunctive Phosphodiesterase-4 Inhibitor Therapy Improves Antibiotic Response to Pulmonary Tuberculosis in a Rabbit Model

    PubMed Central

    Subbian, Selvakumar; Tsenova, Liana; Holloway, Jennifer; Peixoto, Blas; O'Brien, Paul; Dartois, Véronique; Khetani, Vikram; Zeldis, Jerome B.; Kaplan, Gilla

    2016-01-01

    Objectives Adjunctive host-directed therapy is emerging as a new potential approach to improve the outcome of conventional antimicrobial treatment for tuberculosis (TB). We tested the ability of a phosphodiesterase-4 inhibitor (PDE4i) CC-11050, co-administered with the first-line anti-TB drug isoniazid (INH), to accelerate bacillary killing and reduce chronic inflammation in the lungs of rabbits with experimental Mycobacterium tuberculosis (Mtb) infection. Methods A rabbit model of pulmonary TB that recapitulates the pathologic manifestations seen in humans was used. Rabbits were infected with virulent Mtb by aerosol exposure and treated for eight weeks with INH with or without CC-11050, starting at four weeks post infection. The effect of CC-11050 treatment on disease severity, pathology, bacillary load, T cell proliferation and global lung transcriptome profiles were analyzed. Results Significant improvement in bacillary clearance and reduced lung pathology and fibrosis were noted in the rabbits treated for eight weeks with INH + CC-11050, compared to those treated with INH or CC-11050 only. In addition, expression of host genes associated with tissue remodeling, tumor necrosis factor alpha (TNF-α) regulation, macrophage activation and lung inflammation networks was dampened in CC-11050-treated, compared to the untreated rabbits. Conclusions Adjunctive CC-11050 therapy significantly improves the response of rabbits with experimental pulmonary TB to INH treatment. We propose that CC-11050 may be a promising candidate for host directed therapy of patients with pulmonary TB, reducing the duration and improving clinical outcome of antibiotic treatment. PMID:26981575

  7. Does physical therapy and rehabilitation improve outcomes for diabetic foot ulcers?

    PubMed Central

    Turan, Yasemin; Ertugrul, Bulent M; Lipsky, Benjamin A; Bayraktar, Kevser

    2015-01-01

    One of the most common and serious complications of diabetes mellitus is ulceration of the foot. Among persons with diabetes, 12%-25% will present to a healthcare institution for a foot disorder during their lifespan. Despite currently available medical and surgical treatments, these are still the most common diabetes-related cause of hospitalization and of lower extremity amputations. Thus, many adjunctive and complementary treatments have been developed in an attempt to improve outcomes. We herein review the available literature on the effectiveness of several treatments, including superficial and deep heaters, electro-therapy procedures, prophylactic methods, exercise and shoe modifications, on diabetic foot wounds. Overall, although physical therapy modalities seem to be useful in the treatment of diabetic foot wounds, further randomized clinical studies are required. PMID:25992328

  8. School-based telerehabilitation in occupational therapy: using telerehabilitation technologies to promote improvements in student performance.

    PubMed

    Criss, Melanie Joy

    2013-01-01

    This article discusses the use of telerehabilitation technologies in occupational therapy for school-based practice. Telerehabilitation, for the purpose of this program, included the implementation of occupational therapy services via two-way interactive videoconferencing technology. The subjects included in this pilot program were children, ages 6 to 11 years, who attended an online charter school and had difficulties in the areas of fine motor and/or visual motor skills which impacted success with handwriting. Each participant completed a virtual evaluation and six 30-minute intervention sessions. The Print Tool™ Assessment was used to determine progress pre- and post-program. A learning coach/student satisfaction survey was given at the end of the program to determine participant satisfaction. Outcomes revealed improvements in handwriting performance for most students who participated in the program and high satisfaction rates reported by all participants.

  9. Improvement of a p(65)+Be neutron beam for therapy at Cyclone, Louvain-la-Neuve.

    PubMed

    Vynckier, S; Pihet, P; Flémal, J M; Meulders, J P; Wambersie, A

    1983-06-01

    The variable energy cyclotron of the Catholic University of Louvain is used to produce intense neutron beams for neutron therapy purposes. As a first step, neutrons were produced by bombarding a Be target with 50 MeV deuterons; at present they are produced by 65 MeV protons. This paper describes the improvements to the target system. A new (17 mm) Be target together with the old (10 mm) Be target are inserted in a movable support which allows the production of neutrons either by 65 MeV protons or by 50 MeV deuterons. Both targets can be removed for proton beam therapy. The dosimetric characteristics of the p(65)+Be and d(50)+Be neutron beams are compared: dose rate, gamma-contribution, depth dose and room activation.

  10. Improving Therapy of Chronic Lymphocytic Leukemia (CLL) with Chimeric Antigen Receptor (CAR) T Cells

    PubMed Central

    Fraietta, Joseph A.; Schwab, Robert D.; Maus, Marcela V.

    2016-01-01

    Adoptive cell immunotherapy for the treatment of chronic lymphocytic leukemia (CLL) has heralded a new era of synthetic biology. The infusion of genetically-engineered, autologous chimeric antigen receptor (CAR) T cells directed against CD19 expressed by normal and malignant B cells represents a novel approach to cancer therapy. The results of recent clinical trials of CAR T cells in relapsed and refractory CLL have demonstrated long-term disease-free remissions, underscoring the power of harnessing and re-directing the immune system against cancer. This review will briefly summarize T cell therapies in development for CLL disease. We discuss the role of T cell function and phenotype, T cell culture optimization, CAR design, and approaches to potentiate the survival and anti-tumor effects of infused lymphocytes. Future efforts will focus on improving the efficacy of CAR T cells for the treatment of CLL and incorporating adoptive cell immunotherapy into standard medical management of CLL. PMID:27040708

  11. Case report of meningiomatosis with aspiration of a dental bridge improved by comprehensive rehabilitation therapy

    PubMed Central

    Suh, Min Ji; Han, Eun Young; Kim, Bo Ryun; Lee, Jong Hoo

    2016-01-01

    [Purpose] The aim of this study was to ascertain the effect of comprehensive rehabilitation therapy on a quadriplegic patient with meningiomatosis and severe dysphagia. [Subject and Methods] Meningiomatosis is defined as multiple meningiomas involved in several intracranial regions, which occurs more frequently in elderly patients. The prognosis of meningiomatosis is mostly reported as benign, but the prognosis for some malignant cases can be poor. Furthermore, dysphagia in elderly patients with brain lesions may lead to foreign body aspiration, which can be fatal. The removable type of dental prosthesis is a common cause of aspiration, but aspiration is rare with the fixed type. [Results] This report presents a rare case of bronchial aspiration involving a fixed dental prosthesis in an elderly meningiomatosis patient that was improved following comprehensive rehabilitation therapy. [Conclusion] Thorough evaluation and individualized assessment of rehabilitation goals is recommended for the care of severe comorbid elderly patients. PMID:28174477

  12. Patient-Derived Xenograft Models to Improve Targeted Therapy in Epithelial Ovarian Cancer Treatment

    PubMed Central

    Scott, Clare L.; Becker, Marc A.; Haluska, Paul; Samimi, Goli

    2013-01-01

    Despite increasing evidence that precision therapy targeted to the molecular drivers of a cancer has the potential to improve clinical outcomes, high-grade epithelial ovarian cancer (OC) patients are currently treated without consideration of molecular phenotype, and predictive biomarkers that could better inform treatment remain unknown. Delivery of precision therapy requires improved integration of laboratory-based models and cutting-edge clinical research, with pre-clinical models predicting patient subsets that will benefit from a particular targeted therapeutic. Patient-derived xenografts (PDXs) are renewable tumor models engrafted in mice, generated from fresh human tumors without prior in vitro exposure. PDX models allow an invaluable assessment of tumor evolution and adaptive response to therapy. PDX models have been applied to pre-clinical drug testing and biomarker identification in a number of cancers including ovarian, pancreatic, breast, and prostate cancers. These models have been shown to be biologically stable and accurately reflect the patient tumor with regards to histopathology, gene expression, genetic mutations, and therapeutic response. However, pre-clinical analyses of molecularly annotated PDX models derived from high-grade serous ovarian cancer (HG-SOC) remain limited. In vivo response to conventional and/or targeted therapeutics has only been described for very small numbers of individual HG-SOC PDX in conjunction with sparse molecular annotation and patient outcome data. Recently, two consecutive panels of epithelial OC PDX correlate in vivo platinum response with molecular aberrations and source patient clinical outcomes. These studies underpin the value of PDX models to better direct chemotherapy and predict response to targeted therapy. Tumor heterogeneity, before and following treatment, as well as the importance of multiple molecular aberrations per individual tumor underscore some of the important issues addressed in PDX models

  13. Improvements in current treatments and emerging therapies for adult obstructive sleep apnea.

    PubMed

    Freedman, Neil

    2014-01-01

    Obstructive sleep apnea (OSA) is common and is associated with a number of adverse outcomes, including an increased risk for cardiovascular disease. Typical treatment approaches, including positive airway pressure, oral appliances, various upper airway surgeries, and/or weight loss, can improve symptoms and reduce the severity of disease in select patient groups. However, these approaches have several potential limitations, including suboptimal adherence, lack of suitability for all patient groups, and/or absence of adequate outcomes data. Emerging potential therapeutic options, including nasal expiratory positive airway pressure (PAP), oral negative pressure, upper airway muscle stimulation, and bariatric surgery, as well as improvements in existing treatments and the utilization of improving technologies are moving the field forward and should offer effective therapies to a wider group of patients with OSA.

  14. Spatiotemporal neuromodulation therapies engaging muscle synergies improve motor control after spinal cord injury

    PubMed Central

    Wenger, Nikolaus; Moraud, Eduardo Martin; Gandar, Jerome; Musienko, Pavel; Capogrosso, Marco; Baud, Laetitia; Le Goff, Camille G.; Barraud, Quentin; Pavlova, Natalia; Dominici, Nadia; Minev, Ivan R.; Asboth, Leonie; Hirsch, Arthur; Duis, Simone; Kreider, Julie; Mortera, Andrea; Haverbeck, Oliver; Kraus, Silvio; Schmitz, Felix; DiGiovanna, Jack; van den Brand, Rubia; Bloch, Jocelyne; Detemple, Peter; Lacour, Stéphanie P.; Bézard, Erwan; Micera, Silvestro; Courtine, Grégoire

    2016-01-01

    Electrical neuromodulation of lumbar segments improves motor control after spinal cord injury in animal models and humans. However, the physiological principles underlying the effect of this intervention remain poorly understood, which has limited this therapeutic approach to continuous stimulation applied to restricted spinal cord locations. Here, we developed novel stimulation protocols that reproduce the natural dynamics of motoneuron activation during locomotion. For this, we computed the spatiotemporal activation pattern of muscle synergies during locomotion in healthy rats. Computer simulations identified optimal electrode locations to target each synergy through the recruitment of proprioceptive feedback circuits. This framework steered the design of spatially selective spinal implants and real–time control software that modulate extensor versus flexor synergies with precise temporal resolution. Spatiotemporal neuromodulation therapies improved gait quality, weight–bearing capacities, endurance and skilled locomotion in multiple rodent models of spinal cord injury. These new concepts are directly translatable to strategies to improve motor control in humans. PMID:26779815

  15. Improving access to psychological therapies (IAPT) and treatment outcomes: epistemological assumptions and controversies.

    PubMed

    Williams, C H J

    2015-06-01

    Cognitive behaviour therapy (CBT) is recommended as a primary treatment choice in England, for anxiety and depression, by the National Institute for Health and Care Excellence (NICE). It has been argued that CBT has enjoyed political and cultural dominance and this has arguably led to maintained government investment in England for the cognitive and behavioural treatment of mental health problems. The government programme 'Improving Access to Psychological Therapies' (IAPT) aims to improve the availability of CBT. The criticism of the NICE evidence-based guidelines supporting the IAPT programme, has been the dominance of the gold standard randomized controlled trial methodology, with a focus on numerical outcome data, rather than a focus on a recovery narrative. RCT-based research is influenced by a philosophical paradigm called positivism. The IAPT culture is arguably influenced by one research paradigm and such an influence can skew services only towards numerical outcome data as the only truth of 'recovery'. An interpretative paradigm could assist in shaping service-based cultures, alter how services are evaluated and improve the richness of CBT research. This paper explores the theory of knowledge (epistemology) that underpins the evidence-based perspective of CBT and how this influences service delivery. The paper argues that the inclusion of service user narrative (qualitative data) can assist the evaluation of CBT from the user's perspective and can understand the context in which people live and how they access services. A qualitative perspective is discussed as a research strategy, capturing the lived experience of under-represented groups, such as sexual, gender and ethnic minorities. Cognitive behaviour therapy (CBT) has enjoyed political and cultural dominance within mental healthcare, with renewed government investment in England for the'Improving Access to Psychological Therapies' (IAPT) programme. The criticism of the evidence-based guidelines

  16. Comparing uni-modal and multi-modal therapies for improving writing in acquired dysgraphia after stroke.

    PubMed

    Thiel, Lindsey; Sage, Karen; Conroy, Paul

    2016-01-01

    Writing therapy studies have been predominantly uni-modal in nature; i.e., their central therapy task has typically been either writing to dictation or copying and recalling words. There has not yet been a study that has compared the effects of a uni-modal to a multi-modal writing therapy in terms of improvements to spelling accuracy. A multiple-case study with eight participants aimed to compare the effects of a uni-modal and a multi-modal therapy on the spelling accuracy of treated and untreated target words at immediate and follow-up assessment points. A cross-over design was used and within each therapy a matched set of words was targeted. These words and a matched control set were assessed before as well as immediately after each therapy and six weeks following therapy. The two approaches did not differ in their effects on spelling accuracy of treated or untreated items or degree of maintenance. All participants made significant improvements on treated and control items; however, not all improvements were maintained at follow-up. The findings suggested that multi-modal therapy did not have an advantage over uni-modal therapy for the participants in this study. Performance differences were instead driven by participant variables.

  17. Sialendoscopy for Patients with Radioiodine-Induced Sialadenitis and Xerostomia

    PubMed Central

    Bhayani, Mihir K.; Acharya, Varun; Kongkiatkamon, Suchada; Farah, Sally; Roberts, Dianna B.; Sterba, Jennifer; Chambers, Mark S.

    2015-01-01

    Background: We examined outcomes in patients treated for radioactive iodine–induced sialadenitis (RAIS) and xerostomia with sialendoscopy. Methods: Data was prospectively collected for all patients undergoing sialendoscopy for RAIS from a single institution. Interventional details and intraoperative findings were recorded. Qualitative data were obtained through patient examination, telephone interviews, and use of a standard quality of life questionnaire, Xerostomia Questionnaire. Quantitative data were obtained from patients who underwent sialometry. Results: Twenty-six patients (24 women and 2 men; median age, 43 years; age range, 19–57 years) underwent interventional sialendoscopy after conservative management of symptoms proved unsuccessful. Sialadenitis was present in 25 patients and xerostomia in 22 patients. Mucus plugging in the duct of the gland was the most common finding (22 patients) followed by stenosis (18 patients), inflammation (eight patients), and erythema (eight patients). Median follow-up time was 23.4±12.1 months. Sixteen patients (64%) reported complete resolution; seven (28%), partial resolution; one (4%), no change in symptoms; and one (4%), regression in RAIS-related symptoms. Patients subjectively noted the following regarding their xerostomia symptoms: seven (31.8%) had complete resolution; 10 (45.5%), partial resolution; four (18.2%), no change; and one (4.5%), regression. Statistical analysis of the available sialometry data revealed a statistically significant difference in saliva production at 6 months following sialendoscopy for unstimulated saliva production (p=0.028). Conclusion: Sialendoscopy is an effective treatment option for the management of RAIS and xerostomia refractory to conservative therapy and medical management. Patients in our cohort report durable improvement in symptoms after intervention. PMID:25860842

  18. Radioprotective Effect of Epigallocatechin-3-Gallate on Salivary Gland Dysfunction After Radioiodine Ablation in a Murine Model

    PubMed Central

    Choi, Jeong-Seok; An, Hye-Young; Park, In Suh; Kim, Seok-Ki; Kim, Young-Mo; Lim, Jae-Yol

    2016-01-01

    Objectives. Radioiodine (RI) therapy is known to subject cellular components of salivary glands (SG) to oxidative stress leading to SG dysfunction. However, the protective effects of antioxidants on RI-induced SG damage have not been well investigated. The authors investigated the morphometric and functional effects of epigallocatechin-3-gallate (EGCG) administered prior to RI therapy and compared this with the effects of amifostine (a well-known antioxidant) in a murine model of RI sialadenitis. Methods. Four-week-old female C57BL/6 mice (n=48) were divided into four groups; a normal control group, a RI-treated group (0.01 mCi/g mouse, orally), an EGCG and RI-treated group, and an amifostine and RI-treated group. Animals in these groups were divided into 3 subgroups and euthanized at 15, 30, and 90 days post-RI treatment. Salivary flow rates and lag times were measured, and morphologic and histologic examinations and TUNEL (terminal deoxynucleotidyl transferase biotin-dUDP nick end labeling) assays were performed. Changes in salivary 99mTc pertechnetate uptake and excretion were followed by single-photon emission computed tomography. Results. Salivary flow rates and lag times to salivation in the EGCG or amifostine groups were better than in the RI-treated group. Histologic examinations of SGs in the EGCG or amifostine group showed more mucin-rich parenchyma and less periductal fibrosis than in the RI-treated group. Fewer apoptotic cells were observed in acini, ducts, and among endothelial cells in the EGCG or amifostine group than in the RI group. In addition, patterns of 99mTc pertechnetate excretion were quite different in the EGCG or amifostine group than in the RI group. Conclusion. EGCG supplementation before RI therapy could protect from RI-induced SG damage in a manner comparable to amifostine, and thus, offers a possible means of preventing SG damage by RI. PMID:27136365

  19. Virtual Reality Reflection Therapy Improves Balance and Gait in Patients with Chronic Stroke: Randomized Controlled Trials.

    PubMed

    In, Taesung; Lee, Kyeongjin; Song, Changho

    2016-10-28

    BACKGROUND Virtual reality reflection therapy (VRRT) is a technically enhanced version of the mirror therapy concept. The aim of this study was to investigate whether VRRT could improve the postural balance and gait ability of patients with chronic stroke. MATERIAL AND METHODS Twenty-five patients with chronic stroke were randomly allocated into the VRRT group (n=13) and the control group (n=12). The participants in both groups performed a conventional rehabilitation program for 30 minutes. The VRRT group also performed a VRRT program for 30 minutes, five times a week for 4 weeks. The control group performed conventional rehabilitation program and a placebo VRRT program. Outcome measures included Berg Balance Scale (BBS), the Functional Reaching Test (FRT), and the Timed Up and Go (TUG) test (for dynamic balance ability), postural sway (for static balance ability), and 10 meter walking velocity (10 mWV) for gait ability. RESULTS There were statistically significant improvements in the VRRT group compared with the control group for BBS, FRT, TUG, postural sway (mediolateral sway distance with eyes open and eyes closed, anteroposterior and total sway distance with eyes open but not with eyes closed), and 10 mWV (p<0.05). CONCLUSIONS Applying VRRT (even as a home treatment) along with a conventional rehabilitation program for patients with chronic stroke might be even more beneficial than conventional rehabilitation program alone in improving affected lower limb function. Future studies should investigate the effectiveness of VRRT with optimal patient selection, and duration and intensity of training.

  20. Measurement of the Red Blood Cell Distribution Width Improves the Risk Prediction in Cardiac Resynchronization Therapy

    PubMed Central

    Boros, András Mihály; Perge, Péter; Jenei, Zsigmond; Karády, Júlia; Zima, Endre; Molnár, Levente; Becker, Dávid; Gellér, László; Prohászka, Zoltán; Merkely, Béla; Széplaki, Gábor

    2016-01-01

    Objectives. Increases in red blood cell distribution width (RDW) and NT-proBNP (N-terminal pro-B-type natriuretic peptide) predict the mortality of chronic heart failure patients undergoing cardiac resynchronization therapy (CRT). It was hypothesized that RDW is independent of and possibly even superior to NT-proBNP from the aspect of long-term mortality prediction. Design. The blood counts and serum NT-proBNP levels of 134 patients undergoing CRT were measured. Multivariable Cox regression models were applied and reclassification analyses were performed. Results. After separate adjustment to the basic model of left bundle branch block, beta blocker therapy, and serum creatinine, both the RDW > 13.35% and NT-proBNP > 1975 pg/mL predicted the 5-year mortality (n = 57). In the final model including all variables, the RDW [HR = 2.49 (1.27–4.86); p = 0.008] remained a significant predictor, whereas the NT-proBNP [HR = 1.18 (0.93–3.51); p = 0.07] lost its predictive value. On addition of the RDW measurement, a 64% net reclassification improvement and a 3% integrated discrimination improvement were achieved over the NT-proBNP-adjusted basic model. Conclusions. Increased RDW levels accurately predict the long-term mortality of CRT patients independently of NT-proBNP. Reclassification analysis revealed that the RDW improves the risk stratification and could enhance the optimal patient selection for CRT. PMID:26903690

  1. Virtual Reality Reflection Therapy Improves Balance and Gait in Patients with Chronic Stroke: Randomized Controlled Trials

    PubMed Central

    In, Taesung; Lee, Kyeongjin; Song, Changho

    2016-01-01

    Background Virtual reality reflection therapy (VRRT) is a technically enhanced version of the mirror therapy concept. The aim of this study was to investigate whether VRRT could improve the postural balance and gait ability of patients with chronic stroke. Material/Methods Twenty-five patients with chronic stroke were randomly allocated into the VRRT group (n=13) and the control group (n=12). The participants in both groups performed a conventional rehabilitation program for 30 minutes. The VRRT group also performed a VRRT program for 30 minutes, five times a week for 4 weeks. The control group performed conventional rehabilitation program and a placebo VRRT program. Outcome measures included Berg Balance Scale (BBS), the Functional Reaching Test (FRT), and the Timed Up and Go (TUG) test (for dynamic balance ability), postural sway (for static balance ability), and 10 meter walking velocity (10 mWV) for gait ability. Results There were statistically significant improvements in the VRRT group compared with the control group for BBS, FRT, TUG, postural sway (mediolateral sway distance with eyes open and eyes closed, anteroposterior and total sway distance with eyes open but not with eyes closed), and 10 mWV (p<0.05). Conclusions Applying VRRT (even as a home treatment) along with a conventional rehabilitation program for patients with chronic stroke might be even more beneficial than conventional rehabilitation program alone in improving affected lower limb function. Future studies should investigate the effectiveness of VRRT with optimal patient selection, and duration and intensity of training. PMID:27791207

  2. Current strategies for improving access and adherence to antiretroviral therapies in resource-limited settings

    PubMed Central

    Scanlon, Michael L; Vreeman, Rachel C

    2013-01-01

    The rollout of antiretroviral therapy (ART) significantly reduced human immunodeficiency virus (HIV)-related morbidity and mortality, but good clinical outcomes depend on access and adherence to treatment. In resource-limited settings, where over 90% of the world’s HIV-infected population resides, data on barriers to treatment are emerging that contribute to low rates of uptake in HIV testing, linkage to and retention in HIV care systems, and suboptimal adherence rates to therapy. A review of the literature reveals limited evidence to inform strategies to improve access and adherence with the majority of studies from sub-Saharan Africa. Data from observational studies and randomized controlled trials support home-based, mobile and antenatal care HIV testing, task-shifting from doctor-based to nurse-based and lower level provider care, and adherence support through education, counseling and mobile phone messaging services. Strategies with more limited evidence include targeted HIV testing for couples and family members of ART patients, decentralization of HIV care, including through home- and community-based ART programs, and adherence promotion through peer health workers, treatment supporters, and directly observed therapy. There is little evidence for improving access and adherence among vulnerable groups such as women, children and adolescents, and other high-risk populations and for addressing major barriers. Overall, studies are few in number and suffer from methodological issues. Recommendations for further research include health information technology, social-level factors like HIV stigma, and new research directions in cost-effectiveness, operations, and implementation. Findings from this review make a compelling case for more data to guide strategies to improve access and adherence to treatment in resource-limited settings. PMID:23326204

  3. Motivational Deficits Differentially Predict Improvement in a Randomized Trial of Self-System Therapy for Depression

    PubMed Central

    Eddington, Kari M.; Silvia, Paul J.; Foxworth, Tamara E.; Hoet, Ariana; Kwapil, Thomas R.

    2015-01-01

    Objective A randomized trial compared the time course and differential predictors of symptom improvement in two treatments for depression. Method Forty-nine adults (84% female) who were not taking antidepressant medications and met diagnostic criteria for major depressive disorder or dysthymia were randomly assigned either to cognitive-behavioral therapy (CBT) or self-system therapy (SST), a treatment that targets problems in self-regulation, the ongoing process of evaluating progress toward personal goals. Self-regulatory variables (promotion and prevention focus, and goal disengagement and reengagement) were assessed as potential moderators of efficacy. At intake, most participants reported depression in the moderate to severe range and had histories of recurrent episodes and previous treatment attempts. Self-reported symptoms of depression and anxiety were assessed at each therapy session. Multilevel modeling was used to examine (1) differences in change associated with the treatment conditions, and (2) moderation of treatment efficacy by pre-treatment measures of self-regulatory deficits. Results Both treatments were effective and did not show differences in the magnitude or rate of symptom change or in drop-out rates, suggesting that CBT and SST were equally effective in improving depression and anxiety. Patients with self-regulatory deficits, however, showed greater improvement in depressive symptoms with SST. Specifically, patients with low promotion focus and low goal reengagement responded better to SST, while patients with high prevention focus responded better to CBT. Conclusions Overall, these results corroborate previous research suggesting that SST is a viable short-term treatment for depression that is particularly effective in helping patients compensate for self-regulatory deficits. PMID:25867448

  4. Improvements in Bone Density and Structure during Anti-TNF-α Therapy in Pediatric Crohn's Disease

    PubMed Central

    Thayu, Meena; Baldassano, Robert N.; DeBoer, Mark D.; Zemel, Babette S.; Denburg, Michelle R.; Denson, Lee A.; Shults, Justine; Herskovitz, Rita; Long, Jin; Leonard, Mary B.

    2015-01-01

    Context: Pediatric Crohn's Disease (CD) is associated with deficits in trabecular bone mineral density (BMD) and cortical structure, potentially related to TNF-α effects to decrease bone formation and promote bone resorption. Objective: This study aimed to examine changes in bone density and structure in children and adolescents with CD following initiation of anti-TNF-α therapy. Design and Participants: Participants (n = 74; age 5–21 years) with CD completed a 12-month prospective cohort study. Main Outcome Measures: Tibia peripheral quantitative computed tomography scans were obtained at initiation of anti-TNF-α therapy and 12 months later. Musculoskeletal outcomes were expressed as sex-and race-specific z scores relative to age, based on >650 reference participants. Results: At baseline, CD participants had lower height, trabecular BMD, cortical area (due to smaller periosteal and larger endocortical circumferences), and muscle area z scores, compared with reference participants (all P < .01). Pediatric CD activity index decreased during the 10-week induction (P < .001), in association with subsequent gains in height, trabecular BMD, cortical area (due to recovery of endocortical bone), and muscle area z scores over 12 months (height P < .05; others P < .001). Bone-specific alkaline phosphatase levels, a biomarker of bone formation, increased a median of 75% (P < .001) during induction with associated 12-month improvements in trabecular BMD and cortical area z scores (both P < .001). Younger age was associated with greater increases in trabecular BMD z scores (P < .001) and greater linear growth with greater recovery of cortical area (P < .001). Conclusions: Anti-TNF-α therapy was associated with improvements in trabecular BMD and cortical structure. Improvements were greater in younger and growing participants, suggesting a window of opportunity for treatment of bone deficits. PMID:25919459

  5. Current strategies for improving access and adherence to antiretroviral therapies in resource-limited settings.

    PubMed

    Scanlon, Michael L; Vreeman, Rachel C

    2013-01-01

    The rollout of antiretroviral therapy (ART) significantly reduced human immunodeficiency virus (HIV)-related morbidity and mortality, but good clinical outcomes depend on access and adherence to treatment. In resource-limited settings, where over 90% of the world's HIV-infected population resides, data on barriers to treatment are emerging that contribute to low rates of uptake in HIV testing, linkage to and retention in HIV care systems, and suboptimal adherence rates to therapy. A review of the literature reveals limited evidence to inform strategies to improve access and adherence with the majority of studies from sub-Saharan Africa. Data from observational studies and randomized controlled trials support home-based, mobile and antenatal care HIV testing, task-shifting from doctor-based to nurse-based and lower level provider care, and adherence support through education, counseling and mobile phone messaging services. Strategies with more limited evidence include targeted HIV testing for couples and family members of ART patients, decentralization of HIV care, including through home- and community-based ART programs, and adherence promotion through peer health workers, treatment supporters, and directly observed therapy. There is little evidence for improving access and adherence among vulnerable groups such as women, children and adolescents, and other high-risk populations and for addressing major barriers. Overall, studies are few in number and suffer from methodological issues. Recommendations for further research include health information technology, social-level factors like HIV stigma, and new research directions in cost-effectiveness, operations, and implementation. Findings from this review make a compelling case for more data to guide strategies to improve access and adherence to treatment in resource-limited settings.

  6. Early improvement predicts outcome of major depressive patients treated with electroconvulsive therapy.

    PubMed

    Lin, Ching-Hua; Chen, Ming-Chao; Yang, Wei-Cheng; Lane, Hsien-Yuan

    2016-02-01

    The aim of this study was to test whether early symptom improvement predicts final response and remission for patients with major depressive disorder (MDD) receiving electroconvulsive therapy (ECT). MDD inpatients (N=130) requiring ECT were recruited. ECT was generally performed for a maximum of 12 sessions. Symptom severity was assessed using the 17-item Hamilton Depression Rating Scale (HAMD-17) before ECT, after every 3 ECT sessions, and after the last ECT. Early improvement was defined as a reduction in the HAMD-17 score by at least 20%, 25%, or 30% after 3 and 6 ECT sessions. Response was defined as 60% HAMD-17 score reduction, while remission was defined as an end point HAMD-17 score of ≦7. Receiver operating characteristic (ROC) curves were used to determine whether 3 or 6 ECT sessions had better discriminative capacity. Sensitivity, specificity and predictive values were calculated for the different definitions of early improvement. Of the 105 patients entering the analysis, 85.7% (n=90) and 70.5% (n=74) were classified as responders and remitters, respectively. Early improvement after 6 ECT sessions showed better discriminative capacity, with areas under the ROC curve at least 0.8. It had high sensitivity and high negative predictive value for all cutoffs in predicting response and remission. High response and remission rates were observed. Final response and remission could be predicted by early improvement after 6 ECT sessions. Patients without early improvement were unlikely to reach response and remission.

  7. Does antiretroviral therapy improve HIV-associated cognitive impairment? A quantitative review of the literature.

    PubMed

    Al-Khindi, Timour; Zakzanis, Konstantine K; van Gorp, Wilfred G

    2011-11-01

    The development of antiretroviral therapy (ART) has dramatically improved survival for those living with human immunodeficiency virus (HIV), but whether ART improves cognitive functioning remains unclear. The aim of the present review was to examine systematically the extent to which ART improves cognition among individuals with HIV using meta-analytic methods. Twenty-three studies were included in the quantitative review. ART was associated with modest improvements in attention (mean d = .17; p < .001; 95% confidence interval [CI], .09/.25), executive function (mean d = .18; p < .001; 95% CI, .10/.26), and motor function (mean d = .24; p < .001; 95% CI, .16/.32). ART did not improve language, verbal memory, visual memory or visuospatial function. The extent to which cognition improved was correlated with the change in CD4 cell count following ART, suggesting a link between cognitive outcome and immune system integrity. Together, the present findings indicate that the neuropsychological test performance of most HIV patients taking ART is comparable to those not taking ART. Development of pharmaceutical treatments and rehabilitation strategies that target the cognitive effects of HIV infection is needed.

  8. Astym Therapy Improves Bilateral Hamstring Flexibility and Achilles Tendinopathy in a Child with Cerebral Palsy: A Retrospective Case Report

    PubMed Central

    Scheer, Nicole A.; Alstat, Lucas R.; Van Zant, Robert S.

    2016-01-01

    PURPOSE The purpose of this case report was to describe the use of Astym therapy to improve hamstring flexibility and Achilles tendinopathy in a child with cerebral palsy. CASE DESCRIPTION An eight-year-old female with cerebral palsy was referred to physical therapy for the treatment of bilateral hamstring inflexibility and Achilles tendinopathy. Treatment focused on an Astym therapy protocol of eccentric exercise, stretching, active and passive range of motion, gait training, and a home exercise program. The patient underwent a total of 11 physical therapy treatment sessions. OUTCOMES At the conclusion of treatment, the patient demonstrated improved resting muscle tone in bilateral lower extremities with active 90/90 hamstring flexibility measured at 165° and ankle dorsiflexion active range of motion of 5° without pain at 0° and 90° knee flexion. The patient exhibited an improved gait pattern with even stride length and diminished genu recurvatum, decreased pain with standing and walking, discontinued use of ankle–foot orthoses, and improved activity tolerance and overall function for daily activities. DISCUSSION The results of this case report indicate that physical therapy rehabilitation utilizing an Astym therapy protocol can successfully achieve gains in flexibility and strength and allow for improved function of bilateral lower extremities in a patient with cerebral palsy. CONCLUSION Based on the findings of this case report, clinicians should consider the use of Astym therapy in treating musculoskeletal soft tissue dysfunction in pediatric patients with cerebral palsy. PMID:27790051

  9. Update on the Improving Access to Psychological Therapies programme in England: author's reply†

    PubMed Central

    Timimi, Sami

    2015-01-01

    Fonagy & Clark confirm in their rebuttal that they have an ideological commitment to the failed technical model of understanding and intervening in mental health problems that dominates current service provision. They fail to acknowledge the limitations and problems associated with Improving Access to Psychological Therapies (IAPT) and Children's and Young People's IAPT (CYP-IAPT) and offer an unconvincing explanation for why they did not allow some of the vast tax payers' money that they had at their dispoal to be used to implement evidence supported relational models. PMID:26755971

  10. Improving clinical outcome in patients with myelodysplastic syndrome and iron overload using iron chelation therapy.

    PubMed

    Leitch, Heather A

    2007-12-01

    Until recently, little information on the benefits of iron chelation therapy (ICT) in patients with myelodysplastic syndrome (MDS) and iron overload was known. A recent retrospective study showed improved survival in transfusion-dependent patients with MDS (Low or Intermediate-1 risk IPSS) receiving ICT, compared with those not receiving ICT; median overall survival was not reached at 160 months versus 40 months, respectively. Significantly more patients receiving ICT survived to 4 years (80% versus 44%; p < 0.03), suggesting that MDS patients with iron overload might benefit from ICT. Prospective studies to confirm the benefit of ICT in MDS are warranted.

  11. meso-Acetoxymethyl BODIPY dyes for photodynamic therapy: improved photostability of singlet oxygen photosensitizers.

    PubMed

    Lincoln, R; Durantini, A M; Greene, L E; Martínez, S R; Knox, R; Becerra, M C; Cosa, G

    2017-02-15

    We report two BODIPY based photosensitizers (Br2BOAc and I2BOAc) featuring an acetoxymethyl substituent at the meso-position. These photosensitizers show improved photostability against singlet oxygen, when compared to a BODIPY photosensitizer lacking the acetoxymethyl group. Both compounds were evaluated for photodynamic therapy against HeLa cells and photodynamic inactivation against E. coli bacteria. We show that the compounds readily embed in the lipid membranes of HeLa cervical cancer cells and efficiently induced light-dependent apoptosis at nanomolar concentration. Also, both compounds showed a substantial degree of photoinactivation of E. coli bacteria when used at low micromolar concentrations.

  12. Nursing issues in renal replacement therapy: organization, manpower assessment, competency evaluation and quality improvement processes.

    PubMed

    Graham, Patricia; Lischer, Eileen

    2011-01-01

    For the patient with acute kidney injury, continuous renal replacement therapy (CRRT) is a treatment option that has application for the hemodynamically unstable critically ill patient. The decision to initiate a continuous renal replacement modality depends not only on the physician, either the nephrologist or intensivist, but also on the availability of specially trained nursing resources. This article will explore the nursing collaborative model of care at a large university-based research and teaching Medical Center in Southern California. The focus will be on nursing issues in CRRT including organization of educational programs, manpower assessment, competency evaluation, and quality improvement processes.

  13. Metastatic lung cancer in the age of targeted therapy: improving long-term survival

    PubMed Central

    Del Rivero, Jaydira; Thomas, Anish

    2016-01-01

    Epidermal growth factor receptor (EGFR) mutations are the most frequent targetable genetic abnormality observed in non-small cell lung cancer (NSCLC). More than a decade after EGFR mutations were shown to predict sensitivity to EGFR-tyrosine kinase inhibitors (EGFR-TKI), retrospective cohort studies are now identifying and characterizing 5-year survivors. While these studies indicate subsets of patients achieving long-term survival, there is paucity of data pertaining to the long-term survival benefits of these targeted therapies at a population level. Improving access to molecular testing and treatment are key to maximizing the survival benefits at a population level. PMID:28149768

  14. Cauda equina syndrome associated with multiple lumbar arachnoid cysts in ankylosing spondylitis: improvement following surgical therapy.

    PubMed Central

    Shaw, P J; Allcutt, D A; Bates, D; Crawford, P J

    1990-01-01

    A case of cauda equina syndrome with multiple lumbar arachnoid cysts complicating ankylosing spondylitis (AS) is described. The value of computerised tomography (CT) and magnetic resonance imaging (MRI) as a non-invasive means of establishing the diagnosis is emphasised. In contrast to previously reported cases the patient showed neurological improvement following surgical therapy. Surgery may be indicated in some patients, particularly when there is nerve root compression by the arachnoid cysts and when the patient is seen early before irreversible damage to the cauda equina has occurred. Images PMID:2292702

  15. Occupational therapy using sensory integration to improve participation of a child with autism: a case report.

    PubMed

    Schaaf, Roseann C; Hunt, Joanne; Benevides, Teal

    2012-01-01

    In this case report, we describe the changes in adaptive behaviors and participation of 1 child with autism during a 10-wk program of intensive occupational therapy using a sensory integrative approach (OT-SI) following a manualized protocol. This case is part of a larger study examining the efficacy of the OT-SI approach. We found improvement in sensory processing, as measured by the Sensory Integration and Praxis Tests, as well as enhanced participation in home, school, and family activities, as indicated on parent-rated goal attainment scales.

  16. A System for Continual Quality Improvement of Normal Tissue Delineation for Radiation Therapy Treatment Planning

    SciTech Connect

    Breunig, Jennifer; Hernandez, Sophy; Lin, Jeffrey; Alsager, Stacy; Dumstorf, Christine; Price, Jennifer; Steber, Jennifer; Garza, Richard; Nagda, Suneel; Melian, Edward; Emami, Bahman; Roeske, John C.

    2012-08-01

    Purpose: To implement the 'plan-do-check-act' (PDCA) cycle for the continual quality improvement of normal tissue contours used for radiation therapy treatment planning. Methods and Materials: The CT scans of patients treated for tumors of the brain, head and neck, thorax, pancreas and prostate were selected for this study. For each scan, a radiation oncologist and a diagnostic radiologist, outlined the normal tissues ('gold' contours) using Radiation Therapy Oncology Group (RTOG) guidelines. A total of 30 organs were delineated. Independently, 5 board-certified dosimetrists and 1 trainee then outlined the same organs. Metrics used to compare the agreement between the dosimetrists' contours and the gold contours included the Dice Similarity Coefficient (DSC), and a penalty function using distance to agreement. Based on these scores, dosimetrists were re-trained on those organs in which they did not receive a passing score, and they were subsequently re-tested. Results: Passing scores were achieved on 19 of 30 organs evaluated. These scores were correlated to organ volume. For organ volumes <8 cc, the average DSC was 0.61 vs organ volumes {>=}8 cc, for which the average DSC was 0.91 (P=.005). Normal tissues that had the lowest scores included the lenses, optic nerves, chiasm, cochlea, and esophagus. Of the 11 organs that were considered for re-testing, 10 showed improvement in the average score, and statistically significant improvement was noted in more than half of these organs after education and re-assessment. Conclusions: The results of this study indicate the feasibility of applying the PDCA cycle to assess competence in the delineation of individual organs, and to identify areas for improvement. With testing, guidance, and re-evaluation, contouring consistency can be obtained across multiple dosimetrists. Our expectation is that continual quality improvement using the PDCA approach will ensure more accurate treatments and dose assessment in radiotherapy

  17. Systemic peptide-mediated oligonucleotide therapy improves long-term survival in spinal muscular atrophy

    PubMed Central

    Hazell, Gareth; Shabanpoor, Fazel; Saleh, Amer F.; Bowerman, Melissa; Meijboom, Katharina E.; Zhou, Haiyan; Muntoni, Francesco; Talbot, Kevin; Gait, Michael J.; Wood, Matthew J. A.

    2016-01-01

    The development of antisense oligonucleotide therapy is an important advance in the identification of corrective therapy for neuromuscular diseases, such as spinal muscular atrophy (SMA). Because of difficulties of delivering single-stranded oligonucleotides to the CNS, current approaches have been restricted to using invasive intrathecal single-stranded oligonucleotide delivery. Here, we report an advanced peptide-oligonucleotide, Pip6a-morpholino phosphorodiamidate oligomer (PMO), which demonstrates potent efficacy in both the CNS and peripheral tissues in severe SMA mice following systemic administration. SMA results from reduced levels of the ubiquitously expressed survival motor neuron (SMN) protein because of loss-of-function mutations in the SMN1 gene. Therapeutic splice-switching oligonucleotides (SSOs) modulate exon 7 splicing of the nearly identical SMN2 gene to generate functional SMN protein. Pip6a-PMO yields SMN expression at high efficiency in peripheral and CNS tissues, resulting in profound phenotypic correction at doses an order-of-magnitude lower than required by standard naked SSOs. Survival is dramatically extended from 12 d to a mean of 456 d, with improvement in neuromuscular junction morphology, down-regulation of transcripts related to programmed cell death in the spinal cord, and normalization of circulating insulin-like growth factor 1. The potent systemic efficacy of Pip6a-PMO, targeting both peripheral as well as CNS tissues, demonstrates the high clinical potential of peptide-PMO therapy for SMA. PMID:27621445

  18. Improving cancer therapies by targeting the physical and chemical hallmarks of the tumor microenvironment.

    PubMed

    Ivey, Jill W; Bonakdar, Mohammad; Kanitkar, Akanksha; Davalos, Rafael V; Verbridge, Scott S

    2016-09-28

    Tumors are highly heterogeneous at the patient, tissue, cellular, and molecular levels. This multi-scale heterogeneity poses significant challenges for effective therapies, which ideally must not only distinguish between tumorous and healthy tissue, but also fully address the wide variety of tumorous sub-clones. Commonly used therapies either leverage a biological phenotype of cancer cells (e.g. high rate of proliferation) or indiscriminately kill all the cells present in a targeted volume. Tumor microenvironment (TME) targeting represents a promising therapeutic direction, because a number of TME hallmarks are conserved across different tumor types, despite the underlying genetic heterogeneity. Historically, TME targeting has largely focused on the cells that support tumor growth (e.g. vascular endothelial cells). However, by viewing the intrinsic physical and chemical alterations in the TME as additional therapeutic opportunities rather than barriers, a new class of TME-inspired treatments has great promise to complement or replace existing therapeutic strategies. In this review we summarize the physical and chemical hallmarks of the TME, and discuss how these tumor characteristics either currently are, or may ultimately be targeted to improve cancer therapies.

  19. An improved Monte Carlo (MC) dose simulation for charged particle cancer therapy

    NASA Astrophysics Data System (ADS)

    Ying, C. K.; Kamil, W. A.; Shuaib, I. L.; Matsufuji, Naruhiro

    2014-02-01

    Heavy-particle therapy such as carbon ion therapy are more popular nowadays because of the nature characteristics of charged particle and almost no side effect to patients. An effective treatment is achieved with high precision of dose calculation, in this research work, Geant4 based Monte Carlo simulation method has been used to calculate the radiation transport and dose distribution. The simulation have the same setting with the treatment room in Heavy Ion Medical Accelerator, HIMAC. The carbon ion beam at the isocentric gantry nozzle for the therapeutic energy of 290 MeV/u was simulated, experimental work was carried out in National Institute of Radiological Sciences, NIRS, Chiba, Japan by using the HIMAC to confirm the accuracy and qualities dose distribution by MC methods. The Geant4 based simulated dose distribution were verified with measurements for Bragg peak and spread out Bragg peak (SOBP) respectively. The verification of results shows that the Bragg peak depth-dose and SOBP distributions in simulation has good agreement with measurements. In overall, the study showed that Geant4 based can be fully applied in the heavy-ion therapy field for simulation, further works need to be carry on to refine and improve the Geant4 MC simulations.

  20. Routine operation of the University of Washington fast neutron therapy facility and plans for improvements

    SciTech Connect

    Risler, R.; Emery, R.; Laramore, G. E.

    1999-06-10

    The fast neutron therapy facility in Seattle is based on a cyclotron, which produces a 50.5 MeV proton beam. Neutrons are produced in a beryllium target installed in an isocentric gantry equipped with a multi-leaf collimator. The system has been in routine operation for 14 years and over 1800 patients have been treated. Downtime has been minimal, over the past 10 years less than 1.5% of the scheduled daily treatment sessions could not be delivered for equipment related reasons. Fast neutron therapy has been shown to be highly effective for the treatment of salivary gland tumors, sarcomas of bone and soft tissues and for certain prostate cancers. In addition there are situations such as non-small cell lung cancer, where results are promising, but success is limited by normal tissue complications. A relatively small selective increase in the tumor dose might lead to a significant clinical improvement in these situations. The use of a boron neutron capture (BNC) boost, utilizing the moderated slow neutrons naturally present in the tissue during fast neutron therapy, may be beneficial for such patients. Experimental work to adapt the facility for such a modified treatment modality is presently ongoing.

  1. Routine operation of the University of Washington fast neutron therapy facility and plans for improvements

    NASA Astrophysics Data System (ADS)

    Risler, R.; Emery, R.; Laramore, G. E.

    1999-06-01

    The fast neutron therapy facility in Seattle is based on a cyclotron, which produces a 50.5 MeV proton beam. Neutrons are produced in a beryllium target installed in an isocentric gantry equipped with a multi-leaf collimator. The system has been in routine operation for 14 years and over 1800 patients have been treated. Downtime has been minimal, over the past 10 years less than 1.5% of the scheduled daily treatment sessions could not be delivered for equipment related reasons. Fast neutron therapy has been shown to be highly effective for the treatment of salivary gland tumors, sarcomas of bone and soft tissues and for certain prostate cancers. In addition there are situations such as non-small cell lung cancer, where results are promising, but success is limited by normal tissue complications. A relatively small selective increase in the tumor dose might lead to a significant clinical improvement in these situations. The use of a boron neutron capture (BNC) boost, utilizing the moderated slow neutrons naturally present in the tissue during fast neutron therapy, may be beneficial for such patients. Experimental work to adapt the facility for such a modified treatment modality is presently ongoing.

  2. An improved Monte Carlo (MC) dose simulation for charged particle cancer therapy

    SciTech Connect

    Ying, C. K.; Kamil, W. A.; Shuaib, I. L.; Matsufuji, Naruhiro

    2014-02-12

    Heavy-particle therapy such as carbon ion therapy are more popular nowadays because of the nature characteristics of charged particle and almost no side effect to patients. An effective treatment is achieved with high precision of dose calculation, in this research work, Geant4 based Monte Carlo simulation method has been used to calculate the radiation transport and dose distribution. The simulation have the same setting with the treatment room in Heavy Ion Medical Accelerator, HIMAC. The carbon ion beam at the isocentric gantry nozzle for the therapeutic energy of 290 MeV/u was simulated, experimental work was carried out in National Institute of Radiological Sciences, NIRS, Chiba, Japan by using the HIMAC to confirm the accuracy and qualities dose distribution by MC methods. The Geant4 based simulated dose distribution were verified with measurements for Bragg peak and spread out Bragg peak (SOBP) respectively. The verification of results shows that the Bragg peak depth-dose and SOBP distributions in simulation has good agreement with measurements. In overall, the study showed that Geant4 based can be fully applied in the heavy-ion therapy field for simulation, further works need to be carry on to refine and improve the Geant4 MC simulations.

  3. Improved local control for advanced oropharyngeal carcinoma following twice daily radiation therapy

    SciTech Connect

    Wang, C.C.

    1985-12-01

    This paper presents the results of treatment on 99 patients with squamous cell carcinoma of the oropharynx irradiated by the twice-a-day radiation therapy program at the Massachusetts General Hospital. The program consisted of 1.6 Gy per fraction, two fractions per day with 4 hours between fractions, for 12 days, 5 days a week. After 38.4 Gy, the patients were given a 2 week break and then resumed twice-a-day radiation therapy for a total of 64 Gy and occasionally 67.2 Gy. Fifty-two patients had carcinoma of the faucial tonsil and 47 patients had carcinoma of the base of the tongue. For the entire group of patients, the 36 month actuarial local control rate was 58%, and for the T1-2 and T3-4 lesions, the rates were 77% and 48% respectively. In comparison with patients treated by once-a-day radiation therapy for a few years immediately prior to the twice-a-day program, the local control rates were improved to a statistically significant level. Likewise, the results as compared to those published in the literature were no worse and perhaps superior to those of patients treated by the once-a-day schedule.

  4. Radioiodinated methyl-branched fatty acids: Evaluation of catabolites formed in vivo

    SciTech Connect

    Knapp, F.F. Jr.; Reske, S.N.; Kirsch, G.; Ambrose, K.R.; Blystone, S.L.; Goodman, M.M.

    1987-01-01

    Radioiodinated terminal iodophenyl-substituted long-chain fatty acids containing either racemic mono-methyl or geminal dimethyl-branching in the alkyl chain have been shown to exhibit delayed myocardial clearance properties which make these agents useful for the SPECT evaluation of myocardial fatty acid uptake patterns. Although the myocardial clearance rate of 15-(p-iodophenyl)-3-R,S- methylpentadecanoic acid (BMIPP) is considerably delayed, in comparison with the IPPA straight-chain analogue, analysis of the radioiodinated lipids present in the outflow tract of isolated rat hearts administered BMIPP have clearly demonstrated the presence of a polar metabolite. The synthesis of ..beta..-hydroxy fatty acids has been developed to allow investigation of the possible formation of ..beta..-hydroxy catabolites in vivo. The preparation of ..beta..-hydroxy BMIPP and ..beta..-hydroxy IPPA are described, and the possible significance of their formation in vivo discussed. 4 figs.

  5. WT1-specific T cell receptor gene therapy: improving TCR function in transduced T cells.

    PubMed

    Stauss, Hans J; Thomas, Sharyn; Cesco-Gaspere, Michela; Hart, Daniel P; Xue, Shao-An; Holler, Angelika; King, Judy; Wright, Graham; Perro, Mario; Pospori, Constantina; Morris, Emma

    2008-01-01

    Adoptive transfer of antigen-specific T lymphocytes is an attractive form of immunotherapy for haematological malignancies and cancer. The difficulty of isolating antigen-specific T lymphocytes for individual patients limits the more widespread use of adoptive T cell therapy. The demonstration that cloned T cell receptor (TCR) genes can be used to produce T lymphocyte populations of desired specificity offers new opportunities for antigen-specific T cell therapy. The first trial in humans demonstrated that TCR gene-modified T cells persisted for an extended time period and reduced tumor burden in some patients. The WT1 protein is an attractive target for immunotherapy of leukemia and solid cancer since elevated expression has been demonstrated in AML, CML, MDS and in breast, colon and ovarian cancer. In the past, we have isolated high avidity CTL specific for a WT1-derived peptide presented by HLA-A2 and cloned the TCR alpha and beta genes of a WT1-specific CTL line. The genes were inserted into retroviral vectors for transduction of human peripheral blood T lymphocytes of leukemia patients and normal donors. The treatment of leukemia-bearing NOD/SCID mice with T cells transduced with the WT1-specific TCR eliminated leukemia cells in the bone marrow of most mice, while treatment with T cells transduced with a TCR of irrelevant specificity did not diminish the leukemia burden. In order to improve the safety and efficacy of TCR gene therapy, we have developed lentiviral TCR gene transfer. In addition, we employed strategies to enhance TCR expression while avoiding TCR mis-pairing. It may be possible to generate dominant TCR constructs that can suppress the expression of the endogenous TCR on the surface of transduced T cells. The development of new TCR gene constructs holds great promise for the safe and effective delivery of TCR gene therapy for the treatment of malignancies.

  6. Improvement of dose distribution by central beam shielding in boron neutron capture therapy.

    PubMed

    Sakurai, Yoshinori; Ono, Koji

    2007-12-21

    Since boron neutron capture therapy (BNCT) with epithermal neutron beams started at the Kyoto University Reactor (KUR) in June 2002, nearly 200 BNCT treatments have been carried out. The epithermal neutron irradiation significantly improves the dose distribution, compared with the previous irradiation mainly using thermal neutrons. However, the treatable depth limit still remains. One effective technique to improve the limit is the central shield method. Simulations were performed for the incident neutron energies and the annular components of the neutron source. It was clear that thermal neutron flux distribution could be improved by decreasing the lower energy neutron component and the inner annular component of the incident beam. It was found that a central shield of 4-6 cm diameter and 10 mm thickness is effective for the 12 cm diameter irradiation field. In BNCT at KUR, the depth dose distribution can be much improved by the central shield method, resulting in a relative increase of the dose at 8 cm depth by about 30%. In addition to the depth dose distribution, the depth dose profile is also improved. As the dose rate in the central area is reduced by the additional shielding, the necessary irradiation time, however, increases by about 30% compared to normal treatment.

  7. Improved low-power semiconductor diode lasers for photodynamic therapy in veterinary medicine

    NASA Astrophysics Data System (ADS)

    Lee, Susanne M.; Mueller, Eduard K.; Van de Workeen, Brian C.; Mueller, Otward M.

    2001-05-01

    Cryogenically cooling semiconductor diode lasers provides higher power output, longer device lifetime, and greater monochromaticity. While these effects are well known, such improvements have not been quantified, and thus cryogenically operated semiconductor lasers have not been utilized in photodynamic therapy (PDT). We report quantification of these results from laser power meter and photospectrometer data. The emission wavelengths of these low power multiple quantum well semiconductor lasers were found to decrease and become more monochromatic with decreasing temperature. Significant power output improvements also were obtained at cryogenic temperatures. In addition, the threshold current, i.e. the current at which lasing begins, decreased with decreasing temperature. This lower threshold current combined with the increased power output produced dramatically higher device efficiencies. It is proposed that cryogenic operation of semiconductor diode lasers will reduce the number of devices needed to produce the requisite output for many veterinary and medical applications, permitting significant cost reductions.

  8. Glycosylation of Sodium/Iodide Symporter (NIS) Regulates Its Membrane Translocation and Radioiodine Uptake

    PubMed Central

    Chung, Taemoon; Youn, Hyewon; Yeom, Chan Joo; Kang, Keon Wook; Chung, June-Key

    2015-01-01

    Purpose Human sodium/iodide symporter (hNIS) protein is a membrane glycoprotein that transports iodide ions into thyroid cells. The function of this membrane protein is closely regulated by post-translational glycosylation. In this study, we measured glycosylation-mediated changes in subcellular location of hNIS and its function of iodine uptake. Methods HeLa cells were stably transfected with hNIS/tdTomato fusion gene in order to monitor the expression of hNIS. Cellular localization of hNIS was visualized by confocal microscopy of the red fluorescence of tdTomato. The expression of hNIS was evaluated by RT-PCR and immunoblot analysis. Functional activity of hNIS was estimated by radioiodine uptake. Cyclic AMP (cAMP) and tunicamycin were used to stimulate and inhibit glycosylation, respectively. In vivo images were obtained using a Maestro fluorescence imaging system. Results cAMP-mediated Glycosylation of NIS resulted in increased expression of hNIS, stimulating membrane translocation, and enhanced radioiodine uptake. In contrast, inhibition of glycosylation by treatment with tunicamycin dramatically reduced membrane translocation of intracellular hNIS, resulting in reduced radioiodine uptake. In addition, our hNIS/tdTomato fusion reporter successfully visualized cAMP-induced hNIS expression in xenografted tumors from mouse model. Conclusions These findings clearly reveal that the membrane localization of hNIS and its function of iodine uptake are glycosylation-dependent, as our results highlight enhancement of NIS expression and glycosylation with subsequent membrane localization after cAMP treatment. Therefore, enhancing functional NIS by the increasing level of glycosylation may be suggested as a promising therapeutic strategy for cancer patients who show refractory response to conventional radioiodine treatment. PMID:26599396

  9. Childhood Thyroid Radioiodine Exposure and Subsequent Infertility in the Intermountain Fallout Cohort

    PubMed Central

    Stone, Mary Bishop; Lyon, Joseph L.; VanDerslice, James A.; Alder, Stephen C.

    2012-01-01

    Background: Above-ground and underground nuclear weapon detonation at the Nevada Test Site (1951–1992) has resulted in radioiodine exposure for nearby populations. Although the long-term effect of environmental radioiodine exposure on thyroid disease has been well studied, little is known regarding the effect of childhood radioiodine exposure on subsequent fertility. Objectives: We investigated early childhood thyroid radiation exposure from nuclear testing fallout (supplied predominantly by radioactive isotopes of iodine) and self-reported lifetime incidence of male or female infertility or sterility. Methods: Participants were members of the 1965 Intermountain Fallout Cohort, schoolchildren at the time of exposure who were reexamined during two subsequent study phases to collect dietary and reproductive histories. Thyroid radiation exposure was calculated via an updated dosimetry model. We used multivariable logistic regression with robust sandwich estimators to estimate odds ratios for infertility, adjusted for potential confounders and (in separate models) for a medically confirmed history of thyroid disease. Results: Of 1,389 participants with dosimetry and known fertility history, 274 were classified as infertile, including 30 classified as sterile. Childhood thyroid radiation dose was possibly associated with infertility [adjusted odds ratio (AOR) = 1.17; 95% CI: 0.82, 1.67 and AOR = 1.35; 95% CI: 0.96, 1.90 for the middle and upper tertiles vs. the first tertile of exposure, respectively]. The odds ratios were attenuated (AOR = 1.08; 95% CI: 0.75, 1.55 and AOR = 1.29; 95% CI: 0.91, 1.83 for the middle and upper tertiles, respectively) after adjusting for thyroid disease. There was no association of childhood radiation dose and sterility. Conclusion: Our findings suggest that childhood radioiodine exposure from nuclear testing may be related to subsequent adult infertility. Further research is required to confirm this. PMID:23099433

  10. Instantaneous radioiodination of rose bengal at room temperature and a cold kit therefor

    DOEpatents

    O'Brien, Jr., Harold A.; Hupf, Homer B.; Wanek, Philip M.

    1981-01-01

    The disclosure relates to the radioiodination of rose bengal at room temperature and a cold-kit therefor. A purified rose bengal tablet is stirred into acidified ethanol at or near room temperature, until a suspension forms. Reductant-free .sup.125 I.sup.- is added and the resulting mixture stands until the exchange label reaction occurs at room temperature. A solution of sterile isotonic phosphate buffer and sodium hydroxide is added and the final resulting mixture is sterilized by filtration.

  11. Interventions to improve delivery of isoniazid preventive therapy: an overview of systematic reviews

    PubMed Central

    2014-01-01

    Background Uptake of isoniazid preventive therapy (IPT) to prevent tuberculosis has been poor, particularly in the highest risk populations. Interventions to improve IPT delivery could promote implementation. The large number of existing systematic reviews on treatment adherence has made drawing conclusions a challenge. To provide decision makers with the evidence they need, we performed an overview of systematic reviews to compare different organizational interventions to improve IPT delivery as measured by treatment completion among those at highest risk for the development of TB disease, namely child contacts or HIV-infected individuals. Methods We searched the Cochrane Database of Systematic Reviews, the Database of Abstracts of Reviews of Effects (DARE), and MEDLINE up to August 15, 2012. Two authors used a standardized data extraction form and the AMSTAR instrument to independently assess each review. Results Six reviews met inclusion criteria. Interventions included changes in the setting/site of IPT delivery, use of quality monitoring mechanisms (e.g., directly observed therapy), IPT delivery integration into other healthcare services, and use of lay health workers. Most reviews reported a combination of outcomes related to IPT adherence and treatment completion rate but without a baseline or comparison rate. Generally, we found limited evidence to demonstrate that the studied interventions improved treatment completion. Conclusions While most of the interventions were not shown to improve IPT completion, integration of tuberculosis and HIV services yielded high treatment completion rates in some settings. The lack of data from high burden TB settings limits applicability. Further research to assess different IPT delivery interventions, including those that address barriers to care in at-risk populations, is urgently needed to identify the most effective practices for IPT delivery and TB control in high TB burden settings. PMID:24886159

  12. Oral antioxidant therapy improves endothelial function in Type 1 but not Type 2 diabetes mellitus.

    PubMed

    Beckman, Joshua A; Goldfine, Allison B; Gordon, Mary Beth; Garrett, Leslie A; Keaney, John F; Creager, Mark A

    2003-12-01

    Oxidative stress decreases the bioavailability of endothelium-derived nitric oxide in diabetic patients. We investigated whether impaired endothelium-dependent vasodilation (EDV) in diabetes can be improved by long-term administration of oral antioxidants. Forty-nine diabetic subjects [26 Type 1 (T1) and 23 Type 2 (T2)] and 45 matched healthy control subjects were randomized to receive oral vitamin C (1,000 mg) and vitamin E (800 IU) daily or matching placebo for 6 mo. Vascular ultrasonography was used to determine brachial artery EDV and endothelium-independent vasodilation (EIV). EDV was decreased in both T1 (4.9 +/- 0.9%, P = 0.015) and T2 (4.1 +/- 1.0%, P < 0.01) subjects compared with control subjects (7.7 +/- 0.7%). EIV was decreased in T2 (15.0 +/- 1.2%, P < 0.01) but not T1 subjects (18.5 +/- 2.3%, P = 0.3) compared with controls (21.8 +/- 1.8%). Administration of antioxidant vitamins increased EDV in T1 (by 3.4 +/- 1.4%, P = 0.023) but not T2 subjects (by 0.5. +/- 0.4%, P = 0.3). Antioxidant therapy had no significant affect on EIV. Oral antioxidant therapy improves EDV in T1 but not T2 diabetes. These results are consistent with the lack of clinical benefit in studies that have included primarily T2 diabetic patients.

  13. Improving intermittent androgen deprivation therapy: lessons learned from basic and translational research

    PubMed Central

    Parikh, Rahul A; Pascal, Laura E; Davies, Benjamin J; Wang, Zhou

    2014-01-01

    Intermittent androgen deprivation therapy (IADT) is an alternative to continuous androgen deprivation therapy (ADT) in prostate cancer patients with nonmetastatic disease. ADT is associated with numerous side effects such as hot flashes, sexual dysfunction, anemia, fatigue, loss of muscle mass, osteoporosis, metabolic syndrome and premature cardiovascular disease. IADT was developed with the intention of improving the quality of life and to delay progression of prostate cancer to castration resistance. The benefits of slightly improved quality of life by IADT compared to ADT were demonstrated in multiple clinical trials. IADT was noted to be noninferior to ADT in patients with biochemical recurrence of prostate cancer but in studies performed in patients with metastatic prostate cancer, the results were inconclusive. Our recent studies suggested that the administration of 5 alpha-reductase inhibitors during the off-cycle of IADT can significantly prolong the survival of mice bearing androgen-sensitive prostate tumors when off-cycle duration was short. This review discusses the survival benefit of 5 alpha-reductase inhibition in IADT in animal models and the potential translation of this finding into clinic. PMID:24759577

  14. Improvements in performance following optometric vision therapy in a child with dyspraxia.

    PubMed

    Hurst, Caroline M F; Van de Weyer, Sarah; Smith, Claire; Adler, Paul M

    2006-03-01

    SS, an 8-year-old boy with dyspraxia, presented for behavioural optometry assessment. He had been diagnosed with a subtle form of dyspraxia by his paediatric occupational therapist, based on poor proprioception, delayed bilateral integration and poor visual perception. A full visual assessment was carried out. SS was given a programme of reflex inhibition exercises for 3 months. Then, a programme of optometric vision therapy (OVT) exercises was prescribed at home and in practice for a period of 8 months. SS was assessed using a battery of occupational therapy Sensory Integration and Praxis Tests (SIPT) before optometric intervention, and after OVT. There were significant improvements in fusional reserves, accommodative facility and oculomotor control of pursuit and saccadic eye movements. His reading level had changed by 4 years in 11 months. The SIPT results showed improvements in the visual and motor/visual perception subtests, confirming the significant changes in visual perceptual performance. Consideration is given to treatment modalities for dyspraxia, and the studies confirming their effectivity of approach. This case study provides evidence supporting the use of OVT eye exercises in dyspraxia, ocular motility, accommodative dysfunction, learning difficulties and sports performance. The need for further research and inter-professional working is discussed.

  15. Investigation of public exposure resulted from the radioiodine delay tank facility of nuclear medicine department

    SciTech Connect

    Yusof, Mohd Fahmi Mohd Ali, Abdul Muhaimin Mat; Abdullah, Reduan; Idris, Abdullah Waidi

    2016-01-22

    The study is carried out to assess the exposure rate that could contribute to public exposure in a radioiodine ward delay tank facility of Radiotherapy, Oncology and Nuclear Medicine, Department, Hospital Universiti Sains Malaysia (HUSM). The exposure rate at several locations including the delay tank room, doorway and at the public walking route was measured using Victoreen 415P-RYR survey meter. The radioactive level of the {sup 131}I waste was measured using Captus 3000 well counting system. The results showed that exposure rate and total count of the delay tank sample increased when the radioiodine ward was fully occupied with patient and reduced when the ward was vacant. Occupancy of radioiodine ward for two consecutive weeks had dramatically increased the exposure rate around the delay tank and radioactive level of {sup 131}I waste. The highest exposure rate and radioactive level was recorded when the ward was occupied for two consecutive weeks with 177.00 µR/h and 58.36 kcpm respectively. The exposure rate decreased 15.76 % when the door of the delay tank room was closed. The exposure rate at public walking route decreased between 15.58 % and 36.92 % as the distance increased between 1 and 3 m.

  16. Effects of skeleton structure on necrosis targeting and clearance properties of radioiodinated dianthrones.

    PubMed

    Zhang, Dongjian; Jiang, Cuihua; Yang, Shengwei; Gao, Meng; Huang, Dejian; Wang, Xiaoning; Shao, Haibo; Feng, Yuanbo; Sun, Ziping; Ni, Yicheng; Zhang, Jian; Yin, Zhiqi

    2016-01-01

    Necrosis avid agents (NAAs) can be used for diagnose of necrosis-related diseases, evaluation of therapeutic responses and targeted therapeutics of tumor. In order to probe into the effects of molecular skeleton structure on necrosis targeting and clearance properties of radioiodinated dianthrones, four dianthrone compounds with the same substituents but different skeletal structures, namely Hypericin (Hyp), protohypericin (ProHyp), emodin dianthrone mesomer (ED-1) and emodin dianthrone raceme (ED-2) were synthesized and radioiodinated. Then radioiodinated dianthrones were evaluated in vitro for their necrosis avidity in A549 lung cancer cells untreated and treated with H2O2. Their biodistribution and pharmacokinetic properties were determined in rat models of induced necrosis. In vitro cell assay revealed that destruction of rigid skeleton structure dramatically reduced their necrosis targeting ability. Animal studies demonstrated that destruction of rigid skeleton structure dramatically reduced the necrotic tissue uptake and speed up the clearance from the most normal tissues for the studied compounds. Among these (131)I-dianthrones, (131)I-Hyp exhibited the highest uptake and persistent retention in necrotic tissues. Hepatic infarction could be clearly visualized by SPECT/CT using (131)I-Hyp as an imaging probe. The results suggest that the skeleton structure of Hyp is the lead structure for further structure optimization of this class of NAAs.

  17. Influence of radioiodination on the adsorption of IgG and serum albumin to polystyrene

    SciTech Connect

    Walsh, J.; Gosling, J.P.

    1986-11-01

    The adsorption of radioiodinated rabbit IgG and bovine serum albumin (BSA) to polystyrene tubes was investigated. Adsorption isotherms where the proportion of the protein bound was relatively constant over a range of intermediate protein concentrations, and where the proportion bound was protein dependent, were obtained. To investigate the effects of radioiodination, proteins labelled to give a wide range of substitution ratios (0.03 to 3.7 /sup 125/I/ protein molecule) were employed. While labeling did not appear to affect BSA adsorption, the kinetics of IgG binding were altered in a number of ways. The proportion bound in the concentration independent region was decreased even at substitution ratios less than or equal to 0.2. In addition, while all preparations of iodinated BSA, and IgG preparations with less than or equal to 1.6 /sup 125/I/IgG, gave bimodal adsorption isotherms, with more heavily labeled IgG (less than or equal to 2.5 /sup 125/I/IgG) the apparent high affinity binding to the plastic surface was abolished. These results indicate that radioiodination substantially alters the kinetics of the binding of IgG to polystyrene. In addition, the results obtained are discussed with respect to previous relevant and often apparently contradictory findings.

  18. Investigation of public exposure resulted from the radioiodine delay tank facility of nuclear medicine department

    NASA Astrophysics Data System (ADS)

    Yusof, Mohd Fahmi Mohd; Ali, Abdul Muhaimin Mat; Abdullah, Reduan; Idris, Abdullah Waidi

    2016-01-01

    The study is carried out to assess the exposure rate that could contribute to public exposure in a radioiodine ward delay tank facility of Radiotherapy, Oncology and Nuclear Medicine, Department, Hospital Universiti Sains Malaysia (HUSM). The exposure rate at several locations including the delay tank room, doorway and at the public walking route was measured using Victoreen 415P-RYR survey meter. The radioactive level of the 131I waste was measured using Captus 3000 well counting system. The results showed that exposure rate and total count of the delay tank sample increased when the radioiodine ward was fully occupied with patient and reduced when the ward was vacant. Occupancy of radioiodine ward for two consecutive weeks had dramatically increased the exposure rate around the delay tank and radioactive level of 131I waste. The highest exposure rate and radioactive level was recorded when the ward was occupied for two consecutive weeks with 177.00 µR/h and 58.36 kcpm respectively. The exposure rate decreased 15.76 % when the door of the delay tank room was closed. The exposure rate at public walking route decreased between 15.58 % and 36.92 % as the distance increased between 1 and 3 m.

  19. [Improvements in motor and non-motor symptoms in parkinson patients under ropinirole therapy].

    PubMed

    Buchwald, B; Angersbach, D; Jost, W H

    2007-04-01

    Ropinirole is a non-ergoline selective D2 dopamine agonist. Its efficacy and safety has been established in several controlled double-blind studies in patients with early and advanced Parkinson's disease. It is assumed that the improvement in the activities of daily living under ropinirole is not only due to the improved motor symptoms but also due to the improvement of non-motor symptoms like symptoms of mood and anxiety. The objective of this post marketing surveillance study was to show that under the conditions of the daily routine in the neurologic practice ropinirole may not only improve motor symptoms, the activity of daily living and complications of the treatment (dystonia, dyskinesia) but also alleviate symptoms of depression and anxiety. A total of 110 neurological practices enrolled 327 patients in early and advanced stages of the disease (139 females, 188-males; mean age: 67 years). They were treated with ropinirole as monotherapy and as adjunctive therapy with l-dopa over a period of 12 - 14 weeks. Selected symptoms of the Unified Parkinson's Disease Rating Scale (UPDRS) part II-IV and symptoms of depression and anxiety were rated by the clinicians. Mood and functional impairment in job, family and social life were rated by the patients using selected items of the Beck Depression Inventory and the Sheehan Disability Scale (SDS). The different subtypes, i. e. the akinetic-rigid, tremor-dominant and the mixed subtype, are described separately. The total UPDRS score at baseline was similar for all three subtypes and there was also a similar improvement in the three groups under ropinirole. Both according to self-rating and to clinician rating the symptoms of depression and anxiety at baseline were more severe in the akinetic-rigid and the mixed subtype compared to the tremor-dominant subtype. The symptoms considerably improved and were reduced by 48 % under therapy with ropinirole. Adverse events were reported by 7.7 % of the patients. The surveillance

  20. Serial thyroid iodine content in hyperthyroid patients treated with radioiodine

    SciTech Connect

    Lee, G.S.; Sandler, M.P.; Patton, J.A.; Brill, A.B.

    1986-02-01

    X-ray fluorescent scanning was used to measure initial thyroidal iodine content in 64 patients diagnosed as being hyperthyroid and selected for I-131 therapy, and serially in 48 of these patients after therapy in an attempt to determine those patients that were at high risk of becoming hypothyroid. Iodine content fell rapidly after therapy, reaching a nadir at about three months. Based on the population studied, the chance of early hypothyroidism (within 12 months) is about 80% if the iodine content measured at three months is less than 2 mg. If the iodine content is greater than 2 mg, the chance is only about 14%. The serial measurement of thyroidal iodine content (with x-ray fluorescent scanning) may allow early identification of those patients at high risk of developing permanent hypothyroidism following a therapeutic dose of I-131.

  1. Long-term pioglitazone therapy improves arterial stiffness in patients with type 2 diabetes mellitus.

    PubMed

    Harashima, Keiichiro; Hayashi, Junichi; Miwa, Takashi; Tsunoda, Tooru

    2009-06-01

    Pioglitazone, a peroxisome proliferator-activated receptor gamma agonist, not only improves insulin resistance and glycemic control, but may also have additional beneficial vascular effects in patients with type 2 diabetes mellitus. We investigated whether pioglitazone had an influence on arterial stiffness, which is an independent predictor of cardiovascular events, in 204 patients with type 2 diabetes mellitus. A prospective, nonrandomized, open-label trial was performed that involved 41 patients treated with pioglitazone, 46 patients receiving sulfonylureas, 67 patients on insulin, and 50 patients on diet/exercise only. The follow-up period was 56 +/- 3 months. Arterial stiffness was evaluated by using the arterial stiffness index (ASI), which was based on analysis of the pulse wave amplitude pattern obtained during automated blood pressure measurement in the upper limb. The 4 groups had a similar baseline ASI, which was greater than the reference range in each group. Although antidiabetic therapies improved hemoglobin A(1c) and low-density lipoprotein cholesterol, ASI only decreased significantly in the pioglitazone group. Thus, pioglitazone improved abnormal arterial stiffness in patients with type 2 diabetes mellitus via a mechanism beyond the metabolic improvement. These findings may have important clinical implications in the use of pioglitazone in patients with type 2 diabetes mellitus.

  2. Use of a risk assessment method to improve the safety of negative pressure wound therapy.

    PubMed

    Lelong, Anne-Sophie; Martelli, Nicolas; Bonan, Brigitte; Prognon, Patrice; Pineau, Judith

    2014-06-01

    To conduct a risk analysis of the negative pressure wound therapy (NPWT) care process and to improve the safety of NPWT, a working group of nurses, hospital pharmacists, physicians and hospital managers performed a risk analysis for the process of NPWT care. The failure modes, effects and criticality analysis (FMECA) method was used for this analysis. Failure modes and their consequences were defined and classified as a function of their criticality to identify priority actions for improvement. By contrast to classical FMECA, the criticality index (CI) of each consequence was calculated by multiplying occurrence, severity and detection scores. We identified 13 failure modes, leading to 20 different consequences. The CI of consequences was initially 712, falling to 357 after corrective measures were implemented. The major improvements proposed included the establishment of 6-monthly training cycles for nurses, physicians and surgeons and the introduction of computerised prescription for NPWT. The FMECA method also made it possible to prioritise actions as a function of the criticality ranking of consequences and was easily understood and used by the working group. This study is, to our knowledge, the first to use the FMECA method to improve the safety of NPWT.

  3. Targeting of lacZ reporter gene expression with radioiodine-labelled phenylethyl-beta- d-thiogalactopyranoside.

    PubMed

    Lee, Kyung-Han; Byun, Sang Sung; Choi, Joon Hun; Paik, Jin-Young; Choe, Yearn Seong; Kim, Byung-Tae

    2004-03-01

    There has recently been increasing interest in the development of radioprobes that specifically target proteins transcribed from expression of reporter genes of interest. The purpose of this study was to develop a radioprobe that targets one of the most widely used reporter genes, the bacterial lacZ gene. We synthesised and purified radioiodine-labelled phenylethyl-beta- d-thiogalactopyranoside (PETG), a competitive inhibitor specific against Escherichia coli beta-galactosidase. We showed that [(125)I]iodo-PETG specifically binds to beta-galactosidase as verified by column chromatography and polyacrylamide gel electrophoresis after incubation of radiotracer with the protein. We also showed through enzyme kinetic studies that iodo-PETG retains inhibitory action against beta-galactosidase activity. COS-7 cells infected with a recombinant adenovirus expressing the lacZ gene had viral titre-dependent enhancements in [(125)I]iodo-PETG uptake ( r(2)=0.897; P=0.001), which reached up to 642.5%+/-16.7% of control levels ( P<0.00001). Moreover, the level of uptake was highly correlated to luminescent measurements of beta-galactosidase activity ( r(2)=0.878; P<0.0001). These results confirm that radioiodine-labelled PETG specifically targets beta-galactosidase and that its uptake rates faithfully reflect levels of expression of the lacZ reporter gene. Further investigations were performed in nude mice bearing human neuroblastoma tumours transferred with the lacZ gene. Compared with control tumours, lacZ-expressing tumours were slightly better visualised on [(123)I]iodo-PETG images and had a modest increase in tumour to muscle count ratio (2.6+/-0.2 vs 1.9+/-0.1, P<0.05). The present results provide proof-of-principle for the potential of radiolabelled inhibitors as promising radiotracers to monitor lacZ gene expression levels. Future modifications to improve cell permeability should enhance in vivo contrast levels and may allow the use of radiolabelled beta

  4. Improvement in health status following bronchopulmonary hygiene physical therapy in patients with bronchiectasis.

    PubMed

    Mutalithas, Kugathasan; Watkin, Gillian; Willig, Briony; Wardlaw, Andrew; Pavord, Ian D; Birring, Surinder S

    2008-08-01

    Chronic productive cough is a common symptom in patients with bronchiectasis that is associated with a reduction in health-related quality of life (QOL). Bronchopulmonary hygiene physical therapy (BHPT) is widely prescribed for patients with bronchiectasis, although the evidence for its efficacy is limited. We set out to prospectively evaluate the impact of BHPT on health-related QOL in patients with non-cystic fibrosis bronchiectasis. We assessed cough symptoms (0-100mm visual analogue scale; VAS) and cough-related QOL in 53 patients with stable non-cystic fibrosis bronchiectasis at baseline and >4 weeks after outpatient-based BHPT. Cough specific health status was assessed with the Leicester Cough Questionnaire (LCQ; total score range 3-21, higher scores representing better QOL). All patients with bronchiectasis complained of cough as the major symptom and had mean (SEM) FEV(1) of 2.1 (0.1)L. Cough-related health status was reduced at baseline; mean (SEM) LCQ score 14.3 (0.6). There were significant improvements in cough symptoms (mean cough VAS before 43.3 (3.6) vs after 27.5 (3.1); mean difference 15.8; 95% CI of difference 9.6-22; p<0.0001) and cough-related health status after BHPT (mean LCQ total score before 14.2 vs after 17.3; mean difference 3.1; 95% confidence interval of difference 2.4-3.9; p<0.001). A significant improvement was seen in all LCQ health-related domains (physical, psychological and social; all p<0.001). Our findings suggest that bronchopulmonary hygiene physical therapy can lead to a significant improvement in cough-related quality of life.

  5. Magnetic Resonance Therapy Improves Clinical Phenotype and EEG Alpha Power in Posttraumatic Stress Disorder

    PubMed Central

    Taghva, Alexander; Silvetz, Robert; Ring, Alex; Kim, Keun-young A.; Murphy, Kevin T.; Liu, Charles Y.; Jin, Yi

    2015-01-01

    Background: Posttraumatic stress disorder (PTSD) is a disabling and prevalent psychiatric disorder with limited effective treatment options. In addition to the clinical features of the disease, pathologic changes in the electroencephalogram (EEG), including decreased alpha power, have been reported. Objectives: To determine if magnetic brain stimulation can induce normalization of EEG abnormalities and improve clinical symptoms in PTSD in a preliminary, open-label evaluation. Materials and Methods: We reviewed prospectively-collected data on 21 veterans that were consecutively-treated for PTSD. Magnetic resonance therapy (MRT) was administered for two weeks at treatment frequencies based on frequency-domain analysis of each patient’s dominant alpha-band EEG frequencies and resting heart rate. Patients were evaluated on the PTSD checklist (PCL-M) and pre- and post-treatment EEGs before and after MRT. Results: Of the 21 patients who initiated therapy, 16 completed treatment. Clinical improvements on the PCL-M were seen in these 16 patients, with an average pre-treatment score of 54.9 and post-treatment score of 31.8 (P < 0.001). In addition, relative global EEG alpha-band (8 - 13 Hz) power increased from 32.0 to 38.5 percent (P = 0.013), and EEG delta-band (1 - 4 Hz) power decreased from 32.3 percent to 26.8 percent (P = 0.028). Conclusions: These open-label data show trends toward normalization of EEG and concomitant clinical improvement using magnetic stimulation for PTSD. PMID:26839865

  6. Evolution of Technology for Continuous Renal Replacement Therapy: Forty Years of Improvements.

    PubMed

    Ronco, Claudio

    2017-01-01

    Continuous arteriovenous hemofiltration (CAVH) was proposed in 1977 as an alternative treatment for acute renal failure in patients in whom peritoneal dialysis or hemodialysis was clinically or technically precluded. In the mid-1980s, this technique was extended to infants and children. CAVH presented important advantages in the areas of hemodynamic stability, control of circulating volume, and nutritional support. However, there were serious shortcomings such as the need for arterial cannulation and limited solute clearance. These problems were solved by the introduction of continuous arteriovenous hemodiafiltration (CAVHDF) and continuous arteriovenous hemodialysis (CAVHD) where uremic control could be by increasing countercurrent dialysate flow rates to 1.5 or 2 liters/h as necessary, or by venovenous techniques utilizing a double-lumen central venous catheter for vascular access. Thus, continuous venovenous hemofiltration replaced CAVH because of its improved performance and safety. From the initial adoptive technology, specific machines have been designed to permit safe and reliable performance of the therapy. These new machines have progressively undergone a series of technological steps that have resulted in the highly sophisticated equipment utilized today. A significant number of advances have taken place since the beginning of continuous renal replacement therapy. In particular, there have been successful experiments with high-volume hemofiltration and high-permeability hemofiltration. The additional and combined use of sorbent has also been tested successfully. Progress has been made in the technology as well as the understanding of the pathophysiology of acute kidney injury. Today, new biomaterials and new devices are available and new frontiers are on the horizon. Although improvements have been made, a lot remains to be done. Critical care nephrology is expected to further evolve in the near future, especially in the area of information and

  7. Replanning During Intensity Modulated Radiation Therapy Improved Quality of Life in Patients With Nasopharyngeal Carcinoma

    SciTech Connect

    Yang Haihua; Hu Wei; Wang Wei; Chen Peifang; Ding Weijun; Luo Wei

    2013-01-01

    Purpose: Anatomic and dosimetric changes have been reported during intensity modulated radiation therapy (IMRT) in patients with nasopharyngeal carcinoma (NPC). The purpose of this study was to evaluate the effects of replanning on quality of life (QoL) and clinical outcomes during the course of IMRT for NPC patients. Methods and Materials: Between June 2007 and August 2011, 129 patients with NPC were enrolled. Forty-three patients received IMRT without replanning, while 86 patients received IMRT replanning after computed tomography (CT) images were retaken part way through therapy. Chinese versions of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 and Head and Neck Quality of Life Questionnaire 35 were completed before treatment began and at the end of treatment and at 1, 3, 6, and 12 months after the completion of treatment. Overall survival (OS) data were compared using the Kaplan-Meier method. Results: IMRT replanning had a profound impact on the QoL of NPC patients, as determined by statistically significant changes in global QoL and other QoL scales. Additionally, the clinical outcome comparison indicates that replanning during IMRT for NPC significantly improved 2-year local regional control (97.2% vs 92.4%, respectively, P=.040) but did not improve 2-year OS (89.8% vs 82.2%, respectively, P=.475). Conclusions: IMRT replanning improves QoL as well as local regional control in patients with NPC. Future research is needed to determine the criteria for replanning for NPC patients undergoing IMRT.

  8. Neural Stem Cell-Mediated Intratumoral Delivery of Gold Nanorods Improves Photothermal Therapy

    PubMed Central

    2015-01-01

    Plasmonic photothermal therapy utilizes biologically inert gold nanorods (AuNRs) as tumor-localized antennas that convert light into heat capable of eliminating cancerous tissue. This approach has lower morbidity than surgical resection and can potentially synergize with other treatment modalities including chemotherapy and immunotherapy. Despite these advantages, it is still challenging to obtain heating of the entire tumor mass while avoiding unnecessary collateral damage to surrounding healthy tissue. It is therefore critical to identify innovative methods to distribute an effective concentration of AuNRs throughout tumors without depositing them in surrounding healthy tissue. Here we demonstrate that AuNR-loaded, tumor-tropic neural stem cells (NSCs) can be used to improve the intratumoral distribution of AuNRs. A simple UV–vis technique for measuring AuNR loading within NSCs was established. It was then confirmed that NSC viability is unimpaired following AuNR loading and that NSCs retain AuNRs long enough to migrate throughout tumors. We then demonstrate that intratumoral injections of AuNR-loaded NSCs are more efficacious than free AuNR injections, as evidenced by reduced recurrence rates of triple-negative breast cancer (MDA-MB-231) xenografts following NIR exposure. Finally, we demonstrate that the distribution of AuNRs throughout the tumors is improved when transported by NSCs, likely resulting in the improved efficacy of AuNR-loaded NSCs as compared to free AuNRs. These findings highlight the advantage of combining cellular therapies and nanotechnology to generate more effective cancer treatments. PMID:25375246

  9. Has the use of computers in radiation therapy improved the accuracy in radiation dose delivery?

    NASA Astrophysics Data System (ADS)

    Van Dyk, J.; Battista, J.

    2014-03-01

    Purpose: It is well recognized that computer technology has had a major impact on the practice of radiation oncology. This paper addresses the question as to how these computer advances have specifically impacted the accuracy of radiation dose delivery to the patient. Methods: A review was undertaken of all the key steps in the radiation treatment process ranging from machine calibration to patient treatment verification and irradiation. Using a semi-quantitative scale, each stage in the process was analysed from the point of view of gains in treatment accuracy. Results: Our critical review indicated that computerization related to digital medical imaging (ranging from target volume localization, to treatment planning, to image-guided treatment) has had the most significant impact on the accuracy of radiation treatment. Conversely, the premature adoption of intensity-modulated radiation therapy has actually degraded the accuracy of dose delivery compared to 3-D conformal radiation therapy. While computational power has improved dose calibration accuracy through Monte Carlo simulations of dosimeter response parameters, the overall impact in terms of percent improvement is relatively small compared to the improvements accrued from 3-D/4-D imaging. Conclusions: As a result of computer applications, we are better able to see and track the internal anatomy of the patient before, during and after treatment. This has yielded the most significant enhancement to the knowledge of "in vivo" dose distributions in the patient. Furthermore, a much richer set of 3-D/4-D co-registered dose-image data is thus becoming available for retrospective analysis of radiobiological and clinical responses.

  10. Use of peers to improve adherence to antiretroviral therapy: a global network meta-analysis

    PubMed Central

    Kanters, Steve; Park, Jay JH; Chan, Keith; Ford, Nathan; Forrest, Jamie; Thorlund, Kristian; Nachega, Jean B; Mills, Edward J

    2016-01-01

    Introduction It is unclear whether using peers can improve adherence to antiretroviral therapy (ART). To construct the World Health Organization's global guidance on adherence interventions, we conducted a systematic review and network meta-analysis to determine the effectiveness of using peers for achieving adequate adherence and viral suppression. Methods We searched for randomized clinical trials of peer-based interventions to promote adherence to ART in HIV populations. We searched six electronic databases from inception to July 2015 and major conference abstracts within the last three years. We examined the outcomes of adherence and viral suppression among trials done worldwide and those specific to low- and middle-income countries (LMIC) using pairwise and network meta-analyses. Results and discussion Twenty-two trials met the inclusion criteria. We found similar results between pairwise and network meta-analyses, and between the global and LMIC settings. Peer supporter+Telephone was superior in improving adherence than standard-of-care in both the global network (odds-ratio [OR]=4.79, 95% credible intervals [CrI]: 1.02, 23.57) and the LMIC settings (OR=4.83, 95% CrI: 1.88, 13.55). Peer support alone, however, did not lead to improvement in ART adherence in both settings. For viral suppression, we found no difference of effects among interventions due to limited trials. Conclusions Our analysis showed that peer support leads to modest improvement in adherence. These modest effects may be due to the fact that in many settings, particularly in LMICs, programmes already include peer supporters, adherence clubs and family disclosures for treatment support. Rather than introducing new interventions, a focus on improving the quality in the delivery of existing services may be a more practical and effective way to improve adherence to ART. PMID:27914185

  11. Improving performance of Zambia Defence Force antiretroviral therapy providers: evaluation of a standards-based approach

    PubMed Central

    Kim, Young Mi; Banda, Joseph; Kanjipite, Webby; Sarkar, Supriya; Bazant, Eva; Hiner, Cyndi; Tholandi, Maya; Reinhardt, Stephanie; Njobvu, Panganani Dalisani; Kols, Adrienne; Benavides, Bruno

    2013-01-01

    ABSTRACT Background: The Zambia Defence Force (ZDF) has applied the Standards-Based Management and Recognition (SBM-R®) approach, which uses detailed performance standards, at some health facilities to improve HIV-related services offered to military personnel and surrounding civilian communities. This study examines the effectiveness of the SBM-R approach in improving facility readiness and provider performance at ZDF facilities. Methods: We collected data on facility readiness and provider performance before and after the 2010–2012 intervention at 4 intervention sites selected for their relatively poor performance and 4 comparison sites. Assessors observed whether each facility met 16 readiness standards and whether providers met 9 performance standards during consultations with 354 returning antiretroviral therapy (ART) clients. We then calculated the percentages of criteria achieved for each readiness and performance standard and conducted bivariate and multivariate analyses of provider performance data. Results: Facilities' ART readiness scores exceeded 80% before the intervention at both intervention and comparison sites. At endline, scores improved on 4 facility readiness standards in the intervention group but on only 1 standard in the comparison group. Multivariate analysis found that the overall provider performance score increased significantly in the intervention group (from 58% to 84%; P<.01) but not in the comparison group (from 62% to 70%). The before-and-after improvement in scores was significantly greater among intervention sites than among comparison sites for 2 standards—initial assessment of the client's condition and nutrition counseling. Conclusion: The standards-based approach, which involved intensive and mutually reinforcing intervention activities, showed modest improvements in some aspects of providers' performance during ART consultations. Further research is needed to determine whether improvements in provider performance affect

  12. Children with Down Syndrome Improved in Motor Functioning and Muscle Tone Following Massage Therapy

    ERIC Educational Resources Information Center

    Hernandez-Reif, Maria; Field, Tiffany; Largie, Shay; Mora, Dana; Bornstein, Joan; Waldman, Ronnie

    2006-01-01

    Twenty-one moderate to high functioning young children (mean age, two years) with Down syndrome receiving early intervention (physical therapy, occupational therapy and speech therapy) were randomly assigned to additionally receive two 0.5-hour massage therapy or reading sessions (control group) per week for two months. On the first and last day…

  13. Can particle beam therapy be improved using helium ions? - a planning study focusing on pediatric patients.

    PubMed

    Knäusl, Barbara; Fuchs, Hermann; Dieckmann, Karin; Georg, Dietmar

    2016-06-01

    Aim To explore the potential of scanned helium ion beam therapy ((4)He) compared to proton therapy in a comparative planning study focusing on pediatric patients. This was motivated by the superior biological and physical characteristics of (4)He. Material and methods For eleven neuroblastoma (NB), nine Hodgkin lymphoma (HL), five Wilms tumor (WT), five ependymoma (EP) and four Ewing sarcoma (EW) patients, treatment plans were created for protons and (4)He. Dose prescription to the planning target volume (PTV) was 21 Gy [relative biological effectiveness (RBE)] (NB), 19.8 Gy (RBE) (HL), 25.2 Gy (RBE) for the WT boost volume and 54 Gy (RBE) for EP and EW patients. A pencil beam algorithm for protons (constant RBE = 1.1) and (4)He was implemented in the treatment planning system Hyperion. For (4)He the relative biological effectiveness (RBE) was calculated with a 'zonal' model based on different linear energy transfer regions. Results Target constraints were fulfilled for all indications. For NB patients differences for kidneys and liver were observed for all dose-volume areas, except the high-dose volume. The body volume receiving up to 12.6 Gy (RBE) was reduced by up to 10% with (4)He. For WT patients the mean and high-dose volume for the liver was improved when using (4)He. For EP normal tissue dose was reduced using (4)He with 12.7% of the voxels receiving higher doses using protons. For HL and EW sarcoma patients the combination of large PTV volumes with the position of the organs at risk (OARs) obliterated the differences between the two particle species, while patients with the heart close to the PTV could benefit from (4)He. Conclusion Treatment plan quality improved with (4)He compared to proton plans, but advantages in OAR sparing were depending on indication and tumor geometries. These first results of scanned (4)He therapy motivate comprehensive research on (4)He, including acquisition of experimental data to improve modeling of (4)He.

  14. The effects of very early mirror therapy on functional improvement of the upper extremity in acute stroke patients.

    PubMed

    Yeldan, Ipek; Huseyınsınoglu, Burcu Ersoz; Akıncı, Buket; Tarakcı, Ela; Baybas, Sevim; Ozdıncler, Arzu Razak

    2015-11-01

    [Purpose] The aim of the study was to evaluate the effects of a very early mirror therapy program on functional improvement of the upper extremity in acute stroke patients. [Subjects] Eight stroke patients who were treated in an acute neurology unit were included in the study. [Methods] The patients were assigned alternatively to either the mirror therapy group receiving mirror therapy and neurodevelopmental treatment or the neurodevelopmental treatment only group. The primary outcome measures were the upper extremity motor subscale of the Fugl-Meyer Assessment, Motricity Index upper extremity score, and the Stroke Upper Limb Capacity Scale. Somatosensory assessment with the Ayres Southern California Sensory Integration Test, and the Barthel Index were used as secondary outcome measures. [Results] No statistically significant improvements were found for any measures in either group after the treatment. In terms of minimally clinically important differences, there were improvements in Fugl-Meyer Assessment and Barthel Index in both mirror therapy and neurodevelopmental treatment groups. [Conclusion] The results of this pilot study revealed that very early mirror therapy has no additional effect on functional improvement of upper extremity function in acute stroke patients. Multicenter trials are needed to determine the results of early application of mirror therapy in stroke rehabilitation.

  15. The effects of very early mirror therapy on functional improvement of the upper extremity in acute stroke patients

    PubMed Central

    Yeldan, Ipek; Huseyınsınoglu, Burcu Ersoz; Akıncı, Buket; Tarakcı, Ela; Baybas, Sevim; Ozdıncler, Arzu Razak

    2015-01-01

    [Purpose] The aim of the study was to evaluate the effects of a very early mirror therapy program on functional improvement of the upper extremity in acute stroke patients. [Subjects] Eight stroke patients who were treated in an acute neurology unit were included in the study. [Methods] The patients were assigned alternatively to either the mirror therapy group receiving mirror therapy and neurodevelopmental treatment or the neurodevelopmental treatment only group. The primary outcome measures were the upper extremity motor subscale of the Fugl-Meyer Assessment, Motricity Index upper extremity score, and the Stroke Upper Limb Capacity Scale. Somatosensory assessment with the Ayres Southern California Sensory Integration Test, and the Barthel Index were used as secondary outcome measures. [Results] No statistically significant improvements were found for any measures in either group after the treatment. In terms of minimally clinically important differences, there were improvements in Fugl-Meyer Assessment and Barthel Index in both mirror therapy and neurodevelopmental treatment groups. [Conclusion] The results of this pilot study revealed that very early mirror therapy has no additional effect on functional improvement of upper extremity function in acute stroke patients. Multicenter trials are needed to determine the results of early application of mirror therapy in stroke rehabilitation. PMID:26696729

  16. Improving the safety of cell therapy with the TK-suicide gene

    PubMed Central

    Greco, Raffaella; Oliveira, Giacomo; Stanghellini, Maria Teresa Lupo; Vago, Luca; Bondanza, Attilio; Peccatori, Jacopo; Cieri, Nicoletta; Marktel, Sarah; Mastaglio, Sara; Bordignon, Claudio; Bonini, Chiara; Ciceri, Fabio

    2015-01-01

    While opening new frontiers for the cure of malignant and non-malignant diseases, the increasing use of cell therapy poses also several new challenges related to the safety of a living drug. The most effective and consolidated cell therapy approach is allogeneic hematopoietic stem cell transplantation (HSCT), the only cure for several patients with high-risk hematological malignancies. The potential of allogeneic HSCT is strictly dependent on the donor immune system, particularly on alloreactive T lymphocytes, that promote the beneficial graft-versus-tumor effect (GvT), but may also trigger the detrimental graft-versus-host-disease (GvHD). Gene transfer technologies allow to manipulate donor T-cells to enforce GvT and foster immune reconstitution, while avoiding or controlling GvHD. The suicide gene approach is based on the transfer of a suicide gene into donor lymphocytes, for a safe infusion of a wide T-cell repertoire, that might be selectively controlled in vivo in case of GvHD. The herpes simplex virus thymidine kinase (HSV-TK) is the suicide gene most extensively tested in humans. Expression of HSV-TK in donor lymphocytes confers lethal sensitivity to the anti-herpes drug, ganciclovir. Progressive improvements in suicide genes, vector technology and transduction protocols have allowed to overcome the toxicity of GvHD while preserving the antitumor efficacy of allogeneic HSCT. Several phase I-II clinical trials in the last 20 years document the safety and the efficacy of HSV-TK approach, able to maintain its clear value over the last decades, in the rapidly progressing horizon of cancer cellular therapy. PMID:25999859

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

    PubMed

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

    2016-01-01

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

  18. Improvement of plasma endothelin-1 and nitric oxide in patients with systemic sclerosis by bosentan therapy.

    PubMed

    Kawashiri, Shin-ya; Ueki, Yukitaka; Terada, Kaoru; Yamasaki, Satoshi; Aoyagi, Kiyoshi; Kawakami, Atsushi

    2014-02-01

    The aim of this study was to evaluate the effects of bosentan on plasma endothelin-1 (ET-1) and nitric oxide (NO) as pulmonary hypertension (PH)-associated biochemical markers in patients with systemic sclerosis (SSc). Twenty-four SSc patients receiving bosentan for 24 weeks were registered in this prospective observational study. Ten patients were complicated with clinically suspected PH. Plasma levels of ET-1 and NO were assessed at baseline and after 24 weeks of treatment in SSc patients and in 15 healthy controls. Plasma levels of ET-1 and NO at baseline were significantly higher in SSc patients than in healthy controls (p < 0.000), and they were also significantly higher in SSc patients with PH than in those without PH (p < 0.01). Plasma ET-1 levels were significantly decreased after 24 weeks of bosentan therapy (p < 0.0001), and ET-1 levels of SSc patients with PH decreased to a level comparable to that in patients without PH. In the 10 SSc patients with PH, changes in plasma ET-1 levels during the 24 weeks of the study were significantly larger in the 5 patients whose functional class (FC) improved than in the 5 patients whose FC was unchanged (p < 0.05). Plasma NO levels were also slightly decreased in SSc patients after 24 weeks of bosentan therapy. Plasma ET-1 levels could reflect the presence and severity of PH in SSc patients. Additionally, changes in plasma ET-1 levels may indicate the response to bosentan therapy in SSc patients with PH.

  19. Improving the safety of cell therapy with the TK-suicide gene.

    PubMed

    Greco, Raffaella; Oliveira, Giacomo; Stanghellini, Maria Teresa Lupo; Vago, Luca; Bondanza, Attilio; Peccatori, Jacopo; Cieri, Nicoletta; Marktel, Sarah; Mastaglio, Sara; Bordignon, Claudio; Bonini, Chiara; Ciceri, Fabio

    2015-01-01

    While opening new frontiers for the cure of malignant and non-malignant diseases, the increasing use of cell therapy poses also several new challenges related to the safety of a living drug. The most effective and consolidated cell therapy approach is allogeneic hematopoietic stem cell transplantation (HSCT), the only cure for several patients with high-risk hematological malignancies. The potential of allogeneic HSCT is strictly dependent on the donor immune system, particularly on alloreactive T lymphocytes, that promote the beneficial graft-versus-tumor effect (GvT), but may also trigger the detrimental graft-versus-host-disease (GvHD). Gene transfer technologies allow to manipulate donor T-cells to enforce GvT and foster immune reconstitution, while avoiding or controlling GvHD. The suicide gene approach is based on the transfer of a suicide gene into donor lymphocytes, for a safe infusion of a wide T-cell repertoire, that might be selectively controlled in vivo in case of GvHD. The herpes simplex virus thymidine kinase (HSV-TK) is the suicide gene most extensively tested in humans. Expression of HSV-TK in donor lymphocytes confers lethal sensitivity to the anti-herpes drug, ganciclovir. Progressive improvements in suicide genes, vector technology and transduction protocols have allowed to overcome the toxicity of GvHD while preserving the antitumor efficacy of allogeneic HSCT. Several phase I-II clinical trials in the last 20 years document the safety and the efficacy of HSV-TK approach, able to maintain its clear value over the last decades, in the rapidly progressing horizon of cancer cellular therapy.

  20. Combination therapy of orally administered glycyrrhizin and UVB improved active-stage generalized vitiligo

    PubMed Central

    Mou, K.H.; Han, D.; Liu, W.L.; Li, P.

    2016-01-01

    Glycyrrhizin has been used clinically for several years due to its beneficial effect on immunoglobulin E (IgE)-induced allergic diseases, alopecia areata and psoriasis. In this study, glycyrrhizin, ultraviolet B light (UVB) or a combination of both were used to treat active-stage generalized vitiligo. One hundred and forty-four patients between the ages of 3 and 48 years were divided into three groups: group A received oral compound glycyrrhizin (OCG); group B received UVB applications twice weekly, and group C received OCG+UVB. Follow-ups were performed at 2, 4, and 6 months after the treatment was initiated. The Vitiligo Area Scoring Index (VASI) and the Vitiligo Disease Activity (VIDA) instrument were used to assess the affected body surface, at each follow-up. Results showed that 77.1, 75.0 and 87.5% in groups A, B and C, respectively, presented repigmentation of lesions. Responsiveness to therapy seemed to be associated with lesion location and patient compliance. Adverse events were limited and transient. This study showed that, although the three treatment protocols had positive results, OCG and UVB combination therapy was the most effective and led to improvement in disease stage from active to stable. PMID:27464024

  1. Optimizing Timing of Immunotherapy Improves Control of Tumors by Hypofractionated Radiation Therapy

    PubMed Central

    Baird, Jason R.; Savage, Talicia; Cottam, Benjamin; Friedman, David; Bambina, Shelly; Messenheimer, David J.; Fox, Bernard; Newell, Pippa; Bahjat, Keith S.; Gough, Michael J.; Crittenden, Marka R.

    2016-01-01

    The anecdotal reports of promising results seen with immunotherapy and radiation in advanced malignancies have prompted several trials combining immunotherapy and radiation. However, the ideal timing of immunotherapy with radiation has not been clarified. Tumor bearing mice were treated with 20Gy radiation delivered only to the tumor combined with either anti-CTLA4 antibody or anti-OX40 agonist antibody. Immunotherapy was delivered at a single timepoint around radiation. Surprisingly, the optimal timing of these therapies varied. Anti-CTLA4 was most effective when given prior to radiation therapy, in part due to regulatory T cell depletion. Administration of anti-OX40 agonist antibody was optimal when delivered one day following radiation during the post-radiation window of increased antigen presentation. Combination treatment of anti-CTLA4, radiation, and anti-OX40 using the ideal timing in a transplanted spontaneous mammary tumor model demonstrated tumor cures. These data demonstrate that the combination of immunotherapy and radiation results in improved therapeutic efficacy, and that the ideal timing of administration with radiation is dependent on the mechanism of action of the immunotherapy utilized. PMID:27281029

  2. Colloidal gold nanorings for improved photodynamic therapy through field-enhanced generation of reactive oxygen species

    NASA Astrophysics Data System (ADS)

    Hu, Yue; Yang, Yamin; Wang, Hongjun; Du, Henry

    2013-02-01

    Au nanostructures that exhibit strong localized surface plasmon resonance (SPR) have excellent potential for photo-medicine, among a host of other applications. Here, we report the synthesis and use of colloidal gold nanorings (GNRs) with potential for enhanced photodynamic therapy of cancer. The GNRs were fabricated via galvanic replacement reaction of sacrificial Co nanoparticles in gold salt solution with low molecular weight (Mw = 2,500) poly(vinylpyrrolidone) (PVP) as a stabilizing agent. The size and the opening of the GNRs were controlled by the size of the starting Co particles and the concentration of the gold salt. UV-Vis absorption measurements indicated the tunability of the SPR of the GNRs from 560 nm to 780 nm. MTT assay showed that GNRs were non-toxic and biocompatible when incubated with breast cancer cells as well as the healthy counterpart cells. GNRs conjugated with 5-aminolevulinic acid (5-ALA) photosensitizer precursor led to elevated formation of reactive oxygen species and improved efficacy of photodynamic therapy of breast cancer cells under light irradiation compared to 5-ALA alone. These results can be attributed to significantly enhance localized electromagnetic field of the GNRs.

  3. A Multidisciplinary Approach with Hyperbaric Oxygen Therapy Improve Outcome in Snake Bite Injuries

    PubMed Central

    Korambayil, Pradeoth Mukundan; Ambookan, Prashanth Varkey; Abraham, Siju Varghese; Ambalakat, Ajay

    2015-01-01

    Aim: Snakebite injuries are common in tropical India among those who are involved in outdoor activities. These injuries results in cellulitis, gangrene at the bite area, bleeding manifestations, compartment syndrome, regional lymphadenopathy, septicemia, hypotension, and disseminated intravascular coagulation (DIC) resulting in significant morbidity and mortality. The purpose of this study is to share our experience of multidisciplinary approach in the management of snakebite injuries of the extremities with various treatment modalities including hyperbaric oxygen (HBO) therapy, surgical debridement, and soft tissue reconstruction to provide an effective treatment for snake bite injuries. Methods: The study was conducted in the Department of Plastic Surgery, during the period October 2012–December 2014, wherein all the patients who were admitted with snakebite injuries were enrolled and the patients treated in plastic surgery department were included into the study. Out of total 766 patients, there were 323 patients treated with anti snake venom (ASV) and 29 died among the treated patients; 205 patients belonged to pediatric age group. Results: Out of 112 patients referred to Department of Plastic Surgery, 50 cases presented with cellulitis, 24 patients with compartment syndrome, and 38 patients were referred for the management of soft tissue cover over the extremities. Among 112 patients, 77 involved the lower extremity and 35 the upper extremity. Conclusion: Multidisciplinary approach including hyperbaric oxygen (HBO) therapy improves outcome in the management of snakebite injuries of the extremities. PMID:26862269

  4. Expression and function of the novel proto-oncogene PBF in thyroid cancer: a new target for augmenting radioiodine uptake.

    PubMed

    Smith, Vicki E; Franklyn, Jayne A; McCabe, Christopher J

    2011-08-01

    Pituitary tumor-transforming gene (PTTG)-binding factor (PBF; PTTG1IP) was initially identified through its interaction with the human securin, PTTG. Like PTTG, PBF is upregulated in multiple endocrine tumours including thyroid cancer. PBF is believed to induce the translocation of PTTG into the cell nucleus where it can drive tumourigenesis via a number of different mechanisms. However, an independent transforming ability has been demonstrated both in vitro and in vivo, suggesting that PBF is itself a proto-oncogene. Studied in only a limited number of publications to date, PBF is emerging as a protein with a growing repertoire of roles. Recent data suggest that PBF possesses a complex multifunctionality in an increasing number of tumour settings. For example, PBF is upregulated by oestrogen and mediates oestrogen-stimulated cell invasion in breast cancer cells. In addition to a possible role in the induction of thyroid tumourigenesis, PBF overexpression in thyroid cancers inhibits iodide uptake. PBF has been shown to repress sodium iodide symporter (NIS) activity by transcriptional regulation of NIS expression through the human NIS upstream enhancer and further inhibits iodide uptake via a post-translational mechanism of NIS governing subcellular localisation. This review discusses the current data describing PBF expression and function in thyroid cancer and highlights PBF as a novel target for improving radioiodine uptake and thus prognosis in thyroid cancer.

  5. [Inhalation therapy by dose-inhalers: analysis of patients performance and possibilities for improvement].

    PubMed

    Petro, W; Schuppenies, A

    2005-05-01

    Inhalation therapy in chronic obstructive airways disease requires an efficient inhalation technique. This study analyses step by step the mistakes made in the usage of different MDIs, relates these to patient information prior to the testing and examines several teaching procedures for improvement of knowledge and performance of the inhalation technique. 125 patients suffering from COPD were assigned to six different groups according to their background knowledge in the inhalation technique. The performance was assessed in standardized single steps and as overall performance. Furthermore the efficacy of an interactive pc-based-training program was evaluated. The worst performance was seen in patients who only used the suppliers medication leaflet as a guide. Patients trained in outpatient clinics as well as patients trained in small groups during an inpatient stay showed a better performance. A high improvement rate was seen in prior MDI naive patients after they had undergone the interactive pc-based training program. Most problems were detected in the application step "exhalation before inhalation" and in the actuation-inhalation step. Besides the classical and the pc-based training the use of MDI phantoms showed very good results. The practical conclusion of this study is that the ability of patients to use inhalation pharmacotherapy efficiently needs improvement. Training programs of different intensity lead to a different outcome in performance and knowledge depending on prior knowledge. Inhalation pharmacotherapy without adequate training is insufficient.

  6. Contour scanning for penumbra improvement in pencil beam scanned proton therapy

    NASA Astrophysics Data System (ADS)

    Meier, G.; Leiser, D.; Besson, R.; Mayor, A.; Safai, S.; Weber, D. C.; Lomax, A. J.

    2017-03-01

    Proton therapy, especially in the form of pencil beam scanning (PBS), allows for the delivery of highly conformal dose distributions for complex tumor geometries. However, due to scattering of protons inside the patient, lateral dose gradients cannot be arbitrarily steep, which is of importance in cases with organs at risk (OARs) in close proximity to, or overlapping with, planning target volumes (PTVs). In the PBS approach, physical pencil beams are planned using a regular grid orthogonal to the beam direction. In this work, we propose an alternative to this commonly used approach where pencil beams are placed on an irregular grid along concentric paths based on the target contour. Contour driven pencil beam placement is expected to improve dose confirmation by allowing the optimizer to best enhance the penumbra of irregularly shaped targets using edge enhancement. Its effectiveness has been shown to improve dose confirmation to the target volume and reduce doses to OARs in head-and-neck planning studies. Furthermore, the deliverability of such plans, as well as the dosimetric improvements over conventional grid-based plans, have been confirmed in first phantom based verifications.

  7. Improving therapist psychological flexibility while training acceptance and commitment therapy: a pilot study.

    PubMed

    Luoma, Jason B; Vilardaga, Jennifer Plumb

    2013-01-01

    Acceptance and Commitment Therapy (ACT) training often includes experiential elements aimed at improving therapist psychological flexibility, yet the effects of ACT training on therapist psychological flexibility have yet to be evaluated. This pilot study examines the effects of experiential phone consultation as an adjunct to a standard continuing education workshop on psychological flexibility and burnout among therapists learning ACT. In this study, counselors taking a 2-day ACT workshop were randomly assigned to either six 30-min phone consultation sessions (n = 10) or no additional contact (n = 10). The results show that those in the consultation condition reported higher psychological flexibility at the 3-month follow-up compared to the workshop-only condition. Improvements in ACT knowledge, overall burnout, and personal accomplishment were found in both groups, independent of whether they received phone consultation, and this increase was maintained over time. In conclusion, ACT phone consultation contributed to counselor psychological flexibility above the workshop alone and appears to be feasible as a means to improve counselor psychological flexibility.

  8. Contour scanning for penumbra improvement in pencil beam scanned proton therapy.

    PubMed

    Meier, G; Leiser, D; Besson, R; Mayor, A; Safai, S; Weber, D C; Lomax, A J

    2017-03-21

    Proton therapy, especially in the form of pencil beam scanning (PBS), allows for the delivery of highly conformal dose distributions for complex tumor geometries. However, due to scattering of protons inside the patient, lateral dose gradients cannot be arbitrarily steep, which is of importance in cases with organs at risk (OARs) in close proximity to, or overlapping with, planning target volumes (PTVs). In the PBS approach, physical pencil beams are planned using a regular grid orthogonal to the beam direction. In this work, we propose an alternative to this commonly used approach where pencil beams are placed on an irregular grid along concentric paths based on the target contour. Contour driven pencil beam placement is expected to improve dose confirmation by allowing the optimizer to best enhance the penumbra of irregularly shaped targets using edge enhancement. Its effectiveness has been shown to improve dose confirmation to the target volume and reduce doses to OARs in head-and-neck planning studies. Furthermore, the deliverability of such plans, as well as the dosimetric improvements over conventional grid-based plans, have been confirmed in first phantom based verifications.

  9. Dance movement therapy improves emotional responses and modulates neurohormones in adolescents with mild depression.

    PubMed

    Jeong, Young-Ja; Hong, Sung-Chan; Lee, Myeong Soo; Park, Min-Cheol; Kim, Yong-Kyu; Suh, Chae-Moon

    2005-12-01

    This study assessed the profiles of psychological health and changes in neurohormones of adolescents with mild depression after 12 weeks of dance movement therapy (DMT). Forty middle school seniors (mean age: 16 years old) volunteered to participate in this study and were randomly assigned into either a dance movement group (n = 20) or a control group (n = 20). All subscale scores of psychological distress and global scores decreased significantly after the 12 weeks in the DMT group. Plasma serotonin concentration increased and dopamine concentration decreased in the DMT group. These results suggest that DMT may stabilize the sympathetic nervous system. In conclusion, DMT may be effective in beneficially modulating concentrations of serotonin and dopamine, and in improving psychological distress in adolescents with mild depression.

  10. A manual therapy intervention improves symptoms in patients with carpal tunnel syndrome: a pilot study.

    PubMed

    Maddali Bongi, Susanna; Signorini, Massimo; Bassetti, Massimo; Del Rosso, Angela; Orlandi, Martina; De Scisciolo, Giuseppe

    2013-05-01

    In carpal tunnel syndrome (CTS), manual therapy interventions (MTI) reduce tissue adhesion and increase wrist mobility. We evaluated the efficacy of a MTI in relieving CTS signs and symptoms. Twenty-two CTS patients (pts) (41 hands) were treated with a MTI, consisting in 6 treatments (2/week for 3 weeks) of soft tissues of wrist and hands and of carpal bones. Pts were assessed for hand sensitivity, paresthesia, hand strength, hand and forearm pain, night awakening; Phalen test, thenar eminence hypotrophy and Boston Carpal Tunnel Questionnaire (BCTQ) Symptom Severity Scale (SSS) and Functional Status Scale (FSS). Median nerve was studied by sensory nerve conduction velocity (SNCV) and distal motor latency (DML). CTS was scored as minimal, mild, medium, severe and extreme. We considered as control group the same pts assessed before treatment: at baseline (T0a) and after 12 weeks (T0b). Pts were evaluated at the end of treatment (T1) and after 24-week (T2) follow-up. At T0b, versus T0a, forearm pain and Phalen test positivity were increased and hand strength reduced (p < 0.05). BCTQ-SSS and BCTQ-FSS scores improved at T1 versus T0b (p < 0.05) with the amelioration maintained at T2. At T1, the number of pts with paresthesia, night awakening, hypoesthesia, Phalen test, hand strength reduction and hand sensitivity was reduced with the lacking of symptoms maintained at T2 (p < 0.05). No changes in SNCV, DML and CTS scoring were shown. MTI improved CTS signs and symptoms, with benefits maintained at follow-up. Thus, it may be valid as a conservative therapy.

  11. Intensity-Modulated Radiation Therapy Significantly Improves Acute Gastrointestinal Toxicity in Pancreatic and Ampullary Cancers

    SciTech Connect

    Yovino, Susannah; Poppe, Matthew; Jabbour, Salma; David, Vera; Garofalo, Michael; Pandya, Naimesh; Alexander, Richard; Hanna, Nader; Regine, William F.

    2011-01-01

    Purpose: Among patients with upper abdominal malignancies, intensity-modulated radiation therapy (IMRT) can improve dose distributions to critical dose-limiting structures near the target. Whether these improved dose distributions are associated with decreased toxicity when compared with conventional three-dimensional treatment remains a subject of investigation. Methods and Materials: 46 patients with pancreatic/ampullary cancer were treated with concurrent chemoradiation (CRT) using inverse-planned IMRT. All patients received CRT based on 5-fluorouracil in a schema similar to Radiation Therapy Oncology Group (RTOG) 97-04. Rates of acute gastrointestinal (GI) toxicity for this series of IMRT-treated patients were compared with those from RTOG 97-04, where all patients were treated with three-dimensional conformal techniques. Chi-square analysis was used to determine if there was a statistically different incidence in acute GI toxicity between these two groups of patients. Results: The overall incidence of Grade 3-4 acute GI toxicity was low in patients receiving IMRT-based CRT. When compared with patients who had three-dimensional treatment planning (RTOG 97-04), IMRT significantly reduced the incidence of Grade 3-4 nausea and vomiting (0% vs. 11%, p = 0.024) and diarrhea (3% vs. 18%, p = 0.017). There was no significant difference in the incidence of Grade 3-4 weight loss between the two groups of patients. Conclusions: IMRT is associated with a statistically significant decrease in acute upper and lower GI toxicity among patients treated with CRT for pancreatic/ampullary cancers. Future clinical trials plan to incorporate the use of IMRT, given that it remains a subject of active investigation.

  12. Improved efficiency in Monte Carlo simulation for passive-scattering proton therapy

    PubMed Central

    Méndez, J. Ramos; Perl, J.; Schuemann, J.; Shin, J.; Paganetti, H.; Faddegon, B.

    2015-01-01

    The aim of this work was to improve the computational efficiency of Monte Carlo simulations when tracking protons through a proton therapy treatment head. Two proton therapy facilities were considered, the Francis H Burr Proton Therapy Center (FHBPTC) at the Massachusetts General Hospital and the Crocker Lab eye treatment facility used by University of California at San Francisco (UCSFETF). The computational efficiency was evaluated for phase space files scored at the exit of the treatment head to determine optimal parameters to improve efficiency while maintaining accuracy in the dose calculation. For FHBPTC, particles were split by a factor of 8 upstream of the second scatterer and upstream of the aperture. The radius of the region for Russian roulette was set to 2.5 or 1.5 times the radius of the aperture and a secondary particle production cut (PC) of 50 mm was applied. For UCSFETF, particles were split a factor of 16 upstream of a water absorber column and upstream of the aperture. Here, the radius of the region for Russian roulette was set to 4 times the radius of the aperture and a PC of 0.05 mm was applied. In both setups, the cylindrical symmetry of the proton beam was exploited to position the split particles randomly spaced around the beam axis. When simulating a phase space for subsequent water phantom simulations, efficiency gains between a factor of 19.9±0.1 and 52.21±0.04 for the FHTPC setups and 57.3±0.5 for the UCSFETF setups were obtained. For a phase space (PHSP) used as input for simulations in a patient geometry, the gain was a factor of 78.6±7.5. Lateral-dose curves in water were within the accepted clinical tolerance of 2%, with statistical uncertainties of 0.5% for the two facilities. For the patient geometry and by considering the 2% and 2mm criteria, 98.4% of the voxels showed a gamma index lower than unity. An analysis of the dose distribution resulted in systematic deviations below of 0.88% for 20% of the voxels with dose of 20% of

  13. Improved efficiency in Monte Carlo simulation for passive-scattering proton therapy

    NASA Astrophysics Data System (ADS)

    Ramos Méndez, J.; Perl, J.; Schümann, J.; Shin, J.; Paganetti, H.; Faddegon, B.

    2015-07-01

    The aim of this work was to improve the computational efficiency of Monte Carlo simulations when tracking protons through a proton therapy treatment head. Two proton therapy facilities were considered, the Francis H Burr Proton Therapy Center (FHBPTC) at the Massachusetts General Hospital and the Crocker Lab eye treatment facility used by University of California at San Francisco (UCSFETF). The computational efficiency was evaluated for phase space files scored at the exit of the treatment head to determine optimal parameters to improve efficiency while maintaining accuracy in the dose calculation. For FHBPTC, particles were split by a factor of 8 upstream of the second scatterer and upstream of the aperture. The radius of the region for Russian roulette was set to 2.5 or 1.5 times the radius of the aperture and a secondary particle production cut (PC) of 50 mm was applied. For UCSFETF, particles were split a factor of 16 upstream of a water absorber column and upstream of the aperture. Here, the radius of the region for Russian roulette was set to 4 times the radius of the aperture and a PC of 0.05 mm was applied. In both setups, the cylindrical symmetry of the proton beam was exploited to position the split particles randomly spaced around the beam axis. When simulating a phase space for subsequent water phantom simulations, efficiency gains between a factor of 19.9  ±  0.1 and 52.21  ±  0.04 for the FHTPC setups and 57.3  ±  0.5 for the UCSFETF setups were obtained. For a phase space used as input for simulations in a patient geometry, the gain was a factor of 78.6  ±  7.5. Lateral-dose curves in water were within the accepted clinical tolerance of 2%, with statistical uncertainties of 0.5% for the two facilities. For the patient geometry and by considering the 2% and 2mm criteria, 98.4% of the voxels showed a gamma index lower than unity. An analysis of the dose distribution resulted in systematic deviations below of 0.88% for 20% of the

  14. Erlotinib pretreatment improves photodynamic therapy of non-small cell lung carcinoma xenografts via multiple mechanisms

    PubMed Central

    Gallagher-Colombo, Shannon M.; Miller, Joann; Cengel, Keith A.; Putt, Mary E.; Vinogradov, Sergei A.; Busch, Theresa M.

    2015-01-01

    Aberrant expression of the epidermal growth factor receptor (EGFR) is a common characteristic of many cancers including non-small cell lung carcinoma (NSCLC), head and neck squamous cell carcinoma, and ovarian cancer. While EGFR is currently a favorite molecular target for treatment of these cancers, inhibition of the receptor with small molecule inhibitors (i.e.- erlotinib) or monoclonal antibodies (i.e.- cetuximab) does not provide long-term therapeutic benefit as standalone treatment. Interestingly, we have found that addition of erlotinib to photodynamic therapy (PDT) can improve treatment response in typically erlotinib-resistant NSCLC tumor xenografts. Ninety-day complete response rates of 63% are achieved when erlotinib is administered in three doses before PDT of H460 human tumor xenografts, compared to 16% after PDT-alone. Similar benefit is found when erlotinib is added to PDT of A549 NCSLC xenografts. Improved response is accompanied by increased vascular shutdown, and erlotinib increases the in vitro cytotoxicity of PDT to endothelial cells. Tumor uptake of the photosensitizer (benzoporphyrin derivative monoacid ring A; BPD) is increased by the in vivo administration of erlotinib; nevertheless, this elevation of BPD levels only partially accounts for the benefit of erlotinib to PDT. Thus, pretreatment with erlotinib augments multiple mechanisms of PDT effect that collectively lead to large improvements in therapeutic efficacy. These data demonstrate that short-duration administration of erlotinib before PDT can greatly improve the responsiveness of even erlotinib-resistant tumors to treatment. Results will inform clinical investigation of EGFR-targeting therapeutics in conjunction with PDT. PMID:26054596

  15. Economic evaluation of mobile phone text message interventions to improve adherence to HIV therapy in Kenya

    PubMed Central

    Patel, Anik R.; Kessler, Jason; Braithwaite, R. Scott; Nucifora, Kimberly A.; Thirumurthy, Harsha; Zhou, Qinlian; Lester, Richard T.; Marra, Carlo A.

    2017-01-01

    Abstract Background: A surge in mobile phone availability has fueled low cost short messaging service (SMS) adherence interventions. Multiple systematic reviews have concluded that some SMS-based interventions are effective at improving antiretroviral therapy (ART) adherence, and they are hypothesized to improve retention in care. The objective of this study was to evaluate the cost-effectiveness of SMS-based adherence interventions and explore the added value of retention benefits. Methods: We evaluated the cost-effectiveness of weekly SMS interventions compared to standard care among HIV+ individuals initiating ART for the first time in Kenya. We used an individual level micro-simulation model populated with data from two SMS-intervention trials, an East-African HIV+ cohort and published literature. We estimated average quality adjusted life years (QALY) and lifetime HIV-related costs from a healthcare perspective. We explored a wide range of scenarios and assumptions in one-way and multivariate sensitivity analyses. Results: We found that SMS-based adherence interventions were cost-effective by WHO standards, with an incremental cost-effectiveness ratio (ICER) of $1,037/QALY. In the secondary analysis, potential retention benefits improved the cost-effectiveness of SMS intervention (ICER = $864/QALY). In multivariate sensitivity analyses, the interventions remained cost-effective in most analyses, but the ICER was highly sensitive to intervention costs, effectiveness and average cohort CD4 count at ART initiation. SMS interventions remained cost-effective in a test and treat scenario where individuals were assumed to initiate ART upon HIV detection. Conclusions: Effective SMS interventions would likely increase the efficiency of ART programs by improving HIV treatment outcomes at relatively low costs, and they could facilitate achievement of the UNAIDS goal of 90% viral suppression among those on ART by 2020. PMID:28207516

  16. Progress in the development of early diagnosis and a drug with unique pharmacology to improve cancer therapy

    PubMed Central

    Lehotzky, A.; Tőkési, N.; Gonzalez-Alvarez, I.; Merino, V.; Bermejo, M.; Orosz, F.; Lau, P.; Kovacs, G.G.; Ovádi, J.

    2008-01-01

    Cancer continues to be one of the major health and socio-economic problems worldwide, despite considerable efforts to improve its early diagnosis and treatment. The identification of new constituents as biomarkers for early diagnosis of neoplastic cells and the discovery of new type of drugs with their mechanistic actions are crucial to improve cancer therapy. New drugs have entered the market, thanks to industrial and legislative efforts ensuring continuity of pharmaceutical development. New targets have been identified, but cancer therapy and the anti-cancer drug market still partly depend on anti-mitotic agents. The objective of this paper is to show the effects of KAR-2, a potent anti-mitotic compound, and TPPP/p25, a new unstructured protein, on the structural and functional characteristics of the microtubule system. Understanding the actions of these two potential effectors on the microtubule system could be the clue for early diagnosis and improvement of cancer therapy. PMID:18644768

  17. Autophagy inhibition improves the efficacy of curcumin/temozolomide combination therapy in glioblastomas.

    PubMed

    Zanotto-Filho, Alfeu; Braganhol, Elizandra; Klafke, Karina; Figueiró, Fabrício; Terra, Sílvia Resende; Paludo, Francis Jackson; Morrone, Maurílio; Bristot, Ivi Juliana; Battastini, Ana Maria; Forcelini, Cassiano Mateus; Bishop, Alexander James Roy; Gelain, Daniel Pens; Moreira, José Cláudio Fonseca

    2015-03-28

    Glioblastoma is a devastating primary brain tumor resistant to conventional therapies. In this study, we tested the efficacy of combining temozolomide with curcumin, a phytochemical known to inhibit glioblastoma growth, and investigated the mechanisms involved. The data showed that synergy between curcumin and temozolomide was not achieved due to redundant mechanisms that lead to activating protective autophagy both in vitro and in vivo. Autophagy preceded apoptosis, and blocking this response with autophagy inhibitors (3-methyl-adenine, ATG7 siRNA and chloroquine) rendered cells susceptible to temozolomide and curcumin alone or combinations by increasing apoptosis. While curcumin inhibited STAT3, NFκB and PI3K/Akt to affect survival, temozolomide-induced autophagy relied on the DNA damage response and repair components ATM and MSH6, as well as p38 and JNK1/2. However, the most interesting observation was that both temozolomide and curcumin required ERK1/2 to induce autophagy. Blocking this ERK1/2-mediated temozolomide and curcumin induced autophagy with resveratrol, a blood-brain barrier permeable drug, improved temozolomide/curcumin efficacy in brain-implanted tumors. Overall, the data presented demonstrate that autophagy impairs the efficacy of temozolomide/curcumin, and inhibiting this phenomenon could provide novel opportunities to improve brain tumor treatment.

  18. Tailored nutrition education and food assistance improve adherence to HIV antiretroviral therapy: evidence from Honduras.

    PubMed

    Martinez, Homero; Palar, Kartika; Linnemayr, Sebastian; Smith, Alexandria; Derose, Kathryn Pitkin; Ramírez, Blanca; Farías, Hugo; Wagner, Glenn

    2014-10-01

    Food insecurity and malnutrition negatively affect adherence to antiretroviral therapy (ART) and are associated with poor HIV clinical outcomes. We examined the effect of providing household food assistance and nutrition education on ART adherence. A 12-month prospective clinical trial compared the effect of a monthly household food basket (FB) plus nutrition education (NE) versus NE alone on ART adherence on 400 HIV patients at four clinics in Honduras. Participants had been receiving ART for an average of 3.7 years and were selected because they had suboptimal adherence. Primary outcome measures were missed clinic appointments, delayed prescription refills, and self-reported missed doses of ART. These three adherence measures improved for both groups over 12 months (p < 0.01), mostly within 6 months. On-time prescription refills improved for the FB plus NE group by 19.6 % more than the group receiving NE alone after 6 months (p < 0.01), with no further change at 12 months. Change in missed appointments and self-reported missed ART doses did not significantly differ by intervention group.

  19. Is learning mindfulness associated with improved affect after mindfulness-based cognitive therapy?

    PubMed

    Schroevers, Maya J; Brandsma, Rob

    2010-02-01

    The increased popularity of mindfulness-based interventions and the growing body of empirical evidence confirming the positive effects of these interventions on well-being warrant more research to determine if the effects are indeed related to learning mindfulness. The present study extends previous studies, by examining whether and how changes in five core aspects of mindfulness are related to changes in the report of negative and positive affect during an 8-week course of mindfulness-based cognitive therapy. The study was performed in 64 individuals from the community with mild to moderate psychological problems. Data were collected by self-report questionnaires before and directly after the training. Results showed significant decreases in negative affect and increases in positive affect. We also found significant increases in four of the five aspects of mindfulness. Importantly, changes in mindfulness were significantly associated with improved affect, with a distinct pattern found for positive and negative affect. Hereby, our findings extend previous research by showing that learning distinct aspects of mindfulness is differently related to an improved positive affect and a decreased negative affect. Future randomized controlled trials with a larger sample and longer follow-up period are needed to replicate these findings.

  20. Autism-Like Behavior in BTBR Mice Is Improved by Electroconvulsive Therapy.

    PubMed

    Hagen, Eunice; Shprung, Dana; Minakova, Elena; Washington, James; Kumar, Udaya; Shin, Don; Sankar, Raman; Mazarati, Andrey

    2015-07-01

    Autism is a developmental disorder characterized by impairments in social and communication abilities, as well as by restricted and repetitive behaviors. Incidence of autism is higher than earlier estimates, and treatments have limited efficacy and are costly. Limited clinical and experimental evidence suggest that patients with autism may benefit from electroconvulsive therapy (ECT). We examined the therapeutic potential of ECT in BTBR T+ tf/j mice, which represent a validated model of autism. A series of 13 electroconvulsive shocks (ECS) delivered twice a day over 7 days reversed core autism-like behavioral abnormalities-impaired sociability, social novelty, and repetitive behavior-when the animals were tested 24 h after the last ECS. The effect lasted up to 2 weeks after ECT. Neither single ECS nor a series of 6 ECS modified animals' behavior. Chronic infusion into the lateral brain ventricle of a preferential oxytocin receptor blocker (2S)-2-Amino-N-[(1S,2S,4R)-7,7-dimethyl-1-[[[4-(2-methylphenyl)-1-piperazinyl]sulfonyl]methyl]bicyclo[2.2.1]hept-2-yl]-4-(methylsulfonyl)butanamide hydrochloride abolished ECT-induced improvement of sociability and mitigated improvement of social novelty but did not affect ECT-induced reversal of repetitive behavior. These proof-of-principle experiments suggest that ECT may, indeed, be useful in the treatment of autism, and that its therapeutic effects may be mediated, in part, by central oxytocin signaling.

  1. Reducing CTGF/CCN2 slows down mdx muscle dystrophy and improves cell therapy.

    PubMed

    Morales, Maria Gabriela; Gutierrez, Jaime; Cabello-Verrugio, Claudio; Cabrera, Daniel; Lipson, Kenneth E; Goldschmeding, Roel; Brandan, Enrique

    2013-12-15

    In Duchenne muscular dystrophy (DMD) and the mdx mouse model, the absence of the cytoskeletal protein dystrophin causes defective anchoring of myofibres to the basal lamina. The resultant myofibre degeneration and necrosis lead to a progressive loss of muscle mass, increased fibrosis and ultimately fatal weakness. Connective tissue growth factor (CTGF/CCN-2) is critically involved in several chronic fibro-degenerative diseases. In DMD, the role of CTGF might extend well beyond replacement fibrosis secondary to loss of muscle fibres, since its overexpression in skeletal muscle could by itself induce a dystrophic phenotype. Using two independent approaches, we here show that mdx mice with reduced CTGF availability do indeed have less severe muscular dystrophy. Mdx mice with hemizygous CTGF deletion (mdx-Ctgf+/-), and mdx mice treated with a neutralizing anti-CTGF monoclonal antibody (FG-3019), performed better in an exercise endurance test, had better muscle strength in isolated muscles and reduced skeletal muscle impairment, apoptotic damage and fibrosis. Transforming growth factor type-β (TGF-β), pERK1/2 and p38 signalling remained unaffected during CTGF suppression. Moreover, both mdx-Ctgf+/- and FG-3019 treated mdx mice had improved grafting upon intramuscular injection of dystrophin-positive satellite cells. These findings reveal the potential of targeting CTGF to reduce disease progression and to improve cell therapy in DMD.

  2. Sulfur Mustard Research—Strategies for the Development of Improved Medical Therapy

    PubMed Central

    Kehe, Kai; Balszuweit, Frank; Emmler, Judith; Kreppel, Helmut; Jochum, Marianne; Thiermann, Horst

    2008-01-01

    Objective: Sulfur mustard (SM) is a bifunctional alkylating substance being used as chemical warfare agent (vesicant). It is still regarded as a significant threat in chemical warfare and terrorism. Exposure to SM produces cutaneous blisters, respiratory and gastrointestinal tract injury, eye lesions, and bone marrow depression. Victims of World War I as well as those of the Iran-Iraq war have suffered from devastating chronic health impairment. Even decades after exposure, severe long-term effects like chronic obstructive lung disease, lung fibrosis, recurrent corneal ulcer disease, chronic conjunctivitis, abnormal pigmentation of the skin, and different forms of cancer have been diagnosed. Methods: This review briefly summarizes the scientific literature and own results concerning detection, organ toxicity of SM, its proposed toxicodynamic actions, and strategies for the development of improved medical therapy. Results: Despite extensive research efforts during the last century, efficient antidotes against SM have not yet been generated because its mechanism of action is not fully understood. However, deeper insights into these mechanisms gained in the last decade and promising developments of new drugs now offer new chances to minimize SM-induced organ damage and late effects. Conclusion: Polymerase inhibitors, anti-inflammatory drugs, antioxidants, matrix metalloproteinase inhibitors, and probably regulators of DNA damage repair are identified as promising approaches to improve treatment. PMID:18615149

  3. Improving the segmentation of therapy-induced leukoencephalopathy using apriori information and a gradient magnitude threshold

    NASA Astrophysics Data System (ADS)

    Glass, John O.; Reddick, Wilburn E.; Reeves, Cara; Pui, Ching-Hon

    2004-05-01

    Reliably quantifying therapy-induced leukoencephalopathy in children treated for cancer is a challenging task due to its varying MR properties and similarity to normal tissues and imaging artifacts. T1, T2, PD, and FLAIR images were analyzed for a subset of 15 children from an institutional protocol for the treatment of acute lymphoblastic leukemia. Three different analysis techniques were compared to examine improvements in the segmentation accuracy of leukoencephalopathy versus manual tracings by two expert observers. The first technique utilized no apriori information and a white matter mask based on the segmentation of the first serial examination of each patient. MR images were then segmented with a Kohonen Self-Organizing Map. The other two techniques combine apriori maps from the ICBM atlas spatially normalized to each patient and resliced using SPM99 software. The apriori maps were included as input and a gradient magnitude threshold calculated on the FLAIR images was also utilized. The second technique used a 2-dimensional threshold, while the third algorithm utilized a 3-dimensional threshold. Kappa values were compared for the three techniques to each observer, and improvements were seen with each addition to the original algorithm (Observer 1: 0.651, 0.653, 0.744; Observer 2: 0.603, 0.615, 0.699).

  4. Repetitive negative thinking predicts depression and anxiety symptom improvement during brief cognitive behavioral therapy.

    PubMed

    Kertz, Sarah J; Koran, Jennifer; Stevens, Kimberly T; Björgvinsson, Thröstur

    2015-05-01

    Repetitive negative thinking (RNT) is a common symptom across depression and anxiety disorders and preliminary evidence suggests that decreases in rumination and worry are related to improvement in depression and anxiety symptoms. However, despite its prevalence, relatively little is known about transdiagnostic RNT and its temporal associations with symptom improvement during treatment. The current study was designed to examine the influence of RNT on subsequent depression and anxiety symptoms during treatment. Participants (n = 131; 52% female; 93% White; M = 34.76 years) were patients presenting for treatment in a brief, cognitive behavior therapy based, partial hospitalization program. Participants completed multiple assessments of depression (Center for the Epidemiological Studies of Depression-10 scale), anxiety (the 7-item Generalized Anxiety Disorder Scale), and repetitive negative thinking (Perseverative Thinking Questionnaire) over the course of treatment. Results indicated statistically significant between and within person effects of RNT on depression and anxiety, even after controlling for the effect of time, previous symptom levels, referral source, and treatment length. RNT explained 22% of the unexplained variability in depression scores and 15% of the unexplained variability in anxiety scores beyond that explained by the control variables. RNT may be an important transdiagnostic treatment target for anxiety and depression.

  5. Low dose of GRP78-targeting subtilase cytotoxin improves the efficacy of photodynamic therapy in vivo

    PubMed Central

    GABRYSIAK, MAGDALENA; WACHOWSKA, MALGORZATA; BARANKIEWICZ, JOANNA; PILCH, ZOFIA; RATAJSKA, ANNA; SKRZYPEK, EWA; WINIARSKA, MAGDALENA; DOMAGALA, ANTONI; RYGIEL, TOMASZ P.; JOZKOWICZ, ALICJA; BOON, LOUIS; GOLAB, JAKUB; FIRCZUK, MALGORZATA

    2016-01-01

    Photodynamic therapy (PDT) exerts direct cytotoxic effects on tumor cells, destroys tumor blood and lymphatic vessels and induces local inflammation. Although PDT triggers the release of immunogenic antigens from tumor cells, the degree of immune stimulation is regimen-dependent. The highest immunogenicity is achieved at sub-lethal doses, which at the same time trigger cytoprotective responses, that include increased expression of glucose-regulated protein 78 (GRP78). To mitigate the cytoprotective effects of GRP78 and preserve the immunoregulatory activity of PDT, we investigated the in vivo efficacy of PDT in combination with EGF-SubA cytotoxin that was shown to potentiate in vitro PDT cytotoxicity by inactivating GRP78. Treatment of immunocompetent BALB/c mice with EGF-SubA improved the efficacy of PDT but only when mice were treated with a dose of EGF-SubA that exerted less pronounced effects on the number of T and B lymphocytes as well as dendritic cells in mouse spleens. The observed antitumor effects were critically dependent on CD8+ T cells and were completely abrogated in immunodeficient SCID mice. All these results suggest that GRP78 targeting improves in vivo PDT efficacy provided intact T-cell immune system. PMID:27035643

  6. Metabolic acetate therapy improves phenotype in the tremor rat model of Canavan disease.

    PubMed

    Arun, Peethambaran; Madhavarao, Chikkathur N; Moffett, John R; Hamilton, Kristen; Grunberg, Neil E; Ariyannur, Prasanth S; Gahl, William A; Anikster, Yair; Mog, Steven; Hallows, William C; Denu, John M; Namboodiri, Aryan M A

    2010-06-01

    Genetic mutations that severely diminish the activity of aspartoacylase (ASPA) result in the fatal brain dysmyelinating disorder, Canavan disease. There is no effective treatment. ASPA produces free acetate from the concentrated brain metabolite, N-acetylaspartate (NAA). Because acetyl coenzyme A is a key building block for lipid synthesis, we postulated that the inability to catabolize NAA leads to a brain acetate deficiency during a critical period of CNS development, impairing myelination and possibly other aspects of brain development. We tested the hypothesis that acetate supplementation during postnatal myelination would ameliorate the severe phenotype associated with ASPA deficiency using the tremor rat model of Canavan disease. Glyceryltriacetate (GTA) was administered orally to tremor rats starting 7 days after birth, and was continued in food and water after weaning. Motor function, myelin lipids, and brain vacuolation were analyzed in GTA-treated and untreated tremor rats. Significant improvements were observed in motor performance and myelin galactocerebroside content in tremor rats treated with GTA. Further, brain vacuolation was modestly reduced, and these reductions were positively correlated with improved motor performance. We also examined the expression of the acetyl coenzyme A synthesizing enzyme acetyl coenzyme A synthase 1 and found upregulation of expression in tremor rats, with a return to near normal expression levels in GTA-treated tremor rats. These results confirm the critical role played by NAA-derived acetate in brain myelination and development, and demonstrate the potential usefulness of acetate therapy for the treatment of Canavan disease.

  7. Nanoparticles improve biological functions of phthalocyanine photosensitizers used for photodynamic therapy.

    PubMed

    Jia, Xiao; Jia, Lee

    2012-10-01

    Photodynamic therapy (PDT) is a new technology using photodynamic effect for disease diagnosis and treatment. It is a two-step technique involving the uptake of a photosensitizer by cancer tissue followed by light irradiation that excites the photosensitizer to produce highly reactive oxygen species, the latter execute apoptosis of cancerous cells. As a second-generation of photosensitizers, phthalocyanine demonstrates higher absorption in the 650-800 nm range and short tissue accumulation compared to their first generation. However, many potent phthalocyanine photosensitizers are hydrophobic and poorly water-soluble, which limit their therapeutic applications. As a result, advanced delivery systems and different strategies are called for to improve the effectiveness of PDT. Facts have proved that using nanoparticles as carries of photosensitizers is a very promising route. Nanoparticles have the potentials to increase photosensitizers' aqueous solubility, bioavailability and stability, and deliver photosensitizers to the target tissues. This article reviewed the commonly-used nanoparticles, including colloid gold, quantum dots, paramagnetic nanoparticles, silica-based materials, polymer-based nanoparticles, as potential delivery systems for phthalocyanine photosensitizers, and summarized the improved biological functions of phthalocyanine photosensitizers in PDT.

  8. Retrospective Biological Dosimetry at Low and High Doses of Radiation and Radioiodine Impact on Individual Susceptibility to Ionizing Radiation

    PubMed Central

    Cebulska-Wasilewska, Antonina; Krzysiek, Mateusz; Krajewska, Grażyna; Stępień, Artur; Krajewski, Paweł

    2017-01-01

    Iodine-131 (I-131) is often used in thyroid diagnostics and therapy. External and internal exposure to radioiodine can lead to molecular and cellular damage in peripheral blood lymphocytes. The aim of this study was to explore the influence of low and high doses of I-131 on susceptibility to ionizing radiation. Study groups consisted of 30 individuals free of thyroid diseases, 41 patients exposed diagnostically to low doses of I-131, and 37 hyperthyroidism patients exposed therapeutically to high doses. The standardized DNA repair competence assay was used to test the efficacy of the fast DNA repair process in G0 cells. Cytogenetic preparations were made in fresh blood samples before and after challenging cells in vitro with X-ray dose. The frequency of sister chromatid exchanges (SCE) and percentage of cells with significantly elevated numbers of SCE were used as cytogenetic biomarkers associated to homologous recombination and compared to reported earlier cytogenetic biomarkers of cancer risk. Strong individual variation in the biomarkers is observed in all investigated groups before and after challenging. Nevertheless, the efficiency of post challenging fast repair is significantly high in the patients exposed to diagnostic I-131 doses than in unexposed control group and linked to decreased cytogenetic damage. However, 5 weeks after administration of therapeutic doses, significant increases of unrepaired post challenging DNA and cytogenetic damages were observed indicating a health risk. Results also suggest that the appearance of cancers in immediate families might influence DNA repair differently in patients exposed to low than to high doses. PMID:28250909

  9. Physical therapy for airway clearance improves cardiac autonomic modulation in children with acute bronchiolitis

    PubMed Central

    Jacinto, Cynthia P.; Gastaldi, Ada C.; Aguiar, Daniela Y.; Maida, Karina D.; Souza, Hugo C. D.

    2013-01-01

    Background The effects of physical therapy on heart rate variability (HRV), especially in children, are still inconclusive. Objective We investigated the effects of conventional physical therapy (CPT) for airway clearance and nasotracheal suction on the HRV of pediatric patients with acute bronchiolitis. Method 24 children were divided into two groups: control group (CG, n=12) without respiratory diseases and acute bronchiolitis group (BG, n=12). The heart rate was recorded in the BG at four different moments: basal recording (30 minutes), 5 minutes after the CPT (10 minutes), 5 minutes after nasotracheal suction (10 minutes), and 40 minutes after nasotracheal suction (30 minutes). The CG was subjected to the same protocol, except for nasotracheal suction. To assess the HRV, we used spectrum analysis, which decomposes the heart rate oscillations into frequency bands: low frequency (LF=0.04-0.15Hz), which corresponds mainly to sympathetic modulation; and high frequency (HF=0.15-1.2Hz), corresponding to vagal modulation. Results Under baseline conditions, the BG showed higher values in LF oscillations, lower values in HF oscillations, and increased LF/HF ratio when compared to the CG. After CPT, the values for HRV in the BG were similar to those observed in the CG during basal recording. Five minutes after nasotracheal suction, the BG showed a decrease in LF and HF oscillations; however, after 40 minutes, the values were similar to those observed after application of CPT. Conclusions The CPT and nasotracheal suction, both used for airway clearance, promote improvement in autonomic modulation of HRV in children with acute bronchiolitis. PMID:24271093

  10. Valproic Acid Use During Radiation Therapy for Glioblastoma Associated With Improved Survival

    SciTech Connect

    Barker, Christopher A.; Bishop, Andrew J.; Chang, Maria; Beal, Kathryn; Chan, Timothy A.

    2013-07-01

    Purpose: Valproic acid (VA) is an antiepileptic drug (AED) and histone deacetylase (HDAC) inhibitor taken by patients with glioblastoma (GB) to manage seizures, and it can modulate the biologic effects of radiation therapy (RT). We investigated whether VA use during RT for GB was associated with overall survival (OS). Methods and Materials: Medical records of 544 adults with GB were retrospectively reviewed. Analyses were performed to determine the association of Radiation Therapy Oncology Group recursive partitioning analysis (RTOG RPA) class, seizure history, and concurrent temozolomide (TMZ) and AED use during RT with OS. Results: Seizures before the end of RT were noted in 217 (40%) patients, and 403 (74%) were taking an AED during RT; 29 (7%) were taking VA. Median OS in patients taking VA was 16.9 months (vs 13.6 months taking another AED, P=.16). Among patients taking an AED during RT, OS was associated with VA (P=.047; hazard ratio [HR], 0.67; 95% confidence interval [CI], 0.27-1.07), and RTOG RPA class (P<.0001; HR, 1.49; 95% CI, 1.37-1.61). Of the 5 most common AEDs, only VA was associated with OS. Median OS of patients receiving VA and TMZ during RT was 23.9 months (vs 15.2 months for patients taking another AED, P=.26). When the analysis was restricted to patients who received concurrent TMZ, VA use was marginally associated with OS (P=.057; HR, 0.54; 95% CI, −0.09 to 1.17), independently of RTOG RPA class and seizure history. Conclusions: VA use during RT for GB was associated with improved OS, independently of RTOG RPA, seizure history, and concurrent TMZ use. Further studies of treatment that combines HDAC inhibitors and RT are warranted.

  11. Expanding dental hygiene to include dental therapy: improving access to care for children.

    PubMed

    Nash, David A

    2009-01-01

    Oral Health in America: A Report of the Surgeon General, and the subsequent National Call to Action to Promote Oral Health contributed significantly to raising the awareness of the American public and the dental profession regarding the lack of access to oral health care by many Americans, especially minorities and low income populations, with resulting disparities in oral health. The problem is particularly acute among children. The current workforce of dentists in the United States is inadequate to meet the oral health care needs of children in terms of numbers of dentists, as well as their distribution, ethnicity, education, and practice orientation. Dental hygienists trained in an expanded scope of practice, can help address the workforce inadequacy. Dental therapists, educated in 2-year programs of postsecondary education, comparable to America's associate degree dental hygiene programs, have been used throughout the world to provide basic, primary oral health care for children. Research has documented that utilizing dental therapists is a cost effective method of improving access to care for children. Countries that have led the way in introducing dental therapists to care for their children are now integrating their separate 2-year curriculum in dental therapy and dental hygiene into a 3-year curriculum to prepare a clinician dually trained in both dental therapy and dental hygiene. This clinician is being designated an oral health therapist. Expanding the education of dental hygienists in the United States to include skills of the internationally acclaimed dental therapist can produce oral health therapists, individuals capable of addressing the basic preventive, restorative, and minor surgical needs of children, but also able to continue to address the preventive and periodontal needs of adults.

  12. Nanoshell-mediated photothermal therapy improves survival in a murine glioma model.

    PubMed

    Day, Emily S; Thompson, Patrick A; Zhang, Linna; Lewinski, Nastassja A; Ahmed, Nabil; Drezek, Rebekah A; Blaney, Susan M; West, Jennifer L

    2011-08-01

    We are developing a novel treatment for high-grade gliomas using near infrared-absorbing silica-gold nanoshells that are thermally activated upon exposure to a near infrared laser, thereby irreversibly damaging cancerous cells. The goal of this work was to determine the efficacy of nanoshell-mediated photothermal therapy in vivo in murine xenograft models. Tumors were induced in male IcrTac:ICR-Prkdc(SCID) mice by subcutaneous implantation of Firefly Luciferase-labeled U373 human glioma cells and biodistribution and survival studies were performed. To evaluate nanoparticle biodistribution, nanoshells were delivered intravenously to tumor-bearing mice and after 6, 24, or 48 h the tumor, liver, spleen, brain, muscle, and blood were assessed for gold content by inductively coupled plasma-mass spectrometry (ICP-MS) and histology. Nanoshell concentrations in the tumor increased for the first 24 h and stabilized thereafter. Treatment efficacy was evaluated by delivering saline or nanoshells intravenously and externally irradiating tumors with a near infrared laser 24 h post-injection. Success of treatment was assessed by monitoring tumor size, tumor luminescence, and survival time of the mice following laser irradiation. There was a significant improvement in survival for the nanoshell treatment group versus the control (P < 0.02) and 57% of the mice in the nanoshell treatment group remained tumor free at the end of the 90-day study period. By comparison, none of the mice in the control group survived beyond 24 days and mean survival was only 13.3 days. The results of these studies suggest that nanoshell-mediated photothermal therapy represents a promising novel treatment strategy for malignant glioma.

  13. Dynamic trajectory-based couch motion for improvement of radiation therapy trajectories in cranial SRT

    SciTech Connect

    MacDonald, R. Lee; Thomas, Christopher G.

    2015-05-15

    Purpose: To investigate potential improvement in external beam stereotactic radiation therapy plan quality for cranial cases using an optimized dynamic gantry and patient support couch motion trajectory, which could minimize exposure to sensitive healthy tissue. Methods: Anonymized patient anatomy and treatment plans of cranial cancer patients were used to quantify the geometric overlap between planning target volumes and organs-at-risk (OARs) based on their two-dimensional projection from source to a plane at isocenter as a function of gantry and couch angle. Published dose constraints were then used as weighting factors for the OARs to generate a map of couch-gantry coordinate space, indicating degree of overlap at each point in space. A couch-gantry collision space was generated by direct measurement on a linear accelerator and couch using an anthropomorphic solid-water phantom. A dynamic, fully customizable algorithm was written to generate a navigable ideal trajectory for the patient specific couch-gantry space. The advanced algorithm can be used to balance the implementation of absolute minimum values of overlap with the clinical practicality of large-scale couch motion and delivery time. Optimized cranial cancer treatment trajectories were compared to conventional treatment trajectories. Results: Comparison of optimized treatment trajectories with conventional treatment trajectories indicated an average decrease in mean dose to the OARs of 19% and an average decrease in maximum dose to the OARs of 12%. Degradation was seen for homogeneity index (6.14% ± 0.67%–5.48% ± 0.76%) and conformation number (0.82 ± 0.02–0.79 ± 0.02), but neither was statistically significant. Removal of OAR constraints from volumetric modulated arc therapy optimization reveals that reduction in dose to OARs is almost exclusively due to the optimized trajectory and not the OAR constraints. Conclusions: The authors’ study indicated that simultaneous couch and gantry motion

  14. Vascular Dysfunction in Experimental Diabetes Is Improved by Pentaerithrityl Tetranitrate but Not Isosorbide-5-Mononitrate Therapy

    PubMed Central

    Schuhmacher, Swenja; Oelze, Matthias; Bollmann, Franziska; Kleinert, Hartmut; Otto, Christian; Heeren, Tjebo; Steven, Sebastian; Hausding, Michael; Knorr, Maike; Pautz, Andrea; Reifenberg, Kurt; Schulz, Eberhard; Gori, Tommaso; Wenzel, Philip; Münzel, Thomas; Daiber, Andreas

    2011-01-01

    OBJECTIVE Diabetes is associated with vascular oxidative stress, activation of NADPH oxidase, and uncoupling of nitric oxide (NO) synthase (endothelial NO synthase [eNOS]). Pentaerithrityl tetranitrate (PETN) is an organic nitrate with potent antioxidant properties via induction of heme oxygenase-1 (HO-1). We tested whether treatment with PETN improves vascular dysfunction in the setting of experimental diabetes. RESEARCH DESIGN AND METHODS After induction of hyperglycemia by streptozotocin (STZ) injection (60 mg/kg i.v.), PETN (15 mg/kg/day p.o.) or isosorbide-5-mononitrate (ISMN; 75 mg/kg/day p.o.) was fed to Wistar rats for 7 weeks. Oxidative stress was assessed by optical methods and oxidative protein modifications, vascular function was determined by isometric tension recordings, protein expression was measured by Western blotting, RNA expression was assessed by quantitative RT-PCR, and HO-1 promoter activity in stable transfected cells was determined by luciferase assays. RESULTS PETN, but not ISMN, improved endothelial dysfunction. NADPH oxidase and serum xanthine oxidase activities were significantly reduced by PETN but not by ISMN. Both organic nitrates had minor effects on the expression of NADPH oxidase subunits, eNOS and dihydrofolate reductase (Western blotting). PETN, but not ISMN, normalized the expression of GTP cyclohydrolase-1, extracellular superoxide dismutase, and S-glutathionylation of eNOS, thereby preventing eNOS uncoupling. The expression of the antioxidant enzyme, HO-1, was increased by STZ treatment and further upregulated by PETN, but not ISMN, via activation of the transcription factor NRF2. CONCLUSIONS In contrast to ISMN, the organic nitrate, PETN, improves endothelial dysfunction in diabetes by preventing eNOS uncoupling and NADPH oxidase activation, thereby reducing oxidative stress. Thus, PETN therapy may be suited to treat patients with cardiovascular complications of diabetes. PMID:21844097

  15. Low Level Laser Therapy Versus Pharmacotherapy in Improving Myofascial Pain Disorder Syndrome

    PubMed Central

    Khalighi, Hamid Reza; Mortazavi, Hamed; Mojahedi, Seyed Masoud; Azari-Marhabi, Saranaz; Moradi Abbasabadi, Faranak

    2016-01-01

    Introduction: Temporomandibular disorders (TMD) lead to masticatory muscle pain, jaw movement disability and limitation in mouth opening. Pain is the chief complaint in 90% of the TMD patients which leads to disability and severe socioeconomic costs. The purpose of this study was to evaluate the therapeutic effects of low level laser therapy (LLLT) compared to pharmacotherapy with NSAIDs (naproxen) in myofascial pain disorder syndrome (MPDS). Methods: In this randomized controlled clinical trial, 40 MPDS patients were divided into two groups. One group received naproxen 500 mg bid for 3 weeks as treatment modality and also had placebo laser sessions. The other group received active laser (diode 810 nm CW) as treatment and placebo drug. Pain intensity was measured by visual analogue scale (VAS) and maximum painless mouth opening was also measured as a functional index every session and at 2 months follow up. Data was collected and analyzed with SPSS software. Independent t test was used to analyze the data. A P < 0.05 was considered significant. Results: Low level laser caused significant reduction in pain intensity (P < 0.05) and a significant increase in mouth opening. In naproxen group neither pain intensity nor maximum mouth opening had significant improvement. Pain relief, in subjective VAS was observed in third session in LLLT group, but did not occur in naproxen group. Maximum mouth opening increased significantly in laser group compared to the naproxen group from the eighth session. Conclusion: Treatment with LLLT caused a significant improvement in mouth opening and pain intensity in patients with MPDS. Similar improvement was not observed in naproxen group. PMID:27330698

  16. Improved delivery of polymer therapeutics to prostate tumors using plasmonic photothermal therapy

    NASA Astrophysics Data System (ADS)

    Gormley, Adam Joseph

    When a patient is presented with locally advanced prostate cancer, it is possible to provide treatment with curative intent. However, once the disease has formed distant metastases, the chances of survival drops precipitously. For this reason, proper management of the disease while it remains localized is of critical importance. Treating these malignant cells with cytotoxic agents is effective at cell killing; however, the nonspecific toxicity profiles of these drugs often limit their use until the disease has progressed and symptom palliation is required. Incorporation of these drugs in nanocarriers such as polymers help target them to tumors with a degree of specificity, though major vascular barriers limit their effective delivery. In this dissertation, it is shown that plasmonic photothermal therapy (PPTT) can be used to help overcome some of these barriers and improve delivery to prostate tumors. First, the concept of using PPTT to improve the delivery of macromolecules to solid tumors was validated. This was done by measuring the tumor uptake of albumin. Next, the concept of targeting gold nanorods (GNRs) directly to the tumor's vasculature to better modulate vascular response to heating was tested. Surface conjugation of cyclic RGD (Arg-Gly-Asp) to GNRs improved their binding and uptake to endothelial cells in vitro, but not in vivo. Nontargeted GNRs and PPTT were then utilized to guide the location of polymer therapeutic delivery to prostate tumors. N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers, which were designed to be targeted to cells previously exposed to heat shock, were used in this study. Treatment of tumors with PPTT facilitated a burst accumulation of the copolymers over 4 hours, and heat shock targeting to cells allowed them to be retained for an extended period of time. Finally, the tumor localization of the HPMA copolymers following PPTT was evaluated by magnetic resonance imaging (MRI). These results show that PPTT may be a useful tool

  17. SERCA2a Gene Therapy Can Improve Symptomatic Heart Failure in δ-Sarcoglycan-Deficient Animals

    PubMed Central

    Bouyon, Sophie; Roussel, Véronique

    2014-01-01

    Abstract The loss of dystrophin or its associated proteins results in the development of muscle wasting frequently associated with cardiomyopathy. Contractile cardiac tissue is injured and replaced by fibrous tissue or fatty infiltrates, leading to a progressive decrease of the contractile force and finally to end-stage heart failure. At the time symptoms appear, restoration of a functional allele of the causative gene might not be sufficient to prevent disease progression. Alterations in Ca2+ transport and intracellular calcium levels have been implicated in many types of pathological processes, especially in heart disease. On the basis of a gene transfer strategy, we analyzed the therapeutic efficacy of primary gene correction in a δ-sarcoglycan (δ-SG)-deficient animal model versus gene transfer of the Ca2+ pump hSERCA2a (human sarco-endoplasmic reticulum calcium ATPase 2a), at a symptomatic stage of heart disease. Our results strongly suggest that restoration of δ-SG at this stage of disease will not lead to improved clinical outcome. However, restoration of proper Ca2+ handling by means of amplifying SERCA2a expression in the myocardium can lead to functional improvement. Abnormalities in Ca2+ handling play an important role in disease progression toward heart failure, and increased SERCA2a levels appear to significantly improve cardiac contraction and relaxation. Beneficial effects persist at least over a period of 6 months, and the evolution of cardiac functional parameters paralleled those of normal controls. Furthermore, we demonstrate that a plasmid formulation based on amphiphilic block copolymers can provide a safe and efficient platform for myocardial gene therapies. The use of synthetic formulations for myocardial gene transfer might thus overcome one of the major hurdles linked to viral vectors, that is, repeat administrations. PMID:24645914

  18. Synchronized moving aperture radiation therapy (SMART): improvement of breathing pattern reproducibility using respiratory coaching

    NASA Astrophysics Data System (ADS)

    Neicu, Toni; Berbeco, Ross; Wolfgang, John; Jiang, Steve B.

    2006-02-01

    Recently, at Massachusetts General Hospital (MGH) we proposed a new treatment technique called synchronized moving aperture radiation therapy (SMART) to account for tumour motion during radiotherapy. The basic idea of SMART is to synchronize the moving radiation beam aperture formed by a dynamic multileaf collimator with the tumour motion induced by respiration. The two key requirements for being able to successfully use SMART in clinical practice are the precise and fast detection of tumour position during the simulation/treatment and the good reproducibility of the tumour motion pattern. To fulfil the first requirement, an integrated radiotherapy imaging system is currently being developed at MGH. The results of a previous study show that breath coaching techniques are required to make SMART an efficient technique in general. In this study, we investigate volunteer and patient respiratory coaching using a commercial respiratory gating system as a respiration coaching tool. Five healthy volunteers, observed during six sessions, and 33 lung cancer patients, observed during one session when undergoing 4D CT scans, were investigated with audio and visual promptings, with free breathing as a control. For all five volunteers, breath coaching was well tolerated and the intra- and inter-session reproducibility of the breathing pattern was greatly improved. Out of 33 patients, six exhibited a regular breathing pattern and needed no coaching, four could not be coached at all due to the patient's medical condition or had difficulty following the instructions, 13 could only be coached with audio instructions and 10 could follow the instructions of and benefit from audio-video coaching. We found that, for all volunteers and for those patients who could be properly coached, breath coaching improves the duty cycle of SMART treatment. However, about half of the patients could not follow both audio and video instructions simultaneously, suggesting that the current coaching

  19. Improvement in survival end points of patients with metastatic renal cell carcinoma through sequential targeted therapy.

    PubMed

    Calvo, Emiliano; Schmidinger, Manuela; Heng, Daniel Y C; Grünwald, Viktor; Escudier, Bernard

    2016-11-01

    Survival of patients with metastatic renal cell carcinoma (mRCC) has improved since the advent of targeted therapy. Approved agents include the multi-targeted tyrosine kinase inhibitors (TKIs) sunitinib, sorafenib, axitinib, pazopanib, cabozantinib, and lenvatinib (approved in combination with everolimus), the anti-VEGF monoclonal antibody bevacizumab, the mammalian target of rapamycin (mTOR) inhibitors everolimus and temsirolimus, and the programmed death-1 (PD-1) targeted immune checkpoint inhibitor nivolumab. The identification of predictive and prognostic factors of survival is increasing, and both clinical predictive factors and pathology-related prognostic factors are being evaluated. Serum-based biomarkers and certain histologic subtypes of RCC, as well as clinical factors such as dose intensity and the development of some class effect adverse events, have been identified as predictors of survival. Expression levels of microRNAs, expression of chemokine receptor 4, hypermethylation of certain genes, VEGF polymorphisms, and elevation of plasma fibrinogen or d-dimer have been shown to be prognostic indicators of survival. In the future, prognosis and treatment of patients with mRCC might be based on genomic classification, especially of the 4 most commonly mutated genes in RCC (VHL, PBRM1, BAP1, and SETD2). Median overall survival has improved for patients treated with a first-line targeted agent compared with survival of patients treated with first-line interferon-α, and results of clinical trials have shown a survival benefit of sequential treatment with targeted agents. Prognosis of patients with mRCC will likely improve with optimization and individualization of current sequential treatment with targeted agents.

  20. Evaluation of iodovinyl antibody conjugates: Comparison with a p-iodobenzoyl conjugate and direct radioiodination

    SciTech Connect

    Hadley, S.W.; Wilbur, D.S. )

    1990-03-01

    The preparations and conjugations of 2,3,5,6-tetrafluorophenyl 5-(125I/131I)iodo-4-pentenoate (7a) and 2,3,5,6-tetrafluorophenyl 3,3-dimethyl-5-(125I/131I)iodo-4-pentenoate (7b) to monoclonal antibodies are reported. Reagents 7a and 7b were prepared in high radiochemical yield by iododestannylation of their corresponding 5-tri-n-butylstannyl precursors. Radioiodinated antibody conjugates were prepared by reaction of 7a or 7b with the protein at basic pH. Evaluation of these conjugates by several in vitro procedures demonstrated that the radiolabel was attached to the antibody in a stable manner and that the conjugates maintained immunoreactivity. Comparative dual-isotope biodistribution studies of a monoclonal antibody Fab fragment conjugate of 7a and 7b with the same Fab fragment labeled with N-succinimidyl p-(131I)iodobenzoate (PIB, p-iodobenzoate, 2) or directly radioiodinated have been carried out in tumor-bearing nude mice. Coinjection of the Fab conjugate of 7a with the Fab conjugate of 2 demonstrated that the biodistributions were similar in most organs, except the neck tissue (thyroid-containing) and the stomach, which contained substantially increased levels of the 7a label. Coinjection of the Fab conjugate of 7a with the Fab fragment radioiodinated by using the chloramine-T method demonstrated that the biodistributions were remarkably similar, suggesting roughly equivalent in vivo deiodination of these labeled antibody fragments. Coinjection of the Fab conjugate of 7a with the Fab conjugate of 7b indicated that there was {approximately} a 2-fold reduction in the amount of in vivo deiodination of the 7b conjugate as compared to the 7a conjugate.

  1. Art therapy improves experienced quality of life among women undergoing treatment for breast cancer: a randomized controlled study.

    PubMed

    Svensk, A-C; Oster, I; Thyme, K E; Magnusson, E; Sjödin, M; Eisemann, M; Aström, S; Lindh, J

    2009-01-01

    Women with breast cancer are naturally exposed to strain related to diagnosis and treatment, and this influences their experienced quality of life (QoL). The present paper reports the effect, with regard to QoL aspects, of an art therapy intervention among 41 women undergoing radiotherapy treatment for breast cancer. The women were randomized to an intervention group with individual art therapy sessions for 1 h/week (n = 20), or to a control group (n = 21). The WHOQOL-BREF and EORTC Quality of Life Questionnaire-BR23, were used for QoL assessment, and administrated on three measurement occasions, before the start of radiotherapy and 2 and 6 months later. The results indicate an overall improvement in QoL aspects among women in the intervention group. A significant increase in total health, total QoL, physical health and psychological health was observed in the art therapy group. A significant positive difference within the art therapy group was also seen, concerning future perspectives, body image and systemic therapy side effects. The present study provides strong support for the use of art therapy to improve QoL for women undergoing radiotherapy treatment for breast cancer.

  2. Radioiodine in the atmosphere after the Fukushima Dai-ichi nuclear accident.

    PubMed

    Lebel, Luke S; Dickson, Raymond S; Glowa, Glenn A

    2016-01-01

    About 160 PBq of (131)I was released into the atmosphere during the accident at the Fukushima Dai-ichi Nuclear Power Plant. The chemistry of radioiodine is complicated, and it can be released in several different forms. In addition, the different physical forms, like molecular iodine, aerosol-form iodine, or organic iodine, would have all behaved differently once in the atmosphere, and would have been removed at different rates. These releases were detected by monitoring stations throughout Japan, and from these measurements, key insights can be made about the different chemical forms that were released, as well as the persistence of each in the environment.

  3. Improving intensity-modulated radiation therapy using the anatomic beam orientation optimization algorithm

    SciTech Connect

    Potrebko, Peter S.; McCurdy, Boyd M. C.; Butler, James B.; El-Gubtan, Adel S.

    2008-05-15

    A novel, anatomic beam orientation optimization (A-BOO) algorithm is proposed to significantly improve conventional intensity-modulated radiation therapy (IMRT). The A-BOO algorithm vectorially analyses polygonal surface mesh data of contoured patient anatomy. Five optimal (5-opt) deliverable beam orientations are selected based on (1) tangential orientation bisecting the target and adjacent organ's-at-risk (OARs) to produce precipitous dose gradients between them and (2) parallel incidence with polygon features of the target volume to facilitate conformal coverage. The 5-opt plans were compared to standard five, seven, and nine equiangular-spaced beam plans (5-equi, 7-equi, 9-equi) for: (1) gastric, (2) Radiation Therapy Oncology Group (RTOG) P-0126 prostate, and (3) RTOG H-0022 oropharyngeal (stage-III, IV) cancer patients. In the gastric case, the noncoplanar 5-opt plan reduced the right kidney V 20 Gy by 32.2%, 23.2%, and 20.6% compared to plans with five, seven, and nine equiangular-spaced beams. In the prostate case, the coplanar 5-opt plan produced similar rectal sparing as the 7-equi and 9-equi plans with a reduction of the V 75, V 70, V 65, and V 60 Gy of 2.4%, 5.3%, 7.0%, and 9.5% compared to the 5-equi plan. In the stage-III and IV oropharyngeal cases, the noncoplanar 5-opt plan substantially reduced the V 30 Gy and mean dose to the contralateral parotid compared to plans with five, seven, and nine equiangular-spaced beams: (stage-III) 7.1%, 5.2%, 6.8%, and 5.1, 3.5, 3.7 Gy and (stage-IV) 10.2%, 10.2%, 9.8% and 7.0, 7.1, 7.2 Gy. The geometry-based A-BOO algorithm has been demonstrated to be robust for application to a variety of IMRT treatment sites. Beam orientations producing significant improvements in OAR sparing over conventional IMRT can be automatically produced in minutes compared to hours with existing dose-based beam orientation optimization methods.

  4. Family Therapy

    MedlinePlus

    Tests and Procedures Family therapy By Mayo Clinic Staff Family therapy is a type of psychological counseling (psychotherapy) that helps family members improve communication and resolve conflicts. Family therapy is usually provided ...

  5. Improved survival with neoadjuvant therapy and resection for adenocarcinoma of the esophagus.

    PubMed Central

    Stewart, J R; Hoff, S J; Johnson, D H; Murray, M J; Butler, D R; Elkins, C C; Sharp, K W; Merrill, W H; Sawyers, J L

    1993-01-01

    OBJECTIVE: This study sought to determine the impact of preoperative chemotherapy and radiation therapy (neoadjuvant therapy) followed by resection in patients with adenocarcinoma of the esophagus. SUMMARY BACKGROUND DATA: Long-term survival in patients with carcinoma of the esophagus has been poor. An increase in the incidence of adenocarcinoma of the esophagus has been reported recently. METHODS: Fifty-eight patients with biopsy-proven adenocarcinoma of the esophagus treated at this institution from January 1951 through February 1993 were studied. Since 1989, 24 patients were entered prospectively into a multimodality treatment protocol consisting of preoperative cisplatin, 5-fluorouracil (5-FU), and leucovorin with or without etoposide, and concomitant mediastinal radiation (30 Gy). Patients were re-evaluated and offered resection. RESULTS: There were no deaths related to neoadjuvant therapy and toxicity was minimal. Before multimodality therapy was used, the operative mortality rate was 19% (3 of 16 patients). With multimodality therapy, there have been no operative deaths (0 of 23 patients). The median survival time in patients treated before multimodality therapy was 8 months and has yet to be reached for those treated with the neoadjuvant regimen (> 26 months, p < 0.0001). The actuarial survival rate at 24 months was 15% before multimodality therapy and 76% with multimodality therapy. No difference in survival was noted in neoadjuvant protocols with or without etoposide (p = 0.827). CONCLUSIONS: Multimodality therapy with preoperative chemotherapy and radiation therapy followed by resection appears to offer a survival advantage to patients with adenocarcinoma of the esophagus. PMID:8215648

  6. Nonimmunogenic hyperthyroidism: Cumulative hypothyroidism incidence after radioiodine and surgical treatment

    SciTech Connect

    Kinser, J.A.; Roesler, H.; Furrer, T.; Gruetter, D.Z.; Zimmermann, H. )

    1989-12-01

    During 1977, 246 hyperthyroid patients were seen in our departments, 140 (57%) with nonimmunogenic hyperthyroidism (NIH)--101 with a toxic adenoma (TA) and 39 with multifocal functional autonomy (MFA). All patients but one could be followed over 9 yr, 101 after 131I treatment (RIT), another 29 after surgery (S). Ten patients were left untreated. Thirty-four treated (24%) patients died, none as a result of thyroid or post-treatment complications. There was no hyperthyroidism later than 9 mo after therapy. Only 1% (RIT) and 24% (S) were hypothyroid 1 yr after treatment. But 19% of all treated NIH patients were hypothyroid after 9 yr or at the time of their death, 12% after RIT and 41% after S. The cumulative hypothyroidism incidences 1.4%/yr for RIT and 2.2%/yr for S, were not significantly different. Out of the five survivers without RIT or S, two TA patients were hypothyroid. The effect of RIT on goiter related loco-regional complications was not worse than after S. We conclude that RIT is the treatment for NIH, leaving surgery for exceptional cases.

  7. Cognitive training to improve memory in individuals undergoing electroconvulsive therapy: Negative findings.

    PubMed

    Choi, Jimmy; Wang, Yuanjia; Feng, Tianshu; Prudic, Joan

    2017-03-24

    Although electroconvulsive therapy (ECT) remains the most effective treatment for severe depression, some patients report persistent memory problems following ECT that impact their quality of life and their willingness to consent to further ECT. While cognitive training has been shown to improve memory performance in various conditions, this approach has never been applied to help patients regain their memory after ECT. In a double-blind study, we tested the efficacy of a new cognitive training program called Memory Training for ECT (Mem-ECT), specifically designed to target anterograde and retrograde memory that can be compromised following ECT. Fifty-nine patients with treatment-resistant depression scheduled to undergo ultra-brief right unilateral ECT were randomly assigned to either: (a) Mem-ECT, (b) active control comprised of nonspecific mental stimulation, or (c) treatment as usual. Participants were evaluated within one week prior to the start of ECT and then again within 2 weeks following the last ECT session. All three groups improved in global function, quality of life, depression, and self-reported memory abilities without significant group differences. While there was a decline in verbal delayed recall and mental status, there was no decline in general retrograde memory or autobiographical memory in any of the groups, with no significant memory or clinical benefit for the Mem-ECT or active control conditions compared to treatment as usual. While we report negative findings, these results continue to promote the much needed discussion on developing effective strategies to minimize the adverse memory side effects of ECT, in hopes it will make ECT a better and more easily tolerated treatment for patients with severe depression who need this therapeutic option.

  8. Group cognitive behavior therapy for bipolar disorder can improve the quality of life

    PubMed Central

    Costa, R.T.; Cheniaux, E.; Rangé, B.P.; Versiani, M.; Nardi, A.E.

    2012-01-01

    Bipolar disorder (BD) can have an impact on psychosocial functioning and quality of life (QoL). Several studies have shown that structured psychotherapy in conjunction with pharmacotherapy may modify the course of some disorders; however, few studies have investigated the results of group cognitive behavior therapy (G-CBT) for BD. Our objective was to evaluate the effectiveness of 14 sessions of G-CBT for BD patients, comparing this intervention plus pharmacotherapy to treatment as usual (TAU; only pharmacotherapy). Forty-one patients with BD I and II participated in this study and were randomly allocated to each group (G-CBT: N = 27; TAU: N = 14). Thirty-seven participants completed the treatment (women: N = 66.67%; mean age = 41.5 years). QoL and mood symptoms were assessed in all participants. Scores changed significantly by the end of treatment in favor of the G-CBT group. The G-CBT group presented significantly better QoL in seven of the eight sub-items assessed with the Medical Outcomes Survey SF-36 scale. At the end of treatment, the G-CBT group exhibited lower scores for mania (not statistically significant) and depression (statistically significant) as well as a reduction in the frequency and duration of mood episodes (P < 0.01). The group variable was significant for the reduction of depression scores over time. This clinical change may explain the improvement in six of the eight subscales of QoL (P < 0.05). The G-CBT group showed better QoL in absolute values in all aspects and significant improvements in nearly all subscales. These results were not observed in the TAU control group. PMID:22735175

  9. Identifying treatment responders and predictors of improvement after cognitive-behavioral therapy for juvenile fibromyalgia.

    PubMed

    Sil, Soumitri; Arnold, Lesley M; Lynch-Jordan, Anne; Ting, Tracy V; Peugh, James; Cunningham, Natoshia; Powers, Scott W; Lovell, Daniel J; Hashkes, Philip J; Passo, Murray; Schikler, Kenneth N; Kashikar-Zuck, Susmita

    2014-07-01

    The primary objective of this study was to estimate a clinically significant and quantifiable change in functional disability to identify treatment responders in a clinical trial of cognitive-behavioral therapy (CBT) for youth with juvenile fibromyalgia (JFM). The second objective was to examine whether baseline functional disability (Functional Disability Inventory), pain intensity, depressive symptoms (Children's Depression Inventory), coping self-efficacy (Pain Coping Questionnaire), and parental pain history predicted treatment response in disability at 6-month follow-up. Participants were 100 adolescents (11-18 years of age) with JFM enrolled in a recently published clinical trial comparing CBT to a fibromyalgia education (FE) intervention. Patients were identified as achieving a clinically significant change in disability (i.e., were considered treatment responders) if they achieved both a reliable magnitude of change (estimated as a > or = 7.8-point reduction on the FDI) using the Reliable Change Index, and a reduction in FDI disability grade based on established clinical reference points. Using this rigorous standard, 40% of patients who received CBT (20 of 50) were identified as treatment responders, compared to 28% who received FE (14 of 50). For CBT, patients with greater initial disability and higher coping efficacy were significantly more likely to achieve a clinically significant improvement in functioning. Pain intensity, depressive symptoms, and parent pain history did not significantly predict treatment response. Estimating clinically significant change for outcome measures in behavioral trials sets a high bar but is a potentially valuable approach to improve the quality of clinical trials, to enhance interpretability of treatment effects, and to challenge researchers to develop more potent and tailored interventions.

  10. Music therapy: An effective approach in improving social skills of children with autism

    PubMed Central

    Ghasemtabar, Seyyed Nabiollah; Hosseini, Mahbubeh; Fayyaz, Irandokht; Arab, Saeid; Naghashian, Hamed; Poudineh, Zahra

    2015-01-01

    Background: The existing methodological weakness in conducted researches concerning music therapy (MT) for children with autism led to ambiguity and confusion in this scope of studies. The aim of the present research is to identify the effectiveness of MT method in improving social skills of children with autism and its stability, as well. Materials and Methods: In the form of a clinical trial study with design of pretest/posttest/follow-up with control group, among the children with autism in community of Tehran city, on the basis of childhood autism rating scale, 27 children with mild to moderate autism were chosen and were divided into two groups of experiment (n = 13), and control (n = 14). Social skills’ level of both groups was measured and recorded with the help of social skills rating system scale. The children of the experiment group participated in MT programs of Orff–Schulwerk for 45 days in 12 sessions (two sessions of 1-h/week), whereas the control group received no intervention. The data were analyzed with Statistic Package For Social Science (SPSS) software t-test and analysis of covariance was used to compare groups. Results: In posttest, the results of covariance analysis showed a significant increase in social skills’ scores of the experiment group (P < 0.001). Also, results of the paired-sample t-test showed that the effectiveness of MT has been persistent up to the follow-up phase. Conclusions: The study showed that MT is an effective method with deep and consistent effects on improving social skills of children with autism. PMID:26380242

  11. Cellular therapy in combination with cytokines improves survival in a xenograft mouse model of ovarian cancer.

    PubMed

    Ingersoll, Susan B; Ahmad, Sarfraz; McGann, Hasina C; Banks, Robert K; Stavitzski, Nicole M; Srivastava, Milan; Ali, Ghazanfar; Finkler, Neil J; Edwards, John R; Holloway, Robert W

    2015-09-01

    Studies have shown enhanced survival of ovarian cancer patients in which the tumors are infiltrated with tumor infiltrating lymphocytes and natural killer cells showing the importance of immune surveillance and recognition in ovarian cancer. Therefore, in this study, we tested cellular immunotherapy and varying combinations of cytokines (IL-2 and/or pegylated-IFNα-2b) in a xenograft mouse model of ovarian cancer. SKOV3-AF2 ovarian cancer cells were injected intra-peritoneally (IP) into athymic nude mice. On day 7 post-tumor cell injection, mice were injected IP with peripheral blood mononuclear cells (PBMC; 5 × 10(6) PBMC) and cytokine combinations [IL-2 ± pegylated-IFNα-2b (IFN)]. Cytokine injections were continued weekly for IFN (12,000 U/injection) and thrice weekly for IL-2 (4000 U/injection). Mice were euthanized when they became moribund due to tumor burden at which time tumor and ascitic fluid were measured and collected. Treatment efficacy was measured by improved survival at 8 weeks and overall survival by Kaplan-Meier analysis. We observed that the mice tolerated all treatment combinations without significant weight loss or other apparent illness. Mice receiving PBMC plus IL-2 showed improved median survival (7.3 weeks) compared to mice with no treatment (4.2 weeks), IL-2 (3.5 weeks), PBMC (4.0 weeks), or PBMC plus IL-2 and IFN (4.3 weeks), although PBMC plus IL-2 was not statistically different than PBMC plus IFN (5.5 weeks, p > 0.05). We demonstrate that cytokine-stimulated cellular immune therapy with PBMC and IL-2 was well tolerated and resulted in survival advantage compared to untreated controls and other cytokine combinations in the nude-mouse model.

  12. Improved antimicrobial therapy with cationic tetra- and octa-substituted phthalocyanines

    NASA Astrophysics Data System (ADS)

    Angelov, I.; Mantareva, V.; Kussovski, V.; Woehrle, D.; Borisova, E.; Avramov, L.

    2008-12-01

    Photodynamic therapy (PDT) today is an innovative and not yet widespread light-drug initiated treatment that is based on the photoactive compound irradiated with proper light to produce oxygen species that are toxic to the pathogenic biological objects- bacteria, viruses, tumor cells. The obstacles that limited the efficacy of PDT concern to the selectivity and multi-drug resistance prolong time for cellular release and side effects of skin photosensitivity for commercial porphyrin originated photosensitizers (PS). Now there are very intensive investigations for introducing in practice a new, with a least side effects PSs for PDT. The usefulness of the more extended macromolecules structured with proper substituents refers not only to the improved optical properties like far-red and with intensive absorption and emission capacity, but mainly to the ability for selective delivery and adhesion to the target cells, such as bacteria or other pathogens. The present study focuses on the charge effect of photodynamic agent on the uptake capacity toward gram-negative bacteria cells and their further photoinactivation. The multi-drug resistant microorganism Aeromanas hydrophilla, which is causing diseases to fishes and humans, is treated. The new octa-cationic phthalocyanines are designed to compare PDT efficacy to the efficacy of tetra-substituted derivatives with the same functional peripheral substituents. The higher cellular accumulation to the bacteria cells as a result of the high number of positive charges of photosensitizer, leading to the better adhesion to the cellular membranes and improved photoinactivation of bacteria causing superficial and intraorgan infections. These results set a base of a rationale design of covalently octa-substituted phthalocyanines with positive charge for a successful treatment of microorganisms.

  13. Long-term anti-hypertensive therapy with benidipine improves arterial stiffness over blood pressure lowering.

    PubMed

    Kita, Toshihiro; Suzuki, Yoshihiko; Eto, Tanenao; Kitamura, Kazuo

    2005-12-01

    Pulse wave velocity (PWV) reflects arterial stiffness and is an independent predictor of cardiovascular mortality and morbidity. However, because it is closely related to blood pressure (BP), PWV is an imperfect measure for evaluating the effects of anti-hypertensive drugs on arterial wall properties. To clarify the effect of benidipine on arterial properties, we first derived the regression line between BP and PWV changes in a short-term experiment. Using this line, we evaluated the long-term effect of benidipine on PWV changes. In the short-term experiment, 29 participants were intravenously administered nicardipine for 90 min. Maximum decreases of brachial-ankle PWV (baPWV) were plotted against the corresponding decreases in BP. In the long-term experiment, 9 hypertensive patients were treated with benidipine for 1 year, during which BP and baPWV were monitored. After 1 year, benidipine was suspended for 2 weeks, and BP and baPWV were reevaluated. In the short-term experiment, PWV was dependent on BP only, and the equation of the regression line was deltaPWV (cm/s) =10.114 x deltaMBP (mmHg) (r=0.913) or deltaPWV (%) =0.719 x deltaMBP (%) (r=0.926). In the long-term therapy, benidipine treatment achieved stable BP control within 3 months; the real PWV decreases (r-PWV) were almost identical to the PWV decrease estimated (e-PWV) from BP lowering at 3 months. However, r-PWV exceeded e-PWV after 6 months. Relative BP and PWV improvements compared to the control were maintained 2 weeks after suspension of benidipine. In conclusion, long-term benidipine administration improves arterial wall properties beyond what can be accounted for by changes in BP.

  14. Combined exercise and cognitive behavioral therapy improves outcomes in patients with heart failure

    PubMed Central

    Gary, Rebecca A.; Dunbar, Sandra B.; Higgins, Melinda K.; Musselman, Dominique L.; Smith, Andrew L.

    2014-01-01

    Objective The purpose of this study is to compare the effectiveness of a combined 12-week home-based exercise (EX)/cognitive behavioral therapy (CBT) program (n=18) with CBT alone (n=19), EX alone (n=20), and with usual care (UC, n=17) in stable New York Heart Association Class II to III heart failure (HF) patients diagnosed with depression. Methods Depressive symptom severity [Hamilton Rating Scale for Depression (HAM-D)], physical function [6-min walk test (6MWT)], and health-related quality of life (HRQOL) (Minnesota Living with Heart Failure Questionnaire) were evaluated at baseline (T1), after the 12-week intervention/control (T2), and following a 3-month telephone follow-up (T3). A repeated measures analysis of variance was used to determine group differences. Depression severity was dichotomized as minor (HAM-D, 11–14) and moderate-to-major depression (HAM-D, ≥15), and group intervention and control responses were also evaluated on that basis. Results The greatest reduction in HAM-D scores over time occurred in the EX/CBT group (−10.4) followed by CBT (−9.6), EX (−7.3), and UC (−6.2), but none were statistically significant. The combined group showed a significant increase in 6-min walk distance at 24 weeks (F=13.5, P<.001). Among all groups with moderate-to-major depression, only those in CBT/EX had sustained lower HAM-D scores at 12 and 24 weeks, 6MWT distances were significantly greater at 12 (P=.018) and 24 (P=.013) weeks, and the greatest improvement in HRQOL also occurred. Conclusions Interventions designed to improve both physical and psychological symptoms may provide the best method for optimizing functioning and enhancing HRQOL in patients with HF. PMID:20624510

  15. Internet Cognitive Behavioural Therapy for Panic Disorder: Does the Inclusion of Stress Management Information Improve End-State Functioning?

    ERIC Educational Resources Information Center

    Richards, Jeffrey C.; Klein, Britt; Austin, David W.

    2006-01-01

    Previous research has established Internet-based cognitive behavioural therapy (CBT) for panic disorder (PD) as effective in reducing panic severity and frequency. There is evidence, however, that such programs are less effective at improving overall end-state functioning, defined by a PD clinician severity rating of [less than or equal to] 2 and…

  16. ESC Working Group Cellular Biology of the Heart: Position Paper: improving the preclinical assessment of novel cardioprotective therapies

    PubMed Central

    Lecour, Sandrine; Bøtker, Hans E.; Condorelli, Gianluigi; Davidson, Sean M.; Garcia-Dorado, David; Engel, Felix B.; Ferdinandy, Peter; Heusch, Gerd; Madonna, Rosalinda; Ovize, Michel; Ruiz-Meana, Marisol; Schulz, Rainer; Sluijter, Joost P.G.; Van Laake, Linda W.; Yellon, Derek M.; Hausenloy, Derek J.

    2014-01-01

    Ischaemic heart disease (IHD) remains the leading cause of death and disability worldwide. As a result, novel therapies are still needed to protect the heart from the detrimental effects of acute ischaemia–reperfusion injury, in order to improve clinical outcomes in IHD patients. In this regard, although a large number of novel cardioprotective therapies discovered in the research laboratory have been investigated in the clinical setting, only a few of these have been demonstrated to improve clinical outcomes. One potential reason for this lack of success may have been the failure to thoroughly assess the cardioprotective efficacy of these novel therapies in suitably designed preclinical experimental animal models. Therefore, the aim of this Position Paper by the European Society of Cardiology Working Group Cellular Biology of the Heart is to provide recommendations for improving the preclinical assessment of novel cardioprotective therapies discovered in the research laboratory, with the aim of increasing the likelihood of success in translating these new treatments into improved clinical outcomes. PMID:25344369

  17. An Investigation of Bilateral Isokinematic Training and Neurodevelopmental Therapy in Improving Use of the Affected Hand in Children with Hemiplegia

    ERIC Educational Resources Information Center

    Sheppard, Loretta; Mudie, Heather; Froude, Elspeth

    2007-01-01

    Motor impairment in children with hemiplegic cerebral palsy leads to a predominance of use of the unaffected hand. This impedes development of bimanual skills and deprives the affected side of the stimulus needed for normal growth. Occupational therapists aim to improve use of the affected hand, traditionally using Neurodevelopmental Therapy.…

  18. The Development of Macrophage-Mediated Cell Therapy to Improve Skeletal Muscle Function after Injury

    PubMed Central

    Rybalko, Viktoriya; Hsieh, Pei-Ling; Merscham-Banda, Melissa; Suggs, Laura J.; Farrar, Roger P.

    2015-01-01

    Skeletal muscle regeneration following acute injury is a multi-step process involving complex changes in tissue microenvironment. Macrophages (MPs) are one of the key cell types involved in orchestration and modulation of the repair process. Multiple studies highlight the essential role of MPs in the control of the myogenic program and inflammatory response during skeletal muscle regeneration. A variety of MP phenotypes have been identified and characterized in vitro as well as in vivo. As such, MPs hold great promise for cell-based therapies in the field of regenerative medicine. In this study we used bone-marrow derived in vitro LPS/IFN-y-induced M1 MPs to enhance functional muscle recovery after tourniquet-induced ischemia/reperfusion injury (TK-I/R). We detected a 15% improvement in specific tension and force normalized to mass after M1 (LPS/IFN-γ) MP transplantation 24 hours post-reperfusion. Interestingly, we found that M0 bone marrow-derived unpolarized MPs significantly impaired muscle function highlighting the complexity of temporally coordinated skeletal muscle regenerative program. Furthermore, we show that delivery of M1 (LPS/IFN-γ) MPs early in regeneration accelerates myofiber repair, decreases fibrotic tissue deposition and increases whole muscle IGF-I expression. PMID:26717325

  19. Effect of goal-directed therapy on outcome after esophageal surgery: A quality improvement study

    PubMed Central

    Veelo, Denise P.; van Berge Henegouwen, Mark I.; Ouwehand, Kirsten S.; Geerts, Bart F.; Anderegg, Maarten C. J.; van Dieren, Susan; Preckel, Benedikt; Binnekade, Jan M.; Gisbertz, Suzanne S.; Hollmann, Markus W.

    2017-01-01

    Background Goal-directed therapy (GDT) can reduce postoperative complications in high-risk surgery patients. It is uncertain whether GDT has the same benefits in patients undergoing esophageal surgery. Goal of this Quality Improvement study was to evaluate the effects of a stroke volume guided GDT on post-operative outcome. Methods and findings We compared the postoperative outcome of patients undergoing esophagectomy before (99 patients) and after (100 patients) implementation of GDT. There was no difference in the proportion of patients with a complication (56% vs. 54%, p = 0.82), hospital stay and mortality. The incidence of prolonged ICU stay (>48 hours) was reduced (28% vs. 12, p = .005) in patients treated with GDT. Secondary analysis of complication rate showed a decrease in pneumonia (29 vs. 15%, p = .02), mediastinal abscesses (12 vs. 3%, p = .02), and gastric tube necrosis (5% vs. 0%, p = .03) in patients treated with GDT. Patients in the GDT group received significantly less fluids but received more colloids. Conclusions The implementation of GDT during esophagectomy was not associated with reductions in overall morbidity, mortality and hospital length of stay. However, we observed a decrease in pneumonia, mediastinal abscesses, gastric tube necrosis, and ICU length of stay. PMID:28253353

  20. Dipyridamole-thallium-201 tomography documenting improved myocardial perfusion with therapy in Kawasaki disease

    SciTech Connect

    Nienaber, C.A.; Spielmann, R.P.; Hausdorf, G.

    1988-12-01

    Thallium-201 tomographic perfusion studies after pharmacologic vasodilation were performed in seven children (aged 2 years 8 months to 8 years 7 months), 3 to 20 months after the acute stage of the disease. In all patients coronary aneurysms were seen on cross-sectional echocardiograms. The scintigrams of six children showed no significant regional reduction of myocardial thallium-201 uptake. These children had remained asymptomatic in the follow-up period after the acute inflammatory stage of Kawasaki disease. Persistent and transient thallium defects were present in one child with acute posterolateral myocardial infarction; obstruction of two coronary vessels supplying the defect zones was confirmed by contrast angiography. After 8 months of treatment a follow-up nuclear scan showed marked reduction in the size of the defect and almost complete abolishment of the ischemic reaction. Thus tomographic thallium-201 perfusion scintigraphy in conjunction with vasodilation stress is useful to assess myocardial perfusion in children with Kawasaki disease and demonstrates marked improvement in regional perfusion after adequate medical therapy.

  1. Physical therapy-driven quality improvement to promote early mobility in the intensive care unit.

    PubMed

    Harris, Christy L; Shahid, Shafi

    2014-07-01

    Growing evidence shows that early mobilization of patients in the intensive care unit (ICU) is a safe and cost-effective strategy to improve patient outcomes. However, in ICUs where early mobilization has not been practiced, its adoption requires culture change by the multidisciplinary team, including physical therapists, nurses, respiratory therapists, and physicians. We describe a physical therapist-led program to introduce such changes in a medical-surgical and a cardiovascular ICU. Interdisciplinary and multidisciplinary meetings and education sessions informed critical care team members about early mobilization and encouraged knowledge sharing for safety and effectiveness. A lead physical therapist was appointed to advocate for early mobility and developed solutions to overcome the identified barriers. After the initiation of this program, the number of ICU patients receiving physical therapy evaluations increased from 364 in 2011-2012 to 542 in 2012-2013. In this article, we describe our experience from 21 patients who underwent early mobilization. A physical therapist-led initiative can help establish an ICU culture that supports early mobilization, but the change is slow and requires interdisciplinary collaboration to identify and overcome barriers.

  2. Photodynamic therapy can improve warts' discomfort in renal transplant patients prospective multicenter study.

    PubMed

    Sparsa, Agnès; Blaise, Sophie; Tack, Brigitte; Dalmay, François; Leroy, Dominique; Bonnetblanc, Jean-Marie; Béani, Jean-Claude; Bédane, Christophe

    2012-01-01

    Many studies have been conducted showing that aminolevulinic acid (ALA)-photodynamic therapy (PDT) can be an alternative treatment for recalcitrant warts. Recently, we performed a study evaluating methyl-aminolevulinic acid (MAL)-PDT for the treatment of hand warts in a population of renal transplant patients. Two symmetrical targets were selected on each hand and randomly assigned to chemical keratolytic treatment followed by three cycles of ALA-PDT (75 J cm(-2) red light). Patients were evaluated after 3 months and a second run of PDT was performed if the total area and number of warts decreased less than 50%, with evaluation every 3 months for 1 year. Twenty patients were included and 16 were evaluable (9 M, 7 F). After 6 months the reduction of warts' area was 48.4% on the treated side versus 18.4% in the control area (P = 0.021). The decrease in the total number of warts was 41%versus 19.4% (P = NS). The global tolerance of the treatment was good with acceptable pain during irradiation. These results suggest that ALA-PDT is a safe and efficient treatment for transplanted patient warts. The improvement between treated and control zone is 20% due to the decrease in untreated warts' area and number.

  3. New bifunctional metalloproteinase inhibitors: an integrated approach towards biological improvements and cancer therapy.

    PubMed

    Marques, Sérgio M; Abate, Claudia C; Chaves, Sílvia; Marques, Fernanda; Santos, Isabel; Nuti, Elisa; Rossello, Armando; Santos, M Amélia

    2013-10-01

    The key role of some matrix metalloproteinases (MMPs) on several pathological processes, including carcinogenesis and tumor growth, makes the development of MMP inhibitors (MMPIs) an attractive approach for cancer therapy. We present herein an integrated approach for the development of a new series of inhibitors of MMP2 and MMP14, two enzymes over-expressed by human ovarian cancer. As a first step, a new series of single model compounds bearing different zinc-binding groups (ZBGs), such as carboxylic, hydroxamic acid, hydrazide and sulfonylhydrazide groups, were studied and revealed reasonably good capacity for the Zn(II) chelation in solution and for the MMP inhibition. Aimed at further reinforcing the biological activity of these MMPIs as anti-cancer agents, a selection of those models was extra-functionalized with benzothiazole (BTA), a group with recognized antitumor activity. Analysis of the results obtained for these bifunctional compounds, in particular the inhibitory activity against MMP2 and MMP14 as well as the anti-proliferative activity on the A2780 ovarian cancer cell line, allowed to understand the activity dependence on the type of ZBG, as well as the relevance of the BTA moiety. Overall, the evidenced BTA-associated activity improvements on enzyme inhibition and cell antiproliferactivity, combined with the hydrolytic stability revealed by the hydrazide group, suggest that these new bifunctional BTA-hydrazide derivatives should be taken in consideration for the development of new generations of MMPIs with anti-cancer activity.

  4. Predicting Improvement in Depression Across Therapies Using Indicators of Romantic Relationship Functioning: A Preliminary Investigation.

    PubMed

    Woods, Sarah B; Priest, Jacob B; Denton, Wayne H

    2015-01-01

    Depression is a common presenting problem, often affected by couple interactions in unique ways. However, research in the area of romantic relationship functioning and depression often replicates previous research or consists of literature reviews, limiting the clinical relevancy. The purpose of this preliminary study is to expand the research on the effects of relational processes on depression treatment outcomes. We tested whether initiator tendency, attachment anxiety, attachment avoidance, and marital satisfaction predicted improvement in depression for women with Major Depressive Disorder enrolled in a depression treatment clinical trial (n = 17). Women completed treatments of either pharmacotherapy or combined Emotionally Focused Therapy for couples and pharmacotherapy. We found that higher baseline levels of partner initiator tendency resulted in less change in depression (worse outcomes), regardless of treatment type and that higher baseline levels of attachment avoidance predicted better depression outcomes in treatment. Marital satisfaction, however, was not linked to change in depression. Initiator tendency is discussed as a critical romantic relationship factor for depression treatment outcomes.

  5. Bilayered Films Based on Novel Polymer Derivative for Improved Ocular Therapy of Gatifloxacin

    PubMed Central

    Aher, Naval Dinesh; Nair, Hema Ajit

    2014-01-01

    Context. Thiomers could prove to be suitable mucoadhesives for fabrication of ocular inserts. Objective. The study intends to explore the application of thiolated sodium alginate (TSA) to the preparation of bilayered ocular inserts of gatifloxacin. Methods. Cysteine moieties were grafted onto sodium alginate (SA) and the resultant thiomer was characterized for relevant physicochemical properties. Bilayered inserts were fabricated with a mucoadhesive immediate release layer composed of either SA or TSA and a sustained release layer composed of acrylates. Films were prepared by solvent evaporation and evaluated for mechanical properties, drug content, and in vitro release. Results and Discussion. The synthesized TSA possessed 248.80 ± 49.7 μmol thiol groups/gm and its solutions thickened on standing due to disulphide bridging. Its films showed improved mucoadhesion and also a strikingly beneficial property of resisting erosion and remaining as a hydrated adhesive layer for the duration of drug release. The bilayered films were found to be flexible, with good folding endurance, uniform thickness, and appropriate drug content, and showed a release of about 80% of loaded gatifloxacin in 12 h. Conclusion. The study demonstrates promise in employing thiolated polymer in conjunction with acrylates for the design of ocular inserts for twice a day therapy with gatifloxacin. PMID:24516362

  6. Highly Versatile Polyelectrolyte Complexes for Improving the Enzyme Replacement Therapy of Lysosomal Storage Disorders.

    PubMed

    Giannotti, Marina I; Abasolo, Ibane; Oliva, Mireia; Andrade, Fernanda; García-Aranda, Natalia; Melgarejo, Marta; Pulido, Daniel; Corchero, José L; Fernández, Yolanda; Villaverde, Antonio; Royo, Miriam; García-Parajo, María F; Sanz, Fausto; Schwartz, Simó

    2016-10-05

    Lysosomal storage disorders are currently treated by enzyme replacement therapy (ERT) through the direct administration of the unprotected recombinant protein to the patients. Herein we present an ionically cross-linked polyelectrolyte complex (PEC) composed of trimethyl chitosan (TMC) and α-galactosidase A (GLA), the defective enzyme in Fabry disease, with the capability of directly targeting endothelial cells by incorporating peptide ligands containing the RGD sequence. We assessed the physicochemical properties, cytotoxicity, and hemocompatibility of RGD-targeted and untargeted PECs, the uptake by endothelial cells and the intracellular activity of PECs in cell culture models of Fabry disease. Moreover, we also explored the effect of different freeze-drying procedures in the overall activity of the PECs. Our results indicate that the use of integrin-binding RGD moiety within the PEC increases their uptake and the efficacy of the GLA enzyme, while the freeze-drying allows the activity of the therapeutic protein to remain intact. Overall, these results highlight the potential of TMC-based PECs as a highly versatile and feasible drug delivery system for improving the ERT of lysosomal storage disorders.

  7. Heparin improves BMSC cell therapy: Anticoagulant treatment by heparin improves the safety and therapeutic effect of bone marrow-derived mesenchymal stem cell cytotherapy

    PubMed Central

    Liao, Li; Shi, Bingzheng; Chang, Heran; Su, Xiaoxia; Zhang, Lichao; Bi, Chunsheng; Shuai, Yi; Du, Xiaoyan; Deng, Zhihong; Jin, Yan

    2017-01-01

    Systemic infusion of bone marrow-derived mesenchymal stem cells (BMSCs) has become a promising strategy for disease treatment and tissue regeneration. Strategies to enhance the efficiency of BMSC cell therapy are crucial to promote its clinical application. Here, we aimed to improve BMSC cell therapy by inhibiting the BMSC-induced coagulation reaction. Intravenous injection of gradient BMSCs into mice showed that BMSCs were not fully compatible with blood. Large doses of BMSCs induced a series of symptoms of respiratory failure and heart failure. Histological and homeostasis analysis confirmed that large doses of BMSCs induced disseminated intravascular thrombosis, exhaustion of platelets and coagulation factors, and prolonged prothrombin time (PT) and activated partial thromboplastin time (APTT). Similar to mouse BMSCs, goat and human BMSCs also induced coagulation reactions in vitro and in vivo. The coagulation was induced mostly by tissue factor, the overexpression of which enhanced the procoagulant activity of BMSCs during in vitro culture. Notably, clinical doses of BMSCs in cell therapy also induced mild and reversible coagulation, which increased BMSC lung embolism and clearance. Anticoagulation treatment by heparin (400 U/kg) prevented BMSC-induced coagulation and the acute adverse effects of large-dose BMSCs infusion efficiently. Importantly, heparin treatment led to decreased BMSC lung embolism and enhanced migration and maintenance of BMSCs to target organs in cell therapy. Based on an experimental colitis model, we confirmed that heparin treatment enhanced the effect of BMSC therapy efficiently to reduce mortality, prevent weight loss, suppress inflammation reaction and alleviate tissue injury. In conclusion, BMSCs possess procoagulant activity that could induce disseminated coagulation and thrombosis in recipients. Anticoagulation treatment by heparin is a practical strategy to improve both the safety and therapeutic effect of BMSC therapy. PMID

  8. Improving superficial target delineation in radiation therapy with endoscopic tracking and registration

    SciTech Connect

    Weersink, R. A.; Qiu, J.; Hope, A. J.; Daly, M. J.; Cho, B. C. J.; DaCosta, R. S.; Sharpe, M. B.; Breen, S. L.; Chan, H.; Jaffray, D. A.

    2011-12-15

    Purpose: Target delineation within volumetric imaging is a critical step in the planning process of intensity modulated radiation therapy. In endoluminal cancers, endoscopy often reveals superficial areas of visible disease beyond what is seen on volumetric imaging. Quantitatively relating these findings to the volumetric imaging is prone to human error during the recall and contouring of the target. We have developed a method to improve target delineation in the radiation therapy planning process by quantitatively registering endoscopic findings contours traced on endoscopic images to volumetric imaging. Methods: Using electromagnetic sensors embedded in an endoscope, 2D endoscopic images were registered to computed tomography (CT) volumetric images by tracking the position and orientation of the endoscope relative to a CT image set. Regions-of-interest (ROI) in the 2D endoscopic view were delineated. A mesh created within the boundary of the ROI was projected onto the 3D image data, registering the ROI with the volumetric image. This 3D ROI was exported to clinical radiation treatment planning software. The precision and accuracy of the procedure was tested on two solid phantoms with superficial markings visible on both endoscopy and CT images. The first phantom was T-shaped tube with X-marks etched on the interior. The second phantom was an anatomically correct skull phantom with a phantom superficial lesion placed on the pharyngeal surface. Markings were contoured on the endoscope images and compared with contours delineated in the treatment planning system based on the CT images. Clinical feasibility was tested on three patients with early stage glottic cancer. Image-based rendering using manually identified landmarks was used to improve the registration. Results: Using the T-shaped phantom with X-markings, the 2D to 3D registration accuracy was 1.5-3.5 mm, depending on the endoscope position relative to the markings. Intraobserver standard variation was 0

  9. Geometrical splitting technique to improve the computational efficiency in Monte Carlo calculations for proton therapy

    PubMed Central

    Ramos-Méndez, José; Perl, Joseph; Faddegon, Bruce; Schümann, Jan; Paganetti, Harald

    2013-01-01

    Purpose: To present the implementation and validation of a geometrical based variance reduction technique for the calculation of phase space data for proton therapy dose calculation. Methods: The treatment heads at the Francis H Burr Proton Therapy Center were modeled with a new Monte Carlo tool (TOPAS based on Geant4). For variance reduction purposes, two particle-splitting planes were implemented. First, the particles were split upstream of the second scatterer or at the second ionization chamber. Then, particles reaching another plane immediately upstream of the field specific aperture were split again. In each case, particles were split by a factor of 8. At the second ionization chamber and at the latter plane, the cylindrical symmetry of the proton beam was exploited to position the split particles at randomly spaced locations rotated around the beam axis. Phase space data in IAEA format were recorded at the treatment head exit and the computational efficiency was calculated. Depth–dose curves and beam profiles were analyzed. Dose distributions were compared for a voxelized water phantom for different treatment fields for both the reference and optimized simulations. In addition, dose in two patients was simulated with and without particle splitting to compare the efficiency and accuracy of the technique. Results: A normalized computational efficiency gain of a factor of 10–20.3 was reached for phase space calculations for the different treatment head options simulated. Depth–dose curves and beam profiles were in reasonable agreement with the simulation done without splitting: within 1% for depth–dose with an average difference of (0.2 ± 0.4)%, 1 standard deviation, and a 0.3% statistical uncertainty of the simulations in the high dose region; 1.6% for planar fluence with an average difference of (0.4 ± 0.5)% and a statistical uncertainty of 0.3% in the high fluence region. The percentage differences between dose distributions in water for

  10. Antioxidant treatment improves neonatal survival and prevents impaired cardiac function at adulthood following neonatal glucocorticoid therapy

    PubMed Central

    Niu, Youguo; Herrera, Emilio A; Evans, Rhys D; Giussani, Dino A

    2013-01-01

    Glucocorticoids are widely used to treat chronic lung disease in premature infants but their longer-term adverse effects on the cardiovascular system raise concerns. We reported that neonatal dexamethasone treatment in rats induced in the short term molecular indices of cardiac oxidative stress and cardiovascular tissue remodelling at weaning, and that neonatal combined antioxidant and dexamethasone treatment was protective at this time. In this study, we investigated whether such effects of neonatal dexamethasone have adverse consequences for NO bioavailability and cardiovascular function at adulthood, and whether neonatal combined antioxidant and dexamethasone treatment is protective in the adult. Newborn rat pups received daily i.p. injections of a human-relevant tapering dose of dexamethasone (D; n= 8; 0.5, 0.3, 0.1 μg g−1) or D with vitamins C and E (DCE; n= 8; 200 and 100 mg kg−1, respectively) on postnatal days 1–3 (P1–3); vitamins were continued from P4 to P6. Controls received equal volumes of vehicle from P1 to P6 (C; n= 8). A fourth group received vitamins alone (CCE; n= 8). At P100, plasma NO metabolites (NOx) was measured and isolated hearts were assessed under both Working and Langendorff preparations. Relative to controls, neonatal dexamethasone therapy increased mortality by 18% (P < 0.05). Surviving D pups at adulthood had lower plasma NOx concentrations (10.6 ± 0.8 vs. 28.0 ± 1.5 μm), an increased relative left ventricular (LV) mass (70 ± 2 vs. 63 ± 1%), enhanced LV end-diastolic pressure (14 ± 2 vs. 8 ± 1 mmHg) and these hearts failed to adapt output with increased preload (Δcardiac output: 2.9 ± 2.0 vs. 10.6 ± 1.2 ml min−1) or afterload (Δcardiac output: −5.3 ± 2.0 vs.1.4 ± 1.2 ml min−1); all P < 0.05. Combined neonatal dexamethasone with antioxidant vitamins improved postnatal survival, restored plasma NOx and protected against cardiac dysfunction at adulthood. In conclusion, neonatal dexamethasone therapy promotes

  11. Hybrid Assistive Neuromuscular Dynamic Stimulation Therapy: A New Strategy for Improving Upper Extremity Function in Patients with Hemiparesis following Stroke

    PubMed Central

    Honaga, Kaoru; Tochikura, Michi; Abe, Kaoru

    2017-01-01

    Hybrid Assistive Neuromuscular Dynamic Stimulation (HANDS) therapy is one of the neurorehabilitation therapeutic approaches that facilitates the use of the paretic upper extremity (UE) in daily life by combining closed-loop electromyography- (EMG-) controlled neuromuscular electrical stimulation (NMES) with a wrist-hand splint. This closed-loop EMG-controlled NMES can change its stimulation intensity in direct proportion to the changes in voluntary generated EMG amplitudes recorded with surface electrodes placed on the target muscle. The stimulation was applied to the paretic finger extensors. Patients wore a wrist-hand splint and carried a portable stimulator in an arm holder for 8 hours during the daytime. The system was active for 8 hours, and patients were instructed to use their paretic hand as much as possible. HANDS therapy was conducted for 3 weeks. The patients were also instructed to practice bimanual activities in their daily lives. Paretic upper extremity motor function improved after 3 weeks of HANDS therapy. Functional improvement of upper extremity motor function and spasticity with HANDS therapy is based on the disinhibition of the affected hemisphere and modulation of reciprocal inhibition. HANDS therapy may offer a promising option for the management of the paretic UE in patients with stroke. PMID:28191352

  12. Preparation and evaluation of radioiodinated 1-(dialkyl-aminoalkyl)-4-phenylpiperazines as potential brain imaging agents

    SciTech Connect

    Hanson, R.N.; Shourbagy, T.E.

    1985-05-01

    The interest in radioiodinated diamines stems from their similarity to /sup 125/I-HIPDM and to the 1-dialkvlamino-acyl-4-phenylpiperazines that the authors have previously examined as potential brain imaging agents. In this study they converted the 1-(dialkylaminoacyl)-4-phenylpiperazines to their corresponding 1-(dialkylaminoacyl) analogs via reduction with diborane in THF. Radioiodination at the no-carrier-added level with Na/sup 125/I and chloramine-T gave the final compounds, after chromatographic separation, in 30-50% yields. The tissue distributions were determined in rats at 0.25, and 4 hrs after an i.v. injection of the radiochemical. The results indicated that all of the agents were readily extracted by the brain (1.5-2.5% ID) with brain to blood ratios >20. The structure-distribution relationships for this series were, however, decidedly different from the aminoacyl compounds in that morpholino-derivatives had better uptake and retention than the piperidine derivatives. Neither extension of the alkyl chain nor the presence of carrier significantly altered the brain uptake and retention of the radiochemical. Further studies are in progress. In conclusion, they have identified a class of radiotracers that can be readily prepared and show a pattern of brain uptake and retention than the structurally similar 1-dialkylaminoacyl-4-phenylpiperazines.

  13. A rapid and economical method of preparing radioiodinated cyclic nucleotide derivatives for use in radioimmunoassays

    SciTech Connect

    Oehlenschlager, W.F.; Kubalak, S.W.; Currie, M.G. )

    1990-01-01

    2'-O-succinyladenosine 3':5'-cyclic monophosphate tyrosyl methyl ester (ScAMP-TME) and 2'-O-succinylguanosine 3':5'-cyclic monophosphate tyrosyl methyl ester (ScGMP-TME) were radioiodinated using chloramine T and Na125I. The resulting radiolabeled cyclic nucleotide derivatives, ScAMP-125I-TME and ScGMP-125I-TME, were subsequently purified by reverse-phase chromatography on Sep-Pak C18 cartridges (Waters Associates, Milford, MA) and tested as tracers in sensitive radioimmunoassays for cAMP and cGMP, respectively. Purified ScAMP-125I-TME and ScGMP-125I-TME functioned in the respective radioimmunoassays for up to 12 weeks when suspended in a 1:1 (v:v) mixture of n-propanol and 20 mM sodium acetate, pH 6.0. Thus, this purification method enables rapid and economical preparation of tracers for cyclic nucleotide radioimmunoassays. Furthermore, our findings suggest that reverse-phase chromatography may be applicable to the purification of other small polar molecules to which tyrosyl groups have been added for the purpose of radioiodination.

  14. Psychological and metabolic improvement after an outpatient teaching program for functional intensified insulin therapy (FIT).

    PubMed

    Langewitz, W; Wössmer, B; Iseli, J; Berger, W

    1997-09-01

    To be the master of their disease and not its slave is the ultimate goal of many patients with diabetes. Intensified functional insulin therapy (FIT) helps to establish this goal by an intensive patient education: each patient learns in five small-group sessions how s/he reacts to standardized challenges of glucose homeostasis (e.g. 24 h fasting; physical exercise; various carbohydrate loads). We investigated in 43 patients with long-standing diabetes type 1 (mean age: 33 +/- 10 years; mean duration of diabetes: 15 +/- 10 years) whether FIT improves quality of life, influences metabolic control and doctor-patient relationship. The following instruments were used: diabetes specific quality of life questionnaire (DQOL), hierarchical distance and cohesion between doctor and patient (FAST), anxiety and depression (HAD). Pre and post intervention values were compared with paired t-tests. HbA1c and number of hypoglycaemic episodes were also assessed 1 year after FIT and 1 year prior to FIT. Metabolic control was improved: HbA1c in the year before FIT: 6.72 +/- 1.35; 4 months before FIT: 6.61 +/- 1.46; 4 months after FIT: 6.29 +/- 1.09 (P < 0.05 compared to 4 months before FIT); 1 year after FIT: 6.46 +/- 1.12 (n.s. compared to 1 year before FIT). Dissatisfaction with life decreases from 33.3 +/- 8.0 to 28.5 +/- 7.7 (P < 0.001). Moments free of disease-specific strain increase from 74.3 +/- 13.9 to 78.1 +/- 16.1 (P = 0.07). Hierarchical distance between doctor and patient decreases from 1.1 +/- to 0.6 +/- 0.8 (P < 0.001), cohesion increases from 9.3 +/- 1.5 to 9.9 +/- 1.1 (P < 0.001). Anxiety and depression both decreases significantly: anxiety, 6.5 +/- 3.3-->4.6 +/- 3.2 (P < 0.001); depression, 2.7 +/- 2.5-->1.5 +/- 1.6 (P < 0.001). The number of patients with severe hypoglycaemic episodes (level 4) decreases from five (11.6%) to one (2.3%) after intervention (P < 0.05). In conclusion, FIT enhances quality of life in diabetic individuals. It helps to establish a less

  15. Improved dosimetry for targeted radionuclide therapy using nonrigid registration on sequential SPECT images

    SciTech Connect

    Ao, Edwin C. I.; Mok, Greta S. P.; Wu, Nien-Yun; Wang, Shyh-Jen; Song, Na

    2015-02-15

    Purpose: Voxel-level and patient-specific 3D dosimetry for targeted radionuclide therapy (TRT) typically involves serial nuclear medicine scans. Misalignment of the images can result in reduced dosimetric accuracy. Since the scans are typically performed over a period of several days, there will be patient movement between scans and possible nonrigid organ deformation. This work aims to implement and evaluate the use of nonrigid image registration on a series of quantitative SPECT (QSPECT) images for TRT dosimetry. Methods: A population of 4D extended cardiac torso phantoms, comprised of three In-111 Zevalin biokinetics models and three anatomical variations, was generated based on the patient data. The authors simulated QSPECT acquisitions at five time points. At each time point, individual organ and whole-body deformation between scans were modeled by translating/rotating organs and the body up to 5°/voxels, keeping ≤5% difference in organ volume. An analytical projector was used to generate realistic noisy projections for a medium energy general purpose collimator. Projections were reconstructed using OS-EM algorithm with geometric collimator detector response, attenuation, and scatter corrections. The QSPECT images were registered using organ-based nonrigid image registration method. The cumulative activity in each voxel was obtained by integrating the activity over time. Dose distribution images were obtained by convolving the cumulative activity images with a Y-90 dose kernel. Dose volume histograms (DVHs) for organs-of-interest were analyzed. Results: After nonrigid registration, the mean differences in organ doses compared to the case without misalignment were improved from (−15.50 ± 5.59)% to (−2.12 ± 1.05)% and (−7.28 ± 2.30)% to (−0.23 ± 0.71)% for the spleen and liver, respectively. For all organs, the cumulative DVHs showed improvement after nonrigid registration and the normalized absolute error of differential DVHs ranged from 6.79% to

  16. Play Therapy in Elementary Schools: A Best Practice for Improving Academic Achievement

    ERIC Educational Resources Information Center

    Blanco, Pedro J.; Ray, Dee C.

    2011-01-01

    This pilot study of 1st graders who are academically at risk examined the effectiveness of child-centered play therapy (CCPT). The experimental group received biweekly, 30-minute play therapy sessions for 8 weeks. Findings indicated that these 1st graders participating in CCPT (n = 21) demonstrated a statistically significant increase on the Early…

  17. Combined sonodynamic and antimetabolite therapy for the improved treatment of pancreatic cancer using oxygen loaded microbubbles as a delivery vehicle.

    PubMed

    McEwan, Conor; Kamila, Sukanta; Owen, Joshua; Nesbitt, Heather; Callan, Bridgeen; Borden, Mark; Nomikou, Nikolitsa; Hamoudi, Rifat A; Taylor, Mark A; Stride, Eleanor; McHale, Anthony P; Callan, John F

    2016-02-01

    In this manuscript we describe the preparation of an oxygen-loaded microbubble (O2MB) platform for the targeted treatment of pancreatic cancer using both sonodynamic therapy (SDT) and antimetabolite therapy. O2MB were prepared with either the sensitiser Rose Bengal (O2MB-RB) or the antimetabolite 5-fluorouracil (O2MB-5FU) attached to the microbubble (MB) surface. The MB were characterised with respect to size, physical stability and oxygen retention. A statistically significant reduction in cell viability was observed when three different pancreatic cancer cell lines (BxPc-3, MIA PaCa-2 and PANC-1), cultured in an anaerobic cabinet, were treated with both SDT and antimetabolite therapy compared to either therapy alone. In addition, a statistically significant reduction in tumour growth was also observed when ectopic human xenograft BxPC-3 tumours in SCID mice were treated with the combined therapy compared to treatment with either therapy alone. These results illustrate not only the potential of combined SDT/antimetabolite therapy as a stand alone treatment option in pancreatic cancer, but also the capability of O2-loaded MBs to deliver O2 to the tumour microenvironment in order to enhance the efficacy of therapies that depend on O2 to mediate their therapeutic effect. Furthermore, the use of MBs to facilitate delivery of O2 as well as the sensitiser/antimetabolite, combined with the possibility to activate the sensitiser using externally applied ultrasound, provides a more targeted approach with improved efficacy and reduced side effects when compared with conventional systemic administration of antimetabolite drugs alone.

  18. Radioiodinated iodobenzoyl conjugates of a monoclonal antibody Fab fragment. In vivo comparisons with chloramine-T-labeled Fab

    SciTech Connect

    Wilbur, D.S.; Hadley, S.W.; Grant, L.M.; Hylarides, M.D. )

    1991-03-01

    A comparative investigation of the biodistributions of radioiodinated p- and m-iodobenzoyl conjugates of a monoclonal antibody Fab fragment, NR-LU-10 Fab, and the same antibody Fab fragment radioiodinated by the chloramine-T (ChT) method has been carried out in mice. Coinjected, dual-isotope studies in athymic mice with tumor xenografts have demonstrated that there are only minor differences in the in vivo distributions of the iodobenzoyl-labeled Fabs, except in the excretory organs, kidneys, and intestines, where major differences were observed. Similarly, coinjection of either the p-iodobenzoyl or m-iodobenzoyl conjugate of NR-LU-10 Fab with the Fab radioiodinated with ChT/radioiodide into BALB/c mice provided additional data that indicated that the two iodobenzoyl conjugates distributed similar in a number of selected tissues. The tissue-distribution differences of the regioisomeric iodobenzoyl conjugates in relation to the ChT-radioiodinated Fab were large for the stomach and neck, consistent with previous studies. The most notable difference between the two iodobenzoyl conjugates was the kidney activity, where the m-iodobenzoyl conjugate was similar to the directly labeled Fab, but the p-iodobenzoyl-conjugated Fab was higher by nearly a factor of 2.

  19. Postnatal Gene Therapy Improves Spatial Learning Despite the Presence of Neuronal Ectopia in a Model of Neuronal Migration Disorder

    PubMed Central

    Hu, Huaiyu; Liu, Yu; Bampoe, Kevin; He, Yonglin; Yu, Miao

    2016-01-01

    Patients with type II lissencephaly, a neuronal migration disorder with ectopic neurons, suffer from severe mental retardation, including learning deficits. There is no effective therapy to prevent or correct the formation of neuronal ectopia, which is presumed to cause cognitive deficits. We hypothesized that learning deficits were not solely caused by neuronal ectopia and that postnatal gene therapy could improve learning without correcting the neuronal ectopia formed during fetal development. To test this hypothesis, we evaluated spatial learning of cerebral cortex-specific protein O-mannosyltransferase 2 (POMT2, an enzyme required for O-mannosyl glycosylation) knockout mice and compared to the knockout mice that were injected with an adeno-associated viral vector (AAV) encoding POMT2 into the postnatal brains with Barnes maze. The data showed that the knockout mice exhibited reduced glycosylation in the cerebral cortex, reduced dendritic spine density on CA1 neurons, and increased latency to the target hole in the Barnes maze, indicating learning deficits. Postnatal gene therapy restored functional glycosylation, rescued dendritic spine defects, and improved performance on the Barnes maze by the knockout mice even though neuronal ectopia was not corrected. These results indicate that postnatal gene therapy improves spatial learning despite the presence of neuronal ectopia. PMID:27916859

  20. Improved Neural Processing Efficiency in a Chronic Aphasia Patient Following Melodic Intonation Therapy: A Neuropsychological and Functional MRI Study

    PubMed Central

    Tabei, Ken-ichi; Satoh, Masayuki; Nakano, Chizuru; Ito, Ai; Shimoji, Yasuo; Kida, Hirotaka; Sakuma, Hajime; Tomimoto, Hidekazu

    2016-01-01

    Melodic intonation therapy (MIT) is a treatment program for the rehabilitation of aphasic patients with speech production disorders. We report a case of severe chronic non-fluent aphasia unresponsive to several years of conventional therapy that showed a marked improvement following intensive 9-day training on the Japanese version of MIT (MIT-J). The purpose of this study was to verify the efficacy of MIT-J by functional assessment and examine associated changes in neural processing by functional magnetic resonance imaging. MIT improved language output and auditory comprehension, and decreased the response time for picture naming. Following MIT-J, an area of the right hemisphere was less activated on correct naming trials than compared with before training but similarly activated on incorrect trials. These results suggest that the aphasic symptoms of our patient were improved by increased neural processing efficiency and a concomitant decrease in cognitive load. PMID:27698650

  1. A comparison of low versus high radioiodine administered activity in patients with low-risk differentiated thyroid cancer.

    PubMed

    Ben Ghachem, T; Yeddes, I; Meddeb, I; Bahloul, A; Mhiri, A; Slim, I; Ben Slimene, M F

    2017-02-01

    Post-surgical therapeutic management of differentiated thyroid cancer (DTC) is still a controversial subject. Indeed, there is no consensus on the dose of (131)I to be administered, although the current trend towards therapy easing through mini-cures for patients with good prognosis. To confirm the non-inferiority in terms of effectiveness of an ablative mini-cure from 1.11 to 1.85 GBq, over a cure of 3.7 GBq, in patients with DTC operated for low and very low risk. We retrospectively studied 157 patients with very low and low risk DTC, followed in the Nuclear Medicine Department of the Salah Azaiez Institute between 2002 and 2012. These patients had a complementary radioiodine therapy with either low dose (group A) or high dose (group B) with an evaluation at 6 months post treatment and in long-term. The study took place at a referral center. The average age was 42.8 ± 13.7 years with a female predominance (86.7 %). The DTC papillary represented the most common etiology (95 %) with a predominance of pure papillary (68 %) on the follicular variant (27 %). The first cure evaluation did not show statistically significant difference between the two approaches in terms of therapeutic ablative efficiency (p = 0.13). The overall success rate was 77 % (121/157), with 83 % (54/65) in group A and 72.8 % (67/92) in group B. The likelihood of having a remission from the first cure was 1.83 times greater for patients treated with low doses (OR = 1.83, 95 % CI 0.23-1.29). At the end of follow, we have noted one case of refractory disease. The male gender (adjusted OR = 2.71, 95 % CI 0.51-4.23, p = 0.03), and the baseline Tg ≥ 10 (ng/ml) (adjusted OR = 3.48, 95 % CI 1.25-9.67, p = 0.01) were significantly independent predictors of successful first cure ablation. The results provide that mini-dose protocol is not less effective for ablation of the thyroid remnant than 3.7 GBq activity.

  2. Distress among hospitalized pediatric cancer patients modified by pet-therapy intervention to improve quality of life.

    PubMed

    Urbanski, Beth L; Lazenby, Mark

    2012-01-01

    This state of the science, integrative literature review focuses on animal-facilitated therapy (AFT) and the benefits provided to quality of life in hospitalized pediatric oncology patients. Results showed physiological and psychological benefits in pediatric inpatients settings. AFT has been shown to decrease pain, change vital signs, provide distraction, decrease fear, increase socialization, increase pleasure and decrease emotional distress in hospitalized pediatric patients. AFT needs to be implemented with appropriate medical discretion, but for the appropriate high-risk patients, AFT can improve quality of life. Pain, adjustment difficulties, mood changes and symptom management can be improved in inpatient pediatric cancer patients receiving AFT, thus improving overall quality of life.

  3. Complementary traditional Chinese medicine therapy improves survival in patients with metastatic prostate cancer

    PubMed Central

    Liu, Jui-Ming; Lin, Po-Hung; Hsu, Ren-Jun; Chang, Ying-Hsu; Cheng, Kuan-Chen; Pang, See-Tong; Lin, Shun-Ku

    2016-01-01

    Abstract More than 50% of prostate cancer patients have used traditional Chinese medicine (TCM) in Taiwan. However, the long-term clinical efficacy of TCM in prostate cancer patients remains unclear. Here, we investigated the relationship between TCM use and the survival of prostate cancer patients. A retrospective nationwide cohort study of prostate cancer patients was conducted between 1998 and 2003 using the Taiwan National Health Insurance Research Database. Patients were classified as TCM users or nonusers, and monitored from the day of prostate cancer diagnosis to death or end of 2012. The association between death risk and TCM use was determined using Cox proportional-hazards models and Kaplan–Meier curves. Of the 1132 selected prostate cancer patients, 730 (64.5%) and 402 (35.5%) were TCM users and nonusers, respectively. The mean follow-up period was 8.38 years, and 292 (25.8%) deaths were reported. TCM users had a decreased mortality rate (21.9%) compared with nonusers (32.8%). A lower death risk was observed with longer TCM use, especially in patients who used TCM for ≧200 days (adjusted hazard ratio [aHR] 0.61, 95% confidence interval [CI] 0.44–0.84). TCM users with metastatic prostate cancer had a significant lower HR than nonusers (aHR 0.70, 95% CI 0.51–0.95). Chai-Hu-Jia-Long-Gu-Mu-Li-Tang was the most significant TCM formulae for improving survival in metastatic prostate cancer (aHR 0.18, 95% CI 0.04–0.94). The result suggested that complementary TCM therapy might be associated with a reduced risk of death in metastatic prostate cancer patients. PMID:27495088

  4. Targeting tumor perfusion and oxygenation to improve the outcome of anticancer therapy.

    PubMed

    Jordan, Bénédicte F; Sonveaux, Pierre

    2012-01-01

    Radiotherapy and chemotherapy are widespread clinical modalities for cancer treatment. Among other biological influences, hypoxia is a main factor limiting the efficacy of radiotherapy, primarily because oxygen is involved in the stabilization of the DNA damage caused by ionizing radiations. Radiobiological hypoxia is found in regions of rodent and human tumors with a tissue oxygenation level below 10 mmHg at which tumor cells become increasingly resistant to radiation damage. Since hypoxic tumor cells remain clonogenic, their resistance to the treatment strongly influences the therapeutic outcome of radiotherapy. There is therefore an urgent need to identify adjuvant treatment modalities aimed to increase tumor pO(2) at the time of radiotherapy. Since tumor hypoxia fundamentally results from an imbalance between oxygen delivery by poorly efficient blood vessels and oxygen consumption by tumor cells with high metabolic activities, two promising approaches are those targeting vascular reactivity and tumor cell respiration. This review summarizes the current knowledge about the development and use of tumor-selective vasodilators, inhibitors of tumor cell respiration, and drugs and treatments combining both activities in the context of tumor sensitization to X-ray radiotherapy. Tumor-selective vasodilation may also be used to improve the delivery of circulating anticancer agents to tumors. Imaging tumor perfusion and oxygenation is of importance not only for the development and validation of such combination treatments, but also to determine which patients could benefit from the therapy. Numerous techniques have been developed in the preclinical setting. Hence, this review also briefly describes both magnetic resonance and non-magnetic resonance in vivo methods and compares them in terms of sensitivity, quantitative or semi-quantitative properties, temporal, and spatial resolutions, as well as translational aspects.

  5. Porphyrin-based polysilsesquioxane nanoparticles to improve photodynamic therapy for cancer treatment

    NASA Astrophysics Data System (ADS)

    Vivero-Escoto, Juan L.; DeCillis, Daniel; Fritts, Laura; Vega, Daniel L.

    2014-03-01

    Photodynamic therapy (PDT) has emerged as an alternative approach to chemotherapy and radiotherapy for cancer treatment. The photosensitizer (PS) is perhaps the most critical component of PDT, and continues to be an area of intense scientific research. Traditionally, PS molecules (e.g. porphyrins) have dominated the field. Nevertheless, these PS agents have several disadvantages, with low water solubility, poor light absorption and reduced selectivity for targeted tissues being some of the main drawbacks. Polysilsesquioxane (PSilQ) nanoparticles are crosslinked homopolymers formed by the condensation of functionalized trialkoxysilanes or bis(trialkoxysilanes). We believe that PSilQ particles provide an interesting platform for developing PS nanocarriers. Several advantages can be foreseen by using this platform such as carrying a large payload of PS molecules; their surface and composition can be tailored to develop multifunctional systems (e.g. target-specific); and due to their small size, nanoparticles can penetrate deep into tissues and be readily internalized by cells. In this work, PSilQ nanoparticles with a high payload of photosensitizers were synthesized, characterized, and applied in vitro. The network of this nanomaterial is formed by protoporphyrin IX (PpIX) molecules chemically connected via a redox-responsive linker. Under reducing environment such as the one found in cancer cells the nanoparticles can be degraded to efficiently release single photosensitizers in the cytoplasm. The phototoxicity of this porphyrin-based PSilQ nanomaterial was successfully demonstrated in vitro using human cervical (HeLa) cancer cells. We envision that this platform can be further functionalized with polyethylene glycol (PEG) and targeting ligands to improve its biocompatibility and target specificity.

  6. Cognitive behavioral therapy for depression improves pain and perceived control in cardiac surgery patients

    PubMed Central

    Doering, Lynn V; McGuire, Anthony; Eastwood, Jo-Ann; Chen, Belinda; Bodán, Rebecca C; Czer, Lawrence S; Irwin, Michael R

    2015-01-01

    Background Depression after cardiac surgery (CS) is associated with increased pain and decreased sleep quality. While cognitive behavioral therapy (CBT) aimed at depression is effective in relieving depressive symptoms after cardiac surgery, little is known about its ability to ameliorate other common postoperative problems that affect recovery and quality of life. Aims The purpose of this study was to evaluate the effects of CBT for depression on pain severity, pain interference, sleep, and perceived control in patients recovering from CS. Methods Depressed patients recovering from CS were randomized to receive either eight weeks of CBT or usual care. At baseline and post-intervention, patients completed questionnaires for depressive symptoms, pain, sleep, and perceived control. Group comparisons were conducted using t-tests or chi square analysis. Repeated measures analysis was used to assess the effect of the intervention in changes over time. Results The sample (n=53) included 16.9% women and had a mean age of 67.8±9.2 years. CBT for depression increased perceived control (p<0.001) and decreased pain interference (p=0.02) and pain severity (p=0.03). Group effects remained significant (p<0.05) for perceived control and pain interference and a trend was observed for pain severity (p<0.10) after controlling for variables that differed at baseline. There were no group differences in sleep disturbance over time. Conclusions A depression-focused CBT intervention yields benefits in other common postoperative problems, specifically improved perceived control and decreased pain in depressed cardiac surgery patients. PMID:26115954

  7. A next-generation bifunctional photosensitizer with improved water-solubility for photodynamic therapy and diagnosis

    PubMed Central

    Nishie, Hirotada; Kataoka, Hiromi; Yano, Shigenobu; Kikuchi, Jun-ichi; Hayashi, Noriyuki; Narumi, Atsushi; Nomoto, Akihiro; Kubota, Eiji; Joh, Takashi

    2016-01-01

    Photodynamic therapy (PDT) exploits light interactions and photosensitizers to induce cytotoxic reactive oxygen species. Photodynamic diagnosis (PDD) uses the phenomenon of photosensitizer emitting fluorescence to distinguish some tumors from normal tissue. The standard photosensitizer used for PDD is 5-aminolevulinic acid (5-ALA), although it is not entirely satisfactory. We previously reported glucose-conjugated chlorin (G-chlorin) as a more effective photosensitizer than another widely used photosensitizer, talaporfin sodium (TS); however, G-chlorin is hydrophobic. We synthesized oligosaccharide-conjugated chlorin (O-chlorin) with improved water-solubility. We report herein on its accumulation and cytotoxicity. O-chlorin was synthesized and examined for solubility. Flow cytometric analysis was performed to evaluate O-chlorin accumulation in cancer cells. To evaluate the intracellular localization of photosensitizer, cells were stained with O-chlorin and organelle-specific fluorescent probes. We then measured the in vitro fluorescence of various photosensitizers and the half-maximal inhibitory concentrations to evaluate effects in PDD and PDT, respectively. Xenograft tumor models were established, and antitumor and visibility effects were analyzed. O-chlorin was first shown to be hydrophilic. Flow cytometry then revealed a 20- to 40-times higher accumulation of O-chlorin in cancer cells than of TS, and a 7- to 23-times greater fluorescence than 5-ALA. In vitro, the cytotoxicity of O-chlorin PDT was stronger than that of TS PDT, and O-chlorin tended to accumulate in lysosomes. In vivo, O-chlorin showed the best effect in PDT and PDD compared to other photosensitizers. O-chlorin was hydrophilic and showed excellent tumor accumulation and fluorescence. O-chlorin is promising as a next-generation bifunctional photosensitizer candidate for both PDT and PDD. PMID:27708235

  8. Epithelial Junction Opener Improves Oncolytic Adenovirus Therapy in Mouse Tumor Models

    PubMed Central

    Yumul, Roma; Richter, Maximilian; Lu, Zhuo-Zhuang; Saydaminova, Kamola; Wang, Hongjie; Wang, Chung-Huei Katherine; Carter, Darrick; Lieber, André

    2016-01-01

    A central resistance mechanism in solid tumors is the maintenance of epithelial junctions between malignant cells that prevent drug penetration into the tumor. Human adenoviruses (Ads) have evolved mechanisms to breach epithelial barriers. For example, during Ad serotype 3 (Ad3) infection of epithelial tumor cells, massive amounts of subviral penton-dodecahedral particles (PtDd) are produced and released from infected cells to trigger the transient opening of epithelial junctions, thus facilitating lateral virus spread. We show here that an Ad3 mutant that is disabled for PtDd production is significantly less effective in killing of epithelial human xenograft tumors than the wild-type Ad3 virus. Intratumoral spread and therapeutic effect of the Ad3 mutant was enhanced by co-administration of a small recombinant protein (JO; produced in Escherichia coli) that incorporated the minimal junction opening domains of PtDd. We then demonstrated that co-administration of JO with replication-competent Ads that do not produce PtDd (Ad5, Ad35) resulted in greater attenuation of tumor growth than virus injection alone. Furthermore, we genetically modified a conditionally replicating Ad5-based oncolytic Ad (Ad5Δ24) to express a secreted form of JO upon replication in tumor cells. The JO-expressing virus had a significantly greater antitumor effect than the unmodified AdΔ24 version. Our findings indicate that epithelial junctions limit the efficacy of oncolytic Ads and that this problem can be address by co-injection or expression of JO. JO has also the potential for improving cancer therapy with other types of oncolytic viruses. PMID:26993072

  9. Improvement of Right Ventricular Hemodynamics with Left Ventricular Endocardial Pacing during Cardiac Resynchronization Therapy

    PubMed Central

    HYDE, EOIN R.; BEHAR, JONATHAN M.; CROZIER, ANDREW; CLARIDGE, SIMON; JACKSON, TOM; SOHAL, MANAV; GILL, JASWINDER S.; O'NEILL, MARK D.; RAZAVI, REZA; RINALDI, CHRISTOPHER A.

    2016-01-01

    Background Cardiac resynchronization therapy (CRT) with biventricular epicardial (BV‐CS) or endocardial left ventricular (LV) stimulation (BV‐EN) improves LV hemodynamics. The effect of CRT on right ventricular function is less clear, particularly for BV‐EN. Our objective was to compare the simultaneous acute hemodynamic response (AHR) of the right and left ventricles (RV and LV) with BV‐CS and BV‐EN in order to determine the optimal mode of CRT delivery. Methods Nine patients with previously implanted CRT devices successfully underwent a temporary pacing study. Pressure wires measured the simultaneous AHR in both ventricles during different pacing protocols. Conventional epicardial CRT was delivered in LV‐only (LV‐CS) and BV‐CS configurations and compared with BV‐EN pacing in multiple locations using a roving decapolar catheter. Results Best BV‐EN (optimal AHR of all LV endocardial pacing sites) produced a significantly greater RV AHR compared with LV‐CS and BV‐CS pacing (P < 0.05). RV AHR had a significantly increased standard deviation compared to LV AHR (P < 0.05) with a weak correlation between RV and LV AHR (Spearman rs = −0.06). Compromised biventricular optimization, whereby RV AHR was increased at the expense of a smaller decrease in LV AHR, was achieved in 56% of cases, all with BV‐EN pacing. Conclusions BV‐EN pacing produces significant increases in both LV and RV AHR, above that achievable with conventional epicardial pacing. RV AHR cannot be used as a surrogate for optimizing LV AHR; however, compromised biventricular optimization is possible. The beneficial effect of endocardial LV pacing on RV function may have important clinical benefits beyond conventional CRT. PMID:27001004

  10. Polyacrylonitrile-Chalcogel Hybrid Sorbents for Radioiodine Capture

    SciTech Connect

    Brian J. Riley; David A. Pierce; Jaehun Chun; Josef Matyas; William C. Lepry; Troy G. Garn; Jack D. Law; Mercouri G. Kanatzidis

    2014-04-01

    Powders of a Sn2S3 chalcogen-based aerogel (chalcogel) were combined with powdered polyacrylonitrile (PAN) in different mass ratios (SnS33, SnS50, and SnS70; # = mass% of chalcogel), dissolved in dimethyl sulfoxide, and added dropwise to deionized water to form pellets of a porous PAN-chalcogel hybrid material. These pellets, along with pure powdered (SnSp) and granular (SnSg) forms of the chalcogel, were then used to capture iodine gas under both dynamic (dilute) and static (concentrated) conditions. Both SnSp and SnSg chalcogels showed very high iodine loadings at 67.2 and 68.3 mass%, respectively. The SnS50 hybrid sorbent demonstrated a high, although slightly reduced, maximum iodine loading (53.5 mass%) with greatly improved mechanical rigidity. In all cases, X-ray diffraction results showed the formation of crystalline SnI4 and SnI4(S8)2, revealing that the iodine binding in these materials is mainly due to a chemisorption process, although a small amount of physisorption was observed.

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

    SciTech Connect

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

    2005-10-01

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

  12. The Influence of Speech-Language-Hearing Therapy Duration on the Degree of Improvement in Poststroke Language Impairment

    PubMed Central

    Okada, Eisaku; Shibata, Yosuke; Nakamura, Mieko; Ojima, Toshiyuki

    2017-01-01

    Background. The relevance of speech-language-hearing therapy (ST) duration to language impairment remains unclear. Objective. To determine the effect of ST duration on improvement in language impairment as a stroke sequela and to compare the findings with those for occupational therapy (OT) and physical therapy (PT). Methods. Data regarding patients with stroke sequelae who were registered in the Japanese Association of Rehabilitation Medicine database were analyzed. Propensity scores for ST, OT, and PT duration were calculated using logistic regression, followed by inverse probability weighting in generalized estimating equations to examine the odds ratio for improvement in the Functional Independence Measures scores for comprehension, expression, and memory. Analyses stratified by age and dementia severity were also conducted. Results. Compared with short-duration ST, long-duration ST was significantly associated with improved scores for comprehension and expression in the overall study population and in some groups, with higher benefit especially for younger participants (<64 years) and those with more severe dementia. A significant but less pronounced effect was also observed for OT and PT. Conclusion. Long-duration ST is more effective than long-duration OT or PT for improving language impairment occurring as stroke sequela. However, these effects are limited by age and severity of dementia. PMID:28168056

  13. Waon therapy improves quality of life as well as cardiac function and exercise capacity in patients with chronic heart failure.

    PubMed

    Sobajima, Mitsuo; Nozawa, Takashi; Fukui, Yasutaka; Ihori, Hiroyuki; Ohori, Takashi; Fujii, Nozomu; Inoue, Hiroshi

    2015-01-01

    Waon therapy (WT), which in Japanese means soothing warmth, is a repeated sauna therapy that improves cardiac and vascular endothelial function in patients with chronic heart failure (CHF). We investigated whether WT could improve the quality of life (QOL) of CHF patients in addition to improving cardiac function and exercise capacity.A total of 49 CHF patients (69 ± 14 years old) were treated with a 60°C far infrared-ray dry sauna bath for 15 minutes and then kept in a bed covered with blankets for 30 minutes once a day for 3 weeks. At baseline and 3 weeks after starting WT, cardiac function, 6-minute walk distance (6MWD), flow mediated dilation (FMD) of the brachial artery, and SF36-QOL scores were determined.WT significantly improved left ventricular ejection fraction (LVEF), B-type natriuretic peptide (BNP), 6MWD, and FMD (3.6 ± 2.3 to 5.1 ± 2.8%, P < 0.01). Moreover, WT significantly improved not only the physical (PC) but also mental component (MC) of the QOL scores. WT-induced improvement of PC was negatively correlated with changes in BNP (r = -0.327, P < 0.05), but MC improvement was not related directly to changes in BNP, LVEF, or 6MWD. WT-induced changes in MC were not parallel to PC improvement.WT improved QOL as well as cardiac function and exercise capacity in patients with CHF. Mental QOL improved independently of WT-induced improvement of cardiac function and exercise capacity.

  14. Radiation Therapy Is Associated With Improved Survival in the Adjuvant and Definitive Treatment of Intrahepatic Cholangiocarcinoma

    SciTech Connect

    Shinohara, Eric T. Mitra, Nandita; Guo Mengye; Metz, James M.

    2008-12-01

    Purpose: Intrahepatic cholangiocarcinomas (IHC) are rare tumors for which large randomized studies regarding the use of radiation are not available. The purpose of this study was to examine the role of adjuvant and definitive radiation therapy in the treatment of IHC in a large group of patients. Methods and Materials: This is a retrospective analysis of 3,839 patients with IHC collected from the Surveillance, Epidemiology, and End Results (SEER) database. The primary endpoint was overall survival (OS). Results: Patients received either surgery alone (25%), radiation therapy alone (10%), surgery and adjuvant radiation therapy (7%) or no treatment (58%). The median age of the patient population was 73 years (range, 22-102 years); 52% of patients were male and 81% were Caucasian. Median OS was 11 (95% confidence interval [CI], 9-13), 6 (95% CI, 5-6), 7 (95% CI, 6-8), and 3 months for surgery and adjuvant radiation therapy, sugery alone, radiation therapy alone, and no treatment, respectively. The OS was significantly different between surgery alone and surgery and adjuvant radiation therapy (p = 0.014) and radiation therapy alone and no treatment (p < 0.0001). Use of surgery and adjuvant radiation therapy conferred the greatest benefit on OS (HR = 0.40; 95% CI, 0.34-0.47), followed by surgery alone (hazard ratio [HR], 0.49; 95% CI, 0.44-0.54) and radiation therapy alone (HR, 0.68; 95% CI, 0.59-0.77) compared with no treatment, on multivariate analysis. Propensity score adjusted hazard ratios (controlling for age, race/ethnicity, stage, and year of diagnosis) were also significant (surgery and adjuvant radiation therapy vs. surgery alone (HR, 0.82; 95% CI, 0.70-0.96); radiation therapy alone vs. no treatment (HR, 0.67; 95% CI, 0.58-0.76)). Conclusions: The study results suggest that adjuvant and definitive radiation treatment prolong survival, although cure rates remain low. Future studies should evaluate the addition of chemotherapy and biologics to the treatment of

  15. Music Therapy Using Singing Training Improves Psychomotor Speed in Patients with Alzheimer's Disease: A Neuropsychological and fMRI Study

    PubMed Central

    Satoh, Masayuki; Yuba, Toru; Tabei, Ken-ichi; Okubo, Yukari; Kida, Hirotaka; Sakuma, Hajime; Tomimoto, Hidekazu

    2015-01-01

    Background/Aims To investigate the effect of singing training on the cognitive function in Alzheimer's disease (AD) patients. Methods Ten AD patients (mean age 78.1 years) participated in music therapy using singing training once a week for 6 months (music therapy group). Each session was performed with professional musicians using karaoke and a unique voice training method (the YUBA Method). Before and after the intervention period, each patient was assessed by neuropsychological batteries, and functional magnetic resonance imaging (fMRI) was performed while the patients sang familiar songs with a karaoke device. As the control group, another 10 AD patients were recruited (mean age 77.0 years), and neuropsychological assessments were performed twice with an interval of 6 months. Results In the music therapy group, the time for completion of the Japanese Raven's Colored Progressive Matrices was significantly reduced (p = 0.026), and the results obtained from interviewing the patients' caregivers revealed a significant decrease in the Neuropsychiatric Inventory score (p = 0.042) and a prolongation of the patients' sleep time (p = 0.039). The fMRI study revealed increased activity in the right angular gyrus and the left lingual gyrus in the before-minus-after subtraction analysis of the music therapy intervention. Conclusion Music therapy intervention using singing training may be useful for dementia patients by improving the neural efficacy of cognitive processing. PMID:26483829

  16. Improved tumor vascularization after anti-VEGF therapy with carboplatin and nab-paclitaxel associates with survival in lung cancer

    PubMed Central

    Heist, Rebecca S.; Duda, Dan G.; Sahani, Dushyant V.; Ancukiewicz, Marek; Fidias, Panos; Sequist, Lecia V.; Temel, Jennifer S.; Shaw, Alice T.; Pennell, Nathan A.; Neal, Joel W.; Gandhi, Leena; Lynch, Thomas J.; Engelman, Jeffrey A.; Jain, Rakesh K.

    2015-01-01

    Addition of anti-VEGF antibody therapy to standard chemotherapies has improved survival and is an accepted standard of care for advanced non–small cell lung cancer (NSCLC). However, the mechanisms by which anti-VEGF therapy increases survival remain unclear. We evaluated dynamic CT-based vascular parameters and plasma cytokines after bevacizumab alone and after bevacizumab plus chemotherapy with carboplatin and nab-paclitaxel in advanced NSCLC patients to explore potential biomarkers of treatment response and resistance to this regimen. Thirty-six patients were enrolled in this study. The primary end point was 6-mo progression-free survival rate, which was 74% (95% CI: 57, 97). This regimen has a promising overall response rate of 36% and median time to progression of 8.5 (6.0, 38.7) mo and overall survival of 12.2 (9.6, 44.1) mo. We found that anti-VEGF therapy led to a sustained increase in plasma PlGF, a potential pharmacodynamic marker. We also found that higher levels of soluble VEGFR1 measured before starting bevacizumab with chemotherapy were associated with worse survival, supporting its potential role as biomarker of treatment resistance. Our imaging biomarker studies indicate that bevacizumab-based treatment—while reducing blood flow, volume, and permeability in the overall population—may be associated with improved survival in patients with improved tumor vasculature and blood perfusion after treatment. This hypothesis-generating study supports the notion that excessively decreasing vascular permeability and pruning/rarefaction after bevacizumab therapy may negatively impact the outcome of combination therapy in NSCLC patients. This hypothesis warrants further dose-titration studies of bevacizumab to examine the dose effect on tumor vasculature and treatment efficacy. PMID:25605928

  17. Synthesis and evaluation of glycosylated octreotate analogues labeled with radioiodine and 211At via a tin precursor.

    PubMed

    Vaidyanathan, G; Affleck, D J; Schottelius, M; Wester, H; Friedman, H S; Zalutsky, M R

    2006-01-01

    Carbohydration of N-terminus and substitution of a threonine for the threoninol residue at the C-terminus of Tyr3-octreotide (TOC) has resulted in improved pharmacokinetics and tumor targeting of its radioiodinated derivatives. Yet, these peptides are very susceptible to in vivo deiodination due to the similarity of monoiodotyrosine (MIT) to thyroid hormone. The goal of this work was to develop octreotate analogues containing both a sugar moiety and a nontyrosine prosthetic group on which a radioiodine or 211At can be introduced. Solid-phase synthesis and subsequent modifications delivered an iodo standard of the target peptide N(alpha)-(1-deoxy-D-fructosyl)-N(epsilon)-(3-iodobenzoyl)-Lys0-octreotate (GIBLO) and the corresponding tin precursor N(alpha)-(1-deoxy-D-fructosyl)-N(epsilon)-[(3-tri-n-butylstannyl)benzoyl]-Lys0-octreotate (GTBLO). GIBLO displaced [125I]TOC from somatostatin receptor subtype 2 (SSTR2)-positive AR42J rat pancreatic tumor cell membranes with an IC50 of 0.46 +/- 0.05 nM suggesting that GIBLO retained affinity to SSTR2. GTBLO was radiohalogenated to [131I]GIBLO and N(alpha)-(1-deoxy-D-fructosyl)-N(epsilon)-(3-[211At]astatobenzoyl)-Lys0-octreotate ([211At]GABLO) in 21.2 +/- 4.9% and 46.8 +/- 9.5% radiochemical yields, respectively. From a paired-label internalization assay using D341 Med medulloblastoma cells, the maximum specific internalized radioactivity from [131I]GIBLO was 1.78 +/- 0.8% of input dose compared to 9.67 +/- 0.43% for N(alpha)-(1-deoxy-D-fructosyl)-[125I]iodo-Tyr3-octreotate ([125I]I-Gluc-TOCA). Over a 4 h period, the extent of internalization of [131I]GIBLO and [211At]GABLO was similar in this cell line. In D341 Med murine subcutaneous xenografts, the uptake of [125I]I-Gluc-TOCA at 0.5, 1 and 4 h was 21.5 +/- 4.0% ID/g, 18.8 +/- 7.7% ID/g, and 0.9 +/- 0.4% ID/g, respectively. In comparison, these values for [131I]GIBLO were 6.9 +/- 1.2% ID/g, 4.7 +/- 1.4% ID/g, and 0.8 +/- 0.5% ID/g. Both in vitro and in vivo catabolism

  18. Anti-TNF-α therapy improves Treg and suppresses Teff in patients with rheumatoid arthritis.

    PubMed

    Huang, Zhuochun; Yang, Bin; Shi, Yunying; Cai, Bei; Li, Yi; Feng, Weihua; Fu, Yang; Luo, Limei; Wang, Lanlan

    2012-09-01

    Anti-TNF-α therapies have been applied in RA treatment, but the regulatory effect of the drug on immune system is not clear. In this study, we included 33 active RA patients and divided them into two groups. One group received anti-TNF-α mAb+methotrexate for 24 weeks, the other group got placebo+methotrexate for the first 12 weeks and anti-TNF-α mAb+methotrexate for another 12 weeks. Circulatory regulatory T cell (Treg) and effector T cell (Teff) frequency was analyzed pre-therapy and week 12 and week 24 for both group patients by flowcytometry. Our results indicated significantly elevated Treg and decreased Teff at week 24 compared with pre-therapy and week 12 for both group patients, and a little higher Treg and lower Teff frequency in anti-TNF-α therapy group than in placebo therapy patients. Our results demonstrated anti-TNF-α therapy has regulatory effect on immune system of RA patients by promoting Treg proportion increase and suppressing Teff.

  19. Multisystemic Therapy Improves the Patient-Provider Relationship in Families of Adolescents with Poorly Controlled Insulin Dependent Diabetes

    PubMed Central

    Carcone, April Idalski; Ellis, Deborah A.; Chen, Xinguang; Naar-King, Sylvie; Cunningham, Phillippe B.; Moltz, Kathleen

    2015-01-01

    Objective The purpose of this study was to determine if Multisystemic Therapy (MST), an intensive, home and community-based family treatment, significantly improved patient-provider relationships in families where youth had chronic poor glycemic control. Methods One hundred forty-six adolescents with type 1 or 2 diabetes in chronic poor glycemic control (HbA1c ≥ 8%) and their primary caregivers were randomly assigned to MST or a telephone support condition. Caregiver perceptions of their relationship with the diabetes multidisciplinary medical team were assessed at baseline and treatment termination with the Measure of Process of Care-20. Results At treatment termination, MST families reported significant improvement on the Coordinated and Comprehensive Care scale and marginally significant improvement on the Respectful and Supportive Care scale. Improvements on the Enabling and Partnership and Providing Specific Information scales were not significant. Conclusions Results suggest MST improves the ability of the families and the diabetes treatment providers to work together. PMID:25940767

  20. Cognitive Behavior Therapy for Anxious and Depressed Youth: Improving Homework Adherence Through Mobile Technology

    PubMed Central

    Eklund, J Mikael; Milner, Tracy; Kreindler, David; Cheung, Amy; Kovacs, Tim; Shooshtari, Shahin; Astell, Arlene; Ohinmaa, Arto; Henderson, Joanna; Strauss, John; Mills, Rosemary SL

    2016-01-01

    Background Anxiety and mood disorders are the most common mental illnesses, peaking during adolescence and affecting approximately 25% of Canadians aged 14-17 years. If not successfully treated at this age, they often persist into adulthood, exerting a great social and economic toll. Given the long-term impact, finding ways to increase the success and cost-effectiveness of mental health care is a pressing need. Cognitive behavior therapy (CBT) is an evidence-based treatment for mood and anxiety disorders throughout the lifespan. Mental health technologies can be used to make such treatments more successful by delivering them in a format that increases utilization. Young people embrace technologies, and many want to actively manage their mental health. Mobile software apps have the potential to improve youth adherence to CBT and, in turn, improve outcomes of treatment. Objective The purpose of this project is to improve homework adherence in CBT for youth anxiety and/or depression. The objectives are to (1) design and optimize the usability of a mobile app for delivering the homework component of CBT for youth with anxiety and/or depression, (2) assess the app’s impact on homework completion, and (3) implement the app in CBT programs. We hypothesize that homework adherence will be greater in the app group than in the no-app group. Methods Phase 1: exploratory interviews will be conducted with adolescents and therapists familiar with CBT to obtain views and perspectives on the requirements and features of a usable app and the challenges involved in implementation. The information obtained will guide the design of a prototype. The prototype will be optimized via think-aloud procedures involving an iterative process of evaluation, modification, and re-evaluation, culminating in a fully functional version of the prototype that is ready for optimization in a clinical context. Phase 2: a usability study will be conducted to optimize the prototype in the context of

  1. A manual-based individual therapy to improve metacognition in schizophrenia: protocol of a multi-center RCT

    PubMed Central

    2014-01-01

    Background Metacognitive dysfunction has been widely recognized as a feature of schizophrenia. As it is linked with deficits in several aspects of daily life functioning, improvement of metacognition may lead to improvement in functioning. Individual psychotherapy might be a useful form of treatment to improve metacognition in patients with schizophrenia; multiple case reports and a pilot study show promising results. The present study aims to measure the effectiveness of an individual, manual-based therapy (Metacognitive Reflection and Insight Therapy, MERIT) in improving metacognition in patients with schizophrenia. We also want to examine if improvement in metacognitive abilities is correlated with improvements in aspects of daily life functioning namely social functioning, experience of symptoms, quality of life, depression, work readiness, insight and experience of stigma. Methods/Design MERIT is currently evaluated in a multicenter randomized controlled trial. Thirteen therapists in six mental health institutions in the Netherlands participate in this study. Patients are randomly assigned to either MERIT or the control condition: treatment as usual (TAU). Discussion If proven effective, MERIT can be a useful addition to the care for schizophrenia patients. The design brings along some methodological difficulties, these issues are addressed in the discussion of this paper. Trial registration Current Controlled Trials: ISRCTN16659871. PMID:24490942

  2. Correcting delayed circadian phase with bright light therapy predicts improvement in ADHD symptoms: A pilot study.

    PubMed

    Fargason, Rachel E; Fobian, Aaron D; Hablitz, Lauren M; Paul, Jodi R; White, Brittny A; Cropsey, Karen L; Gamble, Karen L

    2017-03-06

    Attention-deficit/hyperactivity disorder (ADHD) is a common condition with comorbid insomnia reported in >70% of children and adults. These patients demonstrate delays in sleep-wake rhythms, nocturnal rise in melatonin, and early morning rise in cortisol. Given that standard psychopharmacologic treatments for ADHD often do not completely control symptoms in participants with circadian rhythm delay, we sought to test whether bright light therapy (BLT) advances circadian rhythms and further reduces ADHD symptoms over standard treatments. In addition to standard of care, participants with ADHD diagnosis underwent 1 week of baseline assessment followed by 2-weeks of 30-min morning 10,000-lux BLT beginning 3 h after mid-sleep time. Participants minimized overhead light after 4 p.m., wore an actigraphy watch, and recorded BLT time on daily sleep logs. Dim Light Melatonin Onset (DLMO) was assessed at baseline and after 2-week treatment. ADHD symptoms were measured by the ADHD-Rating Scales (ADHD-RS). BLT significantly advanced the phase of DLMO by 31 min [mean time (SEM), 20:36 (0:21) advanced to 20:05 (0:20)] and mid-sleep time by 57 min [4:37 (0:22) advanced to 3:40 (0:16); paired t-tests, p = 0.002 and 0.004, respectively). Phase advances (in DLMO or mid-sleep time) were significantly correlated with decreased ADHD-RS total scores (p = 0.027 and 0.044) and Hyperactive-Impulsive sub-scores (p = 0.014 and 0.013, respectively). Actigraphy analysis for a subset of 8 participants with significant DLMO phase advance revealed no significant changes in total sleep time, sleep efficiency, wake after sleep onset, or percent wake during sleep interval. This is the first successful use of BLT for advancing melatonin phase and improving ADHD symptoms in adults. BLT may be a complementary treatment for both delayed sleep timing and ADHD symptoms in adults.

  3. Output calculation of electron therapy at extended SSD using an improved LBR method

    SciTech Connect

    Alkhatib, Hassaan A.; Gebreamlak, Wondesen T. Wright, Ben W.; Neglia, William J.; Tedeschi, David J.; Mihailidis, Dimitris; Sobash, Philip T.; Fontenot, Jonas D.

    2015-02-15

    Purpose: To calculate the output factor (OPF) of any irregularly shaped electron beam at extended SSD. Methods: Circular cutouts were prepared from 2.0 cm diameter to the maximum possible size for 15 × 15 applicator cone. In addition, two irregular cutouts were prepared. For each cutout, percentage depth dose (PDD) at the standard SSD and doses at different SSD values were measured using 6, 9, 12, and 16 MeV electron beam energies on a Varian 2100C LINAC and the distance at which the central axis electron fluence becomes independent of cutout size was determined. The measurements were repeated with an ELEKTA Synergy LINAC using 14 × 14 applicator cone and electron beam energies of 6, 9, 12, and 15 MeV. The PDD measurements were performed using a scanning system and two diodes—one for the signal and the other a stationary reference outside the tank. The doses of the circular cutouts at different SSDs were measured using PTW 0.125 cm{sup 3} Semiflex ion-chamber and EDR2 films. The electron fluence was measured using EDR2 films. Results: For each circular cutout, the lateral buildup ratio (LBR) was calculated from the measured PDD curve using the open applicator cone as the reference field. The effective SSD (SSD{sub eff}) of each circular cutout was calculated from the measured doses at different SSD values. Using the LBR value and the radius of the circular cutout, the corresponding lateral spread parameter [σ{sub R}(z)] was calculated. Taking the cutout size dependence of σ{sub R}(z) into account, the PDD curves of the irregularly shaped cutouts at the standard SSD were calculated. Using the calculated PDD curve of the irregularly shaped cutout along with the LBR and SSD{sub eff} values of the circular cutouts, the output factor of the irregularly shaped cutout at extended SSD was calculated. Finally, both the calculated PDD curves and output factor values were compared with the measured values. Conclusions: The improved LBR method has been generalized to

  4. Improved Outcomes of Breast-Conserving Therapy for Patients With Ductal Carcinoma in Situ

    SciTech Connect

    Halasz, Lia M.; Sreedhara, Meera; Bellon, Jennifer R.; Punglia, Rinaa S.; Wong, Julia S.; Harris, Jay R.

    2012-03-15

    Purpose: Patients treated for ductal carcinoma in situ (DCIS) with breast-conserving surgery (BCS) and radiation therapy (RT) at our center from 1976 to 1990 had a 15% actuarial 10-year local recurrence (LR) rate. Since then, improved mammographic and pathologic evaluation and greater attention to achieving negative margins may have resulted in a lower risk of LR. In addition, clinical implications of hormone receptor and HER-2 status in DCIS remain unclear. We sought to determine the following: LR rates with this more modern approach; the relation between LR and HER-2 status; and clinical and pathologic factors associated with HER-2{sup +} DCIS. Methods and Materials: We studied 246 consecutive patients who underwent BCS and RT for DCIS from 2001 to 2007. Of the patients, 96 (39%) were Grade III and the median number of involved tissue blocks was 3. Half underwent re-excision and 222 (90%) had negative margins (>2 mm). All received whole-breast RT (40-52 Gy) and 99% (244) received a tumor bed boost (8-18 Gy). Routine estrogen receptor (ER), progesterone receptor (PR), and HER-2 immunohistochemistry was instituted in 2003. Results: With median follow-up of 58 months, there were no LRs. Seven patients (3%) developed contralateral breast cancer (4 invasive and 3 in situ). Among 163 patients with immunohistochemistry, 124 were ER/PR{sup +}HER-2{sup -}, 27 were ER/PR{sup +}HER-2{sup +}, 6 were ER{sup -}/PR{sup -}HER-2{sup +}, and 6 were ER{sup -}/PR{sup -}HER-2{sup -}. On univariable analysis, HER-2{sup +}was significantly associated with Grade III, ER{sup -}/PR{sup -}, central necrosis, comedo subtype, more extensive DCIS, and postmenopausal status. On multivariable analysis, Grade III and postmenopausal status remained significantly associated with HER-2{sup +}. Conclusions: In an era of mammographically identified DCIS, larger excisions, widely negative margins and the use of a tumor bed boost, we observed no LR regardless of ER/PR/HER-2 status. Factors associated

  5. Nutraceuticals, nutritional therapy, phytonutrients, and phytotherapy for improvement of human health: a perspective on plant biotechnology application.

    PubMed

    Zhao, Jian

    2007-01-01

    Plants are one of the most important resources of human foods and medicines. Rapidly increasing knowledge on nutrition, medicine, and plant biotechnology has dramatically changed the concepts about food, health and agriculture, and brought in a revolution on them. Nutritional therapy and phytotherapy have emerged as new concepts and healing systems have quickly and widely spread in recent years. Strong recommendations for consumption of nutraceuticals, natural plant foods, and the use of nutritional therapy and phytotherapy have become progressively popular to improve health, and to prevent and treat diseases. With these trends, improving the dietary nutritional values of fruits, vegetables and other crops or even bioactive components in folk herbals has become targets of the blooming plant biotechnology industry. This review attempts to display and remark on these aspects. It summarizes the progress made on nutraceuticals, nutritional therapy, phytonutrients, phytotherapy, and their related epidemiological investigations and clinical studies. It also covers markets of these health-promoting products and disease-preventing or healing systems, as well as regulations behind them that direct the development of biotechnology study and application. Finally, related patents are listed and briefly analyzed, regarding of plant biotechnological research and progress on transgenic crops to improve nutritional value, phytotherapy efficiency, or to produce pharmaceutically important secondary metabolites or high-valued protein medicines such as vaccines and antibodies.

  6. Radioiodine sorption/desorption and speciation transformation by subsurface sediments from the Hanford Site

    SciTech Connect

    Xu, Chen; Kaplan, Daniel I.; Zhang, Saijin; Athon, Matthew; Ho, Yi-Fang; Li, Hsiu-Ping; Yeager, Chris; Schwehr, Kathy; Grandbois, Russell; Wellman, Dawn M.; Santschi, Peter H.

    2015-01-01

    During the last few decades, considerable research efforts have been extended to identify more effective remediation treatment technologies to lower the 129I concentrations to below federal drinking water standards at the Hanford Site (Richland, USA). Few studies have taken iodate into consideration, though recently iodate, instead of iodide, was identified as the major species in the groundwater of 200-West Area within the Hanford Site. The objective of this study was thus to quantify and understand aqueous radioiodine species transformations and uptake by three sediments collected from the semiarid, carbonate-rich environment of the Hanford subsurface. All three sediments reduced iodate (IO-) to iodide (I-), but the loamy-sand sediment reduced more IO3- (100% reduced within 7 days) than the two sand-textured sediments (~20% reduced after 28 days). No dissolved organo-iodine species were observed in any of these studies.

  7. Milk progesterone radioimmunoassay using radioiodinated tracers: a rapid and reliable assay system

    SciTech Connect

    Espinosa, J.; Botana, L.M.; Puentes, E.; Regueiro, B.J.

    1984-09-01

    Both the validity and practicability of a direct progesterone radioimmunoassay based on radioiodinated progesterone tracers were studied. The results obtained show the reliability of the assay; when compared with assays based on /sup 3/H-progesterone tracers there are fewer steps for assay execution, saving time and reducing the number of reagents used. Various commercially available /sup 125/I-progesterone tracers were assayed, and only those with an 11 alpha-hemisuccinate bridge were suitably bound by antisera raised against progesterone-bovine serum albumin conjugates having identical bridge structure. The bridge effect caused no observable alteration in validity parameters. Finally, the results support the utility of this assay as a practical method of early diagnosis of pregnancy and as a reliable experimental technique to monitor cow ovarian function.

  8. Fractionated doses of radioiodine for ablation of postsurgical thyroid tissue remnants

    SciTech Connect

    Arad, E.; Flannery, K.; Wilson, G.A.; O'Mara, R.E. )

    1990-10-01

    Patients who have differentiated thyroid carcinoma and have undergone total thyroidectomy are treated with radioiodine for ablation of functional thyroid remnants. Administration of a single therapeutic dose in excess of 30 mCi of l-131 requires hospitalization. In an attempt to obviate the necessity for hospitalization, the prospective ablative dose was divided into two or three fractions given at weekly intervals on an ambulatory basis. To assess the effectiveness of this approach, this group of patients was compared to a cohort of hospitalized patients treated with a single dose. Ablation was achieved in 9 out of 12 patients treated in a fractionated manner (a 75% success rate), whereas in 16 out of 20 patients given a single dose the thyroid remnants were completely eradicated (an 80% success rate). That the use of split, smaller doses administered at weekly intervals on an ambulatory basis presents a reasonable alternative for ablation of postsurgical, residual-functioning thyroid tissue.

  9. Maintenance of biological activity of pertussis toxin radioiodinated while bound to fetuin-agarose

    SciTech Connect

    Armstrong, G.D.; Peppler, M.S.

    1987-05-01

    We developed a method to produce radioiodinated pertussis toxin (PT) which was active in the goose erythrocyte agglutination and CHO cell assay systems. The procedure used fetuin coupled to agarose to prevent inactivation of the toxin during the iodination reaction. Analysis of the labeled PT by affinity chromatography on fetuin-agarose and wheat germ agglutinin-agarose and by sodium dodecyl sulfate-polyacrylamide gel electrophoresis indicated that there were minimal amounts of labeled fetuin or other contaminants in the labeled PT preparations. All five of the subunits of the toxin appeared to be labeled by the procedure. The labeling method will facilitate further investigations into the nature of the interaction and activity of PT in host tissues.

  10. Brief report: improvements in the behavior of children with autism following massage therapy.

    PubMed

    Escalona, A; Field, T; Singer-Strunck, R; Cullen, C; Hartshorn, K

    2001-10-01

    Twenty children with autism, ages 3 to 6 years, were randomly assigned to massage therapy and reading attention control groups. Parents in the massage therapy group were trained by a massage therapist to massage their children for 15 minutes prior to bedtime every night for 1 month and the parents of the attention control group read Dr. Seuss stories to their children on the same time schedule. Conners Teacher and Parent scales, classroom and playground observations, and sleep diaries were used to assess the effects of therapy on various behaviors, including hyperactivity, stereotypical and off-task behavior, and sleep problems. Results suggested that the children in the massage group exhibited less stereotypic behavior and showed more on-task and social relatedness behavior during play observations at school, and they experienced fewer sleep problems at home.

  11. Myeloid Sarcoma of the Uterine Cervix as Presentation of Acute Myeloid Leukaemia after Treatment with Low-Dose Radioiodine for Thyroid Cancer: A Case Report and Review of the Literature

    PubMed Central

    Weingertner, Anne Sophie; Wilt, Marc; Atallah, Ihab; Fohrer, Cécile; Mauvieux, Laurent; Rodier, Jean-François

    2009-01-01

    The development of acute myeloid leukaemia after low-dose radioiodine therapy and its presentation as a myeloid sarcoma of the uterine cervix are both rare events. We report a case of acute myeloid leukaemia revealed by a myeloid sarcoma of the uterine cervix in a 48-year-old woman, 17 months after receiving a total dose of 100 mCi 131I for papillary thyroid cancer. A strict hematological follow-up of patients treated with any dose of 131I is recommended to accurately detect any hematological complications which might have been underestimated. Unusual presentations, such as chloroma of the uterine cervix, may reveal myeloid malignancy and should be kept in mind. PMID:20844570

  12. Sorption and desorption studies of radioiodine onto silver chloride via batch equilibration with its aqueous media.

    PubMed

    Mostafa, M; Ramadan, H E; El-Amir, M A

    2015-12-01

    The uncontrolled spread out of radioiodine (especially (1)(3)(1)I) produced from nuclear activities or accidents, due to its high volatility, to the biosphere represents an environmental impact because of its concentration in the thyroid gland and accumulation on soil surface. This work represents a simple method for isolation of radioiodine from aqueous solution in the form of insoluble solid compound and further recovery of it in aqueous phase for any further controlled use. Crystalline silver chloride was prepared and characterized. Batch sorption of (131)I onto the prepared AgCl was studied from different aqueous media (H2O and NaOH of different concentrations) and at different I(-):Ag molar ratios (from alkaline media) for different times at 25 °C. It was found that the sorption yield of (131)I from 2.5 M NaOH solution (at I(-):Ag and S2O3(2-):I(-) molar ratios of 0.025 and 2, respectively) reached 97.7% after 6 h and only slightly increased to 98.6% after 16 h of contact time. The presence of H2O2 adversely affected the batch sorption process. The included REDOX and precipitation reactions were discussed. Batch desorption of the sorbed (131)I from AgCl into aqueous phase was studied with NaOCl solutions of different concentrations and different contact times at 25 °C. Desorption yield of (131)I was found to be 94.5% with 10 mL of 0.5 M NaOCl solution after contact time of 16 h. Kinetic analysis has been performed for both batch sorption and desorption processes.

  13. Polymer-supported organotin reagent for prosthetic group labeling of biological macromolecules with radioiodine.

    PubMed

    Gifford, Andrew N; Kuschel, Sonja; Shea, Colleen; Fowler, Joanna S

    2011-03-16

    In this study, we investigated the use of poly-mer-bound precursor for generating a radiolabeled prosthetic group to be used for conjugate labeling of biological macromolecules. For the approach, a trialkyltin chloride in which the tin was bound to a hydrophilic PEG-based resin support via one of the alkyl groups was synthesized. This resin was then used to prepare a resin-bound trialkyltin benzoic acid, which in some cases was further derivatized on-resin by converting it to a succinimidyl ester. Exposure of the resin-bound compounds to electrophilic radioiodine (¹²⁵I) in either an aqueous or methanol solvent liberated either free radiolabeled [¹²⁵I]iodobenzoic acid or its succinimidyl ester without co-release of the resin-bound precursors. Radiochemical yield was between 35% and 75%, depending on the solvent system and precursor. As example applications for the released compounds, the amine-reactive N-succinimidyl-[¹²⁵I]iodobenzoate prosthetic group was used for conjugate radiolabeling of a peptide, tomato plant systemin, and two proteins, albumin and IgG antibody. These results demonstrate that resin-bound organotin precursors in which the compound to be labeled is tethered to the support via the tin group to be substituted can be used to produce radioiodine-labeled aromatic prosthetic groups in good specific activity without the need for HPLC purification. This solid-phase approach is potentially adaptable to kit-formulation for performing conjugate radiolabeling of biological macromolecules.

  14. A study of thyroid radioiodine monitoring by Monte Carlo simulations: implications for equipment design

    NASA Astrophysics Data System (ADS)

    Kramer, Gary H.; Chamberlain, Michael J.; Yiu, Suzanne

    1997-11-01

    Monte Carlo simulations have been performed to evaluate the design of collimated detectors used to measure or in the thyroid gland. Two detector sizes were simulated for each radioisotope: (i) for monitoring 2.54 cm diameter and 7.62 cm diameter and 0.2 cm thickness and (ii) for monitoring 2.54 cm diameter, 3.2 cm thickness and 7.62 cm diameter, 6.4 cm thickness. The virtual thyroid gland was 20 g. Activity was placed in both the gland and the remainder of the body in varying amounts to assess the efficacy of collimation. The results show that the detector should be sufficiently large so that its solid angle of acceptance when placed 15 cm anterior to the skin surface will include the whole of a moderately enlarged thyroid gland. Heavy collimation to reduce the contribution of extrathyroidal radioiodine within the subject's body is not normally required. It may be of more value as a positioning device and spacer ensuring an appropriate and constant neck to detector distance than in cutting down counts from extrathyroidal activity. In specifying a sensitive detector system for monitoring intrathyroidal radioiodine, a wide angle of acceptance and sufficient detector crystal thickness take precedence over collimation and shielding.

  15. Synthesis and characterization of a high affinity radioiodinated probe for the alpha 2-adrenergic receptor

    SciTech Connect

    Lanier, S.M.; Hess, H.J.; Grodski, A.; Graham, R.M.; Homcy, C.J.

    1986-03-01

    The availability of radioiodinated probes has facilitated the localization and molecular characterization of cell membrane receptors for hormones and neurotransmitters. However, such probes are not available for the study of the alpha 2-adrenergic receptor. This report describes the synthesis and characterization of functionalized derivatives of the selective alpha 2-adrenergic antagonists, rauwolscine and yohimbine, which can be radiolabeled to high specific activity with 125I. Following demethylation of rauwolscine or yohimbine, the resultant carboxylic acid derivatives were reacted with 4-aminophenethylamine to yield the respective 4-aminophenethyl carboxamides, 17 alpha-hydroxy-20 alpha-yohimban-16 beta-(N-4-amino-phenethyl)carboxamide (rau-pAPC) and 17 alpha-hydroxy-20 beta-yohimban-16 alpha-(N-4-aminophenethyl)carboxamide. In competitive inhibition studies using rat renal membranes and the radioligand (3H)rauwolscine, rau-pAPC (Ki = 11 +/- 1 nM) exhibited a 14-fold greater affinity than the corresponding yohimbine derivative (Ki = 136 +/- 45 nM). The higher affinity compound, rau-pAPC, was radioiodinated by the chloramine T method, and the product, 125I-rau-pAPC (17 alpha-hydroxy-20 alpha-yohimban-16 beta-(N-4-amino-3 -(125I)iodophenethyl)carboxamide), was purified by reverse phase HPLC to high specific activity (2175 Ci/mmol) and its binding characteristics were investigated in rat kidney membranes. Specific binding of 125I-rau-pAPC was saturable and of high affinity as determined by Scatchard analysis (KD = 1.8 +/- 0.3 nM) or from kinetic studies (KD = k2/k1 = 0.056 +/- 0.013 min-1)/4.3 +/- 0.2 X 10(7) M-1 min-1 = 1.3 +/- 0.3 nM).

  16. Enhanced tumor retention of radioiodinated anti-epidermal growth factor receptor antibody using novel bifunctional iodination linker for radioimmunotherapy

    PubMed Central

    KIM, EUN JUNG; KIM, BYOUNG SOO; CHOI, DAN BEE; CHI, SUNG-GIL; CHOI, TAE HYUN

    2016-01-01

    Radioimmunotherapy (RIT) uses an antibody labeled with a radionuclide to deliver cytotoxic radiation to a target tumor cells. Radioiodine is most commonly employed to prepare radiolabeled proteins (antibodies, peptides) for in vitro and in vivo applications. A major shortcoming of radioiodinated proteins prepared by direct labeling methods is their deiodination in vivo. For the preparation of more stable radioiodinated antibodies, we developed a new linker (N-(4-isothiocyanatobenzyl)-2-(3-(tributylstannyl)phenyl) acetamide (IBPA). This study evaluated the usefulness of IBPA as a linker for the stable radioiodinated internalizing antibody, cetuximab. Directly labeled cetuximab ([125I]-cetuximab) was prepared by the chloramine T method. To prepare indirectly labeled cetuximab using IBPA ([125I]-IBPA-cetuximab), IBPA was radioiodinated using chloramine-T to give N-(4-isothiocyanatobenzyl)-2-(3-[125I]phenyl)acetamide ([125I]-IBPA), which was purified by high performance liquid chromatography. [125I]-IBPA was then conjugated to cetuximab. In vitro target binding and internalizing assays were performed in PC9, LS174T, and FaDu cell lines. In vivo planar images were obtained using an Inveon SPECT scanner 3, 24, 48, and 168 h after i.v. injection of [125I]-cetuximab or [125I]-IBPA-cetuximab in athymic mice bearing LS174T tumor xenografts. Specific binding and internalized radioactivity of [125I]-IBPA-cetuximab were higher than those of [125I]-cetuximab in PC9, LS174T, and FaDu cell lines. In planar images scant radioactivity was evident in thyroid glands after injection of [125I]-IBPA-cetuximab, while a high level of radioactivity was present in thyroid glands after injection of [125I]-cetuximab. Tumor uptake value of [125I]-IBPA-cetuximab was higher than that of [125I]-cetuximab for up to 168 h. [125I]-IBPA-cetuximab is stable and resistant to deiodination in vivo. IBPA is a promising bi-functional linker for radioiodination of internalizing monoclonal antibodies for in

  17. Dimethyl Fumarate Therapy Significantly Improves the Responsiveness of T Cells in Multiple Sclerosis Patients for Immunoregulation by Regulatory T Cells

    PubMed Central

    Schlöder, Janine; Berges, Carsten; Luessi, Felix; Jonuleit, Helmut

    2017-01-01

    Multiple sclerosis (MS) is a chronic autoimmune disease caused by an insufficient suppression of autoreactive T lymphocytes. One reason for the lack of immunological control is the reduced responsiveness of T effector cells (Teff) for the suppressive properties of regulatory T cells (Treg), a process termed Treg resistance. Here we investigated whether the disease-modifying therapy of relapsing-remitting MS (RRMS) with dimethyl fumarate (DMF) influences the sensitivity of T cells in the peripheral blood of patients towards Treg-mediated suppression. We demonstrated that DMF restores responsiveness of Teff to the suppressive function of Treg in vitro, presumably by down-regulation of interleukin-6R (IL-6R) expression on T cells. Transfer of human immune cells into immunodeficient mice resulted in a lethal graft-versus-host reaction triggered by human CD4+ Teff. This systemic inflammation can be prevented by activated Treg after transfer of immune cells from DMF-treated MS patients, but not after injection of Treg-resistant Teff from therapy-naïve MS patients. Furthermore, after DMF therapy, proliferation and expansion of T cells and the immigration into the spleen of the animals is reduced and modulated by activated Treg. In summary, our data reveals that DMF therapy significantly improves the responsiveness of Teff in MS patients to immunoregulation. PMID:28134847

  18. Instructional Strategies Used to Improve Students' Comfort and Skill in Addressing the Occupational Therapy Process

    ERIC Educational Resources Information Center

    Knecht-Sabres, Lisa Jean; Egan, Brad E.; Wallingford, Minetta S.; Kovic, Mark

    2015-01-01

    The purpose of this study was to investigate the effectiveness of an intentional blending of instructional strategies in an occupational therapy (OT) entry-level master's course. The OT Adult Practice course uses case-based instructional strategies, clinical skills labs, and standardized patient experiences in a dovetailed approach across three…

  19. Hypnosis and Rational-Emotive Therapy as Used in Teaching Improved Auto Suggestion.

    ERIC Educational Resources Information Center

    DeRoos, Yosikazu Spencer; Johnson, David Pittman

    1983-01-01

    Detailes a method incorporating hypnosis and Rational-Emotive Therapy (RET) into a procedure termed Rational-Emotive Hypnosis. Indicates several areas in which clients often have difficulty engaging successfully in RET, and offers hypnotic techniques to overcome such problems. Both direct and indirect hypnotic procedures are examined. (JAC)

  20. Microencapsulation with alginate/CaCO3: A strategy for improved phage therapy

    PubMed Central

    Colom, Joan; Cano-Sarabia, Mary; Otero, Jennifer; Aríñez-Soriano, Javier; Cortés, Pilar; Maspoch, Daniel; Llagostera, Montserrat

    2017-01-01

    Bacteriophages are promising therapeutic agents that can be applied to different stages of the commercial food chain. In this sense, bacteriophages can be orally administered to farm animals to protect them against intestinal pathogens. However, the low pH of the stomach, the activities of bile and intestinal tract enzymes limit the efficacy of the phages. This study demonstrates the utility of an alginate/CaCO3 encapsulation method suitable for bacteriophages with different morphologies and to yield encapsulation efficacies of ~100%. For the first time, a cocktail of three alginate/CaCO3-encapsulated bacteriophages was administered as oral therapy to commercial broilers infected with Salmonella under farm-like conditions. Encapsulation protects the bacteriophages against their destruction by the gastric juice. Phage release from capsules incubated in simulated intestinal fluid was also demonstrated, whereas encapsulation ensured sufficient intestinal retention of the phages. Moreover, the small size of the capsules (125–150 μm) enables their use in oral therapy and other applications in phage therapy. This study evidenced that a cocktail of the three alginate/CaCO3-encapsulated bacteriophages had a greater and more durable efficacy than a cocktail of the corresponding non-encapsulated phages in as therapy in broilers against Salmonella, one of the most common foodborne pathogen. PMID:28120922

  1. Decreased Family Accommodation Associated with Improved Therapy Outcome in Pediatric Obsessive-Compulsive Disorder

    ERIC Educational Resources Information Center

    Merlo, Lisa J.; Lehmkuhl, Heather D.; Geffken, Gary R.; Storch, Eric A.

    2009-01-01

    Pediatric obsessive-compulsive disorder (OCD) is a chronic, disabling condition that affects both patients and their families. Despite the identification of efficacious treatments (e.g., cognitive-behavioral therapy and selective serotonin reuptake inhibitor medications), not all patients respond fully. The purpose of the present study was to…

  2. Brief Report: Improvements in the Behavior of Children with Autism Following Massage Therapy.

    ERIC Educational Resources Information Center

    Escalona, Angelica; Field, Tiffany; Singer-Strunck, Ruth; Cullen, Christy; Hartshorn, Kristen

    2001-01-01

    Twenty children with autism, ages 3 to 6 years, received either massage therapy or reading attention by their parents for 15 minutes daily for one month. Evaluation suggested that children in the massage group exhibited less stereotypic behavior and showed more on-task and social relatedness behavior during play observations at school, and they…

  3. Attention Therapy Improves Reading Comprehension in Adjudicated Teens in a Residential Facility

    ERIC Educational Resources Information Center

    Shelley-Tremblay, John; Langhinrichsen-Rohling, Jennifer; Eyer, Joshua

    2012-01-01

    This study quantified the influence of visual Attention Therapy (AT) on reading skills and Coherent Motion Threshold (CMT) in adjudicated teens with moderate reading disabilities (RD) residing in a residential alternative sentencing program. Forty-two students with below-average reading scores were identified using standardized reading…

  4. Mindfulness-Based Sex Therapy Improves Genital-Subjective Arousal Concordance in Women With Sexual Desire/Arousal Difficulties.

    PubMed

    Brotto, Lori A; Chivers, Meredith L; Millman, Roanne D; Albert, Arianne

    2016-11-01

    There is emerging evidence for the efficacy of mindfulness-based interventions for improving women's sexual functioning. To date, this literature has been limited to self-reports of sexual response and distress. Sexual arousal concordance-the degree of agreement between self-reported sexual arousal and psychophysiological sexual response-has been of interest due to the speculation that it may be a key component to healthy sexual functioning in women. We examined the effects of mindfulness-based sex therapy on sexual arousal concordance in a sample of women with sexual desire/arousal difficulties (n = 79, M age 40.8 years) who participated in an in-laboratory assessment of sexual arousal using a vaginal photoplethysmograph before and after four sessions of group mindfulness-based sex therapy. Genital-subjective sexual arousal concordance significantly increased from pre-treatment levels, with changes in subjective sexual arousal predicting contemporaneous genital sexual arousal (but not the reverse). These findings have implications for our understanding of the mechanisms by which mindfulness-based sex therapy improves sexual functioning in women, and suggest that such treatment may lead to an integration of physical and subjective arousal processes. Moreover, our findings suggest that future research might consider the adoption of sexual arousal concordance as a relevant endpoint in treatment outcome research of women with sexual desire/arousal concerns.

  5. Melatonin Treatment Improves Mesenchymal Stem Cells Therapy by Preserving Stemness during Long-term In Vitro Expansion

    PubMed Central

    Shuai, Yi; Liao, Li; Su, Xiaoxia; Yu, Yang; Shao, Bingyi; Jing, Huan; Zhang, Xinjing; Deng, Zhihong; Jin, Yan

    2016-01-01

    Mesenchymal stem cells (MSCs) are promising candidates for tissue regeneration and disease treatment. However, long-term in vitro passaging leads to stemness loss of MSCs, resulting in failure of MSCs therapy. Here, we report a melatonin-based strategy to improve cell therapy of in vitro cultured MSCs. Among four small molecules with anti-aging and stem cell-protection properties (rapamycin, resveratrol, quercetin and melatonin), colony forming, proliferation, and osteogenic differentiation assay showed that melatonin was the most efficient to preserve self-renewal and differentiation properties of rat bone marrow MSCs (BMMSCs) after long-term passaging. Functional assays confirmed melatonin treatment did not affect the colony forming, proliferation and osteogenic differentiation of BMMSCs cultured for 1 or 4 passages, but largely prevented the decline of self-renew and differentiation capacity of BMMSCs cultured for 15 passages in vitro. Furthermore, heterotopic osteogenesis assay, critical size calvarial defects repair assay, osteoporosis treatment and experimental colitis therapy assay strongly certified that melatonin preserved the therapeutic effect of long-term passaged BMMSCs on bone regeneration and immunotherapy in vivo. Mechanistically, melatonin functioned by activating antioxidant defense system, inhibiting the pathway of cell senescence, and preserving the expression of gene governing the stemness. Taken together, our findings showed that melatonin treatment efficiently prevented the dysfunction and therapeutic failure of BMMSCs after long-term passaging, providing a practical strategy to improve the application of BMMSCs in tissue engineering and cytotherapy. PMID:27570559

  6. FRET energy transfer via Pdots improves the efficiency of photodynamic therapy and leads to rapid cell death.

    PubMed

    Haupt, Sara; Lazar, Itay; Weitman, Hana; Shav-Tal, Yaron; Ehrenberg, Benjamin

    2016-11-01

    Photodynamic therapy (PDT) is well established as a clinical treatment modality for various diseases, including cancer and especially for the treatment of superficial tumors. However, one of the disadvantages of the photoactivatable molecules is their low absorbance in the optical window for photosensitizer excitation. The use of nanoparticles in photodynamic therapy can address this deficiency and improve treatment efficiency. Pdots are nano-sized particles, composed of conjugated chromophoric polymers. By mixing them with PEGylated phospholipids they can become soluble and stable colloids. They exhibit a broad absorption band with a strong and narrow emission band. In this study, we examined two types of Pdots (MEH-PPV and CN-PPV) with two different lengths of the PEGylated lipids coating, 350 and 2000. When a photosensitizer, such as mTHPC, comes in close contact with the amphiphilic coating of the Pdots, a very efficient fluorescence resonance energy transfer (FRET) occurs between the donor, the Pdots and the acceptor, the sensitizer. This process, together with the significant uptake of the Pdots-sensitizer pair by MCF-7 cancerous cells causes irreversible damage to the cells. This damage is greater when the Pdots are comprised from the CN-PPV polymer and coated with the PEG2000-PE lipid. Altogether, we demonstrate that implementing FRET energy transfer in the PDT protocol leads to quicker and more aggressive cell death, thus improving the efficacy of the photodynamic therapy.

  7. Executive function needs to be targeted to improve social functioning with Cognitive Remediation Therapy (CRT) in schizophrenia.

    PubMed

    Penadés, Rafael; Catalán, Rosa; Puig, Olga; Masana, Guillem; Pujol, Núria; Navarro, Víctor; Guarch, Joana; Gastó, Cristóbal

    2010-05-15

    While the role of impaired cognition in accounting for functional outcome in schizophrenia is generally established, the relationship between cognitive and functional change in the context of treatments is far from clear. The current paper tries to identify which cognitive changes lead to improvements in daily functioning among persons with chronic schizophrenia who had current negative symptoms and evidenced neuropsychological impairments. In a previous work, Cognitive Remediation Therapy (CRT) was compared with a control therapy, involving similar length of therapist contact but different targets. At the end of treatment, CRT conferred a benefit to people with schizophrenia in cognition and functioning [Schizophrenia Research, 87 (2006) 323-331]. Subsequently, analyses of covariance (ANCOVA) were conducted with baseline and cognitive change scores as covariates to test whether cognitive change predicted change in functioning. Additionally, statistical tests to establish the mediation path with significant variables were performed. Although verbal memory, but not executive functioning, was associated with functioning at baseline, it was the improvement in executive functioning that predicted improved daily functioning. Verbal memory played a mediator role in the change process. Consequently, in order to improve daily functioning with CRT, executive function still needs to be targeted in despite of multiple cognitive impairments being present.

  8. Chronotype and Improved Sleep Efficiency Independently Predict Depressive Symptom Reduction after Group Cognitive Behavioral Therapy for Insomnia

    PubMed Central

    Bei, Bei; Ong, Jason C.; Rajaratnam, Shantha M.W.; Manber, Rachel

    2015-01-01

    Study Objectives: Cognitive behavioral therapy for insomnia (CBT-I) has been shown to improve both sleep and depressive symptoms, but predictors of depression outcome following CBT-I have not been well examined. This study investigated how chronotype (i.e., morningness-eveningness trait) and changes in sleep efficiency (SE) were related to changes in depressive symptoms among recipients of CBT-I. Methods: Included were 419 adult insomnia outpatients from a sleep disorders clinic (43.20% males, age mean ± standard deviation = 48.14 ± 14.02). All participants completed the Composite Scale of Morningness and attended at least 4 sessions of a 6-session group CBT-I. SE was extracted from sleep diary; depressive symptoms were assessed using the Beck Depression Inventory (BDI) prior to (Baseline), and at the end (End) of intervention. Results: Multilevel structural equation modeling revealed that from Baseline to End, SE increased and BDI decreased significantly. Controlling for age, sex, BDI, and SE at Baseline, stronger evening chronotype and less improvement in SE significantly and uniquely predicted less reduction in BDI from Baseline to End. Chronotype did not predict improvement in SE. Conclusions: In an insomnia outpatient sample, SE and depressive symptoms improved significantly after a CBT-I group intervention. All chronotypes benefited from sleep improvement, but those with greater eveningness and/or less sleep improvement experienced less reduction in depressive symptom severity. This suggests that evening preference and insomnia symptoms may have distinct relationships with mood, raising the possibility that the effect of CBT-I on depressive symptoms could be enhanced by assessing and addressing circadian factors. Citation: Bei B, Ong JC, Rajaratnam SM, Manber R. Chronotype and improved sleep efficiency independently predict depressive symptom reduction after group cognitive behavioral therapy for insomnia. J Clin Sleep Med 2015;11(9):1021–1027. PMID

  9. Stem Cell Therapy with Overexpressed VEGF and PDGF Genes Improves Cardiac Function in a Rat Infarct Model

    PubMed Central

    Das, Hiranmoy; George, Jon C.; Joseph, Matthew; Das, Manjusri; Abdulhameed, Nasreen; Blitz, Anna; Khan, Mahmood; Sakthivel, Ramasamy; Mao, Hai-Quan; Hoit, Brian D.; Kuppusamy, Periannan; Pompili, Vincent J.

    2009-01-01

    Background Therapeutic potential was evaluated in a rat model of myocardial infarction using nanofiber-expanded human cord blood derived hematopoietic stem cells (CD133+/CD34+) genetically modified with VEGF plus PDGF genes (VIP). Methods and Findings Myocardial function was monitored every two weeks up to six weeks after therapy. Echocardiography revealed time dependent improvement of left ventricular function evaluated by M-mode, fractional shortening, anterior wall tissue velocity, wall motion score index, strain and strain rate in animals treated with VEGF plus PDGF overexpressed stem cells (VIP) compared to nanofiber expanded cells (Exp), freshly isolated cells (FCB) or media control (Media). Improvement observed was as follows: VIP>Exp> FCB>media. Similar trend was noticed in the exercise capacity of rats on a treadmill. These findings correlated with significantly increased neovascularization in ischemic tissue and markedly reduced infarct area in animals in the VIP group. Stem cells in addition to their usual homing sites such as lung, spleen, bone marrow and liver, also migrated to sites of myocardial ischemia. The improvement of cardiac function correlated with expression of heart tissue connexin 43, a gap junctional protein, and heart tissue angiogenesis related protein molecules like VEGF, pNOS3, NOS2 and GSK3. There was no evidence of upregulation in the molecules of oncogenic potential in genetically modified or other stem cell therapy groups. Conclusion Regenerative therapy using nanofiber-expanded hematopoietic stem cells with overexpression of VEGF and PDGF has a favorable impact on the improvement of rat myocardial function accompanied by upregulation of tissue connexin 43 and pro-angiogenic molecules after infarction. PMID:19809493

  10. The Potential Utility of Acceptance and Commitment Therapy (ACT) for Reducing Stress and Improving Wellbeing in Cancer Patients in Kolkata.

    PubMed

    Datta, Arunima; Aditya, Chandana; Chakraborty, Abhijit; Das, Priyabrata; Mukhopadhyay, Ashis

    2016-12-01

    As soon as a patient comes to know that he/she has cancer, the stress starts and psychological intervention is required. The authors assessed how well a cancer patient can manage stress over the course of the psychological intervention. Data was collected among 107 patients during pre and post intervention and at 2 months follow-up. Intervention was required to measures include acceptance of the disease, managing stress, well -being, and meaning of life. Finally, effects of acceptance and commitment therapy (ACT) were defined in acceptance measured in terms of a significant difference between pre and post intervention scores in the meaning of life and the acceptance level. This acceptance and commitment therapy can be an effective intervention approach for cancer patients that increases acceptance regarding disease and simultaneously leads to improvement in the meaning of life.

  11. Quetiapine add-on therapy improves the depressive behaviors and hippocampal neurogenesis in fluoxetine treatment resistant depressive rats.

    PubMed

    Wang, Ying; Chang, Ting; Chen, Yun-Chun; Zhang, Rui-Guo; Wang, Hua-Ning; Wu, Wen-Jun; Peng, Zheng-Wu; Tan, Qing-Rong

    2013-09-15

    Quetiapine, an atypical antipsychotic, may have efficacy as augmentation therapy in treatment resistant depression (TRD), but evidence is limited and the underlying mechanism remains poorly understood. Therefore, this study was aimed to investigate whether and how quetiapine can be served as an augmentation agent in fluoxetine treatment resistant depressive rats induced by chronic unpredictable mild stress (CUMS). In this study, the effects of CUMS regimen and antidepressant treatment were assessed by behavioral tests and hippocampal neurogenesis. Approximately 20-30% of depressive rats respond poorly to fluoxetine treatment. In their hippocampus, a significant decrease of neurogenesis was also observed. However, quetiapine add-on therapy significantly improved the depressive behaviors and increased the number of the newborn neurons in the hippocampus of fluoxetine treatment resistant depressive rats. Thus, our results suggest that quetiapine may be used as an augmentation agent in the treatment resistant depression partly mediated by increasing the number of newborn neurons in the hippocampus.

  12. Dual Functional Capability of Dendritic Cells – Cytokine-Induced Killer Cells in Improving Side Effects of Colorectal Cancer Therapy

    PubMed Central

    Mosińska, Paula; Gabryelska, Agata; Zasada, Malwina; Fichna, Jakub

    2017-01-01

    The aim of cancer therapy is to eradicate cancer without affecting healthy tissues. Current options available for treating colorectal cancer (CRC), including surgery, chemotherapy or radiotherapy, usually elicit multiple adverse effects and frequently fail to completely remove the tumor cells. Thus, there is a constant need for seeking cancer cell-specific therapeutics to improve the course of cancer therapy and reduce the risk of relapse. In this review we elaborate on the mechanisms underlying the immunotherapy with dendritic cells (DCs) and cytokine-induced killer (CIK) cells, and summarize their effectiveness and tolerability available clinical studies. Finally, we discuss the up-to-date combinatorial adoptive anti-cancer immunotherapy with CIK cells co-cultured with DCs that recently showed encouraging efficacy and usefulness in treating malignant disease, including CRC. PMID:28352234

  13. Add-on therapy of pitavastatin and eicosapentaenoic acid improves outcome of peginterferon plus ribavirin treatment for chronic hepatitis C.

    PubMed

    Kohjima, Motoyuki; Enjoji, Munechika; Yoshimoto, Tsuyoshi; Yada, Ryoko; Fujino, Tatsuya; Aoyagi, Yoko; Fukushima, Nobuyoshi; Fukuizumi, Kunitaka; Harada, Naohiko; Yada, Masayoshi; Kato, Masaki; Kotoh, Kazuhiro; Nakashima, Manabu; Sakamoto, Naoya; Tanaka, Yasuhito; Nakamuta, Makoto

    2013-02-01

    Despite the use of pegylated-interferon (peg-IFN) plus ribavirin combination therapy, many patients infected with hepatitis C virus (HCV)-1b remain HCV-positive. To determine whether addition of pitavastatin and eicosapentaenoic acid (EPA) is beneficial, the "add-on" therapy option (add-on group) was compared retrospectively with unmodified peg-IFN/ribavirin therapy (standard group). Association of host- or virus-related factors with sustained virological response was assessed. In HCV replicon cells, the effects of pitavastatin and/or EPA on HCV replication and expression of innate-immunity- and lipid-metabolism-associated genes were investigated. In patients infected with HCV-1b, sustained virological response rates were significantly higher in the add-on than standard group. In both groups, sustained virological response rates were significantly higher in patients with genotype TT of IL-28B (rs8099917) than in those with non-TT genotype. Among the patients with non-TT genotype, sustained virological response rates were markedly higher in the add-on than standard group. By multivariate analysis, genome variation of IL28B but not add-on therapy remained as a predictive factor of sustained virological response. In replicon cells, pitavastatin and EPA suppressed HCV replication. Activation of innate immunity was obvious in pitavastatin-treated cells and EPA suppressed the expression of sterol regulatory element binding protein-1c and low-density lipoprotein receptor. Addition of pitavastatin and EPA to peg-IFN/ribavirin treatment improved sustained virological response in patients infected with HCV-1b. Genotype variation of IL-28B is a strong predictive factor in add-on therapy.

  14. Does anticoagulant therapy improve pregnancy outcome equally, regardless of specific thrombophilia type?

    PubMed

    Kovac, Mirjana; Mikovic, Zeljko; Mitic, Gorana; Djordjevic, Valentina; Mandic, Vesna; Rakicevic, Ljiljana; Radojkovic, Dragica

    2014-03-01

    The study was conducted to evaluate the effect of anticoagulant therapy in women with thrombophilia and to detect the possible differences among carriers of mutations (factor V [FV] Leiden and FIIG20210) and those with natural anticoagulant deficiency. The 4-year prospective investigation included 85 pregnant women, with a history of recurrent fetal loss (RFL). They were treated with prophylactic doses of low-molecular-weight heparin (nadroparin) starting from 6 to 8 weeks of gestation. Pregnancy outcomes were evaluated based on the thrombophilia type. Carriers of thrombophilic mutations had a live birth rate of 93%, compared to 41.6% for women with natural anticoagulant deficiencies. Significant differences between the groups were also observed for intrauterine fetal death, intrauterine growth restriction, and postpartum thrombosis. The optimal therapy for women with natural anticoagulant deficiency and RFL remains unclear and future prospective study with a large number of patients is required to determine the best treatment for these severe thrombophilic conditions.

  15. Photodynamic therapy-induced angiogenic signaling: consequences and solutions to improve therapeutic response

    PubMed Central

    Gallagher-Colombo, Shannon M.; Maas, Amanda L.; Yuan, Min; Busch, Theresa M.

    2015-01-01

    Photodynamic therapy (PDT) can be a highly effective treatment for diseases ranging from actinic keratosis to cancer. While use of this therapy shows great promise in preclinical and clinical studies, understanding the molecular consequences of PDT is critical to designing better treatment protocols. A number of publications have documented alteration in angiogenic factors and growth factor receptors following PDT, which could abrogate treatment effect by inducing angiogenesis and re-establishment of the tumor vasculature. In response to these findings, work over the past decade has examined the efficacy of combining PDT with molecular targeting drugs, such as anti-angiogenic compounds, in an effort to combat these PDT-induced molecular changes. These combinatorial approaches increase rates of apoptosis, impair pro-tumorigenic signaling, and enhance tumor response. This report will examine the current understanding of PDT-induced angiogenic signaling and address molecular-based approaches to abrogate this signaling or its consequences thereby enhancing PDT efficacy. PMID:26109742

  16. Improved adeno-associated virus (AAV) serotype 1 and 5 vectors for gene therapy.

    PubMed

    Sen, Dwaipayan; Balakrishnan, Balaji; Gabriel, Nishanth; Agrawal, Prachi; Roshini, Vaani; Samuel, Rekha; Srivastava, Alok; Jayandharan, Giridhara R

    2013-01-01

    Despite significant advancements with recombinant AAV2 or AAV8 vectors for liver directed gene therapy in humans, it is well-recognized that host and vector-related immune challenges need to be overcome for long-term gene transfer. To overcome these limitations, alternate AAV serotypes (1-10) are being rigorously evaluated. AAV5 is the most divergent (55% similarity vs. other serotypes) and like AAV1 vector is known to transduce liver efficiently. AAV1 and AAV5 vectors are also immunologically distinct by virtue of their low seroprevalence and minimal cross reactivity against pre-existing AAV2 neutralizing antibodies. Here, we demonstrate that targeted bio-engineering of these vectors, augment their gene expression in murine hepatocytes in vivo (up to 16-fold). These studies demonstrate the feasibility of the use of these novel AAV1 and AAV5 vectors for potential gene therapy of diseases like hemophilia.

  17. Neural substrates predicting short-term improvement of tinnitus loudness and distress after modified tinnitus retraining therapy

    PubMed Central

    Kim, Shin Hye; Jang, Ji Hye; Lee, Sang-Yeon; Han, Jae Joon; Koo, Ja-Won; Vanneste, Sven; De Ridder, Dirk; Song, Jae-Jin

    2016-01-01

    Although tinnitus retraining therapy (TRT) is efficacious in most patients, the exact mechanism is unclear and no predictor of improvement is available. We correlated the extent of improvement with pre-TRT quantitative electroencephalography (qEEG) findings to identify neural predictors of improvement after TRT. Thirty-two patients with debilitating tinnitus were prospectively enrolled, and qEEG data were recorded before their initial TRT sessions. Three months later, these qEEG findings were correlated with the percentage improvements in the Tinnitus Handicap Inventory (THI) scores, and numeric rating scale (NRS) scores of tinnitus loudness and tinnitus perception. The THI score improvement was positively correlated with the pre-treatment activities of the left insula and the left rostral and pregenual anterior cingulate cortices (rACC/pgACC), which control parasympathetic activity. Additionally, the activities of the right auditory cortices and the parahippocampus, areas that generate tinnitus, negatively correlated with improvements in loudness. Improvements in the NRS scores of tinnitus perception correlated positively with the pre-TRT activities of the bilateral rACC/pgACC, areas suggested to form the core of the noise-canceling system. The current study supports both the classical neurophysiological and integrative models of tinnitus; our results serve as a milestone in the development of precision medicine in the context of TRT. PMID:27381994

  18. Morphine and clonidine combination therapy improves therapeutic window in mice: synergy in antinociceptive but not in sedative or cardiovascular effects.

    PubMed

    Stone, Laura S; German, Jonathan P; Kitto, Kelly F; Fairbanks, Carolyn A; Wilcox, George L

    2014-01-01

    Opioids are used to manage all types of pain including acute, cancer, chronic neuropathic and inflammatory pain. Unfortunately, opioid-related adverse effects such as respiratory depression, tolerance, physical dependence and addiction have led to an underutilization of these compounds for adequate pain relief. One strategy to improve the therapeutic utility of opioids is to co-administer them with other analgesic agents such as agonists acting at α2-adrenergic receptors (α2ARs). Analgesics acting at α2ARs and opioid receptors (ORs) frequently synergize when co-administered in vivo. Multimodal analgesic techniques offer advantages over single drug treatments as synergistic combination therapies produce analgesia at lower doses, thus reducing undesired side effects. This inference presumes, however, that the synergistic interaction is limited to the analgesic effects. In order to test this hypothesis, we examined the effects of α2AR/OR combination therapy in acute antinociception and in the often-undesired side effects of sedation and cardiovascular depression in awake unrestrained mice. Morphine, clonidine or their combination was administered by spinal or systemic injection in awake mice. Antinociception was determined using the warm water tail flick assay (52.5°C). Sedation/motor impairment was evaluated using the accelerating rotarod assay and cardiovascular function was monitored by pulse oximetry. Data were converted to percent maximum possible effect and isobolographic analysis was performed to determine if an interaction was subadditive, additive or synergistic. Synergistic interactions between morphine and clonidine were observed in the antinociceptive but not in the sedative/motor or cardiovascular effects. As a result, the therapeutic window was improved ∼200-fold and antinociception was achieved at non-sedating doses with little to no cardiovascular depression. In addition, combination therapy resulted in greater maximum analgesic efficacy over

  19. Angiogenesis Research to Improve Therapies for Vascular Leak Syndromes, Intra-Abdominal Adhesions, and Arterial Injuries

    DTIC Science & Technology

    2009-04-01

    and resuspended in phospate buffer saline (PBS) before use. Preparation of magnetic opsonins Super - paramagnetic beads (1 mm diameter, tosyl-coated...permeability in experimental model systems. These therapies include the following: (i) a newly developed nanoparticle -based oral delivery system for...inhibitors utilized in this study: Lodamin and an Fc-conjugated endostatin fragment. • investigated the efficacy of Lodamin (a nanoparticle -based oral

  20. Mitomycin C: new strategies to improve efficacy of a well-known therapy.

    PubMed

    Ragonese, Mauro; Racioppi, Marco; Bassi, Pier Francesco; Di Gianfrancesco, Luca; Lenci, Niccolò; Filianoti, Alessio; Recupero, Salvatore M

    2016-10-04

    Mitomycin C (MMC) as an intravesical chemotherapeutic agent is a well-known option for treatment of nonmuscle invasive bladder cancer (NMIBC) recurrence; it is probably the most commonly used agent given its low rate of side effects and its efficacy.Both the American Urologic Association (AUA) and European Association of Urology (EAU) consider MMC as a standard treatment for immediate single-dose postoperative treatment and for adjuvant therapy in low and intermediate-risk NMIBC.Despite the popularity of this agent in the treatment of NMIBCs, many questions regarding the optimal approach to MMC therapy remain unanswered and the schedule widely used is empirical.Nevertheless, even when the current optimal approaches to MMC administration are used, a large proportion of NMIBCs recur.This apparent treatment resistance might be overcome by an optimization of standard MMC therapy or with a combination of MMC with other agents that have different mechanisms of action.Strategies to enhance passive delivery of MMC have been well studied and multiple measures are recommended for implementation of use in routine clinical practice.A modified scheme of instillation seems to be an easy and inexpensive alternative to increase efficacy of intravesical MMC and to also use this agent with an ablative intent.Enhancing tumor response with a sequential therapy is another option that has been investigated, mostly for chemo-immunotherapy wherein the different mechanisms of action of Bacillus of Calmette and Guerìn (BCG) and MMC are combined to achieve a higher response.

  1. HIV Cure Strategies: How Good Must They Be to Improve on Current Antiretroviral Therapy?

    PubMed Central

    Sax, Paul E.; Sypek, Alexis; Berkowitz, Bethany K.; Morris, Bethany L.; Losina, Elena; Paltiel, A. David; Kelly, Kathleen A.; Seage, George R.; Walensky, Rochelle P.; Weinstein, Milton C.; Eron, Joseph; Freedberg, Kenneth A.

    2014-01-01

    Background We examined efficacy, toxicity, relapse, cost, and quality-of-life thresholds of hypothetical HIV cure interventions that would make them cost-effective compared to life-long antiretroviral therapy (ART). Methods We used a computer simulation model to assess three HIV cure strategies: Gene Therapy, Chemotherapy, and Stem Cell Transplantation (SCT), each compared to ART. Efficacy and cost parameters were varied widely in sensitivity analysis. Outcomes included quality-adjusted life expectancy, lifetime cost, and cost-effectiveness in dollars/quality-adjusted life year ($/QALY) gained. Strategies were deemed cost-effective with incremental cost-effectiveness ratios <$100,000/QALY. Results For patients on ART, discounted quality-adjusted life expectancy was 16.4 years and lifetime costs were $591,400. Gene Therapy was cost-effective with efficacy of 10%, relapse rate 0.5%/month, and cost $54,000. Chemotherapy was cost-effective with efficacy of 88%, relapse rate 0.5%/month, and cost $12,400/month for 24 months. At $150,000/procedure, SCT was cost-effective with efficacy of 79% and relapse rate 0.5%/month. Moderate efficacy increases and cost reductions made Gene Therapy cost-saving, but substantial efficacy/cost changes were needed to make Chemotherapy or SCT cost-saving. Conclusions Depending on efficacy, relapse rate, and cost, cure strategies could be cost-effective compared to current ART and potentially cost-saving. These results may help provide performance targets for developing cure strategies for HIV. PMID:25397616

  2. De-escalation empirical antibiotic therapy improved survival for patients with severe aplastic anemia treated with antithymocyte globulin

    PubMed Central

    Fu, Rong; Chen, Tong; Song, Jia; Wang, Guojin; Li, Lijuan; Ruan, Erbao; Liu, Hui; Wang, Yihao; Wang, Huaquan; Xing, Limin; Wu, Yuhong; Liu, Hong; Qu, Wen; Shao, Zonghong

    2017-01-01

    Abstract We aimed to investigate the efficacy and safety of de-escalation empirical therapy for controlling infection in patients with severe aplastic anaemia (SAA) treated with antithymocyte globulin (ATG). Eighty-seven ATG-treated SAA patients who had microbiological culture-confirmed infections from 2006 to 2015 in our center were retrospectively analyzed. The efficacy of de-escalation and non-de-escalation therapy was compared. Among all 87 patients, 63 patients were treated with de-escalation therapy and 24 patients with non-de-escalation therapy. More patients showed response to anti-infection treatment in de-escalation group than in non-de-escalation group both on day 7 (60.32% vs. 25.00%, P = 0.003) and on day 30 (79.37% vs. 58.33%, P = 0.047) since the initial antimicrobial therapy. On day 30, more patients had increased absolute neutrophil count in de-escalation group compared with non-de-escalation group (76.19% vs. 45.83%, P = 0.007), and de-escalation group had lower morality rate (17.46% vs. 37.50%, P = 0.047) and better survival outcome (P = 0.023) on day 90. Twenty-three patients in de-escalation group and 5 patients in non-escalation group received granulocyte transfusions. Granulocyte transfusions helped to control infections in both de-escalation group (P = 0.027) and non-de-escalation group (P = 0.042) on day 7, but did not improve survival on day 90. We concluded that de-escalation antibiotics improved survival in SAA patients after ATG treatment. Early administration of broad-spectrum antibiotics pending microbiological cultures combined with a commitment to change to narrow-spectrum antibiotics should be recommended for controlling infections in SAA patients treated with ATG. Granulocyte transfusions might be an adjunctive therapy in controlling infections. PMID:28178130

  3. Probiotics improve the efficacy of standard triple therapy in the eradication of Helicobacter pylori: a meta-analysis

    PubMed Central

    Lau, Christine S M; Ward, Amanda; Chamberlain, Ronald S

    2016-01-01

    probiotics is associated with improved H. pylori eradication rates in both children and adults, as well as Asians and non-Asians. Lactobacillus, Bifidobacterium, Saccharomyces, and mixtures of probiotics appear beneficial in H. pylori eradication. Furthermore, the reduction in antibiotic-associated side effects such as nausea, vomiting, diarrhea, and epigastric pain improves medication tolerance and patient compliance. Given the consequences associated with chronic H. pylori infection, the addition of probiotics to the concurrent triple therapy regimen should be considered in all patients with H. pylori infection. However, further studies are required to identify the optimal probiotic species and dose. PMID:27994474

  4. De-escalation empirical antibiotic therapy improved survival for patients with severe aplastic anemia treated with antithymocyte globulin.

    PubMed

    Fu, Rong; Chen, Tong; Song, Jia; Wang, Guojin; Li, Lijuan; Ruan, Erbao; Liu, Hui; Wang, Yihao; Wang, Huaquan; Xing, Limin; Wu, Yuhong; Liu, Hong; Qu, Wen; Shao, Zonghong

    2017-02-01

    We aimed to investigate the efficacy and safety of de-escalation empirical therapy for controlling infection in patients with severe aplastic anaemia (SAA) treated with antithymocyte globulin (ATG). Eighty-seven ATG-treated SAA patients who had microbiological culture-confirmed infections from 2006 to 2015 in our center were retrospectively analyzed. The efficacy of de-escalation and non-de-escalation therapy was compared. Among all 87 patients, 63 patients were treated with de-escalation therapy and 24 patients with non-de-escalation therapy. More patients showed response to anti-infection treatment in de-escalation group than in non-de-escalation group both on day 7 (60.32% vs. 25.00%, P = 0.003) and on day 30 (79.37% vs. 58.33%, P = 0.047) since the initial antimicrobial therapy. On day 30, more patients had increased absolute neutrophil count in de-escalation group compared with non-de-escalation group (76.19% vs. 45.83%, P = 0.007), and de-escalation group had lower morality rate (17.46% vs. 37.50%, P = 0.047) and better survival outcome (P = 0.023) on day 90. Twenty-three patients in de-escalation group and 5 patients in non-escalation group received granulocyte transfusions. Granulocyte transfusions helped to control infections in both de-escalation group (P = 0.027) and non-de-escalation group (P = 0.042) on day 7, but did not improve survival on day 90. We concluded that de-escalation antibiotics improved survival in SAA patients after ATG treatment. Early administration of broad-spectrum antibiotics pending microbiological cultures combined with a commitment to change to narrow-spectrum antibiotics should be recommended for controlling infections in SAA patients treated with ATG. Granulocyte transfusions might be an adjunctive therapy in controlling infections.

  5. Thermography Improves Clinical Assessment in Patients with Systemic Sclerosis Treated with Ozone Therapy

    PubMed Central

    2017-01-01

    Objective. Treatment of scleroderma is challenging and limited. The aim of our study was to evaluate the usefulness of thermography in assessment of the clinical condition (joints movability and skin thickness) in clinically advanced patients with systemic sclerosis before and after ozone therapy. Method. The study included 42 patients aged 32 to 73 years with advanced systemic sclerosis hospitalized in the university clinic between 2003 and 2006. Thermography and clinical examinations were conducted at baseline and after two series of bath in water with ozone. Results. The comparison of results showed significant increase in skin temperature by 2.5°C, significant increase in interphalangeal joints movability by 18 degrees, and significant decrease in skin score by 14.7 points. The skin temperature was correlated with skin score (r = −0.59) and joints movability (r = +0.8). Conclusions. Ozone therapy shows positive effect on clinical parameters and skin temperature as measured with thermography. The study indicated possibility of introducing ozonotherapy as an independent therapy in cases with low level of progression or during remission periods and as additional treatment in patients with advanced disease requiring immunosuppressive treatment. Thermography is useful in assessment of skin condition showing strong correlation between skin temperature and clinical parameters. PMID:28349063

  6. Photodynamic therapy synergizes with irinotecan to overcome compensatory mechanisms and improve treatment outcomes in pancreatic cancer

    PubMed Central

    Huang, Huang-Chiao; Mallidi, Srivalleesha; Liu, Joyce; Chiang, Chun-Te; Mai, Zhiming; Goldschmidt, Ruth; Ebrahim-Zadeh, Neema; Rizvi, Imran; Hasan, Tayyaba

    2015-01-01

    The ability of tumor cells to adapt to therapeutic regimens by activating alternative survival and growth pathways remains a major challenge in cancer therapy. Therefore, the most effective treatments will involve interactive strategies that target multiple non-overlapping pathways while eliciting synergistic outcomes and minimizing systemic toxicities. Nanoliposomal irinotecan is FDA-approved for gemcitabine-refractory metastatic pancreatic cancer (PanCa). However, the full potential of irinotecan treatment is hindered by several cancer cell survival mechanisms, including ATP-binding cassette G2 (ABCG2) transporter-mediated irinotecan efflux from cells. Here we demonstrate that benzoporphyrin derivative (BPD)-based photodynamic therapy (PDT), a photochemical cytotoxic modality that activates the apoptotic pathway, reduced ABCG2 expression to increase intracellular irinotecan levels in PanCa. Moreover, we show that PDT inhibited survivin expression. While PDT potentiated irinotecan treatment, we also demonstrate that irinotecan reduced the tumoral expression of monocarboxylate transporter 4 (MCT-4), which was upregulated by PDT. Notably, using orthotopic xenograft models, we demonstrate that combination of single low-dose PDT and a subclinical dose of nanoliposomal irinotecan synergistically inhibited tumor growth by 70% for 3-weeks compared to 25% reduction after either monotherapies. Our findings offer new opportunities for the clinical translation of PDT and irinotecan combination therapy for effective PanCa treatment. PMID:26719532

  7. Improved outcomes with intensity modulated radiation therapy combined with temozolomide for newly diagnosed glioblastoma multiforme.

    PubMed

    Aherne, Noel J; Benjamin, Linus C; Horsley, Patrick J; Silva, Thomaz; Wilcox, Shea; Amalaseelan, Julan; Dwyer, Patrick; Tahir, Abdul M R; Hill, Jacques; Last, Andrew; Hansen, Carmen; McLachlan, Craig S; Lee, Yvonne L; McKay, Michael J; Shakespeare, Thomas P

    2014-01-01

    Purpose. Glioblastoma multiforme (GBM) is optimally treated by maximal debulking followed by combined chemoradiation. Intensity modulated radiation therapy (IMRT) is gaining widespread acceptance in other tumour sites, although evidence to support its use over three-dimensional conformal radiation therapy (3DCRT) in the treatment of gliomas is currently lacking. We examined the survival outcomes for patients with GBM treated with IMRT and Temozolomide. Methods and Materials. In all, 31 patients with GBM were treated with IMRT and 23 of these received chemoradiation with Temozolomide. We correlated survival outcomes with patient functional status, extent of surgery, radiation dose, and use of chemotherapy. Results. Median survival for all patients was 11.3 months, with a median survival of 7.2 months for patients receiving 40.05 Gray (Gy) and a median survival of 17.4 months for patients receiving 60 Gy. Conclusions. We report one of the few series of IMRT in patients with GBM. In our group, median survival for those receiving 60 Gy with Temozolomide compared favourably to the combined therapy arm of the largest randomised trial of chemoradiation versus radiation to date (17.4 months versus 14.6 months). We propose that IMRT should be considered as an alternative to 3DCRT for patients with GBM.

  8. Thermography Improves Clinical Assessment in Patients with Systemic Sclerosis Treated with Ozone Therapy.

    PubMed

    Nowicka, Danuta

    2017-01-01

    Objective. Treatment of scleroderma is challenging and limited. The aim of our study was to evaluate the usefulness of thermography in assessment of the clinical condition (joints movability and skin thickness) in clinically advanced patients with systemic sclerosis before and after ozone therapy. Method. The study included 42 patients aged 32 to 73 years with advanced systemic sclerosis hospitalized in the university clinic between 2003 and 2006. Thermography and clinical examinations were conducted at baseline and after two series of bath in water with ozone. Results. The comparison of results showed significant increase in skin temperature by 2.5°C, significant increase in interphalangeal joints movability by 18 degrees, and significant decrease in skin score by 14.7 points. The skin temperature was correlated with skin score (r = -0.59) and joints movability (r = +0.8). Conclusions. Ozone therapy shows positive effect on clinical parameters and skin temperature as measured with thermography. The study indicated possibility of introducing ozonotherapy as an independent therapy in cases with low level of progression or during remission periods and as additional treatment in patients with advanced disease requiring immunosuppressive treatment. Thermography is useful in assessment of skin condition showing strong correlation between skin temperature and clinical parameters.

  9. Concise Review: Mesenchymal Stem Cell Therapy for Pediatric Disease: Perspectives on Success and Potential Improvements.

    PubMed

    Nitkin, Christopher R; Bonfield, Tracey L

    2016-09-13

    : Mesenchymal stem cells (MSCs) represent a potentially revolutionary therapy for a wide variety of pediatric diseases, but the optimal cell-based therapeutics for such diversity have not yet been specified. The published clinical trials for pediatric pulmonary, cardiac, orthopedic, endocrine, neurologic, and hematologic diseases provide evidence that MSCs are indeed efficacious, but the significant heterogeneity in therapeutic approaches between studies raises new questions. The purpose of this review is to stimulate new preclinical and clinical trials to investigate these factors. First, we discuss recent clinical trials for pediatric diseases studying MSCs obtained from bone marrow, umbilical cord and umbilical cord blood, placenta, amniotic fluid, and adipose tissue. We then identify factors, some unique to pediatrics, which must be examined to optimize therapeutic efficacy, including route of administration, dose, timing of administration, the role of ex vivo differentiation, cell culture techniques, donor factors, host factors, and the immunologic implications of allogeneic therapy. Finally, we discuss some of the practicalities of bringing cell-based therapy into the clinic, including regulatory and manufacturing considerations. The aim of this review is to inform future studies seeking to maximize therapeutic efficacy for each disease and for each patient.

  10. Gene therapy in the second eye of RPE65-deficient dogs improves retinal function

    PubMed Central

    Annear, MJ; Bartoe, JT; Barker, SE; Smith, AJ; Curran, PG; Bainbridge, JW; Ali, RR; Petersen-Jones, SM

    2012-01-01

    The purpose of this study was to evaluate whether immune responses interfered with gene therapy rescue using subretinally delivered recombinant adeno-associated viral vector serotype 2 carrying the RPE65 cDNA gene driven by the human RPE65 promoter (rAAV2.hRPE65p.hRPE65) in the second eye of RPE65−/− dogs that had previously been treated in a similar manner in the other eye. Bilateral subretinal injection was performed in nine dogs with the second eye treated 85–180 days after the first. Electroretinography (ERG) and vision testing showed rescue in 16 of 18 treated eyes, with no significant difference between first and second treated eyes. A serum neutralizing antibody (NAb) response to rAAV2 was detected in all treated animals, but this did not prevent or reduce the effectiveness of rescue in the second treated eye. We conclude that successful rescue using subretinal rAAV2.hRPE65p.hRPE65 gene therapy in the second eye is not precluded by prior gene therapy in the contralateral eye of the RPE65−/− dog. This finding has important implications for the treatment of human LCA type II patients. PMID:20703309

  11. Preoperative adjuvant transarterial chemoembolization cannot improve the long term outcome of radical therapies for hepatocellular carcinoma.

    PubMed

    Jianyong, Lei; Jinjing, Zhong; Lunan, Yan; Jingqiang, Zhu; Wentao, Wang; Yong, Zeng; Bo, Li; Tianfu, Wen; Jiaying, Yang

    2017-02-03

    Combinations of transarterial chemoembolization (TACE) and radical therapies (pretransplantation, resection and radiofrequency ablation) for hepatocellular carcinoma (HCC) have been reported as controversial issues in recent years. A consecutive sample of 1560 patients with Barcelona Clinic Liver Cancer (BCLC) stage A/B HCC who underwent solitary Radiofrequency ablation (RFA), resection or liver transplantation (LT) or adjuvant pre-operative TACE were included. The 1-, 3- and 5-year overall survival rates and tumor-free survival rates were comparable between the solitary radical therapy group and TACE combined group in the whole group and in each of the subgroups (RFA, resection and LT) (P > 0.05). In the subgroup analysis, according to BCLC stage A or B, the advantages of adjuvant TACE were also not observed (P > 0.05). A Neutrophil-lymphocyte ratio (NLR) more than 4, multiple tumor targets, BCLC stage B, and poor histological grade were significant contributors to the overall and tumor-free survival rates. In conclusions, our results indicated that preoperative adjuvant TACE did not prolong long-term overall or tumor-free survival, but LT should nevertheless be considered the first choice for BCLC stage A or B HCC patients. Radical therapies should be performed very carefully in BCLC stage B HCC patients.

  12. Preoperative adjuvant transarterial chemoembolization cannot improve the long term outcome of radical therapies for hepatocellular carcinoma

    PubMed Central

    Jianyong, Lei; Jinjing, Zhong; Lunan, Yan; Jingqiang, Zhu; Wentao, Wang; Yong, Zeng; Bo, Li; Tianfu, Wen; Jiaying, Yang

    2017-01-01

    Combinations of transarterial chemoembolization (TACE) and radical therapies (pretransplantation, resection and radiofrequency ablation) for hepatocellular carcinoma (HCC) have been reported as controversial issues in recent years. A consecutive sample of 1560 patients with Barcelona Clinic Liver Cancer (BCLC) stage A/B HCC who underwent solitary Radiofrequency ablation (RFA), resection or liver transplantation (LT) or adjuvant pre-operative TACE were included. The 1-, 3- and 5-year overall survival rates and tumor-free survival rates were comparable between the solitary radical therapy group and TACE combined group in the whole group and in each of the subgroups (RFA, resection and LT) (P > 0.05). In the subgroup analysis, according to BCLC stage A or B, the advantages of adjuvant TACE were also not observed (P > 0.05). A Neutrophil-lymphocyte ratio (NLR) more than 4, multiple tumor targets, BCLC stage B, and poor histological grade were significant contributors to the overall and tumor-free survival rates. In conclusions, our results indicated that preoperative adjuvant TACE did not prolong long-term overall or tumor-free survival, but LT should nevertheless be considered the first choice for BCLC stage A or B HCC patients. Radical therapies should be performed very carefully in BCLC stage B HCC patients. PMID:28155861

  13. The legacy of Cf-252 operations at Savannah River Technology Center: Continuous releases of radioiodine to the atmosphere

    SciTech Connect

    Kantelo, M.V.; Crandall, B.S.

    1992-12-31

    The iodine isotopes I-132, 1-133, I-134, and I-135, which have half-lives ranging from 53 minutes to 21 hours, are measured in the atmospheric effluent from the Savannah River Technology Center (SRTC) at the Savannah River Site (SRS) near Aiken, South Carolina. SRS is operated by Westinghouse Savannah River Company for the US Department of Energy (DOE). The isotopes` release rates range from 10 to 300 microcuries per week compared to the rate. The resulting annual dose from all iodine isotopes is minor; it comprises 0.01 percent of the total offsite dose due to atmospheric releases from SRS in 1990. Circumstantial evidence indicates the radioiodine originates from traces of unencapsulated Cf-252. The determination that spontaneous fission of Cf-252 is the source of the radioiodine has several ramifications. Radioactive fission-product isotopes of the noble gas elements krypton and xenon must also be released. Noble gases are more volatile and mobile than iodine. Also, the released iodine isotopes decay to xenon isotopes. The noble gases decay to non-gaseous elements that are transported along with radioiodine to the terrestrial environment by deposition from the SRTC plume. Only Sr-89 is believed to accumulate sufficiently in the environment to approach detectable levels. Given similar conditions in earlier years, releases of short-lived radioiodine have occurred undetected in routine monitoring since the early 1970s. Release rates 20 years ago would have been 200 times greater than current release rates. This report documents preliminary experiments conducted by SRTC and Environmental Monitoring Section (EMS) scientists. The release process and the environmental impact of fission products from Cf-252 should be thoroughly researched.

  14. The legacy of Cf-252 operations at Savannah River Technology Center: Continuous releases of radioiodine to the atmosphere

    SciTech Connect

    Kantelo, M.V.; Crandall, B.S.

    1992-01-01

    The iodine isotopes I-132, 1-133, I-134, and I-135, which have half-lives ranging from 53 minutes to 21 hours, are measured in the atmospheric effluent from the Savannah River Technology Center (SRTC) at the Savannah River Site (SRS) near Aiken, South Carolina. SRS is operated by Westinghouse Savannah River Company for the US Department of Energy (DOE). The isotopes' release rates range from 10 to 300 microcuries per week compared to the rate. The resulting annual dose from all iodine isotopes is minor; it comprises 0.01 percent of the total offsite dose due to atmospheric releases from SRS in 1990. Circumstantial evidence indicates the radioiodine originates from traces of unencapsulated Cf-252. The determination that spontaneous fission of Cf-252 is the source of the radioiodine has several ramifications. Radioactive fission-product isotopes of the noble gas elements krypton and xenon must also be released. Noble gases are more volatile and mobile than iodine. Also, the released iodine isotopes decay to xenon isotopes. The noble gases decay to non-gaseous elements that are transported along with radioiodine to the terrestrial environment by deposition from the SRTC plume. Only Sr-89 is believed to accumulate sufficiently in the environment to approach detectable levels. Given similar conditions in earlier years, releases of short-lived radioiodine have occurred undetected in routine monitoring since the early 1970s. Release rates 20 years ago would have been 200 times greater than current release rates. This report documents preliminary experiments conducted by SRTC and Environmental Monitoring Section (EMS) scientists. The release process and the environmental impact of fission products from Cf-252 should be thoroughly researched.

  15. Preoperative long-acting octreotide treatment for invasive thyrotropin-secreting pituitary macroadenoma after previous radioiodine thyroid ablation.

    PubMed

    Gruszka, Anna; Zielinski, Grzegorz M; Kunert-Radek, Jolanta

    2014-02-01

    We report a 33-year-old woman with invasive thyrotropin-secreting pituitary adenoma after previous thyroid ablation with radioiodine who was successfully treated with transsphenoidal surgery after pre-treatment with octreotide-LAR for 10 months. Since invasive and aggressive thyrotropin-secreting macroadenomas are more frequently observed in patients who have undergone thyroid ablation, we suggest preoperative treatment with somatostatin analogs should be considered in these patients to reduce serum thyrotropin and stabilize or reduce tumor size.

  16. Instantaneous radioiodination of rose bengal at room temperature and a cold-kit therefor. [DOE patent application

    DOEpatents

    O'Brien, H. Jr.; Hupf, H.B.; Wanek, P.M.

    The disclosure relates to the radioiodination of rose bengal at room temperature and a cold-kit therefor. A purified rose bengal tablet is stirred into acidified ethanol at or near room temperature, until a suspension forms. Reductant-free /sup 125/I/sup -/ is added and the resulting mixture stands until the exchange label reaction occurs at room temperature. A solution of sterile isotonic phosphate buffer and sodium hydroxide is added and the final resulting mixture is sterilized by filtration.

  17. Improving Teacher Awareness of Fine Motor Problems and Occupational Therapy: Education Workshops for Preservice Teachers, General Education Teachers and Special Education Teachers in Canada

    ERIC Educational Resources Information Center

    Chiu, Teresa; Heidebrecht, Melissa; Wehrmann, Susan; Sinclair, Gerry; Reid, Denise

    2008-01-01

    Students with fine motor problems can benefit from occupational therapy. Yet not all students receive the services because of a lack of teacher awareness about the problems and the services. This study aims to evaluate a workshop designed to improve teacher awareness about fine motor problems and occupational therapy. The study involved three…

  18. Recent trends in robot-assisted therapy environments to improve real-life functional performance after stroke

    PubMed Central

    Johnson, Michelle J

    2006-01-01

    Upper and lower limb robotic tools for neuro-rehabilitation are effective in reducing motor impairment but they are limited in their ability to improve real world function. There is a need to improve functional outcomes after robot-assisted therapy. Improvements in the effectiveness of these environments may be achieved by incorporating into their design and control strategies important elements key to inducing motor learning and cerebral plasticity such as mass-practice, feedback, task-engagement, and complex problem solving. This special issue presents nine articles. Novel strategies covered in this issue encourage more natural movements through the use of virtual reality and real objects and faster motor learning through the use of error feedback to guide acquisition of natural movements that are salient to real activities. In addition, several articles describe novel systems and techniques that use of custom and commercial games combined with new low-cost robot systems and a humanoid robot to embody the " supervisory presence" of the therapy as possible solutions to exercise compliance in under-supervised environments such as the home. PMID:17176474

  19. Wii-based Balance Therapy to Improve Balance Function of Children with Cerebral Palsy: A Pilot Study.

    PubMed

    Tarakci, Devrim; Ozdincler, Arzu Razak; Tarakci, Ela; Tutuncuoglu, Fatih; Ozmen, Meral

    2013-09-01

    [Purpose] Cerebral palsy is a sensorimotor disorder that affects the control of posture and movement. The Nintendo(®) Wii Fit offers an inexpensive, enjoyable, suitable alternative to more complex systems for children with cerebral palsy. The aim of this study was to investigate the efficacacy of Wii-based balance therapy for children with ambulatory cerebral palsy. [Subjects] This pilot study design included fourteen ambulatory patients with cerebral palsy (11 males, 3 females; mean age 12.07 ± 3.36 years). [Methods] Balance functions before and after treatment were evaluated using one leg standing, the functional reach test, the timed up and go test, and the 6-minute walking test. The physiotherapist prescribed the Wii Fit activities,and supervised and supported the patients during the therapy sessions. Exercises were performed in a standardized program 2 times a week for 12 weeks. [Results] Balance ability of every patient improved. Statistically significant improvements were found in all outcome measures after 12 weeks. [Conclusion] The results suggest that the Nintendo(®) Wii Fit provides a safe, enjoyable, suitable and effective method that can be added to conventional treatments to improve the static balance of patients with cerebral palsy; however, further work is required.

  20. Radioprotectors and Radiomitigators for Improving Radiation Therapy: The Small Business Innovation Research (SBIR) Gateway for Accelerating Clinical Translation.

    PubMed

    Prasanna, Pataje G S; Narayanan, Deepa; Hallett, Kory; Bernhard, Eric J; Ahmed, Mansoor M; Evans, Gregory; Vikram, Bhadrasain; Weingarten, Michael; Coleman, C Norman

    2015-09-01

    Although radiation therapy is an important cancer treatment modality, patients may experience adverse effects. The use of a radiation-effect modulator may help improve the outcome and health-related quality of life (HRQOL) of patients undergoing radiation therapy either by enhancing tumor cell killing or by protecting normal tissues. Historically, the successful translation of radiation-effect modulators to the clinic has been hindered due to the lack of focused collaboration between academia, pharmaceutical companies and the clinic, along with limited availability of support for such ventures. The U.S. Government has been developing medical countermeasures against accidental and intentional radiation exposures to mitigate the risk and/or severity of acute radiation syndrome (ARS) and the delayed effects of acute radiation exposures (DEARE), and there is now a drug development pipeline established. Some of these medical countermeasures could potentially be repurposed for improving the outcome of radiation therapy and HRQOL of cancer patients. With the objective of developing radiation-effect modulators to improve radiotherapy, the Small Business Innovation Research (SBIR) Development Center at the National Cancer Institute (NCI), supported by the Radiation Research Program (RRP), provided funding to companies from 2011 to 2014 through the SBIR contracts mechanism. Although radiation-effect modulators collectively refer to radioprotectors, radiomitigators and radiosensitizers, the focus of this article is on radioprotection and mitigation of radiation injury. This specific SBIR contract opportunity strengthened existing partnerships and facilitated new collaborations between academia and industry. In this commentary, we assess the impact of this funding opportunity, outline the review process, highlight the organ/site-specific disease needs in the clinic for the development of radiation-effect modulators, provide a general understanding of a framework for gathering

  1. Radioprotectors and Radiomitigators for Improving Radiation Therapy: The Small Business Innovation Research (SBIR) Gateway for Accelerating Clinical Translation

    PubMed Central

    Prasanna, Pataje G. S.; Narayanan, Deepa; Hallett, Kory; Bernhard, Eric J.; Ahmed, Mansoor M.; Evans, Gregory; Vikram, Bhadrasain; Weingarten, Michael; Coleman, C. Norman

    2015-01-01

    Although radiation therapy is an important cancer treatment modality, patients may experience adverse effects. The use of a radiation-effect modulator may help improve the outcome and health-related quality of life (HRQOL) of patients undergoing radiation therapy either by enhancing tumor cell killing or by protecting normal tissues. Historically, the successful translation of radiation-effect modulators to the clinic has been hindered due to the lack of focused collaboration between academia, pharmaceutical companies and the clinic, along with limited availability of support for such ventures. The U.S. Government has been developing medical countermeasures against accidental and intentional radiation exposures to mitigate the risk and/or severity of acute radiation syndrome (ARS) and the delayed effects of acute radiation exposures (DEARE), and there is now a drug development pipeline established. Some of these medical countermeasures could potentially be repurposed for improving the outcome of radiation therapy and HRQOL of cancer patients. With the objective of developing radiation-effect modulators to improve radiotherapy, the Small Business Innovation Research (SBIR) Development Center at the National Cancer Institute (NCI), supported by the Radiation Research Program (RRP), provided funding to companies from 2011 to 2014 through the SBIR contracts mechanism. Although radiation-effect modulators collectively refer to radioprotectors, radiomitigators and radiosensitizers, the focus of this article is on radioprotection and mitigation of radiation injury. This specific SBIR contract opportunity strengthened existing partnerships and facilitated new collaborations between academia and industry. In this commentary, we assess the impact of this funding opportunity, outline the review process, highlight the organ/site-specific disease needs in the clinic for the development of radiation-effect modulators, provide a general understanding of a framework for gathering

  2. Piloting behavioral family systems therapy to improve adherence among adolescents with HIV: a case series intervention study.

    PubMed

    Gray, Wendy N; Janicke, David M; Fennell, Eileen B; Driscoll, Danielle C; Lawrence, Robert M

    2011-07-01

    Adolescents with HIV are at high risk for suboptimal adherence but have been ignored by the literature. Treatment outcome and feasibility data for the first-known adaptation of Behavioral Family Systems Therapy (BFST) targeting adherence among adolescents with HIV are presented for four adolescents with suboptimal adherence. The intervention was delivered in an alternating home-based and telehealth format and a multi-method adherence assessment approach was used. Adherence improved for three adolescents, viral load decreased for two adolescents, and barriers to adherence declined for all participants. Delivery of an adapted BFST intervention was acceptable to families and may be a promising treatment approach.

  3. ICT and mobile health to improve clinical process delivery. a research project for therapy management process innovation.

    PubMed

    Locatelli, Paolo; Montefusco, Vittorio; Sini, Elena; Restifo, Nicola; Facchini, Roberta; Torresani, Michele

    2013-01-01

    The volume and the complexity of clinical and administrative information make Information and Communication Technologies (ICTs) essential for running and innovating healthcare. This paper tells about a project aimed to design, develop and implement a set of organizational models, acknowledged procedures and ICT tools (Mobile & Wireless solutions and Automatic Identification and Data Capture technologies) to improve actual support, safety, reliability and traceability of a specific therapy management (stem cells). The value of the project is to design a solution based on mobile and identification technology in tight collaboration with physicians and actors involved in the process to ensure usability and effectivenes in process management.

  4. Inhibition of Axl improves the targeted therapy against ALK-mutated neuroblastoma

    SciTech Connect

    Xu, Fei; Li, Hongling; Sun, Yong

    2014-11-28

    Highlights: • First reported Axl is co-expressed with ALK in neuroblastoma tissues and cell lines. • Axl activation promotes cell growth and impairs the efficiency of ALK inhibitor. • Further found silence of Axl leads to increased sensitivity to ALK inhibitors. • Axl inhibitor promotes the efficiency of targeted therapy in vitro and in vivo. • Axl activation should be considered in the clinical application of ALK inhibitors. - Abstract: Neuroblastoma (NB) patients harboring mutated ALK can be expected to potentially benefit from targeted therapy based on ALK tyrosine kinase inhibitor (TKI), such as crizotinib and ceritinib. However, the effect of the treatment varies with different individuals, although with the same genic changes. Axl receptor tyrosine kinase is expressed in a variety of human cancers, but little data are reported in NB, particularly in which carrying mutated ALK. In this study, we focus on the roles of Axl in ALK-mutated NB for investigating rational therapeutic strategy. We found that Axl is expressed in ALK-positive NB tissues and cell lines, and could be effectively activated by its ligand GAS6. Ligand-dependent Axl activation obviously rescued crizotinib-mediated suppression of cell proliferation in ALK-mutated NB cells. Genetic inhibition of Axl with specific small interfering RNA markedly increased the sensitivity of cells to ALK-TKIs. Furthermore, a small-molecule inhibitor of Axl significantly enhanced ALK-targeted therapy, as an increased frequency of apoptosis was observed in NB cells co-expressing ALK and Axl. Taken together, our results demonstrated that activation of Axl could lead to insensitivity to ALK inhibitors, and dual inhibition of ALK and Axl might be a potential therapeutic strategy against ALK-mutated NB.

  5. Therapy to Improve Pitch in Young Adults with Profound Hearing Loss.

    ERIC Educational Resources Information Center

    Subtelny, Joanne; And Others

    1989-01-01

    A voice training program to improve pitch register was developed for profoundly hearing-impaired young adults. Ten students of the National Technical Institute for the Deaf completed the program; results showed a significant reduction in pitch level, as well as improvement in pitch control and word intelligibility. (Author/JDD)

  6. Veganism Is a Viable Alternative to Conventional Diet Therapy for Improving Blood Lipids and Glycemic Control.

    PubMed

    Trepanowski, John F; Varady, Krista A

    2015-01-01

    The American Diabetes Association (ADA) and the National Cholesterol Education Program (NCEP) have each outlined a set of dietary recommendations aimed at improving glycemic control and blood lipids, respectively. However, traditional vegan diets (low-fat diets that proscribe animal product consumption) are also effective at improving glycemic control, and dietary portfolios (vegan diets that contain prescribed amounts of plant sterols, viscous fibers, soy protein, and nuts) are also effective at improving blood lipids. The purpose of this review was to compare the effects of traditional vegan diets and dietary portfolios with ADA and NCEP diets on body weight, blood lipids, blood pressure, and glycemic control. The main findings are that traditional vegan diets appear to improve glycemic control better than ADA diets in individuals with type 2 diabetes mellitus (T2DM), while dietary portfolios have been consistently shown to improve blood lipids better than NCEP diets in hypercholesterolemic individuals.

  7. Improved Anticancer Photothermal Therapy Using the Bystander Effect Enhanced by Antiarrhythmic Peptide Conjugated Dopamine-Modified Reduced Graphene Oxide Nanocomposite.

    PubMed

    Yu, Jiantao; Lin, Yu-Hsin; Yang, Lingyan; Huang, Chih-Ching; Chen, Liliang; Wang, Wen-Cheng; Chen, Guan-Wen; Yan, Junyan; Sawettanun, Saranta; Lin, Chia-Hua

    2017-01-01

    Despite tremendous efforts toward developing novel near-infrared (NIR)-absorbing nanomaterials, improvement in therapeutic efficiency remains a formidable challenge in photothermal cancer therapy. This study aims to synthesize a specific peptide conjugated polydopamine-modified reduced graphene oxide (pDA/rGO) nanocomposite that promotes the bystander effect to facilitate cancer treatment using NIR-activated photothermal therapy. To prepare a nanoplatform capable of promoting the bystander effect in cancer cells, we immobilized antiarrhythmic peptide 10 (AAP10) on the surface of dopamine-modified rGO (AAP10-pDA/rGO). Our AAP10-pDA/rGO could promote the bystander effect by increasing the expression of connexin 43 protein in MCF-7 breast-cancer cells. Because of its tremendous ability to absorb NIR absorption, AAP10-pDA/rGO offers a high photothermal effect under NIR irradiation. This leads to a massive death of MCF-7 cells via the bystander effect. Using tumor-bearing mice as the model, it is found that NIR radiation effectively ablates breast tumor in the presence of AAP10-pDA/rGO and inhibits tumor growth by ≈100%. Therefore, this research integrates the bystander and photothermal effects into a single nanoplatform in order to facilitate an efficient photothermal therapy. Furthermore, our AAP10-pDA/rGO, which exhibits both hyperthermia and the bystander effect, can prevent breast-cancer recurrence and, therefore, has great potential for future clinical and research applications.

  8. Probiotics improve efficacy and tolerability of triple therapy to eradicate Helicobacter pylori: a meta-analysis of randomized controlled trials

    PubMed Central

    Gong, Yi; Li, Yan; Sun, Qian

    2015-01-01

    Objective: Gastric colonization by Helicobacter pylori is linked to a host of diseases, but eradication rates have declined in recent years. Some experimental studies suggest that probiotics may inhibit growth of H. pylori. This investigation was conducted to assess the impact of probiotics on both efficacy and tolerability of triple therapy to eradicate H. pylori. Methods: PubMed, Web of Science, and the Cochrane Collaboration were searched for relevant articles published through August 31, 2014. All analytics relied on commercially available software (Stata 11). Results: Twenty-three studies (N = 3900) qualified for meta-analysis. Pooled H. pylori eradication rates for triple therapy used alone and with added probiotics were 1464/2026 (72.26%; 95% CI, 67.66%-74.13) and 1513/1874 (80.74%; 95% CI, 74.68%-82.76%), respectively (odds ratio [OR] = 0.58; 95% CI, 0.50-0.68). Loss of appetite was similar in both groups (OR = 0.94; 95% CI, 0.61-1.45), but most adverse events (nausea, diarrhea, epigastric pain, vomiting, taste distortion, and skin rash) were mitigated through addition of probiotics. Publication bias was not evident, as indicated by Begg’s and Egger’s tests. Conclusions: Probiotics may improve the efficacy of triple therapy in eradicating gastric H. pylori and alleviate most treatment-related adverse events. PMID:26131283

  9. Laboratory evaluation of a new delivery system to improve patient compliance with chelation therapy.

    PubMed

    Lombardo, T; Frontini, V; Ferro, G; Sergi, P; Guidice, A; Lombardo, G

    1996-03-01

    As thalassaemia patients live longer, compliance with chelation therapy becomes more and more of a problem. Teenagers rebel against the continual need for treatment, and young adults with jobs, active social lives and families, find it hard to find the time to prepare and deliver their treatments. In an effort to find a solution to this problem, we evaluated a non-electronic, disposable pump (Infusor 5 ml/h, Baxter Healthcare) to determine its suitability for high dose desferrioxamine (DFO) infusions. We wanted an infusion time of 12 h to support overnight delivery in the patient's home. Because of DFOs viscosity, infusion times vary at different concentrations. We found the optimal prescription for total delivery within 12 h to be a dose of 70 mg/kg x patient's body weight diluted in constant volume of 40 ml of water for injection. Our tests were carried out in vitro and the results show that the 5 ml/h Infusor may be used to deliver high dose DFO chelation therapy within 12 h. The variability of the flow rate, dependent on the concentration of the solution, and the absence of a warning system, are more than compensated for by the simplicity of the pump.

  10. Combination therapy including serratiopeptidase improves outcomes o