Therapeutic dose from a pyroelectric electron accelerator.

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Fullem, T Z; Fazel, K C; Geuther, J A; Danon, Y

2009-11-01

Simple heating of pyroelectric crystals has been used as the basis for compact sources of X rays, electrons, ions and neutrons. We report on the evaluation of the feasibility of using a portable pyroelectric electron accelerator to deliver a therapeutic dose to tissue. Such a device could be mass produced as a handheld, battery-powered instrument. Experiments were conducted with several crystal sizes in which the crystal was heated inside a vacuum chamber and the emitted electrons were allowed to penetrate a thin beryllium window into the surrounding air. A Faraday cup was used to count the number of electrons that exited the window. The energy of these electrons was determined by measuring the energy spectrum of the X rays that resulted from the electron interactions with the Faraday cup. Based on these measurements, the dose that this source could deliver to tissue was calculated using Monte Carlo calculations. It was found that 10(13) electrons with a peak energy of the order of 100 keV were emitted from the beryllium window and could deliver a dose of 1664 Gy to a 2-cm-diameter, 110-microm-deep region of tissue located 1.5 cm from the window with air between the window and the tissue. This dose level is high enough to consider this technology for medical applications in which shallow energy deposition is beneficial.

Single Enteral Loading Dose of Phenobarbital for Achieving Its Therapeutic Serum Levels in Neonates

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Turhan, Ali H.; Atici, Aytug; Okuyaz, Cetin; Uysal, Sercan

2010-01-01

Aim To investigate whether therapeutic serum drug levels may be achieved with a single enteral loading dose of phenobarbital. Methods The study was performed at the Mersin University Hospital in Turkey between April 2004 and August 2006, and included 29 newborn babies with seizure. After the acute treatment of the seizure with midazolam at a dose of 0.1 mg/kg, phenobarbital was administered by orogastric route at a loading dose of 20 mg/kg. Serum phenobarbital concentrations were measured at 0.5, 3, 6, and 12 hours after the loading. Serum phenobarbital levels between 10-30 μg/mL were considered as the therapeutic range. Results The serum phenobarbital levels reached therapeutic values in 9 (31%), 19 (66%), 21 (72%), and 23 (79%) patients at 0.5, 3, 6, and 12 hours after loading, respectively, while they did not reach therapeutic values in 6 patients (21%) after 12 hours. Four of the patients in whom there was no increase in serum phenobarbital levels had hypoxic-ischemic encephalopathy. Conclusion Enteral loading of phenobarbital can achieve therapeutic serum levels in the large majority of newborn babies with seizure and may be safely used in babies with the intact gastrointestinal tract. PMID:20564764

Comparative pharmacokinetics between a microdose and therapeutic dose for clarithromycin, sumatriptan, propafenone, paracetamol (acetaminophen), and phenobarbital in human volunteers.

Science.gov (United States)

Lappin, Graham; Shishikura, Yoko; Jochemsen, Roeline; Weaver, Richard John; Gesson, Charlotte; Brian Houston, J; Oosterhuis, Berend; Bjerrum, Ole J; Grynkiewicz, Grzegorz; Alder, Jane; Rowland, Malcolm; Garner, Colin

2011-06-14

A clinical study was conducted to assess the ability of a microdose (100 μg) to predict the human pharmacokinetics (PK) following a therapeutic dose of clarithromycin, sumatriptan, propafenone, paracetamol (acetaminophen) and phenobarbital, both within the study and by reference to the existing literature on these compounds and to explore the source of any nonlinearity if seen. For each drug, 6 healthy male volunteers were dosed with 100 μg (14)C-labelled compound. For clarithromycin, sumatriptan, and propafenone this labelled dose was administered alone, i.e. as a microdose, orally and intravenously (iv) and as an iv tracer dose concomitantly with an oral non-labelled therapeutic dose, in a 3-way cross over design. The oral therapeutic doses were 250, 50, and 150 mg, respectively. Paracetamol was given as the labelled microdose orally and iv using a 2-way cross over design, whereas phenobarbital was given only as the microdose orally. Plasma concentrations of total (14)C and parent drug were measured using accelerator mass spectrometry (AMS) or HPLC followed by AMS. Plasma concentrations following non-(14)C-labelled oral therapeutic doses were measured using either HPLC-electrochemical detection (clarithromycin) or HPLC-UV (sumatriptan, propafenone). For all five drugs an oral microdose predicted reasonably well the PK, including the shape of the plasma profile, following an oral therapeutic dose. For clarithromycin, sumatriptan, and propafenone, one parameter, oral bioavailability, was marginally outside of the normally acceptable 2-fold prediction interval around the mean therapeutic dose value. For clarithromycin, sumatriptan and propafenone, data obtained from an oral and iv microdose were compared within the same cohort of subjects used in the study, as well as those reported in the literature. For paracetamol (oral and iv) and phenobarbital (oral), microdose data were compared with those reported in the literature only. Where 100 μg iv (14)C-doses were

Employing the therapeutic operating characteristic (TOC) graph for individualised dose prescription

NARCIS (Netherlands)

Hoffmann, A.L.; Huizenga, H.; Kaanders, J.H.A.M.

2013-01-01

BACKGROUND: In current practice, patients scheduled for radiotherapy are treated according to 'rigid' protocols with predefined dose prescriptions that do not consider risk-taking preferences of individuals. The therapeutic operating characteristic (TOC) graph is applied as a decision-aid to assess

3D in radiotherapy - pushing the dose envelope to improve cure

International Nuclear Information System (INIS)

Leibel, Steven A.

1996-01-01

Approximately one in four newly diagnosed cancer patients receive radiation in the initial attempt to cure the tumor. In terms of the 1996 cancer incidence data, this comprises more than 350,000 patients. Inasmuch as 25% of these patients initially relapse at primary tumor sites, the issue of improving local control remains a major challenge to the profession. Recent improvements in treatment planning and delivery have enhanced the precision of radiotherapy, but radiation resistance remains a critical issue that confounds the potential for cure in many tumors. Chemical and biological modifiers of the radiation response have provided an approach with clinical promise, but their therapeutic impact remains to be established. Hence, tumor dose escalation continues to represent the most viable approach to improve local control. Recent experience with new conformal radiotherapy techniques has demonstrated that significant tumor dose escalation is feasible with concomitant reduction in normal tissue toxicity. This experience provides the best hope for immediate improvement in the rates of local tumor control. It remains, nonetheless, unclear how far the dose envelope can be pushed and whether this would be sufficient to overcome the problem of local failure. It may turn out that biological modification of the radiation response may still be necessary to provide a maximal control in certain types of tumors

An analysis of the dose and the therapeutic effect of 131I in treating youngsters with Graves disease

International Nuclear Information System (INIS)

Li Jia; Qin Lan; Ren Zhong; Zhang Youping

2010-01-01

Objective: To analyses the clinical data of 131 I in treating youngsters with Graves disease, and to explore the effective dose range which is appropriate for Chinese youngsters with Graves disease. Methods: Two hundred and thirty-four youngsters with Graves disease were selected in this study, their ages were between 8 and 17, the average quality of their thyroids was (59.0±16.5)g. According to the absorbed dose of 131 I per gram of thyroid gland, 234 patients were divided into five groups: A: 1.11- 2.59 MBq/g. The therapeutic effect was evaluated by observing after treatment. And calculate the recovery rate, the improvement rate and the incidence rate of hypothyroidism. Results: (1) One hundred and fifty-two (64.95%) patients were cured, 56 (23.93%) were much better than before and 26 (11.11%) were hypothyroid. The therapeutic effect of group B was the best in all groups. (2) The recovery rate: there was no significant difference between group B, group C and group D (χ 2 =2.68, P>0.05). The recovery rate of group B was better than group A and group E (χ 2 =10.20 and χ 2 =5.49, P 2 =1.94, P>0.05). The improvement rate of group A was the highest (χ 2 =8.74, χ 2 =6.68, χ 2 =7.01 and χ 2 =11.12, P 2 =2.71, P>0.05). Group E had the highest incidence rate of hypothyroidism (χ 2 =12.36, χ = 11.58, χ 2 =9.37 and χ 2 =4.36, P 131 I is a safe and effective therapeutic approach for youngsters with Graves disease. We suggest the absorbed dose range of 131 I per gram of thyroid gland is 1.48-2.59 MBq/g, which can obtain the better therapeutic effect and can't increase the incidence rate of hypothyroidism. (authors)

An unusual case of hypothermia associated with therapeutic doses of olanzapine: a case report

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Ratnayake Shiroma L

2011-05-01

Full Text Available Abstract Introduction We report a case of a 42-year-old man who had symptomatic hypothermia as a result of taking olanzapine for paranoid schizophrenia. According to published data, only a few cases of hypothermia associated with olanzapine have been reported since its introduction into clinical use. Case presentation A 42-year-old Sri Lankan man with schizophrenia who was being treated with a therapeutic dose of olanzapine presented with reduced level of consciousness. He had a core temperature of 32°C and was bradycardic. At the time of admission, the electrocardiogram showed sinus bradycardia with J waves. He did not have any risk factors for developing hypothermia except the use of olanzapine. There was improvement in his clinical condition with reversal of electrocardiogram changes following gradual rewarming and the omission of olanzapine. Conclusion Hypothermia induced by antipsychotic medications is not uncommon, but olanzapine-induced hypothermia is rare and occurrence has been reported during initiation or increasing the dose. But here the patient developed hypothermia without dose adjustment.

Low-dose cyclophosphamide administered as daily or single dose enhances the antitumor effects of a therapeutic HPV vaccine

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Peng, Shiwen; Lyford-Pike, Sofia; Akpeng, Belinda; Wu, Annie; Hung, Chien-Fu; Hannaman, Drew; Saunders, John R.; Wu, T.-C.

2012-01-01

Although therapeutic HPV vaccines are able to elicit systemic HPV-specific immunity, clinical responses have not always correlated with levels of vaccine-induced CD8+ T cells in human clinical trials. This observed discrepancy may be attributable to an immunosuppressive tumor microenvironment in which the CD8+ T cells are recruited. Regulatory T cells (Tregs) are cells that can dampen cytotoxic CD8+ T-cell function. Cyclophosphamide (CTX) is a systemic chemotherapeutic agent, which can eradicate immune cells, including inhibitory Tregs. The optimal dose and schedule of CTX administration in combination with immunotherapy to eliminate the Treg population without adversely affecting vaccine-induced T-cell responses is unknown. Therefore, we investigated various dosing and administration schedules of CTX in combination with a therapeutic HPV vaccine in a preclinical tumor model. HPV tumor-bearing mice received either a single preconditioning dose or a daily dose of CTX in combination with the pNGVL4a-CRT/E7(detox) DNA vaccine. Both single and daily dosing of CTX in combination with vaccine had a synergistic anti-tumor effect as compared to monotherapy alone. The potent antitumor responses were attributed to the reduction in Treg frequency and increased infiltration of HPV16 E7-specific CD8+ T cells, which led to higher ratios of CD8+/Treg and CD8+/CD11b+Gr-1+ myeloid-derived suppressor cells (MDSCs). There was an observed trend toward decreased vaccine-induced CD8+ T-cell frequency with daily dosing of CTX. We recommend a single, preconditioning dose of CTX prior to vaccination due to its efficacy, ease of administration, and reduced cumulative adverse effect on vaccine-induced T cells. PMID:23011589

Acetaminophen-cysteine adducts during therapeutic dosing and following overdose

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Judge Bryan S

2011-03-01

Full Text Available Abstract Background Acetaminophen-cysteine adducts (APAP-CYS are a specific biomarker of acetaminophen exposure. APAP-CYS concentrations have been described in the setting of acute overdose, and a concentration >1.1 nmol/ml has been suggested as a marker of hepatic injury from acetaminophen overdose in patients with an ALT >1000 IU/L. However, the concentrations of APAP-CYS during therapeutic dosing, in cases of acetaminophen toxicity from repeated dosing and in cases of hepatic injury from non-acetaminophen hepatotoxins have not been well characterized. The objective of this study is to describe APAP-CYS concentrations in these clinical settings as well as to further characterize the concentrations observed following acetaminophen overdose. Methods Samples were collected during three clinical trials in which subjects received 4 g/day of acetaminophen and during an observational study of acetaminophen overdose patients. Trial 1 consisted of non-drinkers who received APAP for 10 days, Trial 2 consisted of moderate drinkers dosed for 10 days and Trial 3 included subjects who chronically abuse alcohol dosed for 5 days. Patients in the observational study were categorized by type of acetaminophen exposure (single or repeated. Serum APAP-CYS was measured using high pressure liquid chromatography with electrochemical detection. Results Trial 1 included 144 samples from 24 subjects; Trial 2 included 182 samples from 91 subjects and Trial 3 included 200 samples from 40 subjects. In addition, we collected samples from 19 subjects with acute acetaminophen ingestion, 7 subjects with repeated acetaminophen exposure and 4 subjects who ingested another hepatotoxin. The mean (SD peak APAP-CYS concentrations for the Trials were: Trial 1- 0.4 (0.20 nmol/ml, Trial 2- 0.1 (0.09 nmol/ml and Trial 3- 0.3 (0.12 nmol/ml. APAP-CYS concentrations varied substantially among the patients with acetaminophen toxicity (0.10 to 27.3 nmol/ml. No subject had detectable APAP

Improved Dose Targeting for a Clinical Epithermal Neutron Capture Beam Using Optional 6Li Filtration

International Nuclear Information System (INIS)

Binns, Peter J.; Riley, Kent J.; Ostrovsky, Yakov; Gao Wei; Albritton, J. Raymond; Kiger, W.S.; Harling, Otto K.

2007-01-01

Purpose: The aim of this study was to construct a 6 Li filter and to improve penetration of thermal neutrons produced by the fission converter-based epithermal neutron beam (FCB) for brain irradiation during boron neutron capture therapy (BNCT). Methods and Materials: Design of the 6 Li filter was evaluated using Monte Carlo simulations of the existing beam line and radiation transport through an ellipsoidal water phantom. Changes in beam performance were determined using three figures of merit: (1) advantage depth (AD), the depth at which the total biologically weighted dose to tumor equals the maximum weighted dose to normal tissue; (2) advantage ratio (AR), the ratio of the integral tumor dose to that of normal tissue averaged from the surface to the AD; and (3) advantage depth dose rate (ADDR), the therapeutic dose rate at the AD. Dosimetry performed with the new filter installed provided calibration data for treatment planning. Past treatment plans were recalculated to illustrate the clinical potential of the filter. Results: The 8-mm-thick Li filter is more effective for smaller field sizes, increasing the AD from 9.3 to 9.9 cm, leaving the AR unchanged at 5.7 but decreasing the ADDR from 114 to 55 cGy min -1 for the 12 cm diameter aperture. Using the filter increases the minimum deliverable dose to deep seated tumors by up to 9% for the same maximum dose to normal tissue. Conclusions: Optional 6 Li filtration provides an incremental improvement in clinical beam performance of the FCB that could help to establish a therapeutic window in the future treatment of deep-seated tumors

Time-dose relationship in radiotherapy of gingival carcinoma. Therapeutic results

International Nuclear Information System (INIS)

Maciejewski, B.; Wojcieszek, Z.; Majewski, S.

1982-01-01

Therapeutic results were analysed in 30 patients with gingival carcinoma irradiated with 60 Co at the Institute of Oncology in Gliwice. Three-year asymptomatic survival rate was 26%. Administration of 1950 rets dose was associated with a high probability of cure and low risk of complications. Tumour diameter exceeding 3 cm, involvement of adjacent anatomical structures and metastases to cervical lymph nodes worsened considerably the prognosis. (author)

Radiation doses by therapeutical practices with iodine 131

International Nuclear Information System (INIS)

Di Trano, J.L.; Rojo, A.M.; Gomez Parada, I.M.; Grassi, E.; Gatica, N.; Kunst, J.J.; Gonzalez, M.

1998-01-01

The aim of this document is to estimate the doses to workers and public due to therapeutical practices with iodine 131. Environmental and personal doses by external irradiation were determined using thermoluminescent dosimeters (TLD). The environmental dosimetry resulted in an equivalent dose H * (10) of approximately 0,1 mSv. The calculated personal equivalent dose Hp (10) was of the order of 0,1 mSv. The exposition rate was measured, being the values obtained in the range of 0,20 and 0,35 mSv/h. (1m from the abdominal wall). Concentrations of iodine 131 were determinate in the air of the room, during the first day in the hospital. Values obtained were between 0,04 Bq/l and 0,20 Bq/l. Surface samples were taken in the service, obtaining levels of contamination in the range of 0,001 and 0,4 Bq/cm 2 . The surface samples obtained in the hospital room were about 0,15 Bq/cm 2 . Urine samples were collected resulting in an eliminated activity of iodine 131, during the first 24 hours, of about 60 % of the administered activity. Samples of sweat of different cutaneous regions were obtained, the maximum values of the activity measured reached 200 Bq/cm 2 . According to the obtained results it is important to elaborate guides to be given to patients as an instrument to reduce the external exposure and to avoid internal contamination. (author)

Hydroxychloroquine Blood Levels in SLE: Clarifying dosing controversies and improving adherence

Science.gov (United States)

Durcan, Laura; Clarke, William A; Magder, Laurence S.; Petri, Michelle

2015-01-01

OBJECTIVES Hydroxychloroquine is used for its effect on systemic lupus erythematosus (SLE) disease activity and long-term benefits. This can be limited by adherence. One way to assess adherence is to measure blood levels. Conflicting data exist regarding blood levels and disease activity. There is dosing controversy; rheumatologists recommend weight-based, while ophthalmologists advocate height-based ‘ideal body weight’ dosing. METHODS Patients were prescribed hydroxychloroquine not to exceed 6.5mg/kg (max400mg/day). In hemodialysis, the dose was 200mg after each session, in renal insufficiency it was 200mg/day. Levels were measured at each visit with a therapeutic range of 500-2000 ng/ml. Patients were divided according to baseline blood level. To assess the impact of measurement and counseling on adherence, we compared the proportion of patients with a level of 500ng/ml or higher based on how many prior assessments the patient had. RESULTS The proportion of patients with hydroxychloroquine levels in the therapeutic range differed significantly by age, gender and vitamin D level. There was a trend toward lower levels with renal failure. Blood levels were similar regardless of height and ideal body weight. Comparing those with undetectable, sub-therapeutic and therapeutic levels, disease activity decreased (SLEDAI 2.92, 2.36 and 2.20)(P=0.04, for trend). At first, 56% were therapeutic and by the third measurement this increased to 80% (p =hydroxychloroquine levels. Renal failure dosing led to sub-optimum levels. We show that weight-based dosing (max 400mg daily) is appropriate and that height does not appear to influence levels. Measurement, counseling and repeated testing can increase adherences rates. PMID:26428205

Erythemal and therapeutic response of psoriasis to PUVA using high-dose UVA

International Nuclear Information System (INIS)

Speight, E.L.; Farr, P.M.

1994-01-01

In PUVA treatment of psoriasis, clinical observation suggests that uninvolved skin is more susceptible to PUVA erythema than lesions of psoriasis. If this is the case, then the efficacy of PUVA treatment might be increased by using localized high-dose UVA restricted to lesional skin. We have therefore studied the erythemal and therapeutic response of psoriasis to PUVA using high-dose UVA and, for comparison, the erythemal response to UVB. This study demonstrates that psoriasis may clear rapidly, without burning, using high-dose UVA. Availability of a suitable irradiation apparatus would allow rapid and effective PUVA treatment to be used for localized, resistant disease. (author)

Three dimensional conformal radiation therapy may improve the therapeutic ratio of radiation therapy after pneumonectomy for lung cancer

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Trouette, R; Causse, N; Elkhadri, M; Caudry, M; Maire, J P; Houlard, J P; Racaldini, L; Demeaux, H

1995-12-01

Three dimensional conformal radiation therapy would allow to decrease the normal tissue dose while maintaining the same target dose as standard treatment. To evaluate the feasibility of normal tissue dose reduction for ten patients with pneumonectomy for lung cancer, we determined the dose distribution to the normal tissue with 3-dimensional conformal radiation therapy (3-DCRT) and conventional treatment planning (CTP). Dose-volume histograms for target and normal tissue (lung, heart) were used for comparison of the different treatment planning. The mean percentages of lung and heart volumes which received 40 Gy with 3-DCRT were respectively 63% and 37% of the mean percentage of lung and volumes which received the same dose with CTP. These preliminary results suggest that conformal therapy may improve the therapeutic ratio by reducing risk to normal tissue.

Efficacy and safety of a therapeutic interchange from high-dose calcium channel blockers to a fixed-dose combination of amlodipine/benazepril in patients with moderate-to-severe hypertension.

Science.gov (United States)

Hilleman, D E; Reyes, A P; Wurdeman, R L; Faulkner, M

2001-08-01

Recent hypertension trials have demonstrated the importance of achieving goal blood pressures to reduce the risk of target organ damage. In patients with moderate to severe hypertension, the use of high-dose monotherapy and/or combinations of drugs are necessary to achieve these goals. Fixed-dose combination products may be useful in these patients by reducing the number of daily doses required to control blood pressure. The objective of the present study was to evaluate the efficacy and safety of a therapeutic interchange between high-dose calcium channel blocker therapy and a fixed-dose combination of amlodipine/ benazepril (Lotrel; Novartis Pharmaceuticals, USA) in patients with moderate to severe hypertension. A total of 75 patients were switched from amlodipine (n = 25), felodipine (n = 25), and nifedipine-GITS (n = 25) to amlodipine/benazepril. Twenty-eight of the 75 patients (37%) were taking either a beta-blocker or a diuretic in addition to the high-dose calcium channel blocker prior to the switch. Blood pressure control, side effects and the cost of the therapeutic interchange were evaluated in the year following the therapeutic interchange. Sixty-six of the 75 (88%) patients were successfully switched with maintenance of blood pressure control and without the development of new dose-limiting side effects. Reasons for treatment failure after the therapeutic interchange included loss of blood pressure control in five patients and the development of new dose-limiting side effects in four patients. These side effects included cough in three patients and rash in one patient. After accounting for differences in drug acquisition cost and costs related to the switch (clinic and emergency room and laboratory tests), a cost savings of $16030 for all 75 patients was realised in the first year. The per patient-per year cost savings was $214. Our data indicate that a therapeutic interchange from selected high-dose calcium channel blockers to a fixed-dose combination

Dose escalation using conformal high-dose-rate brachytherapy improves outcome in unfavorable prostate cancer

International Nuclear Information System (INIS)

Martinez, Alvaro A.; Gustafson, Gary; Gonzalez, Jose; Armour, Elwood; Mitchell, Chris; Edmundson, Gregory; Spencer, William; Stromberg, Jannifer; Huang, Raywin; Vicini, Frank

2002-01-01

Purpose: To overcome radioresistance for patients with unfavorable prostate cancer, a prospective trial of pelvic external beam irradiation (EBRT) interdigitated with dose-escalating conformal high-dose-rate (HDR) prostate brachytherapy was performed. Methods and Materials: Between November 1991 and August 2000, 207 patients were treated with 46 Gy pelvic EBRT and increasing HDR brachytherapy boost doses (5.50-11.5 Gy/fraction) during 5 weeks. The eligibility criteria were pretreatment prostate-specific antigen level ≥10.0 ng/mL, Gleason score ≥7, or clinical Stage T2b or higher. Patients were divided into 2 dose levels, low-dose biologically effective dose 93 Gy (149 patients). No patient received hormones. We used the American Society for Therapeutic Radiology and Oncology definition for biochemical failure. Results: The median age was 69 years. The mean follow-up for the group was 4.4 years, and for the low and high-dose levels, it was 7.0 and 3.4 years, respectively. The actuarial 5-year biochemical control rate was 74%, and the overall, cause-specific, and disease-free survival rate was 92%, 98%, and 68%, respectively. The 5-year biochemical control rate for the low-dose group was 52%; the rate for the high-dose group was 87% (p<0.001). Improvement occurred in the cause-specific survival in favor of the brachytherapy high-dose level (p=0.014). On multivariate analysis, a low-dose level, higher Gleason score, and higher nadir value were associated with increased biochemical failure. The Radiation Therapy Oncology Group Grade 3 gastrointestinal/genitourinary complications ranged from 0.5% to 9%. The actuarial 5-year impotency rate was 51%. Conclusion: Pelvic EBRT interdigitated with transrectal ultrasound-guided real-time conformal HDR prostate brachytherapy boost is both a precise dose delivery system and a very effective treatment for unfavorable prostate cancer. We demonstrated an incremental beneficial effect on biochemical control and cause

Intestinal absorbtion from therapeutic iron doses

International Nuclear Information System (INIS)

Werner, E.

1977-01-01

On a total of 105 persons with normal iron stores, iron depletion, and iron deficiency the intestinal absorption from therapeutic iron doses (100 mg Fe and 50 mg Fe as ferrous glycocoll sulphate) of a special galenic form was measured. The measurements were performed by means of a whole-body counter and preparations labelled with radio iron ( 59 Fe). Mean values of absorption rates from 100 mg Fe in healthy males were 5.0% and in healthy females 5.6% whereas in latent iron deficiency and in iron deficiency anemia mean values of 10% and 13% were obtained, respectively. The maximum absorption rate of 20 to 25% is reached already in the late stage of latent iron deficiency. Advancing severeness of iron deficiency is not followed by an increase of iron absorption. Investigations an 21 persons showed no significant difference between absorption rates of the galenic preparations used when administered orally before or after breakfast, respectively. (orig.) [de

WE-FG-BRA-05: Potential Clinical Benefit of LINAC Flattening-Filter-Free (FFF) Mode - Improvement of Treatment Therapeutic Ratio

International Nuclear Information System (INIS)

Chang, S; Rivera, J; Tian, H; Price, A; Santos, C; Zhang, Y

2016-01-01

Purpose: Ultrahigh dose-rate radiation at >40Gy/s has demonstrated astonishing normal-tissue sparing and tumor control in recent preclinical naive and tumor-bearing rodent studies when compared to the same radiation dose at a conventional dose-rate. The working mechanism of this fascinating dose-rate effect is currently under investigation. The aims of this work include investigating 1) whether LINAC FFF mode radiation at approximately 1Gy/s also has an improved therapeutic ratio compared to the same radiation dose at the conventional dose-rate of 0.05Gy/s, and 2) the dose-rate effect’s potential working mechanism by studying the expression of the P53 gene, linked to tumor suppression and cell regulation after radiation damage. Methods: We used mouse model C57BL/6J, the same as that used in the ultrahigh dose-rate studies, and exposed them to total body irradiation (TBI) using the Elekta Versa accelerator 10MV photons. Mice (N=20) were given a total dose of 12Gy in both the high dose-rate group (n=10) using the FFF-mode and the conventional dose-rate group (n=10) using the conventional does rate mode. The FFF-mode treatment setup consisted of a 15cm×15cm field size setting at 53.2cm SSD while the conventional-mode set-up consisted of a 10cm×10cm field size at 100SSD. Post-radiation, animals were monitored daily for survival analysis and signs of moribundity requiring euthanasia. In addition, mouse spleens were harvested for P53 analysis at different time points. Results: For 12Gy TBI, the 1.3Gy/s FFF-mode high dose-rate produced a statistically significant (p=0.02) improvement in mouse survival compared to the 0.05Gy/s conventional dose-rate. An initial P53 study at the time of death time-point indicates that high dose-rate radiation induced a stronger expression of P53 than conventional dose-rate radiation. Conclusion: Our pilot study indicates that the FFF-mode high dose-rate radiation, which has been used largely to improve clinical throughput, may provide

WE-FG-BRA-05: Potential Clinical Benefit of LINAC Flattening-Filter-Free (FFF) Mode - Improvement of Treatment Therapeutic Ratio

Energy Technology Data Exchange (ETDEWEB)

Chang, S [Department of Radiation Oncology, UNC School of Medicine, Chapel Hill, NC (United States); Department of Biomedical Engineering, University of North Carolina- Chapel Hill/ North Carolina State University, Chapel Hill, North Carolina (United States); Lineberger Clinical Cancer Center, University of North Carolina, Chapel Hill, NC (United States); Rivera, J [Department of Biomedical Engineering, University of North Carolina- Chapel Hill/ North Carolina State University, Chapel Hill, North Carolina (United States); Tian, H [Xuzhou Medical College, Xuzhou, Jiangsu (China); Lineberger Clinical Cancer Center, University of North Carolina, Chapel Hill, NC (United States); Price, A [Department of Radiation Oncology, UNC School of Medicine, Chapel Hill, NC (United States); Santos, C [Lineberger Clinical Cancer Center, University of North Carolina, Chapel Hill, NC (United States); Zhang, Y [Department of Radiation Oncology, UNC School of Medicine, Chapel Hill, NC (United States); Xuzhou Medical College, Xuzhou, Jiangsu (China); Lineberger Clinical Cancer Center, University of North Carolina, Chapel Hill, NC (United States)

2016-06-15

Purpose: Ultrahigh dose-rate radiation at >40Gy/s has demonstrated astonishing normal-tissue sparing and tumor control in recent preclinical naive and tumor-bearing rodent studies when compared to the same radiation dose at a conventional dose-rate. The working mechanism of this fascinating dose-rate effect is currently under investigation. The aims of this work include investigating 1) whether LINAC FFF mode radiation at approximately 1Gy/s also has an improved therapeutic ratio compared to the same radiation dose at the conventional dose-rate of 0.05Gy/s, and 2) the dose-rate effect’s potential working mechanism by studying the expression of the P53 gene, linked to tumor suppression and cell regulation after radiation damage. Methods: We used mouse model C57BL/6J, the same as that used in the ultrahigh dose-rate studies, and exposed them to total body irradiation (TBI) using the Elekta Versa accelerator 10MV photons. Mice (N=20) were given a total dose of 12Gy in both the high dose-rate group (n=10) using the FFF-mode and the conventional dose-rate group (n=10) using the conventional does rate mode. The FFF-mode treatment setup consisted of a 15cm×15cm field size setting at 53.2cm SSD while the conventional-mode set-up consisted of a 10cm×10cm field size at 100SSD. Post-radiation, animals were monitored daily for survival analysis and signs of moribundity requiring euthanasia. In addition, mouse spleens were harvested for P53 analysis at different time points. Results: For 12Gy TBI, the 1.3Gy/s FFF-mode high dose-rate produced a statistically significant (p=0.02) improvement in mouse survival compared to the 0.05Gy/s conventional dose-rate. An initial P53 study at the time of death time-point indicates that high dose-rate radiation induced a stronger expression of P53 than conventional dose-rate radiation. Conclusion: Our pilot study indicates that the FFF-mode high dose-rate radiation, which has been used largely to improve clinical throughput, may provide

Impact of therapeutic and high doses of florfenicol on kidney and liver functional indicators in goat

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Jan Muhammad Shah

2016-10-01

Full Text Available Aim: The aim of this study was to evaluate the impact of therapeutic and high doses of florfenicol on kidney and liver functional indicators in goat species. Materials and Methods: Six mature, healthy goats (combine breed and sex with average weight 25 kg were selected for this study. The therapeutic (20 mg/kg b.w. and high doses (40 and 60 mg of florfenicol were administered for 3 days with 24 h interval. Blood samples were collected at 0, 24, 48, 72, 96, and 120 h following the each administered dose. Results: The results showed that the therapeutic dose of florfenicol produced nonsignificant effect on serum urea, creatinine, total protein (TP, alkaline phosphatase (ALP, gamma-glutamyl transferase (GGT and bilirubin on all timings, and increased (p<0.05 the serum glutamic oxaloacetic transaminase (SGOT and serum glutamate-pyruvate transaminase (SGPT levels for 48 h. Whereas the high doses of florfenicol (40 and 60 mg significantly altered the kidney and liver functional indicators in the blood. In contrast with control, the serum urea level was (p<0.01 increased at all timing points. Creatinine values were altered (p<0.01, <0.05 in increasing manner from 24 to 96 h. The high dose of 40 mg decreased the TP (p<0.05 for 72 h and 60 mg persisted same effect (p<0.01 up to 120 h. The indices of ALP, GGT, SGOT, and SGPT were raised (p<0.01, <0.05 at all timings. The bilirubin indexes also (p<0.05 elevated from 48 to 72. Conclusion: It was concluded that the high doses of florfenicol produced reversible dose-dependent effects on functional indicators of kidney and liver such as urea, creatinine, TP, ALP, SGOT, SGPT, GGT, and bilirubin.

Effects of an acute therapeutic or rewarding dose of amphetamine on acquisition of Pavlovian autoshaping and ventral striatal dopamine signaling.

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Schuweiler, D R; Athens, J M; Thompson, J M; Vazhayil, S T; Garris, P A

2018-01-15

Rewarding doses of amphetamine increase the amplitude, duration, and frequency of dopamine transients in the ventral striatum. Debate continues at the behavioral level about which component of reward, learning or incentive salience, is signaled by these dopamine transients and thus altered in addiction. The learning hypothesis proposes that rewarding drugs result in pathological overlearning of drug-predictive cues, while the incentive sensitization hypothesis suggests that rewarding drugs result in sensitized attribution of incentive salience to drug-predictive cues. Therapeutic doses of amphetamine, such as those used to treat attention-deficit hyperactivity disorder, are hypothesized to enhance the ventral striatal dopamine transients that are critical for reward-related learning and to enhance Pavlovian learning. However, the effects of therapeutic doses of amphetamine on Pavlovian learning are poorly understood, and the effects on dopamine transients are completely unknown. We determined the effects of an acute pre-training therapeutic or rewarding amphetamine injection on the acquisition of Pavlovian autoshaping in the intact rat. We also determined the effects of these doses on electrically evoked transient-like dopamine signals using fast-scan cyclic voltammetry in the anesthetized rat. The rewarding dose enhanced the amplitude and duration of DA signals, caused acute task disengagement, impaired learning for several days, and triggered incentive sensitization. The therapeutic dose produced smaller enhancements in DA signals but did not have similar behavioral effects. These results underscore the necessity of more studies using therapeutic doses, and suggest a hybrid learning/incentive sensitization model may be required to explain the development of addiction. Copyright © 2017 Elsevier B.V. All rights reserved.

Effects of enoxaparin and unfractionated heparin in prophylactic and therapeutic doses on the fertility of female Wistar rats.

Science.gov (United States)

Figueiró-Filho, Ernesto Antonio; Aydos, Ricardo Dutra; Senefonte, Flávio Renato de Almeida; Ferreira, Cristiane Munaretto; Pereira, Erica Freire de Vasconcelos; Oliveira, Vanessa Marcon de; Menezes, Giovanna Pádoa de; Bósio, Marco Antonio Costa

2014-07-01

To evaluate the effects of exposure of enoxaparin and unfractionated heparin (UFH) in prophylactic and therapeutic doses on the fertility rates of pregnant healthy Wistar rats. Enoxaparin and UFH were administered in prophylactic doses 1 mg/Kg/day 72 UI/Kg/day, and in therapeutic doses at 2 mg/kg/day 400UI/Kg/day. The rats were divided into five groups. The number of live and dead foetuses was quantified. The uterine horns were dissected and the presence of early and late reabsorptions (abortions) was determined. A peffect on fertility with the use of anticoagulant drugs in pregnant healthy Wistar rats.

Study of the therapeutic dose and the clinical effect on Graves' disease with I-131 treatment

International Nuclear Information System (INIS)

Dang, Y.

2005-01-01

Full text: Graves' disease is being treated with I-131 for more than 40 years in China. Previously the dose of I-131 used to be calculated using the 'Quimby' formula. We have now observed that the dose of I-131 administered to patients is now lower in recent years than the early years. The radioactive iodine uptake by the thyroid gland has also changed significantly over a period of time. In this paper we intend to explore these reasons and to research the relationship between the dose and the effect as well as the main cause of the incidence of the hypothyroidism. The parameters in 'Quimby' formula including I-131 uptake, effective half-life and thyroid weight were analyzed and compared with each year data from 1961 to 1988 and subjected to multiple regression analysis to determine the influence on the calculation of dose in 4465 patients. The therapeutic effects were compared with the data of the clinical follow-up of patients between 1961-1973 and 1978-1988 in 748 patients. The factors which might lead to the hypothyroidism were investigated with the non-condition logistic regression. The I-131 uptake was repeatedly measured within one week in 100 patients to identify the changing pattern of the I-131 uptake and its influence on the administered therapeutic dose. We observed an increase in the value of I-131 uptake. The value of I-131 uptake showed an increase after 1977, as well as a prolongation of effective half-life after 1973. The main reason for these changes being a replacement of the equipment in 1977 (G-M counter tube was replaced by scintillation counter), and the other reason being salt iodization in China in 1973. These two factors resulted in a significant reduction in the administered dose of I-131 during the period 1974-1988 as compared to the previous period 1961-1973; the mean administered doses being 168.35MBq and 330.33MBq respectively. The result of multiple regression analyses suggested that the thyroid weight and the effective half

Maximum likelihood estimation of dose-response parameters for therapeutic operating characteristic (TOC) analysis of carcinoma of the nasopharynx

International Nuclear Information System (INIS)

Metz, C.E.; Tokars, R.P.; Kronman, H.B.; Griem, M.L.

1982-01-01

A Therapeutic Operating Characteristic (TOC) curve for radiation therapy plots, for all possible treatment doses, the probability of tumor ablation as a function of the probability of radiation-induced complication. Application of this analysis to actual therapeutic situation requires that dose-response curves for ablation and for complication be estimated from clinical data. We describe an approach in which ''maximum likelihood estimates'' of these dose-response curves are made, and we apply this approach to data collected on responses to radiotherapy for carcinoma of the nasopharynx. TOC curves constructed from the estimated dose-response curves are subject to moderately large uncertainties because of the limitations of available data.These TOC curves suggest, however, that treatment doses greater than 1800 rem may substantially increase the probability of tumor ablation with little increase in the risk of radiation-induced cervical myelopathy, especially for T1 and T2 tumors

Therapeutic Effect of Low Doses of Acenocoumarol in the Course of Ischemia/Reperfusion-Induced Acute Pancreatitis in Rats

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Zygmunt Warzecha

2017-04-01

Full Text Available Intravascular activation of coagulation is observed in acute pancreatitis and is related to the severity of this inflammation. The aim of our study was to evaluate the impact of acenocoumarol therapy on the course of acute pancreatitis induced in male rats by pancreatic ischemia followed by reperfusion. Acenocoumarol at a dose of 50, 100, or 150 µg/kg/dose was administered intragastrically once a day, starting the first dose 24 h after the initiation of pancreatic reperfusion. Results: Histological examination showed that treatment with acenocoumarol reduces pancreatic edema, necrosis, and hemorrhages in rats with pancreatitis. Moreover, the administration of acenocoumarol decreased pancreatic inflammatory infiltration and vacuolization of pancreatic acinar cells. These findings were accompanied with a reduction in the serum activity of lipase and amylase, concentration of interleukin-1β, and plasma d-Dimer concentration. Moreover, the administration of acenocoumarol improved pancreatic blood flow and pancreatic DNA synthesis. Acenocoumarol given at a dose of 150 µg/kg/dose was the most effective in the treatment of early phase acute pancreatitis. However later, acenocoumarol given at the highest dose failed to exhibit any therapeutic effect; whereas lower doses of acenocoumarol were still effective in the treatment of acute pancreatitis. Conclusion: Treatment with acenocoumarol accelerates the recovery of ischemia/reperfusion-induced acute pancreatitis in rats.

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

Energy Technology Data Exchange (ETDEWEB)

Ying, C. K. [Advanced Medical and Dental Institute, AMDI, Universiti Sains Malaysia, Penang, Malaysia and School of Medical Sciences, Universiti Sains Malaysia, Kota Bharu (Malaysia); Kamil, W. A. [Advanced Medical and Dental Institute, AMDI, Universiti Sains Malaysia, Penang, Malaysia and Radiology Department, Hospital USM, Kota Bharu (Malaysia); Shuaib, I. L. [Advanced Medical and Dental Institute, AMDI, Universiti Sains Malaysia, Penang (Malaysia); Matsufuji, Naruhiro [Research Centre of Charged Particle Therapy, National Institute of Radiological Sciences, NIRS, Chiba (Japan)

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.

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

International Nuclear Information System (INIS)

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

2014-01-01

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

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

International Nuclear Information System (INIS)

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

2013-01-01

Full-text: 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. (author)

Neuroprotective effect of STAZN, a novel azulenyl nitrone antioxidant, in focal cerebral ischemia in rats: dose-response and therapeutic window

Science.gov (United States)

Ley, James J.; Belayev, Ludmila; Saul, Isabel; Becker, David A.; Ginsberg., Myron D.

2007-01-01

Stilbazulenyl nitrone (STAZN) is a potent antioxidant that, in a rat model of transient focal cerebral ischemia, confers significant enduring functional and morphological neuroprotection. This study investigated the influence of dose and time of administration on the neuroprotective effects of STAZN in the intraluminal-suture model of middle cerebral artery occlusion (MCAo). Dose-Response At 2 and 4h after the onset of MCAo, animals received intravenously either STAZN (low dose=0.07 mg/kg, n=8), (medium dose=0.7 mg/kg, n=9), (high dose=3.5 mg/kg, n=9), an equivalent volume of vehicle (30% Solutol HS15 and 70% isotonic saline, 0.37 ml/kg, n=5), or saline (0.37 ml/kg, n=5). Only the medium dose improved scores (p<0.05) on a standardized neurobehavioral test at 1, 2 and 3d after MCAo. Only the medium dose reduced the total infarction (51%, p=0.014) compared to controls. These results indicate that STAZN exhibits maximal neuroprotection at the 0.7 mg/kg dose. Therapeutic Window STAZN (0.6 mg/kg) dissolved in dimethylsulfoxide was given intra-peritoneally at 2 and 4h (n=11), 3 and 5h (n=10), 4 and 6h (n=10), or 5 and 7h (n=7) after the onset of MCAo. Additional doses were given at 24 and 48h. Vehicle (dimethylsulfoxide, 2.0 ml/kg, n=6) was administered at 3, 5, 24 and 48h. STAZN treatment initiated at 2 or 3h after the onset of MCAo improved neurological scores (p<0.001) and reduced total infarction (42.2%, p<0.05) compared to controls. PMID:17945201

Targeted nanoparticle delivery of therapeutic antisense microRNAs presensitizes glioblastoma cells to lower effective doses of temozolomide in vitro and in a mouse model.

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Malhotra, Meenakshi; Sekar, Thillai Veerapazham; Ananta, Jeyarama S; Devulapally, Rammohan; Afjei, Rayhaneh; Babikir, Husam A; Paulmurugan, Ramasamy; Massoud, Tarik F

2018-04-20

Temozolomide (TMZ) chemotherapy for glioblastoma (GBM) is generally well tolerated at standard doses but it can cause side effects. GBMs overexpress microRNA-21 and microRNA-10b, two known oncomiRs that promote cancer development, progression and resistance to drug treatment. We hypothesized that systemic injection of antisense microRNAs (antagomiR-21 and antagomiR-10b) encapsulated in cRGD-tagged PEG-PLGA nanoparticles would result in high cellular delivery of intact functional antagomiRs, with consequent efficient therapeutic response and increased sensitivity of GBM cells to lower doses of TMZ. We synthesized both targeted and non-targeted nanoparticles, and characterized them for size, surface charge and encapsulation efficiency of antagomiRs. When using targeted nanoparticles in U87MG and Ln229 GBM cells, we showed higher uptake-associated improvement in sensitivity of these cells to lower concentrations of TMZ in medium. Co-inhibition of microRNA-21 and microRNA-10b reduced the number of viable cells and increased cell cycle arrest at G2/M phase upon TMZ treatment. We found a significant increase in expression of key target genes for microRNA-21 and microRNA-10b upon using targeted versus non-targeted nanoparticles. There was also significant reduction in tumor volume when using TMZ after pre-treatment with loaded nanoparticles in human GBM cell xenografts in mice. In vivo targeted nanoparticles plus different doses of TMZ showed a significant therapeutic response even at the lowest dose of TMZ, indicating that preloading cells with antagomiR-21 and antagomiR-10b increases cellular chemosensitivity towards lower TMZ doses. Future clinical applications of this combination therapy may result in improved GBM response by using lower doses of TMZ and reducing nonspecific treatment side effects.

Single therapeutic and supratherapeutic doses of sacubitril/valsartan (LCZ696) do not affect cardiac repolarization.

Science.gov (United States)

Langenickel, Thomas H; Jordaan, Pierre; Petruck, Jesika; Kode, Kiran; Pal, Parasar; Vaidya, Soniya; Chandra, Priya; Rajman, Iris

2016-08-01

Sacubitril/valsartan (LCZ696) is a first-in-class angiotensin receptor neprilysin inhibitor (ARNI) indicated to reduce the risk of cardiovascular death and hospitalization for heart failure in patients with chronic heart failure (NYHA class II-IV) and reduced ejection fraction. This study was aimed to evaluate the effect of single oral therapeutic (400 mg) and supratherapeutic (1200 mg) doses of LCZ696 on cardiac repolarization. This randomized double-blind crossover study in healthy male subjects compared the effect of therapeutic and supratherapeutic doses of LCZ696 with placebo and moxifloxacin 400 mg (open-label treatment) as positive control. The primary assessment was mean baseline- and placebo-corrected QTcF (∆∆QTcF; Fridericia correction). Additional assessments included the ∆∆QTcB (Bazett's correction), PR interval, QRS duration, heart rate (HR), LCZ696 pharmacokinetics, pharmacokinetic/pharmacodynamic relationships, and safety. Of the 84 subjects enrolled, 81 completed the study. The maximum upper bound of the two-sided 90 % confidence interval for ∆∆QTcF for LCZ696 400 mg and 1200 mg were <10 ms, and assay sensitivity was confirmed with moxifloxacin. No relevant treatment-emergent changes were observed in any of the ECG-derived parameters with LCZ696 or placebo, and the incidence of adverse events was comparable among the treatment groups. Single therapeutic and supratherapeutic doses of LCZ696 did not affect cardiac repolarization as defined by the E14 ICH guidelines.

Hydroxychloroquine Blood Levels in Systemic Lupus Erythematosus: Clarifying Dosing Controversies and Improving Adherence.

Science.gov (United States)

Durcan, Laura; Clarke, William A; Magder, Laurence S; Petri, Michelle

2015-11-01

Hydroxychloroquine (HCQ) is used for its effect on systemic lupus erythematosus (SLE) disease activity and longterm benefits. This can be limited by adherence. One way to assess adherence is to measure blood levels. Conflicting data exist regarding blood levels and disease activity. There is disagreement about dosing; rheumatologists recommend weight-based dosing while some other specialists advocate height-based "ideal body weight" dosing. Patients were prescribed HCQ not exceeding 6.5 mg/kg (max 400 mg/day). In hemodialysis, the dose was 200 mg after each session, and in renal insufficiency it was 200 mg/day. Levels were measured at each visit with a therapeutic range of 500-2000 ng/ml. Patients were divided according to baseline blood level. To assess the effect of measurement and counseling on adherence, we compared the proportion of patients with a level of 500 ng/ml or higher based on the number of prior assessments. The proportion of patients with HCQ levels in the therapeutic range differed significantly by age, sex, and Vitamin D level. There was a trend toward lower levels with renal failure. Blood levels were similar regardless of height and ideal body weight. Comparing those with undetectable, subtherapeutic, and therapeutic levels, disease activity decreased (SLE Disease Activity Index 2.92, 2.36, and 2.20, p = 0.04 for trend). At first, 56% were therapeutic, and by the third measurement this increased to 80% (p ≤ 0.0001). There was a trend toward higher disease activity with lower HCQ levels. Renal failure dosing led to suboptimum levels. We show that weight-based dosing (max 400 mg daily) is appropriate and that height does not appear to influence levels. Measurement, counseling, and repeated testing can increase adherence rates.

Toward endobronchial Ir-192 high-dose-rate brachytherapy therapeutic optimization

International Nuclear Information System (INIS)

Gay, H A; Allison, R R; Downie, G H; Mota, H C; Austerlitz, C; Jenkins, T; Sibata, C H

2007-01-01

A number of patients with lung cancer receive either palliative or curative high-dose-rate (HDR) endobronchial brachytherapy. Up to a third of patients treated with endobronchial HDR die from hemoptysis. Rather than accept hemoptysis as an expected potential consequence of HDR, we have calculated the radial dose distribution for an Ir-192 HDR source, rigorously examined the dose and prescription points recommended by the American Brachytherapy Society (ABS), and performed a radiobiological-based analysis. The radial dose rate of a commercially available Ir-192 source was calculated with a Monte Carlo simulation. Based on the linear quadratic model, the estimated palliative, curative and blood vessel rupture radii from the center of an Ir-192 source were obtained for the ABS recommendations and a series of customized HDR prescriptions. The estimated radius at risk for blood vessel perforation for the ABS recommendations ranges from 7 to 9 mm. An optimized prescription may in some situations reduce this radius to 4 mm. The estimated blood perforation radius is generally smaller than the palliative radius. Optimized and individualized endobronchial HDR prescriptions are currently feasible based on our current understanding of tumor and normal tissue radiobiology. Individualized prescriptions could minimize complications such as fatal hemoptysis without sacrificing efficacy. Fiducial stents, HDR catheter centering or spacers and the use of CT imaging to better assess the relationship between the catheter and blood vessels promise to be useful strategies for increasing the therapeutic index of this treatment modality. Prospective trials employing treatment optimization algorithms are needed

Methodology for management of therapeutic dose of I-131; Metodologia para administrar dosis terapeutica de I-131

Energy Technology Data Exchange (ETDEWEB)

Basteris M, J.; Gomez D, R. [Universidad Autonoma de Yucatan, Facultad de Medicina, Merida, Yucatan (Mexico)

2007-07-01

The present work suggests the use of measures guided to eliminate the resulting chronic sialoadenitis of the treatment previously described with a therapeutic dose bigger than ablative of Iodine 131, as well as the use of citric fruits to stimulate the salivation, the administration of liquid post-dose is included to accelerate the gastric emptying avoiding the secondary effects as the vomit. (Author)

Low-dose radiation enhances therapeutic HPV DNA vaccination in tumor-bearing hosts.

Science.gov (United States)

Tseng, Chih-Wen; Trimble, Cornelia; Zeng, Qi; Monie, Archana; Alvarez, Ronald D; Huh, Warner K; Hoory, Talia; Wang, Mei-Cheng; Hung, Chien-Fu; Wu, T-C

2009-05-01

Current therapeutic approaches to treatment of patients with bulky cervical cancer are based on conventional in situ ablative modalities including cisplatin-based chemotherapy and radiation therapy. The 5-year survival of patients with nonresectable disease is dismal. Because over 99% of squamous cervical cancer is caused by persistent infection with an oncogenic strain of human papillomavirus (HPV), particularly type 16 and viral oncoproteins E6 and E7 are functionally required for disease initiation and persistence, HPV-targeted immune strategies present a compelling opportunity in which to demonstrate proof of principle. Sublethal doses of radiation and chemotherapeutic agents have been shown to have synergistic effect in combination with either vaccination against cancer-specific antigens, or with passive transfer of tumor-specific cytotoxic T lymphocytes (CTLs). Here, we explored the combination of low-dose radiation therapy with DNA vaccination with calreticulin (CRT) linked to the mutated form of HPV-16 E7 antigen (E7(detox)), CRT/E7(detox) in the treatment of E7-expressing TC-1 tumors. We observed that TC-1 tumor-bearing mice treated with radiotherapy combined with CRT/E7(detox) DNA vaccination generated significant therapeutic antitumor effects and the highest frequency of E7-specific CD8(+) T cells in the tumors and spleens of treated mice. Furthermore, treatment with radiotherapy was shown to render the TC-1 tumor cells more susceptible to lysis by E7-specific CTLs. In addition, we observed that treatment with radiotherapy during the second DNA vaccination generated the highest frequency of E7-specific CD8(+) T cells in the tumors and spleens of TC-1 tumor-bearing mice. Finally, TC-1 tumor-bearing mice treated with the chemotherapy in combination with radiation and CRT/E7(detox) DNA vaccination generate significantly enhanced therapeutic antitumor effects. The clinical implications of the study are discussed.

A study of the effects of therapeutic doses of ionizing radiation in vitro on Lactobacillus isolates originating from the vagina - a pilot study.

Science.gov (United States)

Gosiewski, Tomasz; Mróz, Tomasz; Ochońska, Dorota; Pabian, Wojciech; Bulanda, Malgorzata; Brzychczy-Wloch, Monika

2016-05-31

Ionizing radiation is used as a therapeutic option in the treatment of certain neoplastic lesions located, among others, in the pelvic region. The therapeutic doses of radiation employed often result in adverse effects manifesting themselves primarily in the form of genital tract infections in patients or diarrhea. The data available in the literature indicate disorders in the microbial ecosystem caused by ionizing radiation, which leads to the problems mentioned above. In the present study, we examined the influence of ionizing radiation on 52 selected strains of bacteria: Lactobacillus crispatus, L. fermentum, L. plantarum, L. reuteri, L. acidophilus L. amylovorus, L. casei, L. helveticus, L. paracasei, L. rhamnosus, L. salivarius and L. gasseri. This collection of Lactobacillus bacteria isolates of various species, obtained from the genital tract and gastrointestinal tract of healthy women, was tested for resistance to therapeutic doses of ionizing radiation. The species studied, were isolated from the genital tract (n = 30) and from the anus (n = 22) of healthy pregnant women. Three doses of 3 Gy (fractionated dose) and 50 Gy (total dose of the whole radiotherapy cycle) were applied. The greatest differences in survival of the tested strains in comparison to the control group (not subjected to radiation) were observed at the dose of 50 Gy. However, the results were not statistically significant. Survival decrease to zero was not demonstrated for any of the tested strains. Therapeutic doses of radiation do not affect the Lactobacillus bacteria significantly.

Evaluation of therapeutic effect of low dose naltrexone in experimentally-induced Crohn's disease in rats.

Science.gov (United States)

Tawfik, Dina Ibrahim; Osman, Afaf Sayed; Tolba, Hedayat Mahmoud; Khattab, Aida; Abdel-Salam, Lubna O; Kamel, Mahmoud M

2016-10-01

Crohn's disease is a relapsing inflammatory condition afflicting the digestive tract. Drugs used for treatment of Crohn's disease may be associated with serious side effects. Endogenous opioid peptides modulate inflammatory cytokine production. Opioid antagonists have been shown to play a role in healing and repair of tissues. This work was designed to detect the possible beneficial effects of opioid antagonist naltrexone in indomethacin-induced Crohn's disease in rats. Enteritis was induced in male albino rats by two subcutaneous injection of indomethacin in a dose of 7.5mg/kg 24h apart started on day one. Salfasalazine, naltrexone and their combination were administered orally from day one of induction of enteritis to day 10. Disease activity index, serum levels of C-reactive protein and tumor necrosis factor-α, macroscopic and microscopic pathological scores and in vitro motility studies were evaluated. Induction of enteritis resulted in significant increase of disease activity index, significant elevation of serum levels of C-reactive protein and tumor necrosis factor-α, significant deterioration of pathological scores and significant increase in the mean contractility response of the isolated ileal segments compared with normal untreated rats. Treatment with sulfasalazine, low dose of natrexone or their combination resulted in significant improvement of all measured parameters compared with enteritis group. The current finding could provide new interesting opportunity for developing new therapeutic approaches for treatment of Crohn's disease. Use of naltrexone, especially in small dose, has little side effects making it of interest for treatment of Crohn's disease. Also, it provides the possibility of reduced doses of other drugs if it is used as combined therapy. Copyright © 2016 Elsevier Ltd. All rights reserved.

Enrofloxacin in therapeutic doses alters cytokine production by porcine PBMCs induced by lipopolysaccharide.

Science.gov (United States)

Pomorska-Mól, Małgorzata; Czyżewska-Dors, Ewelina; Kwit, Krzysztof; Pejsak, Zygmunt

2017-07-01

The effect of enrofloxacin on cytokine secretion by porcine peripheral blood mononuclear cells (PBMCs) was studied. Twenty 8-20-week-old pigs were randomly divided into two groups: control (C, n = 10) and experimental (E, n = 10) were used. Pigs from group E received enrofloxacin at therapeutic dose for 5 consecutive days. Blood samples were collected at 0 (before antibiotic administration), 2, 4 (during antibiotic therapy) 6, 9, 14 21, 35, 49, and 63 d of study (after treatment). PBMCs of pigs from both groups were incubated with or without lipopolysaccharide (LPS). Ex vivo production on interleukin (IL)-4, IL-6, IL-10, INF-γ, and TNF-α were analyzed using ELISA assay. Intramuscular administration of enrofloxacin to healthy pigs for 5 consecutive days induced a transitory reduction of the ex vivo response of PBMCs to LPS in terms of IL-6 and TNF-α secretion. The level of IL-6 returned to day 0 level shortly after end of treatment, while the TNF-α production remained reduced 10 d after the end of treatment. Our results indicate that enrofloxacin given in vivo in therapeutic doses has an immunomodulatory effect through its capacity to inhibit ex vivo secretion of IL-6 and TNF-α by porcine PBMC after LPS stimulation.

Main clinical, therapeutic and technical factors related to patient's maximum skin dose in interventional cardiology procedures

Science.gov (United States)

Journy, N; Sinno-Tellier, S; Maccia, C; Le Tertre, A; Pirard, P; Pagès, P; Eilstein, D; Donadieu, J; Bar, O

2012-01-01

Objective The study aimed to characterise the factors related to the X-ray dose delivered to the patient's skin during interventional cardiology procedures. Methods We studied 177 coronary angiographies (CAs) and/or percutaneous transluminal coronary angioplasties (PTCAs) carried out in a French clinic on the same radiography table. The clinical and therapeutic characteristics, and the technical parameters of the procedures, were collected. The dose area product (DAP) and the maximum skin dose (MSD) were measured by an ionisation chamber (Diamentor; Philips, Amsterdam, The Netherlands) and radiosensitive film (Gafchromic; International Specialty Products Advanced Materials Group, Wayne, NJ). Multivariate analyses were used to assess the effects of the factors of interest on dose. Results The mean MSD and DAP were respectively 389 mGy and 65 Gy cm−2 for CAs, and 916 mGy and 69 Gy cm−2 for PTCAs. For 8% of the procedures, the MSD exceeded 2 Gy. Although a linear relationship between the MSD and the DAP was observed for CAs (r=0.93), a simple extrapolation of such a model to PTCAs would lead to an inadequate assessment of the risk, especially for the highest dose values. For PTCAs, the body mass index, the therapeutic complexity, the fluoroscopy time and the number of cine frames were independent explanatory factors of the MSD, whoever the practitioner was. Moreover, the effect of technical factors such as collimation, cinematography settings and X-ray tube orientations on the DAP was shown. Conclusion Optimising the technical options for interventional procedures and training staff on radiation protection might notably reduce the dose and ultimately avoid patient skin lesions. PMID:22457404

Quantifying the importance of pMHC valency, total pMHC dose and frequency on nanoparticle therapeutic efficacy.

Science.gov (United States)

Sugarman, Jordan; Tsai, Sue; Santamaria, Pere; Khadra, Anmar

2013-05-01

Nanoparticles (NPs) coated with β-cell-specific peptide major histocompatibility complex (pMHC) class I molecules can effectively restore normoglycemia in spontaneously diabetic nonobese diabetic mice. They do so by expanding pools of cognate memory autoreactive regulatory CD8+ T cells that arise from naive low-avidity T-cell precursors to therapeutic levels. Here we develop our previously constructed mathematical model to explore the effects of compound design parameters (NP dose and pMHC valency) on therapeutic efficacy with the underlying hypothesis that the functional correlates of the therapeutic response (expansion of autoregulatory T cells and deletion of autoantigen-loaded antigen-presenting cells by these T cells) are biphasic. We show, using bifurcation analysis, that the model exhibits a 'resonance'-like behavior for a given range of NP dose in which bistability between the healthy state (possessing zero level of effector T-cell population) and autoimmune state (possessing elevated level of the same population) disappears. A heterogeneous population of model mice subjected to several treatment protocols under these new conditions is conducted to quantify both the average percentage of autoregulatory T cells in responsive and nonresponsive model mice, and the average valency-dependent minimal optimal dose needed for effective therapy. Our results reveal that a moderate increase (≥1.6-fold) in the NP-dependent expansion rate of autoregulatory T-cell population leads to a significant increase in the efficacy and the area corresponding to the effective treatment regimen, provided that NP dose ≥8 μg. We expect the model developed here to generalize to other autoimmune diseases and serve as a computational tool to understand and optimize pMHC-NP-based therapies.

Review of time-dose effects in radiation therapy

International Nuclear Information System (INIS)

Peschel, R.E.; Fischer, J.J.

1980-01-01

A historical review of conventional fractionation offers little confidence that such treatment is optimal for all tumors. Thus manipulation of time-dose schedules may provide a relatively inexpensive yet potentially useful technique for improving therapeutic results in radiation therapy. Consideration of basic radiobiological principles and animal model data illustrates the complex and heterogeneous nature of normal tissue and tumor response to time-dose effects and supports the hypothesis that better time-dose prescriptions can be found in clinical practice. The number of possible time-dose prescriptions is very large, and a review of the clinical trials using nonconventional fractionation demonstrates that the sampled portion of the total three-dimensional space of time, fraction number, and dose has been very small. Only carefully designed clinical trials can establish the therapeutic advantage of a new treatment schedule, and methods for selecting the most promising schedules are discussed. The use of simple data reduction formulas for time-dose effects should be discarded since they ignore the very complexity and heterogeneity of tissues and tumors which may form the basis of improved clinical results

Dose escalation using conformal high-dose-rate brachytherapy improves outcome in unfavorable prostate cancer.

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Martinez, Alvaro A; Gustafson, Gary; Gonzalez, José; Armour, Elwood; Mitchell, Chris; Edmundson, Gregory; Spencer, William; Stromberg, Jannifer; Huang, Raywin; Vicini, Frank

2002-06-01

To overcome radioresistance for patients with unfavorable prostate cancer, a prospective trial of pelvic external beam irradiation (EBRT) interdigitated with dose-escalating conformal high-dose-rate (HDR) prostate brachytherapy was performed. Between November 1991 and August 2000, 207 patients were treated with 46 Gy pelvic EBRT and increasing HDR brachytherapy boost doses (5.50-11.5 Gy/fraction) during 5 weeks. The eligibility criteria were pretreatment prostate-specific antigen level >or=10.0 ng/mL, Gleason score >or=7, or clinical Stage T2b or higher. Patients were divided into 2 dose levels, low-dose biologically effective dose 93 Gy (149 patients). No patient received hormones. We used the American Society for Therapeutic Radiology and Oncology definition for biochemical failure. The median age was 69 years. The mean follow-up for the group was 4.4 years, and for the low and high-dose levels, it was 7.0 and 3.4 years, respectively. The actuarial 5-year biochemical control rate was 74%, and the overall, cause-specific, and disease-free survival rate was 92%, 98%, and 68%, respectively. The 5-year biochemical control rate for the low-dose group was 52%; the rate for the high-dose group was 87% (p failure. The Radiation Therapy Oncology Group Grade 3 gastrointestinal/genitourinary complications ranged from 0.5% to 9%. The actuarial 5-year impotency rate was 51%. Pelvic EBRT interdigitated with transrectal ultrasound-guided real-time conformal HDR prostate brachytherapy boost is both a precise dose delivery system and a very effective treatment for unfavorable prostate cancer. We demonstrated an incremental beneficial effect on biochemical control and cause-specific survival with higher doses. These results, coupled with the low risk of complications, the advantage of not being radioactive after implantation, and the real-time interactive planning, define a new standard for treatment.

Incidence of postpartum haemorrhage in women receiving therapeutic doses of low-molecular-weight heparin: results of a retrospective cohort study

NARCIS (Netherlands)

Roshani, Sara; Cohn, Danny M.; Stehouwer, Alexander C.; Wolf, Hans; van der Post, Joris A. M.; Büller, Harry R.; Kamphuisen, Pieter W.; Middeldorp, Saskia

2011-01-01

Background Low-molecular-weight heparin (LMWH) is the drug of choice to prevent venous thrombosis in pregnancy, but the optimal dose for prevention while avoiding bleeding is unclear. This study investigated whether therapeutic doses of LMWH increase the incidence of postpartum haemorrhage (PPH) in

Incidence of postpartum haemorrhage in women receiving therapeutic doses of low-molecular-weight heparin : results of a retrospective cohort study

NARCIS (Netherlands)

Roshani, Sara; Cohn, Danny M; Stehouwer, Alexander C; Wolf, Hans; van der Post, Joris A M; Büller, Harry R; Kamphuisen, Pieter W; Middeldorp, Saskia

2011-01-01

Background Low-molecular-weight heparin (LMWH) is the drug of choice to prevent venous thrombosis in pregnancy, but the optimal dose for prevention while avoiding bleeding is unclear. This study investigated whether therapeutic doses of LMWH increase the incidence of postpartum haemorrhage (PPH) in

Improving Therapeutic Relationships: Joint Crisis Planning for Individuals With Psychotic Disorders.

Science.gov (United States)

Farrelly, Simone; Lester, Helen; Rose, Diana; Birchwood, Max; Marshall, Max; Waheed, Waquas; Henderson, R Claire; Szmukler, George; Thornicroft, Graham

2015-12-01

Outcomes for individuals with psychosis remain far from acceptable. Recently, prominent psychiatrists have called for an improved understanding of the impact of social contexts, and how social contexts might influence the development and maintenance of mental health problems. A key social context for individuals with psychosis is the therapeutic relationship. As part of a trial of joint crisis planning in England, this qualitative study aimed to determine the mechanism through which joint crisis planning might affect the therapeutic relationship. Results suggest that routine processes in mental health care are affected by policy and organizational requirements for risk mitigation-aspects that undermine person-centered approaches. In contrast, strong therapeutic relationships are characterized by individualized care and reliable and respectful treatment. The Joint Crisis Plan intervention partially succeeded in reducing contextual influences on routine role enactments, facilitating the demonstration of respect and improving the therapeutic relationship. © The Author(s) 2015.

Radiation exposure to examiners and patients during therapeutic ERCP: Dose optimisation and risk estimation

International Nuclear Information System (INIS)

Sulieman, A.; Kappas, K.; Theodorou, K.; Paroutoglou, G.; Kapatenakis, A.; Kapsoritakis, A.; Potamianos, S.; Vlychou, M.; Fezoulidis, I.

2008-01-01

Aim: This study intended to optimise the radiation dose during therapeutic ERCP, and to estimate the risk for examiners and patients, to compare the doses based on available data obtained by other researchers and reference levels recommended by international organizations, and to evaluate the technique applied in order to reduce patient and examiners doses. Materials and Methods: 153 patients were studied in two Gastroenterology Departments, (group A, 111; group B, 42). Thermoluminescent dosimeters (TLD) were used to measure the staff and patients entrance surface dose (ESD) at different body sites. Results: The mean ESD, exit and thyroid surface dose per procedure was estimated to be 68.75 mGy, 3.45 mGy and 0.67 mGy, respectively. The mean patient effective dose was 3.44 mSv, and the cancer risk per procedure was estimated to be 190 x10 -6 . The effective dose for the first, second and third examiner was 0.4 μSv, 0.2 μSv and 5.0 μSv, respectively. Conclusion: The patient dose can be optimized by the presence of two experienced examiners and reduction of radiographic images. The examiners should use a wrap around lead apron since the highest dose originating from the X-ray tube, is incident on their side and back. The current formulae, which exist, underestimate the effective dose to the examiners, when they are applied for ERCP procedures. For both patients and examiners, our results were up to 60% lower compared to the lowest values found in previous studies. (authors)

Optimal treatment scheduling of ionizing radiation and sunitinib improves the antitumor activity and allows dose reduction

International Nuclear Information System (INIS)

Kleibeuker, Esther A; Hooven, Matthijs A ten; Castricum, Kitty C; Honeywell, Richard; Griffioen, Arjan W; Verheul, Henk M; Slotman, Ben J; Thijssen, Victor L

2015-01-01

The combination of radiotherapy with sunitinib is clinically hampered by rare but severe side effects and varying results with respect to clinical benefit. We studied different scheduling regimes and dose reduction in sunitinib and radiotherapy in preclinical tumor models to improve potential outcome of this combination treatment strategy. The chicken chorioallantoic membrane (CAM) was used as an angiogenesis in vivo model and as a xenograft model with human tumor cells (HT29 colorectal adenocarcinoma, OE19 esophageal adenocarcinoma). Treatment consisted of ionizing radiation (IR) and sunitinib as single therapy or in combination, using different dose-scheduling regimes. Sunitinib potentiated the inhibitory effect of IR (4 Gy) on angiogenesis. In addition, IR (4 Gy) and sunitinib (4 days of 32.5 mg/kg per day) inhibited tumor growth. Ionizing radiation induced tumor cell apoptosis and reduced proliferation, whereas sunitinib decreased tumor angiogenesis and reduced tumor cell proliferation. When IR was applied before sunitinib, this almost completely inhibited tumor growth, whereas concurrent IR was less effective and IR after sunitinib had no additional effect on tumor growth. Moreover, optimal scheduling allowed a 50% dose reduction in sunitinib while maintaining comparable antitumor effects. This study shows that the therapeutic efficacy of combination therapy improves when proper dose-scheduling is applied. More importantly, optimal treatment regimes permit dose reductions in the angiogenesis inhibitor, which will likely reduce the side effects of combination therapy in the clinical setting. Our study provides important leads to optimize combination treatment in the clinical setting

Observational infant exploratory [14C]-paracetamol pharmacokinetic microdose/therapeutic dose study with accelerator mass spectrometry bioanalysis

NARCIS (Netherlands)

Garner, C.R.; Park, K.B.; French, N.S.; Earnshaw, C.; Schipani, A.; Selby, A.M.; Byrne, L.; Siner, S.; Crawley, F.P.; Vaes, W.H.J.; Duijn, E. van; ligt, R. de; Varendi, H.; Lass, J.; Grynkiewicz, G.; Maruszak, W.; Turner, M.A.

2015-01-01

Aims The aims of the study were to compare [14C]-paracetamol ([14C]-PARA) paediatric pharmacokinetics (PK) after administration mixed in a therapeutic dose or an isolated microdose and to develop further and validate accelerator mass spectrometry (AMS) bioanalysis in the 0-2 year old age group.

Therapeutic Challenges in the Management of Acute Pulmonary Embolism in a Cancer Patient with Chemotherapy-induced Thrombocytopenia

Directory of Open Access Journals (Sweden)

Abuajela Sreh

2017-11-01

Full Text Available This case demonstrates the therapeutic challenges encountered when managing an acute pulmonary embolism in a cancer patient with thrombocytopenia. A 64-year-old man with a history of lung cancer receiving chemotherapy was admitted to Walsall Manor Hospital with haemodynamic instability consistent with a pulmonary embolism, proven on computed tomographic pulmonary angiogram. His platelet count was noted to be 35×109/l (chemotherapy-induced thrombocytopenia. After discussions, he was deemed not suitable for thrombolysis based on risk versus benefits. The patient was initially transfused one adult dose of platelets and treated with half the therapeutic dose of low molecular weight heparin (LMWH. The same management plan was followed until the platelet count exceeded 50×10sup>9/l, after which the patient was established on the full therapeutic dose of LMWH. Clinically, the patient improved and was discharged. Three months after discharge, follow-up revealed sustained clinical improvement while the patient continued to be on the full therapeutic dose of LMWH with a stable platelet count.

Characteristics of therapeutic electron beams and their determination from depth dose curves

Energy Technology Data Exchange (ETDEWEB)

Novotny, J; Pernicka, F [Ceskoslovenska Akademie Ved, Prague. Ustav Dozimetrie Zareni

1980-09-01

The distribution of absorbed dose in the environment irradiated with broad beams of high-energy electrons is analyzed physically and therapeutically. A number of parameters are defined with the aid of which the beams of electrons may be characterized in great detail and compared. The theoretical calculations of individual parameters are compared with the values measured using the Ostron betatron in the central axis of the beam at a distance of 65 cm from the target; the differences found are ascribed to the spectrum of electrons, the scattering of electrons on the homogenizing foils, collimators, monitoring chambers, etc.

Effect of repeated oral therapeutic doses of methylphenidate on food intake and growth rate in rats.

Science.gov (United States)

Alam, Nausheen; Najam, Rahila

2015-01-01

Central nervous system stimulants are known to produce anorexia. Previous data suggest that methylphenidate can have variable effects on caloric intake and growth rate. A dose-response study was performed to monitor caloric intake, liquid intake and growth rate in rats following repeated administration of human oral therapeutic doses 2 mg/kg/day, 5mg/kg/day and 8mg/kg/day of methylphenidate. We found that food intake and water intake, increased in all weeks and at all doses used in the study. Growth rate increased more at higher dose (8mg/kg/day) and at low dose (2mg/kg/day) of methylphenidate in 1(st) and 2(nd) week whereas more decreased by the above doses in 3(rd) week, suggesting that food stimulation leads to initial increase in growth rate but long term administration of methylphenidate attenuate growth rate that is not due to modulation of appetite but may be due to anxiety and increased activity produce by stimulants. A possible role of DA, 5HT receptors in modulation of appetite and anxiety is discussed.

Linezolid in the treatment of drug-resistant tuberculosis: the challenge of its narrow therapeutic index.

Science.gov (United States)

Wasserman, Sean; Meintjes, Graeme; Maartens, Gary

2016-10-01

Linezolid is an oxazolidinone with potent activity against M tuberculosis, and improves culture conversion and cure rates when added to treatment regimens for drug resistant tuberculosis. However, linezolid has a narrow therapeutic window, and the optimal dosing strategy that minimizes the substantial toxicity associated with linezolid's prolonged use in tuberculosis treatment has not been determined, limiting the potential impact of this anti-mycobacterial agent. This paper aims to review and summarize the current knowledge on linezolid for the treatment of drug-resistant tuberculosis. The focus is on the pharmacokinetic-pharmacodynamic determinants of linezolid's efficacy and toxicity in tuberculosis, and how this relates to defining an optimal dose. Mechanisms of linezolid toxicity and resistance, and the potential role of therapeutic drug monitoring are also covered. Expert commentary: Prospective pharmacokinetic-pharmacodynamic studies are required to define optimal therapeutic targets and to inform improved linezolid dosing strategies for drug-resistant tuberculosis.

Dashboard systems: Pharmacokinetic/pharmacodynamic mediated dose optimization for monoclonal antibodies.

Science.gov (United States)

Mould, Diane R; Dubinsky, Marla C

2015-03-01

Many marketed drugs exhibit high variability in exposure and response. While these drugs are efficacious in their approved indications, finding appropriate dose regimens for individual patients is not straightforward. Similar dose adjustment problems are also seen with drugs that have a complex relationship between exposure and response and/or a narrow therapeutic window. This is particularly true for monoclonal antibodies, where prolonged dosing at a sub-therapeutic dose can also elicit anti-drug antibodies which will further compromise safety and efficacy. Thus, finding appropriate doses quickly would represent a substantial improvement in healthcare. Dashboard systems, which are decision-support tools, offer an improved, convenient means of tailoring treatment for individual patients. This article reviews the clinical need for this approach, particularly with monoclonal antibodies, the design, development, and testing of such systems, and the likely benefits of dashboard systems in clinical practice. We focus on infliximab for reference. © 2015, The American College of Clinical Pharmacology.

Improvement of dose evaluation method for employees at severe accident

International Nuclear Information System (INIS)

Onda, Takashi; Yoshida, Yoshitaka; Kudo, Seiichi; Nishimura, Kazuya

2003-01-01

It is expected that the selection of access routes for employees who engage in emergency work at a severe accident in a nuclear power plant makes a difference in their radiation dose values. In order to examine how much difference arises in the dose by the selection of the access routes, in the case of a severe accident in a pressurized water reactor plant, we improved the method to obtain the dose for employees and expanded the analyzing system. By the expansion of the system and the improvement of the method, we have realized the followings: (1) in the whole plant area, the dose evaluation is possible, (2) the efficiency of calculation is increased by the reduction of the number of radiation sources, etc, and (3) the function is improved by introduction of the sky shine calculation into the highest floor, etc. The improved system clarifies the followings: (1) the doses change by selected access routes, and this system can give the difference in the doses quantitatively, and (2) in order to suppress the dose, it is effective to choose the most adequate access route for the employees. (author)

Therapeutic Inhibition of miR-208a Improves Cardiac Function and Survival During Heart Failure

Science.gov (United States)

Montgomery, Rusty L.; Hullinger, Thomas G.; Semus, Hillary M.; Dickinson, Brent A.; Seto, Anita G.; Lynch, Joshua M.; Stack, Christianna; Latimer, Paul A.; Olson, Eric N.; van Rooij, Eva

2012-01-01

Background Diastolic dysfunction in response to hypertrophy is a major clinical syndrome with few therapeutic options. MicroRNAs act as negative regulators of gene expression by inhibiting translation or promoting degradation of target mRNAs. Previously, we reported that genetic deletion of the cardiac-specific miR-208a prevents pathological cardiac remodeling and upregulation of Myh7 in response to pressure overload. Whether this miRNA might contribute to diastolic dysfunction or other forms of heart disease is currently unknown. Methods and Results Here, we show that systemic delivery of an antisense oligonucleotide induces potent and sustained silencing of miR-208a in the heart. Therapeutic inhibition of miR-208a by subcutaneous delivery of antimiR-208a during hypertension-induced heart failure in Dahl hypertensive rats dose-dependently prevents pathological myosin switching and cardiac remodeling while improving cardiac function, overall health, and survival. Transcriptional profiling indicates that antimiR-208a evokes prominent effects on cardiac gene expression; plasma analysis indicates significant changes in circulating levels of miRNAs on antimiR-208a treatment. Conclusions These studies indicate the potential of oligonucleotide-based therapies for modulating cardiac miRNAs and validate miR-208 as a potent therapeutic target for the modulation of cardiac function and remodeling during heart disease progression. PMID:21900086

Therapeutic Enzymes: Applications and Approaches to Pharmacological Improvement.

Science.gov (United States)

Yari, Maryam; Ghoshoon, Mohammad B; Vakili, Bahareh; Ghasemi, Younes

2017-01-01

Among therapeutic proteins, enzymes represent small and of course profitable market. They can be used to treat important, rare, and deadly diseases. Enzyme therapy is the only available treatment for certain disorders. Here, pharmaceutical enzymes are reviewed. They are categorized in four main groups, enzymes in replacement therapy, enzymes in cancer treatment, enzymes for fibrinolysis, and finally enzymes that are used topically for various treatments. Furthermore, enzyme gene therapy and future perspective of therapeutic enzymes are mentioned in brief. There are many important approved enzymes in pharmaceutical market. Several approaches such as point mutation, fusion protein designing, glycoengineering, and PEGylation were used to achieve improved enzymes. Although sometimes enzymes were engineered to facilitate production and purification process, appropriate delivery to target sites, extending half-life, and reducing immunogenicity are among the main goals of engineering approaches. Overall, enzymes play a critical role in treatment of common and rare diseases. Evaluation of new enzymes as well as improvement of approved enzymes are of the most important challenges in biotechnology. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Protective and Therapeutic Role of Low Dose Gamma Radiation on Streptozotocin Induced Diabetes in Rats

International Nuclear Information System (INIS)

Mansour, H.H.; Hafez, H.F.; Shouman, S.A.

2011-01-01

Diabetes mellitus is a multi-factorial disease which is characterized by vascular and renal complication. This study was initiated to investigate the protective and the therapeutic effect of low dose of gamma radiation (LDR) on diabetic complications. A total of 30 adult male rats were divided into 5 groups: Group I: served as control and injected intraperitoneally with 0.2 ml of 0.1 mol/l citrate buffer (ph 4.5), group II: rats became diabetic via intraperitoneal injection with 60 mg/kg streptozotocin (STZ) dissolved in 0.2 ml of 0.1 mol/l citrate buffer (ph 4.5), group III irradiated rats (IRR): submitted to fractionated dose of whole body gamma rays; 0.25 Gy for 2 consecutive days (whole dose 0.5 Gy), group IV diabetic irradiated rats (STZ + IRR): rats became diabetic as group II then four weeks after diabetes induction (day 28), rats were submitted to 2 fractions of whole body gamma rays as in group III, and group V irradiated diabetic rats (IRR + STZ): rats were injected intraperitoneally with 0.2 ml of 0.1 mol/l citrate buffer then submitted to whole body gamma rays; 0.25 Gy for 2 consecutive days then one hour after the last IRR dose, rats were made diabetic as group II. In pre and post-irradiation of STZ rats, significant changes were observed in serum lipid profiles, hepatic and cardiac serum enzymes. Significant decrease in hepatic and cardiac malondialdehyde (MDA) and total nitrate/nitrite (NO(x)) levels, and significant increase in superoxide dismutase (SOD) and glutathione (GSH) levels were observed as compared to diabetic group. The study suggests that LDR may provide useful protective and therapeutic option in the reversal of oxidative stress induced in diabetic rats

Trials to optimize dosimetry for 153Sm-EDTMP therapy to improve therapeutic effects

International Nuclear Information System (INIS)

Riccabona, G.; Moncayo-Naveda, R.; Oberlandstaetter, M.; Donnemiller, E.; Kendler, D.

2001-01-01

In a trial to improve results of therapy with 153 Sm-EDTMP for pain control in patients with disseminated bone metastases dosimetric studies were performed. Out of 30 treated patients 8 were selected for the study at random (5 breast Ca., 3 prostate Ca.). Whole body retention (WBR) of 99m Tc-DPD and 99m Tc-EDTMP was compared with WBR of 153 Sm-EDTMP. Volume of metastases and regional 99 m Tc-phosphonate uptake were assessed by SPECT and conjugated whole body scan data after phantom studies. Effective half-life was estimated also. Clinically results of pain control, side effects and changes of in vitro parameters were followed after therapy for up to 8 months. Therapy was performed in these patients with 55,5 MBq/kg body weight. Results showed an identical pattern of radioactivity distribution on 99 Tc-phosphonate and 153 Sm-EDTMP posttherapy scans, WBR of tracers and therapeutic agent was similar. Tumour volumes were 151-652 mL, count ratios metastases/normal bone 1,72-2,41, so that 6-50% of applied 153 Sm-EDTMP were concentrated in bone lesions. This gave dose estimates of 2,8-13,7 Gy in metastases. Evaluation of clinical results showed that the majority of very good results were observed in patients receiving > 10 Gy (n=3) while with lower doses only 1/4 responded very well. 1 patient was lost to follow-up due to death in the first month after therapy. Moderate and transient myelodepression (platelets) was seen in 3/7 patients without relation to Gy applied. As obviously 153 Sm concentration is not homogenous in bone metastases it can be assumed, that in border zones between tumour and bone 30-40 Gy can be delivered when 10 Gy are calculated for the whole lesion, which would explain the satisfactory therapeutic effect in our study. The dosimetric approach to 153 Sm-EDTMP therapy could necessitate the application of higher amounts of 153 Sm-EDTMP to reach adequate radiation doses in lesions without necessarily increasing risk of myelodepression and with even

Improved dose estimates for nuclear criticality accidents

International Nuclear Information System (INIS)

Wilkinson, A.D.; Basoglu, B.; Bentley, C.L.; Dunn, M.E.; Plaster, M.J.; Dodds, H.L.; Yamamoto, T.

1995-01-01

Slide rules are improved for estimating doses and dose rates resulting from nuclear criticality accidents. The original slide rules were created for highly enriched uranium solutions and metals using hand calculations along with the decades old Way-Wigner radioactive decay relationship and the inverse square law. This work uses state-of-the-art methods and better data to improve the original slide rules and also to extend the slide rule concept to three additional systems; i.e., highly enriched (93.2 wt%) uranium damp (H/ 235 U = 10) powder (U 3 O 8 ) and low-enriched (5 wt%) uranium mixtures (UO 2 F 2 ) with a H/ 235 U ratio of 200 and 500. Although the improved slide rules differ only slightly from the original slide rules, the improved slide rules and also the new slide rules can be used with greater confidence since they are based on more rigorous methods and better nuclear data

Ondansetron. Therapeutic use as an antiemetic

Energy Technology Data Exchange (ETDEWEB)

Milne, R.J.; Heel, R.C. (Adis Drug Information Services, Auckland (New Zealand))

1991-04-01

Ondansetron (GR 38032F) is a highly selective 5-HT3 receptor antagonist, one of a new class of compounds which may have several therapeutic applications. Animal and clinical studies show that ondansetron reduces the 24-hour incidence and severity of nausea and vomiting induced by cytotoxic drugs, including cisplatin, and by single exposure, high dose radiation. Ondansetron is more effective than high dose metoclopramide in the 24 hours following chemotherapy, and preliminary clinical evidence suggests that it is equally effective in the following 4 days. It is also more effective than the moderate doses of metoclopramide used to suppress emesis following radiotherapy. The antiemetic efficacy of ondansetron is enhanced by dexamethasone in cisplatin-treated patients. Importantly, extrapyramidal effects have not been reported with ondansetron. Further comparisons are required with standard combination antiemetic therapy to complement the data presently available. Thus, ondansetron is a promising new agent for prophylaxis against nausea and vomiting in chemotherapy and radiotherapy. It may be particularly useful in young and elderly patients who are more susceptible to extrapyramidal symptoms induced by high dose metoclopramide. With its improved tolerability and clinical response profiles, ondansetron represents an important advance in a difficult area of therapeutics. 101 refs.

Ondansetron. Therapeutic use as an antiemetic

International Nuclear Information System (INIS)

Milne, R.J.; Heel, R.C.

1991-01-01

Ondansetron (GR 38032F) is a highly selective 5-HT3 receptor antagonist, one of a new class of compounds which may have several therapeutic applications. Animal and clinical studies show that ondansetron reduces the 24-hour incidence and severity of nausea and vomiting induced by cytotoxic drugs, including cisplatin, and by single exposure, high dose radiation. Ondansetron is more effective than high dose metoclopramide in the 24 hours following chemotherapy, and preliminary clinical evidence suggests that it is equally effective in the following 4 days. It is also more effective than the moderate doses of metoclopramide used to suppress emesis following radiotherapy. The antiemetic efficacy of ondansetron is enhanced by dexamethasone in cisplatin-treated patients. Importantly, extrapyramidal effects have not been reported with ondansetron. Further comparisons are required with standard combination antiemetic therapy to complement the data presently available. Thus, ondansetron is a promising new agent for prophylaxis against nausea and vomiting in chemotherapy and radiotherapy. It may be particularly useful in young and elderly patients who are more susceptible to extrapyramidal symptoms induced by high dose metoclopramide. With its improved tolerability and clinical response profiles, ondansetron represents an important advance in a difficult area of therapeutics. 101 refs

Therapeutic efficacy and safety of various botulinum toxin A doses and concentrations in spastic foot after stroke: a randomized controlled trial

Directory of Open Access Journals (Sweden)

Jiang Li

2017-01-01

Full Text Available No recommended guidelines currently exist for the therapeutic concentration or dose of botulinum toxin type A (BTXA injected into the muscle to treat limb spasticity. Therefore, in this randomized controlled trial, we explored the safety and efficacy of two concentrations and two doses of BTXA in the treatment of spastic foot after stroke to optimize this treatment in these patients. Eligible patients (n = 104 were randomized into four groups. The triceps surae and tibialis posterior on the affected side were injected with BTXA at one of two doses (200 U or 400 U and two concentrations (50 U/mL or 100 U/mL. The following assessments were conducted before as well as 4 days and 1, 2, 4, and 12 weeks after treatment: spasticity, assessed using the modified Ashworth scale; basic functional mobility, assessed using a timed up and go test; pace, assessed using a 10-meter timed walking test; and the ability to walk, assessed using Holden's graded scale and a visual analog scale. The reported results are based on the 89 patients that completed the study. We found significant differences for the two doses and concentrations of BTXA to improve the ability of patients to walk independently, with the high-dose/low-concentration combination providing the best effect. Onset and duration of the ameliorating effects of BTXA were 4–7 days and 12 weeks, respectively. Thus, BTXA effectively treated foot spasms after stroke at an optimal dose of 400 U and concentration of 50 U/mL.

Absorption kinetics and steady-state plasma concentrations of theophylline following therapeutic doses of two sustained-release preparations

DEFF Research Database (Denmark)

Andersen, O; Nielsen, M K; Eriksen, P B

1983-01-01

Ten healthy volunteers received two sustained-release preparations as a single and multiple dose regimen in an open crossover study. Plasma theophylline concentrations were measured by an enzyme immunoassay. The limited fluctuation of the theophylline levels at steady state, with twice daily...... formulation, whereas this was not the case for the other (r = 0.27 and 0.49). The daily dose necessary to keep the plasma concentration within the therapeutic range of 55-110 mumole/liter varied from 7.9 to 22.9 mg/kg. Only mild side effects were recorded, but they were not correlated to the plasma...... theophylline concentration....

Efficacy and safety of a multifactor intervention to improve therapeutic adherence in patients with chronic obstructive pulmonary disease (COPD: protocol for the ICEPOC study

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Prados-Torres Daniel

2011-02-01

Full Text Available Abstract Background Low therapeutic adherence to medication is very common. Clinical effectiveness is related to dose rate and route of administration and so poor therapeutic adherence can reduce the clinical benefit of treatment. The therapeutic adherence of patients with chronic obstructive pulmonary disease (COPD is extremely poor according to most studies. The research about COPD adherence has mainly focussed on quantifying its effect, and few studies have researched factors that affect non-adherence. Our study will evaluate the effectiveness of a multifactor intervention to improve the therapeutic adherence of COPD patients. Methods/Design A randomized controlled clinical trial with 140 COPD diagnosed patients selected by a non-probabilistic method of sampling. Subjects will be randomly allocated into two groups, using the block randomization technique. Every patient in each group will be visited four times during the year of the study. Intervention: Motivational aspects related to adherence (beliefs and behaviour: group and individual interviews; cognitive aspects: information about illness; skills: inhaled technique training. Reinforcement of the cognitive-emotional aspects and inhaled technique training will be carried out in all visits of the intervention group. Discussion Adherence to a prescribed treatment involves a behavioural change. Cognitive, emotional and motivational aspects influence this change and so we consider the best intervention procedure to improve adherence would be a cognitive and emotional strategy which could be applied in daily clinical practice. Our hypothesis is that the application of a multifactor intervention (COPD information, dose reminders and reinforcing audiovisual material, motivational aspects and inhalation technique training to COPD patients taking inhaled treatment will give a 25% increase in the number of patients showing therapeutic adherence in this group compared to the control group. We will

Patient radiation doses in therapeutic endoscopic retrograde cholangiopancreatography in Patras and the key role of the operator

International Nuclear Information System (INIS)

Hadjiconstanti, Anastasia C.; Messaris, Gerasimos A. T.; Panayiotakis, George S.; Thomopoulos, Konstantinos C.

2017-01-01

The patient radiation doses, in conjunction with the operator experience, in therapeutic endoscopic retrograde cholangiopancreatography (ERCP) procedures, performed in our hospital, were obtained. Ninety-six patients participated in the study and were divided into 3 groups, based on the operator experience. The dosimetric indices, fluoroscopy time (FT), cumulative dose (K a,r ) and air kerma-area product (P KA ), were collected. For the total and weight banding group the third quartile values of the distribution of FT, K a,r and P KA were 2.90 and 2.92 min, 6.89 and 6.93 mGy and 1.84 and 1.85 Gycm 2 , respectively, and were comparative or significantly lower than the corresponding values previously reported. Taking as a criterion the operator, the differences in the patient radiation doses were statistically significant, with the highest dose recorded for the operator of the lowest experience degree. The values obtained could contribute in establishing local and national diagnostic reference levels and in optimising ERCP procedure. (authors)

An evaluation of high-dose jobs for ALARA improvement

International Nuclear Information System (INIS)

Mun, J. H.; Kim, H. S.

1997-01-01

It is well known that about 70 percent of occupational dose have incurred from maintenance jobs at outage period. To reduce occupational dose, first, the high-dose jobs at the outage period should be identified and evaluated. For this, the database program is used, which contains the ORE data of reference plants, Kori Units 3 and 4. As a result, it is found that the jobs related to steam generator are the highest dose jobs in terms of collective ORE dose. From the analysis of the job procedures of those jobs, the ALARA improvements are also derived

Improvement of Off-site Dose Assessment Code for Operating Nuclear Power Plant

Energy Technology Data Exchange (ETDEWEB)

Kim, Juyub; Kim, Juyoul; Shin, Kwangyoung [FNC Technology Co. Ltd., Yongin (Korea, Republic of); You, Songjae; Moon, Jongyi [Korea Institute of Nuclear Safety, Daejeon (Korea, Republic of)

2014-05-15

XOQDOQ code which calculates atmospheric Dispersion factor was included into INDAC also. A research on the improvement of off-site dose assessment system for an operating nuclear power plant was performed by KINS in 2011. As a result, following improvements were derived: - Separation of dose assessment for new and existing facilities - Update of food ingestion data - Consideration of multi-unit operation and so on In order to reflect the results, INDAC is under modification. INDAC is an integrated dose assessment code for an operating nuclear power plant and consists of three main modules: XOQDOQ, GASDOS and LIQDOS. The modules are under modification in order to improve the accuracy of assessment and usability. Assessment points for multi-unit release can be calculated through the improved code and the method on dose assessment for multi-unit release has been modified, so that the dose assessment result of multi-unit site becomes more realistic by relieving excessive conservatism. Finally, as the accuracy of calculation modules has been improved, the reliability of dose assessment result has been strengthened.

Getting Innovative Therapies Faster to Patients at the Right Dose: Impact of Quantitative Pharmacology Towards First Registration and Expanding Therapeutic Use.

Science.gov (United States)

Nayak, Satyaprakash; Sander, Oliver; Al-Huniti, Nidal; de Alwis, Dinesh; Chain, Anne; Chenel, Marylore; Sunkaraneni, Soujanya; Agrawal, Shruti; Gupta, Neeraj; Visser, Sandra A G

2018-03-01

Quantitative pharmacology (QP) applications in translational medicine, drug-development, and therapeutic use were crowd-sourced by the ASCPT Impact and Influence initiative. Highlighted QP case studies demonstrated faster access to innovative therapies for patients through 1) rational dose selection for pivotal trials; 2) reduced trial-burden for vulnerable populations; or 3) simplified posology. Critical success factors were proactive stakeholder engagement, alignment on the value of model-informed approaches, and utilizing foundational clinical pharmacology understanding of the therapy. © 2018 The Authors Clinical Pharmacology & Therapeutics published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

SU-F-T-174: Patient-Specific Point Dose Measurement Using Fiber Optic Radiation Sensor Using Cerenkov Radiation for Proton Therapeutic Beam

Energy Technology Data Exchange (ETDEWEB)

Son, J [Korea University, Seoul, Seoul (Korea, Republic of); National Cancer Center, Goyang-si (Korea, Republic of); Kim, M [Dongnam Institute of Radiological & Medical Sciences, Busan, Busan (Korea, Republic of); Yoon, M [Korea University, Seoul (Korea, Republic of); Shin, D [National Cancer Center, Goyang-si (Korea, Republic of)

2016-06-15

Purpose: A fiber-optic radiation sensor using Cerenkov radiation (FOCR) has been widely studied for use as a dosimeter for proton therapeutic beam. We developed the FOCR, and it applied to patient-specific point dose measurement in order to evaluate the effectiveness of the FOCR system for proton therapy QA. Methods: Calibration of FOCR was performed with an ionization chamber whose absolute doses were determined according to the IAEA TRS-398 protocol. To determine the calibration curve, the FOCR was irradiated perpendicularly to the proton beam at the 13 dose levels steps. We selected five actual patient treatment plans performed at proton therapy center and compared the resulting FOCR measurements with the ionization chamber measurements. Results: The Cerenkov light yield of the FOCR increases linearly with as the dose measured using the ionization chamber increases from 0 cGy to 500 cGy. The results indicate that the fitting curve is linear, suggesting that dose measurement based on the light yield of the FOCR is possible. The results of proton radiation dose QA performed using the FOCR for 10 proton fields and five patients are good agreement with an ionization chamber. Conclusion: We carried out the patient QA using the FOCR for proton therapeutic beam and evaluated the effectiveness of the FOCR as a proton therapy QA tool. Our results indicate that the FOCR is suitable for use in patient QA of clinical proton beams.

Long-Term Impact of Immunosuppressants at Therapeutic Doses on Male Reproductive System in Unilateral Nephrectomized Rats: A Comparative Study

Directory of Open Access Journals (Sweden)

Yehui Chen

2013-01-01

Full Text Available Cyclosporine, tacrolimus, and sirolimus are commonly used in renal transplant recipients to prevent rejection. However, information for comparative effects of these agents on the male productive system is extremely limited and controversial. In a physiologically and clinically relevant rat model of unilateral nephrectomy, we demonstrated that long-term oral administration of both cyclosporine and sirolimus at doses equivalent to the therapeutic levels used for postrenal transplant patients significantly affects testicular development and the hypothalamic-pituitary-gonadal axis accompanied by profound histological changes of testicular structures on both light and electron microscopic examinations. Spermatogenesis was also severely impaired as indicated by low total sperm counts along with reduction of sperm motility and increase in sperm abnormality after treatment with these agents, which may lead to male infertility. On the other hand, treatment with therapeutic dose of tacrolimus only induced mild reduction of sperm count without histological evidence of testicular injury. The current study clearly demonstrates that commonly used immunosuppressants have various impacts on male reproductive system even at therapeutic levels. Our data provide useful information for the assessment of male infertility in renal transplant recipients who wish to father children. Clinical trials to address these issues should be urged.

A therapeutic gain model for brachytherapy

International Nuclear Information System (INIS)

Wigg, D.R.

2003-01-01

When treating with continuous irradiation the potential therapeutic gain or loss depends on several treatment, normal tissue and tumour variables. There are similarities between equations defining tissue effects with fractionated treatment and brachytherapy. The former is sensitive to dose per fraction (and incomplete repair for short intervals between treatments) and the later is sensitive to dose rate and continuous repair factors. Because of these similarities, for typical tumours and normal tissues, dose per fraction and dose rates generally work in similar directions. As the dose per fraction or dose rate increases the therapeutic gain falls. With continuous irradiation the dose rates effects are determined by Beta cell kill and hence the absolute value of Beta . Minimal sensitivity occurs at very low and very high dose rates. The magnitude of cell kill also depends on the Continuous Repair Factor (g) which is a function of the treatment time and the Repair Half Time (in hours) of the tissues (Repair Half Time T 1/2Ln(2)/h, when h the Repair Constant). An interactive optimising model has been written to predict the therapeutic gain or loss as the parameter values are varied. This model includes the tumour and normal tissue parameters alpha and beta Gy (or individual values), their Repair Half Times, dose rates and overall treatment time. The model is based on the Linear-Quadratic equation and the Total Effect (TE) method of Thames and Hendry although the Extrapolated Response Dose (ERD) method of Barendsen produces the same results. The model is written so that the gain or loss may be seen when treatment is always to normal tissue tolerance doses. The magnitude of the therapeutic loss as the dose rate increases and its sensitivity to changes in normal tissue and tumour parameter values is clearly demonstrated

A single dose of oxytocin nasal spray improves higher-order social cognition in schizophrenia.

Science.gov (United States)

Guastella, Adam J; Ward, Philip B; Hickie, Ian B; Shahrestani, Sara; Hodge, Marie Antoinette Redoblado; Scott, Elizabeth M; Langdon, Robyn

2015-11-01

Schizophrenia is associated with significant impairments in both higher and lower order social cognitive performance and these impairments contribute to poor social functioning. People with schizophrenia report poor social functioning to be one of their greatest unmet treatment needs. Recent studies have suggested the potential of oxytocin as such a treatment, but mixed results render it uncertain what aspects of social cognition are improved by oxytocin and, subsequently, how oxytocin might best be applied as a therapeutic. The aim of this study was to determine whether a single dose of oxytocin improved higher-order and lower-order social cognition performance for patients with schizophrenia across a well-established battery of social cognition tests. Twenty-one male patients received both a single dose of oxytocin nasal spray (24IU) and a placebo, two weeks apart in a randomized within-subjects placebo controlled design. Following each administration, participants completed the social cognition tasks, as well as a test of general neurocognition. Results revealed that oxytocin particularly enhanced performance on higher order social cognition tasks, with no effects on general neurocognition. Results for individual tasks showed most improvement on tests measuring appreciation of indirect hints and recognition of social faux pas. These results suggest that oxytocin, if combined to enhance social cognition learning, may be beneficial when targeted at higher order social cognition domains. This study also suggests that these higher order tasks, which assess social cognitive processing in a social communication context, may provide useful markers of response to oxytocin in schizophrenia. Copyright © 2015 Elsevier B.V. All rights reserved.

Evidence Based Digoxin Therapeutic Monitoring - A Lower and Narrower Therapeutic Range

Directory of Open Access Journals (Sweden)

Amine BENLMOUDEN

2016-06-01

Full Text Available Cardiac glycosides have been used for congestive heart failure and certain cardiac arrhythmias for more than 200 years. Despite the introduction of a variety of new classes of drugs for the management of heart failure, specifically angiotensin-converting enzyme (ACE inhibitors, b-adrenergic antagonists (bblockers, and the aldosterone antagonist spironolactone, digoxin continues to have an important role in long-term outpatient management. However, a narrow margin exists between therapeutic and toxic doses of digoxin, resulting in a high incidence of digoxin toxicity in clinical practice.A wide variety of placebo-controlled clinical trials have unequivocally shown that treatment with digoxin can improve symptoms, quality of life, and exercise tolerance in patients with mild, moderate, or severe heart failure. The clinical relevance of digoxin therapeutic monitoring is also proved but the SDC (Serum Digoxin Conentrations required for optimal clinical efficacy and acceptable toxicity remains controversial. In the last years, international guidelines recommend 1.2 ng/mL as acceptable high level.In this bibliographic synthesis, we aim to collect pertinent informations from MedLine database about exposure-effect relationship in order to assess the evidence level scientific of new digoxin therapeutic monitoring. 

Therapeutic drug monitoring: how to improve drug dosage and patient safety in tuberculosis treatment

Directory of Open Access Journals (Sweden)

Giovanni Sotgiu

2015-03-01

Full Text Available In this article we describe the key role of tuberculosis (TB treatment, the challenges (mainly the emergence of drug resistance, and the opportunities represented by the correct approach to drug dosage, based on the existing control and elimination strategies. In this context, the role and contribution of therapeutic drug monitoring (TDM is discussed in detail. Treatment success in multidrug-resistant (MDR TB cases is low (62%, with 7% failing or relapsing and 9% dying and in extensively drug-resistant (XDR TB cases is even lower (40%, with 22% failing or relapsing and 15% dying. The treatment of drug-resistant TB is also more expensive (exceeding €50 000 for MDR-TB and €160 000 for XDR-TB and more toxic if compared to that prescribed for drug-susceptible TB. Appropriate dosing of first- and second-line anti-TB drugs can improve the patient's prognosis and lower treatment costs. TDM is based on the measurement of drug concentrations in blood samples collected at appropriate times and subsequent dose adjustment according to the target concentration. The ‘dried blood spot’ technique offers additional advantages, providing the rationale for discussions regarding a possible future network of selected, quality-controlled reference laboratories for the processing of dried blood spots of difficult-to-treat patients from reference TB clinics around the world.

Therapeutic drug monitoring of antimicrobials

Science.gov (United States)

Roberts, Jason A; Norris, Ross; Paterson, David L; Martin, Jennifer H

2012-01-01

Optimizing the prescription of antimicrobials is required to improve clinical outcome from infections and to reduce the development of antimicrobial resistance. One such method to improve antimicrobial dosing in individual patients is through application of therapeutic drug monitoring (TDM). The aim of this manuscript is to review the place of TDM in the dosing of antimicrobial agents, specifically the importance of pharmacokinetics (PK) and pharmacodynamics (PD) to define the antimicrobial exposures necessary for maximizing killing or inhibition of bacterial growth. In this context, there are robust data for some antimicrobials, including the ratio of a PK parameter (e.g. peak concentration) to the minimal inhibitory concentration of the bacteria associated with maximal antimicrobial effect. Blood sampling of an individual patient can then further define the relevant PK parameter value in that patient and, if necessary, antimicrobial dosing can be adjusted to enable achievement of the target PK/PD ratio. To date, the clinical outcome benefits of a systematic TDM programme for antimicrobials have only been demonstrated for aminoglycosides, although the decreasing susceptibility of bacteria to available antimicrobials and the increasing costs of pharmaceuticals, as well as emerging data on pharmacokinetic variability, suggest that benefits are likely. PMID:21831196

New method for the induction of therapeutic amenorrhea: low dose endometrial afterloading irradiation. Clinical and hormonal studies

Energy Technology Data Exchange (ETDEWEB)

Gronroos, M.; Turunen, T.; Raekallio, J.; Ruotsalinen, P.; Salmi, T. (Turku Univ. (Finland). Dept. of Obstetrics and Gynecology)

1982-08-01

The authors present a new method for the induction of therapeutic amenorrhea: low dose endometrial afterloading irradiation. The problem with this method has been how to inactivate the endometrium while maintaining the physiological function of the ovaries. In 5/29 young patients regular or irregular bleedings occurred after an endometrial dose of 11+-1 Gy. These subjects were given a repeat low dose intrauterine irradiation. Thereafter no bleedings were found in four out of five patients. Two to 9 years after the repeat irradiation the plasma levels of E/sub 1/, E/sub 2/, FSH and LH corresponded closely to those of healthy women in reproductive age in three out of five patients; some high plasma P levels indicated ovulation. In two patients the E/sub 1/, E/sub 2/, and P values were more likely postmenopausal but, on the other hand, FSH and LH values reproductive ones. 19 refs.

Therapeutic drug monitoring in pregnancy.

Science.gov (United States)

Matsui, Doreen M

2012-10-01

Therapeutic drug monitoring (TDM) is commonly recommended to optimize drug dosing regimens of various medications. It has been proposed to guide therapy in pregnant women, in whom physiological changes may lead to altered pharmacokinetics resulting in difficulty in predicting the appropriate drug dosage. Ideally, TDM may play a role in enhancing the effectiveness of treatment while minimizing toxicity of both the mother and fetus. Monitoring of drug levels may also be helpful in assessing adherence to prescribed therapy in selected cases. Limitations exist as therapeutic ranges have only been defined for a limited number of drugs and are based on data obtained in nonpregnant patients. TDM has been suggested for anticonvulsants, antidepressants, and antiretroviral drugs, based on pharmacokinetic studies that have shown reduced drug concentrations. However, there is only relatively limited (and sometimes inconsistent) information regarding the clinical impact of these pharmacokinetic changes during pregnancy and the effect of subsequent dose adjustments. Further studies are required to determine whether implementation of TDM during pregnancy improves outcome and is associated with any benefit beyond that achieved by clinical judgment alone. The cost effectiveness of TDM programs during pregnancy also remains to be examined.

Biological dose estimation for charged-particle therapy using an improved PHITS code coupled with a microdosimetric kinetic model

International Nuclear Information System (INIS)

Sato, Tatsuhiko; Watanabe, Ritsuko; Kase, Yuki; Niita, Koji; Sihver, Lembit

2009-01-01

-particle therapy was established using the improved PHITS coupled with a microdosimetric kinetic (MK) model. The detailed procedures for improving the PHITS code and establishing the biological-dose-estimation method were presented elsewhere. Hence, this report focuses on describing their capabilities to optimize the treatment planning of charged particle therapy, thereby maximizing the therapeutic effect on tumor while minimizing unintended harmful effects on surrounding normal tissues. (author)

Determination of the dose equivalents due to neutrons produced during therapeutic irradiations with a Varian CLINAC 2500

International Nuclear Information System (INIS)

Carrillo, Ricardo E.

1991-01-01

This experiment it was designed to quantify that so important it is the dose equivalent deposited by the neutron flow that is generated by photonuclear reactions during therapeutic irradiations with X rays of produced high-energy for an accelerator Varian CLINAC 2500. This accelerator type is routinely used in the Department of Radiotherapy of the Hospital of the University of Wisconsin, E.U. The equivalent dose was measured in diverse towns of the room of irradiations using the activation of thin sheets of gold put in the center of plastic recipients full with water. In general, the recipients were 1 m or more than the floor and at distances still bigger than the walls. The irradiations were made using photons with the highest energy that you can select with this team - 24 MeV. The due equivalent dose to neutrons taken place here by the energy photons used they were measured and reported. (author)

Therapeutic Doses of Nonsteroidal Anti-Inflammatory Drugs Inhibit Osteosarcoma MG-63 Osteoblast-Like Cells Maturation, Viability, and Biomineralization Potential

Directory of Open Access Journals (Sweden)

E. De Luna-Bertos

2013-01-01

Full Text Available Nonsteroidal anti-inflammatory drugs (NSAIDs are frequently used to reduce pain and inflammation. However, their effect on bone metabolisms is not well known, and results in the literature are contradictory. The present study focusses on the effect of dexketoprofen, ketorolac, metamizole, and acetylsalicylic acid, at therapeutic doses, on different biochemical and phenotypic pathways in human osteoblast-like cells. Osteoblasts (MG-63 cell line were incubated in culture medium with 1–10 μM of dexketoprofen, ketorolac, metamizole, and acetylsalicylic acid. Flow cytometry was used to study antigenic profile and phagocytic activity. The osteoblastic differentiation was evaluated by mineralization and synthesis of collagen fibers by microscopy and alkaline phosphatase activity (ALP by spectrophotometric assay. Short-term treatment with therapeutic doses of NSAIDs modulated differentiation, antigenic profile, and phagocyte activity of osteoblast-like cells. The treatment reduced ALP synthesis and matrix mineralization. However, nonsignificant differences were observed on collagen syntheses after treatments. The percentage of CD54 expression was increased with all treatments. CD80, CD86, and HLA-DR showed a decreased expression, which depended on NSAID and the dose applied. The treatments also decreased phagocyte activity in this cellular population. The results of this paper provide evidences that NSAIDs inhibit the osteoblast differentiation process thus reducing their ability to produce new bone mineralized extracellular matrix.

Therapeutic Doses of Nonsteroidal Anti-Inflammatory Drugs Inhibit Osteosarcoma MG-63 Osteoblast-Like Cells Maturation, Viability, and Biomineralization Potential

Science.gov (United States)

De Luna-Bertos, E.; Ramos-Torrecillas, J.; García-Martínez, O.; Guildford, A.; Santin, M.; Ruiz, C.

2013-01-01

Nonsteroidal anti-inflammatory drugs (NSAIDs) are frequently used to reduce pain and inflammation. However, their effect on bone metabolisms is not well known, and results in the literature are contradictory. The present study focusses on the effect of dexketoprofen, ketorolac, metamizole, and acetylsalicylic acid, at therapeutic doses, on different biochemical and phenotypic pathways in human osteoblast-like cells. Osteoblasts (MG-63 cell line) were incubated in culture medium with 1–10 μM of dexketoprofen, ketorolac, metamizole, and acetylsalicylic acid. Flow cytometry was used to study antigenic profile and phagocytic activity. The osteoblastic differentiation was evaluated by mineralization and synthesis of collagen fibers by microscopy and alkaline phosphatase activity (ALP) by spectrophotometric assay. Short-term treatment with therapeutic doses of NSAIDs modulated differentiation, antigenic profile, and phagocyte activity of osteoblast-like cells. The treatment reduced ALP synthesis and matrix mineralization. However, nonsignificant differences were observed on collagen syntheses after treatments. The percentage of CD54 expression was increased with all treatments. CD80, CD86, and HLA-DR showed a decreased expression, which depended on NSAID and the dose applied. The treatments also decreased phagocyte activity in this cellular population. The results of this paper provide evidences that NSAIDs inhibit the osteoblast differentiation process thus reducing their ability to produce new bone mineralized extracellular matrix. PMID:24170983

Small dose multi-fractionation therapy, its radiobiological aspects and clinics

International Nuclear Information System (INIS)

Iwai, Hiroshi; Katagiri, Shiro; Furuhata, Akihiko; Fukusi, Itsuhisa

1979-01-01

Recent radiobiological data reveal that cell killings by small dose fractionation are almost due to nonrepairable damage with low oxygen enhancement ratio. Then, Small dose multi-fractionation method suggests a higher therapeutic-ratio than that in conventional high dose fractionated irradiation. Using these data of radiobiology, intermittent irradiations three times a day, four hours interval, with 60 - 80 rads for multi-fractionation, with high total doses of 7,200 - 7,500 rads/6.5 - 7 weeks mainly on bladder, laryngeal and esophageal tumour are applied. The results obtained are slightly improved. (author)

Time-dose modifications

International Nuclear Information System (INIS)

Kian Ang, K.

1987-01-01

Changes in fractionation schedule can be made by various approaches. However, from the first principle, it is anticipated that strategies of hyperfractionation and/or accelerated fractionation offer the most promised in improving the therapeutic ratio. Hyperfractionation is defined as a treatment schedule in which a large number of significantly reduced dose fractions (--1.2 Gy/fraction) is used to give a greater total dose in a conventional overall time period. The results of the pilot studies testing the efficacy of hyperfractionation have been encouraging. The most valid clinical trial of pure hyperfractionation, however, is that conducted by the EORTC. This study compared 70 Gy in 35 fractions or 80.5 Gy in 70 fractions over 7 weeks in the treatment of patients with oropharyngeal carcinomas. The local tumor control was significantly improved in the hyperfractionated arm without increasing the morbidity. Accelerated fractionation is defined as a schedule in which the overall time of treatment is reduced without significant changes in the total dose and fraction size. The strategy has been used to treat patients with malignant gliomas, melanomas and Head and Neck cancers. The data in Head and Neck Cancers seem to be promising

Communication techniques for improved acceptance and adherence with therapeutic footwear.

Science.gov (United States)

van Netten, Jaap J; Francis, Anthony; Morphet, Ashley; Fortington, Lauren V; Postema, Klaas; Williams, Anita

2017-04-01

Clients' acceptance and adherence with orthoses can be influenced by a clinician's communication skills. In this clinical note, we describe two communication techniques, in the context of therapeutic footwear. Person-centred communication involves engaging with and listening to the attitudes of the client towards their condition, as well as discussing acceptance and expectations, in a structured consultation. Building a relationship is crucial and requires clients to feel heard and understood. An important influence on the acceptance and adherence is that a client makes a conscious decision to receive their device. This active receipt can be facilitated through shared decision making, wherein clinicians give clear, relevant and meaningful examples, based on clinical evidence, and ensure this is understood. Two communication techniques for clinicians providing therapeutic footwear are described. These can be adapted for use with provision of other assistive technologies to improve client acceptance and adherence. Clinical relevance Small changes in how clinicians communicate to their clients in daily practice can have a big influence on the subsequent acceptance and adherence with therapeutic footwear and indeed other prescribed assistive technologies.

A simple and fast physics-based analytical method to calculate therapeutic and stray doses from external beam, megavoltage x-ray therapy.

Science.gov (United States)

Jagetic, Lydia J; Newhauser, Wayne D

2015-06-21

State-of-the-art radiotherapy treatment planning systems provide reliable estimates of the therapeutic radiation but are known to underestimate or neglect the stray radiation exposures. Most commonly, stray radiation exposures are reconstructed using empirical formulas or lookup tables. The purpose of this study was to develop the basic physics of a model capable of calculating the total absorbed dose both inside and outside of the therapeutic radiation beam for external beam photon therapy. The model was developed using measurements of total absorbed dose in a water-box phantom from a 6 MV medical linear accelerator to calculate dose profiles in both the in-plane and cross-plane direction for a variety of square field sizes and depths in water. The water-box phantom facilitated development of the basic physical aspects of the model. RMS discrepancies between measured and calculated total absorbed dose values in water were less than 9.3% for all fields studied. Computation times for 10 million dose points within a homogeneous phantom were approximately 4 min. These results suggest that the basic physics of the model are sufficiently simple, fast, and accurate to serve as a foundation for a variety of clinical and research applications, some of which may require that the model be extended or simplified based on the needs of the user. A potentially important advantage of a physics-based approach is that the model is more readily adaptable to a wide variety of treatment units and treatment techniques than with empirical models.

A new method for the induction of therapeutic amenorrhea: low dose endometrial afterloading irradiation. Clinical and hormonal studies

International Nuclear Information System (INIS)

Gronroos, M.; Turunen, T.; Raekallio, J.; Ruotsalinen, P.; Salmi, T.

1982-01-01

The authors present a new method for the induction of therapeutic amenorrhea: low dose endometrial afterloading irradiation. The problem with this method has been how to inactivate the endometrium while maintaining the physiological function of the ovaries. In 5/29 young patients regular or irregular bleedings occurred after an endometrial dose of 11+-1 Gy. These subjects were given a repeat low dose intrauterine irradiation. Thereafter no bleedings were found in four out of five patients. Two to 9 years after the repeat irradiation the plasma levels of E 1 , E 2 , FSH and LH corresponded closely to those of healthy women in reproductive age in three out of five patients; some high plasma P levels indicated ovulation. In two patients the E 1 , E 2 , and P values were more likely postmenopausal but, on the other hand, FSH and LH values reproductive ones. (author)

Monte Carlo dose calculation improvements for low energy electron beams using eMC

International Nuclear Information System (INIS)

Fix, Michael K; Frei, Daniel; Volken, Werner; Born, Ernst J; Manser, Peter; Neuenschwander, Hans

2010-01-01

The electron Monte Carlo (eMC) dose calculation algorithm in Eclipse (Varian Medical Systems) is based on the macro MC method and is able to predict dose distributions for high energy electron beams with high accuracy. However, there are limitations for low energy electron beams. This work aims to improve the accuracy of the dose calculation using eMC for 4 and 6 MeV electron beams of Varian linear accelerators. Improvements implemented into the eMC include (1) improved determination of the initial electron energy spectrum by increased resolution of mono-energetic depth dose curves used during beam configuration; (2) inclusion of all the scrapers of the applicator in the beam model; (3) reduction of the maximum size of the sphere to be selected within the macro MC transport when the energy of the incident electron is below certain thresholds. The impact of these changes in eMC is investigated by comparing calculated dose distributions for 4 and 6 MeV electron beams at source to surface distance (SSD) of 100 and 110 cm with applicators ranging from 6 x 6 to 25 x 25 cm 2 of a Varian Clinac 2300C/D with the corresponding measurements. Dose differences between calculated and measured absolute depth dose curves are reduced from 6% to less than 1.5% for both energies and all applicators considered at SSD of 100 cm. Using the original eMC implementation, absolute dose profiles at depths of 1 cm, d max and R50 in water lead to dose differences of up to 8% for applicators larger than 15 x 15 cm 2 at SSD 100 cm. Those differences are now reduced to less than 2% for all dose profiles investigated when the improved version of eMC is used. At SSD of 110 cm the dose difference for the original eMC version is even more pronounced and can be larger than 10%. Those differences are reduced to within 2% or 2 mm with the improved version of eMC. In this work several enhancements were made in the eMC algorithm leading to significant improvements in the accuracy of the dose calculation

Monte Carlo dose calculation improvements for low energy electron beams using eMC.

Science.gov (United States)

Fix, Michael K; Frei, Daniel; Volken, Werner; Neuenschwander, Hans; Born, Ernst J; Manser, Peter

2010-08-21

The electron Monte Carlo (eMC) dose calculation algorithm in Eclipse (Varian Medical Systems) is based on the macro MC method and is able to predict dose distributions for high energy electron beams with high accuracy. However, there are limitations for low energy electron beams. This work aims to improve the accuracy of the dose calculation using eMC for 4 and 6 MeV electron beams of Varian linear accelerators. Improvements implemented into the eMC include (1) improved determination of the initial electron energy spectrum by increased resolution of mono-energetic depth dose curves used during beam configuration; (2) inclusion of all the scrapers of the applicator in the beam model; (3) reduction of the maximum size of the sphere to be selected within the macro MC transport when the energy of the incident electron is below certain thresholds. The impact of these changes in eMC is investigated by comparing calculated dose distributions for 4 and 6 MeV electron beams at source to surface distance (SSD) of 100 and 110 cm with applicators ranging from 6 x 6 to 25 x 25 cm(2) of a Varian Clinac 2300C/D with the corresponding measurements. Dose differences between calculated and measured absolute depth dose curves are reduced from 6% to less than 1.5% for both energies and all applicators considered at SSD of 100 cm. Using the original eMC implementation, absolute dose profiles at depths of 1 cm, d(max) and R50 in water lead to dose differences of up to 8% for applicators larger than 15 x 15 cm(2) at SSD 100 cm. Those differences are now reduced to less than 2% for all dose profiles investigated when the improved version of eMC is used. At SSD of 110 cm the dose difference for the original eMC version is even more pronounced and can be larger than 10%. Those differences are reduced to within 2% or 2 mm with the improved version of eMC. In this work several enhancements were made in the eMC algorithm leading to significant improvements in the accuracy of the dose

A study of the effects of therapeutic doses of ionizing radiation in vitro on Lactobacillus isolates originating from the vagina - a pilot study

OpenAIRE

Gosiewski, Tomasz; Mr?z, Tomasz; Ocho?ska, Dorota; Pabian, Wojciech; Bulanda, Malgorzata; Brzychczy-Wloch, Monika

2016-01-01

Background Ionizing radiation is used as a therapeutic option in the treatment of certain neoplastic lesions located, among others, in the pelvic region. The therapeutic doses of radiation employed often result in adverse effects manifesting themselves primarily in the form of genital tract infections in patients or diarrhea. The data available in the literature indicate disorders in the microbial ecosystem caused by ionizing radiation, which leads to the problems mentioned above. In the pres...

Cosolvent-free polymer gel dosimeters with improved dose sensitivity and resolution for x-ray CT dose response

Energy Technology Data Exchange (ETDEWEB)

Chain, J N M; McAuley, K B [Department of Chemical Engineering, Queen' s University, Kingston, K7L 3N6 (Canada); Jirasek, A [Department of Physics and Astronomy, University of Victoria, Victoria, V8W 3P6 (Canada); Schreiner, L J, E-mail: kim.mcauley@chee.queensu.ca [Cancer Centre of Southeastern Ontario, Kingston, K7L 5P9 (Canada)

2011-04-07

This study reports new N-isopropylacrylamide (NIPAM) polymer gel recipes with increased dose sensitivity and improved dose resolution for x-ray CT readout. NIPAM can be used to increase the solubility of N, N'-methylenebisacrylamide (Bis) in aqueous solutions from approximately 3% to 5.5% by weight, enabling the manufacture of dosimeters containing up to 19.5%T, which is the total concentration of NIPAM and Bis by weight. Gelatin is shown to have a mild influence on dose sensitivity when gels are imaged using x-ray CT, and a stronger influence when gels are imaged optically. Phantoms that contain only 3% gelatin and 5 mM tetrakis hydroxymethyl phosphonium chloride are sufficiently stiff for dosimetry applications. The best cosolvent-free gel formulation has a dose sensitivity in the linear range ({approx}0.88 H Gy{sup -1}) that is a small improvement compared to the best NIPAM-based gels that incorporate isopropanol as a cosolvent ({approx}0.80 H Gy{sup -1}). This new gel formulation results in enhanced dose resolution ({approx}0.052 Gy) for x-ray CT readout, making clinical applications of this imaging modality more feasible.

Cosolvent-free polymer gel dosimeters with improved dose sensitivity and resolution for x-ray CT dose response

International Nuclear Information System (INIS)

Chain, J N M; McAuley, K B; Jirasek, A; Schreiner, L J

2011-01-01

This study reports new N-isopropylacrylamide (NIPAM) polymer gel recipes with increased dose sensitivity and improved dose resolution for x-ray CT readout. NIPAM can be used to increase the solubility of N, N'-methylenebisacrylamide (Bis) in aqueous solutions from approximately 3% to 5.5% by weight, enabling the manufacture of dosimeters containing up to 19.5%T, which is the total concentration of NIPAM and Bis by weight. Gelatin is shown to have a mild influence on dose sensitivity when gels are imaged using x-ray CT, and a stronger influence when gels are imaged optically. Phantoms that contain only 3% gelatin and 5 mM tetrakis hydroxymethyl phosphonium chloride are sufficiently stiff for dosimetry applications. The best cosolvent-free gel formulation has a dose sensitivity in the linear range (∼0.88 H Gy -1 ) that is a small improvement compared to the best NIPAM-based gels that incorporate isopropanol as a cosolvent (∼0.80 H Gy -1 ). This new gel formulation results in enhanced dose resolution (∼0.052 Gy) for x-ray CT readout, making clinical applications of this imaging modality more feasible.

Work management practices that reduce dose and improve efficiency

International Nuclear Information System (INIS)

Miller, D.W.; Hulin, M.

1998-01-01

Work management practices at nuclear power plants can dramatically affect the outcome of annual site dose goals and outage costs. This presentation discusses global work management practices that contribute to dose reduction including work philosophy, work selection, work planning, work scheduling, worker training, work implementation and worker feedback. The presentation is based on a two-year international effort (sponsored by NEA/IAEA ISOE) to study effective work practices that reduce dose. Experts in this area believe that effective work selection and planning practices can substantially reduce occupational dose during refueling outages. For example, some plants represented in the expert group complete refueling outages in 12-18 days (Finland) with doses below 0,90 person-Sv. Other plants typically have 50-75 day outages with substantially higher site doses. The fundamental reasons for longer outages and higher occupational doses are examined. Good work management principles that have a proven track record of reducing occupational dose are summarized. Practical methods to reduce work duration and dose are explained. For example, scheduling at nuclear power plants can be improved by not only sequencing jobs on a time line but also including zone and resource-based considerations to avoid zone congestion and manpower delays. An ongoing, global, benchmarking effort is described which provides current duration and dose information for repetitive jobs to participating utilities world-wide. (author)

Clean focus, dose and CD metrology for CD uniformity improvement

Science.gov (United States)

Lee, Honggoo; Han, Sangjun; Hong, Minhyung; Kim, Seungyoung; Lee, Jieun; Lee, DongYoung; Oh, Eungryong; Choi, Ahlin; Kim, Nakyoon; Robinson, John C.; Mengel, Markus; Pablo, Rovira; Yoo, Sungchul; Getin, Raphael; Choi, Dongsub; Jeon, Sanghuck

2018-03-01

Lithography process control solutions require more exacting capabilities as the semiconductor industry goes forward to the 1x nm node DRAM device manufacturing. In order to continue scaling down the device feature sizes, critical dimension (CD) uniformity requires continuous improvement to meet the required CD error budget. In this study we investigate using optical measurement technology to improve over CD-SEM methods in focus, dose, and CD. One of the key challenges is measuring scanner focus of device patterns. There are focus measurement methods based on specially designed marks on scribe-line, however, one issue of this approach is that it will report focus of scribe line which is potentially different from that of the real device pattern. In addition, scribe-line marks require additional design and troubleshooting steps that add complexity. In this study, we investigated focus measurement directly on the device pattern. Dose control is typically based on using the linear correlation behavior between dose and CD. The noise of CD measurement, based on CD-SEM for example, will not only impact the accuracy, but also will make it difficult to monitor dose signature on product wafers. In this study we will report the direct dose metrology result using an optical metrology system which especially enhances the DUV spectral coverage to improve the signal to noise ratio. CD-SEM is often used to measure CD after the lithography step. This measurement approach has the advantage of easy recipe setup as well as the flexibility to measure critical feature dimensions, however, we observe that CD-SEM metrology has limitations. In this study, we demonstrate within-field CD uniformity improvement through the extraction of clean scanner slit and scan CD behavior by using optical metrology.

Optimal initial dose adjustment of warfarin in orthopedic patients.

Science.gov (United States)

Lenzini, Petra A; Grice, Gloria R; Milligan, Paul E; Gatchel, Susan K; Deych, Elena; Eby, Charles S; Burnett, R Stephen J; Clohisy, John C; Barrack, Robert L; Gage, Brian F

2007-11-01

Warfarin sodium is commonly prescribed for the prophylaxis and treatment of venous thromboembolism. Dosing algorithms have not been widely adopted because they require a fixed initial warfarin dose (eg, 5 mg) and are not tailored to other factors that may affect the international normalized ratio (INR). To develop an algorithm that could predict a therapeutic warfarin dose based on drug interactions, INR response after the initial warfarin doses, and other clinical factors. We used stepwise regression to quantify the relationship between these factors in patients beginning prophylactic warfarin therapy immediately prior to joint replacement. In the derivation cohort (n = 271), we separately modeled the therapeutic dose after 2 and 3 initial doses. We prospectively validated these 2 models in an independent cohort (n = 105). About half of the therapeutic dose variability was predictable after 3 days of therapy: R2 was 53% in the derivation cohort and 42% in the validation cohort. INR response after 3 warfarin doses (INR3) inversely correlated with therapeutic dose (p < 0.001). Intraoperative blood loss transiently, but significantly, elevated the postoperative INR values. Other significant (p < 0.03) predictors were the first and second warfarin doses (+7% and +6%, respectively, per 1 mg), and statin use (-15.0%). The model derived after 2 warfarin doses explained 32% of the variability in therapeutic dose. We developed and validated algorithms that estimate therapeutic warfarin doses based on clinical factors and INR response available after 2-3 days of warfarin therapy. The algorithms are implemented online at www.WarfarinDosing.org.

Stereotactic intracranial radiotherapy: Dose prescription

International Nuclear Information System (INIS)

Schlienger, M.; Lartigau, E.; Nataf, F.; Mornex, F.; Latorzeff, I.; Lisbona, A.; Mahe, M.

2012-01-01

The aim of this article was the study of the successive steps permitting the prescription of dose in stereotactic intracranial radiotherapy, which includes radiosurgery and fractionated stereotactic radiotherapy. The successive steps studied are: the choice of stereotactic intracranial radiotherapy among the therapeutic options, based on curative or palliative treatment intent, then the selection of lesions according to size/volume, pathological type and their number permitting the choice between radiosurgery or fractionated stereotactic radiotherapy, which have the same methodological basis. Clinical experience has determined the level of dose to treat the lesions and limit the irradiation of healthy adjacent tissues and organs at risk structures. The last step is the optimization of the different parameters to obtain a safe compromise between the lesion dose and healthy adjacent structures. Study of dose-volume histograms, coverage indices and 3D imaging permit the optimization of irradiation. For lesions close to or included in a critical area, the prescribed dose is planned using the inverse planing method. Implementation of the successively described steps is mandatory to insure the prescription of an optimized dose. The whole procedure is based on the delineation of the lesion and adjacent healthy tissues. There are sometimes difficulties to assess the delineation and the volume of the target, however improvement of local control rates and reduction of secondary effects are the proof that the totality of the successive procedures are progressively improved. In practice, stereotactic intracranial radiotherapy is a continually improved treatment method, which constantly benefits from improvements in the choice of indications, imaging, techniques of irradiation, planing/optimization methodology and irradiation technique and from data collected from prolonged follow-up. (authors)

Prenatal radiation doses from radiopharmaceuticals

International Nuclear Information System (INIS)

Rojo, A.M.; Gomez Parada, I.M.; Di Trano, J.L.

1998-01-01

The radiopharmaceutical administration with diagnostic or therapeutic purpose during pregnancy implies a prenatal radiation dose. The dose assessment and the evaluation of the radiological risks become relevant due to the great radiosensitivity of the fetal tissues in development. This paper is a revision of the available data for estimating fetal doses in the cases of the more frequently used radiopharmaceuticals in nuclear medicine, taking into account recent investigation in placental crossover. The more frequent diagnostic and therapeutic procedures were analyzed according to the radiation doses implied. (author) [es

Improved preclinical cardiovascular therapeutic indices with long-term inhibition of norepinephrine reuptake using reboxetine

International Nuclear Information System (INIS)

Fossa, Anthony A.; Wisialowski, Todd A.; Cremers, Thomas; Hart, Marieke van der; Tseng, Elaine; Deng, Shibing; Rollema, Hans; Wang, Ellen Q.

2012-01-01

Norepinephrine reuptake inhibitors (NRIs) acutely increase norepinephrine (NE) levels, but therapeutic antidepressant activity is only observed after weeks of treatment because central NE levels progressively increase during continued drug exposure. Similarly, while NRIs acutely increase blood pressure (BP) and heart rate (HR) due to enhanced sympathetic neurotransmission, chronic treatment changes the responsiveness of the central noradrenergic system and suppresses these effects via autonomic regulation. To better understand the relationship between NE increases and cardiovascular safety, we investigated acute and chronic effects of the NRI reboxetine on central NE release and on BP and HR and electrical alternans, a measure of arrhythmia liability, in guinea pigs. NE release was assessed by microdialysis in medial prefrontal cortex (mPFC) and hypothalamic paraventricular nucleus (PVN); BP and HR were measured by telemetry. Animals were treated for 28 days with 15 mg/kg/day of reboxetine or vehicle via an osmotic minipump and then challenged with acute intravenous doses of reboxetine. Animals chronically treated with reboxetine had 2-fold higher extracellular basal NE levels in mPFC and PVN compared to basal levels after chronic vehicle treatment. BP was significantly increased after the first day of treatment, and gradually returned to vehicle levels by day 21. These data indicate that chronic NRI treatment may lead to an increase in central NE levels and a concomitant reduction in BP based on exposure–response curves compared to vehicle treatment, suggesting a larger separation between preclinical estimates of efficacy vs. safety compared to acute NRI treatment. -- Highlights: ► Acute RBX produces blood pressure increases acutely that decrease with chronic RBX ► Chronic RBX increases brain NE levels, a preclinical surrogate of improved efficacy ► Short-term screening of NRI often underestimates the chronic therapeutic index ► Chronic cardiovascular

Improved preclinical cardiovascular therapeutic indices with long-term inhibition of norepinephrine reuptake using reboxetine

Energy Technology Data Exchange (ETDEWEB)

Fossa, Anthony A., E-mail: anthony.fossa@icardiac.com [Department of Global Safety Pharmacology, Department of Pharmacokinetics, Dynamics and Metabolism, and Neuroscience, Pfizer Global Research and Development Eastern Point Road, Groton, CT 06340 (United States); Wisialowski, Todd A. [Department of Global Safety Pharmacology, Department of Pharmacokinetics, Dynamics and Metabolism, and Neuroscience, Pfizer Global Research and Development Eastern Point Road, Groton, CT 06340 (United States); Cremers, Thomas; Hart, Marieke van der [Brains On-Line B.V., University of Groningen, Antonius Deusinglaan 1, 9713 AV Groningen (Netherlands); Tseng, Elaine; Deng, Shibing; Rollema, Hans; Wang, Ellen Q. [Department of Global Safety Pharmacology, Department of Pharmacokinetics, Dynamics and Metabolism, and Neuroscience, Pfizer Global Research and Development Eastern Point Road, Groton, CT 06340 (United States)

2012-11-01

Norepinephrine reuptake inhibitors (NRIs) acutely increase norepinephrine (NE) levels, but therapeutic antidepressant activity is only observed after weeks of treatment because central NE levels progressively increase during continued drug exposure. Similarly, while NRIs acutely increase blood pressure (BP) and heart rate (HR) due to enhanced sympathetic neurotransmission, chronic treatment changes the responsiveness of the central noradrenergic system and suppresses these effects via autonomic regulation. To better understand the relationship between NE increases and cardiovascular safety, we investigated acute and chronic effects of the NRI reboxetine on central NE release and on BP and HR and electrical alternans, a measure of arrhythmia liability, in guinea pigs. NE release was assessed by microdialysis in medial prefrontal cortex (mPFC) and hypothalamic paraventricular nucleus (PVN); BP and HR were measured by telemetry. Animals were treated for 28 days with 15 mg/kg/day of reboxetine or vehicle via an osmotic minipump and then challenged with acute intravenous doses of reboxetine. Animals chronically treated with reboxetine had 2-fold higher extracellular basal NE levels in mPFC and PVN compared to basal levels after chronic vehicle treatment. BP was significantly increased after the first day of treatment, and gradually returned to vehicle levels by day 21. These data indicate that chronic NRI treatment may lead to an increase in central NE levels and a concomitant reduction in BP based on exposure–response curves compared to vehicle treatment, suggesting a larger separation between preclinical estimates of efficacy vs. safety compared to acute NRI treatment. -- Highlights: ► Acute RBX produces blood pressure increases acutely that decrease with chronic RBX ► Chronic RBX increases brain NE levels, a preclinical surrogate of improved efficacy ► Short-term screening of NRI often underestimates the chronic therapeutic index ► Chronic cardiovascular

Interpersonal problems as predictors of therapeutic alliance and symptom improvement in cognitive therapy for depression.

Science.gov (United States)

Renner, Fritz; Jarrett, Robin B; Vittengl, Jeffrey R; Barrett, Marna S; Clark, Lee Anna; Thase, Michael E

2012-05-01

The degree to which interpersonal problems of depressed patients improve over the course of cognitive therapy (CT) and relate to the quality of the therapeutic alliance and to symptom improvement, remains unclear. We analyzed data of adult outpatients (N=523) with major depressive disorder participating in a clinical trial to determine the factor structure of the Inventory of Interpersonal Problems-Circumplex (IIP-C) and to relate the observed factor scores to the quality of the therapeutic alliance and symptom improvement over the course of CT. Patients received 16-20 sessions protocol (50-60 min each) of individual CT according to the treatment manual by Beck et al. (1979). We found a three-factor structure (interpersonal distress, agency, and communion) of interpersonal problems. Interpersonal distress decreased (d=.90), but interpersonal style did not change substantively during CT (communion d=.03; agency d=.14). High initial agency scores related negatively to the therapeutic alliance (β=-.12), whereas high initial communion scores related positively to the therapeutic alliance (β=.15). Elevated pre-treatment interpersonal distress scores were related to both weaker therapeutic alliances (β=.13) and higher symptom levels throughout treatment (β=.10). All patients in this study had recurrent MDD and it is therefore uncertain whether the results would generalize to patients with other psychiatric disorders. This study supports the use of the IIP-C as a comprehensive measure of patients' interpersonal style and interpersonal distress. The IIP-C measured before CT showed some predictive validity with respect to therapeutic alliance measured at the midpoint and therapy outcome. The clinical importance of these findings is discussed. Copyright © 2012 Elsevier B.V. All rights reserved.

Interpersonal problems as predictors of therapeutic alliance and symptom improvement in cognitive therapy for depression

Science.gov (United States)

Renner, Fritz; Jarrett, Robin B.; Vittengl, Jeffrey R.; Barrett, Marna S.; Clark, Lee Anna; Thase, Michael E.

2012-01-01

Background The degree to which interpersonal problems of depressed patients improve over the course of cognitive therapy (CT) and relate to the quality of the therapeutic alliance and to symptom improvement, remain unclear. Methods We analyzed data of adult outpatients (N = 523) with major depressive disorder participating in a clinical trial to determine the factor structure of the Inventory of Interpersonal Problems-Circumplex (IIP-C) and to relate the observed factor scores to the quality of the therapeutic alliance and symptom improvement over the course of CT. Patients received 16–20 sessions protocol (50–60 minutes each) of individual CT according to the treatment manual by Beck et al. (1979). Results We found a three-factor structure (interpersonal distress, agency, and communion) of interpersonal problems. Interpersonal distress decreased (d = .90), but interpersonal style did not change substantively during CT (communion d = .03; agency d = .14). High initial agency scores related negatively to the therapeutic alliance (β = −.12), whereas high initial communion scores related positively to the therapeutic alliance (β = .15). Elevated pre-treatment interpersonal distress scores were related to both weaker therapeutic alliances (β = .13) and higher symptom levels throughout treatment (β = .10). Limitations All patients in this study had recurrent MDD and it is therefore uncertain whether the results would generalize to patients with other psychiatric disorders. Conclusions This study supports the use of the IIP-C as a comprehensive measure of patients' interpersonal style and interpersonal distress. The IIP-C measured before CT showed some predictive validity with respect to therapeutic alliance measured at the midpoint and therapy outcome. The clinical importance of these findings is discussed. PMID:22306232

Pelvic interstitial brachytherapy - improving the therapeutic ratio with magnetic resonance imaging and optimization

International Nuclear Information System (INIS)

Swift, Patrick S.; Hricak, Hedvig; Forstner, Rosemary; Powell, C. Bethan; Purser, Phil; Weaver, Keith; Phillips, Theodore L.

1996-01-01

Introduction Interstitial brachytherapy in the pelvic region is often hampered by the radiation oncologist's inability to precisely differentiate tumor versus normal tissue during the planning and implantation procedures, often resulting in either excessive or incomplete coverage of tumor volume. The marked improvement in pelvic imaging seen with magnetic resonance, in conjunction with isodose optimization programs for remote-afterloading units, has created an opportunity to significantly improve the therapeutic ratio. Methods From 1992-1995, 23 interstitial perineal templates were performed in 22 patients with pelvic malignancies, using the pulsed low-dose-rate Selectron with dose optimization. MR imaging was performed immediately prior to the implant, with a MUPIT placed against the perineum and a vaginal obturator in place. These images were used for tumor volume measurements, determination of the number, depth and angle of needles required for the implant, and identification of position of normal tissues (rectum, small bowel, bladder) relative to the tumor. After implantation of stainless steel needles, orthogonal radiographs were obtained for isodose calculation, and planning carried out with isodose optimization. Patients were followed closely on a routine schedule, until time of last visit or until death. Every effort possible was made to assess local disease status at time of death. Results Sixteen patients with primary disease (14 cervix, 1 vulva, 1 vagina) and 6 with recurrent (2 with prior radiation) were implanted, all but 3 with curative intent. Nine patients with advanced cervix or vulvar cancer received concomitant chemotherapy (5FU + platinum or mitomycin-C) with the external beam therapy. At a median follow-up of 18.1 months for all cases, only three patients have failed locally for an actuarial local control of 85% at 1.5 years. Nine patients are alive and free of disease, 8 are alive with distant disease only (mean follow-up of 19.1 months), 2

Effect of dose increase or cimetidine co-administration on albendazole bioavailability

NARCIS (Netherlands)

Schipper, H. G.; Koopmans, R. P.; Nagy, J.; Butter, J. J.; Kager, P. A.; van Boxtel, C. J.

2000-01-01

The low bioavailability of albendazole affects the therapeutic response in patients with echinococcosis. Cimetidine co-administration is reported to improve bioavailability. To analyze the assumed dose-dependent bioavailability of albendazole, we administered 5 to 30 mg/kg albendazole to 6 male

[Directions for use of corticosteroids and calcineurin inhibitors against generalized myasthenia gravis: therapeutic strategies that can lead to early improvements and veer away from high-dose oral corticosteroids].

Science.gov (United States)

Utsugisawa, Kimiaki; Nagane, Yuriko; Suzuki, Shigeaki; Suzuki, Norihiro

2012-01-01

The advent of effective immune treatment has meant that myasthenia gravis (MG) is most often not lethal. However, many MG patients still find it difficult to maintain daily activities due to chronic residual fatigability and long-term side effects of medication, since full remission without immune treatment is not common. Our analysis demonstrated that disease severity, dose of oral corticosteroids, and depressive state are the major independent factors negatively associated with self-reported QOL (MG-QOL15-J score). It is noteworthy that oral corticosteroid, the first-line agent for MG, is negatively associated with patients' QOL. When the analysis took into account MGFA postintervention status and dose of oral prednisolne (PSL), the MG-QOL15-J score of MM status patients taking ≤ 5 mg PSL per day is identically low (i.e., just as good QOL) as that seen in CSR and is a target of treatment. In order to veer away from high-dose oral corticosteroids and to achieve early MM or better status with PSL ≤ 5 mg/day, we advocate the early aggressive treatment strategy that can achieve early improvement by performing an aggressive therapy using combined treatment with plasmapheresis and high-dose intravenous methylprednisolone and then maintain an improved clinical status using low-dose oral corticosteroids and calcineurin inhibitors (cyclosporine microemulsion and tacrolimus). The early stages of MG are susceptible to treatment with calcineurin inhibitors. When using cyclosporine microemulsion for MG, blood concentrations 2 h after administration (C2) correlate with clinical improvement and immediately before administration (C0) with side effects (increased serum creatinine and/or hypertension). Monitoring of C2 and C0 levels is useful to estimate efficacy and safety of the drug.

Novel high dose rate lip brachytherapy technique to improve dose homogeneity and reduce toxicity by customized mold

International Nuclear Information System (INIS)

Feldman, Jon; Appelbaum, Limor; Sela, Mordechay; Voskoboinik, Ninel; Kadouri, Sarit; Weinberger, Jeffrey; Orion, Itzhak; Meirovitz, Amichay

2014-01-01

The purpose of this study is to describe a novel brachytherapy technique for lip Squamous Cell Carcinoma, utilizing a customized mold with embedded brachytherapy sleeves, which separates the lip from the mandible, and improves dose homogeneity. Seven patients with T2 lip cancer treated with a “sandwich” technique of High Dose Rate (HDR) brachytherapy to the lip, consisting of interstitial catheters and a customized mold with embedded catheters, were reviewed for dosimetry and outcome using 3D planning. Dosimetric comparison was made between the “sandwich” technique to “classic” – interstitial catheters only plan. We compared dose volume histograms for Clinical Tumor Volume (CTV), normal tissue “hot spots” and mandible dose. We are reporting according to the ICRU 58 and calculated the Conformal Index (COIN) to show the advantage of our technique. The seven patients (ages 36–81 years, male) had median follow-up of 47 months. Four patients received Brachytherapy and External Beam Radiation Therapy, 3 patients received brachytherapy alone. All achieved local control, with excellent esthetic and functional results. All patients are disease free. The Customized Mold Sandwich technique (CMS) reduced the high dose region receiving 150% (V150) by an average of 20% (range 1–47%), The low dose region (les then 90% of the prescribed dose) improved by 73% in average by using the CMS technique. The COIN value for the CMS was in average 0.92 as opposed to 0.88 for the interstitial catheter only. All differences (excluding the low dose region) were statistically significant. The CMS technique significantly reduces the high dose volume and increases treatment homogeneity. This may reduce the potential toxicity to the lip and adjacent mandible, and results in excellent tumor control, cosmetic and functionality

Improved Therapeutic Regimens for Treatment of Post-Traumatic Ocular Infections

Science.gov (United States)

2011-05-01

cystoid macular oedema in uveitis . Clin. Exp. Ophthalmol. 29, 2–6 (2001). 36 Campochiaro PA, Lim JI. Aminoglycoside toxicity in the treatment of...TELEPHONE NUMBER (include area code) Standard Form 298 (Rev. 8-98) Prescribed by ANSI Std. Z39.18 Improved Therapeutic Regimens for Treatment of...injury and adequate treatment . This proposal was designed to analyze the effectiveness of antibiotics, anti-inflammatory drugs, and non-conventional

An experimental Toxoplasma gondii dose response challenge model to study therapeutic or vaccine efficacy in cats.

Directory of Open Access Journals (Sweden)

Jan B W J Cornelissen

Full Text Available High numbers of Toxoplasma gondii oocysts in the environment are a risk factor to humans. The environmental contamination might be reduced by vaccinating the definitive host, cats. An experimental challenge model is necessary to quantitatively assess the efficacy of a vaccine or drug treatment. Previous studies have indicated that bradyzoites are highly infectious for cats. To infect cats, tissue cysts were isolated from the brains of mice infected with oocysts of T. gondii M4 strain, and bradyzoites were released by pepsin digestion. Free bradyzoites were counted and graded doses (1000, 100, 50, 10, and 250 intact tissue cysts were inoculated orally into three cats each. Oocysts shed by these five groups of cats were collected from faeces by flotation techniques, counted microscopically and estimated by real time PCR. Additionally, the number of T. gondii in heart, tongue and brains were estimated, and serology for anti T. gondii antibodies was performed. A Beta-Poisson dose-response model was used to estimate the infectivity of single bradyzoites and linear regression was used to determine the relation between inoculated dose and numbers of oocyst shed. We found that real time PCR was more sensitive than microscopic detection of oocysts, and oocysts were detected by PCR in faeces of cats fed 10 bradyzoites but by microscopic examination. Real time PCR may only detect fragments of T. gondii DNA without the presence of oocysts in low doses. Prevalence of tissue cysts of T. gondii in tongue, heart and brains, and anti T. gondii antibody concentrations were all found to depend on the inoculated bradyzoite dose. The combination of the experimental challenge model and the dose response analysis provides a suitable reference for quantifying the potential reduction in human health risk due to a treatment of domestic cats by vaccination or by therapeutic drug application.

Administration of BMSCs with muscone in rats with gentamicin-induced AKI improves their therapeutic efficacy.

Directory of Open Access Journals (Sweden)

Pengfei Liu

Full Text Available The therapeutic action of bone marrow-derived mesenchymal stem cells (BMSCs in acute kidney injury (AKI has been reported by several groups. However, recent studies indicated that BMSCs homed to kidney tissues at very low levels after transplantation. The lack of specific homing of exogenously infused cells limited the effective implementation of BMSC-based therapies. In this study, we provided evidence that the administration of BMSCs combined with muscone in rats with gentamicin-induced AKI intravenously, was a feasible strategy to drive BMSCs to damaged tissues and improve the BMSC-based therapeutic effect. The effect of muscone on BMSC bioactivity was analyzed in vitro and in vivo. The results indicated that muscone could promote BMSC migration and proliferation. Some secretory capacity of BMSC still could be improved in some degree. The BMSC-based therapeutic action was ameliorated by promoting the recovery of biochemical variables in urine or blood, as well as the inhibition of cell apoptosis and inflammation. In addition, the up-regulation of CXCR4 and CXCR7 expression in BMSCs could be the possible mechanism of muscone amelioration. Thus, our study indicated that enhancement of BMSCs bioactivities with muscone could increase the BMSC therapeutic potential and further developed a new therapeutic strategy for the treatment of AKI.

Pharmacogenetics-based warfarin dosing algorithm decreases time to stable anticoagulation and the risk of major hemorrhage: an updated meta-analysis of randomized controlled trials.

Science.gov (United States)

Wang, Zhi-Quan; Zhang, Rui; Zhang, Peng-Pai; Liu, Xiao-Hong; Sun, Jian; Wang, Jun; Feng, Xiang-Fei; Lu, Qiu-Fen; Li, Yi-Gang

2015-04-01

Warfarin is yet the most widely used oral anticoagulant for thromboembolic diseases, despite the recently emerged novel anticoagulants. However, difficulty in maintaining stable dose within the therapeutic range and subsequent serious adverse effects markedly limited its use in clinical practice. Pharmacogenetics-based warfarin dosing algorithm is a recently emerged strategy to predict the initial and maintaining dose of warfarin. However, whether this algorithm is superior over conventional clinically guided dosing algorithm remains controversial. We made a comparison of pharmacogenetics-based versus clinically guided dosing algorithm by an updated meta-analysis. We searched OVID MEDLINE, EMBASE, and the Cochrane Library for relevant citations. The primary outcome was the percentage of time in therapeutic range. The secondary outcomes were time to stable therapeutic dose and the risks of adverse events including all-cause mortality, thromboembolic events, total bleedings, and major bleedings. Eleven randomized controlled trials with 2639 participants were included. Our pooled estimates indicated that pharmacogenetics-based dosing algorithm did not improve percentage of time in therapeutic range [weighted mean difference, 4.26; 95% confidence interval (CI), -0.50 to 9.01; P = 0.08], but it significantly shortened the time to stable therapeutic dose (weighted mean difference, -8.67; 95% CI, -11.86 to -5.49; P pharmacogenetics-based algorithm significantly reduced the risk of major bleedings (odds ratio, 0.48; 95% CI, 0.23 to 0.98; P = 0.04), but it did not reduce the risks of all-cause mortality, total bleedings, or thromboembolic events. Our results suggest that pharmacogenetics-based warfarin dosing algorithm significantly improves the efficiency of International Normalized Ratio correction and reduces the risk of major hemorrhage.

Therapeutic applications of radiopharmaceuticals

International Nuclear Information System (INIS)

Baker, W.J.; Datz, F.L.; Beightol, R.W.

1987-01-01

Whether a radiopharmaceutical has diagnostic or therapeutic application depends on both the isotope and pharmaceutical used. For diagnostic applications, the isotope should undergo only γ-decay, since usually only γ-radiation is detected by nuclear medicine cameras. The half-life should be just long enough to allow the procedure to be performed. In contrast, the isotope needed for therapeutic purposes should have particulate radiation, such as a β-particle (electron), since these are locally absorbed an increase the local radiation dose. γ-Radiation, which penetrates the tissues, produces less radiation dose than do Β-particles. Several references dealing with radioactive decay, particulate interactions, and diagnostic and therapeutic applications of radiopharmaceuticals are available. Radiopharmaceuticals can legally be used only by physicians who are qualified by specific training in the safe handling of radionuclides. The experience and training of these physicians must be approved by the Nuclear Regulatory Commission or Agreement State Agency authorized to license the use of radiopharmaceuticals. A list of all byproduct material and procedures is available in the Code of Federal Regulations. Of the many radiopharmaceuticals available for diagnostic and therapeutic use, only those commonly used are discussed in this chapter

Predicted and observed therapeutic dose exceedances of ionizable pharmaceuticals in fish plasma from urban coastal systems.

Science.gov (United States)

Scott, W Casan; Du, Bowen; Haddad, Samuel P; Breed, Christopher S; Saari, Gavin N; Kelly, Martin; Broach, Linda; Chambliss, C Kevin; Brooks, Bryan W

2016-04-01

Instream flows of the rapidly urbanizing watersheds and estuaries of the Gulf of Mexico in Texas (USA) are increasingly dominated by reclaimed waters. Though ionizable pharmaceuticals have received increasing attention in freshwaters, many research questions remain unanswered, particularly in tidally influenced urban coastal systems, which experience significant spatiotemporal variability in pH that influences bioavailability and bioaccumulation. The authors coupled fish plasma modeling of therapeutic hazard values with field monitoring of water chemistry variability and pharmaceutical occurrence to examine whether therapeutic hazards to fish existed within these urban coastal ecosystems and whether therapeutic hazards differed within and among coastal locations and seasons. Spatial and temporal fluctuations in pH within study sites altered the probability of encountering pharmaceutical hazards to fish. Significant water quality differences were consistently observed among traditional parameters and pharmaceuticals collected from surface and bottom waters, which are rarely sampled during routine surface water quality assessments. The authors then compared modeling predictions of fish plasma concentrations of pharmaceuticals to measured plasma levels from various field-collected fish species. Diphenhydramine and diltiazem were observed in plasma of multiple species, and diltiazem exceeded human therapeutic doses in largemouth bass, catfish, and mullet inhabiting these urban estuaries. Though the present study only examined a small number of target analytes, which represent a microcosm of the exposome of these fish, coastal systems are anticipated to be more strongly influenced by continued urbanization, altered instream flows, and population growth in the future. Unfortunately, aquatic toxicology information for diltiazem and many other pharmaceuticals is not available for marine and estuarine organisms, but such field observations suggest that potential adverse

Fetal absorbed doses by radiopharmaceutical administration

International Nuclear Information System (INIS)

Rojo, Ana M; Gomez Parada, Ines M.; Di Trano, Jose L.

2000-01-01

The radiopharmaceutical administration with diagnostic or therapeutic purpose during pregnancy implies a prenatal radiation dose. The dose assessment and the evaluation of the radiological risks become relevant due to the great radiosensitivity of the fetal tissues in development. This paper is a revision of the available data for estimating fetal doses in the cases of the more frequently used radiopharmaceuticals in nuclear medicine, taking into account recent investigation in placental crossover. The more frequent diagnostic and therapeutic procedures were analyzed according to the radiation doses implied. (author)

WE-AB-303-06: Combining DAO with MV + KV Optimization to Improve Skin Dose Sparing with Real-Time Fluoroscopy

Energy Technology Data Exchange (ETDEWEB)

Grelewicz, Z; Wiersma, R [The University of Chicago, Chicago, IL (United States)

2015-06-15

Purpose: Real-time fluoroscopy may allow for improved patient positioning and tumor tracking, particularly in the treatment of lung tumors. In order to mitigate the effects of the imaging dose, previous studies have demonstrated the effect of including both imaging dose and imaging constraints into the inverse treatment planning object function. That method of combined MV+kV optimization may Result in plans with treatment beams chosen to allow for more gentle imaging beam-on times. Direct-aperture optimization (DAO) is also known to produce treatment plans with fluence maps more conducive to lower beam-on times. Therefore, in this work we demonstrate the feasibility of a combination of DAO and MV+kV optimization for further optimized real-time kV imaging. Methods: Therapeutic and imaging beams were modeled in the EGSnrc Monte Carlo environment, and applied to a patient model for a previously treated lung patient to provide dose influence matrices from DOSXYZnrc. An MV + kV IMRT DAO treatment planning system was developed to compare DAO treatment plans with and without MV+kV optimization. The objective function was optimized using simulated annealing. In order to allow for comparisons between different cases of the stochastically optimized plans, the optimization was repeated twenty times. Results: Across twenty optimizations, combined MV+kV IMRT resulted in an average of 12.8% reduction in peak skin dose. Both non-optimized and MV+kV optimized imaging beams delivered, on average, mean dose of approximately 1 cGy per fraction to the target, with peak doses to target of approximately 6 cGy per fraction. Conclusion: When using DAO, MV+kV optimization is shown to Result in improvements to plan quality in terms of skin dose, when compared to the case of MV optimization with non-optimized kV imaging. The combination of DAO and MV+kV optimization may allow for real-time imaging without excessive imaging dose. Financial support for the work has been provided in part by NIH

Specification of absorbed dose for reporting a therapeutic irradiation

International Nuclear Information System (INIS)

Wambersie, A.; Chassagne, D.

1981-01-01

The problem of dose specification in external beam therapy with photons and electrons has been dealt with in ICRU Report 29 (1978). This problem arises from the fact that the absorbed dose distribution is usually not uniform in the target volume and that for the purpose of treatment reporting a nominal absorbed dose - which will be called target absorbed dose - has to be selected. When comparing the clinical results obtained between radiotherapy centres, the differences in the reported target absorbed doses which can be introduced by differences in the methods of dose specification often are much larger than the differences related to the dosimetric procedures themselves. This shows the importance of the problem. In this paper, some definitions of terms and concepts currently used in radiotherapy are first recalled: tumour volume, target volume, treatment volume, etc. These definitions have been proposed in ICRU Report 29 for photon and electron beams; they can be extended to any kind of irradiation. For external beam therapy with photons and electrons, the target absorbed dose is defined as the absorbed dose at selected point(s) (specification point(s)) having a meaningful relation to the target volume and/or the irradiation beams. Examples are discussed for typical cases. As far as interstitial and intracavitary therapy is concerned, the problem is more complex and no recommendations have so far been made by the ICRU Commission. A major difficulty arises from the sharp dose gradient as a function of the distance to the sources. The particular case of the treatment of cervix carcinoma is considered and some possible methods of specification are discussed: (1) the indication of the sources (in adequate units) and the duration of the application, (2) the absorbed doses at selected reference points (bladder, rectum, bony structures) and (3) the description of the tissue volume (height, width, thickness) encompassed by a given isodose surface (60Gy). (author)

Image guided adaptive brachytherapy with combined intracavitary and interstitial technique improves the therapeutic ratio in locally advanced cervical cancer: Analysis from the retroEMBRACE study

DEFF Research Database (Denmark)

LU, Fokdal; Sturdza, Alina; Mazeron, Renaud

2016-01-01

Background and purpose Image guided adaptive brachytherapy (IGABT) using intracavitary applicators (IC) has led to a significant improvement of local control in locally advanced cervical cancer (LACC). Further improvement has been obtained with combined intracavitary/interstitial (IC/IS) applicat...... IC/IS brachytherapy improves the therapeutic ratio in LACC by enabling a tumour specific dose escalation resulting in significantly higher local control in large tumours without adding treatment related late morbidity.......Background and purpose Image guided adaptive brachytherapy (IGABT) using intracavitary applicators (IC) has led to a significant improvement of local control in locally advanced cervical cancer (LACC). Further improvement has been obtained with combined intracavitary/interstitial (IC....../IS) applicators. The aim of this analysis was to evaluate the impact on local control and late morbidity of application of combined IS/IC brachytherapy in a large multicentre population. Material/methods 610 patients with LACC from the retroEMBRACE study were included. Patients were divided into an IC group (N...

Morphine and clonidine combination therapy improves therapeutic window in mice: synergy in antinociceptive but not in sedative or cardiovascular effects.

Directory of Open Access Journals (Sweden)

Laura S Stone

Full Text Available 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

Therapeutic treatment plan optimization with probability density-based dose prescription

International Nuclear Information System (INIS)

Lian Jun; Cotrutz, Cristian; Xing Lei

2003-01-01

The dose optimization in inverse planning is realized under the guidance of an objective function. The prescription doses in a conventional approach are usually rigid values, defining in most instances an ill-conditioned optimization problem. In this work, we propose a more general dose optimization scheme based on a statistical formalism [Xing et al., Med. Phys. 21, 2348-2358 (1999)]. Instead of a rigid dose, the prescription to a structure is specified by a preference function, which describes the user's preference over other doses in case the most desired dose is not attainable. The variation range of the prescription dose and the shape of the preference function are predesigned by the user based on prior clinical experience. Consequently, during the iterative optimization process, the prescription dose is allowed to deviate, with a certain preference level, from the most desired dose. By not restricting the prescription dose to a fixed value, the optimization problem becomes less ill-defined. The conventional inverse planning algorithm represents a special case of the new formalism. An iterative dose optimization algorithm is used to optimize the system. The performance of the proposed technique is systematically studied using a hypothetical C-shaped tumor with an abutting circular critical structure and a prostate case. It is shown that the final dose distribution can be manipulated flexibly by tuning the shape of the preference function and that using a preference function can lead to optimized dose distributions in accordance with the planner's specification. The proposed framework offers an effective mechanism to formalize the planner's priorities over different possible clinical scenarios and incorporate them into dose optimization. The enhanced control over the final plan may greatly facilitate the IMRT treatment planning process

Five-Week Outcomes From a Dosing Trial of Therapeutic Massage for Chronic Neck Pain

Science.gov (United States)

Sherman, Karen J.; Cook, Andrea J.; Wellman, Robert D.; Hawkes, Rene J.; Kahn, Janet R.; Deyo, Richard A.; Cherkin, Daniel C.

2014-01-01

PURPOSE This trial was designed to evaluate the optimal dose of massage for individuals with chronic neck pain. METHODS We recruited 228 individuals with chronic nonspecific neck pain from an integrated health care system and the general population, and randomized them to 5 groups receiving various doses of massage (a 4-week course consisting of 30-minute visits 2 or 3 times weekly or 60-minute visits 1, 2, or 3 times weekly) or to a single control group (a 4-week period on a wait list). We assessed neck-related dysfunction with the Neck Disability Index (range, 0–50 points) and pain intensity with a numerical rating scale (range, 0–10 points) at baseline and 5 weeks. We used log-linear regression to assess the likelihood of clinically meaningful improvement in neck-related dysfunction (≥5 points on Neck Disability Index) or pain intensity (≥30% improvement) by treatment group. RESULTS After adjustment for baseline age, outcome measures, and imbalanced covariates, 30-minute treatments were not significantly better than the wait list control condition in terms of achieving a clinically meaningful improvement in neck dysfunction or pain, regardless of the frequency of treatments. In contrast, 60-minute treatments 2 and 3 times weekly significantly increased the likelihood of such improvement compared with the control condition in terms of both neck dysfunction (relative risk = 3.41 and 4.98, P = .04 and .005, respectively) and pain intensity (relative risk = 2.30 and 2.73; P = .007 and .001, respectively). CONCLUSIONS After 4 weeks of treatment, we found multiple 60-minute massages per week more effective than fewer or shorter sessions for individuals with chronic neck pain. Clinicians recommending massage and researchers studying this therapy should ensure that patients receive a likely effective dose of treatment. PMID:24615306

Novel approaches to improve the therapeutic index of head and neck radiotherapy: An analysis of data from the PARSPORT randomised phase III trial

International Nuclear Information System (INIS)

Buettner, Florian; Miah, Aisha B.; Gulliford, Sarah L.; Hall, Emma; Harrington, Kevin J.; Webb, Steve; Partridge, Mike; Nutting, Christopher M.

2012-01-01

Purpose: Subjective xerostomia is a common side-effect following radiotherapy for the treatment of head-and-neck cancer. Standard mean dose models previously used to model xerostomia only that partially predict the occurrence of xerostomia. Studies in animal models have suggested that there are regional variations in the radiosensitivity of the parotid glands. In this work we tested the hypothesis that this is also true for the human parotid gland. Methods: We present novel dose–response models explicitly taking the spatial distribution of the radiation dose into account. We considered dose to the submandibular gland and other clinical factors and used a variable-selection algorithm to select the best dose–response model. This methodology was applied to 63 head and neck cancer patients and validated using two independent patient cohorts of 19 and 29 patients, respectively. Results: The predictive accuracy of dose–response models improved significantly when including regional variations of radiosensitivity of the parotid glands compared to standard mean-dose models (p = 0.001, t-test). Beneficial dose-pattern analysis demonstrated the importance of minimising dose to the lateral and cranial component of the human parotid gland in order to avoid xerostomia. Furthermore we found an evidence that surgical removal of the sub-mandibular gland significantly increases the risk of radiation-induced xerostomia. Conclusion: Dose–response models which take the shape of the dose-distribution into account predicted xerostomia significantly better than standard mean-dose models. Our novel model could be used to rank potential treatment plans more reliably according to their therapeutic index and may be useful to generate better treatment plans.

The therapeutic use of I-131 meta-iodobenzylguanidine (MIBG) in neuroblastoma

International Nuclear Information System (INIS)

Hartmann, O.; Lumbroso, J.D.; Lemerle, J.; Schlumberger, M.; Parmentier, C.; Ricard, M.; Aubert, B.; Coornaert, S.; Merlin, L.

1988-01-01

Despite the use of intensified conventional chemotherapy the complete response rate of advanced neuroblastoma remains low. The use of high-dose chemo-radiotherapy followed by bone marrow transplantation (BMT) improved the duration of disease free survival but, even after these high-dose regimens the relapse rate remains high. Metaiodobenzylguanidine (MIBG) labelled with I-131 or I-123 can be used for scintigraphic imaging of neuroblastoma. In order to evaluate the therapeutic role of I-131-MIBG in the treatment of neuroblastoma patients, a phase II study was performed in 12 patients. Results are presented in this paper

Optimization of the therapeutic dose of 131I for thyroid differentiated carcinoma

International Nuclear Information System (INIS)

Lima, Fabiana Farias de

2002-09-01

organs, such as the narrow and gonads, of up to 78.4%.Possible benefits to the institution also include the use of less radioactive material and a reduction in radiation exposures to the staff during the manipulation and administration of the 131 I. To facilitate the calculations of the optimum therapeutic activity of 131 I for individual patients, a simple and fast dose planning program was created (PlanDose). The program has been set up to evaluate thryroid remant ablation, but it can also be used for the calculation of the activity to be administered for treatment of hyperthyroidism. This protocol of calculated optimal patient-specific 131 I. activities allows a better determination of the necessary ablative dose for patients with differentiated carcinoma of the thyroid, and is an example of optimizing the practice of radiation protection. (author)

Is dosing of therapeutic immunoglobulins optimal? – A review of a 3-decade long debate in Europe.

Directory of Open Access Journals (Sweden)

Jacqueline eKerr

2014-12-01

Full Text Available The consumption of immunoglobulins (Ig is increasing due to better recognition of antibody deficiencies, an aging population and new indications. This review aims to examine the various dosing regimens and research developments in the established and in some of the relevant off-label indications in Europe. The background to the current regulatory settings in Europe is provided as a backdrop for the latest developments in primary and secondary immunodeficiencies and in immunomodulatory indications. In these heterogeneous areas, clinical trials encompassing different routes of administration, varying intervals and infusion rates are paving the way towards more individualized therapy regimens.In primary antibody deficiencies adjustments in dosing and intervals will depend on the clinical presentation, effective IgG trough levels and IgG metabolism. Ideally, individual pharmacokinetic profiles in conjunction with the clinical phenotype could lead to highly tailored treatment. In practice, incremental dosage increases are necessary to titrate the optimal dose for more severely ill patients. Higher intravenous doses in these patients also have beneficial immunomodulatory effects beyond mere IgG replacement. Better understanding of the pharmacokinetics of Ig therapy is leading to a move away from simplistic ‘per kg’ dosing.Defective antibody production is common in many secondary immunodeficiencies irrespective of whether the causative factor was lymphoid malignancies (established indications, certain autoimmune disorders, immunosuppressive agents or biologics. This antibody failure, as shown by test immunisation, may be amenable to treatment with replacement Ig therapy. In certain immunomodulatory settings (e.g. ITP selection of patients for Ig therapy may be enhanced by relevant biomarkers in order to exclude non-responders and thus obtain higher response rates. In this review the developments in dosing of therapeutic immunoglobulins have been

Multi-dose drug dispensing as a tool to improve medication adherence: A study in patients using vitamin K antagonists.

Science.gov (United States)

van Rein, Nienke; de Geus, Kristel S; Cannegieter, Suzanne C; Reitsma, Pieter H; van der Meer, Felix J M; Lijfering, Willem M

2018-01-01

Multi-dose drug dispensing (MDD) is a dosing aid that provides patients with disposable bags containing all drugs intended for 1 dosing moment. MDD is believed to increase medication adherence, but studies are based on self-reported data, and results may depend on socially desirable answers. Therefore, our purpose was to determine the effect of MDD on medication adherence in non-adherent patients taking vitamin K antagonists (VKAs), and to compare with instructing patients on medication use. We conducted a before-after study in non-adherent patients where MDD was the exposure and change in adherence after MDD initiation was the outcome (within patient comparison). Time in therapeutic range (TTR) was selected as a measure for adherence, as this reflects stability of VKA treatment. To analyze whether MDD improved adherence as compared with standard care (ie, letters or calls from nurses of the anticoagulation clinic), non-adherent patients without MDD were also followed to estimate their TTR change over time (between patient comparison). Eighty-three non-adherent VKA patients started using MDD. The median TTR was 63% before MDD and 73% 6 months after MDD. The within patient TTR increased on average by 13% (95%CI 6% to 21%) within 1 month after starting MDD and remained stable during the next 5 months. The TTR of MDD-patients increased 10% (95%CI 2% to 19%) higher as compared with non-MDD patients within 1 month but was similar after 4 months (TTR difference 3%, 95%CI -2% to 9%). Adherence improved after initiation of MDD. Compared with instructing patients, MDD was associated with better adherence within 1 month but was associated with similar improvement after 4 months. Copyright © 2017 John Wiley & Sons, Ltd.

Clinical Strategy for Optimal Traditional Chinese Medicine (TCM) Herbal Dose Selection in Disease Therapeutics: Expert Consensus on Classic TCM Herbal Formula Dose Conversion.

Science.gov (United States)

Zha, Lin-Hua; He, Li-Sha; Lian, Feng-Mei; Zhen, Zhong; Ji, Hang-Yu; Xu, Li-Peng; Tong, Xiao-Lin

2015-01-01

The clinical therapeutics of traditional Chinese medicine (TCM) constitutes a complicated process which involves theory, diagnosis, and formula prescription with specific herbal dosage. Zhang Zhong-Jing's classic work, Treatise on Febrile and Miscellaneous Diseases, has been influencing TCM practice for almost 2000 years. However, during this extended period of time in Chinese history, the Chinese weight measurement system experienced noticeable changes. This change in the weight measurement system inevitably, and perhaps even negatively, affected TCM herbal dosage determination and treatment outcome. Thus, in modern society, a full understanding of the accuracy of herbal dose selection has a critical importance in the TCM daily practice of delivering the best treatment to the patients suffering from different illnesses. In the 973 Project of the Chinese National Basic Research Program, expert consensus on classic TCM formula dose conversion has been reached based on extensive literature review and discussion on the dose-effect relationship of classic TCM formulas. One "liang" in classic TCM formulas is equivalent to 13.8 g. However, based on many TCM basic and clinical studies of variable herbal formula prescriptions and herbal drug preparations, the rule of one liang equals 13.8 g should be adjusted according to different disease conditions. Recommended by the committee on TCM formula dose-effect relationship of the China Association of Chinese Medicine and the World Federation of Chinese Medicine Societies, the following expert consensus has been reached: (i) One liang converts to 6-9 g for the severely and critically ill patients. (ii) One liang converts to 3-6 g for the patients suffering from chronic diseases. (iii) One liang converts to 1-3 g in preventive medicine. The above conversions should be used as a future TCM practice guideline. Using this recommended guideline should enhance the effectiveness of daily TCM practice.

Population pharmacokinetics of piperacillin in the early phase of septic shock: does standard dosing result in therapeutic plasma concentrations?

Science.gov (United States)

Öbrink-Hansen, Kristina; Juul, Rasmus Vestergaard; Storgaard, Merete; Thomsen, Marianne Kragh; Hardlei, Tore Forsingdal; Brock, Birgitte; Kreilgaard, Mads; Gjedsted, Jakob

2015-11-01

Antibiotic dosing in septic shock patients poses a challenge for clinicians due to the pharmacokinetic (PK) variability seen in this patient population. Piperacillin-tazobactam is often used for empirical treatment, and initial appropriate dosing is crucial for reducing mortality. Accordingly, we determined the pharmacokinetic profile of piperacillin (4 g) every 8 h, during the third consecutive dosing interval, in 15 patients treated empirically for septic shock. We developed a population pharmacokinetic model to assess empirical dosing and to simulate alternative dosing regimens and modes of administration. Time above the MIC (T>MIC) predicted for each patient was evaluated against clinical breakpoint MIC for Pseudomonas aeruginosa (16 mg/liter). Pharmacokinetic-pharmacodynamic (PK/PD) targets evaluated were 50% fT>4×MIC and 100% fT>MIC. A population PK model was developed using NONMEM, and data were best described by a two-compartment model. Central and intercompartmental clearances were 3.6 liters/h (relative standard error [RSE], 15.7%) and 6.58 liters/h (RSE, 16.4%), respectively, and central and peripheral volumes were 7.3 liters (RSE, 11.8%) and 3.9 liters (RSE, 9.7%), respectively. Piperacillin plasma concentrations varied considerably between patients and were associated with levels of plasma creatinine. Patients with impaired renal function were more likely to achieve predefined PK/PD targets than were patients with preserved or augmented renal function. Simulations of alternative dosing regimens showed that frequent intermittent bolus dosing as well as dosing by extended and continuous infusion increases the probability of attaining therapeutic plasma concentrations. For septic shock patients with preserved or augmented renal function, dose increment or prolonged infusion of the drug needs to be considered. (This study has been registered at ClinicalTrials.gov under registration no. NCT02306928.). Copyright © 2015, American Society for Microbiology

An improved analytical model for CT dose simulation with a new look at the theory of CT dose

International Nuclear Information System (INIS)

Dixon, Robert L.; Munley, Michael T.; Bayram, Ersin

2005-01-01

Gagne [Med. Phys. 16, 29-37 (1989)] has previously described a model for predicting the sensitivity and dose profiles in the slice-width (z) direction for CT scanners. The model, developed prior to the advent of multidetector CT scanners, is still widely used; however, it does not account for the effect of anode tilt on the penumbra or include the heel effect, both of which are increasingly important for the wider beams (up to 40 mm) of contemporary, multidetector scanners. Additionally, it applied only on (or near) the axis of rotation, and did not incorporate the photon energy spectrum. The improved model described herein transcends all of the aforementioned limitations of the Gagne model, including extension to the peripheral phantom axes. Comparison of simulated and measured dose data provides experimental validation of the model, including verification of the superior match to the penumbra provided by the tilted-anode model, as well as the observable effects on the cumulative dose distribution. The initial motivation for the model was to simulate the quasiperiodic dose distribution on the peripheral, phantom axes resulting from a helical scan series in order to facilitate the implementation of an improved method of CT dose measurement utilizing a short ion chamber, as proposed by Dixon [Med. Phys. 30, 1272-1280 (2003)]. A more detailed set of guidelines for implementing such measurements is also presented in this paper. In addition, some fundamental principles governing CT dose which have not previously been clearly enunciated follow from the model, and a fundamental (energy-based) quantity dubbed 'CTDI-aperture' is introduced

Low-dose radiation potentiates the therapeutic efficacy of folate receptor-targeted hapten therapy.

Science.gov (United States)

Sega, Emanuela I; Lu, Yingjuan; Ringor, Michael; Leamon, Christopher P; Low, Philip S

2008-06-01

Human cancers frequently overexpress a high-affinity cell-surface receptor for the vitamin folic acid. Highly immunogenic haptens can be targeted to folate receptor-expressing cell surfaces by administration of folate-hapten conjugates, rendering the decorated tumor cell surfaces more recognizable by the immune system. Treatment of antihapten-immunized mice with folate-hapten constructs results in elimination of moderately sized tumors by the immune system. However, when subcutaneous tumors exceed 300 mm(3) before initiation of therapy, antitumor activity is significantly decreased. In an effort to enhance the efficacy of folate-targeted hapten immunotherapy (FTHI) against large tumors, we explored the combination of targeted hapten immunotherapy with low-dose radiotherapy. Mice bearing 300-mm(3) subcutaneous tumors were treated concurrently with FTHI (500 nmol/kg of folate conjugated to fluorescein isothiocyanate, 20,000 U/dose of interleukin 2, and 25,000 U/dose of interferon alpha) and low-dose radiotherapy (3 Gy/dose focused directly on the desired tumor mass). The efficacy of therapy was evaluated by measuring tumor volume. Tumor growth analyses show that radiotherapy synergizes with FTHI in antihapten-immunized mice, thereby allowing for cures of animals bearing tumors greater than 300 mm(3). More importantly, nonirradiated distal tumor masses in animals containing locally irradiated tumors also showed improved response to hapten immunotherapy, suggesting that not all tumor lesions must be identified and irradiated to benefit from the combination therapy. These results suggest that simultaneous treatment with FTHI and radiation therapy can enhance systemic antitumor activity in tumor-bearing mice.

Low-Dose Radiation Potentiates the Therapeutic Efficacy of Folate Receptor-Targeted Hapten Therapy

International Nuclear Information System (INIS)

Sega, Emanuela I.; Lu Yingjuan; Ringor, Michael; Leamon, Christopher P.; Low, Philip S.

2008-01-01

Purpose: Human cancers frequently overexpress a high-affinity cell-surface receptor for the vitamin folic acid. Highly immunogenic haptens can be targeted to folate receptor-expressing cell surfaces by administration of folate-hapten conjugates, rendering the decorated tumor cell surfaces more recognizable by the immune system. Treatment of antihapten-immunized mice with folate-hapten constructs results in elimination of moderately sized tumors by the immune system. However, when subcutaneous tumors exceed 300 mm 3 before initiation of therapy, antitumor activity is significantly decreased. In an effort to enhance the efficacy of folate-targeted hapten immunotherapy (FTHI) against large tumors, we explored the combination of targeted hapten immunotherapy with low-dose radiotherapy. Methods and Materials: Mice bearing 300-mm 3 subcutaneous tumors were treated concurrently with FTHI (500 nmol/kg of folate conjugated to fluorescein isothiocyanate, 20,000 U/dose of interleukin 2, and 25,000 U/dose of interferon α) and low-dose radiotherapy (3 Gy/dose focused directly on the desired tumor mass). The efficacy of therapy was evaluated by measuring tumor volume. Results: Tumor growth analyses show that radiotherapy synergizes with FTHI in antihapten-immunized mice, thereby allowing for cures of animals bearing tumors greater than 300 mm 3 . More importantly, nonirradiated distal tumor masses in animals containing locally irradiated tumors also showed improved response to hapten immunotherapy, suggesting that not all tumor lesions must be identified and irradiated to benefit from the combination therapy. Conclusions: These results suggest that simultaneous treatment with FTHI and radiation therapy can enhance systemic antitumor activity in tumor-bearing mice

An Approach to Optimise Therapeutic Vancomycin Dosage in a Haemodialysis Population

LENUS (Irish Health Repository)

Gunning, H

2016-10-01

Haemodialysis patients are at risk of gram-positive bacteraemia and commonly require intravenous vancomycin. Intravenously administered vancomycin is primarily excreted by the kidney and exhibits complex pharmacokinetics in haemodialysis patients; achieving therapeutic levels can be challenging. An audit in our unit showed current practises of vancomycin administration resulted in a high proportion of sub-therapeutic levels. A new protocol was developed with fixed weight-based loading and subsequent dosing guided by pre-dialysis levels, target levels were 10-20mg\\/L. Its effectiveness was prospectively evaluated between 24th September 2012, and 8th February 2013. During this period 25 patients commenced vancomycin, 15 were included. In total, 112 vancomycin levels were taken, 94 (84%) were therapeutic, this was a significant improvement compared to previous practise (odds ratio 5.4, CI 3.1-9.4, p < 0.0001). In conclusion, our study shows this protocol can consistently and reliably achieve therapeutic vancomycin levels

Weathering the storm: Improving therapeutic interventions for cytokine storm syndromes by targeting disease pathogenesis.

Science.gov (United States)

Weaver, Lehn K; Behrens, Edward M

2017-03-01

Cytokine storm syndromes require rapid diagnosis and treatment to limit the morbidity and mortality caused by the hyperinflammatory state that characterizes these devastating conditions. Herein, we discuss the current knowledge that guides our therapeutic decision-making and personalization of treatment for patients with cytokine storm syndromes. Firstly, ICU-level supportive care is often required to stabilize patients with fulminant disease while additional diagnostic evaluations proceed to determine the underlying cause of cytokine storm. Pharmacologic interventions should be focused on removing the inciting trigger of inflammation and initiation of an individualized immunosuppressive regimen when immune activation is central to the underlying disease pathophysiology. Monitoring for a clinical response is required to ensure that changes in the therapeutic regimen can be made as clinically warranted. Escalation of immunosuppression may be required if patients respond poorly to the initial therapeutic interventions, while a slow wean of immunosuppression in patients who improve can limit medication-related toxicities. In certain scenarios, a decision must be made whether an individual patient requires hematopoietic cell transplantation to prevent recurrence of disease. Despite these interventions, significant morbidity and mortality remains for cytokine storm patients. Therefore, we use this review to propose a clinical schema to guide current and future attempts to design rational therapeutic interventions for patients suffering from these devastating conditions, which we believe speeds the diagnosis of disease, limits medication-related toxicities, and improves clinical outcomes by targeting the heterogeneous and dynamic mechanisms driving disease in each individual patient.

Diagnostic and therapeutic radiation exposure

Energy Technology Data Exchange (ETDEWEB)

Russell, W J [Radiation Effects Research Foundation, Hiroshima (Japan)

1975-09-01

Diagnostic and therapeutic radiology were studied as possible contaminants in the evaluations of A-bomb survivors in the ABCC-JNIH Adult Health Study for radiation effects. Hiroshima and Nagasaki subjects received X-ray examinations elsewhere within three months of their ABCC visits at rates of 23 and 12%, respectively. Medical X-ray examinations were more frequent among survivors than comparison subjects. Hiroshima and Nagasaki radiologic practice steadily increased since 1948, and differed markedly by city. From 1946-70 the Hiroshima and Nagasaki X-ray bone marrow doses were 2,300 and 1,000 g-rads, respectively. By 1970, cumulated medical X-ray doses approximated A-bomb doses at distances from the hypocenters of 2,000 m in Hiroshima and 2,800 m in Nagasaki. ABCC X-ray examination doses per subject are routinely updated for comparison with A-bomb doses. Each subject's reported fluoroscopy, photofluorography and radiation therapy exposure elsewhere are for future reference. Dental radiography, though increasing, was not currently an important contributor to survivors' overall exposure. Radiation therapy exposures of 137 subjects were confirmed, and doses estimated for most. Two-thirds the treatments were for malignancies; therapy differed markedly by city; and five cancers possibly arose from earlier radiation therapy. This underscores the importance of considering diagnostic and therapeutic radiology when attributing diseases to the atomic bombs.

Implementation of the systems approach to improve a pharmacist-managed vancomycin dosing service.

Science.gov (United States)

Gagnon, David J; Roberts, Russel; Sylvia, Lynne

2014-12-01

Quality improvements achieved by applying the systems approach to assess the clinical effectiveness, operational efficiency, and financial feasibility of a pharmacist-managed vancomycin dosing service are described. Faced with increased patient volumes and resource demands, the pharmacy department at Tufts Medical Center conducted an evaluation of its adult inpatient vancomycin dosing service using the systems approach, which emphasizes multidisciplinary assessment of system inputs, processes, and outcomes and consensus-building methods to identify needed changes and recommended action steps. A multidisciplinary committee composed of representatives of the medical center's pharmacy, internal medicine, infectious diseases, nursing, phlebotomy, and clinical laboratory services was assembled; in a series of three moderated monthly sessions, committee members deliberated and ultimately reached consensus on a list of action items. Relative to a concurrent intradepartmental assessment of the vancomycin dosing service based solely on pharmacist feedback, the systems approach identified a greater number and wider array of needed improvements in key program areas. Quality improvements implemented as a direct result of the systems-based analysis included a policy change authorizing pharmacists to order serum vancomycin determinations without physician cosignature and inclusion of a vancomycin dosing algorithm in the institutional antibiotic dosing guide. Future changes based on deliverable action items will result in a structured process to help direct program resources toward the patients most in need of pharmacist-managed vancomycin dosing services. The systems approach allowed for a comprehensive multidisciplinary evaluation of the service, as indicated by the identification of process improvements not identified by the department of pharmacy alone. Copyright © 2014 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

Therapeutic drug monitoring of aminoglycosides in neonates

NARCIS (Netherlands)

Touw, Daniël J; Westerman, Elsbeth M; Sprij, Arwen J

2009-01-01

The efficacy and toxicity of aminoglycosides show a strong direct positive relationship with blood drug concentrations, therefore, therapy with aminoglycosides in adults is usually guided by therapeutic drug monitoring. Dosing regimens in adults have evolved from multiple daily dosing to

Study on the therapeutic effect of small dose of estradiol and progesterone on post-menopausal osteoporosis

International Nuclear Information System (INIS)

Li Wenqi; Li Xin; Zhou Jiwen; Zhou Zhengli

2004-01-01

Objective: To explore the therapeutic effect and possible adverse side-effects of small dose of estradiol and progesterone on postmenopausal osteoporosis. Methods: Applying a GBD-928 mono-photon BMD radiometer, 68 women (past-menopausal over 3 years, age 52-59, body weight index 2 0.5 mg with MPA (medroxyprogesterone acetate) 0.5 mg daily. The medication laster for a whole years and BMD value was measured again. All subjects underwent gynecological physical examination, vaginal sonography, vaginal smear study and breast examination with infra-red ray both before and after the test period. Results: After one year medication, mean value of BMD in Group A was 0.49 ± 0.05, three percentage points higher than before. In Group B, this was 0.52 ± 0.06, another three percentage points higher. Ten Women with mild lobular hyperplasia and nine women with small uterine myoma ( 3 ) were all allocated to the hormone treated group. The lesions showed either little change or slight regression after the test period. Conclusion: Osteoporotic women receiving additional small doses of female hormones responded much better than those receiving calcium only. The WHI report which advised against HRT should be more critically studied

Therapeutic dosage assessment based on population pharmacokinetics of a novel single-dose transdermal donepezil patch in healthy volunteers.

Science.gov (United States)

Choi, Hee Youn; Kim, Yo Han; Hong, Donghyun; Kim, Seong Su; Bae, Kyun-Seop; Lim, Hyeong-Seok

2015-08-01

We performed population pharmacokinetic (PK) analysis of a novel transdermal donepezil patch in healthy subjects who participated in a phase I trial. We also studied the optimal dosage regimen with repeated patch application for achieving a therapeutic range using a PK simulation model. This study used data from a randomized, single-dose escalation phase I clinical trial conducted in Korea. The population PK analysis was performed using NONMEM software, version 7.3. From the final PK model, we simulated repeat patch application results assuming various transdermal absorption rates. Based on the clinical trial data, novel donepezil patches with doses of 43.75 mg/12.5 cm(2), 87.5 mg/25 cm(2), and 175 mg/50 cm(2) were placed on each subject. A linear one-compartment, first-order elimination with sequential zero- and first-order absorption model best described the donepezil plasma concentrations after patch application. Simulated results on the basis of the PK model showed that repeat application of the patches of 87.5 mg/25 cm(2) and 175 mg/50 cm(2) every 72 h would cover the therapeutic range of donepezil and reach steady-state faster with fewer fluctuations in concentration compared to typical oral administrations. A linear one-compartment with sequential zero- and first-order absorption model was effective for describing the PKs of donepezil after application of patch. Based on this analysis, 87.5 mg/25 cm(2) or 175 mg/50 cm(2) patch application every 72 h is expected to achieve the desired plasma concentration of donepezil.

Ozone dosing alters the biological potential and therapeutic outcomes of plasma rich in growth factors.

Science.gov (United States)

Anitua, E; Zalduendo, M M; Troya, M; Orive, G

2015-04-01

Until now, ozone has been used in a rather empirical way. This in-vitro study investigates, for the first time, whether different ozone treatments of plasma rich in growth factors (PRGF) alter the biological properties and outcomes of this autologous platelet-rich plasma. Human plasma rich in growth factors was treated with ozone using one of the following protocols: a continuous-flow method; or a syringe method in which constant volumes of ozone and PRGF were mixed. In both cases, ozone was added before, during and after the addition of calcium chloride. Three ozone concentrations, of the therapeutic range 20, 40 and 80 μg/mL, were tested. Fibrin clot properties, growth factor content and the proliferative effect on primary osteoblasts and gingival fibroblasts were evaluated. Ozone treatment of PRGF using the continuous flow protocol impaired formation of the fibrin scaffold, drastically reduced the levels of growth factors and significantly decreased the proliferative potential of PRGF on primary osteoblasts and gingival fibroblasts. In contrast, treatment of PRGF with ozone using the syringe method, before, during and after the coagulation process, did not alter the biological outcomes of the autologous therapy. These findings suggest that ozone dose and the way that ozone combines with PRGF may alter the biological potential and therapeutic outcomes of PRGF. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Single-dose radiosurgical treatment for hepatic metastases - therapeutic outcome of 138 treated lesions from a single institution

International Nuclear Information System (INIS)

Habermehl, Daniel; Herfarth, Klaus K; Bermejo, Justo Lorenzo; Hof, Holger; Rieken, Stefan; Kuhn, Sabine; Welzel, Thomas; Debus, Jürgen; Combs, Stephanie E

2013-01-01

Local ablative therapies such as stereotactically guided single-dose radiotherapy or helical intensity-modulated radiotherapy (tomotherapy) with high single-doses are successfully applied in many centers in patients with liver metastasis not suitable for surgical resection. This study presents results from more than 10 years of clinical experience and evaluates long-term outcome and efficacy of this therapeutic approach. From 1997 to 2009 a total of 138 intrahepatic tumors of 90 patients were irradiated with single doses of 17 to 30 Gy (median dose 24 Gy). Median age of the patients was 64 years (range 31–89 years). Most frequent underlying tumor histologies were colorectal adenocarcinoma (70 lesions) and breast cancer (27 lesions). In 35 treatment sessions multiple targets were simultaneously irradiated (up to four lesions at once). Local progression-free (PFS) and overall survival (OS) after treatment were investigated using uni- and multiple survival regression models. Median overall survival of all patients was 24.3 months. Local PFS was 87%, 70% and 59% after 6, 12 and 18 months, respectively. Median time to local progression was 25.5 months. Patients with a single lesion and no further metastases at time of RT had a favorable median PFS of 43.1 months according to the Kaplan-Meier estimator. The type of tumor showed a statistical significant influence on local PFS, with a better prognosis for breast cancer histology than for colorectal carcinoma in uni- and multiple regression analysis (p = 0.05). Multiple regression analysis revealed no influence of planning target volume (PTV), patient age and radiation dose on local PFS. Treatment was well tolerated with no severe adverse events. This study confirms safety of SBRT in liver lesions, with 6- and 12 months local control of 87% and 70%. The dataset represents the clinical situation in a large oncology setting, with many competing treatment options and heterogeneous patient characteristics

Improving dose homogeneity in routine head and neck radiotherapy with custom 3-D compensation

International Nuclear Information System (INIS)

Harari, P.M.; Sharda, N.N.; Brock, L.K.; Paliwal, B.R.

1998-01-01

Background and purpose: Anatomic contour irregularity and tissue inhomogeneity can lead to significant radiation dose variation across the complex treatment volumes found in the head and neck (HandN) region. This dose inhomogeneity can routinely create focal hot or cold spots of 10-20% despite beam shaping with blocks or beam modification with wedges. Since 1992, we have implemented the routine use of 3-D custom tissue compensators fabricated directly from CT scan contour data obtained in the treatment position in order to improve dose uniformity in patients with tumors of the HandN. Materials and methods: Between July 1992 and January 1997, 160 patients receiving comprehensive HandN radiotherapy had 3-D custom compensators fabricated for their treatment course. Detailed dosimetric records have been analyzed for 30 cases. Dose uniformity across the treatment volume and clinically relevant maximum doses to selected anatomic sub-sites were examined with custom-compensated, uncompensated and optimally-wedged plans. Results: The use of 3-D custom compensators resulted in an average reduction of dose variance across the treatment volume from 19±4% for the uncompensated plans to 5±2% with the use of 3-D compensators. Optimally-wedged plans were variable, but on average a 10±3% dose variance was noted. For comprehensive HandN treatment which encompassed the larynx within the primary field design, the peak doses delivered were reduced by 5-15% with 3-D custom compensation as compared to optimal wedging. Conclusions: The use of 3-D custom tissue compensation can improve dose homogeneity within the treatment volume for HandN cancer patients. Maximum doses to clinically important structures which often receive greater than 105-110% of the prescribed dose are routinely reduced with the use of 3-D custom compensators. Improved dose uniformity across the treatment volume can reduce normal tissue complication profiles and potentially allow for delivery of higher total doses in

Improving dose homogeneity in head and neck radiotherapy with custom 3-D compensation

International Nuclear Information System (INIS)

Brock, Linda K.; Harari, Paul M.; Sharda, Navneet N.; Paliwal, Bhudatt R.; Kinsella, Timothy J.

1996-01-01

Purpose/Objective: Anatomic contour irregularities and tissue inhomogeneities can lead to significant radiation dose variation across complex treatment volumes. Such dose non-uniformity occurs routinely in radiation of the head and neck (H and N) despite beam shaping with blocks or beam modification with wedges. Small dose variations are amplified by the high total doses delivered (often >70 Gy) which can thereby influence late normal tissue complications as well as tumor control. We have therefore implemented the routine use of 3-D custom tissue compensators for our H and N cancer patients fabricated directly from CT scan contour data obtained in the treatment position. The capacity of such compensators to improve dose uniformity in patients with tumors of the H and N is herein reported. Materials and Methods: Between July 1992 and March 1995, 80 patients receiving H and N radiotherapy had 3-D custom compensators fabricated for their treatment course. Detailed dosimetric records have been reviewed for thirty cases to date (60 custom compensators). Dose uniformity across the treatment volume, peak dose delivery and maximum doses to selected, clinically relevant, anatomic subsites were analyzed and compared with uncompensated and wedged plans. Dose-volume histograms were generated and volumes receiving greater than 5% and 10% of the prescribed dose noted. Phantom dose measurements were performed for compensated fields using a water chamber and were compared to calculated doses in order to evaluate the accuracy of isodoses generated by the Theraplan treatment planning system. Accuracy of the fabrication and positioning of the custom compensators was verified by direct measurement. Results: Custom compensators resulted in an average reduction of dose variance across the treatment volume from 13.8% (7-20%) for the uncompensated plans to 4.5% (2-7%) with the compensators. Wedged plans were variable but on average an 8% (3-15%) dose variance was noted. Maximum doses

[Dose rate-dependent cellular and molecular effects of ionizing radiation].

Science.gov (United States)

Przybyszewski, Waldemar M; Wideł, Maria; Szurko, Agnieszka; Maniakowski, Zbigniew

2008-09-11

The aim of radiation therapy is to kill tumor cells while minimizing damage to normal cells. The ultimate effect of radiation can be apoptotic or necrotic cell death as well as cytogenetic damage resulting in genetic instability and/or cell death. The destructive effects of radiation arise from direct and indirect ionization events leading to peroxidation of macromolecules, especially those present in lipid-rich membrane structures as well as chromatin lipids. Lipid peroxidative end-products may damage DNA and proteins. A characteristic feature of radiation-induced peroxidation is an inverse dose-rate effect (IDRE), defined as an increase in the degree of oxidation(at constant absorbed dose) accompanying a lower dose rate. On the other hand, a low dose rate can lead to the accumulation of cells in G2, the radiosensitive phase of the cell cycle since cell cycle control points are not sensitive to low dose rates. Radiation dose rate may potentially be the main factor improving radiotherapy efficacy as well as affecting the intensity of normal tissue and whole-body side effects. A better understanding of dose rate-dependent biological effects may lead to improved therapeutic intervention and limit normal tissue reaction. The study reviews basic biological effects that depend on the dose rate of ionizing radiation.

Tumour alpha/beta ratios and dose-rate selection in brachytherapy

International Nuclear Information System (INIS)

Duchesne, G.M.

2003-01-01

Traditionally brachytherapy employed low dose rate (LDR) techniques. Recent adoption of high dose rate (HDR) applications, addressing radiation protection concerns, has sparked debate over possible reductions in therapeutic ratio. The radiobiological characteristics of two contrasting examples, prostate cancer and cervical cancer, are examined. Both in-vitro and clinical observations of prostate cancer suggest a low α/β ratio. Labelling indices are below 2.5%, translating into long potential doubling times (Tpot ) of 16 to 61 days or more. Clinical PSA doubling times are in the order of years. Analysis of clinical endpoints in prostate cancer treated with either LDR or HDR techniques indicates that its α/β ratio may lie between 1 - 4 Gy, similar to slowly proliferating late reacting tissues. As such, therapeutic gain may arise from the use of hypofractionated HDR treatments, exploiting the sensitivity to large fraction sizes, effectively escalating dose. The slow proliferative rate also gives credence to the use of LDR, although several tumour doublings may occur during the effective treatment time, and analysis of the clinical data using a low α/β ratio suggests that LDR doses are only equivalent to 70 Gy with conventional fractionation. Cervical carcinoma is a rapidly proliferating tumour with Tpot values of 3-6 days. LDR implants were delivered over relatively short treatment times, negating repopulation effects, and the 'hyperfractionation' effect of LDR was suited to the high α/β ratio. HDR, although also preventing significant repopulation, has the potential to decrease the therapeutic ratio if low α/β , late-reacting tissues are not protected. Clinical data however show improved outcomes and reduced morbidity with HDR through reduced doses to normal tissues. Choosing the optimal dose rate in brachytherapy depends on tumour behaviour and achievable accuracy. HDR offers some advantages even for high α/β ratio tumours, and may be the technique of

The potential influence of cell protectors for dose escalation in cancer therapy: an analysis of amifostine

International Nuclear Information System (INIS)

McCumber, Linda M.

2004-01-01

The attempt to increase the therapeutic ratio in an effort to improve survival or quality of life is the goal of modern cancer therapy. It is commonly accepted that local and systemic tumor control would increase if the dose intensity of antineoplastic drugs, radiation therapy, or the combination were increased. Radiation dose escalation using intensity-modulated radiation therapy (IMRT), accelerated or hypofractionated radiation schemes, and multidrug chemotherapy regimens are being used to try to increase tumor kill while inflicting minimal injury to normal tissue. Modern chemoradiation techniques have led to improved local regional control and increased cure rates, but the potentially severe and debilitating adverse effects of the therapies prevent them from reaching the ultimate goal of curing the disease while leaving the patient with a good quality of life. Cell protectants such as amifostine function by reducing the effects of therapy on normal cells while maintaining tumor sensitivity to the therapy. In various studies, amifostine has been analyzed and appears to be a potentially powerful adjuvant to current cancer therapy. Administering amifostine may allow dose escalation with less or equal risk to surrounding normal tissues. This could improve therapeutic efficacy, survival, and quality of life for cancer patients

166Ho-HA evaluation as therapeutic agent for rheumatoid arthritis treatment

International Nuclear Information System (INIS)

Chandia, M.C.; Errazu, X.C.; Pinto, L.N.; Godoy, N.O.; Avila, M.J.; Mendoza, P.; Mendoza, J.; Jofre, J.; Sirraalta, P.

2002-01-01

Aim: Rheumatoid arthritis is a limiting disease having, among its pathological features, the inflammation of synovial tissue with progressive and later destruction of the articulation. This leads to joint deformation and loss of its function, generating pain and reducing the mobility of the affected articulation. The aim was to evaluate 166 Ho-Hydroxyapatite ( 166 Ho-HA) as potential radiopharmaceutical for the symptomatic treatment of chronic and acute arthritis. Materials and Methods: Holmiun-166 was produced by irradiation of Ho 2 O 3 at La Reina Research Reactor, Nuclear Chilean Energy Commission. Hydroxyapatite was in-house synthesized. Its labelling and quality controls follows the internationally accepted procedures. An antigen's arthritis was induced to eight New Zealand rabbits with the 166 Ho-HA radiochemical being administered thereafter in two dosage modalities (single and double). The compound therapeutic efficiency was evaluated based upon clinical improvement and images from the inflamated articulation using 67 Ga citrate before and after 166 Ho-HA injection. Results: The radiochemical purity of the inoculated compound was greater than 98% as measured under sterility conditions. Clinically, an inflammation reduction (2 cm), appetite improvement and general well being was observed. The 166 Ho-HA distribution and localization was monitored using gamma camera images taken at 4 and 24 h. There was no evidence of extra articular leakage. From the 67 Ga citrate imaging, the acute group shows an overall improvement of well being corresponding to a lesser uptake at the inflamated articulation, regarding to the chronic group. The 166 Ho-HA double doses, compared to the single doses, suggest a reduced uptake of 67 Ga citrate at the inflamated tissue, meaning an increased therapeutic effect. Conclusions: 166 Ho-HA is useful as therapeutic agent for the symptomatic treatment of rheumatoid arthritis as shown by imaging and clinical examination

Postimplantation Analysis Enables Improvement of Dose-Volume Histograms and Reduction of Toxicity for Permanent Seed Implantation

International Nuclear Information System (INIS)

Wust, Peter; Postrach, Johanna; Kahmann, Frank; Henkel, Thomas; Graf, Reinhold; Cho, Chie Hee; Budach, Volker; Boehmer, Dirk

2008-01-01

Purpose: To demonstrate how postimplantation analysis is useful for improving permanent seed implantation and reducing toxicity. Patients and Methods: We evaluated 197 questionnaires completed by patients after permanent seed implantation (monotherapy between 1999 and 2003). For 70% of these patients, a computed tomography was available to perform postimplantation analysis. The index doses and volumes of the dose-volume histograms (DVHs) were determined and categorized with respect to the date of implantation. Differences in symptom scores relative to pretherapeutic status were analyzed with regard to follow-up times and DVH descriptors. Acute and subacute toxicities in a control group of 117 patients from an earlier study (June 1999 to September 2001) by Wust et al. (2004) were compared with a matched subgroup from this study equaling 110 patients treated between October 2001 and August 2003. Results: Improved performance, identifying a characteristic time dependency of DVH parameters (after implantation) and toxicity scores, was demonstrated. Although coverage (volume covered by 100% of the prescription dose of the prostate) increased slightly, high-dose regions decreased with the growing experience of the users. Improvement in the DVH and a reduction of toxicities were found in the patient group implanted in the later period. A decline in symptoms with follow-up time counteracts this gain of experience and must be considered. Urinary and sexual discomfort was enhanced by dose heterogeneities (e.g., dose covering 10% of the prostate volume, volume covered by 200% of prescription dose). In contrast, rectal toxicities correlated with exposed rectal volumes, especially the rectal volume covered by 100% of the prescription dose. Conclusion: The typical side effects occurring after permanent seed implantation can be reduced by improving the dose distributions. An improvement in dose distributions and a reduction of toxicities were identified with elapsed time between

Prostate cancer: Doses and volumes of radiotherapy

International Nuclear Information System (INIS)

Hennequin, C.; Rivera, S.; Quero, L.; Latorzeff, I.

2010-01-01

Radiotherapy is nowadays a major therapeutic option in prostate cancer. Technological improvements allowed dose escalation without increasing late toxicity. Some randomized trials have shown that dose escalation decreases the biochemical failure rate, without any benefit in survival with the present follow-up. However, some studies indicate that the distant metastases rate is also decreased. Most of these studies have been done without hormonal treatment, and the role of dose escalation in case of long-term androgen deprivation is unknown. The target volume encompassed the whole gland: however, complete or partial focal treatment of the prostate can be done with sophisticated IMRT technique and must be evaluated. Proximal part of the seminal vesicles must be included in the target volumes. The role of nodal irradiation is another debate, but it could be logically proposed for the unfavourable group. (authors)

High-dose estradiol improves cognition for women with AD: results of a randomized study.

Science.gov (United States)

Asthana, S; Baker, L D; Craft, S; Stanczyk, F Z; Veith, R C; Raskind, M A; Plymate, S R

2001-08-28

To characterize the cognitive and neuroendocrine response to treatment with a high dose of estrogen for postmenopausal women with AD. Twenty postmenopausal women with AD were randomized to receive either 0.10 mg/day of 17 beta-estradiol by skin patch or a placebo patch for 8 weeks. Subjects were evaluated at baseline, at weeks 3, 5, and 8 during treatment, and again 8 weeks after treatment termination. During each visit, cognition was assessed with a battery of neuropsychological tests, and blood samples were collected to measure plasma estradiol as well as several other neuroendocrine markers of interest. Significant effects of estrogen treatment were observed on attention (Stroop Color Word Interference Test), verbal memory (Buschke Selective Reminding Test), and visual memory (Figure Copy/Memory). In addition, women treated with estrogen demonstrated improved performance on a test of semantic memory (Boston Naming Test) compared with subjects who received a placebo. Estrogen appeared to have a suppressive effect on the insulin-like growth factor (IGF) system such that plasma concentration of IGF binding protein-3 was significantly reduced and plasma levels of estradiol and IGF-I were negatively correlated during estrogen treatment. Administration of a higher dose of estrogen may enhance attention and memory for postmenopausal women with AD. Although these findings provide further clinical evidence to support a cognitive benefit of estrogen for women with AD, studies evaluating the effect of estradiol administration, in particular, using larger sample sizes and for longer treatment durations are warranted before the therapeutic potential of estrogen replacement for women with AD can be firmly established.

Thermal neutron dose calculation in synovium membrane for BNCS

International Nuclear Information System (INIS)

Abdalla, Khalid; Naqvi, A.A.; Maalej, N.; El-Shahat, B.

2006-01-01

A D(d,n) reaction based setup has been optimized for Boron Neutron Capture Synovectomy (BNCS). The polyethylene moderator and graphite reflector sizes were optimized to deliver the highest ratio of thermal to fast neutron yield. The neutron dose was calculated at various depths in a knee phantom loaded with boron to determine therapeutic ratios of synovium dose/skin dose and synovium dose/bone dose. Normalized to same boron loading in synovium, the values of the therapeutic ratios obtained in the present study are 12-30 times higher than the published values. (author)

Acute Organophosphate Poisonings: Therapeutic Dilemmas and New Potential Therapeutic Agents

International Nuclear Information System (INIS)

Vucinic, S.; Jovanovic, D.; Vucinic, Z.; Todorovic, V.; Segrt, Z.

2007-01-01

It has been six decades since synthesis of organophosphates, but this chapter has not yet come to a closure. Toxic effects of organophosphates are well known and the current therapeutic scheme includes supportive therapy and antidotes. There is a dilemma on whether and when to apply gastric lavage and activated charcoal. According to Position Statement (by EAPCCT) it should be applied only if the patient presents within one hour of ingestion, with potentially lethal ingested dose. Atropine, a competitive antagonist of acetylcholine at m-receptors, which antagonizes bronchosecretion and bronchoconstriction, is the corner stone of acute organophosphate poisoning therapy. There were many attempts to find a more efficient drug, including glycopyrrolate which has been used even in clinical trials, but it still can not replace atropine. The only dilemma about atropine usage which still exists, concerns usage of high atropine dose and scheme of application. The most efficient atropinization is achieved with bolus doses of 1-2mg of atropine i.v push, with repeating the dose on each 5 minutes until signs of atropinization are registered. Diazepam, with its GABA stabilizing effect, reduces central nervous system damage and central respiratory weakness. Oximes reactivate phosphorylated acetylcholinesterase, which still has not gone ageing, reducing acetylcholine concentration and cholinergic crisis. These effects are clearly demonstrated in experimental conditions, but the clinical significance of oximes is still unclear and there are still those who question oxime therapy. For those who approve it, oxime dosage, duration of therapy, the choice of oxime for certain OP is still an open issue. We need new, more efficient antidotes, and those that are in use are only the small part of the therapy which could be used. Experimental studies show favorable therapeutic effect of many agents, but none of them has been introduced in standard treatment of OPI poisoning in the last 30

Correcting Effect of Therapeutic Doses of Optical Radiation on Hematological Parameters of Blood Irradiated In Vivo

Science.gov (United States)

Zalesskaya, G. A.; Laskina, O. V.

2017-07-01

We studied the effect of therapeutic doses of optical radiation on the hematological parameters of blood irradiated in vivo: hemoglobin concentration, hematocrit, and the number of erythrocytes in the peripheral blood of patients during courses of extracorporeal, overvein, and intravenous blood irradiation and after treatment. The reversible changes during the procedures were found to differ from the changes obtained after treatment completion. At the end of the treatment course, the hematological parameters had changed in different directions and became higher, the same, or lower than the initial parameters depending on the initial parameters and photoinduced changes in blood oxygenation. A compensatory effect was found for photohemotherapy on oxygen-dependent processes altering the oxygen inflow into cells as well as the generation of active oxygen species and their inhibition by antioxidant systems.

Cohort-specific imputation of gene expression improves prediction of warfarin dose for African Americans.

Science.gov (United States)

Gottlieb, Assaf; Daneshjou, Roxana; DeGorter, Marianne; Bourgeois, Stephane; Svensson, Peter J; Wadelius, Mia; Deloukas, Panos; Montgomery, Stephen B; Altman, Russ B

2017-11-24

Genome-wide association studies are useful for discovering genotype-phenotype associations but are limited because they require large cohorts to identify a signal, which can be population-specific. Mapping genetic variation to genes improves power and allows the effects of both protein-coding variation as well as variation in expression to be combined into "gene level" effects. Previous work has shown that warfarin dose can be predicted using information from genetic variation that affects protein-coding regions. Here, we introduce a method that improves dose prediction by integrating tissue-specific gene expression. In particular, we use drug pathways and expression quantitative trait loci knowledge to impute gene expression-on the assumption that differential expression of key pathway genes may impact dose requirement. We focus on 116 genes from the pharmacokinetic and pharmacodynamic pathways of warfarin within training and validation sets comprising both European and African-descent individuals. We build gene-tissue signatures associated with warfarin dose in a cohort-specific manner and identify a signature of 11 gene-tissue pairs that significantly augments the International Warfarin Pharmacogenetics Consortium dosage-prediction algorithm in both populations. Our results demonstrate that imputed expression can improve dose prediction and bridge population-specific compositions. MATLAB code is available at https://github.com/assafgo/warfarin-cohort.

Improving abdomen tumor low-dose CT images using a fast dictionary learning based processing

International Nuclear Information System (INIS)

Chen Yang; Shi Luyao; Shu Huazhong; Luo Limin; Coatrieux, Jean-Louis; Yin Xindao; Toumoulin, Christine

2013-01-01

In abdomen computed tomography (CT), repeated radiation exposures are often inevitable for cancer patients who receive surgery or radiotherapy guided by CT images. Low-dose scans should thus be considered in order to avoid the harm of accumulative x-ray radiation. This work is aimed at improving abdomen tumor CT images from low-dose scans by using a fast dictionary learning (DL) based processing. Stemming from sparse representation theory, the proposed patch-based DL approach allows effective suppression of both mottled noise and streak artifacts. The experiments carried out on clinical data show that the proposed method brings encouraging improvements in abdomen low-dose CT images with tumors. (paper)

SU-E-T-622: Identification and Improvement of Patients Eligible for Dose Escalation with Matched Plans

International Nuclear Information System (INIS)

Bush, K; Holcombe, C; Kapp, D; Buyyounouski, M; Hancock, S; Xing, L; Atwood, T; King, M

2014-01-01

Purpose: Radiation-therapy dose-escalation beyond 80Gy may improve tumor control rates for patients with localized prostate cancer. Since toxicity remains a concern, treatment planners must achieve dose-escalation while still adhering to dose-constraints for surrounding structures. Patientmatching is a machine-learning technique that identifies prior patients that dosimetrically match DVH parameters of target volumes and critical structures prior to actual treatment planning. We evaluated the feasibility of patient-matching in (1)identifying candidates for safe dose-escalation; and (2)improving DVH parameters for critical structures in actual dose-escalated plans. Methods: We analyzed DVH parameters from 319 historical treatment plans to determine which plans could achieve dose-escalation (8640cGy) without exceeding Zelefsky dose-constraints (rectal and bladder V47Gy<53%, and V75.6Gy<30%, max-point dose to rectum of 8550cGy, max dose to PTV< 9504cGy). We then estimated the percentage of cases that could achieve safe dose-escalation using software that enables patient matching (QuickMatch, Siris Medical, Mountain View, CA). We then replanned a case that had violated DVH constraints with DVH parameters from patient matching, in order to determine whether this previously unacceptable plan could be made eligible with this automated technique. Results: Patient-matching improved the percentage of patients eligible for dose-escalation from 40% to 63% (p=4.7e-4, t-test). Using a commercial optimizer augmented with patient-matching, we demonstrated a case where patient-matching improved the toxicity-profile such that dose-escalation would have been possible; this plan was rapidly achieved using patientmatching software. In this patient, all lower-dose constraints were met with both the denovo and patient-matching plan. In the patient-matching plan, maximum dose to the rectum was 8385cGy, while the denovo plan failed to meet the maximum rectal constraint at 8571c

The pharmacokinetic profile of a novel fixed-dose combination tablet of ibuprofen and paracetamol

OpenAIRE

Tanner, Trevor; Aspley, Sue; Munn, Andrew; Thomas, Tracy

2010-01-01

Background Ibuprofen and paracetamol differ in their mode of action and related therapeutic effects, suggesting that combined administration may offer improved analgesia. Reported here are the results of two studies on the pharmacokinetic properties of a novel ibuprofen (200 mg) and paracetamol (500 mg) fixed-dose combination tablet. Methods Both studies were open-label, randomised studies in healthy volunteers: Study 1 was a four-way crossover, single-dose study; Study 2 was a two-way cross-...

Performance of commercial platforms for rapid genotyping of polymorphisms affecting warfarin dose.

Science.gov (United States)

King, Cristi R; Porche-Sorbet, Rhonda M; Gage, Brian F; Ridker, Paul M; Renaud, Yannick; Phillips, Michael S; Eby, Charles

2008-06-01

Initiation of warfarin therapy is associated with bleeding owing to its narrow therapeutic window and unpredictable therapeutic dose. Pharmacogenetic-based dosing algorithms can improve accuracy of initial warfarin dosing but require rapid genotyping for cytochrome P-450 2C9 (CYP2C9) *2 and *3 single nucleotide polymorphisms (SNPs) and a vitamin K epoxide reductase (VKORC1) SNP. We evaluated 4 commercial systems: INFINITI analyzer (AutoGenomics, Carlsbad, CA), Invader assay (Third Wave Technologies, Madison, WI), Tag-It Mutation Detection assay (Luminex Molecular Diagnostics, formerly Tm Bioscience, Toronto, Canada), and Pyrosequencing (Biotage, Uppsala, Sweden). We genotyped 112 DNA samples and resolved any discrepancies with bidirectional sequencing. The INFINITI analyzer was 100% accurate for all SNPs and required 8 hours. Invader and Tag-It were 100% accurate for CYP2C9 SNPs, 99% accurate for VKORC1 -1639/3673 SNP, and required 3 hours and 8 hours, respectively. Pyrosequencing was 99% accurate for CYP2C9 *2, 100% accurate for CYP2C9 *3, and 100% accurate for VKORC1 and required 4 hours. Current commercial platforms provide accurate and rapid genotypes for pharmacogenetic dosing during initiation of warfarin therapy.

An improved distance-to-dose correlation for predicting bladder and rectum dose-volumes in knowledge-based VMAT planning for prostate cancer

Science.gov (United States)

Wall, Phillip D. H.; Carver, Robert L.; Fontenot, Jonas D.

2018-01-01

The overlap volume histogram (OVH) is an anatomical metric commonly used to quantify the geometric relationship between an organ at risk (OAR) and target volume when predicting expected dose-volumes in knowledge-based planning (KBP). This work investigated the influence of additional variables contributing to variations in the assumed linear DVH-OVH correlation for the bladder and rectum in VMAT plans of prostate patients, with the goal of increasing prediction accuracy and achievability of knowledge-based planning methods. VMAT plans were retrospectively generated for 124 prostate patients using multi-criteria optimization. DVHs quantified patient dosimetric data while OVHs quantified patient anatomical information. The DVH-OVH correlations were calculated for fractional bladder and rectum volumes of 30, 50, 65, and 80%. Correlations between potential influencing factors and dose were quantified using the Pearson product-moment correlation coefficient (R). Factors analyzed included the derivative of the OVH, prescribed dose, PTV volume, bladder volume, rectum volume, and in-field OAR volume. Out of the selected factors, only the in-field bladder volume (mean R  =  0.86) showed a strong correlation with bladder doses. Similarly, only the in-field rectal volume (mean R  =  0.76) showed a strong correlation with rectal doses. Therefore, an OVH formalism accounting for in-field OAR volumes was developed to determine the extent to which it improved the DVH-OVH correlation. Including the in-field factor improved the DVH-OVH correlation, with the mean R values over the fractional volumes studied improving from  -0.79 to  -0.85 and  -0.82 to  -0.86 for the bladder and rectum, respectively. A re-planning study was performed on 31 randomly selected database patients to verify the increased accuracy of KBP dose predictions by accounting for bladder and rectum volume within treatment fields. The in-field OVH led to significantly more precise

Radiation dose assessment in nuclear medicine

International Nuclear Information System (INIS)

Stabin, M.G.

2002-01-01

In any application involving the use of ionizing radiation in humans, risks and benefits must be properly evaluated and balanced. Radionuclides are used in nuclear medicine in a variety of diagnostic and therapeutic procedures. Recently, interest has grown in therapeutic agents for a number of applications in nuclear medicine, particularly in the treatment of hematologic and non-hematologic malignancies. This has heightened interest in the need for radiation dose calculations and challenged the scientific community to develop more patient-specific and relevant dose models. Consideration of radiation dose in such studies is central to efforts to maximize dose to tumor while sparing normal tissues. In many applications, a significant absorbed dose may be received by some radiosensitive organs, particularly the active marrow. This talk will review the methods and models used in internal dosimetry in nuclear medicine, and discuss some current trends and challenges in this field

Evaluation of a pharmacogenetic-based warfarin dosing algorithm in patients with low time in therapeutic range - study protocol for a randomized controlled trial.

Science.gov (United States)

Marcatto, Leiliane Rodrigues; Sacilotto, Luciana; Bueno, Carolina Tosin; Facin, Mirella; Strunz, Celia Maria Cassaro; Darrieux, Francisco Carlos Costa; Scanavacca, Maurício Ibrahim; Krieger, Jose Eduardo; Pereira, Alexandre Costa; Santos, Paulo Caleb Junior Lima

2016-11-17

Time in therapeutic range (TTR) is a measurement of quality of warfarin therapy and lower TTR values (algorithm specifically calibrated for a Brazilian patient sample. The aims of this study are: to evaluate the impact of a genetic-based algorithm, compared to traditional anticoagulation, in the time to achieve the therapeutic target and in TTR percentage; and to assess the cost-effectiveness of genotype-guided warfarin dosing in a specific cohort of patients with low TTR (algorithm will be used. At the second, third, fourth and fifth consultations (with an interval of 7 days each) INR will be measured and, if necessary, the dose will be adjusted based on guidelines. Afterwards, patients who are INR stable will begin measuring their INR in 30 day intervals; if the patient's INR is not stable, the patient will return in 7 days for a new measurement of the INR. Outcomes measures will include the time to achieve the therapeutic target and the percentage of TTR at 4 and 12 weeks. In addition, as a secondary end-point, pharmacoeconomic analysis will be carried out. Ethical approval was granted by the Ethics Committee for Medical Research on Human Beings of the Clinical Hospital of the University of São Paulo Medical School. This randomized study will include patients with low TTR and it will evaluate whether a population-specific genetic algorithm might be more effective than traditional anticoagulation for a selected group of poorly anticoagulated patients. ClinicalTrials.gov, NCT02592980 . Registered on 29 October 2015.

PET/CT Based Dose Planning in Radiotherapy

DEFF Research Database (Denmark)

Berthelsen, Anne Kiil; Jakobsen, Annika Loft; Sapru, Wendy

2011-01-01

radiotherapy planning with PET/CT prior to the treatment. The PET/CT, including the radiotherapy planning process as well as the radiotherapy process, is outlined in detail. The demanding collaboration between mould technicians, nuclear medicine physicians and technologists, radiologists and radiology......This mini-review describes how to perform PET/CT based radiotherapy dose planning and the advantages and possibilities obtained with the technique for radiation therapy. Our own experience since 2002 is briefly summarized from more than 2,500 patients with various malignant diseases undergoing...... technologists, radiation oncologists, physicists, and dosimetrists is emphasized. We strongly believe that PET/CT based radiotherapy planning will improve the therapeutic output in terms of target definition and non-target avoidance and will play an important role in future therapeutic interventions in many...

Intensity modulated radiation therapy (IMRT: differences in target volumes and improvement in clinically relevant doses to small bowel in rectal carcinoma

Directory of Open Access Journals (Sweden)

Delclos Marc E

2011-06-01

covered by classic bony landmark-derived fields, without incurring penalty with respect to adjacent organs-at-risk. Conclusions For rectal carcinoma, IMRT, compared to 3DCRT, yielded plans superior with respect to target coverage, homogeneity, and conformality, while lowering dose to adjacent organs-at-risk. This is achieved despite treating larger volumes, raising the possibility of a clinically-relevant improvement in the therapeutic ratio through the use of IMRT with a belly-board apparatus.

Combining Radiation Epidemiology With Molecular Biology-Changing From Health Risk Estimates to Therapeutic Intervention.

Science.gov (United States)

Abend, Michael; Port, Matthias

2016-08-01

The authors herein summarize six presentations dedicated to the key session "molecular radiation epidemiology" of the ConRad meeting 2015. These presentations were chosen in order to highlight the promise when combining conventional radiation epidemiology with molecular biology. Conventional radiation epidemiology uses dose estimates for risk predictions on health. However, combined with molecular biology, dose-dependent bioindicators of effect hold the promise to improve clinical diagnostics and to provide target molecules for potential therapeutic intervention. One out of the six presentations exemplified the use of radiation-induced molecular changes as biomarkers of exposure by measuring stabile chromosomal translocations. The remaining five presentations focused on molecular changes used as bioindicators of the effect. These bioindicators of the effect could be used for diagnostic purposes on colon cancers (genomic instability), thyroid cancer (CLIP2), or head and neck squamous cell cancers. Therapeutic implications of gene expression changes were examined in Chernobyl thyroid cancer victims and Mayak workers.

Dose-response relationship in the treatment of gastrointestinal disorders.

Science.gov (United States)

Weihrauch, T R; Demol, P

1989-08-01

Numerous clinical studies have been performed to establish efficacy and safety of drugs in gastroenterological disorders. Only in a few if any of these studies, however, the rationale for the optimal dose and the dose regimens, respectively, have been addressed. Adequate and well-controlled dose finding studies play a key role in the clinical assessment of new drugs and in the evaluation of new indications. Hereby the range from the minimal effective dose to the maximal effective and well tolerated dose can be assessed and thus the optimal dose-range and dosage regimen be determined. Meaningful pharmacodynamic studies can be performed in the gastrointestinal tract also in healthy volunteers provided that a method with a high predictability for the desired therapeutic effect is available such as measurement of gastric acid secretion and its inhibition by a drug. Dose finding studies in gastroenterology can be carried out under two main aspects: First, to assess the pharmacodynamic and therapeutic effect of a compound on the gastrointestinal tract (e.g. anti-ulcer drug). Second, to evaluate the side effects of a drug on the gastrointestinal tract (e.g. gastric mucosal damage by non-steroidal anti-inflammatory drugs). For the evaluation of new drugs in gastrointestinal therapy a number of methods are available which yield accurate and reproducible data. While careful clinical-pharmacological dose-response studies using these methods have been carried out already more than a decade ago, it is surprising that therapeutic dose finding studies have become available only during the past few years. For scientific as well as for ethical reasons more trials which determine the optimal therapeutic dose are warranted.

Cohort-specific imputation of gene expression improves prediction of warfarin dose for African Americans

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Assaf Gottlieb

2017-11-01

Full Text Available Abstract Background Genome-wide association studies are useful for discovering genotype–phenotype associations but are limited because they require large cohorts to identify a signal, which can be population-specific. Mapping genetic variation to genes improves power and allows the effects of both protein-coding variation as well as variation in expression to be combined into “gene level” effects. Methods Previous work has shown that warfarin dose can be predicted using information from genetic variation that affects protein-coding regions. Here, we introduce a method that improves dose prediction by integrating tissue-specific gene expression. In particular, we use drug pathways and expression quantitative trait loci knowledge to impute gene expression—on the assumption that differential expression of key pathway genes may impact dose requirement. We focus on 116 genes from the pharmacokinetic and pharmacodynamic pathways of warfarin within training and validation sets comprising both European and African-descent individuals. Results We build gene-tissue signatures associated with warfarin dose in a cohort-specific manner and identify a signature of 11 gene-tissue pairs that significantly augments the International Warfarin Pharmacogenetics Consortium dosage-prediction algorithm in both populations. Conclusions Our results demonstrate that imputed expression can improve dose prediction and bridge population-specific compositions. MATLAB code is available at https://github.com/assafgo/warfarin-cohort

Glyco-engineering strategies for the development of therapeutic enzymes with improved efficacy for the treatment of lysosomal storage diseases.

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Oh, Doo-Byoung

2015-08-01

Lysosomal storage diseases (LSDs) are a group of inherent diseases characterized by massive accumulation of undigested compounds in lysosomes, which is caused by genetic defects resulting in the deficiency of a lysosomal hydrolase. Currently, enzyme replacement therapy has been successfully used for treatment of 7 LSDs with 10 approved therapeutic enzymes whereas new approaches such as pharmacological chaperones and gene therapy still await evaluation in clinical trials. While therapeutic enzymes for Gaucher disease have N-glycans with terminal mannose residues for targeting to macrophages, the others require N-glycans containing mannose-6-phosphates that are recognized by mannose-6-phosphate receptors on the plasma membrane for cellular uptake and targeting to lysosomes. Due to the fact that efficient lysosomal delivery of therapeutic enzymes is essential for the clearance of accumulated compounds, the suitable glycan structure and its high content are key factors for efficient therapeutic efficacy. Therefore, glycan remodeling strategies to improve lysosomal targeting and tissue distribution have been highlighted. This review describes the glycan structures that are important for lysosomal targeting and provides information on recent glyco-engineering technologies for the development of therapeutic enzymes with improved efficacy.

Poor Safety and Tolerability Hamper Reaching a Potentially Therapeutic Dose in the Use of Thalidomide for Alzheimer's Disease: Results from a Double-Blind, Placebo-Controlled Trial.

Science.gov (United States)

Decourt, Boris; Drumm-Gurnee, Denise; Wilson, Jeffrey; Jacobson, Sandra; Belden, Christine; Sirrel, Sherye; Ahmadi, Michael; Shill, Holly; Powell, Jessica; Walker, Aaron; Gonzales, Amanda; Macias, Mimi; Sabbagh, Marwan N

2017-01-01

To date there is no cure for Alzheimer's disease (AD). After amyloid beta immunotherapies have failed to meet primary endpoints of slowing cognitive decline in AD subjects, the inhibition of the beta-secretase BACE1 appears as a promising therapeutic approach. Pre-clinical data obtained in APP23 mice suggested that the anti-cancer drug thalidomide decreases brainBACE1 and Aβ levels. This prompted us to develop an NIH-supported Phase IIa clinical trial to test the potential of thalidomide for AD. We hypothesized that thalidomide can decrease or stabilize brain amyloid deposits, which would result in slower cognitive decline in drug- versus placebo-treated subjects. This was a 24-week, randomized, double-blind, placebo-controlled, parallel group study with escalating dose regimen of thalidomide with a target dose of 400mg daily in patients with mild to moderate AD. The primary outcome measures were tolerability and cognitive performance assessed by a battery of tests. A total of 185 subjects have been pre-screened, out of which25 were randomized. Mean age of the sample at baseline was 73.64 (±7.20) years; mean education was 14.24 (±2.3) years; mean MMSE score was 21.00 (±5.32); and mean GDS score was 2.76 (±2.28).Among the 25 participants, 14 (56%) terminated early due to adverse events, dramatically decreasing the power of the study. In addition, those who completed the study (44%) never reached the estimated therapeutic dose of 400 mg/day thalidomide because of reported adverse events. The cognitive data showed no difference between the treated and placebo groups at the end of the trial. This study demonstrates AD patients have poor tolerability for thalidomide, and are unable to reach a therapeutic dose felt to be sufficient to have effects on BACE1. Because of poor tolerability, this study failed to demonstrate a beneficial effect on cognition. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Therapeutic strategies to improve control of hypertension.

Science.gov (United States)

Armario, Pedro; Waeber, Bernard

2013-03-01

Blood pressure is poorly controlled in most European countries and the control rate is even lower in high-risk patients such as patients with chronic kidney disease, diabetic patients or previous coronary heart disease. Several factors have been associated with poor control, some of which involve the characteristic of the patients themselves, such as socioeconomic factors, or unsuitable life-styles, other factors related to hypertension or to associated comorbidity, but there are also factors directly associated with antihypertensive therapy, mainly involving adherence problems, therapeutic inertia and therapeutic strategies unsuited to difficult-to-control hypertensive patients. It is common knowledge that only 30% of hypertensive patients can be controlled using monotherapy; all the rest require a combination of two or more antihypertensive drugs, and this can be a barrier to good adherence and log-term persistence in patients who also often need to use other drugs, such as antidiabetic agents, statins or antiplatelet agents. The fixed combinations of three antihypertensive agents currently available can facilitate long-term control of these patients in clinical practice. If well tolerated, a long-term therapeutic regimen that includes a diuretic, an ACE inhibitor or an angiotensin receptor blocker, and a calcium channel blocker is the recommended optimal triple therapy.

The rabbit biodistribution of a therapeutic dose of zoledronic acid labeled with Tc-99m

International Nuclear Information System (INIS)

Asikoglu, Makbule; Gamze Durak, Funda

2009-01-01

The aim of the present study was to label a therapeutic dose of zoledronic acid (ZOL) with Tc-99m, evaluate its in vitro stability and compare its biodistribution to 99m Tc-methylene biphosphonate ( 99m Tc-MDP) in normal rabbits. Preparation of 0.50 mg of 99m Tc-ZOL was carried out by the reduction of 99m Tc-pertechnetate in the presence of stannous chloride. The radiolabeling efficiency was found to be greater than 99%. The labeled complex was stable at least up to 6 h at room temperature determined by paper chromatography. 99m Tc-ZOL and 99m Tc-MDP were administered intravenously to the rabbits for scintigraphic studies. Between 99m Tc-ZOL and 99m Tc-MDP, there were no significant differences in the ratios of femur/BG and lumbar vertebrae/BG, whereas epiphysis/BG and the kidney/BG ratios of 99m Tc-MDP were higher than 99m Tc-ZOL at the static studies.

Dose sculpting with generalized equivalent uniform dose

International Nuclear Information System (INIS)

Wu Qiuwen; Djajaputra, David; Liu, Helen H.; Dong Lei; Mohan, Radhe; Wu, Yan

2005-01-01

With intensity-modulated radiotherapy (IMRT), a variety of user-defined dose distribution can be produced using inverse planning. The generalized equivalent uniform dose (gEUD) has been used in IMRT optimization as an alternative objective function to the conventional dose-volume-based criteria. The purpose of this study was to investigate the effectiveness of gEUD optimization to fine tune the dose distributions of IMRT plans. We analyzed the effect of gEUD-based optimization parameters on plan quality. The objective was to determine whether dose distribution to selected structures could be improved using gEUD optimization without adversely altering the doses delivered to other structures, as in sculpting. We hypothesized that by carefully defining gEUD parameters (EUD 0 and n) based on the current dose distributions, the optimization system could be instructed to search for alternative solutions in the neighborhood, and we could maintain the dose distributions for structures already satisfactory and improve dose for structures that need enhancement. We started with an already acceptable IMRT plan optimized with any objective function. The dose distribution was analyzed first. For structures that dose should not be changed, a higher value of n was used and EUD 0 was set slightly higher/lower than the EUD value at the current dose distribution for critical structures/targets. For structures that needed improvement in dose, a higher to medium value of n was used, and EUD 0 was set to the EUD value or slightly lower/higher for the critical structure/target at the current dose distribution. We evaluated this method in one clinical case each of head and neck, lung and prostate cancer. Dose volume histograms, isodose distributions, and relevant tolerance doses for critical structures were used for the assessment. We found that by adjusting gEUD optimization parameters, the dose distribution could be improved with only a few iterations. A larger value of n could lead to

Improved consistency in dosing anti-tuberculosis drugs in Taipei, Taiwan.

Science.gov (United States)

Chiang, Chen-Yuan; Yu, Ming-Chih; Shih, Hsiu-Chen; Yen, Muh-Yong; Hsu, Yu-Ling; Yang, Shiang-Lin; Lin, Tao-Ping; Bai, Kuan-Jen

2012-01-01

It was reported that 35.5% of tuberculosis (TB) cases reported in 2003 in Taipei City had no recorded pre-treatment body weight and that among those who had, inconsistent dosing of anti-TB drugs was frequent. Taiwan Centers for Disease Control (CDC) have taken actions to strengthen dosing of anti-TB drugs among general practitioners. Prescribing practices of anti-TB drugs in Taipei City in 2007-2010 were investigated to assess whether interventions on dosing were effective. Lists of all notified culture positive TB cases in 2007-2010 were obtained from National TB Registry at Taiwan CDC. A medical audit of TB case management files was performed to collect pretreatment body weight and regimens prescribed at commencement of treatment. Dosages prescribed were compared with dosages recommended. The proportion of patients with recorded pre-treatment body weight was 64.5% in 2003, which increased to 96.5% in 2007-2010 (pTaipei City has remarkably improved after health authorities implemented a series of interventions.

Isocentric integration of intensity-modulated radiotherapy with electron fields improves field junction dose uniformity in postmastectomy radiotherapy.

Science.gov (United States)

Wright, Pauliina; Suilamo, Sami; Lindholm, Paula; Kulmala, Jarmo

2014-08-01

In postmastectomy radiotherapy (PMRT), the dose coverage of the planning target volume (PTV) with additional margins, including the chest wall, supraclavicular, interpectoral, internal mammary and axillar level I-III lymph nodes, is often compromised. Electron fields may improve the medial dose coverage while maintaining organ at risk (OAR) doses at an acceptable level, but at the cost of hot and cold spots at the electron and photon field junction. To improve PMRT dose coverage and uniformity, an isocentric technique combining tangential intensity-modulated (IM)RT fields with one medial electron field was implemented. For 10 postmastectomy patients isocentric IMRT with electron plans were created and compared with a standard electron/photon mix and a standard tangent technique. PTV dose uniformity was evaluated based on the tolerance range (TR), i.e. the ratio of the standard deviation to the mean dose, a dice similarity coefficient (DSC) and the 90% isodose coverage and the hot spot volumes. OAR and contralateral breast doses were also recorded. IMRT with electrons significantly improved the PTV dose homogeneity and conformity based on the TR and DSC values when compared with the standard electron/photon and tangent technique (p < 0.02). The 90% isodose coverage improved to 86% compared with 82% and 80% for the standard techniques (p < 0.02). Compared with the standard electron/photon mix, IMRT smoothed the dose gradient in the electron and photon field junction and the volumes receiving a dose of 110% or more were reduced by a third. For all three strategies, the OAR and contralateral breast doses were within clinically tolerable limits. Based on these results two-field IMRT combined with an electron field is a suitable strategy for PMRT.

Risks, radiation dose and image quality of mammography

International Nuclear Information System (INIS)

Menges, V.

1979-01-01

For some time to come, early detection of breast cancer will remain the only way to improve the therapeutical success. Mammography is an absolutely indispensible way to take advantage of this opportunity. Today, mammography is undoubtedly the most reliable method of examination for an early detection of breast cancer. Only mammography can detect carcinomas smaller than the critical tumour size of 1cm. If carried out properly and with present dose levels, it involves hardly any radiation risk. (orig.) [de

Pharmacist-managed dose adjustment feedback using therapeutic drug monitoring of vancomycin was useful for patients with methicillin-resistant Staphylococcus aureus infections: a single institution experience

Directory of Open Access Journals (Sweden)

Hirano R

2016-10-01

Full Text Available Ryuichi Hirano,1 Yuichi Sakamoto,2 Junichi Kitazawa,2 Shoji Yamamoto,1 Naoki Tachibana2 1Department of Pharmacy, 2Laboratory Medicine and Blood Transfusion, Aomori Prefectural Central Hospital, Aomori-shi, Japan Background: Vancomycin (VCM requires dose adjustment based on therapeutic drug monitoring. At Aomori Prefectural Central Hospital, physicians carried out VCM therapeutic drug monitoring based on their experience, because pharmacists did not participate in the dose adjustment. We evaluated the impact of an Antimicrobial Stewardship Program (ASP on attaining target VCM trough concentrations and pharmacokinetics (PK/pharmacodynamics (PD parameters in patients with methicillin-resistant Staphylococcus aureus (MRSA infections. Materials and methods: The ASP was introduced in April 2012. We implemented a prospective audit of prescribed VCM dosages and provided feedback based on measured VCM trough concentrations. In a retrospective pre- and postcomparison study from April 2007 to December 2011 (preimplementation and from April 2012 to December 2014 (postimplementation, 79 patients were treated for MRSA infection with VCM, and trough concentrations were monitored (pre, n=28; post, n=51. In 65 patients (pre, n=15; post, n=50, 24-hour area under the ­concentration–time curve (AUC 0–24 h/minimum inhibitory concentration (MIC ratios were calculated. Results: Pharmacist feedback, which included recommendations for changing dose or using alternative anti-MRSA antibiotics, was highly accepted during postimplementation (88%, 29/33. The number of patients with serum VCM concentrations within the therapeutic range (10–20 μg/mL was significantly higher during postimplementation (84%, 43/51 than during preimplementation (39%, 11/28 (P<0.01. The percentage of patients who attained target PK/PD parameters (AUC 0–24 h/MIC >400 was significantly higher during postimplementation (84%, 42/50 than during preimplementation (53%, 8/15; P=0.013. There were

Effect of therapeutic doses of enrofloxacin on circulating lymphocyte subpopulations in pigs

Directory of Open Access Journals (Sweden)

Pomorska-Mól Małgorzata

2015-06-01

Full Text Available Twenty pigs of similar genetics (PIC were used. Pigs were randomly divided into two groups: experimental (ENRO, n = 10 and control (C, n = 10. From day 0 to day 4, pigs from ENRO group received enrofloxacin at the recommended therapeutic dose. Pigs from C group received PBS instead of enrofloxacin. Blood samples were collected on days 0 (before antibiotic administration, 2, 4 (during antibiotic therapy, 9, and 13 of the study (after enrofloxacin administration. Haematological examination and flow cytometry were used to establish the relative and absolute counts of various leukocyte subsets. Lymphocyte subpopulations were measured by fluorochrom-labelled antibodies according to following definitions: CD3+ (T cells, CD21+ (B cells, CD4+CD8- (helper T cells, Th, CD4-CD8+ (cytolytic T cells, CLT, CD4+CD8+ (cytolytic and memory T cells. The present study revealed the modulating effect of enrofloxacin on the composition of circulating lymphocytes in pigs. Concentration and percentage of CD8+ cells decreased significantly after treatment with enrofloxacin and as a result the absolute CD4/CD8 ratio increased significantly as compared to control group (P < 0.05.These findings should prompt further studies on the practical significance of the results obtained in terms of clinical implications. In view of the results, it cannot be excluded that enrofloxacin may also have immunomodulatory effects on host response to infection.

Maximizing therapeutic gain with gemcitabine and fractionated radiation

International Nuclear Information System (INIS)

Mason, Kathy A.; Milas, Luka; Hunter, Nancy R.; Elshaikh, Mohamed; Buchmiller, Lara; Kishi, Kazushi; Hittelman, K. Walter; Ang, K. Kian

1999-01-01

Purpose/Objective: The nucleoside analogue gemcitabine inhibits cellular repair and repopulation, induces apoptosis, causes tumor growth delay, and enhances radiation-induced growth delay. After single doses of drug and radiation, maximum enhancement of tumor response was obtained when gemcitabine preceded radiation by at least 24 h. Conversely, the cellular radioresponse of the normal gastrointestinal epithelium was slightly protected when gemcitabine and radiation were separated by 24 h. This differential response created a time frame within which therapeutic gain could be maximized. In our present investigation, we sought to define the most therapeutically beneficial scheme of gemcitabine administration when combined with fractionated radiotherapy. Methods and Materials: C3Hf/Kam mice were given identical drug and radiation schedules of administration, and both normal tissue (jejunal mucosa) and tumor (Sa-NH) responses were measured. Irradiation was given once per day for 5 days in normal tissue and tumor growth delay studies and twice per day for the tumor cure endpoint. A total dose of 25 mg/kg gemcitabine was given i.p. in 1 of 3 schedules: a single dose of 25 mg/kg 24 h before the start of fractionated irradiation, 12.5 mg/kg 24 h before the first and third radiation doses, or 24 h before each of 5 radiation doses. Groups of mice bearing 7- or 8-mm diameter tumors were treated with gemcitabine alone or in combination with fractionated irradiation under ambient or hypoxic conditions. The survival response of the jejunal mucosa was quantified by the microcolony assay and histologically by quantifying apoptosis, mitosis, S-phase fraction, and crypt cellularity. Results: For tumor growth delay, dose-modifying factors (DMFs) were similar (1.34-1.46) for all 3 schedules of drug administration. In contrast, the response of the jejunum was strongly dependent on the schedule of gemcitabine administration. A single dose of gemcitabine before the start of fractionated

The improvement of diagnostic and therapeutic imaging in Africa

International Nuclear Information System (INIS)

2015-02-01

The 8. Pan-African Congress of Radiology and Imaging on the improvement of diagnostic and therapeutic imaging in Africa was hosted in Nairobi Kenya. The conference focusses on Review of Radiation Safety in Medical X-Ray Diagnosis, Medical Practitioners of Radiology & Imaging in the Dock. It also addresses issues Knowledge, Attitude, and Practice of Clinicians, Practicing at the Kenyatta National Hospital on Ionizing Radiation and Procurement in the Imaging Department. The Need for Understanding Technical Specifications,Students Experience in Radiography, Radioiodine Therapy for Graves’ Disease, Role of ultrasound in the diagnosis and management of gestational trophoblastic disease in Rural health facilities were areas interest. Diabetes Mellitus and the Musculoskeletal System, Imaging the Traumatized Spine ‘Clearing the Cervical Spine’, The Radiation Safety Culture: Image Gently and Radiation Protection of the Young Patient: Kenya perspective were discussed during the conference

A Monte Carlo Study of dose enhancement according to the enhancement agents

Energy Technology Data Exchange (ETDEWEB)

Kim, Jung Hoon; Kim, Chang Soo [Dept. of Radiological Science, College of Health Sciences, Catholic University of Pusan, Busan (Korea, Republic of); Hwang, Chul Hwan [Dept. of Radiation Oncology, Pusan National University Hospital, Busan (Korea, Republic of)

2017-03-15

Dose enhancement effects at megavoltage (MV) X and γ-ray energies, and the effects of different energy levels on incident energy, dose enhancement agents, and concentrations were analyzed using Monte Carlo simulations. Gold, gadolinium, Iodine, and iron oxide (Fe2O3) were compared as dose enhancement agents. For incident energy, 4, 6, 10 and 15 MV X-ray spectra produced by a linear accelerator and a Co60 γ-ray were used. The dose enhancement factor (DEF) was calculated using an ICRU Slab phantom for concentrations of 7, 18, and 30 mg/g. The DEF was higher at higher concentrations of dose enhancement agents and at lower incident energies. The calculated DEF ranged from 1.035 to 1.079, and dose enhancement effects were highest for iron oxide, followed by iodine, gadolinium, and gold. Thus, this study contributes to improving the therapeutic ratio by delivering larger doses of radiation to tumor volume, and provides data to support further in vivo and in vitro studies.

Dependence of therapeutic gain factor on stage of oral cancer

International Nuclear Information System (INIS)

Velmurugan, J.; Solomon, J.G.R.; Koteshwer Rao, K.; Supe, S.S.; Prasad, G.N.S.

1998-01-01

To achieve therapeutic gain, unconventional dose per fraction has been employed in radiotherapy, in addition to the conventional dose per fraction of 2 Gy. Dose fractionation factor (DFF) and therapeutic gain factor (TGF) have been utilised to test the efficiency of such unconventional fractionation schedules. In this study, isoeffective dose for 100% tumour regression and mucosal and skin reactions were estimated. CRE, TDF and ERD values for tumour and normal tissue reactions were evaluated. DEF and TGF values have been determined on the basis of dose, CRE, TDF and ERD, in order to understand the influence of these bioeffect models and stage of cancer on TGF associated with differing fractionation schedules. There was a noticeable difference in TGF values determined on the basis of four criteria, which is in agreement with radiobiological phenomenon, that tissues with different α/β values differ in their responsiveness. (author)

Clinical review: Balancing the therapeutic, safety, and economic issues underlying effective antipseudomonal carbapenem use

Science.gov (United States)

Slama, Thomas G

2008-01-01

Antipseudomonal carbapenems have played a useful role in our antimicrobial armamentarium for 20 years. However, a review of their use during that period creates concern that their clinical effectiveness is critically dependent on attainment of an appropriate dosing range. Unfortunately, adequate carbapenem dosing is missed for many reasons, including benefit/risk misconceptions, a narrow therapeutic window for imipenem and meropenem (due to an increased rate of seizures at higher doses), increasingly resistant pathogens requiring higher doses than are typically given, and cost containment issues that may limit their use. To improve the use of carbapenems, several initiatives should be considered: increase awareness about appropriate treatment with carbapenems across hospital departments; determine optimal dosing regimens for settings where multidrug resistant organisms are more likely encountered; use of, or combination with, an alternative antimicrobial agent having more favorable pharmacokinetic, pharmacodynamic, or adverse event profile; and administer a newer carbapenem with lower propensity for resistance development (for example, reduced expression of efflux pumps or greater stability against carbapenemases). PMID:18983709

Head CT: Image quality improvement with ASIR-V using a reduced radiation dose protocol for children.

Science.gov (United States)

Kim, Hyun Gi; Lee, Ho-Joon; Lee, Seung-Koo; Kim, Hyun Ji; Kim, Myung-Joon

2017-09-01

To investigate the quality of images reconstructed with adaptive statistical iterative reconstruction V (ASIR-V), using pediatric head CT protocols. A phantom was scanned at decreasing 20% mA intervals using our standard pediatric head CT protocols. Each study was then reconstructed at 10% ASIR-V intervals. After the phantom study, we reduced mA by 10% in the protocol for ASIR-V and by 30% in the protocol for 3- to 15-year-old patients and applied 40% ASIR-V. Increasing the percentage of ASIR-V resulted in lower noise and higher contrast-to-noise ratio (CNR) and preserved spatial resolution in the phantom study. Compared to a conventional-protocol, reduced-dose protocol with ASIR-V achieved 12.8% to 34.0% of dose reduction and showed images of lower noise (9.22 vs. 10.73, P = 0.043) and higher CNR in different levels (centrum semiovale, 2.14 vs. 1.52, P = 0.003; basal ganglia, 1.46 vs. 1.07, P = 0.001; and cerebellum, 2.18 vs. 1.33, P ASIR-V. Use of ASIR-V allowed a 12.8% to 34.0% dose reduction in each age group with potential to improve image quality. • It is possible to reduce radiation dose and improve image quality with ASIR-V. • We improved noise and CNR and decreased radiation dose. • Sharpness improved with ASIR-V. • Total radiation dose was decreased by 12.8% to 34.0%.

Improved late survival and disability after stroke with therapeutic anticoagulation for atrial fibrillation: a population study.

LENUS (Irish Health Repository)

Hannon, Niamh

2011-09-01

Although therapeutic anticoagulation improves early (within 1 month) outcomes after ischemic stroke in hospital-admitted patients with atrial fibrillation, no information exists on late outcomes in unselected population-based studies, including patients with all stroke (ischemic and hemorrhagic).

Therapeutic Inertia and Treatment Intensification.

Science.gov (United States)

Josiah Willock, Robina; Miller, Joseph B; Mohyi, Michelle; Abuzaanona, Ahmed; Muminovic, Meri; Levy, Phillip D

2018-01-29

This review aims to emphasize how therapeutic inertia, the failure of clinicians to intensify treatment when blood pressure rises or remains above therapeutic goals, contributes to suboptimal blood pressure control in hypertensive populations. Studies reveal that the therapeutic inertia is quite common and contributes to suboptimal blood pressure control. Quality improvement programs and standardized approaches to support antihypertensive treatment intensification are ways to combat therapeutic inertia. Furthermore, programs that utilize non-physician medical professionals such as pharmacists and nurses demonstrate promise in mitigating the effects of this important problem. Therapeutic inertia impedes antihypertensive management and requires a broad effort to reduce its effects. There is an ongoing need for renewed focus and research in this area to improve hypertension control.

Preparation of therapeutic dose of 177Lu-DOTA-TATE using a novel single vial freeze-dried kit: a comparison with 'in-situ' preparation at hospital radiopharmacy.

Science.gov (United States)

Das, Tapas; Banerjee, Sharmila; Shinto, Ajit; Kamaleshwaran, K K; Sarma, H D

2014-01-01

Patient dose of (177)Lu-DOTA-TATE, used for providing radiotherapeutic treatment to the patients suffering from cancers of neuroendocrine origin, could be prepared at the hospital radiopharmacy either 'in-situ' or by using freezedried kits. The objective of the present work is to formulate and evaluate a single vial freeze-dried DOTA-TATE kit, which is capable of producing up to 7.4 GBq (200 mCi) dose of (177)Lu-DOTA-TATE and to compare the two methodologies presently used for the preparation of the agent. Freeze-dried DOTA-TATE kits, comprising a lyophilized mixture of DOTA-TATE, gentisic acid and ammonium acetate, were prepared and used for the formulation of patient doses of (177)Lu-DOTA-TATE. The kits were subjected to detailed radiochemical evaluation and the shelf-life of the kits was determined. The pharmacokinetic behavior of the agent was studied in normal Wistar rats. These kits were utilized for treating the patients suffering from various types of neuroendocrine cancers. The freeze-dried kits were used for the preparation of up to 7.4 GBq (200 mCi) therapeutic doses of (177)Lu- DOTA-TATE with a radiochemical purity of >99% and were found to have sufficiently long shelf-life. Biological studies carried out in normal Wistar rats exhibited no significant accumulation of activity in any of the vital organs/tissue except in kidneys and non-accumulated activity showed major renal clearance. Clinical studies carried out in cancer patients exhibited accumulation of activity in the cancerous lesions and metastatic sites. The kit was useful for the convenient preparation of therapeutic dose of (177)Lu-DOTA-TATE, suitable for human administration. The use of kit is expected to reduce the batch failure and radiation exposure to the working personnel.

Quantification of rabbit bone metabolism (BM) before (B) and after (A) sub-therapeutic doses of (89 Sr) -Initial results

International Nuclear Information System (INIS)

Braga, F.J.H.N.; Kinoshita, A.; Turco, F.P.; Moraes, F.A.; Iazigi, N.; Souza, J.F.; Trad, C.S.

1997-01-01

Full text. Some beta emitters, such as 89 Sr, 153 Sm and 186 Re are in current use worldwide for the palliation of bone pain caused by metastases, mainly in cases of disseminated bone metastases when conventional radiotherapy has already been used to maximum dose and when pain relief does not occur with the use of current drugs. In order to quantifying the reduction of RBM after such procedures, we have studied 10 young rabbits (2.5 months old, 1.5 kg), 2 h after the intravenous injection with 150 MBq of 99 m Tc - M D P. Rabbits were counted for 30 seconds in a scintillation camera. A region of interest (ROI) was drawn in the left knee joint. The knee joint was chosen because of its high BM in young animals. Each rabbit received 1.5 MBq per kilo of 89 Sr intravenously immediately after this initial evaluation (therapeutic doses for humans are 2.0 MBq per kg). One month after, rabbits were evaluated again with 99 M T C- MDP as described before and a second ROI was drawn in the same knee joint.The means of counts observed B and A 89 Sr injection were 11, 222 and 4, 399 respectively. These means are significantly different (p <0.05) and represent a reduction of over 60% in the knee joint BM after the 89 Sr dose

Calculation of cobalt-60 primary and scatter dose in layered heterogeneous phantoms using primary and scatter dose spread arrays

International Nuclear Information System (INIS)

Iwasaki, Akira

1993-01-01

A method of making 60 Co γ-ray primary and scatter dose spread arrays in water is described. The primary dose spread array is made using forward and backward primary dose spread equations (h 1 and h 2 ), where both equations contain a laterally spread primary dose equation (G), made from measured dose data in a cork phantom. The scatter dose spread array is made using differential scatter-maximum ratio (dSMR) and differential backscatter factor (dBSF) equations (k 1 and k 2 ), where both equations are made to be continuous on the boundary. Primary and scatter dose calculations are performed along the beam axis in layered cork heterogeneous phantoms. It is found, even for 60 Co γ-rays, that when a small tumor in the lung is irradiated with a field that just surrounds the tumor, the beam entrance surface and lateral side of the tumor may obtain no therapeutic dose, because of loss of longitudinal and lateral electronic equilibrium, and when a large tumor in the lung is irradiated with a field just surrounding the tumor, the lateral side of the tumor may obtain no therapeutic dose due to loss of lateral electronic equilibrium. (author)

Conformal technique dose escalation in prostate cancer: improved cancer control with higher doses in patients with pretreatment PSA {>=} 10 ngm/ml

Energy Technology Data Exchange (ETDEWEB)

Hanks, G E; Lee, W R; Hanlon, A L; Kaplan, E; Epstein, B; Schultheiss, T

1995-07-01

Purpose: Single institutions and an NCI supported group of institutions have been investigating the value of dose escalation in patients with prostate cancer treated by conformal treatment techniques. Improvement in morbidity has been previously established, while this report identifies the pretreatment PSA level subgroups of patients who benefitted in cancer control from higher dose. Materials and Methods: We report actuarial bNED survival rates for 375 consecutive patients with known pretreatment PSA levels treated with conformal technique between 5/89 and 12/93. The whole pelvis was treated to 45 Gy in 25 fractions in all T2C,3, all Gleason 8, 9, 10 and all patients with pretreatment PSA {>=}20. The prostate {+-} seminal vesicles was boosted at 2.1 Gy/day to the center of the prostate to 65-79 Gy (65-69 N=50), 70-72.49 N=94, 72.5-74.9 N=82, 75-77.49 N=129 and {>=}77.5 N=20). The median followup is 21 mos with a range of 3 to 67 mos. The highest dose patients have the least followup, reducing the impact of the highest dose levels at this time. Patients are analyzed for the entire group divided at 71 Gy and at 73 Gy calculated at the center of the prostate. Each dose group is then subdivided by pretreatment PSA levels <10, 10-19.9, and {>=}20 ngm/ml and dose levels are compared within pretreatment PSA level group. bNED failure is defined as PSA {>=}1.5 ngm/ml and rising on two consecutive values. Results: Table 1 shows the bNED survival rates at 24 and 36 mos for all patients and the three pretreatment PSA level groups. For all patients pooled, there is an overall advantage to using doses {>=}71 Gy (64% vs 85% at 36 mo, p=.006) and {>=}73 Gy (71% vs 86% at 36 mo, p=.07). The subgroup of PSA <10 ngm/ml, however, shows no benefit in bNED survival when using doses over 71 Gy (90% vs 93% at 36 mo) or 73 Gy (91 vs 94% at 36 mo). The subgroup PSA 10 ngm/ml to 19.9 ngm/ml shows improved cancer control when using doses over 71 Gy (61% vs 88% at 36 mo, p=.03) and over 73

Radioactivity of flour, wheat, bread improvers and dose estimates in Sudan

International Nuclear Information System (INIS)

Hamdan, Adam Mahana

2015-10-01

The steady rise in the use of isotopes and nuclear technology in various purposes in human life, both agro-industrial military, medical, may increase the chances of radioactive contamination that increases the exposure of ionizing radiation which raise awareness in increasing the need to know how to assess that exposure. Control of imported foodstuffs to ensure that not contaminated with radioactive materials is very important at this stage. The present study aims to investigating radioactivity in foodstuff consumed in Sudan to measure radionuclide in wheat flour, bread improvers specific objectives to measure radioactive contaminants and to estimate radiation dose from this consumption. The health impact of radionuclide ingestion from foodstuffs was evaluated by the committed effective doses determined in 30 samples of foodstuff. collected in the Port Sudan on the red sea, the radioactivity tracer of K-40, U-238 and Th-232 were measured by gamma ray spectrometry employing an using Nal (Ti) calibration process carried out for gamma spectrometry using MW652 as a reference source which recommended by International Atomic Energy Agency (IAEA) including source Cs-137 and Co-60 with two energy levels. The K-40 activity concentration in the flour samples, rang (303.07-40.48) (Bq/kg), 238U (4.81-1.95) (Bq/kg), Th-232 (7.60-1.61) Bq/kg) wheat samples range k-40 (250.62-27.22) (Bq/kg), U-238 (4.92-190) (Bq/kg), Th-232 (5.74-1.61) (Bq/kg) and bread improvers samples k-40 (68.60-13.61 (Bq/kg) U-238 (5.73-194) (Bq/kg). The total average effective dose for age (>17 years) was found in to flour be 2.35±7.12 mSv/y, 1.15±0.95 mSv/y, 1.65±2.02 mSv/y, the maximum dose values obtained were 6.01 mSv/y, 1.95 mSv/y, 1.57 mSv/y. The total average effective dose for age (>17 years) was found in to wheat 1.58±6.85 mSv/y 1.16±1.33 mSv/y, 0.48±1.14 mSv/y, the maximum dose values obtained were 4.14 mSv/y, 1.66 mSv/y, 0.99 mSv/y. The total average effective dose for age (>17 years) was

Study and evaluation of radiometry in photo therapeutic treatment of the neonatal hyperbilirubinaemia

International Nuclear Information System (INIS)

Caly, Jose Pucci

2009-01-01

Phototherapy is a procedure established more than 50 years ago in the treatment of the newborn jaundice. However there is no a standard method to quantify the photo therapeutic dose in published clinical studies, hindering the comparison of previous studies on photo therapeutic effectiveness, as well as the establishment of safe and predictable doses. The photo therapeutic dose depends, among other factors, on the effective mean irradiance produced by the photo therapeutic unit. There are no standard procedures, however, neither to quantify the effective irradiance, nor to estimate the mean effective irradiance. As a consequence, large measurement variations in a same photo therapeutic unit are observed using different commercially available radiometers, as a consequence of the vast diversity of spectral responsivities of the instruments. An objective of this work was to adapt and to apply the bases of the wideband ultraviolet radiometry to quantify the available irradiance from photo therapeutic units, establishing procedures that allow us to compare measured irradiances from different sources, using radiometers presenting different spectral responsivities. Another objective was to characterize samples of photo therapeutic units commonly used, focusing the problem of the estimation of the effective mean irradiance from photo therapeutic units, proposing a method to estimate of the effective irradiance from focused sources. The experimental results allow us to conclude that it is not only necessary to standardize the photo therapeutic radiometry, but also the method of estimation of the effective mean irradiance. (author)

Effect of different single-session educational modalities on improving medical students' ability to demonstrate proper pressurized metered dose inhaler technique.

Science.gov (United States)

Dominelli, Giulio S; Dominelli, Paolo B; Rathgeber, Steven L; Webster, Sheila B

2012-05-01

Pressurized metered dose inhalers (pMDIs) remain important therapeutic options for obstructive lung diseases. The ability to instruct and evaluate inhaler technique is a crucial skill that all medical professionals should possess; unfortunately, many professionals lack proficiency with pMDIs. We aimed to determine if brief education interventions of differing modalities can positively affect medical students' skills over the long term. The baseline ability of medical students and first year residents to use pMDIs was scored via a 10-point scoring system. Students were randomized to receive no education, one-on-one instruction, or video instruction. Students were then retested immediately after the education and at the 3-month mark for retention of acquired skills. Video, one-on-one and the placebo groups modalities statistically improved the average medical student's score in the immediate retesting (7.5 and 7.4 vs. 4.7, p grades at the immediate recall significantly improved for both modalities. During retention testing, only video education had a statistically significant improvement in pass rate over the control group, as defined by an average score of 7 or better (8 vs. 1, p improve medical students' ability to use pMDIs in short-term testing. However, only video education retained significant improvement compared with control after 3 months. This suggests that compared with traditional one-on-one teaching, video education is an effective means of teaching medical students how to improve their pMDI technique.

Massively parallel de novo protein design for targeted therapeutics

KAUST Repository

Chevalier, Aaron

2017-09-26

De novo protein design holds promise for creating small stable proteins with shapes customized to bind therapeutic targets. We describe a massively parallel approach for designing, manufacturing and screening mini-protein binders, integrating large-scale computational design, oligonucleotide synthesis, yeast display screening and next-generation sequencing. We designed and tested 22,660 mini-proteins of 37-43 residues that target influenza haemagglutinin and botulinum neurotoxin B, along with 6,286 control sequences to probe contributions to folding and binding, and identified 2,618 high-affinity binders. Comparison of the binding and non-binding design sets, which are two orders of magnitude larger than any previously investigated, enabled the evaluation and improvement of the computational model. Biophysical characterization of a subset of the binder designs showed that they are extremely stable and, unlike antibodies, do not lose activity after exposure to high temperatures. The designs elicit little or no immune response and provide potent prophylactic and therapeutic protection against influenza, even after extensive repeated dosing.

Massively parallel de novo protein design for targeted therapeutics

KAUST Repository

Chevalier, Aaron; Silva, Daniel-Adriano; Rocklin, Gabriel J.; Hicks, Derrick R.; Vergara, Renan; Murapa, Patience; Bernard, Steffen M.; Zhang, Lu; Lam, Kwok-Ho; Yao, Guorui; Bahl, Christopher D.; Miyashita, Shin-Ichiro; Goreshnik, Inna; Fuller, James T.; Koday, Merika T.; Jenkins, Cody M.; Colvin, Tom; Carter, Lauren; Bohn, Alan; Bryan, Cassie M.; Ferná ndez-Velasco, D. Alejandro; Stewart, Lance; Dong, Min; Huang, Xuhui; Jin, Rongsheng; Wilson, Ian A.; Fuller, Deborah H.; Baker, David

2017-01-01

De novo protein design holds promise for creating small stable proteins with shapes customized to bind therapeutic targets. We describe a massively parallel approach for designing, manufacturing and screening mini-protein binders, integrating large-scale computational design, oligonucleotide synthesis, yeast display screening and next-generation sequencing. We designed and tested 22,660 mini-proteins of 37-43 residues that target influenza haemagglutinin and botulinum neurotoxin B, along with 6,286 control sequences to probe contributions to folding and binding, and identified 2,618 high-affinity binders. Comparison of the binding and non-binding design sets, which are two orders of magnitude larger than any previously investigated, enabled the evaluation and improvement of the computational model. Biophysical characterization of a subset of the binder designs showed that they are extremely stable and, unlike antibodies, do not lose activity after exposure to high temperatures. The designs elicit little or no immune response and provide potent prophylactic and therapeutic protection against influenza, even after extensive repeated dosing.

Massively parallel de novo protein design for targeted therapeutics

Science.gov (United States)

Chevalier, Aaron; Silva, Daniel-Adriano; Rocklin, Gabriel J.; Hicks, Derrick R.; Vergara, Renan; Murapa, Patience; Bernard, Steffen M.; Zhang, Lu; Lam, Kwok-Ho; Yao, Guorui; Bahl, Christopher D.; Miyashita, Shin-Ichiro; Goreshnik, Inna; Fuller, James T.; Koday, Merika T.; Jenkins, Cody M.; Colvin, Tom; Carter, Lauren; Bohn, Alan; Bryan, Cassie M.; Fernández-Velasco, D. Alejandro; Stewart, Lance; Dong, Min; Huang, Xuhui; Jin, Rongsheng; Wilson, Ian A.; Fuller, Deborah H.; Baker, David

2018-01-01

De novo protein design holds promise for creating small stable proteins with shapes customized to bind therapeutic targets. We describe a massively parallel approach for designing, manufacturing and screening mini-protein binders, integrating large-scale computational design, oligonucleotide synthesis, yeast display screening and next-generation sequencing. We designed and tested 22,660 mini-proteins of 37–43 residues that target influenza haemagglutinin and botulinum neurotoxin B, along with 6,286 control sequences to probe contributions to folding and binding, and identified 2,618 high-affinity binders. Comparison of the binding and non-binding design sets, which are two orders of magnitude larger than any previously investigated, enabled the evaluation and improvement of the computational model. Biophysical characterization of a subset of the binder designs showed that they are extremely stable and, unlike antibodies, do not lose activity after exposure to high temperatures. The designs elicit little or no immune response and provide potent prophylactic and therapeutic protection against influenza, even after extensive repeated dosing. PMID:28953867

Low and moderate doses of caffeine late in exercise improve performance in trained cyclists.

Science.gov (United States)

Talanian, Jason L; Spriet, Lawrence L

2016-08-01

The aim of the present study was to assess if low and moderate doses of caffeine delivered in a carbohydrate-electrolyte solution (CES) late in exercise improved time-trial (TT) performance. Fifteen (11 male, 4 female) cyclists (age, 22.5 ± 0.9 years; body mass, 69.3 ± 2.6 kg; peak oxygen consumption, 64.6 ± 1.9 mL·min(-1)·kg(-1)) completed 4 double-blinded randomized trials. Subjects completed 120 min of cycling at ∼60% peak oxygen consumption with 5 interspersed 120-s intervals at ∼82% peak oxygen consumption, immediately followed by 40-s intervals at 50 W. Following 80 min of cycling, subjects either ingested a 6% CES (PL), a CES with 100 mg (low dose, 1.5 ± 0.1 mg·kg body mass(-1)) of caffeine (CAF1), or a CES with 200 mg (moderate dose, 2.9 ± 0.1 mg·kg body mass(-1)) of caffeine (CAF2). Following the 120-min cycling challenge, cyclists completed a 6-kJ·kg body mass(-1) TT. There was no difference between respiratory, heart rate, glucose, free fatty acid, body mass, hematocrit, or urine specific gravity measurements between treatments. The CAF2 (26:36 ± 0:22 min:s) TT was completed faster than CAF1 (27:36 ± 0:32 min:s, p caffeine delivered late in exercise improved TT performance over the PL trial and the moderate dose (CAF2) improved performance to a greater extent than the low dose (CAF1).

Anticoagulation Endpoints with Clinical Implementation of Warfarin Pharmacogenetic Dosing in a Real-World Setting – A Proposal for a New Pharmacogenetic Dosing Approach

Science.gov (United States)

Arwood, Meghan J.; Deng, Jiexin; Drozda, Katarzyna; Pugach, Oksana; Nutescu, Edith A.; Schmidt, Stephan; Duarte, Julio D.; Cavallari, Larisa H.

2016-01-01

Achieving therapeutic anticoagulation efficiently with warfarin is important to reduce thrombotic and bleeding risks and is influenced by genotype. Utilizing data from a diverse population of 257 patients who received VKORC1 and CYP2C9 genotype-guided warfarin dosing, we aimed to examine genotype-associated differences in anticoagulation endpoints and derive a novel pharmacogenetic nomogram to more optimally dose warfarin. We observed significant differences across patients with 0, 1, or ≥2 reduced-function VKORC1 or CYP2C9 alleles, respectively, in time to achieve therapeutic international normalized ratio (INR) (7.8±5.8, 7.2±4.7, and 5.4±4.6 days, P=0.0004) and mean percentage of time in therapeutic range in the first 28 days (22.2, 27.8, and 32.2%, P=0.0127) with use of existing pharmacogenetic algorithms. These data suggest that more aggressive dosing is necessary for patients with 0 to 1 VKORC1/CYP2C9 variants to more efficiently achieve therapeutic anticoagulation. Herein, we provide a novel kinetic/pharmacodynamic-derived dosing nomogram optimized for a heterogeneous patient population. PMID:28032893

Therapeutical uses of 131I

International Nuclear Information System (INIS)

Lago, Graciela.

1994-01-01

Physiology of thyroid gland, pathology of thyroid , papillary, follicular cancer is considered together as differentiated thyroid cancer with very good results under therapy with iodine, invitro determination of calcitonin, search of metastasis, anaplastic carcinoma, as indifferentiated carcinoma with similar results as medullary carcinoma. This work gives a protocol for therapeutical use of 131I , in hyperthyroidism due to Graves-Basedow disease, thyrotoxic adenoma or Plummer disease, toxic multi nodular goiter, subacute thyroiditis. Is studied too the treatment with pharmaceuticals, surgery and radioactive iodine. A recommended use of each and protocol for iodine administration, fixed dose technique, dose estimation,absorbed dose, recommendations about when to use and not use 131I are included in this work

Dosimetry of atmospheric neutrons: aircrew dosimetry and therapeutic applications

International Nuclear Information System (INIS)

Tatje, Jennifer

2008-01-01

This trainee-ship reports addresses the quantification of the dose received, in real time, by air-crews during commercial flights. Thus, the author first presents the radiative environment which surrounds people and components, and the possible consequences on this exposure. The different parameters influencing the received dose are developed and discussed. The author then describes the French SIEVERT calculation code which is used by all air companies. He also gives a detailed attention to the legal framework regarding radiation protection. In the next part, the author discusses the use of neutrons applied for therapeutic purposes, and their biological effects such as the bystander effect and the radio-sensitivity to low doses. He describes what is a cancer, and presents a therapeutic technique, the Boron Neutron Capture Therapy (BNCT), which is indicated for a certain type of brain cancer, the glioblastoma. The third part proposes an overview of the state-of-the-art of neutron dosimeters, and more particularly those doped with boron, for dose measurement

A randomized controlled trial of vitamin D dosing strategies after acute hip fracture: No advantage of loading doses over daily supplementation

Directory of Open Access Journals (Sweden)

Farrauto Leonardo

2011-06-01

Full Text Available Abstract Background There remains uncertainty regarding the appropriate therapeutic management of hip fracture patients. The primary aim of our study was to examine whether large loading doses in addition to daily vitamin D offered any advantage over a simple daily low-dose vitamin D regimen for increasing vitamin D levels. Methods In this randomized controlled study, patients over age 50 with an acute fragility hip fracture were enrolled from two hospital sites in Ontario, Canada. Participants were randomized to one of three loading dose groups: placebo; 50,000 IU vitamin D2; or 100,000 IU D2. Following a placebo/loading dose, all patients received a daily tablet of 1,000 IU vitamin D3 for 90 days. Serum 25-hydroxy vitamin D (25-OHD was measured at baseline, discharge from acute care (approximately 4-weeks, and 3-months. Results Sixty-five patients were enrolled in the study (44% male. An immediate rise in 25-OHD occurred in the 100,000 group, however there were no significant differences in 25-OHD between the placebo, 50,000 and 100,000 loading dose groups after 4-weeks (69.3, 84.5, 75.6 nmol/L, p = 0.15 and 3-months (86.7, 84.2, 73.3 nmol/L, p = 0.09, respectively. At the end of the study, approximately 75% of the placebo and 50,000 groups had reached the target therapeutic range (75 nmol/L, and 44% of the 100,000 group. Conclusions In correcting vitamin D insufficiency/deficiency in elderly patients with hip fracture, our findings suggest that starting with a lower daily dose of Vitamin D3 achieved similar results as providing an additional large loading dose of Vitamin D2. At the end of the study, all three groups were equally effective in attaining improvement in 25-OHD levels. Given that a daily dose of 1,000 IU vitamin D3 (with or without a loading dose resulted in at least 25% of patients having suboptimal vitamin D status, patients with acute hip fracture may benefit from a higher daily dose of vitamin D. Trial registration Clinical

Pharmacokinetic and pharmacogenomic profiles of telmisartan after the oral microdose and therapeutic dose.

Science.gov (United States)

Ieiri, Ichiro; Nishimura, Chisa; Maeda, Kazuya; Sasaki, Tomohiro; Kimura, Miyuki; Chiyoda, Takeshi; Hirota, Tekeshi; Irie, Shin; Shimizu, Hitoshi; Noguchi, Takanori; Yoshida, Kenji; Sugiyama, Yuichi

2011-08-01

In this study, we evaluated (a) the contribution of SLCO1B3 and UGT1A polymorphisms to the pharmacokinetics of telmisartan in two forms, a microdose (MD) and a therapeutic dose (TD); (b) linkage disequilibrium (LD) between UGT1A1 and UGT1A3; and (c) linearity in the pharmacokinetics of telmisartan between the two forms. Telmisartan was orally administered at MD condition (100 μg), and then at TD condition (80 mg) to 33 healthy volunteers whose genotypes were prescreened by DMET Plus. Plasma concentrations of telmisartan and its glucuronide were measured by LC-MS/MS, and population pharmacokinetic analysis was performed. No obvious effect of SLCO1B3 polymorphisms (334T>G, 699G>A, and rs11045585) on the pharmacokinetics of telmisartan was observed. The strong LD between UGT1A1*6 and UGT1A3*4a, and between UGT1A1*28 and UGT1A3*2a were observed. After both MD and TD administration, the mean area under the curve0-24 (±standard deviation) of telmisartan was significantly lower and higher in individuals with the UGT1A3*2a (TD, 1701±970 ng hr/ml; MD, 978±537 pg hr/ml) and *4a variants (TD, 5340±1168; MD, 3145±1093), respectively, compared with those in individuals with UGT1A3*1/*1 (TD, 2969±1456; MD, 1669±726). These results were quantitatively confirmed by population pharmacokinetic analysis. Nonlinearity of the dose-exposure relationship was observed between the MD and TD. The haplotypes of UGT1A3 significantly influenced pharmacokinetics of telmisartan and a strong LD between UGT1A1 genotype and UGT1A3 haplotype was observed. These findings are potentially of pharmacological and toxicological importance to the development and clinical use of drugs.

Isolation time determination of patients with differentiated thyroid carcinoma treated with therapeutic doses of 131 radioiodine

International Nuclear Information System (INIS)

Sierralta, M.P.; Lillo, R.; Massardo, T.; Jofre, M.J.

2002-01-01

Isolation time determination of patients with differentiated thyroid carcinoma treated with therapeutic doses of 131 radioiodine. Introduction: The coadyuvant treatment with 131 I had proven to be useful in patients with differentiated thyroid carcinoma (DTC). Due to the physical characteristics of this radioisotope these patients must be absolutely isolated in order to reduce the radioactive exposure to other individuals. The aim of the study was to determine the time required to reach the maximum permissible radiation exposure level (0,25mR/h) to general public. Material between August 1999 and May 2000, 30 patients with DTC diagnosis in the University of Chile Clinical Hospital Nuclear Medicine Centre were studied, 25 women (83%) and 5 men (17%), mean age 45 years old (15-71 range). Tumoral histology was 86% papillary and 14% follicular types. Thirty one doses of 131 I were administered ( one patient received 2 doses): 24 of 100 mCi (77%), 5 of 150 mCi (16%) and 2 of 200 mCi (7%); afterwards the 1 m exposition rate in air was measured at neck level with a Geiger-Mueller detector. The procedure was repeated on day 4 and every day following until the predicted radiation exposure levels were reached. Results: The average exposure rate at day 0 ( after given the radiopharmaceutical) was 20,12 mR/h (4-32 range). At day 4 the average rate was 0,21 mR/h (0,08-0,34 ), and 61% (n=19) of the patients reached 0,25 mR/h within that day. On day 5 10% (n=3) reached 0,25 mR/h (0,25-0,26), on day 6 16% (n=5) reached 0,25 mR/h (0,2-0,28), on day 7 6% (n=2) reached 0,39 mR/h (0,25-0,48) and the remaining 7% on day 13 and day 17 (n=2). Conclusion After a treatment dose of 131 iodine over 60% of the cases can finish the isolation on day 4, and 90% on day 7. The measurement of 131 I uptake after 24 hours will help to determine the evolution of post treatment levels

Isolation time determination of patients with differentiated thyroid carcinoma treated with therapeutic doses of 131 radioiodine

Energy Technology Data Exchange (ETDEWEB)

Sierralta, M P [University of Chile Clinical Hospital Nuclear Medicine Centre, Santiago (Chile); Military Hospital Nuclear Medicine Department , Santiago (Chile); Lillo, R; Massardo, T [University of Chile Clinical Hospital Nuclear Medicine Centre, Santiago (Chile); Jofre, M J [Military Hospital Nuclear Medicine Department, Santiago (Chile)

2002-09-01

Isolation time determination of patients with differentiated thyroid carcinoma treated with therapeutic doses of 131 radioiodine. Introduction: The coadyuvant treatment with 131 I had proven to be useful in patients with differentiated thyroid carcinoma (DTC). Due to the physical characteristics of this radioisotope these patients must be absolutely isolated in order to reduce the radioactive exposure to other individuals. The aim of the study was to determine the time required to reach the maximum permissible radiation exposure level (0,25mR/h) to general public. Material between August 1999 and May 2000, 30 patients with DTC diagnosis in the University of Chile Clinical Hospital Nuclear Medicine Centre were studied, 25 women (83%) and 5 men (17%), mean age 45 years old (15-71 range). Tumoral histology was 86% papillary and 14% follicular types. Thirty one doses of 131 I were administered ( one patient received 2 doses): 24 of 100 mCi (77%), 5 of 150 mCi (16%) and 2 of 200 mCi (7%); afterwards the 1 m exposition rate in air was measured at neck level with a Geiger-Mueller detector. The procedure was repeated on day 4 and every day following until the predicted radiation exposure levels were reached. Results: The average exposure rate at day 0 ( after given the radiopharmaceutical) was 20,12 mR/h (4-32 range). At day 4 the average rate was 0,21 mR/h (0,08-0,34 ), and 61% (n=19) of the patients reached 0,25 mR/h within that day. On day 5 10% (n=3) reached 0,25 mR/h (0,25-0,26), on day 6 16% (n=5) reached 0,25 mR/h (0,2-0,28), on day 7 6% (n=2) reached 0,39 mR/h (0,25-0,48) and the remaining 7% on day 13 and day 17 (n=2). Conclusion After a treatment dose of 131 iodine over 60% of the cases can finish the isolation on day 4, and 90% on day 7. The measurement of 131 I uptake after 24 hours will help to determine the evolution of post treatment levels.

Drug persistence and need for dose intensification to adalimumab therapy; the importance of therapeutic drug monitoring in inflammatory bowel diseases.

Science.gov (United States)

Gonczi, Lorant; Kurti, Zsuzsanna; Rutka, Mariann; Vegh, Zsuzsanna; Farkas, Klaudia; Lovasz, Barbara D; Golovics, Petra A; Gecse, Krisztina B; Szalay, Balazs; Molnar, Tamas; Lakatos, Peter L

2017-08-08

Therapeutic drug monitoring (TDM) aid therapeutic decision making in patients with inflammatory bowel disease (IBD) who lose response to anti-TNF therapy. Our aim was to evaluate the frequency and predictive factors of loss of response (LOR) to adalimumab using TDM in IBD patients. One hundred twelve IBD patients (with 214 TDM measurements, CD/UC 84/28, male/female 50/62, mean age CD/UC: 36/35 years) were enrolled in this consecutive cohort from two referral centres in Hungary. Demographic data were comprehensively collected and harmonized monitoring strategy was applied. Previous and current therapy, laboratory data and clinical activity were recorded at the time of TDM. Patients were evaluated either at the time of suspected LOR or during follow-up. TDM measurements were determined by commercial ELISA (LISA TRACKER, Theradiag, France). Among 112 IBD patients, LOR/drug persistence was 25.9%/74.1%. The cumulative ADA positivity (>10 ng/mL) and low TL (<5.0 μg/mL) was 12.1% and 17.8% after 1 year and 17.3% and 29.5% after 2 years of adalimumab therapy. Dose intensification was needed in 29.5% of the patients. Female gender and ADA positivity were associated with LOR (female gender: p < 0.001, OR:7.8 CI 95%: 2.5-24.3, ADA positivity: p = 0.007 OR:3.6 CI 95%: 1.4-9.5). ADA development, low TL and need for dose intensification were frequent during adalimumab therapy and support the selective use of TDM in IBD patients treated with adalimumab. ADA positivity and gender were predictors of LOR.

Dose-dependent response of Trichoderma harzianum in improving drought tolerance in rice genotypes.

Science.gov (United States)

Pandey, Veena; Ansari, Mohammad W; Tula, Suresh; Yadav, Sandep; Sahoo, Ranjan K; Shukla, Nandini; Bains, Gurdeep; Badal, Shail; Chandra, Subhash; Gaur, A K; Kumar, Atul; Shukla, Alok; Kumar, J; Tuteja, Narendra

2016-05-01

This study demonstrates a dose-dependent response of Trichoderma harzianum Th-56 in improving drought tolerance in rice by modulating proline, SOD, lipid peroxidation product and DHN / AQU transcript level, and the growth attributes. In the present study, the effect of colonization of different doses of T. harzianum Th-56 strain in rice genotypes were evaluated under drought stress. The rice genotypes treated with increasing dose of T. harzianum strain Th-56 showed better drought tolerance as compared with untreated control plant. There was significant change in malondialdehyde, proline, higher superoxide dismutase level, plant height, total dry matter, relative chlorophyll content, leaf rolling, leaf tip burn, and the number of scorched/senesced leaves in T. harzianum Th-56 treated rice genotypes under drought stress. This was corroborated with altered expression of aquaporin and dehydrin genes in T. harzianum Th-56 treated rice genotypes. The present findings suggest that a dose of 30 g/L was the most effective in improving drought tolerance in rice, and its potential exploitation will contribute to the advancement of rice genotypes to sustain crop productivity under drought stress. Interaction studies of T. harzianum with three aromatic rice genotypes suggested that PSD-17 was highly benefitted from T. harzianum colonization under drought stress.

Asymmetric fan beams (AFB) for improvement of the craniocaudal dose distribution in helical tomotherapy delivery

International Nuclear Information System (INIS)

Gladwish, Adam; Kron, Tomas; McNiven, Andrea; Bauman, Glenn; Van Dyk, Jake

2004-01-01

Helical tomotherapy (HT) is a novel radiotherapy technique that utilizes intensity modulated fan beams that deliver highly conformal dose distributions in a helical beam trajectory. The most significant limitation in dose delivery with a constant fan beam thickness (FBT) is the penumbra width of the dose distribution in the craniocaudal direction, which is equivalent to the FBT. We propose to employ a half-blocked fan beam at start and stop location to reduce the penumbra width by half. By opening the jaw slowly during the helical delivery until the desired FBT is achieved it is possible to create a sharper edge in the superior and inferior direction from the target. The technique was studied using a tomotherapy beam model implemented on a commercial treatment planning system (Theraplan Plus V3.0). It was demonstrated that the dose distribution delivered using a 25 mm fan beam can be improved significantly, to reduce the dose to normal structures located superiorly and inferiorly of the target. Dosimetry for this technique is straightforward down to a FBT of 15 mm and implementation should be simple as no changes in couch movement are required compared to a standard HT delivery. We conclude that the use of asymmetric collimated fan beams for the start and stop of the helical tomotherapeutic dose delivery has the potential of significantly improving the dose distribution in helical tomotherapy

Trace levels of innate immune response modulating impurities (IIRMIs synergize to break tolerance to therapeutic proteins.

Directory of Open Access Journals (Sweden)

Daniela Verthelyi

Full Text Available Therapeutic proteins such as monoclonal antibodies, replacement enzymes and toxins have significantly improved the therapeutic options for multiple diseases, including cancer and inflammatory diseases as well as enzyme deficiencies and inborn errors of metabolism. However, immune responses to these products are frequent and can seriously impact their safety and efficacy. Of the many factors that can impact protein immunogenicity, this study focuses on the role of innate immune response modulating impurities (IIRMIs that could be present despite product purification and whether these impurities can synergize to facilitate an immunogenic response to therapeutic proteins. Using lipopolysaccharide (LPS and CpG ODN as IIRMIs we showed that trace levels of these impurities synergized to induce IgM, IFNγ, TNFα and IL-6 expression. In vivo, trace levels of these impurities synergized to increase antigen-specific IgG antibodies to ovalbumin. Further, whereas mice treated with human erythropoietin showed a transient increase in hematocrit, those that received human erythropoietin containing low levels of IIRMIs had reduced response to erythropoietin after the 1(st dose and developed long-lasting anemia following subsequent doses. This suggests that the presence of IIRMIs facilitated a breach in tolerance to the endogenous mouse erythropoietin. Overall, these studies indicate that the risk of enhancing immunogenicity should be considered when establishing acceptance limits of IIRMIs for therapeutic proteins.

Trace levels of innate immune response modulating impurities (IIRMIs) synergize to break tolerance to therapeutic proteins.

Science.gov (United States)

Verthelyi, Daniela; Wang, Vivian

2010-12-22

Therapeutic proteins such as monoclonal antibodies, replacement enzymes and toxins have significantly improved the therapeutic options for multiple diseases, including cancer and inflammatory diseases as well as enzyme deficiencies and inborn errors of metabolism. However, immune responses to these products are frequent and can seriously impact their safety and efficacy. Of the many factors that can impact protein immunogenicity, this study focuses on the role of innate immune response modulating impurities (IIRMIs) that could be present despite product purification and whether these impurities can synergize to facilitate an immunogenic response to therapeutic proteins. Using lipopolysaccharide (LPS) and CpG ODN as IIRMIs we showed that trace levels of these impurities synergized to induce IgM, IFNγ, TNFα and IL-6 expression. In vivo, trace levels of these impurities synergized to increase antigen-specific IgG antibodies to ovalbumin. Further, whereas mice treated with human erythropoietin showed a transient increase in hematocrit, those that received human erythropoietin containing low levels of IIRMIs had reduced response to erythropoietin after the 1(st) dose and developed long-lasting anemia following subsequent doses. This suggests that the presence of IIRMIs facilitated a breach in tolerance to the endogenous mouse erythropoietin. Overall, these studies indicate that the risk of enhancing immunogenicity should be considered when establishing acceptance limits of IIRMIs for therapeutic proteins.

Does an individual estimation of halflife improve the results of radioiodine therapy of Graves' disease?

International Nuclear Information System (INIS)

Schneider, P.; Koerber, C.; Koerber-Hafner, N.; Haenscheid, H.; Reiners, Chr.

2002-01-01

Aim: The impact of our dosimetry concept on radioiodine therapy success in Graves' disease (GD) was analysed. Three questions arised: Did individual estimation of pretherapeutic halflife improve therapeutic success? Did individual dosimetry result in accurate dose calculation? Did antithyroid medication have a measurable influence on therapeutic success under the prevailing conditions? Methods: 126 consecutive patients were treated with 200 Gy I-131 in our therapy ward for GD and followed-up six to nine months after therapy. Success quote was assessed using a standardized protocol and treatment was classified as successful when the patients was eu- or hypothyroid, or unsuccessful when he or she presented with a suppressed TSH-level or in hyperthyroid condition after antithyroid medication withdrawal. Antithyroid medication, activity I-131, dose, concentration of fT 3 and fT 4 , specific delivered dose and halflife were put into a multiple regression model to assess their influence on therapeutic success. In order to assess possible factors disturbing the therapeutic outcome, relevant parameters were analyzed using Logit transformation. Results: Out of 126 patients 84 were classified as successfully treated and 42 (33,3%) as failures. A significant influence on the outcome only was found for thyroid mass. However, therapeutic success appeared to be more distinctly determined by the specific delivered dose using an estimated halflife of 5.5 days (Odds: 10.0, p [de

Clinical impact of laboratory error on therapeutic drug monitoring of once-daily tobramycin in cystic fibrosis: Case series

Directory of Open Access Journals (Sweden)

William A Prescott

2014-01-01

Full Text Available Once-daily dosing intravenous tobramycin is commonly used to treat cystic fibrosis pulmonary exacerbations. Clinicians often utilize historical therapeutic drug monitoring data to individualize the dose among patients who have been treated with tobramycin previously. This case series involves three patients with cystic fibrosis who had supra-therapeutic tobramycin levels despite use of a once-daily dosing that produced therapeutic drug levels during a previous hospital admission, raising questions about the validity of these levels. Investigation into several potential sources of error led to the discovery of an analyzer error in the laboratory. Once the laboratory’s tobramycin analyzer was recalibrated, the reported levels were comparable to historical levels. This case series emphasizes the clinical importance of critically analyzing reported levels, and specifically, the importance of utilizing past therapeutic drug monitoring data, if available, for all patients treated with intravenous tobramycin. If a patient was therapeutic on a similar dose of tobramycin during a previous admission, a dose adjustment may not be necessary, and clinicians should consider repeating levels while pursuing alternative explanations for the discrepant serum levels.

Patient dose in image guided radiotherapy: Monte Carlo study of the CBCT dose contribution

OpenAIRE

Leotta, Salvatore; Amato, Ernesto; Settineri, Nicola; Basile, Emilia; Italiano, Antonio; Auditore, Lucrezia; Santacaterina, Anna; Pergolizzi, Stefano

2018-01-01

Image Guided RadioTherapy (IGRT) is a technique whose diffusion is growing thanks to the well-recognized gain in accuracy of dose delivery. However, multiple Cone Beam Computed Tomography (CBCT) scans add dose to patients, and its contribution has to be assessed and minimized. Aim of our work was to evaluate, through Monte Carlo simulations, organ doses in IGRT due to CBCT and therapeutic MV irradiation in head-neck, thorax and pelvis districts. We developed a Monte Carlo simulation in GAMOS ...

Therapeutic Nanodevices

Science.gov (United States)

Lee, Stephen; Ruegsegger, Mark; Barnes, Philip; Smith, Bryan; Ferrari, Mauro

Therapeutic nanotechnology offers minimally invasive therapies with high densities of function concentrated in small volumes, features that may reduce patient morbidity and mortality. Unlike other areas of nanotechnology, novel physical properties associated with nanoscale dimensionality are not the raison d'être of therapeutic nanotechnology, whereas the aggregation of multiple biochemical (or comparably precise) functions into controlled nanoarchitectures is. Multifunctionality is a hallmark of emerging nanotherapeutic devices, and multifunctionality can allow nanotherapeutic devices to perform multistep work processes, with each functional component contributing to one or more nanodevice subroutine such that, in aggregate, subroutines sum to a cogent work process. Cannonical nanotherapeutic subroutines include tethering (targeting) to sites of disease, dispensing measured doses of drug (or bioactive compound), detection of residual disease after therapy and communication with an external clinician/operator. Emerging nanotherapeutics thus blur the boundaries between medical devices and traditional pharmaceuticals. Assembly of therapeutic nanodevices generally exploits either (bio)material self-assembly properties or chemoselective bioconjugation techniques, or both. Given the complexity, composition, and the necessity for their tight chemical and structural definition inherent in the nature of nanotherapeutics, their cost of goods (COGs) might exceed that of (already expensive) biologics. Early therapeutic nanodevices will likely be applied to disease states which exhibit significant unmet patient need (cancer and cardiovascular disease), while application to other disease states well-served by conventional therapy may await perfection of nanotherapeutic design and assembly protocols.

Methodology to administer therapeutic dose of I-131

International Nuclear Information System (INIS)

Basteris M, J.; Gomez D, R.

2007-01-01

The present work suggests the use of measures guided to eliminate the resulting chronic sialoadenitis of the treatment of the thyroid cancer with Iodine-131, as well as the use of citric fruits to stimulate the salivation, the post-dose administration of liquids to accelerate the gastric emptying avoiding the secondary effects as the vomit is included. (Author)

Real time sensor for therapeutic radiation delivery

International Nuclear Information System (INIS)

Bliss, M.; Craig, R.A.; Reeder, P.L.

1998-01-01

The invention is a real time sensor for therapeutic radiation. A probe is placed in or near the patient that senses in real time the dose at the location of the probe. The strength of the dose is determined by either an insertion or an exit probe. The location is determined by a series of vertical and horizontal sensing elements that gives the operator a real time read out dose location relative to placement of the patient. The increased accuracy prevents serious tissue damage to the patient by preventing overdose or delivery of a dose to a wrong location within the body. 14 figs

Therapeutic improvement of colonic anastomotic healing under complicated conditions

DEFF Research Database (Denmark)

Nerstrøm, Malene; Krarup, Peter-Martin; Jørgensen, Lars Nannestad

2016-01-01

AIM: To identify therapeutic agents for the prophylaxis of gastrointestinal anastomotic leakage (AL) under complicated conditions. METHODS: The PubMed and EMBASE databases were searched for English articles published between January 1975 and September 2014. Studies with the primary purpose of imp...... controls in experimental chemotherapeutic models. CONCLUSION: This systematic review identified potential therapeutic agents, but more studies are needed before concluding that any of these are useful for AL prophylaxis....

EcoDoses improving radiological assessment of doses to man from terrestrial ecosystems. A status report for the NKS-B project 2003

Energy Technology Data Exchange (ETDEWEB)

Bergan, T. [Lavrans Skuterud, Haevard Thoerring (Norway); Liland, A. [Norwegian Radiation Protection Authority (NRPA) (Denmark)] (eds.)

2004-05-01

The NKS B-programme EcoDoses project started in 2003 as a collaboration between all the Nordic countries. The aim of the project is to improve the radiological assessments of doses to man from terrestrial ecosystems. The first part, conducted in 2003, has focussed on an extensive collation and review of both published and unpublished data from all the Nordic countries for the nuclear weapons fallout period and the post-Chemobyl period. This included data on radionuclides in air filters, precipitation, soil samples, milk and reindeer. Based on this, an improved model for estimating radioactive fallout based on precipitation data during the nuclear weapons fallout period has been developed. Effective ecological half- lives for 137Cs and 90Sr in milk have been calculated for the nuclear weapons fallout period. For reindeer the ecological half- lives for 137Cs have been calculated for both the nuclear weapons fallout period and the post-Chemobyl period. The data were also used to compare modelling results with observed concentrations. This was done at a workshop where the radioecological food-and-dose module in the ARGOS decision support system was used to predict transfer of deposited radionuclides to foodstuffs and subsequent radiation doses to man. The work conducted the first year is presented in this report and gives interesting, new results relevant for terrestrial radioecology. (au)

Efficacy and persistence of low-dose mirabegron (25 mg) in patients with overactive bladder: analysis in a real-world urological practice.

Science.gov (United States)

Shen, Yuan Chi; Wang, Hung Jen; Chuang, Yao Chi

2018-06-07

Mirabegron is a relatively new drug to treat overactive bladder (OAB). The therapeutic doses are between 25 and 100 mg in clinical trials. We aimed to evaluate the efficacy and persistence of low-dose mirabegron (25 mg) in patients with OAB in daily urological practice. The study was a retrospective consecutive cohort of 177 OAB patients (101 male and 76 female) treated with 25 mg of mirabegron mg since January 2016 to November 2016. The therapeutic outcomes were assessed at baseline, 4, 12, and 24 weeks. Mirabegron usage was associated with a statistically significant decrease in Overactive Bladder Symptom Score, Urgency Severity Score, urge urinary incontinence, International Prostate Symptom Score (both storage and voiding symptom) at 4-week follow-up, and the therapeutic effects were further improved at 12- and 24-week follow-up. Among them, 118 patients (66.7%) and 84 patients (47.5%) were maintained on mirabegron therapy for more than 3 and 6 months, respectively. However, 29 patients (16%) had poor response with drug discontinuation within 3 months and 8 patients (4.5%) stopped medication due to adverse effects. The overall side effect was 10.2%, and the most common side effect was elevated blood pressure (2.8%) and increased post-void residual (2.8%). Between male and female patients, there was no statistical difference of symptom improvement and drug persistence rate. Low-dose mirabegron (25 mg) improves clinical outcomes in two-thirds of OAB patients with good safety profile and high persistence in daily urological practice. The therapeutic effect is similar between the genders.

Pre-therapeutic blood dosimetry in patients with differentiated thyroid carcinoma using 124-iodine. Predicted blood doses correlate with changes in blood cell counts after radioiodine therapy and depend on modes of TSH stimulation and number of preceding radioiodine therapies

International Nuclear Information System (INIS)

Hartung-Knemeyer, V.; Nagarajah, J.; Jentzen, W.; Ruhlmann, M.; Freudenberg, L.S.; Stahl, A.R.; Bockisch, A.; Rosenbaum-Krumme, S.J.

2012-01-01

Pre-therapeutic blood dosimetry prior to a high-dose radioiodine therapy (RAIT) is recommended and a blood dose of 2 Gy is considered to be safe. In this study, changes in the blood cell count after radioiodine therapy of high risk differentiated thyroid carcinoma (DTC) were analyzed and compared with the results of the pre-therapeutic blood dosimetry using 124 I. Moreover, the influence of different modes of TSH stimulation and the number of preceding radioiodine therapies on the blood dose were assessed. 198 patients with locally advanced or metastasized DTC received a pre-therapeutic blood dosimetry using 124 I. To analyze the influence of the modes of TSH stimulation and the number of preceding RAITs on blood dose subgroups were built as follows: patients with endogenous TSH stimulation versus patients with exogenous TSH stimulation and patients with no preceding RAIT versus patients with at least one preceding RAIT. In 124/198 patients subsequent RAIT was performed. In 73/124 patients, hemograms were performed from day 2 to 12 month after RAIT. There was no high-grade bone marrow toxicity (id est (i.e.) ≥grade 3) in patients receiving less than 2 Gy blood dose-independent of the therapeutic history. Within the first month after radioiodine therapy, there was an overall decrease in the white blood cell and platelet counts. The erythrocyte count was essentially stable. There was a correlation between cell count decrease and predicted blood doses (Spearman's correlation coefficient >-0.6 each) for the white cell line and the platelets. With regard to the subgroups, the blood dose per administered 131 I activity (BDpA) was significantly higher in patients with endogenous TSH stimulation (median 0.08 Gy/GBq) than in patients with exogenous TSH stimulation (0.06 Gy/GBq) and in patients with no previous RAIT (0.08 Gy/GBq) compared to patients who had previously undergone at least one RAIT (0.07 Gy/GBq). The range of BDpA among DTC patients is rather wide. Our

A rational quantitative approach to determine the best dosing regimen for a target therapeutic effect: a unified formalism for antibiotic evaluation.

Science.gov (United States)

Li, Jun; Nekka, Fahima

2013-02-21

The determination of an optimal dosing regimen is a critical step to enhance the drug efficacy and avoid toxicity. Rational dosing recommendations based on mathematical considerations are increasingly being adopted in the process of drug development and use. In this paper, we propose a quantitative approach to evaluate the efficacy of antibiotic agents. By integrating both pharmacokinetic (PK) and pharmacodynamic (PD) information, this approach gives rise to a unified formalism able to measure the cause-effect of dosing regimens. This new pharmaco-metric allows to cover a whole range of antibiotics, including the two well known concentration and time dependent classes, through the introduction of the Hill-dependency concept. As a direct fallout, our formalism opens a new path toward the bioequivalence evaluation in terms of PK and PD, which associates the in vivo drug concentration and the in vitro drug effect. Using this new approach, we succeeded to reveal unexpected, but relevant behaviors of drug performance when different drug regimens and drug classes are considered. Of particular notice, we found that the doses required to reach the same therapeutic effect, when scheduled differently, exhibit completely different tendencies for concentration and time dependent drugs. Moreover, we theoretically confirmed the previous experimental results of the superiority of the once daily regimen of aminoglycosides. The proposed methodology is appealing for its computational features and can easily be applicable to design fair clinical protocols or rationalize prescription decisions. Copyright © 2012 Elsevier Ltd. All rights reserved.

Application of organ tolerance dose-constraints in clinical studies in radiation oncology

International Nuclear Information System (INIS)

Doerr, Wolfgang; Herrmann, Thomas; Baumann, Michael

2014-01-01

In modern radiation oncology, tolerance dose-constraints for organs at risk (OAR) must be considered for treatment planning, but particularly in order to design clinical studies. Tolerance dose tables, however, only address one aspect of the therapeutic ratio of any clinical study, i.e., the limitation of adverse events, but not the desired potential improvement in the tumor effect of a novel treatment strategy. A sensible application of ''tolerance doses'' in a clinical situation requires consideration of various critical aspects addressed here: definition of tolerance dose, specification of an endpoint/symptom, consideration of radiation quality and irradiation protocol, exposed volume and dose distribution, and patient-related factors of radiosensitivity. The currently most comprehensive estimates of OAR radiation tolerance are in the QUANTEC compilations (2010). However, these tolerance dose values must only be regarded as a rough orientation and cannot answer the relevant question for the patients, i.e., if the study can achieve a therapeutic advantage; this can obviously be answered only by the final scientific analysis of the study results. Despite all limitations, the design of clinical studies should currently refer to the QUANTEC values for appreciation of the risk of complications, if needed supplemented by one's own data or further information from the literature. The implementation of a consensus on the safety interests of the patients and on an application and approval process committed to progress in medicine, with transparent quality-assuring requirements with regard to the structural safeguarding of the study activities, plays a central role in clinical research in radiation oncology. (orig.) [de

Microdosing clinical study: pharmacokinetic, pharmacogenomic (SLCO2B1), and interaction (grapefruit juice) profiles of celiprolol following the oral microdose and therapeutic dose.

Science.gov (United States)

Ieiri, Ichiro; Doi, Yohei; Maeda, Kazuya; Sasaki, Tomohiro; Kimura, Miyuki; Hirota, Takeshi; Chiyoda, Takeshi; Miyagawa, Mayuko; Irie, Shin; Iwasaki, Kazuhide; Sugiyama, Yuichi

2012-07-01

The authors evaluated the contribution of the SLCO2B1 polymorphism to the pharmacokinetics of celiprolol at a microdose (MD) and therapeutic dose (TD) and compared pharmacokinetic proportionality between the 2 dose forms in 30 SLCO2B1 genotype-matched healthy volunteers. Three drugs (celiprolol, fexofenadine, and atenolol) were orally administered as a cassette dosing following the MD (totally 97.5 µg) and then a TD (100 mg) of celiprolol, with and without grapefruit juice. The mean AUC(0-24) of celiprolol was lower in SLCO2B1*3/*3 individuals (775 ng·h/mL) than in *1/*3 (1097 ng·h/mL) and *1/*1 (1547 ng·h/mL) individuals following the TD, and this was confirmed in population pharmacokinetic analysis with statistical significances; however, SLCO2B1 genotype-dependent differences disappeared following the MD. Dose-normalized AUC of celiprolol at the MD was much lower than that at the TD, explained by the saturation of the efflux transporter. Thus, the effect of SLCO2B1 polymorphism on the AUC of celiprolol clearly observed only at the TD may be due to the saturation of the efflux transport systems.

Improvement of quantification of somatic radiation risks at low doses

International Nuclear Information System (INIS)

Jacobi, W.; Paretzke, H.G.; Henrichs, K.; Hettig, H.; Jacob, P.; Merkle, W.; Messerer, P.; Schindel, F.

1985-10-01

In this research contract several selected topics of basic relevancy for assessment models of radiological consequences of hypothetical reactor accidents have been considered. The investigations focussed on the following areas: 1) Age dependent dose conversion factors for members of the public and their variability for radioisotopes of iodine, strontium, and caesium, - improvement of the accuracy of dose calculations for external gamma irradiation from cloud- and ground-shine; 2) analysis of data and models relevant for the assessment of exposure-time-effect relationships for lethal somatic late effects of lung and breast cancer and of leukemia; 3) analysis of various health status indices (e.g. ''loss of healthy life span'') with respect to their usefulness in addition to incidence, mortality, etc. for the evaluation of the magnitude of a health detriment due to a previous radiation exposure. (orig./HP) [de

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

International Nuclear Information System (INIS)

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

2001-01-01

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

Therapeutic irradiation and brain injury

International Nuclear Information System (INIS)

Sheline, G.E.; Wara, W.M.; Smith, V.

1980-01-01

This is a review and reanalysis of the literature on adverse effects of therapeutic irradiation on the brain. Reactions have been grouped and considered according to time of appearance. The emphasis of the analysis is on delayed reactions, especially those that occur from a few months to several years after irradiation. All dose specifications were converted into equivalent megavoltage rads. The data were analyzed in terms of total dose, overall treatment time and number of treatment fractions. Also discussed were acute radiation reactions, early delayed radiation reactions, somnolence and leukoencephalopathy post-irradiation/chemotherapy and combined effects of radiation and chemotherapy

Improvement of dose distribution of esophageal irradiation using the field-within-a-field technique

International Nuclear Information System (INIS)

Iwai, Tsugunori; Okabe, Keigo; Yamato, Hidetada; Murakami, Jyunji; Nakazawa, Yasuo; Kato, Mitsuyoshi

2002-01-01

The wide radiation field for mediastinal dose distribution should be inhomogeneous with the usual simple opposed beam irradiation. The purpose of this study was to improve the dose distribution of the mediastinum using a conventional planning system with a dose-volume histogram (DVH) and the field-in-field technique. Three-dimensional (3D) dose distribution is obtained in bilateral opposed-field irradiation. An overdose area obtained from the 3D dose distribution is defined and reprojected into the irradiation field. A new reduced field is created by removing the reprojected overdose area. A 3D dose distribution is again obtained and compared with the results from first one. Procedures were repeated until each of the target volumes was within ±5% of the prescribed dose and the irradiation volume within 107% or less of the prescribed dose. From the DVH analysis, our field-within-a-field technique resulted in a more uniform dose distribution within the conventional planning. The field-within-a-field technique involves many parameters, and an inverse planning algorithm is suitable for computation. However, with our method, the forward planning system is adequate for planning, at least in a relatively straightforward planning system such as bilateral opposed fields therapy. (author)

Effect of a therapeutic dose of pseudoephedrine on swimmers ...

African Journals Online (AJOL)

is thought to result from direct stimulation of post-synaptic receptors and inhibition ..... optimal effect could be extensive with the use of nutritional supplements; therefore ... These studies support the theory that higher doses of PSE may result in.

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

International Nuclear Information System (INIS)

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

2008-01-01

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

Evaluation of the Effect of Different Doses of Low Energy Shock Wave Therapy on the Erectile Function of Streptozotocin (STZ-Induced Diabetic Rats

Directory of Open Access Journals (Sweden)

Zhong-Cheng Xin

2013-05-01

Full Text Available To investigate the therapeutic effect of different doses of low energy shock wave therapy (LESWT on the erectile dysfunction (ED in streptozotocin (STZ induced diabetic rats. SD rats (n = 75 were randomly divided into 5 groups (normal control, diabetic control, 3 different dose LESWT treated diabetic groups. Diabetic rats were induced by intra-peritoneal injection of STZ (60 mg/kg and rats with fasting blood glucose ≥ 300 mg/dL were selected as diabetic models. Twelve weeks later, different doses of LESWT (100, 200 and 300 shocks each time treatment on penises were used to treat ED (7.33 MPa, 2 shocks/s three times a week for two weeks. The erectile function was evaluated by intracavernous pressure (ICP after 1 week washout period. Then the penises were harvested for histological study. The results showed LESWT could significantly improve the erectile function of diabetic rats, increase smooth muscle and endothelial contents, up-regulate the expression of α-SMA, vWF, nNOS and VEGF, and down- regulate the expression of RAGE in corpus cavernosum. The therapeutic effect might relate to treatment dose positively, and the maximal therapeutic effect was noted in the LESWT300 group. Consequently, 300 shocks each time might be the ideal LESWT dose for diabetic ED treatment.

What is the best pre-therapeutic dosimetry for successful radioiodine therapy of multifocal autonomy?

Energy Technology Data Exchange (ETDEWEB)

Gotthardt, M. [Radboud Univ. Nijmegen Medical Center, Nijmegen (Netherlands). Dept. of Nuclear Medicine; Philipps Univ., Marburg (Germany). Dept. of Nuclear Medicine; Rubner, C. [Philipps Univ., Marburg (Germany). Dept. of Nuclear Medicine; Bauhofer, A. [Philipps Univ., Marburg (DE). Inst. of Theoretical Surgery] (and others)

2006-07-01

Purpose: Dose calculation for radioiodine therapy (RIT) of multifocal autonomies (MFA) is a problem as therapeutic outcome may be worse than in other kinds of autonomies. We compared different dosimetric concepts in our patients. Patients, methods: Data from 187 patients who had undergone RIT for MFA (Marinelli algorithm, volumetric compromise) were included in the study. For calculation, either a standard or a measured half-life had been used and the dosimetric compromise (150 Gy, total thyroid volume). Therapeutic activities were calculated by 2 alternative concepts and compared to therapeutic success achieved (concept of TcTUs-based calculation of autonomous volume with 300 Gy and TcTUs-based adaptation of target dose on total thyroid volume). Results: If a standard half-life is used, therapeutic success was achieved in 90.2% (hypothyroidism 23,1%, n=143). If a measured half-life was used the success rate was 93.1% (13,6% hypothyroidism, n=44). These differences were statistically not significant, neither for all patients together nor for subgroups eu-, hypo-, or hyperthyroid after therapy (ANOVA, all p>0.05). The alternative dosimetric concepts would have resulted either in significantly lower organ doses (TcTUs-based calculation of autonomous volume; 80.76{+-}80.6 Gy versus 125.6{+-}46.3 Gy; p<0.0001) or in systematic over-treatment with significantly higher doses (TcTUs-adapted concept; 164.2{+-}101.7 Gy versus 125.6{+-}46.3 Gy; p=0.0097). Conclusions: TcTUs-based determination of the autonomous volume should not be performed, the TcTUs-based adaptation of the target dose will only increase the rate of hypothyroidism. A standard half-life may be used in pre-therapeutic dosimetry for RIT of MFA. If so, individual therapeutic activities may be calculated based on thyroid size corrected to the 24h ITUs without using Marinelli's algorithm. (orig.)

What is the best pre-therapeutic dosimetry for successful radioiodine therapy of multifocal autonomy?

International Nuclear Information System (INIS)

Gotthardt, M.; Philipps Univ., Marburg; Rubner, C.; Bauhofer, A.

2006-01-01

Purpose: Dose calculation for radioiodine therapy (RIT) of multifocal autonomies (MFA) is a problem as therapeutic outcome may be worse than in other kinds of autonomies. We compared different dosimetric concepts in our patients. Patients, methods: Data from 187 patients who had undergone RIT for MFA (Marinelli algorithm, volumetric compromise) were included in the study. For calculation, either a standard or a measured half-life had been used and the dosimetric compromise (150 Gy, total thyroid volume). Therapeutic activities were calculated by 2 alternative concepts and compared to therapeutic success achieved (concept of TcTUs-based calculation of autonomous volume with 300 Gy and TcTUs-based adaptation of target dose on total thyroid volume). Results: If a standard half-life is used, therapeutic success was achieved in 90.2% (hypothyroidism 23,1%, n=143). If a measured half-life was used the success rate was 93.1% (13,6% hypothyroidism, n=44). These differences were statistically not significant, neither for all patients together nor for subgroups eu-, hypo-, or hyperthyroid after therapy (ANOVA, all p>0.05). The alternative dosimetric concepts would have resulted either in significantly lower organ doses (TcTUs-based calculation of autonomous volume; 80.76±80.6 Gy versus 125.6±46.3 Gy; p<0.0001) or in systematic over-treatment with significantly higher doses (TcTUs-adapted concept; 164.2±101.7 Gy versus 125.6±46.3 Gy; p=0.0097). Conclusions: TcTUs-based determination of the autonomous volume should not be performed, the TcTUs-based adaptation of the target dose will only increase the rate of hypothyroidism. A standard half-life may be used in pre-therapeutic dosimetry for RIT of MFA. If so, individual therapeutic activities may be calculated based on thyroid size corrected to the 24h ITUs without using Marinelli's algorithm. (orig.)

Improvement in erection hardness and intercourse success with first dose of sildenafil citrate 100 mg

Directory of Open Access Journals (Sweden)

Mulhall JP

2013-11-01

Full Text Available John P Mulhall,1 Dana L Creanga,2 Vera J Stecher31Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA; 2Consultant to Pfizer Inc., New York, NY, USA; 3Medical Affairs, Primary Care Business Unit, Pfizer Inc., New York, NY, USAPurpose: To determine, in men with erectile dysfunction (ED, the extent of improvement in erection hardness and in the rate of successful sexual intercourse (SSI during the final intercourse attempt using sildenafil 50 mg compared with the subsequent initial attempt after a dose increase to 100 mg.Patients and methods: This post hoc analysis used data from two randomized, double-blind, placebo-controlled studies of flexible-dose sildenafil for the treatment of men with ED, who were given sildenafil 50 mg or matching placebo, to be taken as needed before sexual intercourse. After 2 weeks, those with no tolerability concerns were titrated up to 100 mg, forming the subgroup of this analysis. The main outcome measures were event log data, including an Erection Hardness Score (EHS and a question on SSI (“Did your erection last long enough for you to have successful sexual intercourse?”, for each attempt at sexual intercourse, analyzed by study and treatment group (sildenafil or placebo. Statistical comparisons were conducted by using the Fisher's exact test.Results: In both studies, the sildenafil group had a larger proportion of EHS4 (completely hard and fully rigid erections (P < 0.001 and SSI (P < 0.005 compared with the placebo group, both before and after the dose increase. Between the final 50 mg sildenafil dose and the initial 100 mg sildenafil dose, the outcomes improved and significantly so in the larger study.Conclusion: The improved efficacy with sildenafil 100 mg versus 50 mg, which occurs rapidly, suggests that patients should be encouraged to use 100 mg if they are unable to achieve completely hard and fully rigid erections or SSI with the 50 mg dose

Low-dose vaporized cannabis significantly improves neuropathic pain.

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Wilsey, Barth; Marcotte, Thomas; Deutsch, Reena; Gouaux, Ben; Sakai, Staci; Donaghe, Haylee

2013-02-01

We conducted a double-blind, placebo-controlled, crossover study evaluating the analgesic efficacy of vaporized cannabis in subjects, the majority of whom were experiencing neuropathic pain despite traditional treatment. Thirty-nine patients with central and peripheral neuropathic pain underwent a standardized procedure for inhaling medium-dose (3.53%), low-dose (1.29%), or placebo cannabis with the primary outcome being visual analog scale pain intensity. Psychoactive side effects and neuropsychological performance were also evaluated. Mixed-effects regression models demonstrated an analgesic response to vaporized cannabis. There was no significant difference between the 2 active dose groups' results (P > .7). The number needed to treat (NNT) to achieve 30% pain reduction was 3.2 for placebo versus low-dose, 2.9 for placebo versus medium-dose, and 25 for medium- versus low-dose. As these NNTs are comparable to those of traditional neuropathic pain medications, cannabis has analgesic efficacy with the low dose being as effective a pain reliever as the medium dose. Psychoactive effects were minimal and well tolerated, and neuropsychological effects were of limited duration and readily reversible within 1 to 2 hours. Vaporized cannabis, even at low doses, may present an effective option for patients with treatment-resistant neuropathic pain. The analgesia obtained from a low dose of delta-9-tetrahydrocannabinol (1.29%) in patients, most of whom were experiencing neuropathic pain despite conventional treatments, is a clinically significant outcome. In general, the effect sizes on cognitive testing were consistent with this minimal dose. As a result, one might not anticipate a significant impact on daily functioning. Published by Elsevier Inc.

Biology of dose rate in brachytherapy

International Nuclear Information System (INIS)

Brenner, David J.

1995-01-01

Purpose: This course is designed for practitioners and beginners in brachytherapy. The aim is to review biological principles underlying brachytherapy, to understand why current treatment regimes are the way they are, and to discuss what the future may hold in store. Brachytherapy has a long history. It was suggested as long ago as 1903 by Alexander Graham Bell, and the optimal application of this technique has been a subject of debate ever since. 'Brachy' means 'short', and the essential features of conventional brachytherapy are: positioning of the source a short distance from, or in, the tumor, allowing good dose distributions; short overall treatment times, to counter tumor repopulation; low dose rate, enabling a good therapeutic advantage between tumor control and damage to late-responding tissue. The advantages of good dose distributions speak for themselves; in some situations, as we shall see, computer-based dose optimization can be used to improve them still further. The advantages of short overall times stem from the fact that accelerated repopulation of the tumor typically begins a few weeks after the start of a radiation treatment. If all the radiation can be crammed in before that time, the risks of tumor repopulation can be considerably reduced. In fact even external-beam radiotherapy is moving in this direction, with the use of highly accelerated protocols. The advantages of low dose rate stem from the differential response to fractionation of early- and late-responding tissues. Essentially, lowering the dose rate spares late-responding tissue more than it does early-responding tissue such as tumors. We shall also discuss some recent innovations in the context of the general principles that have been outlined. For example, High dose rate brachytherapy, particularly for the uterine cervix: Does it work? If so, when and why? Use of Ir-192 sources, with a half life of 70 days: Should corrections be made for changing biological effectiveness as the dose

Use of an electron reflector to improve dose uniformity at the vertex during total skin electron therapy

International Nuclear Information System (INIS)

Peters, V.G.

2000-01-01

Purpose: The vertex of the scalp is always tangentially irradiated during total skin electron therapy (TSET). This study was conducted to determine the dose distribution at the vertex for a commonly used irradiation technique and to evaluate the use of an electron reflector, positioned above the head, as a means of improving the dose uniformity. Methods and Materials: Phantoms, simulating the head of a patient, were irradiated using our standard procedure for TSET. The technique is a six-field irradiation using dual angled electron beams at a treatment distance of 3.6 meters. Vertex dosimetry was performed using ionization methods and film. Measurements were made for an unmodified 6 MeV electron beam and for a 4 MeV beam obtained by placing an acrylic scattering plate in the beam line. Studies were performed to examine the effect of electron scattering on vertex dose when a lead reflector, 50 x 50 cm in area, was positioned above the phantom. Results: The surface dose at the vertex, in the absence of the reflector, was found to be less than 40% of the prescribed skin dose. Use of the lead reflector increased this value to 73% for the 6 MeV beam and 99% for the degraded 4 MeV beam. Significant improvements in depth dose were also observed. The dose enhancement is not strongly dependent on reflector distance or angulation since the reflector acts as a large source of broadly scattered electrons. Conclusion: The vertex may be significantly underdosed using standard techniques for total skin electron therapy. Use of an electron reflector improves the dose uniformity at the vertex and may reduce or eliminate the need for supplemental irradiation

Clinical Implications of Complex Pharmacokinetics for Daratumumab Dose Regimen in Patients With Relapsed/Refractory Multiple Myeloma

DEFF Research Database (Denmark)

Xu, Xu Steven; Yan, Xiaoyu; Puchalski, Thomas

2017-01-01

New therapeutic strategies are urgently needed to improve clinical outcomes in patients with multiple myeloma (MM). Daratumumab is a first-in-class, CD38 human immunoglobulin G1κ monoclonal antibody approved for treatment of relapsed or refractory MM. Identification of an appropriate dose regimen...... for daratumumab is challenging due to its target-mediated drug disposition, leading to time- and concentration-dependent pharmacokinetics. We describe a thorough evaluation of the recommended dose regimen for daratumumab in patients with relapsed or refractory MM. This article is protected by copyright. All...

Combined administration of the GPVI-Fc fusion protein Revacept with low-dose thrombolysis in the treatment of stroke

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Andreas Reimann

2016-04-01

Full Text Available BackgroundThrombolytic therapy with recombinant tissue plasminogen activator (rtPA remains the only approved medication for acute ischemic stroke, but incurs significant bleeding risks. Therefore, approaches to combine lower doses of thrombolytic therapy with other effective drugs aim at improving efficacy and reducing bleeding rates. We examined the safety and therapeutic effects of various dosings of rtPA, either alone or combined with glycoprotein VI-Fc fusion protein (GPVI-Fc, Revacept on experimental stroke in mice.Methods and resultsThe effect of filament-induced intracerebral thrombus formation and embolization was investigated after a one-hour occlusion of the middle cerebral artery.In accordance with previous studies, treatment with 10 mg/kg rtPA significantly improved functional outcome, cerebral infarct size and edema, but also resulted in markedly increased intracranial bleeding volumes. In contrast, low doses of rtPA (0.1 or 0.35 mg/kg body weight did not change outcome parameters. However, addition of 1 mg/kg Revacept to 0.35 mg/kg rtPA led to improved reperfusion compared to rtPA alone. Moreover, these combined treatments resulted in improved grip strength, compared to the respective dose of rtPA alone. Infarct-surrounding edema improved after combined treatments, but not after respective single rtPA dosings. Intracranial bleeding volumes were below controls after all low-dose rtPA therapies, given either alone or combined with Revacept.ConclusionsIn contrast to using the equally effective full dose of rtPA, intracranial bleeding was not increased by low-dose rtPA combined with Revacept. Therefore, addition of Revacept to low-dose rtPA does not incur safety risks, but improves efficacy of treatment.

Dual-color bioluminescent sensor proteins for therapeutic drug monitoring of antitumor antibodies

NARCIS (Netherlands)

van Rosmalen, M.; Ni, Y.; Vervoort, D.F.M.; Arts, R.; Ludwig, S.K.J.; Merkx, M.

2018-01-01

Monitoring the levels of therapeutic antibodies in individual patients would allow patient-specific dose optimization, with the potential for major therapeutic and financial benefits. Our group recently developed a new platform of bioluminescent sensor proteins (LUMABS; LUMinescent AntiBody Sensor)

Low Dose Vaporized Cannabis Significantly Improves Neuropathic Pain

Science.gov (United States)

Wilsey, Barth; Marcotte, Thomas D.; Deutsch, Reena; Gouaux, Ben; Sakai, Staci; Donaghe, Haylee

2013-01-01

We conducted a double-blind, placebo-controlled, crossover study evaluating the analgesic efficacy of vaporized cannabis in subjects, the majority of whom were experiencing neuropathic pain despite traditional treatment. Thirty-nine patients with central and peripheral neuropathic pain underwent a standardized procedure for inhaling either medium dose (3.53%), low dose (1.29%), or placebo cannabis with the primary outcome being VAS pain intensity. Psychoactive side-effects, and neuropsychological performance were also evaluated. Mixed effects regression models demonstrated an analgesic response to vaporized cannabis. There was no significant difference between the two active dose groups’ results (p>0.7). The number needed to treat (NNT) to achieve 30% pain reduction was 3.2 for placebo vs. low dose, 2.9 for placebo vs. medium dose, and 25 for medium vs. low dose. As these NNT are comparable to those of traditional neuropathic pain medications, cannabis has analgesic efficacy with the low dose being, for all intents and purposes, as effective a pain reliever as the medium dose. Psychoactive effects were minimal and well-tolerated, and neuropsychological effects were of limited duration and readily reversible within 1–2 hours. Vaporized cannabis, even at low doses, may present an effective option for patients with treatment-resistant neuropathic pain. PMID:23237736

Dose-Effect Relationship in Chemoradiotherapy for Locally Advanced Rectal Cancer

DEFF Research Database (Denmark)

Jakobsen, Anders; Ploen, John; Vuong, Té

2012-01-01

PURPOSE: Locally advanced rectal cancer represents a major therapeutic challenge. Preoperative chemoradiation therapy is considered standard, but little is known about the dose-effect relationship. The present study represents a dose-escalation phase III trial comparing 2 doses of radiation...

Thyroid abnormalities after therapeutic external radiation

Energy Technology Data Exchange (ETDEWEB)

Hancock, S.L.; McDougall, I.R. [Stanford Univ. School of Medicine, Stanford, CA (United States); Constine, L.S. [Strong Memorial Hospital, Rochester, NY (United States)

1995-03-30

The thyroid gland is the largest pure endocrine gland in the body and one of the organs most likely to produce clinically significant abnormalities after therapeutic external radiation. Radiation doses to the thyroid that exceed approximately 26 Gy frequently produce hypothyroidism, which may be clinically overt or subclinical, as manifested by increased serum thyrotropin and normal serum-free thyroxine concentrations. Pituitary or hypothalamic hypothyroidism may arise when the pituitary region receives doses exceeding 50 Gy with conventional, 1.8-2 Gy fractionation. Direct irradiation of the thyroid may increase the risk of Graves` disease or euthyroid Graves` ophthalmopathy. Silent thyroiditis, cystic degeneration, benign adenoma, and thyroid cancer have been observed after therapeutically relevant doses of external radiation. Direct or incidental thyroid irradiation increases the risk for well-differentiated, papillary, and follicular thyroid cancer from 15- to 53-fold. Thyroid cancer risk is highest following radiation at a young age, decreases with increasing age at treatment, and increases with follow-up duration. The potentially prolonged latent period between radiation exposure and the development of thyroid dysfunction, thyroid nodularity, and thyroid cancer means that individuals who have received neck or pituitary irradiation require careful, periodic clinical and laboratory evaluation to avoid excess morbidity. 39 refs.

Thyroid abnormalities after therapeutic external radiation

International Nuclear Information System (INIS)

Hancock, Steven L.; McDougall, I. Ross; Constine, Louis S.

1995-01-01

The thyroid gland is the largest pure endocrine gland in the body and one of the organs most likely to produce clinically significant abnormalities after therapeutic external radiation. Radiation doses to the thyroid that exceed approximately 26 Gy frequently produce hypothyroidism, which may be clinically overt or subclinical, as manifested by increased serum thyrotropin and normal serum-free thyroxine concentrations. Pituitary or hypothalamic hypothyroidism may arise when the pituitary region receives doses exceeding 50 Gy with conventional, 1.8-2 Gy fractionation. Direct irradiation of the thyroid may increase the risk of Graves' disease or euthyroid Graves' opthalmopathy. Silent thyroiditis, cystic degeneration, benign adenoma, and thyroid cancer have been observed after therapeutically relevant doses of external radiation. Direct or incidental thyroid irradiation increases the risk for well-differentiated, papillary, and follicular thyroid cancer from 15- to 53-fold. Thyroid cancer risk is highest following radiation at a young age, decreases with increasing age at treatment, and increases with follow-up duration. The potentially prolonged latent period between radiation exposure and the development of thyroid dysfunction, thyroid nodularity, and thyroid cancer means that individuals who have received neck or pituitary irradiation require careful, periodic clinical and laboratory evaluation to avoid excess morbidity

The History of Therapeutic Aerosols: A Chronological Review.

Science.gov (United States)

Stein, Stephen W; Thiel, Charles G

2017-02-01

In 1956, Riker Laboratories, Inc., (now 3 M Drug Delivery Systems) introduced the first pressurized metered dose inhaler (MDI). In many respects, the introduction of the MDI marked the beginning of the modern pharmaceutical aerosol industry. The MDI was the first truly portable and convenient inhaler that effectively delivered drug to the lung and quickly gained widespread acceptance. Since 1956, the pharmaceutical aerosol industry has experienced dramatic growth. The signing of the Montreal Protocol in 1987 led to a surge in innovation that resulted in the diversification of inhaler technologies with significantly enhanced delivery efficiency, including modern MDIs, dry powder inhalers, and nebulizer systems. The innovative inhalers and drugs discovered by the pharmaceutical aerosol industry, particularly since 1956, have improved the quality of life of literally hundreds of millions of people. Yet, the delivery of therapeutic aerosols has a surprisingly rich history dating back more than 3500 years to ancient Egypt. The delivery of atropine and related compounds has been a crucial inhalation therapy throughout this period and the delivery of associated structural analogs remains an important therapy today. Over the centuries, discoveries from many cultures have advanced the delivery of therapeutic aerosols. For thousands of years, therapeutic aerosols were prepared by the patient or a physician with direct oversight of the patient using custom-made delivery systems. However, starting with the Industrial Revolution, advancements in manufacturing resulted in the bulk production of therapeutic aerosol delivery systems produced by people completely disconnected from contact with the patient. This trend continued and accelerated in the 20th century with the mass commercialization of modern pharmaceutical inhaler products. In this article, we will provide a summary of therapeutic aerosol delivery from ancient times to the present along with a look to the future. We

The route of administration (oral vs intravenous) does not influence dose or outcome in Graves' disease and unifocal autonomy

International Nuclear Information System (INIS)

Schneider, Peter; Biko, Johannes; Haenscheid, Heribert; Hilliger, Stephan; Koutsampelas, Christos; Kranzfelder, Michael; Ladner, Stephan; Reiners, Christoph

2005-01-01

In a prospective randomised study, we investigated the influence of the route of administration of radioiodide on dosimetry and therapy outcome. Fifty-four patients suffering from Graves' disease (GD) and 60 patients with unifocal autonomy (UA) participated in the study and were randomly treated with either orally or intravenously administered radioiodide. Pretherapeutic dosimetry was based on single uptake measurements with a calibrated uptake probe system. The radioiodine kinetics during hospitalisation was assessed by daily bedside uptake measurements. Therapeutic dose was determined by half-life and thyroid uptake at the time of discharge using the same uptake probe as for the radioiodine test. No improvement in accuracy of dosimetry was achieved when radioiodide was administered intravenously. Mean therapeutic doses were identical following intravenous or oral administration. Variation in the achieved dose was slightly higher in the patients receiving oral administration, this being attributable to larger deviations in discrete activities of the capsules administered as compared with the values determined by dosimetry. No differences according to treatment modality were found with regard to therapeutic outcome. Eighty-seven patients attended 6-month follow-up after therapy. In the UA group, successful treatment, defined as a normal or elevated TSH level, was observed in 94% of patients after oral administration and in 80% after intravenous administration; corresponding figures in the GD group were 68% and 65%. The causes of individual differences between targeted and therapeutically achieved doses remain undetermined. Variations in the bioavailability of radioiodide or other parameters affecting thyroid status may be involved, and further investigations are needed to clarify this. (orig.)

Providing Quality Therapeutics in Switzerland: Role of the Stakeholders and Recent Incentives for Further Improvements.

Science.gov (United States)

Besson, Marie; Samer, Caroline; Rollason, Victoria; Dayer, Pierre; Desmeules, Jules

2015-07-01

Quality therapeutics play an important role in Switzerland's health care and economy. Switzerland holds a key position in the world of research and development, as well as in drug production. Recently, new emphasis has been placed on promoting clinical research and maintaining Switzerland's position as a center of excellence in the field. Recent revisions to the law regarding medical trials in human research allow for better allocation of regulatory resources and simplified procedures for drugs already authorized in Switzerland. The country has its own regulatory agency, the Swiss Agency for Therapeutic Products (Swissmedic), which is a public institution of the Swiss government. Swissmedic is responsible for ensuring safety in medicines, particularly regarding authorizations and market surveillance in the sector of medicinal products and medical devices. Although the centralized authorization procedure of the European Union for medicines does not apply to Switzerland, there are mutual recognition mechanisms between the Swiss medicine regulatory authority and the European Medicines Agency. Swissmedic is also in charge of postmarketing safety and oversees the national pharmacovigilance center, which collaborates closely with the World Health Organization center in Uppsala. In addition, university hospital-based clinical pharmacologists, who are involved in basic science and clinical research, regulatory affairs, ethics committees, and pharmacovigilance, promote quality therapeutics. This article discusses the role of the various stakeholders and the recent efforts made to provide a better allocation of resources aimed at further improving quality therapeutics in Switzerland. Copyright © 2015 Elsevier HS Journals, Inc. All rights reserved.

Therapeutic riding followed by rhythmic auditory stimulation to improve balance and gait in a subject with orthopedic pathologies.

Science.gov (United States)

Ungermann, Cathryn M; Gras, Laura Z

2011-12-01

The study objectives were to investigate the effect of therapeutic riding with a subject who had an orthopedic diagnosis. This is a single-subject case report. The study was conducted at an equestrian facility with an indoor riding arena. The subject was a 59-year-old woman with grade I spondylolisthesis at L4/L5 and multilevel lumbar spinal stenosis in central and foraminal canals. The subject had an anterior cervical fusion of C3-C7. The subject has been ambulating with a straight cane due to her history of frequent falls. Gait, agility, strength, range of motion, and balance testing were performed. The subject had impairments of bilateral lower extremities with an ataxic gait pattern and was at risk for continued falls according to the balance measures. The intervention comprised therapeutic riding sessions 3 times a week for 20 minutes for 4 weeks. Each riding session was immediately followed by a 10-minute independent walking program with a metronome for rhythmic auditory stimulation. The outcome measures were as follows: Manual muscle testing and range of motion of the lower extremities, Gait Speed Test, Dynamic Gait Index, Four-Square Step Test, Chair Stand Test, Single Leg Stance. Improvements were seen in lower extremity strength and range of motion and balance. The subject improved on balance scores, placing her out of the risk for falls category. Therapeutic riding followed by rhythmic auditory stimulation improved lower extremity range of motion, strength, and balance with this subject.

Study on dose distribution of therapeutic proton beams with prompt gamma measurement

Energy Technology Data Exchange (ETDEWEB)

Kim, J. W. [National Cancer Center, Seoul (Korea, Republic of); Min, C. H.; Kim, C. H.; Kim, D. K.; Yoon, M. Y. [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

2007-03-15

The proton beam has an advantage of the sharp dose falloff in dose distribution called Bragg peak while conventional radiation therapy modalities such as photons exhibit considerable amount of exit dose. To take advantage of this property it is important to know the exact location of the distal dose falloff. An error can cause overdose to the normal tissue or underdose to the tumor volume. The only way of finding out the dose distribution in-situ in particle therapy is to measure the gammas produced by nuclear reactions with tissue materials. Two kinds of gammas can be used: one is prompt gamma and the other is coincident gamma from the positron-emission isotopes. We chose to detect prompt gammas, and developed a prompt gamma scanning system (PGS). The proton beams of the proton therapy facility at National Cancer Center were used. The gamma distribution was compared to the dose distribution measured by an ionization chamber at three different energies of 100, 150, 200 MeV's. The two distributions were well correlated within 1-2 mm. The effect of high-energy neutron appeared as blurred distribution near the distal dose falloff at the energy of 200 MeV. We then tested the PGS shielding design by adding additional layer of paraffin plates outside of the PGS, and found that fast neutrons significantly affect the background level. But the location of the dose fall-off was nearly coincident. The analysis of gamma energy spectrum showed that cut-off energy in gamma counting can be adjusted to enhance the signal to noise ratio. Further the ATOM phantom, which has similar tissue structure to human, was used to investigate the gamma distribution for the case of inhomogeneous matter. The location of dose falloff region was found to be well defined as for water phantom. Next an actual therapy beam, which was produced by the double scattering method, was used, for which the dose falloff by the gamma distribution was completely wiped out by background neutrons. It is not

Intranasal mesenchymal stem cell treatment for neonatal brain damage: long-term cognitive and sensorimotor improvement.

Directory of Open Access Journals (Sweden)

Vanessa Donega

Full Text Available Mesenchymal stem cell (MSC administration via the intranasal route could become an effective therapy to treat neonatal hypoxic-ischemic (HI brain damage. We analyzed long-term effects of intranasal MSC treatment on lesion size, sensorimotor and cognitive behavior, and determined the therapeutic window and dose response relationships. Furthermore, the appearance of MSCs at the lesion site in relation to the therapeutic window was examined. Nine-day-old mice were subjected to unilateral carotid artery occlusion and hypoxia. MSCs were administered intranasally at 3, 10 or 17 days after hypoxia-ischemia (HI. Motor, cognitive and histological outcome was investigated. PKH-26 labeled cells were used to localize MSCs in the brain. We identified 0.5 × 10(6 MSCs as the minimal effective dose with a therapeutic window of at least 10 days but less than 17 days post-HI. A single dose was sufficient for a marked beneficial effect. MSCs reach the lesion site within 24 h when given 3 or 10 days after injury. However, no MSCs were detected in the lesion when administered 17 days following HI. We also show for the first time that intranasal MSC treatment after HI improves cognitive function. Improvement of sensorimotor function and histological outcome was maintained until at least 9 weeks post-HI. The capacity of MSCs to reach the lesion site within 24 h after intranasal administration at 10 days but not at 17 days post-HI indicates a therapeutic window of at least 10 days. Our data strongly indicate that intranasal MSC treatment may become a promising non-invasive therapeutic tool to effectively reduce neonatal encephalopathy.

Renal excretion of iodine-131 labelled meta-iodobenzylguanidine and metabolites after therapeutic doses in patients suffering from different neural crest-derived tumours

International Nuclear Information System (INIS)

Wafelman, A.R.; Hoefnagel, C.A.; Maessen, H.J.M.; Maes, R.A.A.; Beijnen, J.H.

1997-01-01

Iodine-131 labelled meta-iodobenzylguanidine ([ 131 I[MIBG) is used for diagnostic scintigraphy and radionuclide therapy of neural crest-derived tumours. After administration of therapeutic doses of [ 131 I[MIBG (3.1-7.5 GBq) to 17 patients (n=32 courses), aged 2-73 years, 56%±10%, 73%±11%, 80%±10% and 83%±10% of the dose was cumulatively excreted as total radioactivity in urine at t=24 h, 48 h, 72 h and 96 h, respectively. Except for two adult patients, who showed excretion of 14%-18% of [ 131 I[meta-iodohippuric acid ([ 131 I[MIHA), the cumulatively excreted radioactivity consisted of >85% [ 131 I[MIBG, with 6% of the dose excreted as free [ 131 I[iodide, 4% as [ 131 I[MIHA and 2.5% as an unknown iodine-131 labelled metabolite. Cumulative renal excretion rates of total radioactivity and of [ 131 I[MIBG appeared to be higher in neuroblastoma and phaeochromocytoma patients than in carcinoid patients. Based on the excretion of small amounts of [ 131 I[meta-iodobenzoic acid in two patients, a possible metabolic pathway for [ 131 I[MIBG is suggested. The degree of metabolism was not related to the extent of liver uptake of radioactivity. (orig.). With 2 figs., 5 tabs

Therapeutic drug management of linezolid: a missed opportunity for clinicians?

Science.gov (United States)

Cattaneo, Dario; Gervasoni, Cristina; Cozzi, Valeria; Castoldi, Simone; Baldelli, Sara; Clementi, Emilio

2016-12-01

Some studies have shown that adjustments to the linezolid dose guided by therapeutic drug monitoring (TDM) can reduce interindividual variability in drug exposure and improve linezolid tolerability. In this study, 6 years of linezolid TDM, a diagnostic service for our hospital and others in the Milan (Italy) area, is described. Samples were collected immediately before the morning dose intake (trough concentrations) in steady-state conditions. Linezolid concentrations were quantified by a validated high-performance liquid chromatography (HPLC) method. Four hundred linezolid trough concentrations from 220 patients were collected. A 20-fold variability in linezolid levels was observed. Positive and significant correlations between linezolid trough concentrations and patient age (r = 0.325, P linezolid concentrations with time was observed in a subgroup of patients with more than one TDM assessment. Elderly patients, especially those aged >80 years and with impaired renal function, are at a higher risk of overexposure to linezolid. Despite the observed progressive increase in linezolid concentrations over time, most physicians did not change the drug dose according to the TDM results, even in the presence of frank overexposure to linezolid. Copyright © 2016 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

Improving the in vivo therapeutic index of siRNA polymer conjugates through increasing pH responsiveness.

Science.gov (United States)

Guidry, Erin N; Farand, Julie; Soheili, Arash; Parish, Craig A; Kevin, Nancy J; Pipik, Brenda; Calati, Kathleen B; Ikemoto, Nori; Waldman, Jacob H; Latham, Andrew H; Howell, Bonnie J; Leone, Anthony; Garbaccio, Robert M; Barrett, Stephanie E; Parmar, Rubina Giare; Truong, Quang T; Mao, Bing; Davies, Ian W; Colletti, Steven L; Sepp-Lorenzino, Laura

2014-02-19

Polymer based carriers that aid in endosomal escape have proven to be efficacious siRNA delivery agents in vitro and in vivo; however, most suffer from cytotoxicity due in part to a lack of selectivity for endosomal versus cell membrane lysis. For polymer based carriers to move beyond the laboratory and into the clinic, it is critical to find carriers that are not only efficacious, but also have margins that are clinically relevant. In this paper we report three distinct categories of polymer conjugates that improve the selectivity of endosomal membrane lysis by relying on the change in pH associated with endosomal trafficking, including incorporation of low pKa heterocycles, acid cleavable amino side chains, or carboxylic acid pH sensitive charge switches. Additionally, we determine the therapeutic index of our polymer conjugates in vivo and demonstrate that the incorporation of pH responsive elements dramatically expands the therapeutic index to 10-15, beyond that of the therapeutic index (less than 3), for polymer conjugates previously reported.

Dose-rate and the reciprocity law: TL response of Ge-doped SiO2 optical fibers at therapeutic radiation doses

International Nuclear Information System (INIS)

Abdul Rahman, A.T.; Nisbet, A.; Bradley, D.A.

2011-01-01

An investigation has been made on commercially available Ge-doped SiO 2 optical fibers as a novel thermoluminescence system for radiotherapy dosimetry. This dosimeter has previously been shown by the group to provide sensitive dosimetry over a wide range of electron and photon dose, suitable for the needs of radiotherapy. In addition the optical fiber offers small physical size (125 μm diameter) and hence high spatial resolution. The reciprocity between thermoluminescence (TL) yield of Ge-doped SiO 2 optical fibers and dose has been investigated for fixed radiation dose for a range of photon and electron dose rates. For electron beams of nominal energies in the range of 9-20 MeV, we have investigated the TL response of these fibers for dose rates between 100 and 1000 cGy min -1 . For photon beams of nominal energies in the range of 6-15 MV, we have used dose rates of 100-600 cGy min -1 . Reproducibility and fading at fixed absorbed dose (3 Gy) and dose rate for the optical fibers were also investigated. At fixed dose rates, the TL optical fibers were found to produce a flat TL yield within 4% (1σ) and 3% (1σ) for electron and photon beams, respectively. The optical fibers demonstrated good reproducibility (±1.5%), low residual signal for a readout temperature of 300 o C and negligible fading. A weak dependence on dose-rate has been observed in the range of 3.4-3.9% for electrons (with an associated uncertainty of 4%) and 2.4-2.9% for photons (with an associated uncertainty of <4%). For electron and photon energies we note a consistent trend towards lower response in the TL yield of between 3.4-3.9% and 2.4-2.7%, respectively, at the higher dose rates in comparison with the response at lower dose rates. In addition we note an appreciable systematic energy dependence for both electron and photon beams. It is important to take such factors into account for providing precise and accurate radiotherapy dosimetry. It is also apparent that the optical fibers can be re

EcoDoses. Improving radiological assessment of doses to man from terrestrial ecosystems. A status report for the NKS-B project 2004

Energy Technology Data Exchange (ETDEWEB)

Nielsen, Sven P.; Isaksson, M.; Nilsson, Elisabeth (and others)

2005-07-01

The NKS B-programme EcoDoses project started in 2003 as a collaboration between all the Nordic countries. The aim of the project is to improve the radiological assessments of doses to man from terrestrial ecosystems. The present report sums up the work performed in the second phase of the project. The main topics in 2004 have been: (i) A continuation of previous work with a better approach for estimating global fallout on a regional or national scale, based on a correlation between precipitation and deposition rates. (ii) Fur-ther extension of the EcoDoses milk database. Estimation of effective ecological half lives of {sup 137}Cs in cows milk focussing on suitable post-Chernobyl time-series. Modelling integrated transfer of {sup 13}7{sup C}s to cow's milk from Nordic countries. (iii) Determination of effective ecological half lives for fresh water fish from Nordic lakes. (iv) Investigate ra-dioecological sensitivity for Nordic populations. (v) Food-chain modelling using the Eco-sys-model, which is the underlying food- and dose-module in several computerised deci-sion-making systems. (au)

EcoDoses. Improving radiological assessment of doses to man from terrestrial ecosystems. A status report for the NKS-B project 2004

International Nuclear Information System (INIS)

Nielsen, Sven P.; Isaksson, M.; Nilsson, Elisabeth

2005-07-01

The NKS B-programme EcoDoses project started in 2003 as a collaboration between all the Nordic countries. The aim of the project is to improve the radiological assessments of doses to man from terrestrial ecosystems. The present report sums up the work performed in the second phase of the project. The main topics in 2004 have been: (i) A continuation of previous work with a better approach for estimating global fallout on a regional or national scale, based on a correlation between precipitation and deposition rates. (ii) Fur-ther extension of the EcoDoses milk database. Estimation of effective ecological half lives of 137 Cs in cows milk focussing on suitable post-Chernobyl time-series. Modelling integrated transfer of 13 7 C s to cow's milk from Nordic countries. (iii) Determination of effective ecological half lives for fresh water fish from Nordic lakes. (iv) Investigate ra-dioecological sensitivity for Nordic populations. (v) Food-chain modelling using the Eco-sys-model, which is the underlying food- and dose-module in several computerised deci-sion-making systems. (au)

External dose measurements for patients receiving therapeutic I-131 for thyroid cancer

International Nuclear Information System (INIS)

Molfetas, M.; Kottou, S.

2002-01-01

Iodine-131 is a well established and effective treatment, supplementing surgery, in differentiated thyroid carcinoma. Iodine-131 except from its β-emission, that generates a cell-killing effect in a small area, has also a γ-emission irradiating distant tissues and even people who are close enough with the treated patient. The International Commission on Radiation Protection, ICRP has estimated the probability of a radiation-induced fatal cancer for the whole population at 5.0 % per sievert for low doses and at low dose rates and at 1.3 % for serious genetic diseases. For elderly people the probability seems to be 3 to 10 times lower, whereas for children up to the age of 10 years, 2-3 times higher. These findings led the ICRP to recommend new dose limits, lower than the previous ones. The European Union has endorsed the ICRP recommendations and the Council issued two directives, with which the Greek legislation complied recently. The current annual public dose limit is 1 mSv, while in the new Greek legislation the concept of dose constrains (0.5 m Sv in Greece) has also been proposed as a goal to reach whenever possible

Improvement of dose determination using glass display of mobile phones for accident dosimetry

International Nuclear Information System (INIS)

Discher, M.; Woda, C.; Fiedler, I.

2013-01-01

Previous studies have demonstrated that mobile phones can be used as suitable emergency dosimeters in case of an accidental radiation overexposure. Glass samples extracted from displays of mobile phones are sensitive to ionizing radiation and can be measured using the thermoluminescence (TL) method. A non-radiation induced background signal (so-called zero dose signal) was observed which overlaps with the radiation induced signal and consequently limits the minimum detectable dose. Investigations of several glasses from different displays showed that it is possible to reduce the zero dose signal up to 90% by etching the glass surface with concentrated hydrofluoric acid. With this approach a reduction of the detection limit of a factor of four, corresponding to approximately 80 mGy, was achieved. Dosimetric properties of etched samples are presented and developed protocols validated by dose recovery tests under realistic conditions. With the improvements in sample preparation the proposed method of dose determination is a competitive alternative to OSL/TL measurements of electronic components and chip cards and provides a useful option for retrospective accident dosimetry. -- Highlights: ► Glass displays from mobile phones have good potential for emergency dosimetry. ► The background signal can be reduced by etching glass samples with hydrofluoric acid. ► The minimum detectable dose can be lowered to approximately 80 mGy

Computational assessment of effective dose and patient specific doses for kilovoltage stereotactic radiosurgery of wet age-related macular degeneration

Science.gov (United States)

Hanlon, Justin Mitchell

Age-related macular degeneration (AMD) is a leading cause of vision loss and a major health problem for people over the age of 50 in industrialized nations. The current standard of care, ranibizumab, is used to help slow and in some cases stabilize the process of AMD, but requires frequent invasive injections into the eye. Interest continues for stereotactic radiosurgery (SRS), an option that provides a non-invasive treatment for the wet form of AMD, through the development of the IRay(TM) (Oraya Therapeutics, Inc., Newark, CA). The goal of this modality is to destroy choroidal neovascularization beneath the pigment epithelium via delivery of three 100 kVp photon beams entering through the sclera and overlapping on the macula delivering up to 24 Gy of therapeutic dose over a span of approximately 5 minutes. The divergent x-ray beams targeting the fovea are robotically positioned and the eye is gently immobilized by a suction-enabled contact lens. Device development requires assessment of patient effective dose, reference patient mean absorbed doses to radiosensitive tissues, and patient specific doses to the lens and optic nerve. A series of head phantoms, including both reference and patient specific, was derived from CT data and employed in conjunction with the MCNPX 2.5.0 radiation transport code to simulate treatment and evaluate absorbed doses to potential tissues-at-risk. The reference phantoms were used to evaluate effective dose and mean absorbed doses to several radiosensitive tissues. The optic nerve was modeled with changeable positions based on individual patient variability seen in a review of head CT scans gathered. Patient specific phantoms were used to determine the effect of varying anatomy and gaze. The results showed that absorbed doses to the non-targeted tissues were below the threshold levels for serious complications; specifically the development of radiogenic cataracts and radiation induced optic neuropathy (RON). The effective dose

Improvement of Dose Homogeneity in a 3-Dimensional Conformal Radiotherapy for Head and Neck Cancer

International Nuclear Information System (INIS)

Kim, Yong Nam; Lee, Chang Geol; Chung, Kyeong Keun; Kim, Joo Young; Seong, Jin Sil

2007-01-01

When an electron field is abutted at the surface with a photon field for head-and-neck cancer (HNC) treatment, the traditional method using bilateral field gives rise to an extreme inhomogeneity of dose distribution with both very hot and very cold regions. When we consider clinically only tumor doses of primary concern regardless of dose to normal tissues, the hot spots can be accepted, depending on their magnitude, extent, and location. However, an extreme inhomogeneity inside the radiation field is generally undesirable. An overdose to normal tissues around a target region or an underdosage in the tumor may be problematic. This study intends to develop a novel approach to improve the dose distribution inside the photon-electron abutting fields for HNC treatment

Successful treatment of methicillin-resistant Staphylococcus aureus osteomyelitis with combination therapy using linezolid and rifampicin under therapeutic drug monitoring.

Science.gov (United States)

Ashizawa, Nobuyuki; Tsuji, Yasuhiro; Kawago, Koyomi; Higashi, Yoshitsugu; Tashiro, Masato; Nogami, Makiko; Gejo, Ryuichi; Narukawa, Munetoshi; Kimura, Tomoatsu; Yamamoto, Yoshihiro

2016-05-01

Linezolid is an effective antibiotic against most gram-positive bacteria including drug-resistant strains such as methicillin-resistant Staphylococcus aureus. Although linezolid therapy is known to result in thrombocytopenia, dosage adjustment or therapeutic drug monitoring of linezolid is not generally necessary. In this report, however, we describe the case of a 79-year-old woman with recurrent methicillin-resistant S. aureus osteomyelitis that was successfully treated via surgery and combination therapy using linezolid and rifampicin under therapeutic drug monitoring for maintaining an appropriate serum linezolid concentration. The patient underwent surgery for the removal of the artificial left knee joint and placement of vancomycin-impregnated bone cement beads against methicillin-resistant S. aureus after total left knee implant arthroplasty for osteoarthritis. We also initiated linezolid administration at a conventional dose of 600 mg/h at 12-h intervals, but reduced it to 300 mg/h at 12-h intervals on day 9 because of a decrease in platelet count and an increase in serum linezolid trough concentration. However, when the infection exacerbated, we again increased the linezolid dose to 600 mg/h at 12-h intervals and performed combination therapy with rifampicin, considering their synergistic effects and the control of serum linezolid trough concentration via drug interaction. Methicillin-resistant S. aureus infection improved without reducing the dose of or discontinuing linezolid. The findings in the present case suggest that therapeutic drug monitoring could be useful for ensuring the therapeutic efficacy and safety of combination therapy even in patients with osteomyelitis who require long-term antibiotic administration. Copyright © 2015 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Variation in radiation doses in paediatric cardiac catheterisation procedures

International Nuclear Information System (INIS)

Al-Haj, A. N.; Lobriguito, A. M.; Rafeh, W.

2008-01-01

Paediatric cardiac catheterisation involves diagnostic and therapeutic procedures that range from simple to complex and can subject paediatric patients to varying radiation doses. The study aims to determine the variation in entrance doses in patients in terms of dose-area product (DAP) values and to investigate the methods for optimising radiation protection. A total of 190 paediatric patients belonging to age groups 0, 1, 5 and 10 y who underwent diagnostic and six selected therapeutic procedures at King Faisal Specialist Hospital and Research Centre, Riyadh (Saudi Arabia) were included in the study. Therapeutic procedures include coarctation (COA), patent ductus arteriosus (PDA), radiofrequency ablation, pulmonary, embolisation and septostomy. Fluoroscopy and cine radiography were used in all procedures. Patient demography (weight, age, gender and height), radiographic technique factors, fluoroscopy and cine time, frame rate, and DAP values were taken from patients records. Effective doses for each procedure were estimated from the DAP values. The mean DAP per procedure were analysed for correlation with patient equivalent cylindrical diameter, weight, fluoroscopy time and number of frames. Factors influencing the variation in doses were investigated. Initial results show that PDA occlusion has the highest mean DAP value of 23.21 Gy-cm 2 , while the diagnostic and septostomy procedures have the lowest value of 7.77 and 6.95 Gy-cm 2 , respectively. (authors)

Extracorporeal adsorption therapy: A Method to improve targeted radiation delivered by radiometal-labeled monoclonal antibodies

International Nuclear Information System (INIS)

Nemecek, Eneida R.; Green, Damian J.; Fisher, Darrell R.; Pagal, John M.; Lin, Yukang; Gopal, A. K.; Durack, Lawrence D.; Rajendran, Joseph G.; Wilbur, D. S.; Nilsson, Rune; Sandberg, Bengt; Press, Oliver W.

2008-01-01

Many investigators have demonstrated the ability to treat hematologic malignancies with radiolabeled monoclonal antibodies targeting hematopoietic antigens such as anti-CD20 and anti-CD45. [1-5] Although the remission rates achieved with radioimmunotherapy (RIT) are relatively high, many patients subsequently relapse presumably due to suboptimal delivery of enough radiation to eradicate the malignancy. The dose-response of leukemia and lymphoma to radiation has been proven. Substantial amounts of radiation can be delivered by RIT if followed by hematopoietic cell transplantation to rescue the bone marrow from myeloablation.[ref] However, the maximum dose of RIT that can be used is still limited by toxicity to normal tissues affected by nonspecific delivery of radiation. Efforts to improve RIT focus on improving the therapeutic ratios of radiation in target versus non-target tissues by removing the fraction of radioisotope that fails to bind to target tissues and circulates freely in the bloodstream perfusing non-target tissues. Our group and others have explored several alternatives for removal of unbound circulating antibody. [refs] One such method, extracorporeal adsorption therapy (ECAT) consists of removing unbound antibody by a method similar to plasmapheresis after critical circulation time and distribution of antibody into target tissues have been achieved. Preclinical studies of ECAT in murine xenograft models demonstrated significant improvement in therapeutic ratios of radioactivity. Chen and colleagues demonstrated that a 2-hour ECAT procedure could remove 40 to 70% of the radioactivity from liver, lung and spleen. [ref] Although isotope concentration in the tumor was initially unaffected, a 50% decrease was noted approximately 36 hours after the procedure. This approach was also evaluated in a limited phase I pilot study of patients with refractory B-cell lymphoma. [ref] After radiographic confirmation of tumor localization of a test dose of anti-CD20

Improved metabolic control in tetrahydrobiopterin (BH4), responsive phenylketonuria with sapropterin administered in two divided doses vs. a single daily dose.

Science.gov (United States)

Kör, Deniz; Yılmaz, Berna Şeker; Bulut, Fatma Derya; Ceylaner, Serdar; Mungan, Neslihan Önenli

2017-07-26

Phenylketonuria (PKU) often requires a lifelong phenylalanine (Phe)-restricted diet. Introduction of 6R-tetrahydrobiopterin (BH4) has made a huge difference in the diets of patients with PKU. BH4 is the co-factor of the enzyme phenylalanine hydroxylase (PAH) and improves PAH activity and, thus, Phe tolerance in the diet. A limited number of published studies suggest a pharmacodynamic profile of BH4 more suitable to be administered in divided daily doses. After a 72-h BH4 loading test, sapropterin was initiated in 50 responsive patients. This case-control study was conducted by administering the same daily dose of sapropterin in group 1 (n=24) as a customary single dose or in two divided doses in group 2 (n=26) over 1 year. Mean daily consumption of Phe increased significantly after the first year of BH4 treatment in group 2 compared to group 1 (p<0.05). At the end of the first year of treatment with BH4, another dramatic difference observed between the two groups was the ability to transition to a Phe-free diet. Eight patients from group 2 and two from group 1 could quit dietary restriction. When given in two divided daily doses, BH4 was more efficacious than a single daily dose in increasing daily Phe consumption, Phe tolerance and the ability to transition to a Phe-unrestricted diet at the end of the first year of treatment.

High-Dose-Rate Endobronchial Brachytherapy for Recurrent Airway Obstruction From Hyperplastic Granulation Tissue

International Nuclear Information System (INIS)

Tendulkar, Rahul D.; Fleming, Peter A.; Reddy, Chandana A.; Gildea, Thomas R.; Machuzak, Michael; Mehta, Atul C.

2008-01-01

Purpose: Benign endobronchial granulation tissue causes airway obstruction in up to 20% of patients after lung transplantation or stent placement. High-dose-rate endobronchial brachytherapy (HDR-EB) has been successful in some cases refractory to standard bronchoscopic interventions. Methods and Materials: Between September 2004 and May 2005, 8 patients with refractory benign airway obstruction were treated with HDR-EB, using one to two fractions of Ir-192 prescribed to 7.1 Gy at a radius of 1 cm. Charts were retrospectively reviewed to evaluate subjective clinical response, forced expiratory volume in 1 second (FEV 1 ), and frequency of therapeutic bronchoscopies over 6-month periods before and after HDR-EB. Results: The median follow-up was 14.6 months, and median survival was 10.5 months. The mean number of bronchoscopic interventions improved from 3.1 procedures in the 6-month pretreatment period to 1.8 after HDR-EB. Mean FEV 1 improved from 36% predicted to 46% predicted. Six patients had a good-to-excellent subjective early response, but only one maintained this response beyond 6 months, and this was the only patient treated with HDR-EB within 24 h from the most recent bronchoscopic intervention. Five patients have expired from causes related to their chronic pulmonary disease, including one from hemoptysis resulting from a bronchoarterial fistula. Conclusion: High-dose-rate-EB may be an effective treatment for select patients with refractory hyperplastic granulation tissue causing recurrent airway stenosis. Performing HDR-EB within 24-48 h after excision of obstructive granulation tissue could further improve outcomes. Careful patient selection is important to maximize therapeutic benefit and minimize toxicity. The optimal patient population, dose, and timing of HDR-EB should be investigated prospectively

An industry update: the latest developments in Therapeutic delivery.

Science.gov (United States)

Steinbach, Oliver C

2018-05-01

The present industry update covers the period of 1 January-31 January 2018, with information sourced from company press releases, regulatory and patent agencies as well as scientific literature. Several public offerings (Gecko, Insmed), licensing (Foresee) and commercialization agreements (Alnylam, Collegium Pharmaceutical) as well as patent filings (Elute) continue to prove the sustained investments in the drug delivery market. In increasing numbers, more effective ways to deliver the active ingredient to the right location and the right dose through devices (Boehringer Ingelheim's Respimat, Medtronics' SynchroMedII) or improved compound properties through formulation (Aquestive Therapeutics' PharmFilm, Noven Pharmaceuticals' transdermal patch) are reaching the market. Furthering biologics and gene delivery (Avacta, Bracco) proves that novel drug delivery technologies are successfully addressing more challenging drug formats.

Stealth Properties to Improve Therapeutic Efficacy of Drug Nanocarriers

Directory of Open Access Journals (Sweden)

Stefano Salmaso

2013-01-01

Full Text Available Over the last few decades, nanocarriers for drug delivery have emerged as powerful tools with unquestionable potential to improve the therapeutic efficacy of anticancer drugs. Many colloidal drug delivery systems are underdevelopment to ameliorate the site specificity of drug action and reduce the systemic side effects. By virtue of their small size they can be injected intravenously and disposed into the target tissues where they release the drug. Nanocarriers interact massively with the surrounding environment, namely, endothelium vessels as well as cells and blood proteins. Consequently, they are rapidly removed from the circulation mostly by the mononuclear phagocyte system. In order to endow nanosystems with long circulation properties, new technologies aimed at the surface modification of their physicochemical features have been developed. In particular, stealth nanocarriers can be obtained by polymeric coating. In this paper, the basic concept underlining the “stealth” properties of drug nanocarriers, the parameters influencing the polymer coating performance in terms of opsonins/macrophages interaction with the colloid surface, the most commonly used materials for the coating process and the outcomes of this peculiar procedure are thoroughly discussed.

[Relation between dose, plasma concentration and therapeutic effect of theophylline in children with sleep apnea].

Science.gov (United States)

Rodríguez-Palomares, C; Ugartechea, J C; Palma-Aguirre, J A; Juárez-Olguín, H; Calderón-Mandujano, B

1989-12-01

The plasma concentration of theophylline was determined in twelve children with infantile sleep apnea (average age 48.5 days). The purpose of the study was to correlate concentrations with the dosages given, the therapeutic response and any adverse effects which could arise. In addition, other pharmacokinetic values were found, half-life (t 1/2) and clearance concentrations (Clss). The oral maintenance dose used was 4 mg/kg/24 h. The serum concentration of theophylline was determined by a homogeneous immunoassay enzyme technique (EMIT). A bad correlation was found (r = 0.45) between the oral dosage given and the plasma concentrations found. This was probably due to variations in the clearance of the drug. Yet, plasma concentrations fell between 3.0 and 12.6 micrograms/mL, enough to satisfactorily control apneic episodes in all the children included in the study without undesirable side-effects. Only one patient had some trouble in falling asleep and showed signs of irritability. The half-life was 13.30 +/- 7.46 hours and Clss was 36.64 +/- 12.98 mL/h/kg. In general, our results correlate with those reported in the literature. The accuracy of the pharmacokinetic parameters with two samples is reliable, therefore avoiding the use of multiple sampling in this group of children.

Development of a methodology to determine optimized therapeutic doses of {sup 131}I for the treatment of hyperthyroidism

Energy Technology Data Exchange (ETDEWEB)

Araujo, Francisco de; Santas, Bernardo Maranhao; Dantas, Ana Leticia Almeida; Lucena, Eder Augusto [Instituto de Radioprotecao e Dosimetria (IRD/CNEN-RJ), Rio de Janeiro, RJ (Brazil)]. E-mail: faraujo@ird.gov.br; Melo, Rossana Corbo de; Rebelo, Ana Maria de Oliveira [Universidade Federal, Rio de Janeiro, RJ (Brazil). Faculdade de Medicina

2007-07-01

Several methods can be used to determine the activity of {sup 131}I to be administered for the treatment of hyperthyroidism. However, some of them do not take into consideration the dose absorbed by the thyroid, while others do not consider all the parameters necessary for dose calculation. The relationship between the dose absorbed by the thyroid and the activity administered depends basically on three parameters: mass of the organ, iodine uptake and effective half-life of iodine in the thyroid. Such parameters should be individually determined for each patient in order to optimize the administered activity. The objective of this work is to develop a methodology to evaluate therapeutic doses through the determination of biokinetic parameters and the activity of {sup 131}I deposited in the thyroid of patients submitted to the treatment of hyperthyroidism with {sup 131}I. A neck-thyroid phantom developed at the In Vivo Monitoring Laboratory of IRD, containing a known amount of {sup 131}I, was used to calibrate a scintillation camera and a uptake probe available at the Nuclear Medicine Center of the University Hospital of Rio de Janeiro. The optimization of the counting geometry was carried out by the determination of the characteristic curves of the view angle of the collimator-detector assembly. The calculation of the calibration factor of the scintillation camera allows the determination of activities in the thyroid of patients in pre-established time periods through a 48-hours uptake curve. The view angle of the collimator-detector assembly presented values compatible with the size of the organ for distances of 25 cm (uptake probe) and 45.8 cm (scintillation camera). The calibration factors (in cpm/kBq) and the associated uncertainty related to these distances were 39.3 {+-} 0.8 and 4.3 {+-} 0.2 respectively. The time period between 14 and 30 hours of the retention curve allows the calculation of the activity between those two points. It is concluded that the use

A possible method using baseline hormonal levels to prescribe the appropriate oral therapeutic radioiodine dosage for Graves' disease

International Nuclear Information System (INIS)

Nakajo, Masayuki; Tsuchimochi, Shinsaku; Jinguji, Megumi; Tanabe, Hiroaki; Umanodan, Tomoichi; Nakabeppu, Yoshiaki

2007-01-01

The purpose of this study was to retrospectively examine the correlations of hormonal ratios with radioiodine I-131 therapeutic parameters and the potentiality of prescribing the therapeutic I-131 target dosage for an individual patient with Graves' disease using baseline serum levels of thyroid hormones. Serum T3, T4, and FT4 levels 6 and 12 months after I-131 therapy/baseline levels (hormonal ratios) were calculated for a total of 68 therapeutic courses in 57 patients with Graves' disease. The therapeutic parameters were absorbed dose (Gy), dose concentration (μCi/g) and oral dose (mCi). Linear regression analysis was performed for correlating hormonal ratios (X) and therapeutic parameters (Y). Significant (P<0.05) negative correlations of the hormonal ratios were observed with absorbed dose (R -0.50 for T3, -0.61 for T4, and -0.46 for FT4 at 6 months, and -0.29 for T3, -0.44 for T4 at 12 months) and dose concentration (R -0.57 for T3, -0.58 for T4, and -0.49 for FT4 at 6 months and -0.27 for T3, -0.27 for T4 at 12 months), but not with oral dose at 6 months and 12 months or the absorbed dose and dose concentration for FT4 at 12 months. The correlations were higher at 6 months than at 12 months and in serum T4 than in serum T3 and FT4. The formulae for serum T4 at 6 months were as follows: Y (Gy)=109-53X and Y (μCi/g)=109-52X. These results suggest that the hormonal ratios are significantly correlated with the absorbed dose and dose concentration. The formulae for serum T4 at 6 months may serve to prescribe the individual oral dosage for Graves' disease, although the correlation coefficients are about -0.6. (author)

Cost reduction from resolution/improvement of carcinoid syndrome symptoms following treatment with above-standard dose of octreotide LAR.

Science.gov (United States)

Huynh, Lynn; Totev, Todor; Vekeman, Francis; Neary, Maureen P; Duh, Mei S; Benson, Al B

2017-09-01

To calculate the cost reduction associated with diarrhea/flushing symptom resolution/improvement following treatment with above-standard dose octreotide-LAR from the commercial payor's perspective. Diarrhea and flushing are two major carcinoid syndrome symptoms of neuroendocrine tumor (NET). Previously, a study of NET patients from three US tertiary oncology centers (NET 3-Center Study) demonstrated that dose escalation of octreotide LAR to above-standard dose resolved/improved diarrhea/flushing in 79% of the patients within 1 year. Time course of diarrhea/flushing symptom data were collected from the NET 3-Center Study. Daily healthcare costs were calculated from a commercial claims database analysis. For the patient cohort experiencing any diarrhea/flushing symptom resolution/improvement, their observation period was divided into days of symptom resolution/improvement or no improvement, which were then multiplied by the respective daily healthcare cost and summed over 1 year to yield the blended mean annual cost per patient. For patients who experienced no diarrhea/flushing symptom improvement, mean annual daily healthcare cost of diarrhea/flushing over a 1-year period was calculated. The economic model found that 108 NET patients who experienced diarrhea/flushing symptom resolution/improvement within 1 year had statistically significantly lower mean annual healthcare cost/patient than patients with no symptom improvement, by $14,766 (p = .03). For the sub-set of 85 patients experiencing resolution/improvement of diarrhea, their cost reduction was more pronounced, at $18,740 (p = .01), statistically significantly lower than those with no improvement; outpatient costs accounted for 56% of the cost reduction (p = .02); inpatient costs, emergency department costs, and pharmacy costs accounted for the remaining 44%. The economic model relied on two different sources of data, with some heterogeneity in the prior treatment and disease status of patients

On the impact of improved dosimetric accuracy on head and neck high dose rate brachytherapy.

Science.gov (United States)

Peppa, Vasiliki; Pappas, Eleftherios; Major, Tibor; Takácsi-Nagy, Zoltán; Pantelis, Evaggelos; Papagiannis, Panagiotis

2016-07-01

To study the effect of finite patient dimensions and tissue heterogeneities in head and neck high dose rate brachytherapy. The current practice of TG-43 dosimetry was compared to patient specific dosimetry obtained using Monte Carlo simulation for a sample of 22 patient plans. The dose distributions were compared in terms of percentage dose differences as well as differences in dose volume histogram and radiobiological indices for the target and organs at risk (mandible, parotids, skin, and spinal cord). Noticeable percentage differences exist between TG-43 and patient specific dosimetry, mainly at low dose points. Expressed as fractions of the planning aim dose, percentage differences are within 2% with a general TG-43 overestimation except for the spine. These differences are consistent resulting in statistically significant differences of dose volume histogram and radiobiology indices. Absolute differences of these indices are however small to warrant clinical importance in terms of tumor control or complication probabilities. The introduction of dosimetry methods characterized by improved accuracy is a valuable advancement. It does not appear however to influence dose prescription or call for amendment of clinical recommendations for the mobile tongue, base of tongue, and floor of mouth patient cohort of this study. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

The outcome of adjusted accumulation dose of treatment of Graves' disease

International Nuclear Information System (INIS)

Gomi, Yukari; Inoue, Takeshi; Suzuki, Seiji; Hamada, Noboru; Yoshimura, Hiroshi; Ishikawa, Naofumi; Momotani, Naoko; Ito, Kunihiko.

1997-01-01

We evaluated the outcome of 131 I treatment of Graves' disease in two different protocols (old and new protocol) of adjusted accumulation dose from 1988 to 1995. Adjusted accumulation doses of patients with above 50 g thyroid weights were increased by 5-20 Gy/g tissue in new protocol compared to those in old one. In 166 patients treated with single and plural doses of 131 I treatment in 1990 (Group In), the therapeutic doses were calculated according to new protocol and in 130 patients in 1988 (Group Io), according to old one, modification of Quimby's formula. The patients treated with plural doses were classified as hyperthyroidism because the efficacies of the first treatments with 131 I were insufficient. At the 5-yr follow up, the incidence of hypothyroid in Group In was 9%, subclinical hypothyroid 17%, euthyroid 30%, subclinical hyperthyroid 7%, hyperthyroid 37%. In Group Io, 11% of the patients were hypothyroid, 6% subclinical hypothyroid, 29% euthyroid, 3% subclinical hyperthyroid, 51% hyperthyroid. The incidence of hyperthyroid in Group In was lower than that in Group Io (p 131 I in relation to the patients' thyroid weight shows some room for improvement. (author)

Functionalized bioengineered spider silk spheres improve nuclease resistance and activity of oligonucleotide therapeutics providing a strategy for cancer treatment.

Science.gov (United States)

Kozlowska, Anna Karolina; Florczak, Anna; Smialek, Maciej; Dondajewska, Ewelina; Mackiewicz, Andrzej; Kortylewski, Marcin; Dams-Kozlowska, Hanna

2017-09-01

Cell-selective delivery and sensitivity to serum nucleases remain major hurdles to the clinical application of RNA-based oligonucleotide therapeutics, such as siRNA. Spider silk shows great potential as a biomaterial due to its biocompatibility and biodegradability. Self-assembling properties of silk proteins allow for processing into several different morphologies such as fibers, scaffolds, films, hydrogels, capsules and spheres. Moreover, bioengineering of spider silk protein sequences can functionalize silk by adding peptide moieties with specific features including binding or cell recognition domains. We demonstrated that modification of silk protein by adding the nucleic acid binding domain enabled the development of a novel oligonucleotide delivery system that can be utilized to improve pharmacokinetics of RNA-based therapeutics, such as CpG-siRNA. The MS2 bioengineered silk was functionalized with poly-lysine domain (KN) to generate hybrid silk MS2KN. CpG-siRNA efficiently bound to MS2KN in contrary to control MS2. Both MS2KN complexes and spheres protected CpG-siRNA from degradation by serum nucleases. CpG-siRNA molecules encapsulated into MS2KN spheres were efficiently internalized and processed by TLR9-positive macrophages. Importantly, CpG-STAT3siRNA loaded in silk spheres showed delayed and extended target gene silencing compared to naked oligonucleotides. The prolonged Stat3 silencing resulted in the more pronounced downregulation of interleukin 6 (IL-6), a proinflammatory cytokine and upstream activator of STAT3, which limits the efficacy of TLR9 immunostimulation. Our results demonstrate the feasibility of using spider silk spheres as a carrier of therapeutic nucleic acids. Moreover, the modified kinetic and activity of the CpG-STAT3siRNA embedded into silk spheres is likely to improve immunotherapeutic effects in vivo. We demonstrated that modification of silk protein by adding the nucleic acid binding domain enabled the development of a novel

Two-dimensional pencil beam scaling: an improved proton dose algorithm for heterogeneous media

International Nuclear Information System (INIS)

Szymanowski, Hanitra; Oelfke, Uwe

2002-01-01

New dose delivery techniques with proton beams, such as beam spot scanning or raster scanning, require fast and accurate dose algorithms which can be applied for treatment plan optimization in clinically acceptable timescales. The clinically required accuracy is particularly difficult to achieve for the irradiation of complex, heterogeneous regions of the patient's anatomy. Currently applied fast pencil beam dose calculations based on the standard inhomogeneity correction of pathlength scaling often cannot provide the accuracy required for clinically acceptable dose distributions. This could be achieved with sophisticated Monte Carlo simulations which are still unacceptably time consuming for use as dose engines in optimization calculations. We therefore present a new algorithm for proton dose calculations which aims to resolve the inherent problem between calculation speed and required clinical accuracy. First, a detailed derivation of the new concept, which is based on an additional scaling of the lateral proton fluence is provided. Then, the newly devised two-dimensional (2D) scaling method is tested for various geometries of different phantom materials. These include standard biological tissues such as bone, muscle and fat as well as air. A detailed comparison of the new 2D pencil beam scaling with the current standard pencil beam approach and Monte Carlo simulations, performed with GEANT, is presented. It was found that the new concept proposed allows calculation of absorbed dose with an accuracy almost equal to that achievable with Monte Carlo simulations while requiring only modestly increased calculation times in comparison to the standard pencil beam approach. It is believed that this new proton dose algorithm has the potential to significantly improve the treatment planning outcome for many clinical cases encountered in highly conformal proton therapy. (author)

Improving lithium therapeutics by crystal engineering of novel ionic cocrystals.

Science.gov (United States)

Smith, Adam J; Kim, Seol-Hee; Duggirala, Naga K; Jin, Jingji; Wojtas, Lukasz; Ehrhart, Jared; Giunta, Brian; Tan, Jun; Zaworotko, Michael J; Shytle, R Douglas

2013-12-02

Current United States Food and Drug Administration (FDA)-approved lithium salts are plagued with a narrow therapeutic window. Recent attempts to find alternative drugs have identified new chemical entities, but lithium's polypharmacological mechanisms for treating neuropsychiatric disorders are highly debated and are not yet matched. Thus, re-engineering current lithium solid forms in order to optimize performance represents a low cost and low risk approach to the desired therapeutic outcome. In this contribution, we employed a crystal engineering strategy to synthesize the first ionic cocrystals (ICCs) of lithium salts with organic anions. We are unaware of any previous studies that have assessed the biological efficacy of any ICCs, and encouragingly we found that the new speciation did not negatively affect established bioactivities of lithium. We also observed that lithium ICCs exhibit modulated pharmacokinetics compared to lithium carbonate. Indeed, the studies detailed herein represent an important advancement in a crystal engineering approach to a new generation of lithium therapeutics.

Improving tumour response

International Nuclear Information System (INIS)

Bentzen, S.

2003-01-01

Radiation oncology is in the middle of the most exciting developments in its 100-year history. Progress in treatment planning and delivery, in medical imaging and in basic cancer and normal tissue biology is likely to change the indication for radiotherapy as well as the way it is prescribed and delivered. Technological and conceptual advances, in particular the development of the multi-leaf collimator and the concept of inverse treatment planning, have led to the introduction of intensity modulated radiation therapy (IMRT) with its capability to plan and deliver non-uniform dose distributions in the clinic. This has forced us to re-think radiation oncology: refining the indication for radiotherapy, optimizing the prescription of dose distributions and considering how, based on clinical evidence, radiation can best be combined with other treatment modalities, surgery, cytotoxic chemotherapy and biologically targeted therapies. The attraction of radiation therapy as an element of multi-modality cancer therapy is that it induces DNA damage that can be modulated in space and time. Progress in basic cancer biology, genomics and proteomics, as well as biological imaging provides novel avenues for individualization of cancer therapy and for biological optimization of radiotherapy. In improving cancer care, it is the therapeutic ratio, rather than tumour control per se, that must be optimised. Interestingly, the two main avenues for improving the effectiveness of radiotherapy currently being actively pursued in the clinic generally aim at different sides of the therapeutic ratio: 3D conformal radiotherapy and IMRT predominantly aim to reduce normal-tissue side effects - and by doing this, open the way for dose escalation that may lead to increased tumour control rates - whereas combined radio-chemotherapy aims to improve tumour response - while keeping the fingers crossed that this will not increase normal-tissue complications to the same extent. In parallel with these

Improvement of heart function in postinfarct heart failure swine models after hepatocyte growth factor gene transfer: comparison of low-, medium- and high-dose groups.

Science.gov (United States)

Yang, Zhi-jian; Chen, Bo; Sheng, Zhang; Zhang, Ding-guo; Jia, En-zhi; Wang, Wei; Ma, Dong-chao; Zhu, Tie-bing; Wang, Lian-sheng; Li, Chun-jian; Wang, Hui; Cao, Ke-jiang; Ma, Wen-zhu

2010-04-01

Despite advances in surgical and reperfusion therapy, there is no effective therapy currently exists to prevent the progressive decline in cardiac function following myocardial infarction. Hepatocyte growth factor has potent angiogenic and anti-apoptotic activities. The aim of this study was to investigate the therapeutic effect and dose-effect relationship on postinfarction heart failure with different doses of adenovirus-mediated human hepatocyte growth factor (Ad(5)-HGF) transference in swine models. Totally twenty swine were randomly divided into four groups: (a) control group (null- Ad(5), 1 ml); (b) low-dose group (1 x 10(9) Pfu/ml Ad(5)-HGF, 1 ml); (c) medium-dose group (5 x 10(9) Pfu/ml Ad(5)-HGF, 1 ml); (d) high-dose group (1 x 10(10) Pfu/ml Ad(5)-HGF, 1 ml). Four weeks after left anterior descending coronary artery (LAD) ligation, different doses of Ad(5)-HGF were transferred in three therapeutic groups via right coronary artery. Four and seven weeks after LAD ligation, gate cardiac perfusion imaging was performed to evaluate cardiac perfusion and left ventricular ejection fraction (LVEF). Seven weeks after surgery, the apoptotic index of cardiocyte was observed by TUNEL, the expression of Bcl-2, Bax, alpha-SMA and Factor VIII in the border zones were evaluated by immunohistochemistry, respectively. Four weeks after myocardial infarction, no significant difference was observed among four groups. Three weeks after Ad(5)-HGF transfer, the improvement of cardiac perfusion and LVEF was obviously observed, especially after 1 x 10(10) Pfu Ad(5)-HGF transfer. TUNEL assay showed that 5 x 10(9) Pfu and 1 x 10(10) Pfu Ad(5)-HGF treatment had a obvious reduction in the apoptotic index compared with the null-Ad(5) group, especially after 1 x 10(10) Pfu Ad(5)-HGF treatment. The expression of Bcl-2 protein was increased and the expression of Bax protein was inhibited in the 5 x 10(9) Pfu and 1 x 10(10) Pfu Ad(5)-HGF groups compared with the null-Ad(5) group. The vessel

Responses of rat R-1 cells to low dose rate gamma radiation and multiple daily dose fractions

International Nuclear Information System (INIS)

Kal, H.B.; Bijman, J.Th.

1981-01-01

Multifraction irradiation may offer the same therapeutic gain as continuous irradiation. Therefore, a comparison of the efficacy of low dose rate irradiation and multifraction irradiation was the main objective of the experiments to be described. Both regimens were tested on rat rhabdomyosarcoma (R-1) cells in vitro and in vivo. Exponentially growing R-1 cells were treated in vitro by a multifraction irradiation procedure with dose fractions of 2 Gy gamma radiation and time intervals of 1 to 3 h. The dose rate was 1.3 Gy.min -1 . The results indicate that multifractionation of the total dose is more effective with respect to cell inactivation than continuous irradiation. (Auth.)

Mechanistic and single-dose in vivo therapeutic studies of Cry5B anthelmintic action against hookworms.

Directory of Open Access Journals (Sweden)

Yan Hu

Full Text Available Hookworm infections are one of the most important parasitic infections of humans worldwide, considered by some second only to malaria in associated disease burden. Single-dose mass drug administration for soil-transmitted helminths, including hookworms, relies primarily on albendazole, which has variable efficacy. New and better hookworm therapies are urgently needed. Bacillus thuringiensis crystal protein Cry5B has potential as a novel anthelmintic and has been extensively studied in the roundworm Caenorhabditis elegans. Here, we ask whether single-dose Cry5B can provide therapy against a hookworm infection and whether C. elegans mechanism-of-action studies are relevant to hookworms.To test whether the C. elegans invertebrate-specific glycolipid receptor for Cry5B is relevant in hookworms, we fed Ancylostoma ceylanicum hookworm adults Cry5B with and without galactose, an inhibitor of Cry5B-C. elegans glycolipid interactions. As with C. elegans, galactose inhibits Cry5B toxicity in A. ceylanicum. Furthermore, p38 mitogen-activated protein kinase (MAPK, which controls one of the most important Cry5B signal transduction responses in C. elegans, is functionally operational in hookworms. A. ceylanicum hookworms treated with Cry5B up-regulate p38 MAPK and knock down of p38 MAPK activity in hookworms results in hypersensitivity of A. ceylanicum adults to Cry5B attack. Single-dose Cry5B is able to reduce by >90% A. ceylanicum hookworm burdens from infected hamsters, in the process eliminating hookworm egg shedding in feces and protecting infected hamsters from blood loss. Anthelmintic activity is increased about 3-fold, eliminating >97% of the parasites with a single 3 mg dose (∼30 mg/kg, by incorporating a simple formulation to help prevent digestion in the acidic stomach of the host mammal.These studies advance the development of Cry5B protein as a potent, safe single-dose anthelmintic for hookworm therapy and make available the information of how

Dose-rate and the reciprocity law: TL response of Ge-doped SiO{sub 2} optical fibers at therapeutic radiation doses

Energy Technology Data Exchange (ETDEWEB)

Abdul Rahman, A.T., E-mail: a.t.abdulrahman@surrey.ac.uk [Centre for Nuclear and Radiation Physics, Department of Physics, University of Surrey, Guildford GU2 7XH, Surrey (United Kingdom); School of Physics and Material Studies, Faculty of Applied Sciences, Universiti Teknologi MARA Malaysia (UiTM), Campus of Negeri Sembilan, 72000 Kuala Pilah (Malaysia); Nisbet, A. [Centre for Nuclear and Radiation Physics, Department of Physics, University of Surrey, Guildford GU2 7XH, Surrey (United Kingdom); Departments of Medical Physics, the Royal Surrey County Hospital (RSCH) NHS Trust, Edgerton Road, Guildford GU2 7XX, Surrey (United Kingdom); Bradley, D.A. [Centre for Nuclear and Radiation Physics, Department of Physics, University of Surrey, Guildford GU2 7XH, Surrey (United Kingdom)

2011-10-01

An investigation has been made on commercially available Ge-doped SiO{sub 2} optical fibers as a novel thermoluminescence system for radiotherapy dosimetry. This dosimeter has previously been shown by the group to provide sensitive dosimetry over a wide range of electron and photon dose, suitable for the needs of radiotherapy. In addition the optical fiber offers small physical size (125 {mu}m diameter) and hence high spatial resolution. The reciprocity between thermoluminescence (TL) yield of Ge-doped SiO{sub 2} optical fibers and dose has been investigated for fixed radiation dose for a range of photon and electron dose rates. For electron beams of nominal energies in the range of 9-20 MeV, we have investigated the TL response of these fibers for dose rates between 100 and 1000 cGy min{sup -1}. For photon beams of nominal energies in the range of 6-15 MV, we have used dose rates of 100-600 cGy min{sup -1}. Reproducibility and fading at fixed absorbed dose (3 Gy) and dose rate for the optical fibers were also investigated. At fixed dose rates, the TL optical fibers were found to produce a flat TL yield within 4% (1{sigma}) and 3% (1{sigma}) for electron and photon beams, respectively. The optical fibers demonstrated good reproducibility ({+-}1.5%), low residual signal for a readout temperature of 300 {sup o}C and negligible fading. A weak dependence on dose-rate has been observed in the range of 3.4-3.9% for electrons (with an associated uncertainty of 4%) and 2.4-2.9% for photons (with an associated uncertainty of <4%). For electron and photon energies we note a consistent trend towards lower response in the TL yield of between 3.4-3.9% and 2.4-2.7%, respectively, at the higher dose rates in comparison with the response at lower dose rates. In addition we note an appreciable systematic energy dependence for both electron and photon beams. It is important to take such factors into account for providing precise and accurate radiotherapy dosimetry. It is also

Predicting the usefulness of therapeutic drug monitoring of mycophenolic acid: a computer simulation

NARCIS (Netherlands)

van Hest, Reinier; Mathot, Ron; Vulto, Arnold; Weimar, Willem; van Gelder, Teun

2005-01-01

The usefulness of therapeutic drug monitoring (TDM) of mycophenolate mofetil (MMF) was investigated with a computer simulation model. For a fixed-dose (FD) and a concentration-controlled (CC) MMF dosing regimen exposure to mycophenolic acid (MPA) was compared. A nonlinear mixed-effects model

Recombinant IκBα-loaded curcumin nanoparticles for improved cancer therapeutics

International Nuclear Information System (INIS)

Banerjee, Subhamoy; Ghosh, Siddhartha Sankar; Sahoo, Amaresh Kumar; Chattopadhyay, Arun

2014-01-01

The field of recombinant protein therapeutics has been evolving rapidly, making significant impact on clinical applications for several diseases, including cancer. However, the functional aspects of proteins rely exclusively on their structural integrity, in which nanoparticle mediated delivery offers unique advantages over free proteins. In the present work, a novel strategy has been developed where the nanoparticles (NPs) used for the delivery of the recombinant protein could contribute to enhancing the therapeutic efficacy of the recombinant protein. The transcription factor, NFκB, involved in cell growth and its inhibitor, IκBα, regulates its proliferation. Another similar naturally available molecule, which inhibits the function of NFκB, is curcumin. Hence, we have developed a ‘green synthesis’ method for preparing water-soluble curcumin nanoparticles to stabilize recombinant IκBα protein. The NPs were characterized by UV–vis and fluorescence spectroscopy, transmission electron microscopy (TEM) and dynamic light scattering before administration into human cervical carcinoma (HeLa) and glioblastoma (U87MG) cells. Experimental results demonstrated that this combined module had enhanced therapeutic efficacy, causing apoptotic cell death, which was confirmed by cytotoxicity assay and flowcytometry analyses. The expression of apoptotic genes studied by semi-quantitative reverse transcription PCR delineated the molecular pathways involved in cell death. Thus, our study revealed that the functional delivery of recombinant IκBα-loaded curcumin NPs has promise as a natural-product-based protein therapeutics against cancer cells. (paper)

Recombinant IκBα-loaded curcumin nanoparticles for improved cancer therapeutics

Science.gov (United States)

Banerjee, Subhamoy; Sahoo, Amaresh Kumar; Chattopadhyay, Arun; Sankar Ghosh, Siddhartha

2014-08-01

The field of recombinant protein therapeutics has been evolving rapidly, making significant impact on clinical applications for several diseases, including cancer. However, the functional aspects of proteins rely exclusively on their structural integrity, in which nanoparticle mediated delivery offers unique advantages over free proteins. In the present work, a novel strategy has been developed where the nanoparticles (NPs) used for the delivery of the recombinant protein could contribute to enhancing the therapeutic efficacy of the recombinant protein. The transcription factor, NFκB, involved in cell growth and its inhibitor, IκBα, regulates its proliferation. Another similar naturally available molecule, which inhibits the function of NFκB, is curcumin. Hence, we have developed a ‘green synthesis’ method for preparing water-soluble curcumin nanoparticles to stabilize recombinant IκBα protein. The NPs were characterized by UV-vis and fluorescence spectroscopy, transmission electron microscopy (TEM) and dynamic light scattering before administration into human cervical carcinoma (HeLa) and glioblastoma (U87MG) cells. Experimental results demonstrated that this combined module had enhanced therapeutic efficacy, causing apoptotic cell death, which was confirmed by cytotoxicity assay and flowcytometry analyses. The expression of apoptotic genes studied by semi-quantitative reverse transcription PCR delineated the molecular pathways involved in cell death. Thus, our study revealed that the functional delivery of recombinant IκBα-loaded curcumin NPs has promise as a natural-product-based protein therapeutics against cancer cells.

Prediction of a Therapeutic Dose for Buagafuran, a Potent Anxiolytic Agent by Physiologically Based Pharmacokinetic/Pharmacodynamic Modeling Starting from Pharmacokinetics in Rats and Human

Directory of Open Access Journals (Sweden)

Fen Yang

2017-10-01

Full Text Available Physiologically based pharmacokinetic (PBPK/pharmacodynamic (PD models can contribute to animal-to-human extrapolation and therapeutic dose predictions. Buagafuran is a novel anxiolytic agent and phase I clinical trials of buagafuran have been completed. In this paper, a potentially effective dose for buagafuran of 30 mg t.i.d. in human was estimated based on the human brain concentration predicted by a PBPK/PD modeling. The software GastroPlusTM was used to build the PBPK/PD model for buagafuran in rat which related the brain tissue concentrations of buagafuran and the times of animals entering the open arms in the pharmacological model of elevated plus-maze. Buagafuran concentrations in human plasma were fitted and brain tissue concentrations were predicted by using a human PBPK model in which the predicted plasma profiles were in good agreement with observations. The results provided supportive data for the rational use of buagafuran in clinic.

SU-D-BRB-02: Combining a Commercial Autoplanning Engine with Database Dose Predictions to Further Improve Plan Quality

Energy Technology Data Exchange (ETDEWEB)

Robertson, SP; Moore, JA; Hui, X; Cheng, Z; McNutt, TR [Johns Hopkins University, Baltimore, MD (United States); DeWeese, TL; Tran, P; Quon, H [John Hopkins Hospital, Baltimore, MD (United States); Bzdusek, K [Philips, Fitchburg, WI (United States); Kumar, P [Philips India Limited, Bangalore, Karnataka (India)

2016-06-15

Purpose: Database dose predictions and a commercial autoplanning engine both improve treatment plan quality in different but complimentary ways. The combination of these planning techniques is hypothesized to further improve plan quality. Methods: Four treatment plans were generated for each of 10 head and neck (HN) and 10 prostate cancer patients, including Plan-A: traditional IMRT optimization using clinically relevant default objectives; Plan-B: traditional IMRT optimization using database dose predictions; Plan-C: autoplanning using default objectives; and Plan-D: autoplanning using database dose predictions. One optimization was used for each planning method. Dose distributions were normalized to 95% of the planning target volume (prostate: 8000 cGy; HN: 7000 cGy). Objectives used in plan optimization and analysis were the larynx (25%, 50%, 90%), left and right parotid glands (50%, 85%), spinal cord (0%, 50%), rectum and bladder (0%, 20%, 50%, 80%), and left and right femoral heads (0%, 70%). Results: All objectives except larynx 25% and 50% resulted in statistically significant differences between plans (Friedman’s χ{sup 2} ≥ 11.2; p ≤ 0.011). Maximum dose to the rectum (Plans A-D: 8328, 8395, 8489, 8537 cGy) and bladder (Plans A-D: 8403, 8448, 8527, 8569 cGy) were significantly increased. All other significant differences reflected a decrease in dose. Plans B-D were significantly different from Plan-A for 3, 17, and 19 objectives, respectively. Plans C-D were also significantly different from Plan-B for 8 and 13 objectives, respectively. In one case (cord 50%), Plan-D provided significantly lower dose than plan C (p = 0.003). Conclusion: Combining database dose predictions with a commercial autoplanning engine resulted in significant plan quality differences for the greatest number of objectives. This translated to plan quality improvements in most cases, although special care may be needed for maximum dose constraints. Further evaluation is warranted

Multiple factor analysis of the therapeutic effect of 131I in treating 783 cases of Graves disease

International Nuclear Information System (INIS)

Cai Min; Li Xianfeng; Li Sijin; Chen Haibin

2008-01-01

Objective: To study the factors influencing therapeutic effect of 131 I in treating 783 cases of Graves disease. Methods: The values of various indexes were quantized on influencing factors such as age, sex, course of disease, mass of thyroid gland, the absorbed dose of 131 I per gram of thryoid gland, the given dose of 131 I, thyroid 24 h 131 I uptaking percentage, thyroid hormone and thyroid autoantibodys. The assessment of the therapeutic effect was made according to complete remission (including hypothyroidism) and partial remission after 131 I therapy. CMH χ 2 , Wilcoxon signed-rank test and Logistic regression were used to analyze the variable parameters before the treatment. Results: The therapeutic effect of 131 I is significant in the follow-up period (CMH χ 2 =69.21, P 131 I therapy for 12 months. The therapeutic effect was related to such factors as age thyroid mass, the absorbed dose of 131 I per gram of thryoid gland, thyroid 24 h 131 I uptaking percentage, etc (all the values of P 131 I uptaking percentage is higher, thyroid mass is bigger, thyroid gland is with noduses, the given dose of 131 I should be increased. Conversely decreased. (authors)

Absorbed dose to active red bone marrow from diagnostic and therapeutic uses of radiation

International Nuclear Information System (INIS)

Solomon, S.B.

1980-06-01

The bone-marrow dose arising from radiological procedures as carried out in Australia have been determined as part of a survey of population doses. This paper describes the method of calculation of the radiation doses to the active bone marrow from diagnostic radiography, fluoroscopy and radiotherapy. The results of the calculations are compared with the results of other models of bone-marrow dose for a number of diagnostic X-ray procedures

Relieving Pain using Dose-Extending Placebos: A Scoping Review

Science.gov (United States)

Colloca, Luana; Enck, Paul; DeGrazia, David

2017-01-01

Placebos are often used by clinicians, usually deceptively and with little rationale or evidence of benefit, making their use ethically problematic. In contrast with their typical current use, a provocative line of research suggests that placebos can be intentionally exploited to extend analgesic therapeutic effects. Is it possible to extend the effects of drug treatments by interspersing placebos? We reviewed a database of placebo studies, searching for studies that indicate that placebos given after repeated administration of active treatments acquire medication-like effects. We found a total of 22studies in both animals and humans hinting of evidence that placebos may work as a sort of dose extender of active painkillers. Wherever effective in relieving clinical pain, such placebo use would offer several advantages. First, extending the effects of a painkiller through the use of placebos may reduce total drug intake and side effects. Second, dose-extending placebos may decrease patient dependence. Third, using placebos along with active medication, for part of the course of treatment, should limit dose escalation and lower costs. Importantly, provided that nondisclosure is pre-authorized in the informed consent process and that robust evidence indicates therapeutic benefit comparable to that of standard full-dose therapeutic regimens, introducing dose-extending placebos into the clinical arsenal should be considered. This novel prospect of placebo use has the potential to change our general thinking about painkiller treatments, the typical regimens of painkiller applications, and the ways in which treatments are evaluated. PMID:27023425

Improvement of the clinical use of computed radiography for mobile chest imaging: Image quality and patient dose

Science.gov (United States)

Rill, Lynn Neitzey

Chest radiography is technically difficult because of the wide variation of tissue attenuations in the chest and limitations of screen-film systems. Mobile chest radiography, performed bedside on hospital inpatients, presents additional difficulties due to geometrical and equipment limitations inherent to mobile x-ray procedures and the severity of illness in patients. Computed radiography (CR) offers a new approach for mobile chest radiography by utilizing a photostimulable phosphor. Photostimulable phosphors are more efficient in absorbing lower-energy x-rays than standard intensifying screens and overcome some image quality limitations of mobile chest imaging, particularly because of the inherent latitude. This study evaluated changes in imaging parameters for CR to take advantage of differences between CR and screen-film radiography. Two chest phantoms, made of acrylic and aluminum, simulated x-ray attenuation for average-sized and large- sized adult chests. The phantoms contained regions representing the lungs, heart and subdiaphragm. Acrylic and aluminum disks (1.9 cm diameter) were positioned in the chest regions to make signal-to-noise ratio (SNR) measurements for different combinations of imaging parameters. Disk thicknesses (contrast) were determined from disk visibility. Effective dose to the phantom was also measured for technique combinations. The results indicated that using an anti-scatter grid and lowering x- ray tube potential improved the SNR significantly; however, the dose to the phantom also increased. An evaluation was performed to examine the clinical applicability of the observed improvements in SNR. Parameter adjustments that improved phantom SNRs by more than 50% resulted in perceived image quality improvements in the lung region of clinical mobile chest radiographs. Parameters that produced smaller improvements in SNR had no apparent effect on clinical image quality. Based on this study, it is recommended that a 3:1 grid be used for

Acute personalized habitual caffeine doses improve attention and have selective effects when considering the fractionation of executive functions.

Science.gov (United States)

Lanini, Juliana; Galduróz, José Carlos Fernandes; Pompéia, Sabine

2016-01-01

Caffeine is widely used, often consumed with food, and improves simple and complex/executive attention under fasting conditions. We investigated whether these cognitive effects are observed when personalized habitual doses of caffeine are ingested by caffeine consumers, whether they are influenced by nutriments and if various executive domains are susceptible to improvement. This was a double-blind, placebo-controlled study including 60 young, healthy, rested males randomly assigned to one of four treatments: placebo fasting, caffeine fasting, placebo meal and caffeine meal. Caffeine doses were individualized for each participant based on their self-reported caffeine consumption at the time of testing (morning). The test battery included measures of simple and sustained attention, executive domains (inhibiting, updating, shifting, dual tasking, planning and accessing long-term memory), control measures of subjective alterations, glucose and insulin levels, skin conductance, heart rate and pupil dilation. Regardless of meal intake, acute habitual doses of caffeine decreased fatigue, and improved simple and sustained attention and executive updating. This executive effect was not secondary to the habitual weekly dose consumed, changes in simple and sustained attention, mood, meal ingestion and increases in cognitive effort. We conclude that the morning caffeine "fix" has positive attentional effects and selectively improved executive updating whether or not caffeine is consumed with food. Copyright © 2015 John Wiley & Sons, Ltd.

Optimization of the therapeutic dose of {sup 131}I for thyroid differentiated carcinoma; Otimizacao da dose terapeutica com {sup 131}I para carcinoma diferenciado da tiroide

Energy Technology Data Exchange (ETDEWEB)

Lima, Fabiana Farias de

2002-09-01

reduction for many organs, such as the narrow and gonads, of up to 78.4%.Possible benefits to the institution also include the use of less radioactive material and a reduction in radiation exposures to the staff during the manipulation and administration of the {sup 131} I. To facilitate the calculations of the optimum therapeutic activity of {sup 131} I for individual patients, a simple and fast dose planning program was created (PlanDose). The program has been set up to evaluate thryroid remant ablation, but it can also be used for the calculation of the activity to be administered for treatment of hyperthyroidism. This protocol of calculated optimal patient-specific {sup 131} I. activities allows a better determination of the necessary ablative dose for patients with differentiated carcinoma of the thyroid, and is an example of optimizing the practice of radiation protection. (author)

Transient Treg depletion enhances therapeutic anti‐cancer vaccination

Science.gov (United States)

Aston, Wayne J.; Chee, Jonathan; Khong, Andrea; Cleaver, Amanda L.; Solin, Jessica N.; Ma, Shaokang; Lesterhuis, W. Joost; Dick, Ian; Holt, Robert A.; Creaney, Jenette; Boon, Louis; Robinson, Bruce; Lake, Richard A.

2016-01-01

Abstract Introduction Regulatory T cells (Treg) play an important role in suppressing anti‐ immunity and their depletion has been linked to improved outcomes. To better understand the role of Treg in limiting the efficacy of anti‐cancer immunity, we used a Diphtheria toxin (DTX) transgenic mouse model to specifically target and deplete Treg. Methods Tumor bearing BALB/c FoxP3.dtr transgenic mice were subjected to different treatment protocols, with or without Treg depletion and tumor growth and survival monitored. Results DTX specifically depleted Treg in a transient, dose‐dependent manner. Treg depletion correlated with delayed tumor growth, increased effector T cell (Teff) activation, and enhanced survival in a range of solid tumors. Tumor regression was dependent on Teffs as depletion of both CD4 and CD8 T cells completely abrogated any survival benefit. Severe morbidity following Treg depletion was only observed, when consecutive doses of DTX were given during peak CD8 T cell activation, demonstrating that Treg can be depleted on multiple occasions, but only when CD8 T cell activation has returned to base line levels. Finally, we show that even minimal Treg depletion is sufficient to significantly improve the efficacy of tumor‐peptide vaccination. Conclusions BALB/c.FoxP3.dtr mice are an ideal model to investigate the full therapeutic potential of Treg depletion to boost anti‐tumor immunity. DTX‐mediated Treg depletion is transient, dose‐dependent, and leads to strong anti‐tumor immunity and complete tumor regression at high doses, while enhancing the efficacy of tumor‐specific vaccination at low doses. Together this data highlight the importance of Treg manipulation as a useful strategy for enhancing current and future cancer immunotherapies. PMID:28250921

Therapeutic Applications of Monte Carlo Calculations in Nuclear Medicine

CERN Document Server

Sgouros, George

2003-01-01

This book examines the applications of Monte Carlo (MC) calculations in therapeutic nuclear medicine, from basic principles to computer implementations of software packages and their applications in radiation dosimetry and treatment planning. It is written for nuclear medicine physicists and physicians as well as radiation oncologists, and can serve as a supplementary text for medical imaging, radiation dosimetry and nuclear engineering graduate courses in science, medical and engineering faculties. With chapters is written by recognised authorities in that particular field, the book covers the entire range of MC applications in therapeutic medical and health physics, from its use in imaging prior to therapy to dose distribution modelling targeted radiotherapy. The contributions discuss the fundamental concepts of radiation dosimetry, radiobiological aspects of targeted radionuclide therapy and the various components and steps required for implementing a dose calculation and treatment planning methodology in ...

Patient and staff doses in interventional neuroradiology

International Nuclear Information System (INIS)

Bor, D.; Cekirge, S.; Tuerkay, T.; Turan, O.; Guelay, M.; Oenal, E.; Cil, B.

2005-01-01

Radiation doses for interventional examinations are generally high and therefore necessitate dose monitoring for patients and staff. Relating the staff dose to a patient dose index, such as dose-area product (DAP), could be quite useful for dose comparisons. In this study, DAP and skin doses of 57 patients, who underwent neuro-interventional examinations, were measured simultaneously with staff doses. Although skin doses were comparable with the literature data, higher DAP values of 215 and 188.6 Gy cm 2 were measured for the therapeutical cerebral and carotid examinations, respectively, owing to the use of biplane system and complexity of the procedure. Mean staff doses for eye, finger and thyroid were measured as 80.6, 77.6 and 28.8 μGy per procedure. The mean effective dose per procedure for the radiologists was 32 μSv. In order to allow better comparisons to be made, DAP normalised doses were also presented. (authors)

Measures taken by the supervisory authority to reduce extremity doses in nuclear medicine facilities in Switzerland

International Nuclear Information System (INIS)

Stritt, Nicolas; Linder, Reto

2011-01-01

In its capacity as the supervisory authority, the Swiss Federal Office of Public Health (SFOPH) has responded to the increase in extremity doses observed in nuclear medicine facilities in Switzerland over the past decade by introducing facility-specific radiation protection audits. These audits have raised the awareness of the staff members concerned with the problem of high extremity doses which arise from handling beta emitters and PET nuclides and prevented any further rise in the extremity doses. However, the evaluation of these audits has also shown that there is still considerable scope for improvement in terms of reducing extremity doses and that further measures are therefore required. Facility-specific and person-specific investigations are currently being conducted with the support of the SFOPH. Their aim is to show facilities which operations during the preparation and application of diagnostic and therapeutic radiopharmaceuticals lead to high extremity doses. This will enable the reduction of extremity doses for nuclear medicine staff as well as ensure that the dose limits are adhered to, in spite of the increasing numbers of examinations.

Therapeutic Use of Cannabis in Inflammatory Bowel Disease

Science.gov (United States)

Katz, Seymour

2016-01-01

The marijuana plant Cannabis sativa and its derivatives, cannabinoids, have grown increasingly popular as a potential therapy for inflammatory bowel disease (IBD). Studies have shown that modulation of the endocannabinoid system, which regulates various functions in the body and has been shown to play a key role in the pathogenesis of IBD, has a therapeutic effect in mouse colitis. Epidemiologic data and human therapy studies reveal a possible role for cannabinoids in the symptomatic treatment of IBD, although it has yet to be determined in human populations whether cannabinoids have therapeutic anti-inflammatory effects in IBD or are simply masking its many debilitating symptoms. Large, double-blind, randomized, placebo-controlled trials using serial inflammatory markers, biopsy findings, and endoscopic disease severity to demonstrate objective improvement in IBD are necessary before cannabis can be empirically accepted and recommended as an IBD treatment option. Questions concerning its safety profile and adverse effects prompt the need for further research, particularly in regard to dosing and route of administration to maximize benefits and limit potential harms. Cannabis use should be reserved for symptomatic control in patients with severe IBD refractory to the currently available standard-of-care and complementary and alternative medicines. PMID:28035196

Comparing the cardiovascular therapeutic indices of glycopyrronium and tiotropium in an integrated rat pharmacokinetic, pharmacodynamic and safety model

International Nuclear Information System (INIS)

Trifilieff, Alexandre; Ethell, Brian T.; Sykes, David A.; Watson, Kenny J.; Collingwood, Steve; Charlton, Steven J.; Kent, Toby C.

2015-01-01

Long acting inhaled muscarinic receptor antagonists, such as tiotropium, are widely used as bronchodilator therapy for chronic obstructive pulmonary disease (COPD). Although this class of compounds is generally considered to be safe and well tolerated in COPD patients the cardiovascular safety of tiotropium has recently been questioned. We describe a rat in vivo model that allows the concurrent assessment of muscarinic antagonist potency, bronchodilator efficacy and a potential for side effects, and we use this model to compare tiotropium with NVA237 (glycopyrronium bromide), a recently approved inhaled muscarinic antagonist for COPD. Anaesthetized Brown Norway rats were dosed intratracheally at 1 or 6 h prior to receiving increasing doses of intravenous methacholine. Changes in airway resistance and cardiovascular function were recorded and therapeutic indices were calculated against the ED 50 values for the inhibition of methacholine-induced bronchoconstriction. At both time points studied, greater therapeutic indices for hypotension and bradycardia were observed with glycopyrronium (19.5 and 28.5 fold at 1 h; > 200 fold at 6 h) than with tiotropium (1.5 and 4.2 fold at 1 h; 4.6 and 5.5 fold at 6 h). Pharmacokinetic, protein plasma binding and rat muscarinic receptor binding properties for both compounds were determined and used to generate an integrated model of systemic M 2 muscarinic receptor occupancy, which predicted significantly higher M 2 receptor blockade at ED 50 doses with tiotropium than with glycopyrronium. In our preclinical model there was an improved safety profile for glycopyrronium when compared with tiotropium. - Highlights: • We use an in vivo rat model to study CV safety of inhaled muscarinic antagonists. • We integrate protein and receptor binding and PK of tiotropium and glycopyrrolate. • At ED 50 doses for bronchoprotection we model systemic M 2 receptor occupancy. • Glycopyrrolate demonstrates lower M 2 occupancy at

Comparing the cardiovascular therapeutic indices of glycopyrronium and tiotropium in an integrated rat pharmacokinetic, pharmacodynamic and safety model

Energy Technology Data Exchange (ETDEWEB)

Trifilieff, Alexandre; Ethell, Brian T. [Respiratory Disease Area, Novartis Institutes for Biomedical Research, Wimblehurst Road, Horsham, West Sussex RH12 5AB (United Kingdom); Sykes, David A. [Respiratory Disease Area, Novartis Institutes for Biomedical Research, Wimblehurst Road, Horsham, West Sussex RH12 5AB (United Kingdom); School of Life Sciences, Queen' s Medical Centre, University of Nottingham, Nottingham, NG7 2UH (United Kingdom); Watson, Kenny J.; Collingwood, Steve [Respiratory Disease Area, Novartis Institutes for Biomedical Research, Wimblehurst Road, Horsham, West Sussex RH12 5AB (United Kingdom); Charlton, Steven J. [Respiratory Disease Area, Novartis Institutes for Biomedical Research, Wimblehurst Road, Horsham, West Sussex RH12 5AB (United Kingdom); School of Life Sciences, Queen' s Medical Centre, University of Nottingham, Nottingham, NG7 2UH (United Kingdom); Kent, Toby C., E-mail: tobykent@me.com [Respiratory Disease Area, Novartis Institutes for Biomedical Research, Wimblehurst Road, Horsham, West Sussex RH12 5AB (United Kingdom)

2015-08-15

Long acting inhaled muscarinic receptor antagonists, such as tiotropium, are widely used as bronchodilator therapy for chronic obstructive pulmonary disease (COPD). Although this class of compounds is generally considered to be safe and well tolerated in COPD patients the cardiovascular safety of tiotropium has recently been questioned. We describe a rat in vivo model that allows the concurrent assessment of muscarinic antagonist potency, bronchodilator efficacy and a potential for side effects, and we use this model to compare tiotropium with NVA237 (glycopyrronium bromide), a recently approved inhaled muscarinic antagonist for COPD. Anaesthetized Brown Norway rats were dosed intratracheally at 1 or 6 h prior to receiving increasing doses of intravenous methacholine. Changes in airway resistance and cardiovascular function were recorded and therapeutic indices were calculated against the ED{sub 50} values for the inhibition of methacholine-induced bronchoconstriction. At both time points studied, greater therapeutic indices for hypotension and bradycardia were observed with glycopyrronium (19.5 and 28.5 fold at 1 h; > 200 fold at 6 h) than with tiotropium (1.5 and 4.2 fold at 1 h; 4.6 and 5.5 fold at 6 h). Pharmacokinetic, protein plasma binding and rat muscarinic receptor binding properties for both compounds were determined and used to generate an integrated model of systemic M{sub 2} muscarinic receptor occupancy, which predicted significantly higher M{sub 2} receptor blockade at ED{sub 50} doses with tiotropium than with glycopyrronium. In our preclinical model there was an improved safety profile for glycopyrronium when compared with tiotropium. - Highlights: • We use an in vivo rat model to study CV safety of inhaled muscarinic antagonists. • We integrate protein and receptor binding and PK of tiotropium and glycopyrrolate. • At ED{sub 50} doses for bronchoprotection we model systemic M{sub 2} receptor occupancy. • Glycopyrrolate demonstrates lower M

Team-based learning to improve learning outcomes in a therapeutics course sequence.

Science.gov (United States)

Bleske, Barry E; Remington, Tami L; Wells, Trisha D; Dorsch, Michael P; Guthrie, Sally K; Stumpf, Janice L; Alaniz, Marissa C; Ellingrod, Vicki L; Tingen, Jeffrey M

2014-02-12

To compare the effectiveness of team-based learning (TBL) to that of traditional lectures on learning outcomes in a therapeutics course sequence. A revised TBL curriculum was implemented in a therapeutic course sequence. Multiple choice and essay questions identical to those used to test third-year students (P3) taught using a traditional lecture format were administered to the second-year pharmacy students (P2) taught using the new TBL format. One hundred thirty-one multiple-choice questions were evaluated; 79 tested recall of knowledge and 52 tested higher level, application of knowledge. For the recall questions, students taught through traditional lectures scored significantly higher compared to the TBL students (88%±12% vs. 82%±16%, p=0.01). For the questions assessing application of knowledge, no differences were seen between teaching pedagogies (81%±16% vs. 77%±20%, p=0.24). Scores on essay questions and the number of students who achieved 100% were also similar between groups. Transition to a TBL format from a traditional lecture-based pedagogy allowed P2 students to perform at a similar level as students with an additional year of pharmacy education on application of knowledge type questions. However, P3 students outperformed P2 students regarding recall type questions and overall. Further assessment of long-term learning outcomes is needed to determine if TBL produces more persistent learning and improved application in clinical settings.

Low-dose add-back therapy during postoperative GnRH agonist treatment

Directory of Open Access Journals (Sweden)

Hsiao-Wen Tsai

2016-02-01

Conclusion: Low dose add-back therapy could effectively ameliorate hypoestrogenic side effects and simultaneously maintain the therapeutic response of GnRH agonist treatment. The treatment dropout was lower compared with a regular dose. Therefore, low dose add-back therapy can be considered a treatment choice during postoperative GnRH agonist treatment.

Improved tissue assignment using dual-energy computed tomography in low-dose rate prostate brachytherapy for Monte Carlo dose calculation

Energy Technology Data Exchange (ETDEWEB)

Côté, Nicolas [Département de Physique, Université de Montréal, Pavillon Roger-Gaudry (D-428), 2900 Boulevard Édouard-Montpetit, Montréal, Québec H3T 1J4 (Canada); Bedwani, Stéphane [Département de Radio-Oncologie, Centre Hospitalier de l’Université de Montréal (CHUM), 1560 Rue Sherbrooke Est, Montréal, Québec H2L 4M1 (Canada); Carrier, Jean-François, E-mail: jean-francois.carrier.chum@ssss.gouv.qc.ca [Département de Physique, Université de Montréal, Pavillon Roger-Gaudry (D-428), 2900 Boulevard Édouard-Montpetit, Montréal, Québec H3T 1J4, Canada and Département de Radio-Oncologie, Centre Hospitalier de l’Université de Montréal (CHUM), 1560 Rue Sherbrooke Est, Montréal, Québec H2L 4M1 (Canada)

2016-05-15

Purpose: An improvement in tissue assignment for low-dose rate brachytherapy (LDRB) patients using more accurate Monte Carlo (MC) dose calculation was accomplished with a metallic artifact reduction (MAR) method specific to dual-energy computed tomography (DECT). Methods: The proposed MAR algorithm followed a four-step procedure. The first step involved applying a weighted blend of both DECT scans (I {sub H/L}) to generate a new image (I {sub Mix}). This action minimized Hounsfield unit (HU) variations surrounding the brachytherapy seeds. In the second step, the mean HU of the prostate in I {sub Mix} was calculated and shifted toward the mean HU of the two original DECT images (I {sub H/L}). The third step involved smoothing the newly shifted I {sub Mix} and the two original I {sub H/L}, followed by a subtraction of both, generating an image that represented the metallic artifact (I {sub A,(H/L)}) of reduced noise levels. The final step consisted of subtracting the original I {sub H/L} from the newly generated I {sub A,(H/L)} and obtaining a final image corrected for metallic artifacts. Following the completion of the algorithm, a DECT stoichiometric method was used to extract the relative electronic density (ρ{sub e}) and effective atomic number (Z {sub eff}) at each voxel of the corrected scans. Tissue assignment could then be determined with these two newly acquired physical parameters. Each voxel was assigned the tissue bearing the closest resemblance in terms of ρ{sub e} and Z {sub eff}, comparing with values from the ICRU 42 database. A MC study was then performed to compare the dosimetric impacts of alternative MAR algorithms. Results: An improvement in tissue assignment was observed with the DECT MAR algorithm, compared to the single-energy computed tomography (SECT) approach. In a phantom study, tissue misassignment was found to reach 0.05% of voxels using the DECT approach, compared with 0.40% using the SECT method. Comparison of the DECT and SECT D

Therapeutic abortion on account of x-ray examination during pregnancy

Energy Technology Data Exchange (ETDEWEB)

Hammer-Jacobsen, E

1959-06-15

Previous studies on radiation injury to the foetus are reviewed. Very little is known about possible injuries due to the small radiation doses in diagnostic radiology. Eleven pregnant women had one or more abdominal X-ray examinations during the first three months of pregnancy. Subsequently, 8 had therapeutic abortion, whereas 3 went to term. The case histories are reported. The calculated foetal doses range from 0.03 to 3.7 r (0.01-18.9). The author makes the following preliminary suggestions about irradiation during the first four months of pregnancy: Foetal doses below about one r do not indicate induction of abortion. Foetal doses between about one r and about ten r indicate therapeutic abortion only in the presence of additional indications. Foetal doses above about 10 r presumably always indicate abortion. One of the pregnancies that was carried to term ought to have been interrupted. Four of the induced abortions ought not to have been performed. X-ray examinations of the abdomen should not be performed during the first four months of pregnancy. In order to avoid irradiation in the early stages of pregnancy, the following routine precaution is suggested: In fertile women X-ray examination of the abdomen should be carried out only during the first ten days after a regular menstrual period of normal intensity and duration. (author)

Therapeutic abortion on account of x-ray examination during pregnancy

International Nuclear Information System (INIS)

Hammer-Jacobsen, E.

1959-06-01

Previous studies on radiation injury to the foetus are reviewed. Very little is known about possible injuries due to the small radiation doses in diagnostic radiology. Eleven pregnant women had one or more abdominal X-ray examinations during the first three months of pregnancy. Subsequently, 8 had therapeutic abortion, whereas 3 went to term. The case histories are reported. The calculated foetal doses range from 0.03 to 3.7 r (0.01-18.9). The author makes the following preliminary suggestions about irradiation during the first four months of pregnancy: Foetal doses below about one r do not indicate induction of abortion. Foetal doses between about one r and about ten r indicate therapeutic abortion only in the presence of additional indications. Foetal doses above about 10 r presumably always indicate abortion. One of the pregnancies that was carried to term ought to have been interrupted. Four of the induced abortions ought not to have been performed. X-ray examinations of the abdomen should not be performed during the first four months of pregnancy. In order to avoid irradiation in the early stages of pregnancy, the following routine precaution is suggested: In fertile women X-ray examination of the abdomen should be carried out only during the first ten days after a regular menstrual period of normal intensity and duration. (author)

Maximizing the biological effect of proton dose delivered with scanned beams via inhomogeneous daily dose distributions

Energy Technology Data Exchange (ETDEWEB)

Zeng Chuan; Giantsoudi, Drosoula; Grassberger, Clemens; Goldberg, Saveli; Niemierko, Andrzej; Paganetti, Harald; Efstathiou, Jason A.; Trofimov, Alexei [Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114 (United States)

2013-05-15

control probability (TCP) and normal tissue complication probability (NTCP). To assess potential local RBE variations, LET distributions were calculated with Monte Carlo, and compared for different plans. The results were assessed in terms of their sensitivity to uncertainties in model parameters and delivery. Results: IFD courses included equal number of fractions boosting either hemisphere, thus, the combined physical dose was close to uniform throughout the prostate. However, for the entire course, the prostate EUD in IFD was higher than in conventional FTP by up to 14%, corresponding to the estimated increase in TCP to 96% from 88%. The extent of gain depended on the mixing factor, i.e., relative weights used to combine FTP and STP spot weights. Increased weighting of STP typically yielded a higher target EUD, but also led to increased sensitivity of dose to variations in the proton's range. Rectal and bladder EUD were same or lower (per normalization), and the NTCP for both remained below 1%. The LET distributions in IFD also depended strongly on the mixing weights: plans using higher weight of STP spots yielded higher LET, indicating a potentially higher local RBE. Conclusions: In proton therapy delivered by pencil beam scanning, improved therapeutic outcome can potentially be expected with delivery of IFD distributions, while administering the prescribed quasi-uniform dose to the target over the entire course. The biological effectiveness of IFD may be further enhanced by optimizing the LET distributions. IFD distributions are characterized by a dose gradient located in proximity of the prostate's midplane, thus, the fidelity of delivery would depend crucially on the precision with which the proton range could be controlled.

Maximizing the biological effect of proton dose delivered with scanned beams via inhomogeneous daily dose distributions

International Nuclear Information System (INIS)

Zeng Chuan; Giantsoudi, Drosoula; Grassberger, Clemens; Goldberg, Saveli; Niemierko, Andrzej; Paganetti, Harald; Efstathiou, Jason A.; Trofimov, Alexei

2013-01-01

control probability (TCP) and normal tissue complication probability (NTCP). To assess potential local RBE variations, LET distributions were calculated with Monte Carlo, and compared for different plans. The results were assessed in terms of their sensitivity to uncertainties in model parameters and delivery. Results: IFD courses included equal number of fractions boosting either hemisphere, thus, the combined physical dose was close to uniform throughout the prostate. However, for the entire course, the prostate EUD in IFD was higher than in conventional FTP by up to 14%, corresponding to the estimated increase in TCP to 96% from 88%. The extent of gain depended on the mixing factor, i.e., relative weights used to combine FTP and STP spot weights. Increased weighting of STP typically yielded a higher target EUD, but also led to increased sensitivity of dose to variations in the proton's range. Rectal and bladder EUD were same or lower (per normalization), and the NTCP for both remained below 1%. The LET distributions in IFD also depended strongly on the mixing weights: plans using higher weight of STP spots yielded higher LET, indicating a potentially higher local RBE. Conclusions: In proton therapy delivered by pencil beam scanning, improved therapeutic outcome can potentially be expected with delivery of IFD distributions, while administering the prescribed quasi-uniform dose to the target over the entire course. The biological effectiveness of IFD may be further enhanced by optimizing the LET distributions. IFD distributions are characterized by a dose gradient located in proximity of the prostate's midplane, thus, the fidelity of delivery would depend crucially on the precision with which the proton range could be controlled.

Maximizing the biological effect of proton dose delivered with scanned beams via inhomogeneous daily dose distributions.

Science.gov (United States)

Zeng, Chuan; Giantsoudi, Drosoula; Grassberger, Clemens; Goldberg, Saveli; Niemierko, Andrzej; Paganetti, Harald; Efstathiou, Jason A; Trofimov, Alexei

2013-05-01

(TCP) and normal tissue complication probability (NTCP). To assess potential local RBE variations, LET distributions were calculated with Monte Carlo, and compared for different plans. The results were assessed in terms of their sensitivity to uncertainties in model parameters and delivery. IFD courses included equal number of fractions boosting either hemisphere, thus, the combined physical dose was close to uniform throughout the prostate. However, for the entire course, the prostate EUD in IFD was higher than in conventional FTP by up to 14%, corresponding to the estimated increase in TCP to 96% from 88%. The extent of gain depended on the mixing factor, i.e., relative weights used to combine FTP and STP spot weights. Increased weighting of STP typically yielded a higher target EUD, but also led to increased sensitivity of dose to variations in the proton's range. Rectal and bladder EUD were same or lower (per normalization), and the NTCP for both remained below 1%. The LET distributions in IFD also depended strongly on the mixing weights: plans using higher weight of STP spots yielded higher LET, indicating a potentially higher local RBE. In proton therapy delivered by pencil beam scanning, improved therapeutic outcome can potentially be expected with delivery of IFD distributions, while administering the prescribed quasi-uniform dose to the target over the entire course. The biological effectiveness of IFD may be further enhanced by optimizing the LET distributions. IFD distributions are characterized by a dose gradient located in proximity of the prostate's midplane, thus, the fidelity of delivery would depend crucially on the precision with which the proton range could be controlled.

Therapeutic hypothermia for acute stroke

DEFF Research Database (Denmark)

Olsen, Tom Skyhøj; Weber, Uno Jakob; Kammersgaard, Lars Peter

2003-01-01

Experimental evidence and clinical experience show that hypothermia protects the brain from damage during ischaemia. There is a growing hope that the prevention of fever in stroke will improve outcome and that hypothermia may be a therapeutic option for the treatment of stroke. Body temperature...... obvious therapeutic potential, hypothermia as a form of neuroprotection for stroke has been investigated in only a few very small studies. Therapeutic hypothermia is feasible in acute stroke but owing to serious side-effects--such as hypotension, cardiac arrhythmia, and pneumonia--it is still thought...

Intranasal administration of a therapeutic HIV vaccine (Vacc-4x induces dose-dependent systemic and mucosal immune responses in a randomized controlled trial.

Directory of Open Access Journals (Sweden)

Kristin Brekke

Full Text Available Vacc-4x, a Gag p24-based therapeutic HIV vaccine, has been shown to reduce viral load set-points after intradermal administration. In this randomized controlled pilot study we investigate intranasal administration of Vacc-4x with Endocine as adjuvant.Safety and immunogenicity were tested in patients on effective ART. They were randomized to low, medium or high dose Vacc-4x or adjuvant alone, administered four times at weekly intervals with no booster. Vacc-4x-specific T cell responses were measured in vitro by proliferation and in vivo by a single DTH skin test at the end of study. Nasal and rectal mucosal secretions were analyzed for Vacc-4x-specific antibodies by ELISA. Immune regulation induced by Vacc-4x was assessed by functional blockade of the regulatory cytokines IL-10 and TGF-β.Vacc-4x proliferative T cell responses increased only among the vaccinated (p ≤ 0.031. The low dose group showed the greatest increase in Vacc-4x CD8+T cell responses (p = 0.037 and developed larger DTH (p = 0.005 than the adjuvant group. Rectal (distal Vacc-4x IgA and IgG antibodies also increased (p = 0.043 in this group. In contrast, the high dose generated higher nasal (local Vacc-4x IgA (p = 0.028 and serum IgG (p = 0.030 antibodies than the adjuvant. Irrespective of dose, increased Vacc-4x CD4+T cell responses were associated with low proliferation (r = -0.82, p < 0.001 and high regulation (r = 0.61, p = 0.010 at baseline.Intranasal administration of Vacc-4x with Endocine was safe and induced dose-dependent vaccine-specific T cell responses and both mucosal and systemic humoral responses. The clinical significance of dose, immune regulation and mucosal immunity warrants further investigation.ClinicalTrials.gov NCT01473810.

Protective effect and the therapeutic index of indralin in juvenile rhesus monkeys

International Nuclear Information System (INIS)

Vasin, Mikhail V.; Antipov, Vsevolod V.; Ushakov, Igor B.; Semenov, Leonid F.; Lapin, Boris A.; Suvorov, Nikolai N.; Ilyin, Leonid A.

2014-01-01

The radioprotective effect of indralin in rhesus monkeys was examined over 60 d following gamma irradiation. Male and female rhesus macaques (Macaca mulatta) 2-3-years-old and weighing 2.1-3.5 kg were used. Animals were exposed to total-body gamma irradiation from 60 Co at a dose of 6.8 Gy (lethal dose, 100% lethality over 30 days). Indralin (40-120 mg kg -1 ) was administered intramuscularly 5 min prior to radiation exposure. Indralin taken at a dose of 120 mg kg -1 protected five out of six monkeys (compared with the radiation control group, in which all 10 animals died). The average effective dose of indralin in the monkeys exposed to gamma irradiation for 30 min was equal to 77.3 (63.3-94.3) mg kg -1 , and the maximum tolerated dose of indralin administered to monkeys was 800 mg kg -1 . Indralin reduced radiation-induced injuries in macaques, thus resulting in a less severe course of acute radiation syndrome. Delayed and less pronounced manifestation of the haemorrhagic syndrome of the disease, and milder forms of both leukopenia and anaemia were also noted. The therapeutic index for indralin, expressed as the ratio of the maximum tolerated dose to the average effective dose, was equal to 10. Therefore, indralin has a significant radioprotective effect against radiation and has a high therapeutic index in rhesus monkeys. (author)

Poster - 53: Improving inter-linac DMLC IMRT dose precision by fine tuning of MLC leaf calibration

International Nuclear Information System (INIS)

Nakonechny, Keith; Tran, Muoi; Sasaki, David; Beck, James; Poirier, Yannick; Malkoske, Kyle

2016-01-01

Purpose: To develop a method to improve the inter-linac precision of DMLC IMRT dosimetry. Methods: The distance between opposing MLC leaf banks (“gap size”) can be finely tuned on Varian linacs. The dosimetric effect due to small deviations from the nominal gap size (“gap error”) was studied by introducing known errors for several DMLC sliding gap sizes, and for clinical plans based on the TG119 test cases. The plans were delivered on a single Varian linac and the relationship between gap error and the corresponding change in dose was measured. The plans were also delivered on eight Varian 2100 series linacs (at two institutions) in order to quantify the inter-linac variation in dose before and after fine tuning the MLC calibration. Results: The measured dose differences for each field agreed well with the predictions of LoSasso et al. Using the default MLC calibration, the variation in the physical MLC gap size was determined to be less than 0.4 mm between all linacs studied. The dose difference between the linacs with the largest and smallest physical gap was up to 5.4% (spinal cord region of the head and neck TG119 test case). This difference was reduced to 2.5% after fine tuning the MLC gap calibration. Conclusions: The inter-linac dose precision for DMLC IMRT on Varian linacs can be improved using a simple modification of the MLC calibration procedure that involves fine adjustment of the nominal gap size.

Poster - 53: Improving inter-linac DMLC IMRT dose precision by fine tuning of MLC leaf calibration

Energy Technology Data Exchange (ETDEWEB)

Nakonechny, Keith; Tran, Muoi; Sasaki, David; Beck, James; Poirier, Yannick; Malkoske, Kyle [Simcoe-Muskoka Regional Cancer Centre (Canada)

2016-08-15

Purpose: To develop a method to improve the inter-linac precision of DMLC IMRT dosimetry. Methods: The distance between opposing MLC leaf banks (“gap size”) can be finely tuned on Varian linacs. The dosimetric effect due to small deviations from the nominal gap size (“gap error”) was studied by introducing known errors for several DMLC sliding gap sizes, and for clinical plans based on the TG119 test cases. The plans were delivered on a single Varian linac and the relationship between gap error and the corresponding change in dose was measured. The plans were also delivered on eight Varian 2100 series linacs (at two institutions) in order to quantify the inter-linac variation in dose before and after fine tuning the MLC calibration. Results: The measured dose differences for each field agreed well with the predictions of LoSasso et al. Using the default MLC calibration, the variation in the physical MLC gap size was determined to be less than 0.4 mm between all linacs studied. The dose difference between the linacs with the largest and smallest physical gap was up to 5.4% (spinal cord region of the head and neck TG119 test case). This difference was reduced to 2.5% after fine tuning the MLC gap calibration. Conclusions: The inter-linac dose precision for DMLC IMRT on Varian linacs can be improved using a simple modification of the MLC calibration procedure that involves fine adjustment of the nominal gap size.

Improved walking ability and reduced therapeutic stress with an electromechanical gait device.

Science.gov (United States)

Freivogel, Susanna; Schmalohr, Dieter; Mehrholz, Jan

2009-09-01

To evaluate the effectiveness of repetitive locomotor training using a newly developed electromechanical gait device compared with treadmill training/gait training with respect to patient's ambulatory motor outcome, necessary personnel resources, and discomfort experienced by therapists and patients. Randomized, controlled, cross-over trial. Sixteen non-ambulatory patients after stroke, severe brain or spinal cord injury sequentially received 2 kinds of gait training. Study intervention A: 20 treatments of locomotor training with an electromechanical gait device; control intervention B: 20 treatments of locomotor training with treadmill or task-oriented gait training. The primary variable was walking ability (Functional Ambulation Category). Secondary variables included gait velocity, Motricity-Index, Rivermead-Mobility-Index, number of therapists needed, and discomfort and effort of patients and therapists during training. Gait ability and the other motor outcome related parameters improved for all patients, but without significant difference between intervention types. However, during intervention A, significantly fewer therapists were needed, and they reported less discomfort and a lower level of effort during training sessions. Locomotor training with or without an electromechanical gait trainer leads to improved gait ability; however, using the electromechanical gait trainer requires less therapeutic assistance, and therapist discomfort is reduced.

What is the best dose of nature and green exercise for improving mental health? A multi-study analysis.

Science.gov (United States)

Barton, Jo; Pretty, Jules

2010-05-15

Green exercise is activity in the presence of nature. Evidence shows it leads to positive short and long-term health outcomes. This multistudy analysis assessed the best regime of dose(s) of acute exposure to green exercise required to improve self-esteem and mood (indicators of mental health). The research used meta-analysis methodology to analyze 10 UK studies involving 1252 participants. Outcomes were identified through a priori subgroup analyses, and dose-responses were assessed for exercise intensity and exposure duration. Other subgroup analyses included gender, age group, starting health status, and type of habitat. The overall effect size for improved self-esteem was d = 0.46 (CI 0.34-0.59, p exercise, and then diminishing but still positive returns. Every green environment improved both self-esteem and mood; the presence of water generated greater effects. Both men and women had similar improvements in self-esteem after green exercise, though men showed a difference for mood. Age groups: for self-esteem, the greatest change was in the youngest, with diminishing effects with age; for mood, the least change was in the young and old. The mentally ill had one of the greatest self-esteem improvements. This study confirms that the environment provides an important health service.

Improvements in dose calculation accuracy for small off-axis targets in high dose per fraction tomotherapy

Energy Technology Data Exchange (ETDEWEB)

Hardcastle, Nicholas; Bayliss, Adam; Wong, Jeannie Hsiu Ding; Rosenfeld, Anatoly B.; Tome, Wolfgang A. [Department of Human Oncology, University of Wisconsin-Madison, WI, 53792 (United States); Department of Physical Sciences, Peter MacCallum Cancer Centre, Melbourne, VIC 3002 (Australia) and Centre for Medical Radiation Physics, University of Wollongong, Wollongong, NSW 2522 (Australia); Department of Human Oncology, University of Wisconsin-Madison, WI 53792 (United States); Centre for Medical Radiation Physics, University of Wollongong, Wollongong, NSW 2522 (Australia) and Department of Biomedical Imaging, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur (Malaysia); Centre for Medical Radiation Physics, University of Wollongong, Wollongong, NSW 2522 (Australia); Department of Medical Physics, University of Wisconsin-Madison, Madison, Wisconsin 53792 (United States); Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, Wisconsin 53792 (United States); Einstein Institute of Oncophysics, Albert Einstein College of Medicine of Yeshiva University, Bronx, New York 10461 (United States) and Centre for Medical Radiation Physics, University of Wollongong, Wollongong, NSW 2522 (Australia)

2012-08-15

Purpose: A recent field safety notice from TomoTherapy detailed the underdosing of small, off-axis targets when receiving high doses per fraction. This is due to angular undersampling in the dose calculation gantry angles. This study evaluates a correction method to reduce the underdosing, to be implemented in the current version (v4.1) of the TomoTherapy treatment planning software. Methods: The correction method, termed 'Super Sampling' involved the tripling of the number of gantry angles from which the dose is calculated during optimization and dose calculation. Radiochromic film was used to measure the dose to small targets at various off-axis distances receiving a minimum of 21 Gy in one fraction. Measurements were also performed for single small targets at the center of the Lucy phantom, using radiochromic film and the dose magnifying glass (DMG). Results: Without super sampling, the peak dose deficit increased from 0% to 18% for a 10 mm target and 0% to 30% for a 5 mm target as off-axis target distances increased from 0 to 16.5 cm. When super sampling was turned on, the dose deficit trend was removed and all peak doses were within 5% of the planned dose. For measurements in the Lucy phantom at 9.7 cm off-axis, the positional and dose magnitude accuracy using super sampling was verified using radiochromic film and the DMG. Conclusions: A correction method implemented in the TomoTherapy treatment planning system which triples the angular sampling of the gantry angles used during optimization and dose calculation removes the underdosing for targets as small as 5 mm diameter, up to 16.5 cm off-axis receiving up to 21 Gy.

Improvements in dose calculation accuracy for small off-axis targets in high dose per fraction tomotherapy

International Nuclear Information System (INIS)

Hardcastle, Nicholas; Bayliss, Adam; Wong, Jeannie Hsiu Ding; Rosenfeld, Anatoly B.; Tomé, Wolfgang A.

2012-01-01

Purpose: A recent field safety notice from TomoTherapy detailed the underdosing of small, off-axis targets when receiving high doses per fraction. This is due to angular undersampling in the dose calculation gantry angles. This study evaluates a correction method to reduce the underdosing, to be implemented in the current version (v4.1) of the TomoTherapy treatment planning software. Methods: The correction method, termed “Super Sampling” involved the tripling of the number of gantry angles from which the dose is calculated during optimization and dose calculation. Radiochromic film was used to measure the dose to small targets at various off-axis distances receiving a minimum of 21 Gy in one fraction. Measurements were also performed for single small targets at the center of the Lucy phantom, using radiochromic film and the dose magnifying glass (DMG). Results: Without super sampling, the peak dose deficit increased from 0% to 18% for a 10 mm target and 0% to 30% for a 5 mm target as off-axis target distances increased from 0 to 16.5 cm. When super sampling was turned on, the dose deficit trend was removed and all peak doses were within 5% of the planned dose. For measurements in the Lucy phantom at 9.7 cm off-axis, the positional and dose magnitude accuracy using super sampling was verified using radiochromic film and the DMG. Conclusions: A correction method implemented in the TomoTherapy treatment planning system which triples the angular sampling of the gantry angles used during optimization and dose calculation removes the underdosing for targets as small as 5 mm diameter, up to 16.5 cm off-axis receiving up to 21 Gy.

Improving the Accuracy of a Heliocentric Potential (HCP Prediction Model for the Aviation Radiation Dose

Directory of Open Access Journals (Sweden)

Junga Hwang

2016-12-01

Full Text Available The space radiation dose over air routes including polar routes should be carefully considered, especially when space weather shows sudden disturbances such as coronal mass ejections (CMEs, flares, and accompanying solar energetic particle events. We recently established a heliocentric potential (HCP prediction model for real-time operation of the CARI-6 and CARI-6M programs. Specifically, the HCP value is used as a critical input value in the CARI-6/6M programs, which estimate the aviation route dose based on the effective dose rate. The CARI-6/6M approach is the most widely used technique, and the programs can be obtained from the U.S. Federal Aviation Administration (FAA. However, HCP values are given at a one month delay on the FAA official webpage, which makes it difficult to obtain real-time information on the aviation route dose. In order to overcome this critical limitation regarding the time delay for space weather customers, we developed a HCP prediction model based on sunspot number variations (Hwang et al. 2015. In this paper, we focus on improvements to our HCP prediction model and update it with neutron monitoring data. We found that the most accurate method to derive the HCP value involves (1 real-time daily sunspot assessments, (2 predictions of the daily HCP by our prediction algorithm, and (3 calculations of the resultant daily effective dose rate. Additionally, we also derived the HCP prediction algorithm in this paper by using ground neutron counts. With the compensation stemming from the use of ground neutron count data, the newly developed HCP prediction model was improved.

[Nuclear transfer and therapeutic cloning].

Science.gov (United States)

Xu, Xiao-Ming; Lei, An-Min; Hua, Jin-Lian; Dou, Zhong-Ying

2005-03-01

Nuclear transfer and therapeutic cloning have widespread and attractive prospects in animal agriculture and biomedical applications. We reviewed that the quality of oocytes and nuclear reprogramming of somatic donor cells were the main reasons of the common abnormalities in cloned animals and the low efficiency of cloning and showed the problems and outlets in therapeutic cloning, such as some basic problems in nuclear transfer affected clinical applications of therapeutic cloning. Study on isolation and culture of nuclear transfer embryonic stem (ntES) cells and specific differentiation of ntES cells into important functional cells should be emphasized and could enhance the efficiency. Adult stem cells could help to cure some great diseases, but could not replace therapeutic cloning. Ethics also impeded the development of therapeutic cloning. It is necessary to improve many techniques and reinforce the research of some basic theories, then somatic nuclear transfer and therapeutic cloning may apply to agriculture reproduction and benefit to human life better.

Differentiated thyroid cancer treatment with therapeutic doses of 131I calculated by dosimetry: our experience

International Nuclear Information System (INIS)

Fadel, Ana M.; Chebel, G.M.; Valdivieso, C.M.; Degrossi, Osvaldo J.; Cabrejas, R.; Cabrejas, M.L.

2006-01-01

The optimum dose for the differentiated thyroid cancer treatment is a motive of controversy. There exist two ways of deciding the dose to administer: the empirical method (fixed doses) and dosimetric calculation method. The use of fixed doses has demonstrated safety and effectiveness. Nevertheless there are cases in which the use of several small doses not resolves the metastases illness of the patients. Using the Benua-Leeper method for dosimetric calculation we have evaluated the maximum dose treatment that could be administered to 20 patients who showed persistent disease after several treatments with 131 I. (author) [es

Efficacy of various single-dose regimens of ceftriaxone in ...

African Journals Online (AJOL)

The therapeutic efficacy of single intramuscular doses of ceftriaxone (Rocephin; Roche) (62,S, 125 and 250 mg), administered without probenecid, was evaluated in 167 adult males with uncomplicated acute gonococcal urethritis. Cure rates of 100% were achieved at 62,5 mg and 250 mg. In the 125 mg dose group, ...

Mid-ventilation position planning: Optimal model for dose distribution in lung tumour

International Nuclear Information System (INIS)

Benchalal, M.; Leseur, J.; Chajon, E.; Cazoulat, G.; Haigron, P.; Simon, A.; Bellec, J.; Lena, H.; Crevoisier, R. de

2012-01-01

Purpose. - The dose distribution for lung tumour is estimated using a 3D-CT scan, and since a person breathes while the images are captured, the dose distribution doesn't reflect the reality. A 4D-CT scan integrates the motion of the tumour during breathing and, therefore, provides us with important information regarding tumour's motion in all directions, the motion volume (ITV) and the time-weighted average position (MVP). Patient and methods. - Based on these two concepts, we have estimated, for a lung carcinoma case a 3D dose distribution from a 3D-CT scan, and a 4D dose distribution from a 4-D CT scan. To this, we have applied a non-rigid registration to estimate the cumulative dose. Results. - Our study shows that the 4D dose estimation of the GTV is almost the same when made using MVP and ITV concepts, but sparring of the healthy lung is better done using the MPV model (MVP), as compared to the ITV model. This improvement of the therapeutic index allows, from a projection on the theoretical maximal dose to PTV (strictly restricted to doses for the lungs and the spinal cord), for an increase of about 11% on the total dose (maximal dose of 86 Gy for the ITV and 96 Gy for the MVP). Conclusion. - Further studies with more patients are needed to confirm our data. (authors)

Cocoa consumption dose-dependently improves flow-mediated dilation and arterial stiffness decreasing blood pressure in healthy individuals.

Science.gov (United States)

Grassi, Davide; Desideri, Giovambattista; Necozione, Stefano; di Giosia, Paolo; Barnabei, Remo; Allegaert, Leen; Bernaert, Herwig; Ferri, Claudio

2015-02-01

Cocoa flavonoids exert beneficial vascular effects and reduce the risk of cardiovascular morbidity and mortality. Nevertheless, the involved mechanisms have not been clarified and no study has yet focused on the dose-response effects. We aimed to investigate the effects of different doses of cocoa flavonoids on flow-mediated dilation (FMD), endothelin-1 (ET-1), pulse wave velocity (PWV), and SBP and DBP. According to a randomized, double-blind, controlled, cross-over design, 20 healthy volunteers (1.5% improvement in FMD in 20 individuals: 0.99 at alpha = 0.05) were assigned to receive either five treatments with daily intake of 10 g cocoa (0, 80, 200, 500 and 800 mg cocoa flavonoids/day) in five periods lasting 1 week each. Cocoa dose-dependently increased FMD from 6.2% (control) to 7.3, 7.6, 8.1 and 8.2% after the different flavonoid doses, respectively (P cocoa flavonoids per day increased FMD (P Cocoa dose-dependently decreased PWV (P Cocoa intake decreased office blood pressure (BP) (SBP: -4.8 ± 1.03  mmHg, P cocoa ingestion decreased 24-h (P = 0.05) and daytime (P = 0.038) SBP, and 24-h (P = 0.0064), daytime (P = 0.0088) and night-time (P = 0.0352) pulse pressure. Compared with the control, cocoa dose-dependently decreased ET-1 levels [from 17.1 (control) to 15.2, 14.5, 14.2 and 14.1 pg/ml, after the different flavonoid doses, respectively (P for treatment cocoa dose-dependently improved FMD and decreased PWV and ET-1 also by ameliorating office and monitored BP. Our findings are clinically relevant, suggesting cocoa, with very low calorie intake, might be reasonably incorporated into a dietary approach, representing a consistent tool in cardiovascular prevention.

A matter of timing: identifying significant multi-dose radiotherapy improvements by numerical simulation and genetic algorithm search.

Directory of Open Access Journals (Sweden)

Simon D Angus

Full Text Available Multi-dose radiotherapy protocols (fraction dose and timing currently used in the clinic are the product of human selection based on habit, received wisdom, physician experience and intra-day patient timetabling. However, due to combinatorial considerations, the potential treatment protocol space for a given total dose or treatment length is enormous, even for relatively coarse search; well beyond the capacity of traditional in-vitro methods. In constrast, high fidelity numerical simulation of tumor development is well suited to the challenge. Building on our previous single-dose numerical simulation model of EMT6/Ro spheroids, a multi-dose irradiation response module is added and calibrated to the effective dose arising from 18 independent multi-dose treatment programs available in the experimental literature. With the developed model a constrained, non-linear, search for better performing cadidate protocols is conducted within the vicinity of two benchmarks by genetic algorithm (GA techniques. After evaluating less than 0.01% of the potential benchmark protocol space, candidate protocols were identified by the GA which conferred an average of 9.4% (max benefit 16.5% and 7.1% (13.3% improvement (reduction on tumour cell count compared to the two benchmarks, respectively. Noticing that a convergent phenomenon of the top performing protocols was their temporal synchronicity, a further series of numerical experiments was conducted with periodic time-gap protocols (10 h to 23 h, leading to the discovery that the performance of the GA search candidates could be replicated by 17-18 h periodic candidates. Further dynamic irradiation-response cell-phase analysis revealed that such periodicity cohered with latent EMT6/Ro cell-phase temporal patterning. Taken together, this study provides powerful evidence towards the hypothesis that even simple inter-fraction timing variations for a given fractional dose program may present a facile, and highly cost

A matter of timing: identifying significant multi-dose radiotherapy improvements by numerical simulation and genetic algorithm search.

Science.gov (United States)

Angus, Simon D; Piotrowska, Monika Joanna

2014-01-01

Multi-dose radiotherapy protocols (fraction dose and timing) currently used in the clinic are the product of human selection based on habit, received wisdom, physician experience and intra-day patient timetabling. However, due to combinatorial considerations, the potential treatment protocol space for a given total dose or treatment length is enormous, even for relatively coarse search; well beyond the capacity of traditional in-vitro methods. In constrast, high fidelity numerical simulation of tumor development is well suited to the challenge. Building on our previous single-dose numerical simulation model of EMT6/Ro spheroids, a multi-dose irradiation response module is added and calibrated to the effective dose arising from 18 independent multi-dose treatment programs available in the experimental literature. With the developed model a constrained, non-linear, search for better performing cadidate protocols is conducted within the vicinity of two benchmarks by genetic algorithm (GA) techniques. After evaluating less than 0.01% of the potential benchmark protocol space, candidate protocols were identified by the GA which conferred an average of 9.4% (max benefit 16.5%) and 7.1% (13.3%) improvement (reduction) on tumour cell count compared to the two benchmarks, respectively. Noticing that a convergent phenomenon of the top performing protocols was their temporal synchronicity, a further series of numerical experiments was conducted with periodic time-gap protocols (10 h to 23 h), leading to the discovery that the performance of the GA search candidates could be replicated by 17-18 h periodic candidates. Further dynamic irradiation-response cell-phase analysis revealed that such periodicity cohered with latent EMT6/Ro cell-phase temporal patterning. Taken together, this study provides powerful evidence towards the hypothesis that even simple inter-fraction timing variations for a given fractional dose program may present a facile, and highly cost-effecitive means

The Therapeutic Effect of Human Embryonic Stem Cell-Derived Multipotent Mesenchymal Stem Cells on Chemical-Induced Cystitis in Rats

Directory of Open Access Journals (Sweden)

Sang Wook Lee

2018-01-01

Full Text Available Purpose To evaluate the therapeutic effect of human embryonic stem cell (hESC-derived multipotent mesenchymal stem cells (M-MSCs on ketamine-induced cystitis (KC in rats. Methods To induce KC, 10-week-old female rats were injected with 25-mg/kg ketamine hydrochloride twice weekly for 12 weeks. In the sham group, phosphate buffered saline (PBS was injected instead of ketamine. One week after the final injection of ketamine, the indicated doses (0.25, 0.5, and 1×106 cells of M-MSCs (KC+M-MSC group or PBS vehicle (KC group were directly injected into the bladder wall. One week after M-MSC injection, the therapeutic outcomes were evaluated via cystometry, histological analyses, and measurement of gene expression. Next, we compared the efficacy of M-MSCs at a low dose (1×105 cells to that of an identical dose of adult bone marrow (BM-derived MSCs. Results Rats in the KC group exhibited increased voiding frequency and reduced bladder capacity compared to rats of the sham group. However, these parameters recovered after transplantation of M-MSCs at all doses tested. KC bladders exhibited markedly increased mast cell infiltration, apoptosis, and tissue fibrosis. Administration of M-MSCs significantly reversed these characteristic histological alterations. Gene expression analyses indicated that several genes associated with tissue fibrosis were markedly upregulated in KC bladders. However the expression of these genes was significantly suppressed by the administration of M-MSCs. Importantly, M-MSCs ameliorated bladder deterioration in KC rats after injection of a low dose (1×105 of cells, at which point BM-derived MSCs did not substantially improve bladder function. Conclusions This study demonstrates for the first time the therapeutic efficacy of hESC-derived M-MSCs on KC in rats. M-MSCs restored bladder function more effectively than did BM-derived MSCs, protecting against abnormal changes including mast cell infiltration, apoptosis and fibrotic

Dose-volume considerations in stereotaxic brain radiation therapy

International Nuclear Information System (INIS)

Houdek, P.V.; Schwade, J.G.; Pisciotta, V.J.; Medina, A.J.; Lewin, A.A.; Abitbol, A.A.; Serago, C.F.

1988-01-01

Although brain radiation therapy experience suggests that a gain in the therapeutic ratio may be achieved by optimizing the dose-volume relationship, no practical system for quantitative assessment of dose-volume data has been developed. This presentation describes the rationale for using the integral dose function for this purpose and demonstrates that with the use of a conventional treatment planning computer and a series of computed tomographic scans, first-order optimization of the dose-volume function can be accomplished in two steps: first, high-dose volume is minimized by selecting an appropriate treatment technique and tumor margin, and then dosage is maximized by calculating the brain tolerance dose as a function of the irradiated volume

Regulatory requirements for marketing fixed dose combinations

Directory of Open Access Journals (Sweden)

B G Jayasheel

2010-01-01

Full Text Available The development of fixed-dose combinations (FDCs is becoming increasingly important from a public health perspective. FDCs have advantages when there is an identifiable patient population for whom treatment with a particular combination of actives in a fixed ratio is safe and effective and when all of the actives contribute to the overall therapeutic effect. Such combinations of drugs are particularly useful in the management of chronic diseases. In addition, there can be real clinical benefits in the form of increased efficacy and/or a reduced incidence of adverse effects. Additional advantages of FDCs are potentially lower costs of manufacturing compared to the costs of producing separate products administered concurrently, simpler logistics of distribution and reduced development of resistance in the case of antimicrobials. Above all, FDC therapy reduces pill burden and improves medication compliance. Although, FDCs seem to be ideal under certain pre-defined circumstances, if a dosing adjustment is warranted, there may not be an FDC available in the most appropriate strength for the patient and if an adverse drug reaction occurs from using an FDC, it may be difficult to identify the active ingredient responsible for causing the reaction. Appendix VI of Schedule Y (Drugs & Cosmetics Rules 1945, India states the requirements for marketing approval of various types of FDCs. The same is further elaborated in this article to provide a detailed guidance including the clinical trial requirements. However, the heterogeneity of the therapeutic field makes it difficult to develop a standard guidance document.

An investigation of dose changes for therapeutic kilovoltage x-ray beams with underlying lead shielding

International Nuclear Information System (INIS)

Hill, Robin; Healy, Brendan; Holloway, Lois; Baldock, Clive

2007-01-01

Kilovoltage x-ray beams are used to treat cancer on or close to the skin surface. Many clinical cases use high atomic number materials as shielding to reduce dose to underlying healthy tissues. In this work, we have investigated the effect on both the surface dose and depth doses in a water phantom with lead shielding at depth in the phantom. The EGSnrc Monte Carlo code was used to simulate the water phantom and to calculate the surface doses and depth doses using primary x-ray beam spectra derived from an analytical model. The x-ray beams were in the energy range of 75-135 kVp with field sizes of 2, 5 and 8 cm diameter. The lead sheet was located beneath the water surface at depths ranging from 0.5-7.5 cm. The surface dose decreased as the lead was positioned closer to the water surface and as the field size was increased. The variation in surface dose as a function of x-ray beam energy was only small but the maximum reduction occurred for the 100 kVp x-ray beam. For the 8 cm diameter field with the lead at 1 cm depth and using the 100 kVp x-ray beam, the surface dose was reduced to 0.898 of the surface dose in the water phantom only. Measured surface dose changes, using a Farmer-type ionization chamber, agreed with the Monte Carlo calculated doses. Calculated depth doses in water with a lead sheet positioned below the surface showed that the dose fall-off increased as the lead was positioned closer to the water surface as compared to the depth dose in the water phantom only. Monte Carlo calculations of the total x-ray beam spectrum at the water surface showed that the total fluence decreased due to a reduction in backscatter from within the water and very little backscatter from the lead. The mean energy of the x-ray spectrum varied less than 1 keV, with the lead at 1 cm beneath the water phantom surface. As the Monte Carlo calculations showed good agreement with the measured results, this method can be used to verify surface dose changes in clinical situations

Quantifying the Effectiveness of Dose Individualization by Simulation for a Drug With Moderate Pharmacokinetic Variability.

Science.gov (United States)

Liefaard, Lia; Chen, Chao

2015-10-01

Dose individualization can reduce variability in exposure. The objective of this work was to quantify, through pharmacokinetic (PK) simulation, the potential for reducing the variability in exposure by dose individualization for a drug with moderate PK variability between subjects and between occasions within a subject, and a narrow therapeutic window. Using a population PK model that includes between-subject and between-occasion variability for apparent clearance, individual PK profiles in a trial of 300 subjects after a test dose were simulated. From the simulated data, datasets were created mimicking various sampling regimens (from single predose sample to full profile samples over 12 hours) on 1 or more occasions (1, 2, 3, 5, or 10 visits). Using these datasets, individual apparent clearance values were estimated, which were then used to calculate an individualized dose for a predefined target area under the concentration-time curve (AUC), based on the available formulation strengths. The proportion of people whose mean AUC was within a predefined therapeutic AUC range was calculated for the test (before) and the individualized dose (after), and compared between the different sampling scenarios. The maximum increase in proportion of subjects with an AUC within the range was 20%. To achieve this benefit, PK samples over 4 hours from 100 dosing occasions were required. As a result of the dose adjustment, the AUC of 7.3% of the subjects moved from inside the therapeutic range to outside of the range. This work shows how modeling and simulation can help assess the benefit and risk of dose individualization for a compound with variability between subjects and between occasions. The framework can be applied to similar situations with a defined set of conditions (eg, therapeutic window, tablet strengths, and PK and/or pharmacodynamic sampling scheme) to inform dose change and to assess the utility of dose individualization against certain success criteria.

Improved estimates of external gamma dose rates in the environs of Hinkley Point Power Station

International Nuclear Information System (INIS)

Macdonald, H.F.; Thompson, I.M.G.

1988-07-01

The dominant source of external gamma dose rates at centres of population within a few kilometres of Hinkley Point Power Station is the routine discharge of 41-Ar from the 'A' station magnox reactors. Earlier estimates of the 41-Ar radiation dose rates were based upon measured discharge rates, combined with calculations using standard plume dispersion and cloud-gamma integration models. This report presents improved dose estimates derived from environmental gamma dose rate measurements made at distances up to about 1 km from the site, thus minimising the degree of extrapolation introduced in estimating dose rates at locations up to a few kilometres from the site. In addition, results from associated chemical tracer measurements and wind tunnel simulations covering distances up to about 4 km from the station are outlined. These provide information on the spatial distribution of the 41-Ar plume during the initial stages of its dispersion, including effects due to plume buoyancy and momentum and behaviour under light wind conditions. In addition to supporting the methodology used for the 41-Ar dose calculations, this information is also of generic interest in the treatment of a range of operational and accidental releases from nuclear power station sites and will assist in the development and validation of existing environmental models. (author)

Low-dose budesonide treatment improves lung function in patients with infrequent asthma symptoms at baseline

DEFF Research Database (Denmark)

Reddel, H. K.; Busse, W. W.; Pedersen, Søren

2015-01-01

symptom frequency groups (Figure). CONCLUSIONS: Long-term, once-daily, low-dose budesonide treatment plus usual asthma medication improves lung function in patients with mild, recent-onset asthma. These beneficial effects were seen even in patients with the lowest baseline asthma symptom frequency (0......RATIONALE: Inhaled corticosteroids (ICS) are highly effective in low doses for improving asthma outcomes, including lung function. In the past, ICS treatment was recommended for patients with 'persistent' asthma, defined by symptoms >2 days/week.1 However, evidence is lacking for the benefit of ICS...... in patients with less frequent symptoms at presentation. This was investigated in a post-hoc analysis of the multinational inhaled Steroid Treatment As Regular Therapy in early asthma (START) study.2 METHODS: Patients aged 4-66 years (median 21 years) with a history of recent-onset mild asthma (11 years...

Consensus Guidelines for Therapeutic Drug Monitoring in Neuropsychopharmacology: Update 2017.

Science.gov (United States)

Hiemke, C; Bergemann, N; Clement, H W; Conca, A; Deckert, J; Domschke, K; Eckermann, G; Egberts, K; Gerlach, M; Greiner, C; Gründer, G; Haen, E; Havemann-Reinecke, U; Hefner, G; Helmer, R; Janssen, G; Jaquenoud, E; Laux, G; Messer, T; Mössner, R; Müller, M J; Paulzen, M; Pfuhlmann, B; Riederer, P; Saria, A; Schoppek, B; Schoretsanitis, G; Schwarz, M; Gracia, M Silva; Stegmann, B; Steimer, W; Stingl, J C; Uhr, M; Ulrich, S; Unterecker, S; Waschgler, R; Zernig, G; Zurek, G; Baumann, P

2018-01-01

Therapeutic drug monitoring (TDM) is the quantification and interpretation of drug concentrations in blood to optimize pharmacotherapy. It considers the interindividual variability of pharmacokinetics and thus enables personalized pharmacotherapy. In psychiatry and neurology, patient populations that may particularly benefit from TDM are children and adolescents, pregnant women, elderly patients, individuals with intellectual disabilities, patients with substance abuse disorders, forensic psychiatric patients or patients with known or suspected pharmacokinetic abnormalities. Non-response at therapeutic doses, uncertain drug adherence, suboptimal tolerability, or pharmacokinetic drug-drug interactions are typical indications for TDM. However, the potential benefits of TDM to optimize pharmacotherapy can only be obtained if the method is adequately integrated in the clinical treatment process. To supply treating physicians and laboratories with valid information on TDM, the TDM task force of the Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie (AGNP) issued their first guidelines for TDM in psychiatry in 2004. After an update in 2011, it was time for the next update. Following the new guidelines holds the potential to improve neuropsychopharmacotherapy, accelerate the recovery of many patients, and reduce health care costs. © Georg Thieme Verlag KG Stuttgart · New York.

Therapeutic alliance in a randomized clinical trial for bulimia nervosa.

Science.gov (United States)

Accurso, Erin C; Fitzsimmons-Craft, Ellen E; Ciao, Anna; Cao, Li; Crosby, Ross D; Smith, Tracey L; Klein, Marjorie H; Mitchell, James E; Crow, Scott J; Wonderlich, Stephen A; Peterson, Carol B

2015-06-01

This study examined the temporal relation between therapeutic alliance and outcome in two treatments for bulimia nervosa (BN). Eighty adults with BN symptoms were randomized to 21 sessions of integrative cognitive-affective therapy (ICAT) or enhanced cognitive-behavioral therapy (CBT-E). Bulimic symptoms (i.e., frequency of binge eating and purging) were assessed at each session and posttreatment. Therapeutic alliance (Working Alliance Inventory) was assessed at Sessions 2, 8, 14, and posttreatment. Repeated-measures analyses using linear mixed models with random intercepts were conducted to determine differences in alliance growth by treatment and patient characteristics. Mixed-effects models examined the relation between alliance and symptom improvement. Overall, patients in both treatments reported strong therapeutic alliances. Regardless of treatment, greater therapeutic alliance between (but not within) subjects predicted greater reductions in bulimic behavior; reductions in bulimic behavior also predicted improved alliance. Patients with higher depression, anxiety, or emotion dysregulation had a stronger therapeutic alliance in CBT-E than ICAT, while those with more intimacy problems had greater improvement in therapeutic alliance in ICAT compared to CBT-E. Therapeutic alliance has a unique impact on outcome, independent of the impact of symptom improvement on alliance. Within- and between-subjects effects revealed that changes in alliance over time did not predict symptom improvement, but rather that individuals who had a stronger alliance overall had better bulimic symptom outcomes. These findings indicate that therapeutic alliance is an important predictor of outcome in the treatment of BN. (c) 2015 APA, all rights reserved).

Doses received by organs in interventional cardiology; Les doses recues aux organes en cardiologie interventionnelle

Energy Technology Data Exchange (ETDEWEB)

Maccia, C. [Centre d' Assurance de qualite des Applications Technologiques dans le domaine de la Sante, (CAATS) - 43, Bd du Marechal Joffre, 92 - Bourg-La-Reine (France)

2009-07-01

After a discussion of several publications about patient dosimetry in interventional cardiology, the author recalls that the in vivo assessment of the dose received by some organs is uneasy because invasive. Therefore, the assessment requires the use of physical or mathematical dosimetric phantoms which simulate patient morphology as well as the incident photon attenuation phenomenon. He evokes some characteristics and applications of these phantoms. He outlines the different sources and origins of the dose received by the patient, and discusses results obtained by collecting data from 177 patients submitted to diagnosis or therapeutic procedures

Improving the dose-myelotoxicity correlation in radiometabolic therapy of bone metastases with {sup 153}Sm-EDTMP

Energy Technology Data Exchange (ETDEWEB)

Pacilio, Massimiliano; Basile, Chiara [Azienda Ospedaliera San Camillo Forlanini, Rome (Italy). Dept. of Medical Physics; Ventroni, Guido; Mango, Lucio [Azienda Ospedaliera San Camillo Forlanini, Rome (Italy). Dept. of Nuclear Medicine; Ialongo, Pasquale [Azienda Ospedaliera San Camillo Forlanini, Rome (Italy). Dept. of Radiology; Becci, Domenico [University of Rome, Health Physics Postgraduate School, Rome (Italy)

2014-02-15

{sup 153}Sm-ethylene diamine tetramethylene phosphonic acid ({sup 153}Sm-EDTMP) is widely used to palliate pain from bone metastases, and is being studied for combination therapy beyond palliation. Conceptually, red marrow (RM) dosimetry allows myelotoxicity to be predicted, but the correlation is poor due to dosimetric uncertainty, individual sensitivity and biological effects from previous treatments. According to EANM guidelines, basic dosimetric procedures have been studied to improve the correlation between dosimetry and myelotoxicity in {sup 153}Sm-EDTMP therapy. RM dosimetry for 33 treatments of bone metastases from breast, prostate and lung tumours was performed prospectively (with {sup 99m}Tc-MDP) and retrospectively, acquiring whole-body scans early and late after injection. The {sup 153}Sm-EDTMP activity was calculated by prospective dosimetry based on measured skeletal uptake and full physical retention, with the RM absorbed dose not exceeding 3.8 Gy. Patient-specific RM mass was evaluated by scaling in terms of body weight (BW), lean body mass (LBM) and trabecular volume (TV) estimated from CT scans of the L2-L4 vertebrae. Correlations with toxicity were determined in a selected subgroup of 27 patients, in which a better correlation between dosimetry and myelotoxicity was expected. Skeletal uptakes of {sup 99m}Tc and {sup 153}Sm (Tc{sub %} and Sm{sub %}) were well correlated. The median Sm{sub %} was higher in prostate cancer (75.3 %) than in lung (60.5 %, p = 0.005) or breast (60.8 %, p = 0.008). PLT and WBC nadirs were not correlated with administered activity, but were weakly correlated with uncorrected RM absorbed doses, and the correlation improved after rescaling in terms of BW, LBM and TV. Most patients showed transient toxicity (grade 1-3), which completely and spontaneously recovered over a few days. Using TV, RM absorbed dose was in the range 2-5 Gy, with a median of 312 cGy for PLT in patients with toxicity and 247 cGy in those with no

Breviscapine Injection Improves the Therapeutic Effect of Western Medicine on Angina Pectoris Patients.

Science.gov (United States)

Wang, Chuan; Li, Yafeng; Gao, Shoucui; Cheng, Daxin; Zhao, Sihai; Liu, Enqi

2015-01-01

To evaluate the beneficial and adverse effects of breviscapine injection in combination with Western medicine on the treatment of patients with angina pectoris. The Cochrane Central Register of Controlled Trials, Medline, Science Citation Index, EMBASE, the China National Knowledge Infrastructure, the Wanfang Database, the Chongqing VIP Information Database and the China Biomedical Database were searched to identify randomized clinical trials (RCTs) that evaluated the effects of Western medicine compared to breviscapine injection plus Western medicine on angina pectoris patients. The included studies were analyzed using RevMan 5.1.0 software. The literature search yielded 460 studies, wherein 16 studies matched the selection criteria. The results showed that combined therapy using Breviscapine plus Western medicine was superior to Western medicine alone for improving angina pectoris symptoms (OR=3.77, 95% Cl: 2.76~5.15) and also resulted in increased electrocardiogram (ECG) improvement (OR=2.77, 95% Cl: 2.16~3.53). The current evidence suggests that Breviscapine plus Western medicine achieved a superior therapeutic effect compared to Western medicine alone.

Head CT: Image quality improvement of posterior fossa and radiation dose reduction with ASiR - comparative studies of CT head examinations.

Science.gov (United States)

Guziński, Maciej; Waszczuk, Łukasz; Sąsiadek, Marek J

2016-10-01

To evaluate head CT protocol developed to improve visibility of the brainstem and cerebellum, lower bone-related artefacts in the posterior fossa and maintain patient radioprotection. A paired comparison of head CT performed without Adaptive Statistical Iterative Reconstruction (ASiR) and a clinically indicated follow-up with 40 % ASiR was acquired in one group of 55 patients. Patients were scanned in the axial mode with different scanner settings for the brain and the posterior fossa. Objective image quality analysis was performed with signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR). Subjective image quality analysis was based on brain structure visibility and evaluation of the artefacts. We achieved 19 % reduction of total DLP and significantly better image quality of posterior fossa structures. SNR for white and grey matter in the cerebellum were 34 % to 36 % higher, respectively, CNR was improved by 142 % and subjective analyses were better for images with ASiR. When imaging parameters are set independently for the brain and the posterior fossa imaging, ASiR has a great potential to improve CT performance: image quality of the brainstem and cerebellum is improved, and radiation dose for the brain as well as total radiation dose are reduced. •With ASiR it is possible to lower radiation dose or improve image quality •Sequentional imaging allows setting scan parameters for brain and posterior-fossa independently •We improved visibility of brainstem structures and decreased radiation dose •Total radiation dose (DLP) was decreased by 19.

The use of inexpensive broad spectrum lower toxicity therapeutics in chronic lymphocytic leukemia.

Science.gov (United States)

Marjanovic, Goran

2017-01-01

The use of new and highly efficient targeted therapies for chronic lymphocytic leukemia (CLL) is costly and out of reach for many health care systems. On the other hand, in recent years, few inexpensive, broad-spectrum low-toxicity therapeutics have proven to be effective both in the preclinical and clinical settings. In early-stage CLL, the use of 2000 mg of epigallocatechin-3-gallate (EGCG) from the green tea extract twice a day was able to reduce the absolute leukocyte count. Supplementation of >2000 IU/day of Vitamin D in early low-risk CLL patients is able to delay disease progression and postpone the moment of initiation of the first treatment. The doses of both vitamin D and EGCG were shown to be safe in older patients. Vitamin D, EGCG and Curcumin, either as monotherapy or in combination, have additive and synergistic effects with conventional chemotherapy. Further observations have identified the improvement of response to rituximab-fludarabine-cyclophosphamide (R-FC) therapy with concomitant administration of statin and aspirin combination in relapsed/refractory CLL. Finally, high dose dexamethasone with 40mg/m 2 /day for 4 days, every 28 days, either alone or with monoclonal antibody, might be used as a salvage therapy or for debulking before transplantation in refractory/resistant cases. Dexamethasone therapy is followed by transient response and high rate of infections, but fluid retention and other toxicities are lower compared to high dose methylprednisolone schedules. The low cost therapeutics discussed in this review could not be a substitute for the more effective targeted therapies, but their use in every day practice might postpone the need for early implementation of new and costly medications.

Crystalline dose of interventional radiologists; Dosis en cristalino de radiologicos intervencionistas

Energy Technology Data Exchange (ETDEWEB)

Hernandez Concepcion, E.; Diaz Romero, F.; Catalan Acosta, A.; Hernandez Armas, J.

2013-07-01

The measured dose area product in radiology equipment used in angio radiology during different diagnostic and therapeutic can be used to estimate the value of the dose in the lens of doctors or medical personnel carrying out such interventions. (Author)

Individualized Dose Prescription for Hypofractionation in Advanced Non-Small-Cell Lung Cancer Radiotherapy: An in silico Trial

Energy Technology Data Exchange (ETDEWEB)

Hoffmann, Aswin L.; Troost, Esther G.C.; Huizenga, Henk; Kaanders, Johannes H.A.M. [Radboud University Nijmegen Medical Centre, Department of Radiation Oncology, Nijmegen (Netherlands); Bussink, Johan, E-mail: j.bussink@rther.umcn.nl [Radboud University Nijmegen Medical Centre, Department of Radiation Oncology, Nijmegen (Netherlands)

2012-08-01

Purpose: Local tumor control and outcome remain poor in patients with advanced non-small-cell lung cancer (NSCLC) treated by external beam radiotherapy. We investigated the therapeutic gain of individualized dose prescription with dose escalation based on normal tissue dose constraints for various hypofractionation schemes delivered with intensity-modulated radiation therapy. Methods and Materials: For 38 Stage III NSCLC patients, the dose level of an existing curative treatment plan with standard fractionation (66 Gy) was rescaled based on dose constraints for the lung, spinal cord, esophagus, brachial plexus, and heart. The effect on tumor total dose (TTD) and biologic tumor effective dose in 2-Gy fractions (TED) corrected for overall treatment time (OTT) was compared for isotoxic and maximally tolerable schemes given in 15, 20, and 33 fractions. Rescaling was accomplished by altering the dose per fraction and/or the number of fractions while keeping the relative dose distribution of the original treatment plan. Results: For 30 of the 38 patients, dose escalation by individualized hypofractionation yielded therapeutic gain. For the maximally tolerable dose scheme in 33 fractions (MTD{sub 33}), individualized dose escalation resulted in a 2.5-21% gain in TTD. In the isotoxic schemes, the number of fractions could be reduced with a marginal increase in TED. For the maximally tolerable dose schemes, the TED could be escalated up to 36.6%, and for all patients beyond the level of the isotoxic and the MTD{sub 33} schemes (range, 3.3-36.6%). Reduction of the OTT contributed to the therapeutic gain of the shortened schemes. For the maximally tolerable schemes, the maximum esophageal dose was the dominant dose-limiting constraint in most patients. Conclusions: This modeling study showed that individualized dose prescription for hypofractionation in NSCLC radiotherapy, based on scaling of existing treatment plans up to normal tissue dose constraints, enables dose

Daily high doses of fluoxetine for weight loss and improvement in lifestyle before bariatric surgery

NARCIS (Netherlands)

Dolfing, JG; Wolffenbuttel, BHR; Oei, HI; ten Hoor-Aukerna, NM; Schweitzer, DH

Background: The number of gastric restrictive bariatric operations is increasing each year, but about one-fifth of patients will become disappointed due to unsatisfactory weight reduction or annoying complications. We questioned whether weight reduction by taking high doses of fluoxetine improves

A new therapeutic effect of simvastatin revealed by functional improvement in muscular dystrophy.

Science.gov (United States)

Whitehead, Nicholas P; Kim, Min Jeong; Bible, Kenneth L; Adams, Marvin E; Froehner, Stanley C

2015-10-13

Duchenne muscular dystrophy (DMD) is a lethal, degenerative muscle disease with no effective treatment. DMD muscle pathogenesis is characterized by chronic inflammation, oxidative stress, and fibrosis. Statins, cholesterol-lowering drugs, inhibit these deleterious processes in ischemic diseases affecting skeletal muscle, and therefore have potential to improve DMD. However, statins have not been considered for DMD, or other muscular dystrophies, principally because skeletal-muscle-related symptoms are rare, but widely publicized, side effects of these drugs. Here we show positive effects of statins in dystrophic skeletal muscle. Simvastatin dramatically reduced damage and enhanced muscle function in dystrophic (mdx) mice. Long-term simvastatin treatment vastly improved overall muscle health in mdx mice, reducing plasma creatine kinase activity, an established measure of muscle damage, to near-normal levels. This reduction was accompanied by reduced inflammation, more oxidative muscle fibers, and improved strength of the weak diaphragm muscle. Shorter-term treatment protected against muscle fatigue and increased mdx hindlimb muscle force by 40%, a value comparable to current dystrophin gene-based therapies. Increased force correlated with reduced NADPH Oxidase 2 protein expression, the major source of oxidative stress in dystrophic muscle. Finally, in old mdx mice with severe muscle degeneration, simvastatin enhanced diaphragm force and halved fibrosis, a major cause of functional decline in DMD. These improvements were accompanied by autophagy activation, a recent therapeutic target for DMD, and less oxidative stress. Together, our findings highlight that simvastatin substantially improves the overall health and function of dystrophic skeletal muscles and may provide an unexpected, novel therapy for DMD and related neuromuscular diseases.

Pitfalls associated with the therapeutic reference pricing practice of asthma medication.

Science.gov (United States)

Kalo, Zoltan; Abonyi-Toth, Zsolt; Bartfai, Zoltan; Voko, Zoltan

2012-07-20

Therapeutic reference pricing (TRP) based on the WHO daily defined dose (DDD) is a method frequently employed for the cost-containment of pharmaceuticals. Our objective was to compare average drug use in the real world with DDD and to evaluate whether TRP based on DDD could result in cost savings on maintenance medication and the total direct health expenditures for asthma patients treated with Symbicort Turbuhaler (SYT) and Seretide Diskus (SED) in Hungary. Real-world data were derived from the Hungarian National Health Insurance Fund database. Average doses and costs were compared between the high-dose and medium-dose SYT and SED groups. Multiple linear regressions were employed to adjust the data for differences in the gender and age distribution of patients. 27,779 patients with asthma were included in the analysis. Average drug use was lower than DDD in all groups, 1.38-1.95 inhalations in both SED groups, 1.28-1.97 and 1.74-2.49 inhalations in the medium and high-dose SYT groups, respectively. Although the cost of SED based on the DDD would be much lower than the cost of SYT in the medium-dose groups, no difference was found in the actual cost of the maintenance therapy. No significant differences were found between the groups in terms of total medical costs. Cost-containment initiatives by payers may influence clinical decisions. TRP for inhalation asthma drugs raises special concern, because of differences in the therapeutic profile of pharmaceuticals and the lack of proven financial benefits after exclusion of the effect of generic price erosion. Our findings indicate that the presented TRP approach of asthma medications based on the daily therapeutic costs according to the WHO DDD does not result in reduced public healthcare spending in Hungary. Further analysis is required to show whether TRP generates additional expenditures by inducing switching costs and reducing patient compliance. Potential confounding factors may limit the generalisability of our

[End therapeutic nihilism towards COPD].

Science.gov (United States)

Juergens, Uwe R

2007-03-15

Prevention of COPD requires appropriate patient education, especially of adolescents, as well as the establishment of an effective national health policy. The new GOLD guidelines represent the current standard of knowledge on the management of chronic, progressive, obstructive pulmonary diseases. It points out that COPD is avoidable and treatable,and hence, there is no reason for therapeutic nihilism. Chronic bronchitis preceding a progressive respiratory obstruction cannot be improved with the presently available respiratory therapeutics. For this reason, therapeutic measures concentrate on the avoidance of exacerbations, which are primarily responsible for the severity of the course of COPD.

Patient-Centered Prescription Model to improve therapeutic adherence in patients with multimorbidity

Directory of Open Access Journals (Sweden)

Javier González-Bueno

2018-05-01

Full Text Available To date, interventions to improve medication adherence in patients with multimorbidity have shown modest and inconsistent efficacy among available studies. Thereby, we should define new approaches aimed at improving medication adherence tailored to effective prescribing, with a multidisciplinary approach and patient-centered. In this regard, the Patient-Centered Prescription Model has shown its usefulness on improving appropriateness of drug treatments in patients with clinical complexity. For that, this strategy addresses the following four steps: 1 Patient-Centered assessment; 2 Diagnosis-Centered assessment; 3 Medication-Centered assessment; and 4 Therapeutic Plan. We propose through a clinical case an adaptation of the Patient-Centered Prescription Model to enhance both appropriateness and medication adherence in patients with multimorbidity. To this end, we have included on its first step the Spanish version of a cross-culturally adapted scale for the multidimensional assessment of medication adherence. Furthermore, we suggest a set of interventions to be applied in the three remaining steps of the model. These interventions were firstly identified by an overview of systematic reviews and then selected by a panel of experts based on Delphi methodology. All of these elements have been considered appropriate in patients with multimorbidity according to three criteria: strength of their supporting evidence, usefulness in the target population and feasibility of implementation in clinical practice. The proposed approach intends to lay the foundations for an innovative way in tackling medication adherence in patients with multimorbidity.

Keeping an eye on the ring: COMS plaque loading optimization for improved dose conformity and homogeneity.

Science.gov (United States)

Gagne, Nolan L; Cutright, Daniel R; Rivard, Mark J

2012-09-01

To improve tumor dose conformity and homogeneity for COMS plaque brachytherapy by investigating the dosimetric effects of varying component source ring radionuclides and source strengths. The MCNP5 Monte Carlo (MC) radiation transport code was used to simulate plaque heterogeneity-corrected dose distributions for individually-activated source rings of 14, 16 and 18 mm diameter COMS plaques, populated with (103)Pd, (125)I and (131)Cs sources. Ellipsoidal tumors were contoured for each plaque size and MATLAB programming was developed to generate tumor dose distributions for all possible ring weighting and radionuclide permutations for a given plaque size and source strength resolution, assuming a 75 Gy apical prescription dose. These dose distributions were analyzed for conformity and homogeneity and compared to reference dose distributions from uniformly-loaded (125)I plaques. The most conformal and homogeneous dose distributions were reproduced within a reference eye environment to assess organ-at-risk (OAR) doses in the Pinnacle(3) treatment planning system (TPS). The gamma-index analysis method was used to quantitatively compare MC and TPS-generated dose distributions. Concentrating > 97% of the total source strength in a single or pair of central (103)Pd seeds produced the most conformal dose distributions, with tumor basal doses a factor of 2-3 higher and OAR doses a factor of 2-3 lower than those of corresponding uniformly-loaded (125)I plaques. Concentrating 82-86% of the total source strength in peripherally-loaded (131)Cs seeds produced the most homogeneous dose distributions, with tumor basal doses 17-25% lower and OAR doses typically 20% higher than those of corresponding uniformly-loaded (125)I plaques. Gamma-index analysis found > 99% agreement between MC and TPS dose distributions. A method was developed to select intra-plaque ring radionuclide compositions and source strengths to deliver more conformal and homogeneous tumor dose distributions than

Radon as a medicine. Therapeutic effectiveness, biological mechanism and comparative risk assessment

International Nuclear Information System (INIS)

Deetjen, Peter; Falkenbach, Albrecht; Harder, Dietrich; Joeckel, Hans; Kaul, Alexander; Philipsborn, Henning von

2014-01-01

Proofs of the therapeutic efficiency of balneological radon applications administered to patients suffering from rheumatic diseases, investigations into the biological action mechanism associated with the alpha particles emitted by radon and its radioactive daughter products, and the comparative risk assessment of radon treatment and medicinal pain therapy have been the research projects whose results are summarized in this book. Controlled clinical studies, if possible performed as prospective, randomized and placebo-controlled double blind studies, have given evidence that the therapeutic effects of balneological radon applications - long-lasting pain reduction and reduced consumption of medicines compared with controls - are significantly persisting over many post-treatment months. The molecular and cellular mechanism of action underlying these long-lasting therapeutic effects has been identified as the down-regulation of cellular immune responses, initiated by cellular apoptosis sequential to low alpha particle doses and by the subsequent release of anti-inflammatory cytokines. The unwanted side-effects of non-steroidal anti-rheumatic drug treatments have to be compared with the absence of side effects from the balneological radon applications which merely involve radiation doses well below the mean value and the fluctuation width of the annual doses attributable to everybody's natural radiation exposure.

Radon as a medicine. Therapeutic effectiveness, biological mechanism and comparative risk assessment

Energy Technology Data Exchange (ETDEWEB)

Deetjen, Peter; Falkenbach, Albrecht; Harder, Dietrich; Joeckel, Hans; Kaul, Alexander; Philipsborn, Henning von

2014-07-01

Proofs of the therapeutic efficiency of balneological radon applications administered to patients suffering from rheumatic diseases, investigations into the biological action mechanism associated with the alpha particles emitted by radon and its radioactive daughter products, and the comparative risk assessment of radon treatment and medicinal pain therapy have been the research projects whose results are summarized in this book. Controlled clinical studies, if possible performed as prospective, randomized and placebo-controlled double blind studies, have given evidence that the therapeutic effects of balneological radon applications - long-lasting pain reduction and reduced consumption of medicines compared with controls - are significantly persisting over many post-treatment months. The molecular and cellular mechanism of action underlying these long-lasting therapeutic effects has been identified as the down-regulation of cellular immune responses, initiated by cellular apoptosis sequential to low alpha particle doses and by the subsequent release of anti-inflammatory cytokines. The unwanted side-effects of non-steroidal anti-rheumatic drug treatments have to be compared with the absence of side effects from the balneological radon applications which merely involve radiation doses well below the mean value and the fluctuation width of the annual doses attributable to everybody's natural radiation exposure.

EcoDoses. Improving radiological assessment of doses to man from terrestrial ecosystems: A status report for the NKS-B activity 2006

Energy Technology Data Exchange (ETDEWEB)

Nielsen, S.; Andersson, K.G. (Technical Univ. of Denmark, Risoe National Lab. for Sustainable Energy, Roskilde (Denmark)); Thoerring, H.; Liland, A. (Norwegian Radiation Protection Authority (Norway)); Joensen, H.P. (Frooskaparsetur Foeroya, Faroe Islands, Torshavn (Denmark)); Isaksson, M. (Goeteborg Univ. (Sweden)); Saxen, R.; Kostiainen, E. (Radiation and Nuclear Safety Authority (STUK) (Finland)); Suolanen, V. (VTT Technical Research Centre of Finland, Espoo (Finland)); Palsson, S.E. (Geislavarnir rikisins (Iceland))

2009-03-15

The overall aim of the NKS-B EcoDoses activity is to improve the prediction of doses to humans from consumption of radioactively contaminated food. For this purpose, various published and unpublished datasets have been compiled and applied in developing refined parameterisation for existing food dose models. The ECOSYS model developed in Germany after the Chernobyl accident has been applied as the basis for the investigations. This model can be operated both with discrete releases adequately representing a nuclear power plant accident, and with continuous or multiple releases, as observed in the nuclear weapons testing period. The modelling has revealed that it is essential to ensure that case-specific values are applied for a range of parameters, adequately reflecting the actual conditions with respect to geology, season, climate and demography. In connection with this year's work on the activity, sensitivity studies have been conducted with the ECOSYS model, in which the influence on ingestion dose estimates of a number of parameters has been evaluated in relation to Faroese conditions. The importance of applying location specific data to estimate dose is pinpointed, and it is also concluded that dose predictions for a small and distinct area like the Faroese, where not all of the many parameters required to run ECOSYS optimally have been adequately assessed in recent years, can be associated with considerable uncertainty. A Finnish study has been made in relation to modelling of radiocaesium behaviour in lakes. This study was carried out using a compartmental model that is included as a module in the DETRA dose assessment tool. A total of nine different input parameters (distribution coefficients, run-off from the catchment, erosion from the catchment, sedimentation rate in the lakes, lake water exchange rate, and biological half-lives in four fish species) were varied, and particularly distribution coefficients and lake water exchange rates were

EcoDoses. Improving radiological assessment of doses to man from terrestrial ecosystems: A status report for the NKS-B activity 2006

International Nuclear Information System (INIS)

Nielsen, S.; Andersson, K.G.; Thoerring, H.; Liland, A.; Joensen, H.P.; Isaksson, M.; Saxen, R.; Kostiainen, E.; Suolanen, V.; Palsson, S.E.

2009-03-01

The overall aim of the NKS-B EcoDoses activity is to improve the prediction of doses to humans from consumption of radioactively contaminated food. For this purpose, various published and unpublished datasets have been compiled and applied in developing refined parameterisation for existing food dose models. The ECOSYS model developed in Germany after the Chernobyl accident has been applied as the basis for the investigations. This model can be operated both with discrete releases adequately representing a nuclear power plant accident, and with continuous or multiple releases, as observed in the nuclear weapons testing period. The modelling has revealed that it is essential to ensure that case-specific values are applied for a range of parameters, adequately reflecting the actual conditions with respect to geology, season, climate and demography. In connection with this year's work on the activity, sensitivity studies have been conducted with the ECOSYS model, in which the influence on ingestion dose estimates of a number of parameters has been evaluated in relation to Faroese conditions. The importance of applying location specific data to estimate dose is pinpointed, and it is also concluded that dose predictions for a small and distinct area like the Faroese, where not all of the many parameters required to run ECOSYS optimally have been adequately assessed in recent years, can be associated with considerable uncertainty. A Finnish study has been made in relation to modelling of radiocaesium behaviour in lakes. This study was carried out using a compartmental model that is included as a module in the DETRA dose assessment tool. A total of nine different input parameters (distribution coefficients, run-off from the catchment, erosion from the catchment, sedimentation rate in the lakes, lake water exchange rate, and biological half-lives in four fish species) were varied, and particularly distribution coefficients and lake water exchange rates were demonstrated to

A second dose of kisspeptin-54 improves oocyte maturation in women at high risk of ovarian hyperstimulation syndrome: a Phase 2 randomized controlled trial.

Science.gov (United States)

Abbara, Ali; Clarke, Sophie; Islam, Rumana; Prague, Julia K; Comninos, Alexander N; Narayanaswamy, Shakunthala; Papadopoulou, Deborah; Roberts, Rachel; Izzi-Engbeaya, Chioma; Ratnasabapathy, Risheka; Nesbitt, Alexander; Vimalesvaran, Sunitha; Salim, Rehan; Lavery, Stuart A; Bloom, Stephen R; Huson, Les; Trew, Geoffrey H; Dhillo, Waljit S

2017-09-01

Can increasing the duration of LH-exposure with a second dose of kisspeptin-54 improve oocyte maturation in women at high risk of ovarian hyperstimulation syndrome (OHSS)? A second dose of kisspeptin-54 at 10 h following the first improves oocyte yield in women at high risk of OHSS. Kisspeptin acts at the hypothalamus to stimulate the release of an endogenous pool of GnRH from the hypothalamus. We have previously reported that a single dose of kisspeptin-54 results in an LH-surge of ~12-14 h duration, which safely triggers oocyte maturation in women at high risk of OHSS. Phase-2 randomized placebo-controlled trial of 62 women at high risk of OHSS recruited between August 2015 and May 2016. Following controlled ovarian stimulation, all patients (n = 62) received a subcutaneous injection of kisspeptin-54 (9.6 nmol/kg) 36 h prior to oocyte retrieval. Patients were randomized 1:1 to receive either a second dose of kisspeptin-54 (D; Double, n = 31), or saline (S; Single, n = 31) 10 h thereafter. Patients, embryologists, and IVF clinicians remained blinded to the dosing allocation. Study participants: Sixty-two women aged 18-34 years at high risk of OHSS (antral follicle count ≥23 or anti-Mullerian hormone level ≥40 pmol/L). Setting: Single centre study carried out at Hammersmith Hospital IVF unit, London, UK. Primary outcome: Proportion of patients achieving an oocyte yield (percentage of mature oocytes retrieved from follicles ≥14 mm on morning of first kisspeptin-54 trigger administration) of at least 60%. Secondary outcomes: Reproductive hormone levels, implantation rate and OHSS occurrence. A second dose of kisspeptin-54 at 10 h following the first induced further LH-secretion at 4 h after administration. A higher proportion of patients achieved an oocyte yield ≥60% following a second dose of kisspeptin-54 (Single: 14/31, 45%, Double: 21/31, 71%; absolute difference +26%, CI 2-50%, P = 0.042). Patients receiving two doses of kisspeptin-54 had a variable LH

Improvement of dose evaluation system for employees at severe accident in a nuclear power plant. Introduction of the dose rate conversion coefficient and addition of the access route edit function

International Nuclear Information System (INIS)

Sasaki, Yasuhiro; Minami, Noritoshi; Yoshida, Yoshitaka

2006-01-01

Institute of Nuclear Safety System, Inc. had developed the dose evaluation system to evaluate the radiation dose of employees at severe accident in a nuclear power plant. This system has features, which are (1) the dose rate of any evaluation point can be evaluated, (2) the dose rate at any time can be evaluated in consideration of the change in the radioactive source, (3) the dose rate map in the plant can be displayed (4) the dose along the access route when moving can be evaluated, and it is possible to use it for examination of the accident management guideline on the dose side etc.. To upgrade the dose evaluation function of this system, the improvements had been done which were introduction of the dose rate conversion coefficient and addition of the access route edit function. By introducing the dose rate conversion coefficient, the calculation time of the dose rate map in the plant was shortened at about 20 seconds, and a new function to evaluate time-dependent dose rate of any evaluation point was added. By adding the access route edit function, it became possible to re-calculate the dose easily at the route change. (author)

The therapeutic relationship after psychiatric admission.

LENUS (Irish Health Repository)

Roche, Eric

2014-03-01

The therapeutic relationship is one of the most central and important factors in the treatment of mental health disorders. A better therapeutic relationship is associated with service engagement, medication adherence, and satisfaction with services. This study aimed to compare the demographic and clinical factors associated with the therapeutic relationship in voluntarily and involuntarily admitted psychiatric service users. We found that individuals who had been admitted involuntarily, who had a diagnosis of a psychotic disorder, and who reported higher levels of perceived pressures on admission were more likely to have a poorer therapeutic relationship with their consultant psychiatrist. Greater levels of insight and treatment satisfaction, together with higher levels of procedural justice experienced on admission, were associated with a better therapeutic relationship. We found that the level of perceived coercion on admission was not related to the therapeutic relationship. Targeted interventions to improve the therapeutic relationship, particularly for involuntarily admitted service users, are discussed.

Uterine radiation dose from open sources: The potential for underestimation

International Nuclear Information System (INIS)

Cox, P.H.; Klijn, J.G.M.; Pillay, M.; Bontebal, M.; Schoenfeld, D.H.W.

1990-01-01

Recent observations on the biodistribution of a therapeutic dose of sodium iodide I 131 in a patient with an unsuspected early pregnancy lead us to suspect that current dose estimates with respect to uterine exposure (ARSAC 1988) may seriously underestimate the actual exposure of the developing foetus. (orig.)

Dose to the Developing Dentition During Therapeutic Irradiation: Organ at Risk Determination and Clinical Implications

International Nuclear Information System (INIS)

Thompson, Reid F.; Schneider, Ralf A.; Albertini, Francesca; Lomax, Antony J.; Ares, Carmen; Goitein, Gudrun; Hug, Eugen B.

2013-01-01

Purpose: Irradiation of pediatric facial structures can cause severe impairment of permanent teeth later in life. We therefore focused on primary and permanent teeth as organs at risk, investigating the ability to identify individual teeth in children and infants and to correlate dose distributions with subsequent dental toxicity. Methods and Materials: We retrospectively reviewed 14 pediatric patients who received a maximum dose >20 Gy(relative biological effectiveness, RBE) to 1 or more primary or permanent teeth between 2003 and 2009. The patients (aged 1-16 years) received spot-scanning proton therapy with 46 to 66 Gy(RBE) in 23 to 33 daily fractions for a variety of tumors, including rhabdomyosarcoma (n=10), sarcoma (n=2), teratoma (n=1), and carcinoma (n=1). Individual teeth were contoured on axial slices from planning computed tomography (CT) scans. Dose-volume histogram data were retrospectively obtained from total calculated delivered treatments. Dental follow-up information was obtained from external care providers. Results: All primary teeth and permanent incisors, canines, premolars, and first and second molars were identifiable on CT scans in all patients as early as 1 year of age. Dose-volume histogram analysis showed wide dose variability, with a median 37 Gy(RBE) per tooth dose range across all individuals, and a median 50 Gy(RBE) intraindividual dose range across all teeth. Dental follow-up revealed absence of significant toxicity in 7 of 10 patients but severe localized toxicity in teeth receiving >20 Gy(RBE) among 3 patients who were all treated at <4 years of age. Conclusions: CT-based assessment of dose distribution to individual teeth is feasible, although delayed calcification may complicate tooth identification in the youngest patients. Patterns of dental dose exposure vary markedly within and among patients, corresponding to rapid dose falloff with protons. Severe localized dental toxicity was observed in a few patients receiving the

In vitro modeling of skin dose and monitoring of DCA following therapeutic intervention

International Nuclear Information System (INIS)

Balajee, Adayabalam S.; Dainiak, Nicholas

2016-01-01

Human skin is the largest organ of the body accounting for approximately 16% of the total bodyweight. Skin is readily exposed to ionizing radiation during either accidental or intentional exposure such as radiotherapy or other medical procedures because it constitutes the interface between environment and internal organs. Estimation of accurate entrance skin dose and maximum absorbed dose (MAD) is crucial to prevent serious skin injuries. Cutaneous Radiation Syndrome (CRS) is defined by a number of pathological changes manifested in the skin and severity of these changes depend on Liner Energy Transfer (LET), dose, dose-rate, geometry of exposure and volume of body part exposed. In most of the radiological accident scenarios, reconstructive dosimetry in the skin has been performed using physical (thermoluminescence and optical stimulated luminescence), biological (cytogenetics) and computational methods/models to manage radiation exposed victims.Results of the cytogenetic testing performed at the CBL on a few patients will be discussed to illustrate the potential use of DCA and other cytogenetic techniques such as micronuclei and multicolor FISH in monitoring the health of radiotherapy patients

Predicted allowable doses to normal organs for biologically targeted radiotherapy

International Nuclear Information System (INIS)

O'Donoghue, J.A.; Wheldon, T.E.; Western Regional Hospital Board, Glasgow

1988-01-01

The authors have used Dale's extension to the ''linear quadratic'' (LQ) model (Dale, 1985) to evaluate ''equivalent doses'' in cases involving exponentially decaying dose rates. This analysis indicates that the dose-rate effect will be a significant determinant of allowable doses to organs such as liver, kidney and lung. These organ tolerance doses constitute independent constraints on the therapeutic intensity of biologically targeted radiotherapy in exactly the same way as for conventional external beam radiotherapy. In the context of marrow rescue they will in all likelihood constitute the dose-limiting side-effects and thus be especially important. (author)

Milrinone therapeutic drug monitoring in a pediatric population: Development and validation of a quantitative liquid chromatography-tandem mass spectrometry method.

Science.gov (United States)

Raizman, Joshua E; Taylor, Katherine; Parshuram, Christopher; Colantonio, David A

2017-05-01

Milrinone is a potent selective phosphodiesterase type III inhibitor which stimulates myocardial function and improves myocardial relaxation. Although therapeutic monitoring is crucial to maintain therapeutic outcome, little data is available. A proof-of-principle study has been initiated in our institution to evaluate the clinical impact of optimizing milrinone dosing through therapeutic drug monitoring (TDM) in children following cardiac surgery. We developed a robust LC-MS/MS method to quantify milrinone in serum from pediatric patients in real-time. A liquid-liquid extraction procedure was used to prepare samples for analysis prior to measurement by LC-MS/MS. Performance characteristics, such as linearity, limit of quantitation (LOQ) and precision, were assessed. Patient samples were acquired post-surgery and analyzed to determine the concentration-time profile of the drug as well as to track turn-around-times. Within day precision was milrinone levels were either sub-therapeutic or in the toxic range, highlighting the importance for milrinone TDM. This simplified and quick method proved to be analytically robust and able to provide therapeutic monitoring of milrinone in real-time in patients post-cardiac surgery. Copyright © 2017. Published by Elsevier B.V.

Follow-up on thyroidal uptake after radioiodine therapy. How robust is the peri-therapeutic dosimetry?

International Nuclear Information System (INIS)

Eschner, Wolfgang; Kobe, Carsten; Schicha, Harald

2011-01-01

Radioiodine therapy (RIT) for benign thyroid diseases in Germany requires the patient to stay in a nuclear medicine therapy ward for at least 48 hours and the dose to the thyroid to be computed from activity measurements performed during that stay. A major part of the total dose will be delivered after the patient's discharge from the hospital and thus has to be predicted through extrapolation with the effective half-life measured peri-therapeutically. We performed repeated thyroid uptake measurements on patients up to five months post therapy to investigate post-therapeutic changes in their effective half-lives and examine the dosimetric consequences. 12 patients (4 m, 8 f; age 36 - 76 y; 4 Graves' disease, 4 toxic adenoma, 3 toxic goitre, 1 non-toxic goitre) underwent late uptake measurements (1 - 7 meas., 13 - 154 d post administration, median 54 d, performed with thyroid probe resp. whole body counter at lower activities). Doses calculated from late measurements were compared to those predicted at discharge; half-lives calculated from the late measurement closest to the median delay (54 d) were compared to those determined at time of discharge. A cross-calibration between activity calibrator, thyroid probe, and whole body counter over an activity range from 52 MBq down to 45 Bq revealed linearity to within 6%, which was considered sufficient. In 9 out of 12 patients the achieved dose was within the range predicted at discharge. Averaged deviation between achieved and predicted dose was 3.1 ± 2.2% (median 2.5%, range 0.7% - 7.2%). Averaged deviation between post- and peri-therapeutic half-lives was 5.1 ± 3.9% (median 3.5%, range 1.3% - 12.5%). For n=5 patients discharged after 3 days, averaged deviations were greater (dose 4.0%, half-life 5.6%) than for those patients (n = 7) who stayed in the hospital for a minimum of 4 days (dose 2.5%, half-life 4.8%). Excretion of iodine from the thyroid remains practically unchanged for at least two months after RIT. The

Negative Allosteric Modulators of Metabotropic Glutamate Receptors Subtype 5 in Addiction: a Therapeutic Window

Science.gov (United States)

2016-01-01

Background: Abundant evidence at the anatomical, electrophysiological, and molecular levels implicates metabotropic glutamate receptor subtype 5 (mGluR5) in addiction. Consistently, the effects of a wide range of doses of different mGluR5 negative allosteric modulators (NAMs) have been tested in various animal models of addiction. Here, these studies were subjected to a systematic review to find out if mGluR5 NAMs have a therapeutic potential that can be translated to the clinic. Methods: Literature on consumption/self-administration and reinstatement of drug seeking as outcomes of interest published up to April 2015 was retrieved via PubMed. The review focused on the effects of systemic (i.p., i.v., s.c.) administration of the mGluR5 NAMs 3-((2-Methyl-4-thiazolyl)ethynyl)pyridine (MTEP) and 2-Methyl-6-(phenylethynyl)pyridine (MPEP) on paradigms with cocaine, ethanol, nicotine, and food in rats. Results: MTEP and MPEP were found to reduce self-administration of cocaine, ethanol, and nicotine at doses ≥1mg/kg and 2.5mg/kg, respectively. Dose-response relationship resembled a sigmoidal curve, with low doses not reaching statistical significance and high doses reliably inhibiting self-administration of drugs of abuse. Importantly, self-administration of cocaine, ethanol, and nicotine, but not food, was reduced by MTEP and MPEP in the dose range of 1 to 2mg/kg and 2.5 to 3.2mg/kg, respectively. This dose range corresponds to approximately 50% to 80% mGluR5 occupancy. Interestingly, the limited data found in mice and monkeys showed a similar therapeutic window. Conclusion: Altogether, this review suggests a therapeutic window for mGluR5 NAMs that can be translated to the treatment of substance-related and addictive disorders. PMID:26802568

Studies on the dose distribution and treatment technique of high energy electron beams

International Nuclear Information System (INIS)

Lee, D.H.; Chu, S.S.

1978-01-01

Some important properties of high energy electron beams from the linear accelerator, LMR-13, installed in the Yonsei Cancer Center were studied. The results of experimental studies on the problems associated with the 8, 10, and 12 MeV electron beam therapy were as followings; The ionization type dosemeters calibrated by 90 Sr standard source were suitable to the measurements of the outputs and the obsorbed doses in accuracy point of view, and dose measurements using ionization chambers were difficult when measuring doses in small field size and the regions of rapid fall off. The electron energies were measured precisely with an energy spectrometer, and the practical electron energy was calculated within 5% error in the maximum range of the high energy electron beam in water. The correcting factors of perturbated dose distributions owing to radiation field, energy, and materials of the treatment cone were checked and described systematically and thus the variation of dose distributions due to the non-homogeneities of tissues and slopping skin surfaces were completely compensated. The electron beams were adequately diffused using the scatterers, and minimized the bremsstrahlung, irradiation field size, and materials of scatterers. Thus, the therapeutic capacity with the limited electron energy could be extended by improving the dose distributions. (author)

Warfarin Dosing Algorithms Underpredict Dose Requirements in Patients Requiring ≥7 mg Daily: A Systematic Review and Meta-analysis.

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Saffian, S M; Duffull, S B; Wright, Dfb

2017-08-01

There is preliminary evidence to suggest that some published warfarin dosing algorithms produce biased maintenance dose predictions in patients who require higher than average doses. We conducted a meta-analysis of warfarin dosing algorithms to determine if there exists a systematic under- or overprediction of dose requirements for patients requiring ≥7 mg/day across published algorithms. Medline and Embase databases were searched up to September 2015. We quantified the proportion of over- and underpredicted doses in patients whose observed maintenance dose was ≥7 mg/day. The meta-analysis included 47 evaluations of 22 different warfarin dosing algorithms from 16 studies. The meta-analysis included data from 1,492 patients who required warfarin doses of ≥7 mg/day. All 22 algorithms were found to underpredict warfarin dosing requirements in patients who required ≥7 mg/day by an average of 2.3 mg/day with a pooled estimate of underpredicted doses of 92.3% (95% confidence interval 90.3-94.1, I 2 = 24%). © 2017 American Society for Clinical Pharmacology and Therapeutics.

Anuvasan Basti in escalating dose is an alternative for Snehapana before Vamana and Virechana: Trends from a pilot study

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Priyadarshani Arvind Kadus

2014-01-01

Full Text Available Oral administration of medicated fats (oil or ghee is termed as Snehapana. It is an essential step before Vamana (therapeutic emesis and Virechana (therapeutic purgation. Ayurveda physicians often experience a poor compliance in 10-15% patients for oral administration of medicated fats especially in escalating doses. Incomplete Snehapana sometimes creates a problem for a physician to prepare the patient for these processes. These inconveniences made us think about effective alternatives to counter drawbacks and improve acceptance of Snehapana. The present study was planned to assess the efficacy of Anuvasana Basti (oil enema in escalating doses as an alternative for Snehapana. Anuvasana Basti of medicated sesame oil with rock salt was administered in 10 patients for three to seven days till they showed signs and symptoms of complete Snehana. The symptoms of Snehana like semisolid or loose stools, feeling exhausted without much exertion, lightness of body and oiliness of skin were observed. Though the Snehana symptoms varied in intensity, they were similar as they are produced after oral administration of fats. This trend suggests Anuvasana Basti in escalating dose is an alternative for Snehapana before administration of Shodhana therapy like Vamana or Virechana.

Anuvasan Basti in escalating dose is an alternative for Snehapana before Vamana and Virechana: Trends from a pilot study.

Science.gov (United States)

Kadus, Priyadarshani Arvind; Vedpathak, Surendra M

2014-01-01

Oral administration of medicated fats (oil or ghee) is termed as Snehapana. It is an essential step before Vamana (therapeutic emesis) and Virechana (therapeutic purgation). Ayurveda physicians often experience a poor compliance in 10-15% patients for oral administration of medicated fats especially in escalating doses. Incomplete Snehapana sometimes creates a problem for a physician to prepare the patient for these processes. These inconveniences made us think about effective alternatives to counter drawbacks and improve acceptance of Snehapana. The present study was planned to assess the efficacy of Anuvasana Basti (oil enema) in escalating doses as an alternative for Snehapana. Anuvasana Basti of medicated sesame oil with rock salt was administered in 10 patients for three to seven days till they showed signs and symptoms of complete Snehana. The symptoms of Snehana like semisolid or loose stools, feeling exhausted without much exertion, lightness of body and oiliness of skin were observed. Though the Snehana symptoms varied in intensity, they were similar as they are produced after oral administration of fats. This trend suggests Anuvasana Basti in escalating dose is an alternative for Snehapana before administration of Shodhana therapy like Vamana or Virechana.

Radioimmunotherapy for liver micrometastases in mice. Pharmacokinetics, dose estimation, and long-term effect

International Nuclear Information System (INIS)

Saga, Tsuneo; Sakahara, Harumi; Nakamoto, Yuji; Sato, Noriko; Zhao, Songji; Iida, Yasuhiko; Konishi, Junji; Kuroki, Masahide; Endo, Keigo

1999-01-01

The pharmacokinetics of a therapeutic dose of 131 I-labeled antibody and the absorbed dose in liver micrometastases of human colon cancer LS174T in female BALB/c nu/nu mice were investigated, along with the long-term therapeutic effect. Mice with liver micrometastases were given an intravenous injection of 131 I-labeled anti-carcinoembryonic antigen (CEA) antibody F33-104 (8.88 MBq/40 μg). The biodistribution of the antibody was determined 1, 2, 4, 6, and 10 days later. The absorbed dose was estimated for three hypothetical tumor diameters; 1,000, 500, and 300 μm. Autoradiography showed a homogeneous distribution of radioactivity in the micrometastases, and a high uptake was maintained until day 6 (24.0% injected dose (ID)/g on day 1 to 17.8% ID/g on day 6), but decreased thereafter. The absorbed doses in the 1,000-, 500-, and 300-μm tumors were calculated to be 19.1, 12.0, and 8.2 Gy, respectively. The intravenous injection of the 131 I-labeled antibody also showed a dose-dependent therapeutic effect (all mice of the nontreated group died, with a mean survival period of 4 weeks; 3 of the 8 mice that received 9.25 MBq survived up to 120 days with no sign of liver metastasis). These data give further evidence that micrometastasis is a good target of radioimmunotherapy, and that an absorbed dose of less than 20 Gy can effectively control small metastatic lesions. (author)

Potential benefits of therapeutic splenectomy for patients with Hodgkin's disease and non-Hodgkin's lymphomas

International Nuclear Information System (INIS)

Schreiber, D.P.; Jacobs, C.; Rosenberg, S.A.; Cox, R.S.; Hoppe, R.T.

1985-01-01

Thirty-four patients with Hodgkin's disease and non-Hodgkin's lymphoma underwent therapeutic splenectomies to improve hematologic tolerance for chemotherapy. The mean age was 40 years; there were 16 males and 18 females. Fourteen had Hodgkin's disease, 19 had non-Hodgkin's lymphoma, and 1 had malignant histocytosis. Nineteen had palpable splenomegaly, 19 had marrow involvement and 20 had splenic involvement by lymphoma. The following data were analyzed before and after splenectomy: mean white blood cell count (WBC) and platelet count on planned first day of cycle, delay ratio of chemotherapy delivery and percent maximal dose rate. Thirteen patients had non-Hodgkin's lymphoma, splenomegaly and positive bone marrow and showed significant benefit in all of the aforementioned parameters. Of the patients with prior irradiation, only those who completed their radiation greater than six months prior to splenectomy showed benefit. Ten patients had Hodgkin's disease, negative bone marrow and no splenomegaly. This group showed significant improvement in mean platelet count but more limited benefit in delay ratio and percent maximal dose rate. Thus, selected patients with lymphoma who are experiencing delays in chemotherapy because of poor count tolerance may benefit from splenectomy

Measured dose to ovaries and testes from Hodgkin's fields and determination of genetically significant dose

International Nuclear Information System (INIS)

Niroomand-Rad, A.; Cumberlin, R.

1993-01-01

The purpose of this study was to determine the genetically significant dose from therapeutic radiation exposure with Hodgkin's fields by estimating the doses to ovaries and testes. Phantom measurements were performed to verify estimated doses to ovaries and testes from Hodgkin's fields. Thermoluminescent LiF dosimeters (TLD-100) of 1 x 3 x 3 mm 3 dimensions were embedded in phantoms and exposed to standard mantle and paraaortic fields using Co-60, 4 MV, 6 MV, and 10 MV photon beams. The results show that measured doses to ovaries and testes are about two to five times higher than the corresponding graphically estimated doses for Co-60 and 4 MVX photon beams as depicted in ICRP publication 44. In addition, the measured doses to ovaries and testes are about 30% to 65% lower for 10 MV photon beams than for their corresponding Co-60 photon beams. The genetically significant dose from Hodgkin's treatment (less than 0.01 mSv) adds about 4% to the genetically significant dose contribution to medical procedures and adds less than 1% to the genetically significant dose from all sources. Therefore, the consequence to society is considered to be very small. The consequences for the individual patient are, likewise, small. 28 refs., 3 figs., 5 tabs

Focal Radiation Therapy Dose Escalation Improves Overall Survival in Locally Advanced Pancreatic Cancer Patients Receiving Induction Chemotherapy and Consolidative Chemoradiation

Energy Technology Data Exchange (ETDEWEB)

Krishnan, Sunil, E-mail: skrishnan@mdanderson.org [Department of Radiation Oncology, The University of Texas, Houston, Texas (United States); Chadha, Awalpreet S. [Department of Radiation Oncology, The University of Texas, Houston, Texas (United States); Suh, Yelin [Department of Radiation Physics, The University of Texas, Houston, Texas (United States); Chen, Hsiang-Chun [Department of Biostatistics, MD Anderson Cancer Center, Houston, Texas (United States); Rao, Arvind [Department of Bioinformatics and Computational Biology, MD Anderson Cancer Center, Houston, Texas (United States); Das, Prajnan; Minsky, Bruce D.; Mahmood, Usama; Delclos, Marc E. [Department of Radiation Oncology, The University of Texas, Houston, Texas (United States); Sawakuchi, Gabriel O. [Department of Radiation Physics, The University of Texas, Houston, Texas (United States); Graduate School of Biomedical Sciences, The University of Texas, Houston, Texas (United States); Beddar, Sam [Department of Radiation Physics, The University of Texas, Houston, Texas (United States); Katz, Matthew H.; Fleming, Jason B. [Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Javle, Milind M.; Varadhachary, Gauri R.; Wolff, Robert A. [Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Crane, Christopher H. [Department of Radiation Oncology, The University of Texas, Houston, Texas (United States)

2016-03-15

Purpose: To review outcomes of locally advanced pancreatic cancer (LAPC) patients treated with dose-escalated intensity modulated radiation therapy (IMRT) with curative intent. Methods and Materials: A total of 200 patients with LAPC were treated with induction chemotherapy followed by chemoradiation between 2006 and 2014. Of these, 47 (24%) having tumors >1 cm from the luminal organs were selected for dose-escalated IMRT (biologically effective dose [BED] >70 Gy) using a simultaneous integrated boost technique, inspiration breath hold, and computed tomographic image guidance. Fractionation was optimized for coverage of gross tumor and luminal organ sparing. A 2- to 5-mm margin around the gross tumor volume was treated using a simultaneous integrated boost with a microscopic dose. Overall survival (OS), recurrence-free survival (RFS), local-regional and distant RFS, and time to local-regional and distant recurrence, calculated from start of chemoradiation, were the outcomes of interest. Results: Median radiation dose was 50.4 Gy (BED = 59.47 Gy) with a concurrent capecitabine-based (86%) regimen. Patients who received BED >70 Gy had a superior OS (17.8 vs 15.0 months, P=.03), which was preserved throughout the follow-up period, with estimated OS rates at 2 years of 36% versus 19% and at 3 years of 31% versus 9% along with improved local-regional RFS (10.2 vs 6.2 months, P=.05) as compared with those receiving BED ≤70 Gy. Degree of gross tumor volume coverage did not seem to affect outcomes. No additional toxicity was observed in the high-dose group. Higher dose (BED) was the only predictor of improved OS on multivariate analysis. Conclusion: Radiation dose escalation during consolidative chemoradiation therapy after induction chemotherapy for LAPC patients improves OS and local-regional RFS.

3D representation of radioisotopic dose rates within nuclear plants for improved radioprotection and plant safety

International Nuclear Information System (INIS)

Vabo, Rune; Rindahl, Grete; Piotrowski, Leon

2010-01-01

A better awareness of the origin and nature of gamma doses in nuclear environments is demonstrated by visualizing the dose maps created by individual radionucleides that are present in radioactive contaminations. This isotopic representation of doses is much more informative than showing a map of the measured total doses. Two practical examples are given : (a) the placing of protections, and (b) using radiation decay to help plan dismantling operations. The necessary radionucleide information can be easily obtained by the new EDF CZT gamma spectrometer that is now used by all its NPPs. Defining radioactive sources based on such information enables the reconstruction of the radiation situation in a virtual 3-D environment. In such a virtual environment, dose rates can be calculated in any position in space and information about how much each radionucleide contributes can be extracted. Such 3D visualisations increase the awareness and knowledge of the distribution of radiation in a nuclear facility and can be considered as an educational tool for training and improved ALARA procedures. (author)

Therapeutical evaluation of different dose regimens of praziquantel in schistosomiasis mansoni, based on the quantitative oogram technique

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Aloísio Sales da Cunha

1987-10-01

Full Text Available A clinical trial involving 80 patients of both sexes, from ages 15 to 55, with chronic intestinal or hepatointestinal schistosomiasis mansoni, was carried out to evaluate the therapeutical efficacy of different dose regimens of praziquantel. The patients were randomly allocated into four groups with an equal number of cases and were then treated with one of the following dosages: 60 mg/kg for 1 day; 60 mg/kg daily for 2 days; 60 mg/kg daily for 3 days; and 30 mg/kg daily for 6 days. The assessment of parasitological cure was based on the quantitative oogram technique through rectal mucosa biopsies which were undertaken prior to, as well as, 1,2,4 and 6 months post-treatment. Concurrently, stool examinations according to the qualitative Hoffman, Pons & Janer (HPJ and the quantitative Kato-Katz (K-K methods were also performed. The best tolerability was observed with 30 mg/kg daily for 6 days whereas the highest incidence of side-effects (mainly dizziness and nausea was found with 60 mg/kg daily for 3 days. No serious adverse drug reaction has occurred. The achieved cure rates were: 25% with 60 mg/kg for 1 day; 60% with 60 mg/kg daily for 2 days; 89.5% with 60 mg/kg daily for 3 days; and 90% with 30 mg/kg daily for 6 days. At the same time there has been a downfall of 64%, 73%, 87% and 84% respectively, in the median number of viable S. mansoni ova per gram of tissue. Thus, a very clear direct correlation between dose and effect could be seen. The corresponding cure rates according to stool examinations by HPJ were 39%, 80%, 100% and 95%; by K-K 89%, 100%, 100% and 100%. This discrepancy in results amongst the three parasitological methods is certainly due to their unequal accuracy. In fact, when the number of viable eggs per gram of tissue fell below 5,000 the difference in the percentage of false negative findings between HPJ (28% and K-K (80% became significative. When this number dropped to less than 2,000 the percentage of false negative

Hypertonic Saline in Conjunction with High-Dose Furosemide Improves Dose-Response Curves in Worsening Refractory Congestive Heart Failure.

Science.gov (United States)

Paterna, Salvatore; Di Gaudio, Francesca; La Rocca, Vincenzo; Balistreri, Fabio; Greco, Massimiliano; Torres, Daniele; Lupo, Umberto; Rizzo, Giuseppina; di Pasquale, Pietro; Indelicato, Sergio; Cuttitta, Francesco; Butler, Javed; Parrinello, Gaspare

2015-10-01

14% for urine output; 29, 24, and 16% for total sodium excretion; 45, 34, and 20% for urinary osmolarity; and 27, 36, and 32% for total furosemide excretion in groups 1, 2, and 3, respectively. These findings were translated in an improvement in the furosemide dose-response curves in these patients. These results may serve as new pathophysiological basis for HSS use in the treatment of refractory CHF.

Preemptive warfarin dose reduction after initiation of sulfamethoxazole-trimethoprim or metronidazole.

Science.gov (United States)

Powers, Anna; Loesch, Erin B; Weiland, Anthony; Fioravanti, Nicole; Lucius, David

2017-07-01

To evaluate the utility of a preemptive warfarin dose reduction at the time of initiation of either sulfamethoxazole-trimethoprim or metronidazole, a retrospective chart review of patients who received an outpatient prescription for warfarin and either sulfamethoxazole-trimethoprim and/or metronidazole from July 1, 2011 to July 1, 2015 was conducted. Clinical outcomes compared Veterans who had a warfarin dose reduction and those who did not within 120 h (5 days) of antibiotic initiation. The primary outcome compared the pre-and post-antibiotic International Normalized Ratio (INR) of patients in the intervention group (warfarin dose reduction) with those in the control group (no intervention). Secondary outcomes assessed incidence of thromboembolic and major bleeding events within 30 days of antibiotic completion. Fifty patients were assessed. Forty-nine patients had at least one follow-up appointment; 126 follow-up visits were evaluated. There was a statistically significant difference for the change in therapeutic INR at the first follow-up appointment (p = 0.029) for those patients in the control group. On average, the patients in the intervention group required fewer follow-up visits (p = 0.019). There were no statistically significant differences for the overall rate of therapeutic INR values between groups, as well as no instances of a thromboembolic or major bleeding events during the follow-up period. Clinically significant differences were observed for patients who received a preemptive warfarin dose reduction upon initiation of sulfamethoxazole-trimethoprim or metronidazole. Patients in the intervention group required fewer follow-up appointments and were more likely maintain a therapeutic INR within the 30 days following the antibiotic course. Results of this study will be presented the at Pharmacy and Therapeutics committee in an effort to seek approval for policy development to initiate a local preemptive warfarin dose adjustment as a standard

Therapeutical aspect of trichomoniasis

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Vukićević Jelica

2003-01-01

Full Text Available Trichomoniasis is frequent, parasitic and sexually transmitted infection of genitourinary tract. It is treated by metronidazole (5-nitroimidazole according to protocol recommended by Center for Disease Control (CDC formerly called: Communicable Disease Center [19]. The resistance of Trichomonas vaginalis (TV strains to metronidazole (MND was described in USA in 1960, and later on in many European countries [8, 9, 10, 11, 12, 13]. In these cases, due to persistent trichomonas infection, it is necessary to repeat MND treatment with moderate modification of dose and/or length of its application. Nevertheless, oncogenic and toxic effects of MND have to be taken into consideration. OBJECT The aim of this study was to investigate and analyze the incidence of TV in STD and lower susceptibility of certain TV strains to MND were analyzed. MATERIAL AND METHODS In three-year period (1999-2001 612 patients (244 females and 368 males suspected of STD were examined clinically and microbiologically at the Institute of Dermatovenereology in Belgrade. The patients detected for TV were treated according to CDC protocol. The affected were considered cured if there was no manifest clinical infection, and no TV verified by microbiological test. Results TV was isolated in 216 patients (35.29 % of all subjects. Trichomonas infection was found in 90 (36.88 % out of 244 tested females and in 126 (32.34 % of 368 males. Clinically manifested infection, with extensive urethral and vaginal secretion, was recorded in 161 patients, while the asymptomatic form was found in 55 subjects. This result indicates the predominance of manifested trichomonas infections (75.54 % of cases. The difference of distribution of clinical forms of trichomoniasis, in relation to sex, was not statistically significant (c2=0.854; p>0.05. The patients with verified trichomonas infection were treated by metronidazole according to CDC protocol. The recommended therapeutical scheme consisted of three

Practical considerations in the development of hemoglobin-based oxygen therapeutics.

Science.gov (United States)

Kim, Hae Won; Estep, Timothy N

2012-09-01

The development of hemoglobin based oxygen therapeutics (HBOCs) requires consideration of a number of factors. While the enabling technology derives from fundamental research on protein biochemistry and biological interactions, translation of these research insights into usable medical therapeutics demands the application of considerable technical expertise and consideration and reconciliation of a myriad of manufacturing, medical, and regulatory requirements. The HBOC development challenge is further exacerbated by the extremely high intravenous doses required for many of the indications contemplated for these products, which in turn implies an extremely high level of purity is required. This communication discusses several of the important product configuration and developmental considerations that impact the translation of fundamental research discoveries on HBOCs into usable medical therapeutics.

Dose- and time-dependence of the host-mediated response to paclitaxel therapy: a mathematical modeling approach.

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Benguigui, Madeleine; Alishekevitz, Dror; Timaner, Michael; Shechter, Dvir; Raviv, Ziv; Benzekry, Sebastien; Shaked, Yuval

2018-01-05

It has recently been suggested that pro-tumorigenic host-mediated processes induced in response to chemotherapy counteract the anti-tumor activity of therapy, and thereby decrease net therapeutic outcome. Here we use experimental data to formulate a mathematical model describing the host response to different doses of paclitaxel (PTX) chemotherapy as well as the duration of the response. Three previously described host-mediated effects are used as readouts for the host response to therapy. These include the levels of circulating endothelial progenitor cells in peripheral blood and the effect of plasma derived from PTX-treated mice on migratory and invasive properties of tumor cells in vitro . A first set of mathematical models, based on basic principles of pharmacokinetics/pharmacodynamics, did not appropriately describe the dose-dependence and duration of the host response regarding the effects on invasion. We therefore provide an alternative mathematical model with a dose-dependent threshold, instead of a concentration-dependent one, that describes better the data. This model is integrated into a global model defining all three host-mediated effects. It not only precisely describes the data, but also correctly predicts host-mediated effects at different doses as well as the duration of the host response. This mathematical model may serve as a tool to predict the host response to chemotherapy in cancer patients, and therefore may be used to design chemotherapy regimens with improved therapeutic outcome by minimizing host mediated effects.

Disrupting the Scaffold to Improve Focal Adhesion Kinase–Targeted Cancer Therapeutics

Science.gov (United States)

Cance, William G.; Kurenova, Elena; Marlowe, Timothy; Golubovskaya, Vita

2013-01-01

Focal adhesion kinase (FAK) is emerging as a promising cancer target because it is highly expressed at both the transcriptional and translational level in cancer and is involved in many aspects of tumor growth, invasion, and metastasis. Existing FAK-based therapeutics focus on inhibiting the kinase's catalytic function and not the large scaffold it creates that includes many oncogenic receptor tyrosine kinases and tumor suppressor proteins. Targeting the FAK scaffold is a feasible and promising approach for developing highly specific therapeutics that disrupt FAK signaling pathways in cancer. PMID:23532331

Disrupting the scaffold to improve focal adhesion kinase-targeted cancer therapeutics.

Science.gov (United States)

Cance, William G; Kurenova, Elena; Marlowe, Timothy; Golubovskaya, Vita

2013-03-26

Focal adhesion kinase (FAK) is emerging as a promising cancer target because it is highly expressed at both the transcriptional and translational level in cancer and is involved in many aspects of tumor growth, invasion, and metastasis. Existing FAK-based therapeutics focus on inhibiting the kinase's catalytic function and not the large scaffold it creates that includes many oncogenic receptor tyrosine kinases and tumor suppressor proteins. Targeting the FAK scaffold is a feasible and promising approach for developing highly specific therapeutics that disrupt FAK signaling pathways in cancer.

Concept for quantifying the dose from image guided radiotherapy

International Nuclear Information System (INIS)

Schneider, Uwe; Hälg, Roger; Besserer, Jürgen

2015-01-01

Radiographic image guidance is routinely used for patient positioning in radiotherapy. All radiographic guidance techniques can give a significant radiation dose to the patient. The dose from diagnostic imaging is usually managed by using effective dose minimization. In contrast, image-guided radiotherapy adds the imaging dose to an already high level of therapeutic radiation which cannot be easily managed using effective dose. The purpose of this work is the development of a concept of IGRT dose quantification which allows a comparison of imaging dose with commonly accepted variations of therapeutic dose. It is assumed that dose variations of the treatment beam which are accepted in the spirit of the ALARA convention can also be applied to the additional imaging dose. Therefore we propose three dose categories: Category I: The imaging dose is lower than a 2 % variation of the therapy dose. Category II: The imaging dose is larger than in category I, but lower than the therapy dose variations between different treatment techniques. Category III: The imaging dose is larger than in Category II. For various treatment techniques dose measurements are used to define the dose categories. The imaging devices were categorized according to the measured dose. Planar kV-kV imaging is a category I imaging procedure. kV-MV imaging is located at the edge between category I and II and is for increasing fraction size safely a category I imaging technique. MV-MV imaging is for all imaging technologies a category II procedure. MV fan beam CT for localization is a category I technology. Low dose protocols for kV CBCT are located between category I and II and are for increasing fraction size a category I imaging technique. All other investigated Pelvis-CBCT protocols are category II procedures. Fan beam CT scout views are category I technology. Live imaging modalities are category III for conventional fractionation, but category II for stereotactic treatments. Dose from radiotherapy

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

International Nuclear Information System (INIS)

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

2007-01-01

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

Therapeutic termination of second trimester pregnancies with low dose misoprostol

International Nuclear Information System (INIS)

Liaquat, N.F.; Javed, I.; Shuja, S.; Shoaib, T.; Bano, K.; Waheed, S.; Ansar, A.

2006-01-01

To determine the effectiveness of 50 micro g misoprostol for midtrimester termination of pregnancies. The study subjects were 54 pregnant women admitted during the 2nd trimester (14-26 weeks) of gestation, willing or requiring termination of pregnancy. Those patients were included in the study who were admitted with closed cervical os, either had intrauterine death, fetal anomaly, medical disorder (hypertension or diabetes) or history of previous ceasrean section. Cases of placenta previa, acute asthma, glaucoma, cardiac diseases and allergy to prostaglandins were excluded. Each patient received 50 micro g misoprostol intravaginally. Maximum 4 doses were given at 4 hours interval and state of cervical os was assessed by vaginal examination before insertion of next dose or at the onset of uterine contractions. After 4 doses of misoprostol, patients were kept under observation and watched for uterine contractions to start or for expulsion of products. Syntocinon infusion was started to augment labour where products of conception failed to expel out inspite of open os. Outcome measures include success rate of termination within 12, 24, 36 and 48 hours, mean induction - abortion time interval and maternal side effects. Results: The success rate of termination within 12, 24, 36 and 48 hours were 27.7%, 83.3%, 94.4% and 96.3% respectively. Mean induction to abortion time interval, in case of abortion within 48 hours, was found to be 18.9 +- 11.58 (range 4-48 hours). Dead fetuses were aborted earlier than alive fetuses. The mean induction abortion time interval was 17.01+-8.7 hours in dead and 23.4 +- 15.9 hours in alive fetuses (t -value:1.9, p: 0.05). Two patients failed to deliver within 48 hours of induction. Two patients suffered from febrile illness. Vaginal administration of 50 micro g misoprostol every 4 hourly is an effective and safe agent for ripening of cervix and convenient way of inducing abortion during 2nd trimester of pregnancy in a women either with

Imaging enabled platforms for development of therapeutics

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Celli, Jonathan; Rizvi, Imran; Blanden, Adam R.; Evans, Conor L.; Abu-Yousif, Adnan O.; Spring, Bryan Q.; Muzikansky, Alona; Pogue, Brian W.; Finkelstein, Dianne M.; Hasan, Tayyaba

2011-03-01

Advances in imaging and spectroscopic technologies have enabled the optimization of many therapeutic modalities in cancer and noncancer pathologies either by earlier disease detection or by allowing therapy monitoring. Amongst the therapeutic options benefiting from developments in imaging technologies, photodynamic therapy (PDT) is exceptional. PDT is a photochemistry-based therapeutic approach where a light-sensitive molecule (photosensitizer) is activated with light of appropriate energy (wavelength) to produce reactive molecular species such as free radicals and singlet oxygen. These molecular entities then react with biological targets such as DNA, membranes and other cellular components to impair their function and lead to eventual cell and tissue death. Development of PDT-based imaging also provides a platform for rapid screening of new therapeutics in novel in vitro models prior to expensive and labor-intensive animal studies. In this study we demonstrate how an imaging platform can be used for strategizing a novel combination treatment strategy for multifocal ovarian cancer. Using an in vitro 3D model for micrometastatic ovarian cancer in conjunction with quantitative imaging we examine dose and scheduling strategies for PDT in combination with carboplatin, a chemotherapeutic agent presently in clinical use for management of this deadly form of cancer.

Patient dose in image guided radiotherapy: Monte Carlo study of the CBCT dose contribution

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Salvatore Leotta

2018-02-01

Full Text Available Image Guided RadioTherapy (IGRT is a technique whose diffusion is growing thanks to the well-recognized gain in accuracy of dose delivery. However, multiple Cone Beam Computed Tomography (CBCT scans add dose to patients, and its contribution has to be assessed and minimized. Aim of our work was to evaluate, through Monte Carlo simulations, organ doses in IGRT due to CBCT and therapeutic MV irradiation in head-neck, thorax and pelvis districts. We developed a Monte Carlo simulation in GAMOS (Geant4-based Architecture for Medicine-Oriented Simulations, reproducing an Elekta Synergy medical linac operating at 6 and 10 MV photon energy, and we set up a scalable anthropomorphic model. After a validation by comparison with the experimental quality indexes, we evaluated the average doses to all organs and tissues belonging to the model for the three cases of irradiated district. Scattered radiation in therapy is larger than that diffused by CBCT by one to two orders of magnitude.

Improvement of the following accident dose assessment system

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Kim, Enn Han; Han, Moon Hee; Suh, Kyung Suk; Hwang, Won Tae; Choi, Young Gil [Korea Advanced Institute of Science and Technology, Taejon (Korea, Republic of)

1999-12-15

The FADAS has been updates for calculating the real-time wind fields continuously at the nuclear sites in Korea. The system has been constructed to compute the wind fields using its own process for the dummy meteorological data, and dose not effect on the overall wind field module. If the radioactive materials are released into the atmosphere in real situation, the calculations of wind fields and exposure dose in the previous FADAS are performed in the case of the recognition of the above situation in the source term evaluation module. The current version of FADAS includes the program for evaluating the effect of the predicted accident and the assumed scenario together. The dose assessment module is separated into the real-time and the supposed accident respectively.

Sleep disturbance as detected by actigraphy in pre-pubertal juvenile monkeys receiving therapeutic doses of fluoxetine.

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Golub, Mari S; Hogrefe, Casey E

2016-01-01

Sleep disturbance is a reported side effect of antidepressant drugs in children. Using a nonhuman primate model of childhood selective serotonin reuptake inhibitor (SSRI) therapy, sleep was studied quantitatively with actigraphy. Two 48-h sessions were recorded in the home cage environment of juvenile male rhesus monkeys at two and three years of age, after one and two years of treatment with a therapeutic dose of the SSRI fluoxetine, and compared to vehicle treated controls. A third session was conducted one year after discontinuation of treatment at four years of age. During treatment, the fluoxetine group demonstrated sleep fragmentation as indexed by a greater number of rest-activity transitions compared to controls. In addition fluoxetine led to more inactivity during the day as indexed by longer duration of rest periods and the reduced activity during these periods. The fluoxetine effect on sleep fragmentation, but not on daytime rest, was modified by the monkey's genotype for polymorphisms of monoamine oxidase A (MAOA), an enzyme that metabolizes serotonin. After treatment, the fluoxetine effect on nighttime rest-activity transitions persisted, but daytime activity was not affected. The demonstration in this nonhuman primate model of sleep disturbance in connection with fluoxetine treatment and specific genetic polymorphisms, and in the absence of diagnosed psychopathology, can help inform use of this drug in children. Copyright © 2016 Elsevier Inc. All rights reserved.

Tomotherapy – a different way of dose delivery in radiotherapy

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Skórska, Małgorzata; Jodda, Agata; Ryczkowski, Adam; Kaźmierska, Joanna; Adamska, Krystyna; Karczewska-Dzionk, Aldona; Żmijewska-Tomczak, Małgorzata; Włodarczyk, Hanna

2012-01-01

Aim of the study Helical tomotherapy is one of the methods of radiotherapy. This method enables treatment implementation for a wide spectrum of clinical cases. The vast array of therapeutic uses of helical tomotherapy results directly from the method of dose delivery, which is significantly different from the classic method developed for conventional linear accelerators. The paper discusses the method of dose delivery by a tomotherapy machine. Moreover, an analysis and presentation of treatment plans was performed in order to show the therapeutic possibilities of the applied technology. Dose distributions were obtained for anaplastic medulloblastoma, multifocal metastases to brain, vulva cancer, tongue cancer, metastases to bones, and advanced skin cancer. Tomotherapy treatment plans were compared with conventional linear accelerator plans. Results Following the comparative analysis of tomotherapy and conventional linear accelerator plans, in each case we obtained the increase in dose distribution conformity manifested in greater homogeneity of doses in the radiation target area for anaplastic medulloblastoma, multifocal metastases to brain, vulva cancer, metastases to bones, and advanced skin cancer, and the reduction of doses in organs at risk (OAR) for anaplastic medulloblastoma, vulva cancer, tongue cancer, and advanced skin cancer. The time of treatment delivery in the case of a tomotherapy machine is comparable to the implementation of the plan prepared in intensity-modulated radiotherapy (IMRT) technique for a conventional linear accelerator. In the case of tomotherapy the application of a fractional dose was carried out in each case during one working period of the machine. For a conventional linear accelerator the total value of the fractional dose in the case of anaplastic medulloblastoma and metastases to bones was delivered using several treatment plans, for which a change of set-up was necessary during a fraction. Conclusion The obtained results

Right dose, right now: using big data to optimize antibiotic dosing in the critically ill.

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Elbers, Paul W G; Girbes, Armand; Malbrain, Manu L N G; Bosman, Rob

2015-01-01

Antibiotics save lives and are essential for the practice of intensive care medicine. Adequate antibiotic treatment is closely related to outcome. However this is challenging in the critically ill, as their pharmacokinetic profile is markedly altered. Therefore, it is surprising that critical care physicians continue to rely on standard dosing regimens for every patient, regardless of the actual clinical situation. This review outlines the pharmacokinetic and pharmacodynamic principles that underlie the need for individualized and personalized drug dosing. At present, therapeutic drug monitoring may be of help, but has major disadvantages, remains unavailable for most antibiotics and has produced mixed results. We therefore propose the AutoKinetics concept, taking decision support for antibiotic dosing back to the bedside. By direct interaction with electronic patient records, this opens the way for the use of big data for providing the right dose at the right time in each patient.