[A novel serial port auto trigger system for MOSFET dose acquisition].

PubMed

Luo, Guangwen; Qi, Zhenyu

2013-01-01

To synchronize the radiation of microSelectron-HDR (Nucletron afterloading machine) and measurement of MOSFET dose system, a trigger system based on interface circuit was designed and corresponding monitor and trigger program were developed on Qt platform. This interface and control system was tested and showed stable operate and reliable work. This adopted serial port detect technique may expand to trigger application of other medical devices.

10 CFR 35.643 - Periodic spot-checks for remote afterloader units.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 1 2010-01-01 2010-01-01 false Periodic spot-checks for remote afterloader units. 35.643... spot-checks for remote afterloader units. (a) A licensee authorized to use a remote afterloader unit for medical use shall perform spot-checks of each remote afterloader facility and on each unit— (1...

DOE Office of Scientific and Technical Information (OSTI.GOV)

Einck, John P., E-mail: jeinck@ucsd.edu; Hudson, Alana; Shulman, Adam C.

West Africa has one of the highest incidence rates of carcinoma of the cervix in the world. The vast majority of women do not have access to screening or disease treatment, leading to presentation at advanced stages and to high mortality rates. Compounding this problem is the lack of radiation treatment facilities in Senegal and many other parts of the African continent. Senegal, a country of 13 million people, had a single {sup 60}Co teletherapy unit before our involvement and no brachytherapy capabilities. Radiating Hope, a nonprofit organization whose mission is to provide radiation therapy equipment to countries in themore » developing world, provided a high-dose-rate afterloading unit to the cancer center for curative cervical cancer treatment. Here we describe the implementation of high-dose-rate brachytherapy in Senegal requiring a nonstandard fractionation schedule and a novel treatment planning approach as a possible blueprint to providing this technology to other developing countries.« less

Characterization of a fiber-coupled Al2O3:C luminescence dosimetry system for online in vivo dose verification during 192Ir brachytherapy.

PubMed

Andersen, Claus E; Nielsen, Søren Kynde; Greilich, Steffen; Helt-Hansen, Jakob; Lindegaard, Jacob Christian; Tanderup, Kari

2009-03-01

A prototype of a new dose-verification system has been developed to facilitate prevention and identification of dose delivery errors in remotely afterloaded brachytherapy. The system allows for automatic online in vivo dosimetry directly in the tumor region using small passive detector probes that fit into applicators such as standard needles or catheters. The system measures the absorbed dose rate (0.1 s time resolution) and total absorbed dose on the basis of radioluminescence (RL) and optically stimulated luminescence (OSL) from aluminum oxide crystals attached to optical fiber cables (1 mm outer diameter). The system was tested in the range from 0 to 4 Gy using a solid-water phantom, a Varian GammaMed Plus 192Ir PDR afterloader, and dosimetry probes inserted into stainless-steel brachytherapy needles. The calibrated system was found to be linear in the tested dose range. The reproducibility (one standard deviation) for RL and OSL measurements was 1.3%. The measured depth-dose profiles agreed well with the theoretical expectations computed with the EGSNRC Monte Carlo code, suggesting that the energy dependence for the dosimeter probes (relative to water) is less than 6% for source-to-probe distances in the range of 2-50 mm. Under certain conditions, the RL signal could be greatly disturbed by the so-called stem signal (i.e., unwanted light generated in the fiber cable upon irradiation). The OSL signal is not subject to this source of error. The tested system appears to be adequate for in vivo brachytherapy dosimetry.

Comparison of the efficiency of rat papillary muscles during afterloaded isotonic contractions and contractions with sinusoidal length changes.

PubMed

Mellors, L J; Gibbs, C L; Barclay, C J

2001-05-01

The results of previous studies suggest that the maximum mechanical efficiency of rat papillary muscles is lower during a contraction protocol involving sinusoidal length changes than during one involving afterloaded isotonic contractions. The aim of this study was to compare directly the efficiency of isolated rat papillary muscle preparations in isotonic and sinusoidal contraction protocols. Experiments were performed in vitro (27 degrees C) using left ventricular papillary muscles from adult rats. Each preparation performed three contraction protocols: (i) low-frequency afterloaded isotonic contractions (10 twitches at 0.2 Hz), (ii) sinusoidal length change contractions with phasic stimulation (40 twitches at 2 Hz) and (iii) high-frequency afterloaded isotonic contractions (40 twitches at 2 Hz). The first two protocols resembled those used in previous studies and the third combined the characteristics of the first two. The parameters for each protocol were adjusted to those that gave maximum efficiency. For the afterloaded isotonic protocols, the afterload was set to 0.3 of the maximum developed force. The sinusoidal length change protocol incorporated a cycle amplitude of +/-5% resting length and a stimulus phase of -10 degrees. Measurements of force output, muscle length change and muscle temperature change were used to calculate the work and heat produced during and after each protocol. Net mechanical efficiency was defined as the proportion of the energy (enthalpy) liberated by the muscle that appeared as work. The efficiency in the low-frequency, isotonic contraction protocol was 21.1+/-1.4% (mean +/- s.e.m., N=6) and that in the sinusoidal protocol was 13.2+/-0.7%, consistent with previous results. This difference was not due to the higher frequency or greater number of twitches because efficiency in the high-frequency, isotonic protocol was 21.5+/-1.0%. Although these results apparently confirm that efficiency is protocol-dependent, additional experiments designed to measure work output unambiguously indicated that the method used to calculate work output in isotonic contractions overestimated actual work output. When net work output, which excludes work done by parallel elastic elements, rather than total work output was used to determine efficiency in afterloaded isotonic contractions, efficiency was similar to that for sinusoidal contractions. The maximum net mechanical efficiency of rat papillary muscles performing afterloaded isotonic or sinusoidal length change contractions was between 10 and 15%.

10 CFR 35.2647 - Records of additional technical requirements for mobile remote afterloader units.

Code of Federal Regulations, 2010 CFR

2010-01-01

... remote afterloader units. 35.2647 Section 35.2647 Energy NUCLEAR REGULATORY COMMISSION MEDICAL USE OF BYPRODUCT MATERIAL Records § 35.2647 Records of additional technical requirements for mobile remote afterloader units. (a) A licensee shall retain a record of each check for mobile remote afterloader units...

10 CFR 35.2647 - Records of additional technical requirements for mobile remote afterloader units.

Code of Federal Regulations, 2013 CFR

2013-01-01

... remote afterloader units. 35.2647 Section 35.2647 Energy NUCLEAR REGULATORY COMMISSION MEDICAL USE OF BYPRODUCT MATERIAL Records § 35.2647 Records of additional technical requirements for mobile remote afterloader units. (a) A licensee shall retain a record of each check for mobile remote afterloader units...

10 CFR 35.2647 - Records of additional technical requirements for mobile remote afterloader units.

Code of Federal Regulations, 2011 CFR

2011-01-01

... remote afterloader units. 35.2647 Section 35.2647 Energy NUCLEAR REGULATORY COMMISSION MEDICAL USE OF BYPRODUCT MATERIAL Records § 35.2647 Records of additional technical requirements for mobile remote afterloader units. (a) A licensee shall retain a record of each check for mobile remote afterloader units...

10 CFR 35.2647 - Records of additional technical requirements for mobile remote afterloader units.

Code of Federal Regulations, 2014 CFR

2014-01-01

... remote afterloader units. 35.2647 Section 35.2647 Energy NUCLEAR REGULATORY COMMISSION MEDICAL USE OF BYPRODUCT MATERIAL Records § 35.2647 Records of additional technical requirements for mobile remote afterloader units. (a) A licensee shall retain a record of each check for mobile remote afterloader units...

10 CFR 35.2647 - Records of additional technical requirements for mobile remote afterloader units.

Code of Federal Regulations, 2012 CFR

2012-01-01

... remote afterloader units. 35.2647 Section 35.2647 Energy NUCLEAR REGULATORY COMMISSION MEDICAL USE OF BYPRODUCT MATERIAL Records § 35.2647 Records of additional technical requirements for mobile remote afterloader units. (a) A licensee shall retain a record of each check for mobile remote afterloader units...

SU-E-T-457: Design and Characterization of An Economical 192Ir Hemi-Brain Small Animal Irradiator

DOE Office of Scientific and Technical Information (OSTI.GOV)

Grams, M; Wilson, Z; Sio, T

Purpose: To describe the design and dosimetric characterization of a simple and economical small animal irradiator. Methods: A high dose rate 192Ir brachytherapy source from a commercially available afterloader was used with a 1.3 centimeter thick tungsten collimator to provide sharp beam penumbra suitable for hemi-brain irradiation of mice. The unit is equipped with continuous gas anesthesia to allow robust animal immobilization. Dosimetric characterization of the device was performed with Gafchromic film. The penumbra from the small animal irradiator was compared under similar collimating conditions to the penumbra from 6 MV photons, 6 MeV electrons, and 20 MeV electrons frommore » a linear accelerator as well as 300 kVp photons from an orthovoltage unit and Monte Carlo simulated 90 MeV protons. Results: The tungsten collimator provides a sharp penumbra suitable for hemi-brain irradiation, and dose rates on the order of 200 cGy/minute were achieved. The sharpness of the penumbra attainable with this device compares favorably to those measured experimentally for 6 MV photons, and 6 and 20 MeV electron beams from a linear accelerator. Additionally, the penumbra was comparable to those measured for a 300 kVp orthovoltage beam and a Monte Carlo simulated 90 MeV proton beam. Conclusions: The small animal irradiator described here can be built for under $1,000 and used in conjunction with any commercial brachytherapy afterloader to provide a convenient and cost-effective option for small animal irradiation experiments. The unit offers high dose rate delivery and sharp penumbra, which is ideal for hemi-brain irradiation of mice. With slight modifications to the design, irradiation of sites other than the brain could be accomplished easily. Due to its simplicity and low cost, the apparatus described is an attractive alternative for small animal irradiation experiments requiring a sharp penumbra.« less

10 CFR 35.2643 - Records of periodic spot-checks for remote afterloader units.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 1 2010-01-01 2010-01-01 false Records of periodic spot-checks for remote afterloader... Records § 35.2643 Records of periodic spot-checks for remote afterloader units. (a) A licensee shall retain a record of each spot-check for remote afterloader units required by § 35.643 for 3 years. (b) The...

10 CFR 35.2643 - Records of periodic spot-checks for remote afterloader units.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 1 2012-01-01 2012-01-01 false Records of periodic spot-checks for remote afterloader... Records § 35.2643 Records of periodic spot-checks for remote afterloader units. (a) A licensee shall retain a record of each spot-check for remote afterloader units required by § 35.643 for 3 years. (b) The...

10 CFR 35.2643 - Records of periodic spot-checks for remote afterloader units.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 1 2014-01-01 2014-01-01 false Records of periodic spot-checks for remote afterloader... Records § 35.2643 Records of periodic spot-checks for remote afterloader units. (a) A licensee shall retain a record of each spot-check for remote afterloader units required by § 35.643 for 3 years. (b) The...

10 CFR 35.2643 - Records of periodic spot-checks for remote afterloader units.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 1 2013-01-01 2013-01-01 false Records of periodic spot-checks for remote afterloader... Records § 35.2643 Records of periodic spot-checks for remote afterloader units. (a) A licensee shall retain a record of each spot-check for remote afterloader units required by § 35.643 for 3 years. (b) The...

10 CFR 35.2643 - Records of periodic spot-checks for remote afterloader units.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 1 2011-01-01 2011-01-01 false Records of periodic spot-checks for remote afterloader... Records § 35.2643 Records of periodic spot-checks for remote afterloader units. (a) A licensee shall retain a record of each spot-check for remote afterloader units required by § 35.643 for 3 years. (b) The...

WE-DE-201-08: Multi-Source Rotating Shield Brachytherapy Apparatus for Prostate Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dadkhah, H; Wu, X; Kim, Y

Purpose: To introduce a novel multi-source rotating shield brachytherapy (RSBT) apparatus for the precise simultaneous angular and linear positioning of all partially-shielded 153Gd radiation sources in interstitial needles for treating prostate cancer. The mechanism is designed to lower the detrimental dose to healthy tissues, the urethra in particular, relative to conventional high-dose-rate brachytherapy (HDR-BT) techniques. Methods: Following needle implantation, the delivery system is docked to the patient template. Each needle is coupled to a multi-source afterloader catheter by a connector passing through a shaft. The shafts are rotated by translating a moving template between two stationary templates. Shaft walls asmore » well as moving template holes are threaded such that the resistive friction produced between the two parts exerts enough force on the shafts to bring about the rotation. Rotation of the shaft is then transmitted to the shielded source via several keys. Thus, shaft angular position is fully correlated with the position of the moving template. The catheter angles are simultaneously incremented throughout treatment as needed, and only a single 360° rotation of all catheters is needed for a full treatment. For each rotation angle, source depth in each needle is controlled by a multi-source afterloader, which is proposed as an array of belt-driven linear actuators, each of which drives a source wire. Results: Optimized treatment plans based on Monte Carlo dose calculations demonstrated RSBT with the proposed apparatus reduced urethral D{sub 1cc} below that of conventional HDR-BT by 35% for urethral dose gradient volume within 3 mm of the urethra surface. Treatment time to deliver 20 Gy with multi-source RSBT apparatus using nineteen 62.4 GBq {sup 153}Gd sources is 117 min. Conclusions: The proposed RSBT delivery apparatus in conjunction with multiple nitinol catheter-mounted platinum-shielded {sup 153}Gd sources enables a mechanically feasible urethra-sparing treatment technique for prostate cancer in a clinically reasonable timeframe.« less

Vasodilators in Acute Heart Failure: Review of the Latest Studies.

PubMed

Levy, Phillip D; Laribi, Said; Mebazaa, Alexandre

2014-06-01

Vasodilators play an important role in the management of acute heart failure, particularly when increased afterload is the precipitating cause of decompensation. The time-honored approach to afterload reduction has been largely focused on use of intravenous nitrovasodilators and, when properly dosed, this class of agents does provide substantial symptom relief for patients with acute hypertensive heart failure. Despite this, nitrovasodilators have never been shown to diminish mortality or provide any post-discharge outcome benefit leading to an on-going search for viable and more effective alternatives. While no new vasodilators have been approved for use in acute heart failure since nesiritide more than a decade ago, a number of novel agents have been developed, with some showing significant promise in recent clinical trials. In this review, we summarize the latest study data as it relates to vasodilator therapy and provide a glimpse into the not too distant future state of acute heart failure care.

Radiation bronchitis and stenosis secondary to high dose rate endobronchial irradiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Speiser, B.L.; Spratling, L.

The purpose of the study was to describe a new clinical entity observed in follow-up bronchoscopies in patients who were treated with high dose rate and medium dose rate remote afterloading brachytherapy of the tracheobronchial tree. Patients were treated by protocol with medium dose rate, 47 patients receiving 1000 cGy at a 5 mm depth times three fractions, high dose rate 144 patients receiving 1000 cGy at a 10 mm depth for three fractions and high dose rate 151 patients receiving cGy at a 10 mm depth for three fractions followed by bronchoscopy. Incidence of this entity was 9% formore » the first group, 12% for the second, and 13% for the third group. Reactions were grade 1 consisting of mild inflammatory response with a partial whitish circumferential membrane in an asymptomatic patient; grade 2, thicker complete white circumferential membrane with cough and/or obstructive problems requiring intervention; grade 3, severe inflammatory response with marked membranous exudate and mild fibrotic reaction; and grade 4 a predominant fibrotic reaction with progressive stenosis. Variables associated with a slightly increased incidence of radiation bronchitis and stenosis included: large cell carcinoma histology, curative intent, prior laser photoresection, and/or concurrent external radiation. Survival was the strongest predictor of the reaction. Radiation bronchitis and stenosis is a new clinical entity that must be identified in bronchial brachytherapy patients and treated appropriately. 23 refs., 3 figs., 7 tabs.« less

10 CFR 35.647 - Additional technical requirements for mobile remote afterloader units.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 1 2013-01-01 2013-01-01 false Additional technical requirements for mobile remote afterloader units. 35.647 Section 35.647 Energy NUCLEAR REGULATORY COMMISSION MEDICAL USE OF BYPRODUCT MATERIAL Photon Emitting Remote Afterloader Units, Teletherapy Units, and Gamma Stereotactic Radiosurgery...

10 CFR 35.647 - Additional technical requirements for mobile remote afterloader units.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 1 2014-01-01 2014-01-01 false Additional technical requirements for mobile remote afterloader units. 35.647 Section 35.647 Energy NUCLEAR REGULATORY COMMISSION MEDICAL USE OF BYPRODUCT MATERIAL Photon Emitting Remote Afterloader Units, Teletherapy Units, and Gamma Stereotactic Radiosurgery...

10 CFR 35.647 - Additional technical requirements for mobile remote afterloader units.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 1 2012-01-01 2012-01-01 false Additional technical requirements for mobile remote afterloader units. 35.647 Section 35.647 Energy NUCLEAR REGULATORY COMMISSION MEDICAL USE OF BYPRODUCT MATERIAL Photon Emitting Remote Afterloader Units, Teletherapy Units, and Gamma Stereotactic Radiosurgery...

10 CFR 35.647 - Additional technical requirements for mobile remote afterloader units.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 1 2011-01-01 2011-01-01 false Additional technical requirements for mobile remote afterloader units. 35.647 Section 35.647 Energy NUCLEAR REGULATORY COMMISSION MEDICAL USE OF BYPRODUCT MATERIAL Photon Emitting Remote Afterloader Units, Teletherapy Units, and Gamma Stereotactic Radiosurgery...

10 CFR 35.633 - Full calibration measurements on remote afterloader units.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 1 2010-01-01 2010-01-01 false Full calibration measurements on remote afterloader units. 35.633 Section 35.633 Energy NUCLEAR REGULATORY COMMISSION MEDICAL USE OF BYPRODUCT MATERIAL Photon Emitting Remote Afterloader Units, Teletherapy Units, and Gamma Stereotactic Radiosurgery Units § 35.633...

10 CFR 35.643 - Periodic spot-checks for remote afterloader units.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 1 2012-01-01 2012-01-01 false Periodic spot-checks for remote afterloader units. 35.643 Section 35.643 Energy NUCLEAR REGULATORY COMMISSION MEDICAL USE OF BYPRODUCT MATERIAL Photon Emitting Remote Afterloader Units, Teletherapy Units, and Gamma Stereotactic Radiosurgery Units § 35.643 Periodic...

10 CFR 35.633 - Full calibration measurements on remote afterloader units.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 1 2011-01-01 2011-01-01 false Full calibration measurements on remote afterloader units. 35.633 Section 35.633 Energy NUCLEAR REGULATORY COMMISSION MEDICAL USE OF BYPRODUCT MATERIAL Photon Emitting Remote Afterloader Units, Teletherapy Units, and Gamma Stereotactic Radiosurgery Units § 35.633...

10 CFR 35.643 - Periodic spot-checks for remote afterloader units.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 1 2014-01-01 2014-01-01 false Periodic spot-checks for remote afterloader units. 35.643 Section 35.643 Energy NUCLEAR REGULATORY COMMISSION MEDICAL USE OF BYPRODUCT MATERIAL Photon Emitting Remote Afterloader Units, Teletherapy Units, and Gamma Stereotactic Radiosurgery Units § 35.643 Periodic...

10 CFR 35.643 - Periodic spot-checks for remote afterloader units.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 1 2011-01-01 2011-01-01 false Periodic spot-checks for remote afterloader units. 35.643 Section 35.643 Energy NUCLEAR REGULATORY COMMISSION MEDICAL USE OF BYPRODUCT MATERIAL Photon Emitting Remote Afterloader Units, Teletherapy Units, and Gamma Stereotactic Radiosurgery Units § 35.643 Periodic...

10 CFR 35.633 - Full calibration measurements on remote afterloader units.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 1 2013-01-01 2013-01-01 false Full calibration measurements on remote afterloader units. 35.633 Section 35.633 Energy NUCLEAR REGULATORY COMMISSION MEDICAL USE OF BYPRODUCT MATERIAL Photon Emitting Remote Afterloader Units, Teletherapy Units, and Gamma Stereotactic Radiosurgery Units § 35.633...

10 CFR 35.643 - Periodic spot-checks for remote afterloader units.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 1 2013-01-01 2013-01-01 false Periodic spot-checks for remote afterloader units. 35.643 Section 35.643 Energy NUCLEAR REGULATORY COMMISSION MEDICAL USE OF BYPRODUCT MATERIAL Photon Emitting Remote Afterloader Units, Teletherapy Units, and Gamma Stereotactic Radiosurgery Units § 35.643 Periodic...

10 CFR 35.633 - Full calibration measurements on remote afterloader units.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 1 2014-01-01 2014-01-01 false Full calibration measurements on remote afterloader units. 35.633 Section 35.633 Energy NUCLEAR REGULATORY COMMISSION MEDICAL USE OF BYPRODUCT MATERIAL Photon Emitting Remote Afterloader Units, Teletherapy Units, and Gamma Stereotactic Radiosurgery Units § 35.633...

10 CFR 35.633 - Full calibration measurements on remote afterloader units.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 1 2012-01-01 2012-01-01 false Full calibration measurements on remote afterloader units. 35.633 Section 35.633 Energy NUCLEAR REGULATORY COMMISSION MEDICAL USE OF BYPRODUCT MATERIAL Photon Emitting Remote Afterloader Units, Teletherapy Units, and Gamma Stereotactic Radiosurgery Units § 35.633...

10 CFR 35.610 - Safety procedures and instructions for remote afterloader units, teletherapy units, and gamma...

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 1 2010-01-01 2010-01-01 false Safety procedures and instructions for remote afterloader units, teletherapy units, and gamma stereotactic radiosurgery units. 35.610 Section 35.610 Energy NUCLEAR REGULATORY COMMISSION MEDICAL USE OF BYPRODUCT MATERIAL Photon Emitting Remote Afterloader Units...

10 CFR 35.615 - Safety precautions for remote afterloader units, teletherapy units, and gamma stereotactic...

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 1 2013-01-01 2013-01-01 false Safety precautions for remote afterloader units, teletherapy units, and gamma stereotactic radiosurgery units. 35.615 Section 35.615 Energy NUCLEAR REGULATORY COMMISSION MEDICAL USE OF BYPRODUCT MATERIAL Photon Emitting Remote Afterloader Units, Teletherapy Units, and...

10 CFR 35.610 - Safety procedures and instructions for remote afterloader units, teletherapy units, and gamma...

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 1 2012-01-01 2012-01-01 false Safety procedures and instructions for remote afterloader units, teletherapy units, and gamma stereotactic radiosurgery units. 35.610 Section 35.610 Energy NUCLEAR REGULATORY COMMISSION MEDICAL USE OF BYPRODUCT MATERIAL Photon Emitting Remote Afterloader Units...

10 CFR 35.610 - Safety procedures and instructions for remote afterloader units, teletherapy units, and gamma...

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 1 2013-01-01 2013-01-01 false Safety procedures and instructions for remote afterloader units, teletherapy units, and gamma stereotactic radiosurgery units. 35.610 Section 35.610 Energy NUCLEAR REGULATORY COMMISSION MEDICAL USE OF BYPRODUCT MATERIAL Photon Emitting Remote Afterloader Units...

10 CFR 35.615 - Safety precautions for remote afterloader units, teletherapy units, and gamma stereotactic...

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 1 2011-01-01 2011-01-01 false Safety precautions for remote afterloader units, teletherapy units, and gamma stereotactic radiosurgery units. 35.615 Section 35.615 Energy NUCLEAR REGULATORY COMMISSION MEDICAL USE OF BYPRODUCT MATERIAL Photon Emitting Remote Afterloader Units, Teletherapy Units, and...

10 CFR 35.615 - Safety precautions for remote afterloader units, teletherapy units, and gamma stereotactic...

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 1 2014-01-01 2014-01-01 false Safety precautions for remote afterloader units, teletherapy units, and gamma stereotactic radiosurgery units. 35.615 Section 35.615 Energy NUCLEAR REGULATORY COMMISSION MEDICAL USE OF BYPRODUCT MATERIAL Photon Emitting Remote Afterloader Units, Teletherapy Units, and...

10 CFR 35.610 - Safety procedures and instructions for remote afterloader units, teletherapy units, and gamma...

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 1 2011-01-01 2011-01-01 false Safety procedures and instructions for remote afterloader units, teletherapy units, and gamma stereotactic radiosurgery units. 35.610 Section 35.610 Energy NUCLEAR REGULATORY COMMISSION MEDICAL USE OF BYPRODUCT MATERIAL Photon Emitting Remote Afterloader Units...

10 CFR 35.610 - Safety procedures and instructions for remote afterloader units, teletherapy units, and gamma...

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 1 2014-01-01 2014-01-01 false Safety procedures and instructions for remote afterloader units, teletherapy units, and gamma stereotactic radiosurgery units. 35.610 Section 35.610 Energy NUCLEAR REGULATORY COMMISSION MEDICAL USE OF BYPRODUCT MATERIAL Photon Emitting Remote Afterloader Units...

10 CFR 35.615 - Safety precautions for remote afterloader units, teletherapy units, and gamma stereotactic...

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 1 2012-01-01 2012-01-01 false Safety precautions for remote afterloader units, teletherapy units, and gamma stereotactic radiosurgery units. 35.615 Section 35.615 Energy NUCLEAR REGULATORY COMMISSION MEDICAL USE OF BYPRODUCT MATERIAL Photon Emitting Remote Afterloader Units, Teletherapy Units, and...

Optimal pressure regulation of the pneumatic ventricular assist device with bellows-type driver.

PubMed

Lee, Jung Joo; Kim, Bum Soo; Choi, Jaesoon; Choi, Hyuk; Ahn, Chi Bum; Nam, Kyoung Won; Jeong, Gi Seok; Lim, Choon Hak; Son, Ho Sung; Sun, Kyung

2009-08-01

The bellows-type pneumatic ventricular assist device (VAD) generates pneumatic pressure with compression of bellows instead of using an air compressor. This VAD driver has a small volume that is suitable for portable devices. However, improper pneumatic pressure setup can not only cause a lack of adequate flow generation, but also cause durability problems. In this study, a pneumatic pressure regulation system for optimal operation of the bellows-type VAD has been developed. The optimal pneumatic pressure conditions according to various afterload conditions aiming for optimal flow rates were investigated, and an afterload estimation algorithm was developed. The developed regulation system, which consists of a pressure sensor and a two-way solenoid valve, estimates the current afterload and regulates the pneumatic pressure to the optimal point for the current afterload condition. Experiments were performed in a mock circulation system. The afterload estimation algorithm showed sufficient performance with the standard deviation of error, 8.8 mm Hg. The flow rate could be stably regulated with a developed system under various afterload conditions. The shortcoming of a bellows-type VAD could be handled with this simple pressure regulation system.

Introduction of a hybrid treatment delivery system used for quality assurance in multi-catheter interstitial brachytherapy

NASA Astrophysics Data System (ADS)

Kallis, Karoline; Kreppner, Stephan; Lotter, Michael; Fietkau, Rainer; Strnad, Vratislav; Bert, Christoph

2018-05-01

Multi-catheter interstitial brachytherapy (iBT) is a treatment option for breast cancer patients after breast conserving surgery. Typically, only a few additional quality interventions after the first irradiation have been introduced to ensure the planned treatment delivery. Therefore, the purpose of this study is to show the possibilities of an electromagnetic tracking (EMT) system integrated into the afterloader for quality assurance (QA) in high-dose rate (HDR) iBT of patients with breast cancer. The hybrid afterloader system equipped with an electromagnetic sensor was used for all phantom and patient measurements. Phantom measurements were conducted to estimate the quality of different evaluation schemes. After a coherent point drift registration of the EMT traces to the reconstructed catheters based on computed tomograms the dwell positions (DP) were defined. Different fitting and interpolation methods were analyzed for the reconstruction of DPs. All estimated DPs were compared to the DPs defined in treatment planning. Until now, the implant geometry of 20 patients treated with HDR brachytherapy was acquired and explored. Regarding the reconstruction techniques, both fitting and interpolation were able to detect manually introduced shifts and swaps. Nonetheless, interpolation showed superior results (RMSE  =  1.27 mm), whereas fitting seemed to be more stable to distortion and motion. The EMT system proved to be beneficial for QA in brachytherapy and furthermore, clinical feasibility was proven.

Effective palliation for advanced esophageal cancer using intralumenal irradiation.

PubMed

Makarewicz, R; Czechowicz, W; Kabacińska, R

1996-01-01

Palliative treatment by intracavitary irradiation alone has been used in 15 patients with advanced carcinoma of the esophagus. Most of them had already failed other palliative modalities including external irradiation, chemoradiotherapy, laserotherapy and dilatation. Intracavitary irradiation was carried out with a microSelectron HDR afterloading device and usually 22.5 Gy was given in three fractions repeated weekly. Up to three month after treatment, complete endoscopic regression was seen in 1 patient, partial endoscopic regression in 8 patients, no response in one and progressive disease in 5 patients. The median survival time is 6.2 months. There were not severe complications. We conclude that high dose rate intracavitary irradiation is a useful palliative modality in patients with advanced or recurrent esophageal cancer.

Estimation of Filling and Afterload Conditions by Pump Intrinsic Parameters in a Pulsatile Total Artificial Heart.

PubMed

Cuenca-Navalon, Elena; Laumen, Marco; Finocchiaro, Thomas; Steinseifer, Ulrich

2016-07-01

A physiological control algorithm is being developed to ensure an optimal physiological interaction between the ReinHeart total artificial heart (TAH) and the circulatory system. A key factor for that is the long-term, accurate determination of the hemodynamic state of the cardiovascular system. This study presents a method to determine estimation models for predicting hemodynamic parameters (pump chamber filling and afterload) from both left and right cardiovascular circulations. The estimation models are based on linear regression models that correlate filling and afterload values with pump intrinsic parameters derived from measured values of motor current and piston position. Predictions for filling lie in average within 5% from actual values, predictions for systemic afterload (AoPmean , AoPsys ) and mean pulmonary afterload (PAPmean ) lie in average within 9% from actual values. Predictions for systolic pulmonary afterload (PAPsys ) present an average deviation of 14%. The estimation models show satisfactory prediction and confidence intervals and are thus suitable to estimate hemodynamic parameters. This method and derived estimation models are a valuable alternative to implanted sensors and are an essential step for the development of a physiological control algorithm for a fully implantable TAH. Copyright © 2015 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

HDR {sup 192}Ir source speed measurements using a high speed video camera

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fonseca, Gabriel P.; Viana, Rodrigo S. S.; Yoriyaz, Hélio

Purpose: The dose delivered with a HDR {sup 192}Ir afterloader can be separated into a dwell component, and a transit component resulting from the source movement. The transit component is directly dependent on the source speed profile and it is the goal of this study to measure accurate source speed profiles. Methods: A high speed video camera was used to record the movement of a {sup 192}Ir source (Nucletron, an Elekta company, Stockholm, Sweden) for interdwell distances of 0.25–5 cm with dwell times of 0.1, 1, and 2 s. Transit dose distributions were calculated using a Monte Carlo code simulatingmore » the source movement. Results: The source stops at each dwell position oscillating around the desired position for a duration up to (0.026 ± 0.005) s. The source speed profile shows variations between 0 and 81 cm/s with average speed of ∼33 cm/s for most of the interdwell distances. The source stops for up to (0.005 ± 0.001) s at nonprogrammed positions in between two programmed dwell positions. The dwell time correction applied by the manufacturer compensates the transit dose between the dwell positions leading to a maximum overdose of 41 mGy for the considered cases and assuming an air-kerma strength of 48 000 U. The transit dose component is not uniformly distributed leading to over and underdoses, which is within 1.4% for commonly prescribed doses (3–10 Gy). Conclusions: The source maintains its speed even for the short interdwell distances. Dose variations due to the transit dose component are much lower than the prescribed treatment doses for brachytherapy, although transit dose component should be evaluated individually for clinical cases.« less

Radiobiological equivalent of low/high dose rate brachytherapy and evaluation of tumor and normal responses to the dose.

PubMed

Manimaran, S

2007-06-01

The aim of this study was to compare the biological equivalent of low-dose-rate (LDR) and high-dose-rate (HDR) brachytherapy in terms of the more recent linear quadratic (LQ) model, which leads to theoretical estimation of biological equivalence. One of the key features of the LQ model is that it allows a more systematic radiobiological comparison between different types of treatment because the main parameters alpha/beta and micro are tissue-specific. Such comparisons also allow assessment of the likely change in the therapeutic ratio when switching between LDR and HDR treatments. The main application of LQ methodology, which focuses on by increasing the availability of remote afterloading units, has been to design fractionated HDR treatments that can replace existing LDR techniques. In this study, with LDR treatments (39 Gy in 48 h) equivalent to 11 fractions of HDR irradiation at the experimental level, there are increasing reports of reproducible animal models that may be used to investigate the biological basis of brachytherapy and to help confirm theoretical predictions. This is a timely development owing to the nonavailability of sufficient retrospective patient data analysis. It appears that HDR brachytherapy is likely to be a viable alternative to LDR only if it is delivered without a prohibitively large number of fractions (e.g., fewer than 11). With increased scientific understanding and technological capability, the prospect of a dose equivalent to HDR brachytherapy will allow greater utilization of the concepts discussed in this article.

SU-F-T-28: Evaluation of BEBIG HDR Co-60 After-Loading System for Skin Cancer Treatment Using Conical Surface Applicator

DOE Office of Scientific and Technical Information (OSTI.GOV)

Safigholi, H; Soliman, A; Song, W Y

Purpose: To evaluate the possibility of utilizing the BEBIG HDR 60Co remote after-loading system for malignant skin surface treatment using Monte Carlo (MC) simulation technique. Methods: First TG-43 parameters of BEBIG-Co-60 and Nucletron Ir-192-mHDR-V2 brachytherapy sources were simulated using MCNP6 code to benchmark the sources against the literature. Second a conical tungsten-alloy with 3-cm diameter of Planning-Target-Volume (PTV) at surface for use with a single stepping HDR source is designed. The HDR source is modeled parallel to treatment plane at the center of the conical applicator with a source surface distance (SSD) of 1.5-cm and a removable plastic end-cap withmore » a 1-mm thickness. Third, MC calculated dose distributions from HDR Co-60 for conical surface applicator were compared with the simulated data using HDR Ir-192 source. The initial calculations were made with the same conical surface applicator (standard-applicator) dimensions as the ones used with the Ir-192 system. Fourth, the applicator wall-thickness for the Co-60 system was increased (doubled) to diminish leakage dose to levels received when using the Ir-192 system. With this geometry, percentage depth dose (PDD), and relative 2D-dose profiles in transverse/coronal planes were normalized at 3-mm prescription-depth evaluated along the central axis. Results: PDD for Ir-192 and Co-60 were similar with standard and thick-walled applicator. 2D-relative dose distribution of Co-60, inside the standard-conical-applicator, generated higher penumbra (7.6%). For thick-walled applicator, it created smaller penumbra (<4%) compared to Ir-192 source in the standard-conicalapplicator. Dose leakage outside of thick-walled applicator with Co-60 source was approximately equal (≤3%) with standard applicator using Ir-192 source. Conclusion: Skin cancer treatment with equal quality can be performed with Co-60 source and thick-walled conical applicators instead of Ir-192 with standard applicators. These conical surface applicator must be used with a protective plastic end-cap to eliminate electron contamination and over-dosage of the skin.« less

Impact of afterload on the assessment of severity of aortic stenosis.

PubMed

Chang, Sung-A; Kim, Hyung-Kwan; Sohn, Dae-Won

2012-06-01

Aortic stenosis (AS) is increasingly diagnosed in current aging society. Echocardiography is the most important tool in the assessment of AS and its severity. However, load-dependency of Doppler measurement could affect the accuracy of AS severity assessment. We tried to evaluate the impact of afterload on the assessment of AS severity by modification of afterload using pneumatic compression (Pcom). Forty patients diagnosed as moderate or severe AS [effective orifice area of aortic valve (EOA(AV)) by continuity equation of < 1.5 cm(2)] were consecutively enrolled. Patients with severely uncontrolled hypertension, severe left ventricular (LV) dysfunction, and other significant valve disease were excluded. Comprehensive echocardiography was performed at baseline to assess AS severity. Then, pneumatic compression of the lower extremities by 100 mmHg was applied to increase LV afterload. After 3 minutes, echocardiography was repeated to assess AS severity. Mean blood pressure was significantly increased under Pcom (p < 0.001), while heart rate remained unchanged. Peak aortic valve velocity (V(max)) was slightly, but significantly decreased under Pcom (p = 0.03). However, Doppler velocity index and EOA(AV) by continuity equation were not affected by Pcom. AS severity assessment by echocardiography was not dependent on the change of LV afterload imposed by Pcom. AV V(max) was slightly decreased with LV afterload increment, but these changes were too small to alter treatment plan of AS patients. EOA(AV) and Doppler velocity index are more stable parameters for AS severity assessment.

10 CFR 35.647 - Additional technical requirements for mobile remote afterloader units.

Code of Federal Regulations, 2010 CFR

2010-01-01

... on the remote afterloader unit, on the control console, and in the facility; (3) Viewing and intercom... monitors used to indicate room exposures; (6) Source positioning (accuracy); and (7) Radiation monitors...

Development of a TLD mailed system for remote dosimetry audit for (192)Ir HDR and PDR sources.

PubMed

Roué, Amélie; Venselaar, Jack L M; Ferreira, Ivaldo H; Bridier, André; Van Dam, Jan

2007-04-01

In the framework of an ESTRO ESQUIRE project, the BRAPHYQS Physics Network and the EQUAL-ESTRO laboratory have developed a procedure for checking the absorbed dose to water in the vicinity of HDR or PDR sources using a mailed TLD system. The methodology and the materials used in the procedure are based on the existing EQUAL-ESTRO external radiotherapy dose checks. A phantom for TLD postal dose assurance service, adapted to accept catheters from different HDR afterloaders, has been developed. The phantom consists of three PMMA tubes supporting catheters placed at 120 degrees around a central TLD holder. A study on the use of LiF powder type DTL 937 (Philitech) has been performed in order to establish the TLD calibration in dose-to-water at a given distance from (192)Ir source, as well as to determine all correction factors to convert the TLD reading into absorbed dose to water. The dosimetric audit is based on the comparison between the dose to water measured with the TL dosimeter and the dose calculated by the clinical TPS. Results of the audits are classified in four different levels depending on the ratio of the measured dose to the stated dose. The total uncertainty budget in the measurement of the absorbed dose to water using TLD near an (192)Ir HDR source, including TLD reading, correction factors and TLD calibration coefficient, is determined as 3.27% (1s). To validate the procedures, the external audit was first tested among the members of the BRAPHYQS Network. Since November 2004, the test has been made available for use by all European brachytherapy centres. To date, 11 centres have participated in the checks and the results obtained are very encouraging. Nevertheless, one error detected has shown the usefulness of this audit. A method of absorbed dose to water determination in the vicinity of an (192)Ir brachytherapy source was developed for the purpose of a mailed TL dosimetry system. The accuracy of the procedure was determined. This method allows a check of the whole dosimetry chain for this type of brachytherapy afterloading system and can easily be performed by mail to any institution in the European area and elsewhere. Such an external audit can be an efficient QC method complementary to internal quality control as it can reveal some errors which are not observable by other means.

A multicenter study to quantify systematic variations and associated uncertainties in source positioning with commonly used HDR afterloaders and ring applicators for the treatment of cervical carcinomas

DOE Office of Scientific and Technical Information (OSTI.GOV)

Awunor, O., E-mail: onuora.awunor@stees.nhs.uk; Berger, D.; Kirisits, C.

Purpose: The reconstruction of radiation source position in the treatment planning system is a key part of the applicator reconstruction process in high dose rate (HDR) brachytherapy treatment of cervical carcinomas. The steep dose gradients, of as much as 12%/mm, associated with typical cervix treatments emphasize the importance of accurate and precise determination of source positions. However, a variety of methodologies with a range in associated measurement uncertainties, of up to ±2.5 mm, are currently employed by various centers to do this. In addition, a recent pilot study by Awunor et al. [“Direct reconstruction and associated uncertainties of {sup 192}Irmore » source dwell positions in ring applicators using gafchromic film in the treatment planning of HDR brachytherapy cervix patients,” Phys. Med. Biol. 58, 3207–3225 (2013)] reported source positional differences of up to 2.6 mm between ring sets of the same type and geometry. This suggests a need for a comprehensive study to assess and quantify systematic source position variations between commonly used ring applicators and HDR afterloaders across multiple centers. Methods: Eighty-six rings from 20 European brachytherapy centers were audited in the form of a postal audit with each center collecting the data independently. The data were collected by setting up the rings using a bespoke jig and irradiating gafchromic films at predetermined dwell positions using four afterloader types, MicroSelectron, Flexitron, GammaMed, and MultiSource, from three manufacturers, Nucletron, Varian, and Eckert & Ziegler BEBIG. Five different ring types in six sizes (Ø25–Ø35 mm) and two angles (45° and 60°) were used. Coordinates of irradiated positions relative to the ring center were determined and collated, and source position differences quantified by ring type, size, and angle. Results: The mean expanded measurement uncertainty (k = 2) along the direction of source travel was ±1.4 mm. The standard deviation associated with the source position reproducibility was within ±1.0 mm for all afterloaders. Maximum source positional variations of 2.1 and 3.9, 1.8 and 5.4, and 2.3 and 3.4 mm were observed at standard treatment positions for the Ø26, Ø30, and Ø32 mm sized 45° and 60° rings, respectively. Mean positional differences between a majority of the rings were within ±1.0 mm. Mean positional differences between a majority of the intracenter ring sets were within the expanded measurement uncertainty. When comparing the 45°–60° source paths, mean differences of 1.6, 0.9, and 0.9 mm were observed across the Ø26, Ø30 (MicroSelectron), and Ø32 mm (GammaMed) rings, respectively. When comparing to manufacturer source path models, maximum offsets of 1.9 and 2.1, 2.6 and 2.3, and 0.8 and 1.6 mm were observed for the Ø26, Ø30 (MicroSelectron), and Ø30 mm (Flexitron) sized 45° and 60° rings, respectively. When comparing the audit to ring commissioning data of participating centers, mean differences of up to 2.4 mm were observed. Conclusions: A majority of the audited rings showed a good degree of manufacturer consistency; however, substantial positional variation observed between some rings emphasizes the importance of commissioning each ring before clinical use. Differences observed between audit and commissioning data also indicate some variation in source treatment positions across centers.« less

10 CFR 35.600 - Use of a sealed source in a remote afterloader unit, teletherapy unit, or gamma stereotactic...

Code of Federal Regulations, 2010 CFR

2010-01-01

... COMMISSION MEDICAL USE OF BYPRODUCT MATERIAL Photon Emitting Remote Afterloader Units, Teletherapy Units, and..., teletherapy unit, or gamma stereotactic radiosurgery unit. A licensee shall use sealed sources in photon...

10 CFR 35.600 - Use of a sealed source in a remote afterloader unit, teletherapy unit, or gamma stereotactic...

Code of Federal Regulations, 2011 CFR

2011-01-01

... COMMISSION MEDICAL USE OF BYPRODUCT MATERIAL Photon Emitting Remote Afterloader Units, Teletherapy Units, and..., teletherapy unit, or gamma stereotactic radiosurgery unit. A licensee shall use sealed sources in photon...

10 CFR 35.600 - Use of a sealed source in a remote afterloader unit, teletherapy unit, or gamma stereotactic...

Code of Federal Regulations, 2014 CFR

2014-01-01

... COMMISSION MEDICAL USE OF BYPRODUCT MATERIAL Photon Emitting Remote Afterloader Units, Teletherapy Units, and..., teletherapy unit, or gamma stereotactic radiosurgery unit. A licensee shall use sealed sources in photon...

10 CFR 35.600 - Use of a sealed source in a remote afterloader unit, teletherapy unit, or gamma stereotactic...

Code of Federal Regulations, 2013 CFR

2013-01-01

... COMMISSION MEDICAL USE OF BYPRODUCT MATERIAL Photon Emitting Remote Afterloader Units, Teletherapy Units, and..., teletherapy unit, or gamma stereotactic radiosurgery unit. A licensee shall use sealed sources in photon...

10 CFR 35.600 - Use of a sealed source in a remote afterloader unit, teletherapy unit, or gamma stereotactic...

Code of Federal Regulations, 2012 CFR

2012-01-01

... COMMISSION MEDICAL USE OF BYPRODUCT MATERIAL Photon Emitting Remote Afterloader Units, Teletherapy Units, and..., teletherapy unit, or gamma stereotactic radiosurgery unit. A licensee shall use sealed sources in photon...

High-dose-rate (HDR) brachytherapy for the treatment of benign obstructive endobronchial granulation tissue

DOE Office of Scientific and Technical Information (OSTI.GOV)

Madu, Chika N.; Machuzak, Michael S.; Sterman, Daniel H.

Background: Severe airway obstruction can occur in the setting of benign granulation tissue forming at bronchial anastomotic sites after lung transplantation in up to 20% of patients. Many of these benign lesions respond to stent placement, laser ablation, or balloon bronchoplasty. However, in certain cases, proliferation of granulation tissue may persist despite all therapeutic attempts. This study describes a series of refractory patients treated with high-dose-rate (HDR) brachytherapy for benign proliferation of granulation tissue, causing airway compromise. Methods and Materials: Between April 2002 and June 2005, 5 patients with significant airway compromise from recurrent granulation tissue were treated with HDRmore » brachytherapy. All patients had previously failed to maintain a patent airway despite multiple bronchoscopic interventions. Treatment was delivered using an HDR brachytherapy afterloader with {sup 192}Ir. Dose prescription was to a depth of 1 cm. All patients were treated weekly, with total doses ranging from 10 Gy to 21 Gy in two to three fractions. Results: The median follow-up was 12 months. All patients experienced a reduction in therapeutic bronchoscopic procedures after HDR brachytherapy compared with the pretreatment period. With the exception of possible radiation-induced bronchitis in 1 patient, there were no other treatment related complications. At the time of this report, 2 patients have died and the other 3 are alive with marked symptomatic improvement and reduced bronchoscopic procedures. Conclusion: High-dose-rate brachytherapy is an effective treatment for benign proliferation of granulation tissue causing airway obstruction. The early response to therapy is encouraging and further follow-up is necessary to determine long-term durability and late effects.« less

NOTE: Monte Carlo evaluation of kerma in an HDR brachytherapy bunker

NASA Astrophysics Data System (ADS)

Pérez-Calatayud, J.; Granero, D.; Ballester, F.; Casal, E.; Crispin, V.; Puchades, V.; León, A.; Verdú, G.

2004-12-01

In recent years, the use of high dose rate (HDR) after-loader machines has greatly increased due to the shift from traditional Cs-137/Ir-192 low dose rate (LDR) to HDR brachytherapy. The method used to calculate the required concrete and, where appropriate, lead shielding in the door is based on analytical methods provided by documents published by the ICRP, the IAEA and the NCRP. The purpose of this study is to perform a more realistic kerma evaluation at the entrance maze door of an HDR bunker using the Monte Carlo code GEANT4. The Monte Carlo results were validated experimentally. The spectrum at the maze entrance door, obtained with Monte Carlo, has an average energy of about 110 keV, maintaining a similar value along the length of the maze. The comparison of results from the aforementioned values with the Monte Carlo ones shows that results obtained using the albedo coefficient from the ICRP document more closely match those given by the Monte Carlo method, although the maximum value given by MC calculations is 30% greater.

A retrospective analysis of rectal and bladder dose for gynecological brachytherapy treatments with GZP6 HDR afterloading system.

PubMed

Bahreyni Toossi, Mohammad Taghi; Ghorbani, Mahdi; Makhdoumi, Yasha; Taheri, Mojtaba; Homaee Shandiz, Fatemeh; Zahed Anaraki, Siavash; Soleimani Meigooni, Ali

2012-01-01

The aim of this work is to evaluate rectal and bladder dose for the patients treated for gynecological cancers. The GZP6 high dose rate brachytherapy system has been recently introduced to a number of radiation therapy departments in Iran, for treatment of various tumor sites such as cervix and vagina. Our analysis was based on dose measurements for 40 insertions in 28 patients, treated by a GZP6 unit between June 2009 and November 2010. Treatments consisted of combined teletherapy and intracavitary brachytherapy. In vivo dosimetry was performed with TLD-400 chips and TLD-100 microcubes in the rectum and bladder. The average of maximum rectal and bladder dose values were found to be 7.62 Gy (range 1.72-18.55 Gy) and 5.17 Gy (range 0.72-15.85 Gy), respectively. It has been recommended by the ICRU that the maximum dose to the rectum and bladder in intracavitary treatment of vaginal or cervical cancer should be lower than 80% of the prescribed dose to point A in the Manchester system. In this study, of the total number of 40 insertions, maximum rectal dose in 29 insertions (72.5% of treatment sessions) and maximum bladder dose in 18 insertions (45% of treatments sessions) were higher than 80% of the prescribed dose to the point of dose prescription. In vivo dosimetry for patients undergoing treatment by GZP6 brachytherapy system can be used for evaluation of the quality of brachytherapy treatments by this system. This information could be used as a base for developing the strategy for treatment of patients treated with GZP6 system.

A retrospective analysis of rectal and bladder dose for gynecological brachytherapy treatments with GZP6 HDR afterloading system

PubMed Central

Bahreyni Toossi, Mohammad Taghi; Ghorbani, Mahdi; Makhdoumi, Yasha; Taheri, Mojtaba; Homaee Shandiz, Fatemeh; Zahed Anaraki, Siavash; Soleimani Meigooni, Ali

2012-01-01

Aim The aim of this work is to evaluate rectal and bladder dose for the patients treated for gynecological cancers. Background The GZP6 high dose rate brachytherapy system has been recently introduced to a number of radiation therapy departments in Iran, for treatment of various tumor sites such as cervix and vagina. Materials and methods Our analysis was based on dose measurements for 40 insertions in 28 patients, treated by a GZP6 unit between June 2009 and November 2010. Treatments consisted of combined teletherapy and intracavitary brachytherapy. In vivo dosimetry was performed with TLD-400 chips and TLD-100 microcubes in the rectum and bladder. Results The average of maximum rectal and bladder dose values were found to be 7.62 Gy (range 1.72–18.55 Gy) and 5.17 Gy (range 0.72–15.85 Gy), respectively. It has been recommended by the ICRU that the maximum dose to the rectum and bladder in intracavitary treatment of vaginal or cervical cancer should be lower than 80% of the prescribed dose to point A in the Manchester system. In this study, of the total number of 40 insertions, maximum rectal dose in 29 insertions (72.5% of treatment sessions) and maximum bladder dose in 18 insertions (45% of treatments sessions) were higher than 80% of the prescribed dose to the point of dose prescription. Conclusion In vivo dosimetry for patients undergoing treatment by GZP6 brachytherapy system can be used for evaluation of the quality of brachytherapy treatments by this system. This information could be used as a base for developing the strategy for treatment of patients treated with GZP6 system. PMID:24377037

Cardiopulmonary physiology: why the heart and lungs are inextricably linked.

PubMed

Verhoeff, Kevin; Mitchell, Jamie R

2017-09-01

Because the heart and lungs are confined within the thoracic cavity, understanding their interactions is integral for studying each system. Such interactions include changes in external constraint to the heart, blood volume redistribution (venous return), direct ventricular interaction (DVI), and left ventricular (LV) afterload. During mechanical ventilation, these interactions can be amplified and result in reduced cardiac output. For example, increased intrathoracic pressure associated with mechanical ventilation can increase external constraint and limit ventricular diastolic filling and, therefore, output. Similarly, high intrathoracic pressures can alter blood volume distribution and limit diastolic filling of both ventricles while concomitantly increasing pulmonary vascular resistance, leading to increased DVI, which may further limit LV filling. While LV afterload is generally considered to decrease with increased intrathoracic pressure, the question arises if the reduced LV afterload is primarily a consequence of a reduced LV preload. A thorough understanding of the interaction between the heart and lungs can be complicated but is essential for clinicians and health science students alike. In this teaching review, we have attempted to highlight the present understanding of certain salient aspects of cardiopulmonary physiology and pathophysiology, as well as provide a resource for multidisciplined health science educators and students. Copyright © 2017 the American Physiological Society.

NOTE: A Monte Carlo study of dose rate distribution around the specially asymmetric CSM3-a 137Cs source

NASA Astrophysics Data System (ADS)

Pérez-Calatayud, J.; Lliso, F.; Ballester, F.; Serrano, M. A.; Lluch, J. L.; Limami, Y.; Puchades, V.; Casal, E.

2001-07-01

The CSM3 137Cs type stainless-steel encapsulated source is widely used in manually afterloaded low dose rate brachytherapy. A specially asymmetric source, CSM3-a, has been designed by CIS Bio International (France) substituting the eyelet side seed with an inactive material in the CSM3 source. This modification has been done in order to allow a uniform dose level over the upper vaginal surface when this `linear' source is inserted at the top of the dome vaginal applicators. In this study the Monte Carlo GEANT3 simulation code, incorporating the source geometry in detail, was used to investigate the dosimetric characteristics of this special CSM3-a 137Cs brachytherapy source. The absolute dose rate distribution in water around this source was calculated and is presented in the form of an along-away table. Comparison of Sievert integral type calculations with Monte Carlo results are discussed.

High dose rate brachytherapy with customized applicators for malignant facial skin lesions.

PubMed

Jumeau, R; Renard-Oldrini, S; Courrech, F; Buchheit, I; Oldrini, G; Vogin, G; Peiffert, D

2016-07-01

Brachytherapy is a well-known treatment in the management of skin tumors. For facial or scalp lesions, applicators have been developed to deliver non-invasive treatment. We present cases treated with customized applicators with high dose rate system. Patients with poor performance status treated for malignant skin lesions of the scalp or the facial skin between 2011 and 2014 were studied. Afterloading devices were chosen between Freiburg(®) Flap, silicone-mold or wax applicators. The clinical target volume (CTV) was created by adding margins to lesions (10mm to 20mm). The dose schedules were 25Gy in five fractions for postoperative lesions, 30Gy in six fractions for exclusive treatments and a single session of 8Gy could be considered for palliative treatments. In 30 months, 11 patients received a treatment for a total of 12 lesions. The median age was 80 years. The median follow-up was 17 months and the 2-year local control rate was 91%. The mean CTV surface was 41.1cm(2) with a mean thickness of 6.1mm. We conceived three wax applicators, used our silicone-mold eight times and the Freiburg(®) Flap one time. We observed only low-grade radiodermitis (grade I: 50%, grade II: 33%), and no high-grade skin toxicity. High dose rate brachytherapy with customized applicators for facial skin and scalp lesions is efficient and safe. It is a good modality to treat complex lesions in patients unfit for invasive treatment. Copyright © 2016 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.

Intravaginal high-dose-rate brachytherapy for stage I endometrial cancer: A randomized study of two dose-per-fraction levels

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sorbe, Bengt; Straumits, Andris; Karlsson, Leif

2005-08-01

Purpose To compare two different fractionation schedules for postoperative vaginal high-dose-rate (HDR) irradiation in endometrial carcinomas. Methods and Materials In a complete geographic series of 290 low-risk endometrial carcinomas, the efficacy and side effects of two different fractionation schedules for postoperative vaginal irradiation were evaluated. The patients were treated during the years 1989-2003. The tumors were in International Federation of Gynecology and Obstetrics Stages IA-IB and Grades 1-2. The HDR MicroSelectron afterloading equipment (iridium-192) was used. Perspex vaginal applicators with diameters of 20-30 mm were used, and the dose was specified at 5 mm from the surface of the applicator.more » Six fractions were given, and the overall treatment time was 8 days. The size of the dose per fraction was randomly set to 2.5 Gy (total dose of 15.0 Gy) or 5.0 Gy (total dose of 30.0 Gy). One hundred forty-four patients were treated with the 2.5-Gy fraction and 146 patients with the 5.0-Gy fraction. Results The overall locoregional recurrence rate of the complete series was 1.4% and the rate of vaginal recurrences 0.7%. There was no difference between the two randomized groups. The vaginal shortening measured by colpometry was not significant (p = 0.159) in the 2.5-Gy group (mean, 0.3 cm) but was highly significant (p < 0.000001) in the 5.0-Gy group (mean 2.1 cm) after 5 years. Mucosal atrophy and bleedings were significantly more frequent in the 5.0-Gy group. Symptoms noted in the 2.5-Gy group were not different from what could be expected in a normal group of postmenopausal women. Conclusion The fractionation schedule recommended for postoperative vaginal irradiation in low-risk endometrial carcinoma is six fractions of 2.5 Gy when the HDR technique is used.« less

A new after-loading intrauterine packing device: ten years experience.

PubMed

Sklaroff, D M; Baker, A S; Tasbas, M

1985-12-01

A new variation of the uterine packing device for the treatment of endometrial carcinoma is described. It combines the advantages of the Holter technique with the after-loading method described by Simon. This device has been in use for more than 10 years and has been found most satisfactory.

The effect of lifelong exercise frequency on arterial stiffness.

PubMed

Shibata, Shigeki; Fujimoto, Naoki; Hastings, Jeffrey L; Carrick-Ranson, Graeme; Bhella, Paul S; Hearon, Christopher; Levine, Benjamin D

2018-05-20

This study examined the effect of different 'doses' of lifelong (>25 years) exercise on arterial stiffening (a hallmark of vascular ageing) in older adults. There are clear dose-dependent effects of lifelong exercise training on human arterial stiffness that vary according to the site and size of the arteries. Similar to what we have observed previously with ventricular stiffening, 4-5 days week -1 of committed exercise over a lifetime are necessary to preserve 'youthful' vascular compliance, especially of the large central arteries. Casual exercise training of two to three times per week may be sufficient for middle-sized arteries like the carotid to minimize arterial stiffening with ageing. However, there is little effect of exercise training on the small-sized peripheral arteries at any dose. Central arterial stiffness increases with sedentary ageing. While near-daily, vigorous lifelong (>25 years) endurance exercise training prevents arterial stiffening with ageing, this rigorous routine of exercise training over a lifetime is impractical for most individuals. The aim was to examine whether a less frequent 'dose' of lifelong exercise training (four to five sessions per week for > 30 min) that is consistent with current physical activity recommendations elicits similar benefits on central arterial stiffening with ageing. A cross-sectional examination of 102 seniors (>60 years old) who had a consistent lifelong exercise history was performed. Subjects were stratified into four groups based on exercise frequency as an index of exercise 'dose': sedentary: fewer than two sessions per week; casual exercisers: two to three sessions per week; committed exercisers: four to five sessions per week; and Masters athletes: six to seven sessions per week plus regular competitions. Detailed measurements of arterial stiffness and left ventricular afterload were collected. Biological aortic age and central pulse wave velocity were younger in committed exercisers and Masters athletes compared to sedentary seniors. Total arterial compliance index (TACi) was lower, while carotid β-stiffness index and effective arterial elastance were higher in sedentary seniors compared to the other groups. There appeared to be a dose-response threshold for carotid β-stiffness index and TACi. Peripheral arterial stiffness was not significantly different among the groups. These data suggest that four to five weekly exercise sessions over a lifetime is associated with reduced central arterial stiffness in the elderly. A less frequent dose of lifelong exercise (two to three sessions per week) is associated with decreased ventricular afterload and peripheral resistance, while peripheral arterial stiffness is unaffected by any dose of exercise. © 2018 The Authors. The Journal of Physiology © 2018 The Physiological Society.

A compliant, banded outflow cannula for decreased afterload sensitivity of rotary right ventricular assist devices.

PubMed

Gregory, Shaun D; Schummy, Emma; Pearcy, Mark; Pauls, Jo P; Tansley, Geoff; Fraser, John F; Timms, Daniel

2015-02-01

Biventricular support with dual rotary ventricular assist devices (VADs) has been implemented clinically with restriction of the right VAD (RVAD) outflow cannula to artificially increase afterload and, therefore, operate within recommended design speed ranges. However, the low preload and high afterload sensitivity of these devices increase the susceptibility of suction events. Active control systems are prone to sensor drift or inaccurate inferred (sensor-less) data, therefore an alternative solution may be of benefit. This study presents the in vitro evaluation of a compliant outflow cannula designed to passively decrease the afterload sensitivity of rotary RVADs and minimize left-sided suction events. A one-way fluid-structure interaction model was initially used to produce a design with suitable flow dynamics and radial deformation. The resultant geometry was cast with different initial cross-sectional restrictions and concentrations of a softening diluent before evaluation in a mock circulation loop. Pulmonary vascular resistance (PVR) was increased from 50 dyne s/cm(5) until left-sided suction events occurred with each compliant cannula and a rigid, 4.5 mm diameter outflow cannula for comparison. Early suction events (PVR ∼ 300 dyne s/cm(5) ) were observed with the rigid outflow cannula. Addition of the compliant section with an initial 3 mm diameter restriction and 10% diluent expanded the outflow restriction as PVR increased, thus increasing RVAD flow rate and preventing left-sided suction events at PVR levels beyond 1000 dyne s/cm(5) . Therefore, the compliant, restricted outflow cannula provided a passive control system to assist in the prevention of suction events with rotary biventricular support while maintaining pump speeds within normal ranges of operation. Copyright © 2014 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

Poster - 07: Investigations of the Advanced Collapsed-cone Engine for HDR Brachytherapy Scalp Treatments

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cawston-Grant, Brie; Morrison, Hali; Sloboda, Ron

Purpose: To present an investigation of the Advanced Collapsed-cone Engine (ACE) in Oncentraê Brachy (OcB) v4.5 using a tissue equivalent phantom modeling scalp brachytherapy (BT) treatments. Methods: A slab phantom modeling the skin, skull, brain and mold was used. A dose of 400cGy was prescribed to just above the skull layer using TG-43 and was delivered using an HDR afterloader. Measurements were made using Gafchromic™ EBT3 film at four depths within the phantom. The TG-43 planned and film measured doses were compared to the standard (sACE) and high (hACE) accuracy ACE options in OcB between the surface and below themore » skull. Results: The average difference between the TG-43 calculated and film measured doses was −11.25±3.38% when there was no air gap between the mold and skin; sACE and hACE doses were on average lower than TG-43 calculated doses by 3.41±0.03% and 2.45±0.03%, respectively. With a 3mm air gap between the mold and skin, the difference between the TG-43 calculated and measured doses was −8.28±5.76%; sACE and hACE calculations yielded average doses 1.87±0.03% and 1.78±0.04% greater than TG-43, respectively. Conclusions: TG-43, sACE, and hACE were found to overestimate doses below the skull layer compared to film. With a 3mm air gap between the mold and skin, sACE and hACE more accurately predicted the film dose to the skin surface than TG-43. More clinical variations and their implications are currently being investigated.« less

Design and characterization of a new high-dose-rate brachytherapy Valencia applicator for larger skin lesions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Candela-Juan, C., E-mail: ccanjuan@gmail.com; Niatsetski, Y.; Laarse, R. van der

Purpose: The aims of this study were (i) to design a new high-dose-rate (HDR) brachytherapy applicator for treating surface lesions with planning target volumes larger than 3 cm in diameter and up to 5 cm in size, using the microSelectron-HDR or Flexitron afterloader (Elekta Brachytherapy) with a {sup 192}Ir source; (ii) to calculate by means of the Monte Carlo (MC) method the dose distribution for the new applicator when it is placed against a water phantom; and (iii) to validate experimentally the dose distributions in water. Methods: The PENELOPE2008 MC code was used to optimize dwell positions and dwell times.more » Next, the dose distribution in a water phantom and the leakage dose distribution around the applicator were calculated. Finally, MC data were validated experimentally for a {sup 192}Ir mHDR-v2 source by measuring (i) dose distributions with radiochromic EBT3 films (ISP); (ii) percentage depth–dose (PDD) curve with the parallel-plate ionization chamber Advanced Markus (PTW); and (iii) absolute dose rate with EBT3 films and the PinPoint T31016 (PTW) ionization chamber. Results: The new applicator is made of tungsten alloy (Densimet) and consists of a set of interchangeable collimators. Three catheters are used to allocate the source at prefixed dwell positions with preset weights to produce a homogenous dose distribution at the typical prescription depth of 3 mm in water. The same plan is used for all available collimators. PDD, absolute dose rate per unit of air kerma strength, and off-axis profiles in a cylindrical water phantom are reported. These data can be used for treatment planning. Leakage around the applicator was also scored. The dose distributions, PDD, and absolute dose rate calculated agree within experimental uncertainties with the doses measured: differences of MC data with chamber measurements are up to 0.8% and with radiochromic films are up to 3.5%. Conclusions: The new applicator and the dosimetric data provided here will be a valuable tool in clinical practice, making treatment of large skin lesions simpler, faster, and safer. Also the dose to surrounding healthy tissues is minimal.« less

10 CFR 35.690 - Training for use of remote afterloader units, teletherapy units, and gamma stereotactic...

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 1 2014-01-01 2014-01-01 false Training for use of remote afterloader units, teletherapy units, and gamma stereotactic radiosurgery units. 35.690 Section 35.690 Energy NUCLEAR REGULATORY...) Radiation physics and instrumentation; (B) Radiation protection; (C) Mathematics pertaining to the use and...

10 CFR 35.690 - Training for use of remote afterloader units, teletherapy units, and gamma stereotactic...

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 1 2011-01-01 2011-01-01 false Training for use of remote afterloader units, teletherapy units, and gamma stereotactic radiosurgery units. 35.690 Section 35.690 Energy NUCLEAR REGULATORY...) Radiation physics and instrumentation; (B) Radiation protection; (C) Mathematics pertaining to the use and...

10 CFR 35.690 - Training for use of remote afterloader units, teletherapy units, and gamma stereotactic...

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 1 2013-01-01 2013-01-01 false Training for use of remote afterloader units, teletherapy units, and gamma stereotactic radiosurgery units. 35.690 Section 35.690 Energy NUCLEAR REGULATORY...) Radiation physics and instrumentation; (B) Radiation protection; (C) Mathematics pertaining to the use and...

10 CFR 35.690 - Training for use of remote afterloader units, teletherapy units, and gamma stereotactic...

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 1 2012-01-01 2012-01-01 false Training for use of remote afterloader units, teletherapy units, and gamma stereotactic radiosurgery units. 35.690 Section 35.690 Energy NUCLEAR REGULATORY...) Radiation physics and instrumentation; (B) Radiation protection; (C) Mathematics pertaining to the use and...

Thoracic Epidural Anesthesia Reduces Right Ventricular Systolic Function With Maintained Ventricular-Pulmonary Coupling.

PubMed

Wink, Jeroen; de Wilde, Rob B P; Wouters, Patrick F; van Dorp, Eveline L A; Veering, Bernadette Th; Versteegh, Michel I M; Aarts, Leon P H J; Steendijk, Paul

2016-10-18

Blockade of cardiac sympathetic fibers by thoracic epidural anesthesia may affect right ventricular function and interfere with the coupling between right ventricular function and right ventricular afterload. Our main objectives were to study the effects of thoracic epidural anesthesia on right ventricular function and ventricular-pulmonary coupling. In 10 patients scheduled for lung resection, right ventricular function and its response to increased afterload, induced by temporary, unilateral clamping of the pulmonary artery, was tested before and after induction of thoracic epidural anesthesia using combined pressure-conductance catheters. Thoracic epidural anesthesia resulted in a significant decrease in right ventricular contractility (ΔESV 25 : +25.5 mL, P=0.0003; ΔEes: -0.025 mm Hg/mL, P=0.04). Stroke work, dP/dt MAX , and ejection fraction showed a similar decrease in systolic function (all P<0.05). A concomitant decrease in effective arterial elastance (ΔEa: -0.094 mm Hg/mL, P=0.004) yielded unchanged ventricular-pulmonary coupling. Cardiac output, systemic vascular resistance, and mean arterial blood pressure were unchanged. Clamping of the pulmonary artery significantly increased afterload (ΔEa: +0.226 mm Hg/mL, P<0.001). In response, right ventricular contractility increased (ΔESV 25 : -26.6 mL, P=0.0002; ΔEes: +0.034 mm Hg/mL, P=0.008), but ventricular-pulmonary coupling decreased (Δ(Ees/Ea) = -0.153, P<0.0001). None of the measured indices showed significant interactive effects, indicating that the effects of increased afterload were the same before and after thoracic epidural anesthesia. Thoracic epidural anesthesia impairs right ventricular contractility but does not inhibit the native positive inotropic response of the right ventricle to increased afterload. Right ventricular-pulmonary arterial coupling was decreased with increased afterload but not affected by the induction of thoracic epidural anesthesia. URL: http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2844. Unique identifier: NTR2844. © 2016 American Heart Association, Inc.

Results of treatment of choroidal malignant melanoma with high-dose-rate strontium-90 brachytherapy. A retrospective study of 46 patients treated between 1983 and 1995.

PubMed

Missotten, L; Dirven, W; Van der Schueren, A; Leys, A; De Meester, G; Van Limbergen, E

1998-03-01

We review the results of treatment of small to medium-sized choroidal malignant melanomas after high-dose-rate brachytherapy with a strontium-90 applicator. The applicator is positioned against the sclera using an afterloading technique. Brachytherapy is completed in a single session lasting 2-4 h with the patient under local anaesthesia. From September 1983 until March 1995, 46 eyes were treated in this way. Most tumours were 7-11 mm in diameter (range from 4.5-15 mm) with a mean height of approximately 3 mm (range from 1.5-7 mm). Follow-up ranged from 6 months to 12 years (mean 49 months). Thirty of the 46 eyes had at the final evaluation a nonevolutive scar (20 of these after a single application, the others with some additional treatment). In 13 eyes the tumours were in involution but their complete destruction was not yet certain, and 3 eyes were enucleated for local recurrence. Three patients developed systemic metastases. No radiogenic complications were noticed. Strontium-90 brachytherapy is a valuable and safe treatment technique for small to medium-sized choroidal malignant melanomas. In addition the use of a strontium-90 applicator is inexpensive thanks to this element's long half-life and the short application time.

A technical evaluation of the Nucletron FIRST system: conformance of a remote afterloading brachytherapy seed implantation system to manufacturer specifications and AAPM Task Group report recommendations.

PubMed

Rivard, Mark J; Evans, Dee-Ann Radford; Kay, Ian

2005-01-01

The Fully Integrated Real-time Seed Treatment (FIRST) system by Nucletron has been available in Europe since November 2001 and is being used more and more in Canada and the United States. Like the conventional transrectal ultrasound implant procedure, the FIRST system utilizes an ultrasound probe, needles, and brachytherapy seeds. However, this system is unique in that it (1) utilizes a low-dose-rate brachytherapy seed remote afterloader (the seedSelectron), (2) utilizes 3D image reconstruction acquired from electromechanically controlled, nonstepping rotation of the ultrasound probe, (3) integrates the control of a remote afterloader with electromechanical control of the ultrasound probe for integrating the clinical procedure into a single system, and (4) automates the transfer of planning information and seed delivery to improve quality assurance and radiation safety. This automated delivery system is specifically intended to address reproducibility and accuracy of seed positioning during implantation. The FIRST computer system includes two software environments: SPOT PRO and seedSelectron; both are used to facilitate treatment planning and brachytherapy seed implantation from beginning to completion of the entire procedure. In addition to these features, the system is reported to meet certain product specifications for seed delivery positioning accuracy and reproducibility, seed calibration accuracy and reliability, and brachytherapy dosimetry calculations. Consequently, a technical evaluation of the FIRST system was performed to determine adherence to manufacturer specifications and to the American Association of Physicists in Medicine (AAPM) Task Group Reports 43, 53, 56, 59, and 64 and recommendations of the American Brachytherapy Society (ABS). The United States Nuclear Regulatory Commission (NRC) has recently added Licensing Guidance for the seedSelectron system under 10 CFR 35.1000. Adherence to licensing guidance is made by referencing applicable AAPM Task Group recommendations. In general, results of this evaluation indicated that the system met its claimed specifications as well as the applicable recommendations outlined in the AAPM and ABS reports.

Dosimetric evaluation of internal shielding in a high dose rate skin applicator

PubMed Central

Granero, Domingo; Perez-Calatayud, Jose; Carmona, Vicente; Pujades, M Carmen; Ballester, Facundo

2011-01-01

Purpose The Valencia HDR applicators are accessories of the microSelectron HDR afterloading system (Nucletron) shaped as truncated cones. The base of the cone is either 2 or 3 cm diameter. They are intended to treat skin lesions, being the typical prescription depth 3 mm. In patients with eyelid lesions, an internal shielding is very useful to reduce the dose to the ocular globe. The purpose of this work was to evaluate the dose enhancement from potential backscatter and electron contamination due to the shielding. Material and methods Two methods were used: a) Monte Carlo simulation, performed with the GEANT4 code, 2 cm Valencia applicator was placed on the surface of a water phantom in which 2 mm lead slab was located at 3 mm depth; b) radiochromic EBT films, used to verify the Monte Carlo results, positioning the films at 1.5, 3, 5 and 7 mm depth, inside the phantom. Two irradiations, with and without the lead shielding slab, were carried out. Results The Monte Carlo results showed that due to the backscatter component from the lead, the dose level raised to about 200% with a depth range of 0.5 mm. Under the lead the dose level was enhanced to about 130% with a depth range of 1 mm. Two millimeters of lead reduce the dose under the slab with about 60%. These results agree with film measurements within uncertainties. Conclusions In conclusion, the use of 2 mm internal lead shielding in eyelid skin treatments with the Valencia applicators were evaluated using MC methods and EBT film dosimetry. The minimum bolus thickness that was needed above and below the shielding was 0.5 mm and 1 mm respectively, and the shielding reduced the absorbed dose delivered to the ocular globe by about 60%. PMID:27877198

Impact of tachycardia and sympathetic stimulation by cold pressor test on cardiac diastology and arterial function in elderly females.

PubMed

Johnson, Jonas; Håkansson, Felicia; Shahgaldi, Kambiz; Manouras, Aristomenis; Norman, Mikael; Sahlén, Anders

2013-04-01

Abnormal vascular-ventricular coupling has been suggested to contribute to heart failure with preserved ejection fraction in elderly females. Failure to increase stroke volume (SV) during exercise occurs in parallel with dynamic changes in arterial physiology leading to increased afterload. Such adverse vascular reactivity during stress may reflect either sympathoexcitation or be due to tachycardia. We hypothesized that afterload elevation induces SV failure by transiently attenuating left ventricular relaxation, a phenomenon described in animal research. The respective roles of tachycardia and sympathoexcitation were investigated in n = 28 elderly females (70 ± 4 yr) carrying permanent pacemakers. At rest, during atrial tachycardia pacing (ATP; 100 min(-1)) and during cold pressor test (hand immersed in ice water), we performed Doppler echocardiography (maximal untwist rate analyzed by speckle tracking imaging of rotational mechanics) and arterial tonometry (arterial stiffness estimated as augmentation index). Estimation of arterial compliance was based on an exponential relationship between arterial pressure and volume. We found that ATP produced central hypovolemia and a reduction in SV which was larger in patients with stiffer arteries (higher augmentation index). There was an associated adverse response of arterial compliance and vascular resistance during ATP and cold pressor test, causing an overall increase in afterload, but nonetheless enhanced maximal rate of untwist and no evidence of afterload-dependent failure of relaxation. In conclusion, tachycardia and cold provocation in elderly females produces greater vascular reactivity and SV failure in the presence of arterial stiffening, but SV failure does not arise secondary to afterload-dependent attenuation of relaxation.

10 CFR 35.604 - Surveys of patients and human research subjects treated with a remote afterloader unit.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 1 2011-01-01 2011-01-01 false Surveys of patients and human research subjects treated... Stereotactic Radiosurgery Units § 35.604 Surveys of patients and human research subjects treated with a remote... shall survey the patient or the human research subject and the remote afterloader unit with a portable...

10 CFR 35.604 - Surveys of patients and human research subjects treated with a remote afterloader unit.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 1 2012-01-01 2012-01-01 false Surveys of patients and human research subjects treated... Stereotactic Radiosurgery Units § 35.604 Surveys of patients and human research subjects treated with a remote... shall survey the patient or the human research subject and the remote afterloader unit with a portable...

10 CFR 35.604 - Surveys of patients and human research subjects treated with a remote afterloader unit.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 1 2010-01-01 2010-01-01 false Surveys of patients and human research subjects treated... Stereotactic Radiosurgery Units § 35.604 Surveys of patients and human research subjects treated with a remote... shall survey the patient or the human research subject and the remote afterloader unit with a portable...

10 CFR 35.604 - Surveys of patients and human research subjects treated with a remote afterloader unit.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 1 2014-01-01 2014-01-01 false Surveys of patients and human research subjects treated... Stereotactic Radiosurgery Units § 35.604 Surveys of patients and human research subjects treated with a remote... shall survey the patient or the human research subject and the remote afterloader unit with a portable...

10 CFR 35.604 - Surveys of patients and human research subjects treated with a remote afterloader unit.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 1 2013-01-01 2013-01-01 false Surveys of patients and human research subjects treated... Stereotactic Radiosurgery Units § 35.604 Surveys of patients and human research subjects treated with a remote... shall survey the patient or the human research subject and the remote afterloader unit with a portable...

Selective reduction of afterload in right heart assist therapy: a mock loop study†.

PubMed

Hsu, Po-Lin; Hatam, Nima; Unterkofler, Jan; Goetzenich, Andreas; McIntyre, Madeleine; Wong, Kai Chun; Egger, Christina; Schmitz-Rode, Thomas; Autschbach, Rüdiger; Steinseifer, Ulrich

2014-07-01

The treatment of right ventricular failure is closely linked to effects on pulmonary vascular resistance and thus the right ventricular (RV) afterload. Medical therapy includes afterload-decreasing drugs such as nitric oxide and prostacycline. However, current devices for mechanical unloading of the right ventricle aim at a decrease in preload increasing the pulmonary volume loading. In our concept study, we tested a minimally invasive right ventricular assist device (MIRVAD) that specifically reduces the afterload. The MIRVAD is supposed to be a foldable device for temporary transvascular placement in the pulmonary artery. We incorporated a MIRVAD prototype into a mock circulatory loop that can reproduce haemodynamic interaction between the pump and the physiological system. Pulmonary hypertension (PH), right heart failure (RHF) and MIRVAD-assisted cases were simulated. The key haemodynamic parameters for RV unloading were recorded. Mock loop simulation attested to a sufficient right ventricular unloading by serial application of a miniaturized impeller pump in the pulmonary artery. The afterload, represented by the pulmonary arterial root pressure, was recovered to the healthy range (32.62-10.93 mmHg) for the simulated PH case. In the simulated RHF case, the impaired pulmonary perfusion increased from 43.4 to 88.8% of the healthy level and the total ventricular work reduced from 0.381 to 0.197 J at a pump speed of 3500 rpm. At pump speeds higher than 3500 rpm, the pulmonary valve remains constantly open and the right ventricular configuration changes into a simple perfused hollow body. The feasibility of RV unloading by a selective decrease in RV afterload was proved in principle. By alternation of the pump speed, gradual reloading in sense of a myocardial training may be achieved. The results will be validated by future animal trials where the relationship between the level of support and pulmonary vascular pressure can be investigated in vivo. Further device design concerning foldable impeller leaflets will be carried out. At a final stage, the crimped version is supposed to reach a size below 1 cm to facilitate minimally invasive insertion. © The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Altered LV inotropic reserve and mechanoenergetics early in the development of heart failure.

PubMed

Prabhu, S D; Freeman, G L

2000-03-01

To test the hypothesis that alterations in left ventricular (LV) mechanoenergetics and the LV inotropic response to afterload manifest early in the evolution of heart failure, we examined six anesthetized dogs instrumented with LV micromanometers, piezoelectric crystals, and coronary sinus catheters before and after 24 h of rapid ventricular pacing (RVP). After autonomic blockade, the end-systolic pressure-volume relation (ESPVR), myocardial O(2) consumption (MVO(2)), and LV pressure-volume area (PVA) were defined at several different afterloads produced by graded infusions of phenylephrine. Short-term RVP resulted in reduced preload with proportionate reductions in stroke work and the maximum first derivative of LV pressure but with no significant reduction in baseline LV contractile state. In response to increased afterload, the baseline ESPVR shifted to the left with maintained end-systolic elastance (E(es)). In contrast, after short-term RVP, in response to comparable increases in afterload, the ESPVR displayed reduced E(es) (P < 0.05) and significantly less leftward shift compared with control (P < 0.05). Compared with the control MVO(2)-PVA relation, short-term RVP significantly increased the MVO(2) intercept (P < 0.05) with no change in slope. These results indicate that short-term RVP produces attenuation of afterload-induced enhancement of LV performance and increases energy consumption for nonmechanical processes with maintenance of contractile efficiency, suggesting that early in the development of tachycardia heart failure, there is blunting of length-dependent activation and increased O(2) requirements for excitation-contraction coupling, basal metabolism, or both. Rather than being adaptive mechanisms, these abnormalities may be primary defects involved in the progression of the heart failure phenotype.

Assessment of N-terminal prohormone B-type natriuretic peptide as a measure of vascular and ventricular function in pediatric pulmonary arterial hypertension

PubMed Central

Dunning, Jamie; Truong, Uyen; Ivy, D. Dunbar; Hunter, Kendall A.; Shandas, Robin

2015-01-01

Abstract Pulmonary arterial hypertension (PAH) is a progressive disease that puts excessive mechanical loads on the ventricle due to a gradual increase in pulmonary vascular impedance. We hypothesize that the increase in right ventricular (RV) afterload is reflected in the concentration of circulating biochemical markers of ventricular strain and stress (B-type natriuretic peptide [BNP] and N-terminal prohormone BNP [NT-proBNP]). We retrospectively analyzed right heart catheterization (RHC) and serum biochemical analysis data () for a pediatric PAH cohort with no sign of left ventricular dysfunction. Using RHC data, we computed an estimate of pulmonary vascular resistance (PVR), compliance, and ventricular-vascular coupling. We also compared how the early onset of interventricular decoupling (characterized as septal flattening) impacts serum NT-proBNP concentrations. Our data revealed correlated NT-proBNP expression with both the resistive and reactive components of RV afterload, an estimate of ventricular-vascular coupling, and a significant increase in biomarker expression in patients with a flattened interventricular septum. Furthermore, the strong correlation between PVR and NT-proBNP appears to break down under flat septum morphology. Over 80% of resistive RV afterload variance is reflected in serum NT-proBNP concentration in pediatric patients with PAH with no sign of left ventricular dysfunction. Reactive afterload appears to contribute to myocardial NT-proBNP release at advanced stages of PAH. Therefore, in mild-to-moderate PAH, resistive afterload is likely the greatest contributor to RV wall stress. These findings could also be used to estimate invasive RHC measurements from serum biochemical analysis, but more work is needed to improve correlations and overcome the issue of interventricular decoupling. PMID:26697173

Intrinsic increase in lymphangion muscle contractility in response to elevated afterload

PubMed Central

Scallan, Joshua P.; Wolpers, John H.; Muthuchamy, Mariappan; Gashev, Anatoliy A.; Zawieja, David C.

2012-01-01

Collecting lymphatic vessels share functional and biochemical characteristics with cardiac muscle; thus, we hypothesized that the lymphatic vessel pump would exhibit behavior analogous to homeometric regulation of the cardiac pump in its adaptation to elevated afterload, i.e., an increase in contractility. Single lymphangions containing two valves were isolated from the rat mesenteric microcirculation, cannulated, and pressurized for in vitro study. Pressures at either end of the lymphangion [input pressure (Pin), preload; output pressure (Pout), afterload] were set by a servo controller. Intralymphangion pressure (PL) was measured using a servo-null micropipette while internal diameter and valve positions were monitored using video methods. The responses to step- and ramp-wise increases in Pout (at low, constant Pin) were determined. PL and diameter data recorded during single contraction cycles were used to generate pressure-volume (P-V) relationships for the subsequent analysis of lymphangion pump behavior. Ramp-wise Pout elevation led to progressive vessel constriction, a rise in end-systolic diameter, and an increase in contraction frequency. Step-wise Pout elevation produced initial vessel distention followed by time-dependent declines in end-systolic and end-diastolic diameters. Significantly, a 30% leftward shift in the end-systolic P-V relationship accompanied an 84% increase in dP/dt after a step increase in Pout, consistent with an increase in contractility. Calculations of stroke work from the P-V loop area revealed that robust pumps produced net positive work to expel fluid throughout the entire afterload range, whereas weaker pumps exhibited progressively more negative work as gradual afterload elevation led to pump failure. We conclude that lymphatic muscle adapts to output pressure elevation with an intrinsic increase in contractility and that this compensatory mechanism facilitates the maintenance of lymph pump output in the face of edemagenic and/or gravitational loads. PMID:22886407

The feasibility study and characterization of a two-dimensional diode array in "magic phantom" for high dose rate brachytherapy quality assurance.

PubMed

Espinoza, A; Beeksma, B; Petasecca, M; Fuduli, I; Porumb, C; Cutajar, D; Corde, S; Jackson, M; Lerch, M L F; Rosenfeld, A B

2013-11-01

High dose rate (HDR) brachytherapy is a radiation treatment technique capable of delivering large dose rates to the tumor. Radiation is delivered using remote afterloaders to drive highly active sources (commonly (192)Ir with an air KERMA strength range between 20,000 and 40,000 U, where 1 U = 1 μGy m(2)/h in air) through applicators directly into the patient's prescribed region of treatment. Due to the obvious ramifications of incorrect treatment while using such an active source, it is essential that there are methods for quality assurance (QA) that can directly and accurately verify the treatment plan and the functionality of the remote afterloader. This paper describes the feasibility study of a QA system for HDR brachytherapy using a phantom based two-dimensional 11 × 11 epitaxial diode array, named "magic phantom." The HDR brachytherapy treatment plan is translated to the phantom with two rows of 10 (20 in total) HDR source flexible catheters, arranged above and below the diode array "magic plate" (MP). Four-dimensional source tracking in each catheter is based upon a developed fast iterative algorithm, utilizing the response of the diodes in close proximity to the (192)Ir source, sampled at 100 ms intervals by a fast data acquisition (DAQ) system. Using a (192)Ir source in a solid water phantom, the angular response of the developed epitaxial diodes utilized in the MP and also the variation of the MP response as a function of the source-to-detector distance (SDD) were investigated. These response data are then used by an iterative algorithm for source dwelling position determination. A measurement of the average transit speed between dwell positions was performed using the diodes and a fast DAQ. The angular response of the epitaxial diode showed a variation of 15% within 360°, with two flat regions above and below the detector face with less than 5% variation. For SDD distances of between 5 and 30 mm the relative response of the epitaxial diodes used in the MP is in good agreement (within 8%) with radial dose function measurements found within the TG-43 protocol, with SDD of up to 70 mm showing a 40% over response. A method for four-dimensional localization of the HDR source was developed, allowing the source dwell position to be derived within 0.50 mm of the expected position. An estimation of the average transit speed for varying step sizes was determined and was found to increase from (12.8 ± 0.3) up to (38.6 ± 0.4) cm/s for a step size of 2.5 and 50 mm, respectively. Our characterization of the designed QA "magic phantom" with MP in realistic HDR photon fields demonstrates the promising performance for real-time source position tracking in four dimensions and measurements of transit times. Further development of this system will allow a full suite for QA in HDR brachytherapy and analysis, and for future in vivo tracking.

A LabVIEW model incorporating an open-loop arterial impedance and a closed-loop circulatory system.

PubMed

Cole, R T; Lucas, C L; Cascio, W E; Johnson, T A

2005-11-01

While numerous computer models exist for the circulatory system, many are limited in scope, contain unwanted features or incorporate complex components specific to unique experimental situations. Our purpose was to develop a basic, yet multifaceted, computer model of the left heart and systemic circulation in LabVIEW having universal appeal without sacrificing crucial physiologic features. The program we developed employs Windkessel-type impedance models in several open-loop configurations and a closed-loop model coupling a lumped impedance and ventricular pressure source. The open-loop impedance models demonstrate afterload effects on arbitrary aortic pressure/flow inputs. The closed-loop model catalogs the major circulatory waveforms with changes in afterload, preload, and left heart properties. Our model provides an avenue for expanding the use of the ventricular equations through closed-loop coupling that includes a basic coronary circuit. Tested values used for the afterload components and the effects of afterload parameter changes on various waveforms are consistent with published data. We conclude that this model offers the ability to alter several circulatory factors and digitally catalog the most salient features of the pressure/flow waveforms employing a user-friendly platform. These features make the model a useful instructional tool for students as well as a simple experimental tool for cardiovascular research.

Quality control in interstitial brachytherapy of the breast using pulsed dose rate: treatment planning and dose delivery with an Ir-192 afterloading system.

PubMed

Mangold, C A; Rijnders, A; Georg, D; Van Limbergen, E; Pötter, R; Huyskens, D

2001-01-01

In the Radiotherapy Department of Leuven, about 20% of all breast cancer patients treated with breast conserving surgery and external radiotherapy receive an additional boost with pulsed dose rate (PDR) Ir-192 brachytherapy. An investigation was performed to assess the accuracy of the delivered PDR brachytherapy treatment. Secondly, the feasibility of in vivo measurements during PDR dose delivery was investigated. Two phantoms are manufactured to mimic a breast, one for thermoluminescent dosimetry (TLD) measurements, and one for dosimetry using radiochromic films. The TLD phantom allows measurements at 34 dose points in three planes including the basal dose points. The film phantom is designed in such a way that films can be positioned in a plane parallel and orthogonal to the needles. The dose distributions calculated with the TPS are in good agreement with both TLD and radiochromic film measurements (average deviations of point doses <+/-5%). However, close to the interface tissue-air the dose is overestimated by the TPS since it neglects the finite size of a breast and the associated lack of backscatter (average deviations of point doses -14%). Most deviations between measured and calculated doses, are in the order of magnitude of the uncertainty associated with the source strength specification, except for the point doses measured close to the skin. In vivo dosimetry during PDR brachytherapy treatment was found to be a valuable procedure to detect large errors, e.g. errors caused by an incorrect data transfer.

High- and low-dose-rate intraoperative radiotherapy for thoracic malignancies resected with close or positive margins.

PubMed

Fleming, Christopher; Rimner, Andreas; Cohen, Gil'ad N; Woo, Kaitlin M; Zhang, Zhigang; Rosenzweig, Kenneth E; Alektiar, Kaled M; Zelefsky, Michael J; Bains, Manjit S; Wu, Abraham J

2016-01-01

Local recurrence is a significant problem after surgical resection of thoracic tumors. As intraoperative radiotherapy (IORT) can deliver radiation directly to the threatened margin, we have used this therapy in an attempt to reduce local recurrence, using high-dose-rate (HDR) as well as low-dose-rate (LDR) techniques. We performed a retrospective review of patients undergoing LDR ((125)I) mesh placement or HDR ((192)Ir) afterloading therapy during lung tumor resection between 2001 and 2013 at our institution. Competing risks methods were used to estimate the cumulative incidence of local failure. We also assessed possible predictive factors of local failure. Fifty-nine procedures (41 LDR and 18 HDR) were performed on 58 patients. Median follow-up was 55.1 months. Cumulative incidence of local failure at 1, 2, and 3 years was 28.5%, 34.2%, and 34.2%, respectively. Median overall survival was 39.9 months. There was no significant difference in local failure according to margin status, HDR vs. LDR, use of adjuvant external beam radiotherapy, or metastatic vs. primary tumor. Two patients (3.4%) experienced Grade 3+ toxicities likely related to brachytherapy. Additionally, 7 patients experienced Grade 3+ postsurgical complications unlikely related to brachytherapy. IORT is associated with good local control after resection of thoracic tumors otherwise at very high risk for local recurrence. There is a low incidence of severe toxicity attributable to brachytherapy. HDR-IORT appears to have equivalent outcomes to LDR-IORT. HDR or LDR-IORT can, therefore, be considered in situations where the oncologic completeness of thoracic tumor resection is in doubt. Copyright © 2016 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

Race-related differences in left ventricular structural and functional remodeling in response to increased afterload: the Atherosclerosis Risk in Communities Study

PubMed Central

Fernandes-Silva, Miguel M; Shah, Amil M; Hegde, Sheila; Goncalves, Alexandra; Claggett, Brian; Cheng, Susan; Nadruz, Wilson; Kitzman, Dalane W.; Konety, Suma H.; Matsushita, Kunihiro; Mosley, Thomas; Lam, Carolyn S.P.; Borlaug, Barry A.; Solomon, Scott D

2016-01-01

Background Chronic increasing in arterial afterload may be an important trigger for left ventricular (LV) remodeling and dysfunction that lead to heart failure (HF). Racial differences in the predisposition to HF are well described, but the underlying mechanisms remain unclear. Objective We evaluated the racial differences in arterial elastance (Ea), which reflects the arterial afterload faced by the LV, and its associations with cardiac structure and function. We hypothesize that the LV in blacks displays heightened afterload sensitivity as compared to whites. Methods We studied 5727 community-based, elderly Atherosclerosis Risk in Community (ARIC) Study participants (22% black), who underwent echocardiography between 2011 and 2013. Results Blacks were younger (75 ± 5 vs 76 ± 5 years old), more frequently women (66 vs 57%), and had higher prevalence of obesity (46 vs 31%), hypertension (94 vs 80%), and diabetes mellitus (47 vs 34%) than whites. Adjusting for these baseline differences, Ea was higher among blacks (1.96 ± 0.01 vs 1.80 ± 0.01 mmHg/mL). In blacks, Ea was associated with greater LV remodeling (LV mass index, β = 3.21 ± 0.55 g/m2, p<0.001) and higher LV filling pressures (E/e′ ratio, β = 0.42 ± 0.11, p<0.001). These relationships were not observed in whites (LV mass, β = 0.16 ± 0.32 g/m2, p=0.61, p for interaction <0.001; E/e′ratio, β = −0.32 ± 0.06, p<0.001, p for interaction <0.001).. Conclusion These community-based data suggest that black Americans display heightened afterload sensitivity as a stimulus for LV structural and functional remodeling, which may contribute to their greater risk of HF, as compared to white Americans. PMID:28017356

Afterload mismatch in aortic and mitral valve disease: implications for surgical therapy.

PubMed

Ross, J

1985-04-01

In the management of patients with valvular heart disease, an understanding of the effects of altered loading conditions on the left ventricle is important in reaching a proper decision concerning the timing of corrective operation. In acquired valvular aortic stenosis, concentric hypertrophy generally maintains left ventricular chamber size and ejection fraction within normal limits, but in late stage disease function can deteriorate as preload reserve is lost and aortic stenosis progresses. In this setting, even when the ejection fraction is markedly reduced (less than 25%), it can improve to normal after aortic valve replacement, suggesting that afterload mismatch rather than irreversibly depressed myocardial contractility was responsible for left ventricular failure. Therefore, patients with severe aortic stenosis and symptoms should not be denied operation because of impaired cardiac function. In chronic severe aortic and mitral regurgitation, operation is generally recommended when symptoms are present, but whether to recommend operation to prevent irreversible myocardial damage in patients with few or no symptoms has remained controversial. In aortic regurgitation, left ventricular function generally improves postoperatively, even if it is moderately impaired preoperatively, indicating correction of afterload mismatch. Most such patients can be carefully followed by echocardiography. However, in some patients, severe left ventricular dysfunction fails to improve postoperatively. Therefore, when echocardiographic studies in the patient with severe aortic regurgitation show an ejection fraction of less than 40% (fractional shortening less than 25%) plus enlarging left ventricular end-diastolic diameter (approaching 38 mm/m2 body surface area) and end-systolic diameter (approaching 50 mm or 26 mm/m2), confirmation of these findings by cardiac catheterization and consideration of operation are advisable even in patients with minimal symptoms. In chronic mitral regurgitation, maintenance of a normal ejection fraction can mask depressed myocardial contractility. Pre- and postoperative studies in such patients have shown a poor clinical result after mitral valve replacement, associated with a sharp decrease in the ejection fraction after operation. This response appears to reflect unmasking of decreased myocardial contractility by mitral valve replacement, with ejection of the total stroke volume into the high impedance of the aorta (afterload mismatch produced by operation).(ABSTRACT TRUNCATED AT 400 WORDS)

Circulating miRNAs in Pediatric Pulmonary Hypertension Show Promise as Biomarkers of Vascular Function

PubMed Central

Sucharov, Carmen C.; Truong, Uyen; Dunning, Jamie; Ivy, Dunbar; Miyamoto, Shelley; Shandas, Robin

2017-01-01

Background/Objectives The objective of this study was to evaluate the utility of circulating miRNAs as biomarkers of vascular function in pediatric pulmonary hypertension. Method Fourteen pediatric pulmonary arterial hypertension patients underwent simultaneous right heart catheterization (RHC) and blood biochemical analysis. Univariate and stepwise multivariate linear regression was used to identify and correlate measures of reactive and resistive afterload with circulating miRNA levels. Furthermore, circulating miRNA candidates that classified patients according to a 20% decrease in resistive afterload in response to oxygen (O2) or inhaled nitric oxide (iNO) were identified using receiver-operating curves. Results Thirty-two circulating miRNAs correlated with the pulmonary vascular resistance index (PVRi), pulmonary arterial distensibility, and PVRi decrease in response to O2 and/or iNO. Multivariate models, combining the predictive capability of multiple promising miRNA candidates, revealed a good correlation with resistive (r = 0.97, P2−tailed < 0.0001) and reactive (r = 0.86, P2−tailed < 0.005) afterloads. Bland-Altman plots showed that 95% of the differences between multivariate models and RHC would fall within 0.13 (mmHg−min/L)m2 and 0.0085/mmHg for resistive and reactive afterloads, respectively. Circulating miR-663 proved to be a good classifier for vascular responsiveness to acute O2 and iNO challenges. Conclusion This study suggests that circulating miRNAs may be biomarkers to phenotype vascular function in pediatric PAH. PMID:28819545

Isovolumic relaxation period as an index of left ventricular relaxation under different afterload conditions--comparison with the time constant of left ventricular pressure decay in the dog.

PubMed

Ochi, H; Ikuma, I; Toda, H; Shimada, T; Morioka, S; Moriyama, K

1989-12-01

In order to determine whether isovolumic relaxation period (IRP) reflects left ventricular relaxation under different afterload conditions, 17 anesthetized, open chest dogs were studied, and the left ventricular pressure decay time constant (T) was calculated. In 12 dogs, angiotensin II and nitroprusside were administered, with the heart rate constant at 90 beats/min. Multiple linear regression analysis showed that the aortic dicrotic notch pressure (AoDNP) and T were major determinants of IRP, while left ventricular end-diastolic pressure was a minor determinant. Multiple linear regression analysis, correlating T with IRP and AoDNP, did not further improve the correlation coefficient compared with that between T and IRP. We concluded that correction of the IRP by AoDNP is not necessary to predict T from additional multiple linear regression. The effects of ascending aortic constriction or angiotensin II on IRP were examined in five dogs, after pretreatment with propranolol. Aortic constriction caused a significant decrease in IRP and T, while angiotensin II produced a significant increase in IRP and T. IRP was affected by the change of afterload. However, the IRP and T values were always altered in the same direction. These results demonstrate that IRP is substituted for T and it reflects left ventricular relaxation even in different afterload conditions. We conclude that IRP is a simple parameter easily used to evaluate left ventricular relaxation in clinical situations.

Survey of brachytherapy practice in the United States: a report of the Clinical Research Committee of the American Endocurietherapy Society.

PubMed

Nag, S; Owen, J B; Farnan, N; Pajak, T F; Martinez, A; Porter, A; Blasko, J; Harrison, L B

1995-01-01

To obtain reliable data on the extent of the brachytherapy practice in the United States by conducting a comprehensive survey of all facilities. The Clinical Research Committee of the AES surveyed all 1321 radiation oncology facilities identified in the Patterns of Care Study (PCS) of the American College of Radiology (ACR). Multiple mailings and follow-up were made to obtain a high response rate. Survey responders and nonresponders were compared using chi-square tests. Summary statistics were reported. Of the 1321 facilities, 1054 responded (80%). Hospital-based and larger facilities had a statistically significant higher rate of response. Brachytherapy was being performed at 819 facilities (the median number of procedures = 21-50). Two hundred and two facilities did no brachytherapy. The common isotopes used were 137Cs (705 facilities), 192Ir (585 facilities), 125I (236 facilities), and 131I (194 facilities). The common brachytherapy techniques used were intracavitary (751 facilities), interstitial (536 facilities), intraluminal (310 facilities), and plaques (148 facilities). Remote afterloaded brachytherapy was used at 205 centers as follows: high dose rate (HDR) (164), medium dose rate (MDR) (5), and low dose rate (LDR) (36). Computerized dosimetry was most commonly used (790 facilities), followed by Patterson-Parker (104 facilities) and Quimby (72 facilities). The common sites treated were cervix (701 facilities), endometrium (565 facilities), head and neck (354 facilities), and lung (344 facilities). Data regarding brachytherapy practice has been obtained from a large percentage (80%) of all facilities in the United States. The majority (78-81%) of radiation oncology facilities perform brachytherapy; however, its use is restricted to gynecological implants in many of these centers. The results from this survey will be used to develop a pattern of care study and data registry in brachytherapy.

Use of an iPad App to simulate pressure-volume loops and cardiovascular physiology.

PubMed

Leisman, Staci; Burkhoff, Daniel

2017-09-01

The purpose of this laboratory exercise is to model the changes in preload, afterload, and contractility on a simulated pressure-volume loop and to correlate those findings with common measurements of clinical cardiovascular physiology. Once students have modeled these changes on a healthy heart, the students are asked to look at a simulated case of cardiogenic shock. Effects on preload, contractility, and afterload are explored, as well as the hemodynamic effects of a number of student-suggested treatment strategies. Copyright © 2017 the American Physiological Society.

Review of clinical brachytherapy uncertainties: Analysis guidelines of GEC-ESTRO and the AAPM☆

PubMed Central

Kirisits, Christian; Rivard, Mark J.; Baltas, Dimos; Ballester, Facundo; De Brabandere, Marisol; van der Laarse, Rob; Niatsetski, Yury; Papagiannis, Panagiotis; Hellebust, Taran Paulsen; Perez-Calatayud, Jose; Tanderup, Kari; Venselaar, Jack L.M.; Siebert, Frank-André

2014-01-01

Background and purpose A substantial reduction of uncertainties in clinical brachytherapy should result in improved outcome in terms of increased local control and reduced side effects. Types of uncertainties have to be identified, grouped, and quantified. Methods A detailed literature review was performed to identify uncertainty components and their relative importance to the combined overall uncertainty. Results Very few components (e.g., source strength and afterloader timer) are independent of clinical disease site and location of administered dose. While the influence of medium on dose calculation can be substantial for low energy sources or non-deeply seated implants, the influence of medium is of minor importance for high-energy sources in the pelvic region. The level of uncertainties due to target, organ, applicator, and/or source movement in relation to the geometry assumed for treatment planning is highly dependent on fractionation and the level of image guided adaptive treatment. Most studies to date report the results in a manner that allows no direct reproduction and further comparison with other studies. Often, no distinction is made between variations, uncertainties, and errors or mistakes. The literature review facilitated the drafting of recommendations for uniform uncertainty reporting in clinical BT, which are also provided. The recommended comprehensive uncertainty investigations are key to obtain a general impression of uncertainties, and may help to identify elements of the brachytherapy treatment process that need improvement in terms of diminishing their dosimetric uncertainties. It is recommended to present data on the analyzed parameters (distance shifts, volume changes, source or applicator position, etc.), and also their influence on absorbed dose for clinically-relevant dose parameters (e.g., target parameters such as D90 or OAR doses). Publications on brachytherapy should include a statement of total dose uncertainty for the entire treatment course, taking into account the fractionation schedule and level of image guidance for adaptation. Conclusions This report on brachytherapy clinical uncertainties represents a working project developed by the Brachytherapy Physics Quality Assurances System (BRAPHYQS) subcommittee to the Physics Committee within GEC-ESTRO. Further, this report has been reviewed and approved by the American Association of Physicists in Medicine. PMID:24299968

MO-AB-BRA-03: Development of Novel Real Time in Vivo EPID Treatment Verification for Brachytherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fonseca, G; Podesta, M; Reniers, B

2016-06-15

Purpose: High Dose Rate (HDR) brachytherapy treatments are employed worldwide to treat a wide variety of cancers. However, in vivo dose verification remains a challenge with no commercial dosimetry system available to verify the treatment dose delivered to the patient. We propose a novel dosimetry system that couples an independent Monte Carlo (MC) simulation platform and an amorphous silicon Electronic Portal Imaging Device (EPID) to provide real time treatment verification. Methods: MC calculations predict the EPID response to the photon fluence emitted by the HDR source by simulating the patient, the source dwell positions and times, and treatment complexities suchmore » as tissue compositions/densities and different applicators. Simulated results are then compared against EPID measurements acquired with ∼0.14s time resolution which allows dose measurements for each dwell position. The EPID has been calibrated using an Ir-192 HDR source and experiments were performed using different phantoms, including tissue equivalent materials (PMMA, lung and bone). A source positioning accuracy of 0.2 mm, without including the afterloader uncertainty, was ensured using a robotic arm moving the source. Results: An EPID can acquire 3D Cartesian source positions and its response varies significantly due to differences in the material composition/density of the irradiated object, allowing detection of changes in patient geometry. The panel time resolution allows dose rate and dwell time measurements. Moreover, predicted EPID images obtained from clinical treatment plans provide anatomical information that can be related to the patient anatomy, mostly bone and air cavities, localizing the source inside of the patient using its anatomy as reference. Conclusion: Results obtained show the feasibility of the proposed dose verification system that is capable to verify all the brachytherapy treatment steps in real time providing data about treatment delivery quality and also applicator/structure motion during or between treatments.« less

Unique strain history during ejection in canine left ventricle.

PubMed

Douglas, A S; Rodriguez, E K; O'Dell, W; Hunter, W C

1991-05-01

Understanding the relationship between structure and function in the heart requires a knowledge of the connection between the local behavior of the myocardium (e.g., shortening) and the pumping action of the left ventricle. We asked the question, how do changes in preload and afterload affect the relationship between local myocardial deformation and ventricular volume? To study this, a set of small radiopaque beads was implanted in approximately 1 cm3 of the isolated canine heart left ventricular free wall. Using biplane cineradiography, we tracked the motion of these markers through various cardiac cycles (controlling pre- and afterload) using the relative motion of six markers to quantify the local three dimensional Lagrangian strain. Two different reference states (used to define the strains) were considered. First, we used the configuration of the heart at end diastole for that particular cardiac cycle to define the individual strains (which gave the local "shortening fraction") and the ejection fraction. Second, we used a single reference state for all cardiac cycles i.e., the end-diastolic state at maximum volume, to define absolute strains (which gave local fractional length) and the volume fraction. The individual strain versus ejection fraction trajectories were dependent on preload and afterload. For any one heart, however, each component of absolute strain was more tightly correlated to volume fraction. Around each linear regression, the individual measurements of absolute strain scattered with standard errors that averaged less than 7% of their range. Thus the canine hearts examined had a preferred kinematic (shape) history during ejection, different from the kinematics of filling and independent or pre-or afterload and of stroke volume.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schnapauff, Dirk, E-mail: dirk.schnapauff@charite.de; Denecke, Timm; Grieser, Christian

Purpose: This study was designed to investigate the clinical outcome of patients with irresectable, intrahepatic cholangiocarcinoma (IHC) treated with computed tomography (CT)-guided HDR-brachytherapy (CT-HDRBT) for local tumor ablation.MethodFifteen consecutive patients with histologically proven cholangiocarcinoma were selected for this retrospective study. Patients were treated by high-dose-rate internal brachytherapy (HDRBT) using an Iridium-192 source in afterloading technique through CT-guided percutaneous placed catheters. A total of 27 brachytherapy treatments were performed in these patients between 2006 and 2009. Median tumor enclosing target dose was 20 Gy, and mean target volume of the radiated tumors was 131 ({+-} 90) ml (range, 10-257 ml). Follow-upmore » consisted of clinical visits and magnetic resonance imaging of the liver every third month. Statistical evaluation included survival analysis using the Kaplan-Meier method. Results: After a median follow-up of 18 (range, 1-27) months after local ablation, 6 of the 15 patients are still alive; 4 of them did not get further chemotherapy and are regarded as disease-free. The reached median local tumor control was 10 months; median local tumor control, including repetitive local ablation, was 11 months. Median survival after local ablation was 14 months and after primary diagnosis 21 months. Conclusion: In view of current clinical data on the clinical outcome of cholangiocarcinoma, locally ablative treatment with CT-HDRBT represents a promising and safe technique for patients who are not eligible for tumor resection.« less

Human factors evaluation of remote afterloading brachytherapy. Volume 2, Function and task analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Callan, J.R.; Gwynne, J.W. III; Kelly, T.T.

1995-05-01

A human factors project on the use of nuclear by-product material to treat cancer using remotely operated afterloaders was undertaken by the Nuclear Regulatory Commission. The purpose of the project was to identify factors that contribute to human error in the system for remote afterloading brachytherapy (RAB). This report documents the findings from the first phase of the project, which involved an extensive function and task analysis of RAB. This analysis identified the functions and tasks in RAB, made preliminary estimates of the likelihood of human error in each task, and determined the skills needed to perform each RAB task.more » The findings of the function and task analysis served as the foundation for the remainder of the project, which evaluated four major aspects of the RAB system linked to human error: human-system interfaces; procedures and practices; training and qualifications of RAB staff; and organizational practices and policies. At its completion, the project identified and prioritized areas for recommended NRC and industry attention based on all of the evaluations and analyses.« less

Commissioning a CT-compatible LDR tandem and ovoid applicator using Monte Carlo calculation and 3D dosimetry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Adamson, Justus; Newton, Joseph; Yang Yun

2012-07-15

Purpose: To determine the geometric and dose attenuation characteristics of a new commercially available CT-compatible LDR tandem and ovoid (T and O) applicator using Monte Carlo calculation and 3D dosimetry. Methods: For geometric characterization, we quantified physical dimensions and investigated a systematic difference found to exist between nominal ovoid angle and the angle at which the afterloading buckets fall within the ovoid. For dosimetric characterization, we determined source attenuation through asymmetric gold shielding in the buckets using Monte Carlo simulations and 3D dosimetry. Monte Carlo code MCNP5 was used to simulate 1.5 Multiplication-Sign 10{sup 9} photon histories from a {supmore » 137}Cs source placed in the bucket to achieve statistical uncertainty of 1% at a 6 cm distance. For 3D dosimetry, the distribution about an unshielded source was first measured to evaluate the system for {sup 137}Cs, after which the distribution was measured about sources placed in each bucket. Cylindrical PRESAGE{sup Registered-Sign} dosimeters (9.5 cm diameter, 9.2 cm height) with a central channel bored for source placement were supplied by Heuris Inc. The dosimeters were scanned with the Duke Large field of view Optical CT-Scanner before and after delivering a nominal dose at 1 cm of 5-8 Gy. During irradiation the dosimeter was placed in a water phantom to provide backscatter. Optical CT scan time lasted 15 min during which 720 projections were acquired at 0.5 Degree-Sign increments, and a 3D distribution was reconstructed with a (0.05 cm){sup 3} isotropic voxel size. The distributions about the buckets were used to calculate a 3D distribution of transmission rate through the bucket, which was applied to a clinical CT-based T and O implant plan. Results: The systematic difference in bucket angle relative to the nominal ovoid angle (105 Degree-Sign ) was 3.1 Degree-Sign -4.7 Degree-Sign . A systematic difference in bucket angle of 1 Degree-Sign , 5 Degree-Sign , and 10 Degree-Sign caused a 1%{+-} 0.1%, 1.7%{+-} 0.4%, and 2.6%{+-} 0.7% increase in rectal dose, respectively, with smaller effect to dose to Point A, bladder, sigmoid, and bowel. For 3D dosimetry, 90.6% of voxels had a 3D {gamma}-index (criteria = 0.1 cm, 3% local signal) below 1.0 when comparing measured and expected dose about the unshielded source. Dose transmission through the gold shielding at a radial distance of 1 cm was 85.9%{+-} 0.2%, 83.4%{+-} 0.7%, and 82.5%{+-} 2.2% for Monte Carlo, and measurement for left and right buckets, respectively. Dose transmission was lowest at oblique angles from the bucket with a minimum of 56.7%{+-} 0.8%, 65.6%{+-} 1.7%, and 57.5%{+-} 1.6%, respectively. For a clinical T and O plan, attenuation from the buckets leads to a decrease in average Point A dose of {approx}3.2% and decrease in D{sub 2cc} to bladder, rectum, bowel, and sigmoid of 5%, 18%, 6%, and 12%, respectively. Conclusions: Differences between dummy and afterloading bucket position in the ovoids is minor compared to effects from asymmetric ovoid shielding, for which rectal dose is most affected. 3D dosimetry can fulfill a novel role in verifying Monte Carlo calculations of complex dose distributions as are common about brachytherapy sources and applicators.« less

Commissioning a CT-compatible LDR tandem and ovoid applicator using Monte Carlo calculation and 3D dosimetry.

PubMed

Adamson, Justus; Newton, Joseph; Yang, Yun; Steffey, Beverly; Cai, Jing; Adamovics, John; Oldham, Mark; Chino, Junzo; Craciunescu, Oana

2012-07-01

To determine the geometric and dose attenuation characteristics of a new commercially available CT-compatible LDR tandem and ovoid (T&O) applicator using Monte Carlo calculation and 3D dosimetry. For geometric characterization, we quantified physical dimensions and investigated a systematic difference found to exist between nominal ovoid angle and the angle at which the afterloading buckets fall within the ovoid. For dosimetric characterization, we determined source attenuation through asymmetric gold shielding in the buckets using Monte Carlo simulations and 3D dosimetry. Monte Carlo code MCNP5 was used to simulate 1.5 × 10(9) photon histories from a (137)Cs source placed in the bucket to achieve statistical uncertainty of 1% at a 6 cm distance. For 3D dosimetry, the distribution about an unshielded source was first measured to evaluate the system for (137)Cs, after which the distribution was measured about sources placed in each bucket. Cylindrical PRESAGE(®) dosimeters (9.5 cm diameter, 9.2 cm height) with a central channel bored for source placement were supplied by Heuris Inc. The dosimeters were scanned with the Duke Large field of view Optical CT-Scanner before and after delivering a nominal dose at 1 cm of 5-8 Gy. During irradiation the dosimeter was placed in a water phantom to provide backscatter. Optical CT scan time lasted 15 min during which 720 projections were acquired at 0.5° increments, and a 3D distribution was reconstructed with a (0.05 cm)(3) isotropic voxel size. The distributions about the buckets were used to calculate a 3D distribution of transmission rate through the bucket, which was applied to a clinical CT-based T&O implant plan. The systematic difference in bucket angle relative to the nominal ovoid angle (105°) was 3.1°-4.7°. A systematic difference in bucket angle of 1°, 5°, and 10° caused a 1% ± 0.1%, 1.7% ± 0.4%, and 2.6% ± 0.7% increase in rectal dose, respectively, with smaller effect to dose to Point A, bladder, sigmoid, and bowel. For 3D dosimetry, 90.6% of voxels had a 3D γ-index (criteria = 0.1 cm, 3% local signal) below 1.0 when comparing measured and expected dose about the unshielded source. Dose transmission through the gold shielding at a radial distance of 1 cm was 85.9% ± 0.2%, 83.4% ± 0.7%, and 82.5% ± 2.2% for Monte Carlo, and measurement for left and right buckets, respectively. Dose transmission was lowest at oblique angles from the bucket with a minimum of 56.7% ± 0.8%, 65.6% ± 1.7%, and 57.5% ± 1.6%, respectively. For a clinical T&O plan, attenuation from the buckets leads to a decrease in average Point A dose of ∼3.2% and decrease in D(2cc) to bladder, rectum, bowel, and sigmoid of 5%, 18%, 6%, and 12%, respectively. Differences between dummy and afterloading bucket position in the ovoids is minor compared to effects from asymmetric ovoid shielding, for which rectal dose is most affected. 3D dosimetry can fulfill a novel role in verifying Monte Carlo calculations of complex dose distributions as are common about brachytherapy sources and applicators.

Impact of the vaginal applicator and dummy pellets on the dosimetry parameters of Cs-137 brachytherapy source.

PubMed

Sina, Sedigheh; Faghihi, Reza; Meigooni, Ali S; Mehdizadeh, Simin; Mosleh Shirazi, M Amin; Zehtabian, Mehdi

2011-05-19

In this study, dose rate distribution around a spherical 137Cs pellet source, from a low-dose-rate (LDR) Selectron remote afterloading system used in gynecological brachytherapy, has been determined using experimental and Monte Carlo simulation techniques. Monte Carlo simulations were performed using MCNP4C code, for a single pellet source in water medium and Plexiglas, and measurements were performed in Plexiglas phantom material using LiF TLD chips. Absolute dose rate distribution and the dosimetric parameters, such as dose rate constant, radial dose functions, and anisotropy functions, were obtained for a single pellet source. In order to investigate the effect of the applicator and surrounding pellets on dosimetric parameters of the source, the simulations were repeated for six different arrangements with a single active source and five non-active pellets inside central metallic tubing of a vaginal cylindrical applicator. In commercial treatment planning systems (TPS), the attenuation effects of the applicator and inactive spacers on total dose are neglected. The results indicate that this effect could lead to overestimation of the calculated F(r,θ), by up to 7% along the longitudinal axis of the applicator, especially beyond the applicator tip. According to the results obtained in this study, in a real situation in treatment of patients using cylindrical vaginal applicator and using several active pellets, there will be a large discrepancy between the result of superposition and Monte Carlo simulations.

In situ cardiac perfusion reveals interspecific variation of intraventricular flow separation in reptiles.

PubMed

Joyce, William; Axelsson, Michael; Altimiras, Jordi; Wang, Tobias

2016-07-15

The ventricles of non-crocodilian reptiles are incompletely divided and provide an opportunity for mixing of oxygen-poor blood and oxygen-rich blood (intracardiac shunting). However, both cardiac morphology and in vivo shunting patterns exhibit considerable interspecific variation within reptiles. In the present study, we develop an in situ double-perfused heart approach to characterise the propensity and capacity for shunting in five reptile species: the turtle Trachemys scripta, the rock python Python sebae, the yellow anaconda Eunectes notaeus, the varanid lizard Varanus exanthematicus and the bearded dragon Pogona vitticeps To simulate changes in vascular bed resistance, pulmonary and systemic afterloads were independently manipulated and changes in blood flow distribution amongst the central outflow tracts were monitored. As previously demonstrated in Burmese pythons, rock pythons and varanid lizards exhibited pronounced intraventricular flow separation. As pulmonary or systemic afterload was raised, flow in the respective circulation decreased. However, flow in the other circulation, where afterload was constant, remained stable. This correlates with the convergent evolution of intraventricular pressure separation and the large intraventricular muscular ridge, which compartmentalises the ventricle, in these species. Conversely, in the three other species, the pulmonary and systemic flows were strongly mutually dependent, such that the decrease in pulmonary flow in response to elevated pulmonary afterload resulted in redistribution of perfusate to the systemic circuit (and vice versa). Thus, in these species, the muscular ridge appeared labile and blood could readily transverse the intraventricular cava. We conclude that relatively minor structural differences between non-crocodilian reptiles result in the fundamental changes in cardiac function. Further, our study emphasises that functionally similar intracardiac flow separation evolved independently in lizards (varanids) and snakes (pythons) from an ancestor endowed with the capacity for large intracardiac shunts. © 2016. Published by The Company of Biologists Ltd.

Cardio-ankle vascular index relates to left ventricular ejection fraction in patients with heart failure. A retrospective study.

PubMed

Zhang, Chengmin; Ohira, Masahiro; Iizuka, Takuo; Mikamo, Hiroshi; Nakagami, Takahiro; Suzuki, Masayo; Hirano, Keiichi; Takahashi, Mao; Shimizu, Kazuhiro; Sugiyama, Yuko; Yamaguchi, Takashi; Kawana, Hidetoshi; Endo, Kei; Saiki, Atsuhito; Oyama, Tomokazu; Kurosu, Takumi; Tomaru, Takanobu; Wang, Hongyu; Noike, Hirofumi; Shirai, Kohji

2013-01-01

The cardio-ankle vascular index (CAVI) has been proposed as a new noninvasive marker of arterial stiffness independent of blood pressure. Arterial stiffness is closely related to afterload, and elevated afterload aggravates heart failure. We hypothesized that CAVI is a potential marker of afterload in patients with heart failure. Thirty patients who were admitted because of acute heart failure were identified retrospectively from a review of clinical records. Plasma brain natriuretic peptide (BNP) levels, CAVI, cardiothoracic ratio (CTR), and echocardiographic parameters obtained during acute and chronic phases of heart failure were analyzed. Left ventricular ejection fraction (LVEF) increased significantly and CTR, BNP and CAVI decreased significantly after treatment of heart failure. A significant negative correlation was observed between the change in CAVI and change in LVEF in all subjects (r = -0.3272, P < 0.05). To examine the relationship between CAVI and LVEF, we divided the patients into two subgroups (∆CAVI < -0.5; CAVI decrease group, ∆CAVI ≥ -0.5; CAVI non-decrease group). CAVI was significantly improved after heart failure treatment only in the CAVI decrease group. LVEF decreased significantly in both groups, but the P value was smaller in the CAVI decrease group than in the CAVI non-decrease group. The change in LVEF correlated significantly with the change in CAVI in the CAVI decrease group (r = -0.4201, P < 0.05), whereas no significant correlation was found in the CAVI non-decrease group. CAVI correlates inversely with LVEF after heart failure treatment. Our results suggest that CAVI might partially reflect the afterload in patients with heart failure.

Biological equivalence between LDR and PDR in cervical cancer: multifactor analysis using the linear-quadratic model.

PubMed

Couto, José Guilherme; Bravo, Isabel; Pirraco, Rui

2011-09-01

The purpose of this work was the biological comparison between Low Dose Rate (LDR) and Pulsed Dose Rate (PDR) in cervical cancer regarding the discontinuation of the afterloading system used for the LDR treatments at our Institution since December 2009. In the first phase we studied the influence of the pulse dose and the pulse time in the biological equivalence between LDR and PDR treatments using the Linear Quadratic Model (LQM). In the second phase, the equivalent dose in 2 Gy/fraction (EQD(2)) for the tumor, rectum and bladder in treatments performed with both techniques was evaluated and statistically compared. All evaluated patients had stage IIB cervical cancer and were treated with External Beam Radiotherapy (EBRT) plus two Brachytherapy (BT) applications. Data were collected from 48 patients (26 patients treated with LDR and 22 patients with PDR). In the analyses of the influence of PDR parameters in the biological equivalence between LDR and PDR treatments (Phase 1), it was calculated that if the pulse dose in PDR was kept equal to the LDR dose rate, a small the-rapeutic loss was expected. If the pulse dose was decreased, the therapeutic window became larger, but a correction in the prescribed dose was necessary. In PDR schemes with 1 hour interval between pulses, the pulse time did not influence significantly the equivalent dose. In the comparison between the groups treated with LDR and PDR (Phase 2) we concluded that they were not equivalent, because in the PDR group the total EQD(2) for the tumor, rectum and bladder was smaller than in the LDR group; the LQM estimated that a correction in the prescribed dose of 6% to 10% was ne-cessary to avoid therapeutic loss. A correction in the prescribed dose was necessary; this correction should be achieved by calculating the PDR dose equivalent to the desired LDR total dose.

Biological equivalence between LDR and PDR in cervical cancer: multifactor analysis using the linear-quadratic model

PubMed Central

Bravo, Isabel; Pirraco, Rui

2011-01-01

Purpose The purpose of this work was the biological comparison between Low Dose Rate (LDR) and Pulsed Dose Rate (PDR) in cervical cancer regarding the discontinuation of the afterloading system used for the LDR treatments at our Institution since December 2009. Material and methods In the first phase we studied the influence of the pulse dose and the pulse time in the biological equivalence between LDR and PDR treatments using the Linear Quadratic Model (LQM). In the second phase, the equivalent dose in 2 Gy/fraction (EQD2) for the tumor, rectum and bladder in treatments performed with both techniques was evaluated and statistically compared. All evaluated patients had stage IIB cervical cancer and were treated with External Beam Radiotherapy (EBRT) plus two Brachytherapy (BT) applications. Data were collected from 48 patients (26 patients treated with LDR and 22 patients with PDR). Results In the analyses of the influence of PDR parameters in the biological equivalence between LDR and PDR treatments (Phase 1), it was calculated that if the pulse dose in PDR was kept equal to the LDR dose rate, a small the-rapeutic loss was expected. If the pulse dose was decreased, the therapeutic window became larger, but a correction in the prescribed dose was necessary. In PDR schemes with 1 hour interval between pulses, the pulse time did not influence significantly the equivalent dose. In the comparison between the groups treated with LDR and PDR (Phase 2) we concluded that they were not equivalent, because in the PDR group the total EQD2 for the tumor, rectum and bladder was smaller than in the LDR group; the LQM estimated that a correction in the prescribed dose of 6% to 10% was ne-cessary to avoid therapeutic loss. Conclusions A correction in the prescribed dose was necessary; this correction should be achieved by calculating the PDR dose equivalent to the desired LDR total dose. PMID:23346123

Intracavitary applicator in relation to complications of pelvic radiation: the Ernst system

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rotman, M.; John, M.J.; Roussis, K.

Case studies were reviewed for 100 consecutive patients with carcinoma of the cervix, Stages I to III, who were treated prior to 1968 at a large municipal hospital in New York City. Treatments consisted of orthovoltage therapy prior to or following intracavitary radium. A 250 kV x-ray unit delivered a 3000 rad tumor dose in 3 weeks through four oblique fields. Intracavitary radium delivered 6000 to 7200 mg hr using the Ernst applicator. The 9% incidence of fistulae was 4-fold higher than that found in subsequent years using /sup 60/Co teletherapy and the afterloading Fletcher-Suit applicator. A review of themore » dosimetry relating to the use of the Ernst applicator demonstrates inherent structural characteristics which lend themselves to such complications. Where less than an ideal application is possible, this rigid applicator compacts itself in accordion-like fashion, producing a so-called short-system. Coupled with a reduced source to applicator-surface distance, such applications result in unacceptable dose anisotropy and excessive radiation of critical structures where a predetermined dose is to be delivered to anatomic Point A. Information gleaned from this study can be extrapolated to other rigid unprotected short-surface distance intra-vaginal applicators that have proliferated in recent years.« less

Superiority of desflurane over sevoflurane and isoflurane in the presence of pressure-overload right ventricle hypertrophy in rats.

PubMed

Blaudszun, Grégoire; Morel, Denis R

2012-11-01

Pulmonary hypertension and associated pressure-overload right ventricular (RV) hypertrophy represent a tremendous challenge for the anesthesiologist, as optimal perioperative management is mandatory. However, the ideal anesthetic agent remains unknown because scientific evidence is lacking. Twenty-eight rats were randomly assigned to a control or a monocrotaline group (60 mg kg). Four weeks later, animals were anesthetized, instrumented with a RV conductance catheter, and underwent well-controlled dose-responses to isoflurane, desflurane, and sevoflurane inhalation (minimum alveolar concentrations 0.5, 1.0, 1.5). Compared with controls, rats injected with monocrotaline presented with RV hypertrophy, increased afterload, and contractility, without change in cardiac output. The ratio of pressures in the right over the left circulation increased. The halogenated volatiles differently altered hemodynamics. Sevoflurane reduced RV contractility (more than 50%) and the right over left pressures ratio increased (from 0.41 ± 0.08 [SD] to 0.82 ± 0.14; P < 0.0001) secondary to profound concomitant systemic vasodilation, demonstrating a critical pressure gradient between right and left circulations. Despite significantly higher RV systolic pressures and afterload, desflurane decreased RV contractility much less (<10%; P < 0.0001 vs. sevoflurane) and maintained the right over left pressures ratio at more favorable values (0.47 ± 0.07; P < 0.0001 vs. sevoflurane). Isoflurane presented intermediate effects. In the presence of pressure-overload RV hypertrophy, hemodynamics are better preserved under desflurane inhalation, whereas sevoflurane-and to a lesser extent isoflurane-cause large discrepancies on the left and right circulations, raising the right over left pressures ratio to critical levels despite a conserved cardiac output.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sen, A

Purpose: Accuboost treatment planning uses dwell times from a nomogram designed with Monte Carlo calculations for round and D-shaped applicators. A quick dose calculation method has been developed for verification of the HDR Brachytherapy dose as a second check. Methods: Accuboost breast treatment uses several round and D-shaped applicators to be used non-invasively with an Ir-192 source from a HDR Brachytherapy afterloader after the breast is compressed in a mammographic unit for localization. The breast thickness, source activity, the prescription dose and the applicator size are entered into a nomogram spreadsheet which gives the dwell times to be manually enteredmore » into the delivery computer. Approximating the HDR Ir-192 as a point source, and knowing the geometry of the round and D-applicators, the distances from the source positions to the midpoint of the central plane are calculated. Using the exposure constant of Ir-192 and medium as human tissue, the dose at a point is calculated as: D(cGy) = 1.254 × A × t/R2, where A is the activity in Ci, t is the dwell time in sec and R is the distance in cm. The dose from each dwell position is added to get the total dose. Results: Each fraction is delivered in two compressions: cranio-caudally and medial-laterally. A typical APBI treatment in 10 fractions requires 20 compressions. For a patient treated with D45 applicators and an average of 5.22 cm thickness, this calculation was 1.63 % higher than the prescription. For another patient using D53 applicators in the CC direction and 7 cm SDO applicators in the ML direction, this calculation was 1.31 % lower than the prescription. Conclusion: This is a simple and quick method to double check the dose on the central plane for Accuboost treatment.« less

SU-E-T-413: Examining Acquisition Rate for Using MatriXX Ion Chamber Array to Measure HDR Brachytherapy Treatments

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wagar, M; Bhagwat, M; O’Farrell, D

2015-06-15

Purpose: There are unique obstacles to implementing the MatriXX ionchamber array as a QA tool in Brachytherapy given that the device is designed for use in the MV energy range. One of the challenges we investigate is the affect of acquisition rates on dose measurement accuracy for HDR treatment plans. Methods: A treatment plan was optimized in Oncentra Brachy TPS to deliver a planar dose to a 5×5cm region at 10mm depth. The applicator was affixed to the surface of the MatriXX array. The plan was delivered multiple times using a Nucleatron HDR afterloader with a 2.9Ci Ir192 source. Formore » each measurement the sampling rate of the MatriXX movie mode was varied (30ms and 500ms). This experiment was repeated with identical parameters, following a source exchange, with an 11.2Ci Ir192 source. Finally, a single snap measurement was acquired. Analysis was preformed to evaluate the fidelity of the dose delivery for each iteration of the experiment. Evaluation was based on the comparison between the measured and TPS predicted dose. Results: Higher sample rates induce a greater discrepancy between the predicted and measured dose. Delivering the plan using a lower activity source also produced greater discrepancy in the measurement due to the increased delivery time. Analyzing the single snap measurement showed little difference from the 500ms integral dose measurement. Conclusion: The advantage of using movie mode for HDR treatment delivery QA is the ability for real time source tracking in addition to dose measurement. Our analysis indicates that 500ms is an optimal frame rate.« less

Single dose irradiation response of pig skin: a comparison of brachytherapy using a single, high dose rate iridium-192 stepping source with 200 kV X-rays.

PubMed

Hamm, P C; Bakker, E J; van den Berg, A P; van den Aardweg, G J; Visser, A G; Levendag, P C

2000-07-01

An experimental brachytherapy model has been developed to study acute and late normal tissue reactions as a tool to examine the effects of clinically relevant multifractionation schedules. Pig skin was used as a model since its morphology, structure, cell kinetics and radiation-induced responses are similar to human skin. Brachytherapy was performed using a microSelectron high dose rate (HDR) afterloading machine with a single stepping source and a custom-made template. In this study the acute epidermal reactions of erythema and moist desquamation and the late dermal reactions of dusky mauve erythema and necrosis were evaluated after single doses of irradiation over a follow-up period of 16 weeks. The major aims of this work were: (a) to compare the effects of iridium-192 (192Ir) irradiation with effects after X-irradiation; (b) to compare the skin reactions in Yorkshire and Large White pigs; and (c) to standardize the methodology. For 192Ir irradiation with 100% isodose at the skin surface, the 95% isodose was estimated at the basal membrane, while the 80% isodose covered the dermal fat layers. After HDR 192Ir irradiation of Yorkshire pig skin the ED50 values (95% isodose) for moderate/severe erythema and moist desquamation were 24.8 Gy and 31.9 Gy, respectively. The associated mean latent period (+/- SD) was 39 +/- 7 days for both skin reactions. Late skin responses of dusky mauve erythema and dermal necrosis were characterized by ED50 values (80% isodose) of 16.3 Gy and 19.5 Gy, with latent periods of 58 +/- 7 days and 76 +/- 12 days, respectively. After X-irradiation, the incidence of the various skin reactions and their latent periods were similar. Acute and late reactions were well separated in time. The occurrence of skin reactions and the incidence of effects were comparable in Yorkshire and Large White pigs for both X-irradiation and HDR 192Ir brachytherapy. This pig skin model is feasible for future studies on clinically relevant multifractionation schedules in a brachytherapy setting.

Relationships of left ventricular strain and strain rate to wall stress and their afterload dependency.

PubMed

Murai, Daisuke; Yamada, Satoshi; Hayashi, Taichi; Okada, Kazunori; Nishino, Hisao; Nakabachi, Masahiro; Yokoyama, Shinobu; Abe, Ayumu; Ichikawa, Ayako; Ono, Kota; Kaga, Sanae; Iwano, Hiroyuki; Mikami, Taisei; Tsutsui, Hiroyuki

2017-05-01

Whether and how left ventricular (LV) strain and strain rate correlate with wall stress is not known. Furthermore, it is not determined whether strain or strain rate is less dependent on the afterload. In 41 healthy young adults, LV global peak strain and systolic peak strain rate in the longitudinal direction (LS and LSR, respectively) and circumferential direction (CS and CSR, respectively) were measured layer-specifically using speckle tracking echocardiography (STE) before and during a handgrip exercise. Among all the points before and during the exercise, all the STE parameters significantly correlated linearly with wall stress (LS: r = -0.53, p < 0.01, LSR: r = -0.28, p < 0.05, CS in the inner layer: r = -0.72, p < 0.01, CSR in the inner layer: r = -0.47, p < 0.01). Strain more strongly correlated with wall stress than strain rate (r = -0.53 for LS vs. r = -0.28 for LSR, p < 0.05; r = -0.72 for CS vs. r = -0.47 for CSR in the inner layer, p < 0.05), whereas the interobserver variability was similar between strain and strain rate (longitudinal 6.2 vs. 5.2 %, inner circumferential 4.8 vs. 4.7 %, mid-circumferential 7.9 vs. 6.9 %, outer circumferential 10.4 vs. 9.7 %), indicating that the differences in correlation coefficients reflect those in afterload dependency. It was thus concluded that LV strain and strain rate linearly and inversely correlated with wall stress in the longitudinal and circumferential directions, and strain more strongly depended on afterload than did strain rate. Myocardial shortening should be evaluated based on the relationships between these parameters and wall stress.

SU-E-T-783: Using Matrixx to Determine Transit Dose Contribution Over Clinically Useful Limits of HDR Source Activity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bhagwat, M; O’Farrell, D; Wagar, M

2015-06-15

Purpose: Most HDR brachytherapy treatment planning systems (TPS) use TG-43 formalism to calculate dose without including transit dose corrections. Historically, measurement of this contribution has required sophisticated apparatus unavailable in most hospitals. We use Matrixx to investigate several scenarios where transit dose contribution may effect a clinical treatment. Methods: Treatment plans were generated using Oncentra Brachy TPS (Version 4.3.0.410, Nucletron ) on a CT scan of a 24-catheter Freiburg applicator (Nucletron ) laid flat on the MatriXX (IBA) detector. This detector is an array of 1020 parallel plate ion chambers. All 24 catheters were digitized and dwells within a centralmore » square region of 5×5cm of the applicator were activated. Each of the active catheters had 6 dwells in increments of 1.0cm. The plans were normalized to 10mm. This places the 100% isodose line at the correct effective point of measurement, which lies half-way between the parallel plates of the ion chambers. It is also within the clinically relevant treatment depth for superficial applications. A total of 6 plans were delivered for 3 prescription doses, 1Gy, 2Gy and 4Gy using source activities of 2.9Ci and 11.2Ci. The MatriXX array was operated to capture dosimetric snaps every 500ms and yielded an integral dose at the end of treatment. Results: A comparison of integral dose from 2 different source activities shows that the transit dose contribution is larger when the source activity is higher. It is also observed that the relative transit dose contribution decreases as prescription dose increases. This is quantified by the Gamma analysis. Conclusion: We have demonstrated that the Matrixx detector can be used to evaluate the contribution for a HDR source during transit from the HDR afterloader to a dwell location, and between adjacent dwell locations.« less

TU-C-201-02: Clinical Implementation of HDR: Afterloader and Applicator Selection

DOE Office of Scientific and Technical Information (OSTI.GOV)

Esthappan, J.

2015-06-15

Recent use of HDR has increased while planning has become more complex often necessitating 3D image-based planning. While many guidelines for the use of HDR exist, they have not kept pace with the increased complexity of 3D image-based planning. Furthermore, no comprehensive document exists to describe the wide variety of current HDR clinical indications. This educational session aims to summarize existing national and international guidelines for the safe implementation of an HDR program. A summary of HDR afterloaders available on the market and their existing applicators will be provided, with guidance on how to select the best fit for eachmore » institution’s needs. Finally, the use of checklists will be discussed as a means to implement a safe and efficient HDR program and as a method by which to verify the quality of an existing HDR program. This session will provide the perspective of expert HDR physicists as well as the perspective of a new HDR user. Learning Objectives: Summarize national and international safety and staffing guidelines for HDR implementation Discuss the process of afterloader and applicator selection for gynecologic, prostate, breast, interstitial, surface treatments Learn about the use of an audit checklist tool to measure of quality control of a new or existing HDR program Describe the evolving use of checklists within an HDR program.« less

New method for obtaining position and time structure of source in HDR remote afterloading brachytherapy unit utilizing light emission from scintillator

PubMed Central

Hanada, Takashi; Katsuta, Shoichi; Yorozu, Atsunori; Maruyama, Koichi

2009-01-01

When using a HDR remote afterloading brachytherapy unit, results of treatment can be greatly influenced by both source position and treatment time. The purpose of this study is to obtain information on the source of the HDR remote afterloading unit, such as its position and time structure, with the use of a simple system consisting of a plastic scintillator block and a charge‐coupled device (CCD) camera. The CCD camera was used for recording images of scintillation luminescence at a fixed rate of 30 frames per second in real time. The source position and time structure were obtained by analyzing the recorded images. For a preset source‐step‐interval of 5 mm, the measured value of the source position was 5.0±1.0mm, with a pixel resolution of 0.07 mm in the recorded images. For a preset transit time of 30 s, the measured value was 30.0±0.6 s, when the time resolution of the CCD camera was 1/30 s. This system enabled us to obtain the source dwell time and movement time. Therefore, parameters such as I192r source position, transit time, dwell time, and movement time at each dwell position can be determined quantitatively using this plastic scintillator‐CCD camera system. PACS number: 87.53.Jw

Impact of aortic root size on left ventricular afterload and stroke volume.

PubMed

Sahlén, Anders; Hamid, Nadira; Amanullah, Mohammed Rizwan; Fam, Jiang Ming; Yeo, Khung Keong; Lau, Yee How; Lam, Carolyn S P; Ding, Zee Pin

2016-07-01

The left ventricle (LV) ejects blood into the proximal aorta. Age and hypertension are associated with stiffening and dilation of the aortic root, typically viewed as indicative of adverse remodeling. Based on analytical considerations, we hypothesized that a larger aortic root should be associated with lower global afterload (effective arterial elastance, EA) and larger stroke volume (SV). Moreover, as antihypertensive drugs differ in their effect on central blood pressure, we examined the role of antihypertensive drugs for the relation between aortic root size and afterload. We studied a large group of patients (n = 1250; 61 ± 12 years; 78 % males; 64 % hypertensives) from a single-center registry with known or suspected coronary artery disease. Aortic root size was measured by echocardiography as the diameter of the tubular portion of the ascending aorta. LV outflow tract Doppler was used to record SV. In the population as a whole, after adjusting for key covariates in separate regression models, aortic root size was an independent determinant of both SV and EA. This association was found to be heterogeneous and stronger in patients taking a calcium channel blocker (CCB; 10.6 % of entire population; aortic root size accounted for 8 % of the explained variance of EA). Larger aortic root size is an independent determinant of EA and SV. This association was heterogeneous and stronger in patients on CCB therapy.

A pig model of acute right ventricular afterload increase by hypoxic pulmonary vasoconstriction.

PubMed

Knai, Kathrine; Skjaervold, Nils Kristian

2017-01-03

The aim of this study was to construct a non-invasive model for acute right ventricular afterload increase by hypoxic pulmonary vasoconstriction. Intact animal models are vital to improving our understanding of the pathophysiology of acute right ventricular failure. Acute right ventricular failure is caused by increased afterload of the right ventricle by chronic or acute pulmonary hypertension combined with regionally or globally reduced right ventricular contractile capacity. Previous models are hampered by their invasiveness; this is unfortunate as the pulmonary circulation is a low-pressure system that needs to be studied in closed chest animals. Hypoxic pulmonary vasoconstriction is a mechanism that causes vasoconstriction in alveolar vessels in response to alveolar hypoxia. In this study we explored the use of hypoxic pulmonary vasoconstriction as a means to increase the pressure load on the right ventricle. Pulmonary hypertension was induced by lowering the FiO 2 to levels below the physiological range in eight anesthetized and mechanically ventilated pigs. The pigs were monitored with blood pressure measurements and blood gases. The mean pulmonary artery pressures (mPAP) of the animals increased from 18.3 (4.2) to 28.4 (4.6) mmHg and the pulmonary vascular resistance (PVR) from 254 (76) dyns/cm 5 to 504 (191) dyns/cm 5 , with a lowering of FiO 2 from 0.30 to 0.15 (0.024). The animals' individual baseline mPAPs varied substantially as did their response to hypoxia. The reduced FiO 2 level yielded an overall lowering in oxygen offer, but the global oxygen consumption was unaltered. We showed in this study that the mPAP and the PVR could be raised by approximately 100% in the study animals by lowering the FiO 2 from 0.30 to 0.15 (0.024). We therefore present a novel method for minimally invasive (closed chest) right ventricular afterload manipulations intended for future studies of acute right ventricular failure. The method should in theory be reversible, although this was not studied in this work.

Impact of intravenous nitroglycerin in the management of acute decompensated heart failure.

PubMed

den Uil, Corstiaan A; Brugts, Jasper J

2015-02-01

Intravenous nitroglycerin is a well-known, but underused, treatment for acute decompensated heart failure. Nitroglycerin has a rapid onset of action and short half-life and there is a clear dose-response curve on both global hemodynamics and peripheral circulation. IV nitroglycerin reduces LV and RV filling pressures and afterload. In the case of acute decompensated heart failure, there is a typical decreased bioavailability of nitric oxide (NO), which needs to be supplemented by exogenous nitrates. Additionally, there is benefit on clinical endpoints, such as fast optimization of arterial oxygenation, lower rates of mechanical ventilation, and improved survival. Drawbacks of therapy include not only side effects such as headache, resistance, and development of tolerability to nitrates but also free radical production. However, nitrates in combination with diuretics remain the cornerstone of acute decompensated heart failure treatment. We propose a more aggressive use of nitrates and a more limited use of inotropes (due to ischemic demand and pro-arrhythmogenic characteristics) in normo- or hypertensive patients with acute heart failure.

Evaluation of time, attendance of medical staff, and resources during interstitial brachytherapy for prostate cancer : DEGRO-QUIRO trial.

PubMed

Tselis, N; Maurer, U; Popp, W; Sack, H; Zamboglou, N

2014-04-01

The German Society of Radiation Oncology initiated a multicenter trial to evaluate core processes and subprocesses of radiotherapy by prospective evaluation of all important procedures in the most frequent malignancies treated by radiation therapy. The aim of this analysis was to assess the required resources for interstitial high-dose-rate (HDR) and low-dose-rate (LDR) prostate brachytherapy (BRT) based on actual time measurements regarding allocation of personnel and room occupation needed for specific procedures. Two radiotherapy centers (community hospital of Offenbach am Main and community hospital of Eschweiler) participated in this prospective study. Working time of the different occupational groups and room occupancies for the workflow of prostate BRT were recorded and methodically assessed during a 3-month period. For HDR and LDR BRT, a total of 560 and 92 measurements, respectively, were documented. The time needed for treatment preplanning was median 24 min for HDR (n = 112 measurements) and 6 min for LDR BRT (n = 21). Catheter implantation with intraoperative HDR real-time planning (n = 112), postimplantation HDR treatment planning (n = 112), and remotely controlled HDR afterloading irradiation (n = 112) required median 25, 39, and 50 min, respectively. For LDR real-time planning (n = 39) and LDR treatment postplanning (n = 32), the assessed median duration was 91 and 11 min, respectively. Room occupancy and overall mean medical staff times were 194 and 910 min respectively, for HDR, and 113 and 371 min, respectively, for LDR BRT. In this prospective analysis, the resource requirements for the application of HDR and LDR BRT of prostate cancer were assessed methodically and are presented for first time.

Patterns of care for brachytherapy in Europe. Results in Spain.

PubMed

López Torrecilla, J; Guedea, F; Heeren, G; Nissin, R; Ellison, T; Cottier, B

2006-05-01

In 2003 ESTRO began a project whose primary objective, was to make a map in the European area of infrastructures in technology and personnel for brachytherapy. A survey and a web site were elaborated. The survey was sent to the 76 Spanish Radiation Oncology departments in May 2003. By the end of 2003, 66 (86.8%) services had responded, 40 (71.4%) of which had brachytherapy. The services with brachytherapy treated 73.5% of the total patients, an average of 1,199 patients. The mean number of patients treated with brachytherapy by department was 135.5 and the number of applications was 265 annually. The average number of specialists was 7, 4 of them trained in brachytherapy. The average weekly work load of the radiation oncologists, physicists, and technicians was 22.6 h, 13.8 h and 21.0 h, respectively. The mean time dedicated to each patient by radiation oncologists, physicists and technicians was 9.2 h; 6.19 h; 7.2 h, respectively. The total number of afterloaders was 43 (22 HDR, 18 LDR, 3 PDR). The tumours most frequently treated with brachytherapy were gynaecological (56.24%), breast (14.2%) and prostate (11.7%). High dose rate was used in 47.46% of the patients and low dose rate in 47.24%. Between 1997 and 2002 there was an increase of 50.53% in patients treated with brachytherapy. The survey shows the brachytherapy resources and activity in Spain up to 2003. Increased use of brachytherapy in prostate tumours, prevalence of gynaecology brachytherapy and similar number of treatments with HDR and LDR are demonstrated in the Patterns of Care of Brachytherapy in Europe (PCBE) study in Spain.

Embryo transfer by reproductive endocrinology fellows vs attending physicians: are live birth rates comparable?

PubMed

Eaton, Jennifer L; Zhang, Xingqi; Barnes, Randall B

2014-11-01

To compare live birth rates following ultrasound-guided embryo transfer (ET) by reproductive endocrinology and infertility fellows versus attending physicians. Women who underwent their first day-3, fresh, nondonor ET between Oct. 1, 2005, and April 1, 2011, at our academic center were included in this retrospective cohort study. Embryos were designated high quality if they had 8 cells, less than 10% fragmentation, and no asymmetry. ET was performed with the afterload technique under ultrasound guidance. Categorical variables were evaluated with the χ(2) test and continuous variables with the Student t test. Logistic regression was performed to assess the relationship between ET physician and live birth rate while adjusting for potential confounders. Seven hundred sixty women underwent ET by an attending physician, and 104 by a fellow. Baseline characteristics were similar between the groups. The live birth rate was 31% following ET by an attending physician, compared with 34% following ET by a fellow (P = .65). Logistic regression adjusting for potential confounders demonstrated no significant association between ET physician and live birth rate. This retrospective study demonstrated no significant difference in live birth rates following ultrasound-guided ET by fellows vs attending physicians at our institution. These data suggest that academic practices using the afterload method and ultrasound guidance can train fellows to perform ET without compromising success rates. Copyright © 2014 Elsevier Inc. All rights reserved.

Female exposure to high G: echocardiographic evaluation for chronic changes in cardiac function.

PubMed

Albery, W B; Ten Eyck, R P; Wolfe, M

1998-09-01

Significant changes in cardiac preload and afterload are generated by a number of factors present during the operation of high performance aircraft. These include high levels of +Gz, positive pressure breathing and anti-G straining maneuvers. Centrifuge subjects are exposed to these same factors in doses that are comparable to their operational counterparts. The question of whether such exposures produce long-term adverse effects on the heart has not been definitively answered. In an effort to further address this issue, a longitudinal study was conducted on 18 newly recruited centrifuge panel members (7 males and 11 females) who did not have a previous history of significant high +Gz exposure. In order to document the cumulative long-term effects of high +Gz exposure and G protection measures, baseline echocardiographic studies were conducted prior to any +Gz exposure on the Dynamic Environment Simulator (DES) centrifuge. The echocardiograms were repeated after each panel member completed eight sessions of indoctrination. These follow-up echos were performed after all 18 subjects had been exposed to over 45 min (cumulative) of sustained acceleration > or = 2 G. Each subject served as his/her own control. All studies were evaluated independently by a cardiologist who was blinded to the order in which the studies were performed. Although complete echocardiographic studies were performed, only the parameters identified as significant in prior studies were evaluated. No significant differences were found between the initial and follow-up echo parameters. No significant differences were found between male and female responses. We found no significant differences in cardiac function after 45 min (cumulative) of exposure to G > or = 2 in men or women. These subjects will be monitored during a longitudinal study throughout their centrifuge subject career.

SU-G-201-07: Dosimetric Verification of a 3D Printed HDR Skin Brachytherapy Applicator

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rasmussen, K; Stanley, D; Eng, T

Purpose: The use of radiation as a treatment modality for skin cancer has increased significantly over the last decade with standardized applicators. Utilizing 3D printing, the ability to make applicators specifically designed for each patient’s anatomy has become economically feasible. With this in mind it was the aim of this study to determine the dosimetric accuracy of a 3-D printed HDR brachytherapy applicator for the skin. Methods: A CT reference image was used to generate a custom applicator based on an anthropomorphic head and neck phantom. To create the applicator a 1cm expansion anteriorly with 0.5cmX0.5cm trenches on the outermore » surface that were spaced 1cm sup-inf to accommodate standard 6F flexible catheters. The applicator was printed using PLA material using a printrbot simple printer. A treatment plan optimized to deliver a clinically representative volume was created in Oncentra and delivered with a nucletron afterloader. Measurements were made using TLDs and EBT3 gafchromic film that were placed between the applicator and the phantom’s forehead. An additional piece of film was also used to qualitatively asses the dose distribution in the transverse plane. Using a standard vaginal cylinder and bolus, a standardized curve correlating TLD and film exposure-to-radiation dose was established by irradiating film to known doses (200,500,700 cGy) at a 3.5 cm radius distance. Results: Evaluated TLDs showed the absolute dose delivered to the skin surface using the 3-D printed bolus was 615cGy±6%, with a mean predicted TPS value in the measured area of 617.5±7%. Additionally, planar dose distributions had good qualitative agreement with calculated TPS isodoses. Conclusion: This work demonstrates patient specific 3-D printed HDR brachytherapy applicators for skin cancer treatments are practical and accurate in TPS calculations but additional measurements are needed to verify additional sites and dose at depth.« less

Diabetes Mellitus Associates with Increased Right Ventricular Afterload and Remodeling in Pulmonary Arterial Hypertension.

PubMed

Whitaker, Morgan E; Nair, Vineet; Sinari, Shripad; Dherange, Parinita A; Natarajan, Balaji; Trutter, Lindsey; Brittain, Evan L; Hemnes, Anna R; Austin, Eric D; Patel, Kumar; Black, Stephen M; Garcia, Joe G N; Yuan Md PhD, Jason X; Vanderpool, Rebecca R; Rischard, Franz; Makino, Ayako; Bedrick, Edward J; Desai, Ankit A

2018-06-01

Diabetes mellitus is associated with left ventricular hypertrophy and dysfunction. Parallel studies have also reported associations between diabetes mellitus and right ventricular dysfunction and reduced survival in patients with pulmonary arterial hypertension. However, the impact of diabetes mellitus on the pulmonary vasculature has not been well characterized. We hypothesized that diabetes mellitus and hyperglycemia could specifically influence right ventricular afterload and remodeling in patients with Group I pulmonary arterial hypertension, providing a link to their known susceptibility to right ventricular dysfunction. Using an adjusted model for age, sex, pulmonary vascular resistance, and medication use, associations of fasting blood glucose, glycated hemoglobin, and the presence of diabetes mellitus were evaluated with markers of disease severity in 162 patients with pulmonary arterial hypertension. A surrogate measure of increased pulmonary artery stiffness, elevated pulmonary arterial elastance (P = .012), along with reduced log(pulmonary artery capacitance) (P = .006) were significantly associated with the presence of diabetes mellitus in patients with pulmonary arterial hypertension in a fully adjusted model. Similar associations between pulmonary arterial elastance and capacitance were noted with both fasting blood glucose and glycated hemoglobin. Furthermore, right ventricular wall thickness on echocardiography was greater in pulmonary arterial hypertension patients with diabetes, supporting the link between right ventricular remodeling and diabetes. Cumulatively, these data demonstrate that an increase in right ventricular afterload, beyond pulmonary vascular resistance alone, may influence right ventricular remodeling and provide a mechanistic link between the susceptibility to right ventricular dysfunction in patients with both diabetes mellitus and pulmonary arterial hypertension. Copyright © 2018 Elsevier Inc. All rights reserved.

Dose-Response Head-to-Head Comparison of Inodilators Dobutamine, Milrinone, and Levosimendan in Chronic Experimental Pulmonary Hypertension.

PubMed

Tavares-Silva, Marta; Alaa, Mohamed; Leite, Sara; Oliveira-Pinto, José; Lopes, Lucas; Leite-Moreira, Adelino F; Lourenço, André P

2017-09-01

The choice of inodilator drug in the acute management of patients with pulmonary hypertension (PH) having right ventricular (RV) failure remains unsettled and challenging. Comprehensive experimental evaluations may provide further insight and fundamental translational research clues to support inodilator selection and clinical trial design. Our aim was to compare acute dose-response hemodynamic effects of inodilators dobutamine (DOB), milrinone (MIL), and levosimendan (LEV) in chronic experimental PH. Seven-week-old male Wistar rats were randomly injected with 60 mg·kg -1 monocrotaline (MCT) or vehicle (Ctrl, n = 7) and underwent systemic and pulmonary artery (PA) pressure and RV pressure-volume (PV) hemodynamic evaluation under halogenate anesthesia 24 to 30 days after injection. The MCT-injected animals (n = 7 each) randomly received dose-response infusions of DOB (1, 3, 6 and 12 μg·kg -1 ·min -1 ), MIL (MIL: 1, 3, 6 and 12 μg·kg -1 ·min -1 ), or LEV (0.3, 0.6, 1.2 and 2.4 μg·kg -1 ·min -1 ). Load-independent indexes were obtained by inferior vena cava occlusion at baseline and after the last dose. All inodilators increased RV ejection fraction, preload recruitable stroke work, and ventricular-vascular coupling without jeopardizing perfusion pressure. Dobutamine raised heart rate and PA pressure. Only LEV increased cardiac index and decreased PA elastance and pulmonary vascular resistance (PVR). Moreover, only LEV downward-shifted the end-diastolic PV relationship, thereby improving RV compliance. Adding sildenafil to LEV further decreased PVR. Levosimendan had beneficial acute systolic and diastolic functional effects in experimental chronic PH and RV afterload compared to DOB and MIL. It should be further tested in clinical trials enrolling patients with PH in the perioperative and critical care settings.

10 CFR 35.690 - Training for use of remote afterloader units, teletherapy units, and gamma stereotactic...

Code of Federal Regulations, 2010 CFR

2010-01-01

... measurement of radioactivity; and (D) Radiation biology; and (ii) 500 hours of work experience, under the... section, and has achieved a level of competency sufficient to function independently as an authorized user...

Effects of intra-aortic balloon pump versus centrifugal pump on myocardial energetics and systemic circulation in a porcine model of rapidly worsening acute heart failure.

PubMed

Ntalianis, Argyrios S; Drakos, Stavros G; Charitos, Christos; Dolou, Paraskevi; Pierrakos, Charalampos N; Terrovitis, John V; Papaioannou, Theodoros; Charitos, Efstratios; Nanas, John N

2008-01-01

The present experimental study compared the effectiveness of counterpulsation provided by the intra-aortic balloon pump (IABP) versus that of a nonpulsatile, radial-flow centrifugal pump (CFP) in rapidly worsening acute heart failure (HF). Eighteen pigs were included in the study. After the induction of acute moderate HF, circulatory support was randomly provided with either the IABP or CFP. No significant change in cardiac output (CO) and mean aortic pressure (MAP) was observed with either pump. The IABP caused a significantly greater decrease than the CFP in 1) double product (13.138 +/- 2.476 mm Hg/min vs. 14.217 +/- 2.673 mm Hg/min, p = 0.023), 2) left ventricular systolic pressure (LVSP, 100 +/- 8 mm Hg vs. 106 +/- 10 mm Hg, p = 0.046), and 3) end-diastolic aortic pressure (EDAP, 70 +/- 6 mm Hg vs. 86 +/- 6 mm Hg, p = 0.000). The effects of both pumps on total tension time index and LAD flow were similar. After the induction of severe HF, the IABP had its main effects on afterload and decreased LVSP from 88 +/- 6 mm Hg to 78 +/- 9 mm Hg, (p = 0.008), and EDAP from 57 +/- 9 mm Hg to 49 +/- 14 mm Hg, (p = 0.044), whereas the CFP exerted its effects mainly on preload, lowering LV end-diastolic pressure from 19 +/- 5 mm Hg to 11 +/- 4 mm Hg, (p = 0.002). CO and MAP were similarly increased by both assist systems. The IABP (by lowering afterload) and CFP (by lowering preload) both offered significant mechanical support in acute HF. However, afterload reduction offered principally by the IABP seems preferable for the recovery of the acutely failing heart.

Afterload-dependent flow fluctuation of centrifugal pump: should it be actively fixed?

PubMed

Nishida, H; Akazawa, T; Nishinaka, T; Aomi, S; Endo, M; Koyanagi, H

1998-05-01

To evaluate the clinical meaning and effects of afterload-dependent flow fluctuation in a centrifugal pump, concomitant measurement of flow rate and mixed venous oxygen saturation (SVO2) was performed in 5 cases of open heart surgery in which the patients underwent cardiopulmonary bypass (CPB) with the Terumo Capiox centrifugal pump. Continuous measurement of SVO2 using the 3M CDI System 100 was performed with a disposable cuvette incorporated into the drainage circuit. After the target flow rate of 2.4 L/min/m2 was obtained under a nonbeating condition, the pump rotational speed was fixed. During the cooling and low temperature period, SVO2 decreased as the flow rate spontaneously decreased but still stayed around 80% even with a 15-20% decrease in blood flow rate. This indicates that a luxury perfusion condition is ensured as long as the body temperature is kept low. In contrast, during the rewarming period, SVO2 decreased to around 70-75% despite a 15-25% spontaneous increase in flow rate. Although this level of SVO2 still indicates adequate systemic perfusion, there is a possibility of regional hypoperfusion in patients with such conditions as cerebrovascular disease. In conclusion, although diligent adjustment of the physiological fluctuating flow rate in the centrifugal pump seems unnecessary during conventional open heart surgery, manual control may be necessary especially during the rewarming period, normothermic surgery, or circulatory assist for shocked patients. From this study, we also conclude that the major benefit of the afterload-independent autoflow control system of the centrifugal pump is the improvement of safety in terms of the fixed reservoir level and the handling of cardiopulmonary bypass.

Blood Pressure and Arterial Load After Transcatheter Aortic Valve Replacement for Aortic Stenosis.

PubMed

Lindman, Brian R; Otto, Catherine M; Douglas, Pamela S; Hahn, Rebecca T; Elmariah, Sammy; Weissman, Neil J; Stewart, William J; Ayele, Girma M; Zhang, Feifan; Zajarias, Alan; Maniar, Hersh S; Jilaihawi, Hasan; Blackstone, Eugene; Chinnakondepalli, Khaja M; Tuzcu, E Murat; Leon, Martin B; Pibarot, Philippe

2017-07-01

After aortic valve replacement, left ventricular afterload is often characterized by the residual valve obstruction. Our objective was to determine whether higher systemic arterial afterload-as reflected in blood pressure, pulsatile and resistive load-is associated with adverse clinical outcomes after transcatheter aortic valve replacement (TAVR). Total, pulsatile, and resistive arterial load were measured in 2141 patients with severe aortic stenosis treated with TAVR in the PARTNER I trial (Placement of Aortic Transcatheter Valve) who had systolic blood pressure (SBP) and an echocardiogram obtained 30 days after TAVR. The primary end point was 30-day to 1-year all-cause mortality. Lower SBP at 30 days after TAVR was associated with higher mortality (20.0% for SBP 100-129 mm Hg versus 12.0% for SBP 130-170 mm Hg; P <0.001). This association remained significant after adjustment, was consistent across subgroups, and confirmed in sensitivity analyses. In adjusted models that included SBP, higher total and pulsatile arterial load were associated with increased mortality ( P <0.001 for all), but resistive load was not. Patients with low 30-day SBP and high pulsatile load had a 3-fold higher mortality than those with high 30-day SBP and low pulsatile load (26.1% versus 8.1%; hazard ratio, 3.62; 95% confidence interval, 2.36-5.55). Even after relief of valve obstruction in patients with aortic stenosis, there is an independent association between post-TAVR blood pressure, systemic arterial load, and mortality. Blood pressure goals in patients with a history of aortic stenosis may need to be redefined. Increased pulsatile arterial load, rather than blood pressure, may be a target for adjunctive medical therapy to improve outcomes after TAVR. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00530894. © 2017 American Heart Association, Inc.

Increased temperature, not cardiac load, activates heat shock transcription factor 1 and heat shock protein 72 expression in the heart.

PubMed

Staib, Jessica L; Quindry, John C; French, Joel P; Criswell, David S; Powers, Scott K

2007-01-01

The expression of myocardial heat shock protein 72 (HSP72) postexercise is initiated by the activation of heat shock transcription factor 1 (HSF1). However, it remains unknown which physiological stimuli govern myocardial HSF1 activation during exercise. These experiments tested the hypothesis that thermal stress and mechanical load, concomitant with simulated exercise, provide independent stimuli for HSF1 activation and ensuing cardiac HSP72 gene expression. To elucidate the independent roles of increased temperature and cardiac workload in the exercise-mediated upregulation of left-ventricular HSP72, hearts from adult male Sprague-Dawley rats were randomly assigned to one of five simulated exercise conditions. Upon reaching a surgical plane of anesthesia, each experimental heart was isolated and perfused using an in vitro working heart model, while independently varying temperatures (i.e., 37 degrees C vs. 40 degrees C) and cardiac workloads (i.e., low preload and afterload vs. high preload and afterload) to mimic exercise responses. Results indicate that hyperthermia, independent of cardiac workload, promoted an increase in nuclear translocation and phosphorylation of HSF1 compared with normothermic left ventricles. Similarly, hyperthermia, independent of workload, resulted in significant increases in cardiac levels of HSP72 mRNA. Collectively, these data suggest that HSF1 activation and HSP72 gene transcriptional competence during simulated exercise are linked to elevated heart temperature and are not a direct function of increased cardiac workload.

10 CFR 35.605 - Installation, maintenance, adjustment, and repair.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 1 2010-01-01 2010-01-01 false Installation, maintenance, adjustment, and repair. 35.605 Section 35.605 Energy NUCLEAR REGULATORY COMMISSION MEDICAL USE OF BYPRODUCT MATERIAL Photon Emitting Remote Afterloader Units, Teletherapy Units, and Gamma Stereotactic Radiosurgery Units § 35.605...

10 CFR 35.605 - Installation, maintenance, adjustment, and repair.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 1 2014-01-01 2014-01-01 false Installation, maintenance, adjustment, and repair. 35.605 Section 35.605 Energy NUCLEAR REGULATORY COMMISSION MEDICAL USE OF BYPRODUCT MATERIAL Photon Emitting Remote Afterloader Units, Teletherapy Units, and Gamma Stereotactic Radiosurgery Units § 35.605...

10 CFR 35.605 - Installation, maintenance, adjustment, and repair.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 1 2012-01-01 2012-01-01 false Installation, maintenance, adjustment, and repair. 35.605 Section 35.605 Energy NUCLEAR REGULATORY COMMISSION MEDICAL USE OF BYPRODUCT MATERIAL Photon Emitting Remote Afterloader Units, Teletherapy Units, and Gamma Stereotactic Radiosurgery Units § 35.605...

10 CFR 35.605 - Installation, maintenance, adjustment, and repair.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 1 2013-01-01 2013-01-01 false Installation, maintenance, adjustment, and repair. 35.605 Section 35.605 Energy NUCLEAR REGULATORY COMMISSION MEDICAL USE OF BYPRODUCT MATERIAL Photon Emitting Remote Afterloader Units, Teletherapy Units, and Gamma Stereotactic Radiosurgery Units § 35.605...

10 CFR 35.605 - Installation, maintenance, adjustment, and repair.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 1 2011-01-01 2011-01-01 false Installation, maintenance, adjustment, and repair. 35.605 Section 35.605 Energy NUCLEAR REGULATORY COMMISSION MEDICAL USE OF BYPRODUCT MATERIAL Photon Emitting Remote Afterloader Units, Teletherapy Units, and Gamma Stereotactic Radiosurgery Units § 35.605...

Cardiovascular studies using the chimpanzee (Pan troglodytes)

NASA Technical Reports Server (NTRS)

Hinds, J. E.; Cothran, L. N.; Hawthorne, E. W.

1977-01-01

Despite the phylogenetic similarities between chimpanzees and man, there exists a paucity of reliable data on normal cardiovascular function and the physiological responses of the system to standard interventions. Totally implanted biotelemetry systems or hardwire analog techniques were used to examine the maximum number of cardiovascular variables which could be simultaneously monitored without significantly altering the system's performance. This was performed in order to acquire base-line data not previously obtained in this species, to determine cardiovascular response to specific forcing functions such as ventricular pacing, drug infusions, and lower body negative pressure. A cardiovascular function profile protocol was developed in order to adjust independently the three major factors which modify ventricular performance, namely, left ventricular performance, left ventricular preload, afterload, and contractility. Cardiac pacing at three levels above the ambient rate was used to adjust end diastolic volume (preload). Three concentrations of angiotensin were infused continuously to evaluate afterload in a stepwide fashion. A continuous infusion of dobutamine was administered to raise the manifest contractile state of the heart.

Cocoa flavanols reduce N-terminal pro-B-type natriuretic peptide in patients with chronic heart failure.

PubMed

De Palma, Rodney; Sotto, Imelda; Wood, Elizabeth G; Khan, Noorafza Q; Butler, Jane; Johnston, Atholl; Rothman, Martin T; Corder, Roger

2016-06-01

Poor prognosis in chronic heart failure (HF) is linked to endothelial dysfunction for which there is no specific treatment currently available. Previous studies have shown reproducible improvements in endothelial function with cocoa flavanols, but the clinical benefit of this effect in chronic HF has yet to be determined. Therefore, the aim of this study was to assess the potential therapeutic value of a high dose of cocoa flavanols in patients with chronic HF, by using reductions in N-terminal pro-B-type natriuretic peptide (NT-proBNP) as an index of improved cardiac function. Thirty-two patients with chronic HF, stable on guideline-directed medical therapy, were randomized to consume 50 g/day of high-flavanol dark chocolate (HFDC; 1064 mg of flavanols/day) or low-flavanol dark chocolate (LFDC; 88 mg of flavanols/day) for 4 weeks and then crossed over to consume the alternative dark chocolate for a further 4 weeks. Twenty-four patients completed the study. After 4 weeks of HFDC, NT-proBNP (mean decrease % ± standard deviation) was significantly reduced compared with baseline (-44 ± 69%), LFDC (-33 ± 72%), and follow-up (-41 ± 77%) values. HFDC also reduced diastolic blood pressure compared with values after LFDC (-6.7 ± 10.1 mmHg). Reductions in blood pressure and NT-proBNP after HFDC indicate decreased vascular resistance resulting in reduced left ventricular afterload. These effects warrant further investigation in patients with chronic HF.

10 CFR 35.655 - Five-year inspection for teletherapy and gamma stereotactic radiosurgery units.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 1 2010-01-01 2010-01-01 false Five-year inspection for teletherapy and gamma stereotactic radiosurgery units. 35.655 Section 35.655 Energy NUCLEAR REGULATORY COMMISSION MEDICAL USE OF BYPRODUCT MATERIAL Photon Emitting Remote Afterloader Units, Teletherapy Units, and Gamma Stereotactic...

10 CFR 35.655 - Five-year inspection for teletherapy and gamma stereotactic radiosurgery units.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 1 2014-01-01 2014-01-01 false Five-year inspection for teletherapy and gamma stereotactic radiosurgery units. 35.655 Section 35.655 Energy NUCLEAR REGULATORY COMMISSION MEDICAL USE OF BYPRODUCT MATERIAL Photon Emitting Remote Afterloader Units, Teletherapy Units, and Gamma Stereotactic...

10 CFR 35.655 - Five-year inspection for teletherapy and gamma stereotactic radiosurgery units.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 1 2013-01-01 2013-01-01 false Five-year inspection for teletherapy and gamma stereotactic radiosurgery units. 35.655 Section 35.655 Energy NUCLEAR REGULATORY COMMISSION MEDICAL USE OF BYPRODUCT MATERIAL Photon Emitting Remote Afterloader Units, Teletherapy Units, and Gamma Stereotactic...

10 CFR 35.642 - Periodic spot-checks for teletherapy units.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 1 2014-01-01 2014-01-01 false Periodic spot-checks for teletherapy units. 35.642 Section 35.642 Energy NUCLEAR REGULATORY COMMISSION MEDICAL USE OF BYPRODUCT MATERIAL Photon Emitting Remote Afterloader Units, Teletherapy Units, and Gamma Stereotactic Radiosurgery Units § 35.642 Periodic spot-checks...

10 CFR 35.655 - Five-year inspection for teletherapy and gamma stereotactic radiosurgery units.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 1 2011-01-01 2011-01-01 false Five-year inspection for teletherapy and gamma stereotactic radiosurgery units. 35.655 Section 35.655 Energy NUCLEAR REGULATORY COMMISSION MEDICAL USE OF BYPRODUCT MATERIAL Photon Emitting Remote Afterloader Units, Teletherapy Units, and Gamma Stereotactic...

10 CFR 35.655 - Five-year inspection for teletherapy and gamma stereotactic radiosurgery units.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 1 2012-01-01 2012-01-01 false Five-year inspection for teletherapy and gamma stereotactic radiosurgery units. 35.655 Section 35.655 Energy NUCLEAR REGULATORY COMMISSION MEDICAL USE OF BYPRODUCT MATERIAL Photon Emitting Remote Afterloader Units, Teletherapy Units, and Gamma Stereotactic...

10 CFR 35.642 - Periodic spot-checks for teletherapy units.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 1 2012-01-01 2012-01-01 false Periodic spot-checks for teletherapy units. 35.642 Section 35.642 Energy NUCLEAR REGULATORY COMMISSION MEDICAL USE OF BYPRODUCT MATERIAL Photon Emitting Remote Afterloader Units, Teletherapy Units, and Gamma Stereotactic Radiosurgery Units § 35.642 Periodic spot-checks...

10 CFR 35.642 - Periodic spot-checks for teletherapy units.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 1 2013-01-01 2013-01-01 false Periodic spot-checks for teletherapy units. 35.642 Section 35.642 Energy NUCLEAR REGULATORY COMMISSION MEDICAL USE OF BYPRODUCT MATERIAL Photon Emitting Remote Afterloader Units, Teletherapy Units, and Gamma Stereotactic Radiosurgery Units § 35.642 Periodic spot-checks...

10 CFR 35.642 - Periodic spot-checks for teletherapy units.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 1 2011-01-01 2011-01-01 false Periodic spot-checks for teletherapy units. 35.642 Section 35.642 Energy NUCLEAR REGULATORY COMMISSION MEDICAL USE OF BYPRODUCT MATERIAL Photon Emitting Remote Afterloader Units, Teletherapy Units, and Gamma Stereotactic Radiosurgery Units § 35.642 Periodic spot-checks...

Efficacy of a new intraaortic propeller pump vs the intraaortic balloon pump: an animal study.

PubMed

Dekker, André; Reesink, Koen; van der Veen, Erik; Van Ommen, Vincent; Geskes, Gijs; Soemers, Cecile; Maessen, Jos

2003-06-01

To compare the efficacy of a new intraaortic propeller pump (PP) to provide hemodynamic support to the intraaortic balloon pump (IABP) in an acute mitral regurgitation (MR) animal model. A new intraaortic PP (Reitan catheter pump; Jomed; Helsingborg, Sweden) recently has been introduced. The pump's aim is a reduction in afterload via a deployable propeller that is placed in the high descending aorta and can be set at rotational speeds of

The use of the oesophageal Doppler in perioperative medicine: new opportunities in research and clinical practice.

PubMed

Pinto, Bernardo Bollen; Atlas, Glen; Geerts, Bart F; Bendjelid, Karim

2017-10-01

The oesophageal Doppler (OD) is a minimally invasive haemodynamic monitor used in the surgical theatre and the ICU. Using the OD, goal-directed therapy (GDT) has been shown to reduce perioperative complications in high-risk surgical patients. However, most GDT protocols currently in use are limited to stroke volume optimisation. In the present manuscript, we examine the conceptual models behind new OD-based measurements. These would provide the clinician with a comprehensive view of haemodynamic pathophysiology; including pre-load, contractility, and afterload. Specifically, volume status could be estimated using mean systemic filling pressure (MSFP), the pressure to which all intravascular pressures equilibrate during asystole. Using the OD, MSFP could be readily estimated by simultaneous measurements of aortic blood flow and arterial pressure with sequential manoeuvres of increasing airway pressure. This would result in subsequent reductions in cardiac output and arterial pressure and would allow for a linear extrapolation of a static MSFP value to a "zero flow" state. In addition, we also demonstrate that EF is proportional to mean blood flow velocity measured in the descending thoracic aorta with the OD. Furthermore, OD-derived indexes of blood flow velocity and acceleration, as well as force and kinetic energy, can be derived and used for continuous assessment of cardiac contractility at the bedside. Using OD-derived parameters, the different components of afterload: inertia, resistance and elastance, could also be individually determined. The integration of these additional haemodynamic parameters could assist the clinician in optimising and individualising haemodynamic performance in unstable patients.

Embryo transfer techniques: an American Society for Reproductive Medicine survey of current Society for Assisted Reproductive Technology practices.

PubMed

Toth, Thomas L; Lee, Malinda S; Bendikson, Kristin A; Reindollar, Richard H

2017-04-01

To better understand practice patterns and opportunities for standardization of ET. Cross-sectional survey. Not applicable. Not applicable. An anonymous 82-question survey was emailed to the medical directors of 286 Society for Assisted Reproductive Technology member IVF practices. A follow-up survey composed of three questions specific to ET technique was emailed to the same medical directors. Descriptive statistics of the results were compiled. The survey assessed policies, protocols, restrictions, and specifics pertinent to the technique of ET. There were 117 (41%) responses; 32% practice in academic settings and 68% in private practice. Responders were experienced clinicians, half of whom had performed <10 procedures during training. Ninety-eight percent of practices allowed all practitioners to perform ET; half did not follow a standardized ET technique. Multiple steps in the ET process were identified as "highly conserved;" others demonstrated discordance. ET technique is divided among [1] trial transfer followed immediately with ET (40%); [2] afterload transfer (30%); and [3] direct transfer without prior trial or afterload (27%). Embryos are discharged in the upper (66%) and middle thirds (29%) of the endometrial cavity and not closer than 1-1.5 cm from fundus (87%). Details of each step were reported and allowed the development of a "common" practice ET procedure. ET training and practices vary widely. Improved training and standardization based on outcomes data and best practices are warranted. A common practice procedure is suggested for validation by a systematic literature review. Copyright © 2017 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Mechanisms of right heart disease in pulmonary hypertension (2017 Grover Conference Series).

PubMed

Asosingh, Kewal; Erzurum, Serpil

2018-01-01

Current dogma is that pathological hypertrophy of the right ventricle is a direct consequence of pulmonary vascular remodeling. However, progression of right ventricle dysfunction is not always lung-dependent. Increased afterload caused by pulmonary vascular remodeling initiates the right ventricle hypertrophy, but determinants leading to adaptive or maladaptive hypertrophy and failure remain unknown. Ischemia in a hypertrophic right ventricle may directly contribute to right heart failure. Rapidly enlarging cardiomyocytes switch from aerobic to anaerobic energy generation resulting in cell growth under relatively hypoxic conditions. Cardiac muscle reacts to an increased afterload by over-activation of the sympathetic system and uncoupling and downregulation of β-adrenergic receptors. Recent studies suggest that β blocker therapy in PH is safe, well tolerated, and preserves right ventricle function and cardiac output by reducing right ventricular glycolysis. Fibrosis, an evolutionary conserved process in host defense and wound healing, is dysregulated in maladaptive cardiac tissue contributing directly to right ventricle failure. Despite several mechanisms having been suggested in right heart disease, the causes of maladaptive cardiac remodeling remain unknown and require further research.

Design of a pulsatile DC electromagnetic blood pump for ECMO.

PubMed

Liu, Jingjing; Ge, Bin; Lu, Tong

2017-08-09

Extracorporeal membrane oxygenation (ECMO) has developed rapidly and becomes a significant treatment for emergency. Current blood pumps for ECMO have different disadvantages. To design a pulsatile DC electromagnetic blood pump for ECMO. The design is presented with a driving principle which the rectilinear reciprocation of a magnet inside energized solenoids is implemented, and with a structure of solenoids with compensation coils. Furthermore, a prototype was constructed and the performance indexes of it were measured with the experimental evaluations, where the acceleration experiment was performed without any loads, and the flows were measured in the ranges of preload and afterload are 5 to 30 mmHg and 50 to 80 mmHg respectively when the frequency of the motion is 80 beats per minute. The electromagnetic force is greater than 1.4 N when the DC reaches 2.7 A and the flow of the prototype is greater than 3.0 L/min except the differences between the preload and the afterload are greater than or equal to 70 mmHg. The design of the blood pump for ECMO meets the theoretical and clinical requirements.

Extracorporeal Cardiopulmonary Resuscitation in the Pediatric Cardiac Population: In Search of a Standard of Care.

PubMed

Lasa, Javier J; Jain, Parag; Raymond, Tia T; Minard, Charles G; Topjian, Alexis; Nadkarni, Vinay; Gaies, Michael; Bembea, Melania; Checchia, Paul A; Shekerdemian, Lara S; Thiagarajan, Ravi

2018-02-01

Although clinical and pharmacologic guidelines exist for the practice of cardiopulmonary resuscitation in children (Pediatric Advanced Life Support), the practice of extracorporeal cardiopulmonary resuscitation in pediatric cardiac patients remains without universally accepted standards. We aim to explore variation in extracorporeal cardiopulmonary resuscitation procedures by surveying clinicians who care for this high-risk patient population. A 28-item cross-sectional survey was distributed via a web-based platform to clinicians focusing on cardiopulmonary resuscitation practices and extracorporeal membrane oxygenation team dynamics immediately prior to extracorporeal membrane oxygenation cannulation. Pediatric hospitals providing extracorporeal mechanical support services to patients with congenital and/or acquired heart disease. Critical care/cardiology specialist physicians, cardiothoracic surgeons, advanced practice nurse practitioners, respiratory therapists, and extracorporeal membrane oxygenation specialists. None. Survey web links were distributed over a 2-month period with critical care and/or cardiology physicians comprising the majority of respondents (75%). Nearly all respondents practice at academic/teaching institutions (97%), 89% were from U.S./Canadian institutions and 56% reported less than 10 years of clinical experience. During extracorporeal cardiopulmonary resuscitation, a majority of respondents reported adherence to guideline recommendations for epinephrine bolus dosing (64%). Conversely, 19% reported using only one to three epinephrine bolus doses regardless of extracorporeal cardiopulmonary resuscitation duration. Inotropic support is held after extracorporeal membrane oxygenation cannulation "most of the time" by 58% of respondents and 94% report using afterload reducing/antihypertensive agents "some" to "most of the time" after achieving full extracorporeal membrane oxygenation support. Interruptions in chest compressions are common during active cannulation according to 77% of respondents. The results of this survey identify wide variability in resuscitative practices during extracorporeal cardiopulmonary resuscitation in the pediatric cardiac population. The deviations from established Pediatric Advanced Life Support CPR guidelines support a call for further inquiry into the pharmacologic and logistical care surrounding extracorporeal cardiopulmonary resuscitation.

Right Ventricular Perfusion: Physiology and Clinical Implications.

PubMed

Crystal, George J; Pagel, Paul S

2018-01-01

Regulation of blood flow to the right ventricle differs significantly from that to the left ventricle. The right ventricle develops a lower systolic pressure than the left ventricle, resulting in reduced extravascular compressive forces and myocardial oxygen demand. Right ventricular perfusion has eight major characteristics that distinguish it from left ventricular perfusion: (1) appreciable perfusion throughout the entire cardiac cycle; (2) reduced myocardial oxygen uptake, blood flow, and oxygen extraction; (3) an oxygen extraction reserve that can be recruited to at least partially offset a reduction in coronary blood flow; (4) less effective pressure-flow autoregulation; (5) the ability to downregulate its metabolic demand during coronary hypoperfusion and thereby maintain contractile function and energy stores; (6) a transmurally uniform reduction in myocardial perfusion in the presence of a hemodynamically significant epicardial coronary stenosis; (7) extensive collateral connections from the left coronary circulation; and (8) possible retrograde perfusion from the right ventricular cavity through the Thebesian veins. These differences promote the maintenance of right ventricular oxygen supply-demand balance and provide relative resistance to ischemia-induced contractile dysfunction and infarction, but they may be compromised during acute or chronic increases in right ventricle afterload resulting from pulmonary arterial hypertension. Contractile function of the thin-walled right ventricle is exquisitely sensitive to afterload. Acute increases in pulmonary arterial pressure reduce right ventricular stroke volume and, if sufficiently large and prolonged, result in right ventricular failure. Right ventricular ischemia plays a prominent role in these effects. The risk of right ventricular ischemia is also heightened during chronic elevations in right ventricular afterload because microvascular growth fails to match myocyte hypertrophy and because microvascular dysfunction is present. The right coronary circulation is more sensitive than the left to α-adrenergic-mediated constriction, which may contribute to its greater propensity for coronary vasospasm. This characteristic of the right coronary circulation may increase its vulnerability to coronary vasoconstriction and impaired right ventricular perfusion during administration of α-adrenergic receptor agonists.

Patient-specific computational modeling of blood flow in the pulmonary arterial circulation.

PubMed

Kheyfets, Vitaly O; Rios, Lourdes; Smith, Triston; Schroeder, Theodore; Mueller, Jeffrey; Murali, Srinivas; Lasorda, David; Zikos, Anthony; Spotti, Jennifer; Reilly, John J; Finol, Ender A

2015-07-01

Computational fluid dynamics (CFD) modeling of the pulmonary vasculature has the potential to reveal continuum metrics associated with the hemodynamic stress acting on the vascular endothelium. It is widely accepted that the endothelium responds to flow-induced stress by releasing vasoactive substances that can dilate and constrict blood vessels locally. The objectives of this study are to examine the extent of patient specificity required to obtain a significant association of CFD output metrics and clinical measures in models of the pulmonary arterial circulation, and to evaluate the potential correlation of wall shear stress (WSS) with established metrics indicative of right ventricular (RV) afterload in pulmonary hypertension (PH). Right Heart Catheterization (RHC) hemodynamic data and contrast-enhanced computed tomography (CT) imaging were retrospectively acquired for 10 PH patients and processed to simulate blood flow in the pulmonary arteries. While conducting CFD modeling of the reconstructed patient-specific vasculatures, we experimented with three different outflow boundary conditions to investigate the potential for using computationally derived spatially averaged wall shear stress (SAWSS) as a metric of RV afterload. SAWSS was correlated with both pulmonary vascular resistance (PVR) (R(2)=0.77, P<0.05) and arterial compliance (C) (R(2)=0.63, P<0.05), but the extent of the correlation was affected by the degree of patient specificity incorporated in the fluid flow boundary conditions. We found that decreasing the distal PVR alters the flow distribution and changes the local velocity profile in the distal vessels, thereby increasing the local WSS. Nevertheless, implementing generic outflow boundary conditions still resulted in statistically significant SAWSS correlations with respect to both metrics of RV afterload, suggesting that the CFD model could be executed without the need for complex outflow boundary conditions that require invasively obtained patient-specific data. A preliminary study investigating the relationship between outlet diameter and flow distribution in the pulmonary tree offers a potential computationally inexpensive alternative to pressure based outflow boundary conditions. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Monte Carlo modeling of the MammoSite(Reg) treatments: Dose effects of air pockets

NASA Astrophysics Data System (ADS)

Huang, Yu-Huei Jessica

In the treatment of early-stage breast cancer, MammoSiteRTM has been used as one of the partial breast irradiation techniques after breast-conserving surgery. The MammoSiteRTM applicator is a single catheter with an inflatable balloon at its distal end that can be placed in the resected cavity (tumor bed). The treatment is performed by delivering the Ir-192 high-dose-rate source through the center lumen of the catheter by a remote afterloader while the balloon is inflated in the tumor bed cavity. In the MammoSiteRTM treatment, it has been found that air pockets occasionally exist and can be seen and measured in CT images. Experiences have shown that about 90% of the patients have air pockets when imaged two days after the balloon placement. The criterion for the air pocket volume is less than or equal to 10% of the planning target volume in volume. The purpose of this study is to quantify dose errors occurring at the interface of the air pocket in MammoSiteRTM treatments with Monte Carlo calculations, so that the dosimetric effects from the air pocket can be fully understood. Modern brachytherapy treatment planning systems typically consider patient anatomy as a homogeneous water medium, and incorrectly model lateral and backscatter radiation during treatment delivery. Heterogeneities complicate the problem and may result in overdosage to the tissue located near the medium interface. This becomes a problem in MammoSiteRTM brachytherapy when air pocket appears during the treatment. The resulting percentage dose difference near the air-tissue interface is hypothesized to be greater than 10% when comparing Monte Carlo N-Particle (version 5) with current treatment planning systems. The specific aims for this study are: (1) Validate Monte Carlo N-Particle (Version 5) source modeling. (2) Develop phantom. (3) Calculate phantom doses with Monte Carlo N-Particle (Version 5) and investigate doses difference between thermoluminescent dosimeter measurement, treatment planning system, and Monte Carlo results. (4) Calculate dose differences for various treatment parameters. The results from thermoliminescent dosimeter phantom measurements proves that with correct geometric and source models, Monte Carlo method can be used to estimate homogeneity and heterogeneity doses in MammoSiteRTM treatment. The resulting dose differences at various points of interests in Monte Carlo calculations were presented and compared between different calculation methods. The air pocket doses were found to be underestimated by the treatment planning system. It was concluded that after correcting for inverse square law, the underestimation error from the treatment planning system will be less than +/- 2.0%, and +/- 3.5%, at the air pocket surface and air pocket planning target volume, respectively, when comparing Monte Carlo N-Particle (version 5) results. If the skin surface is located close to the air pocket, the underestimation effect at the air pocket surface and air pocket planning target volume doses becomes less because the air outside of the skin surface reduces the air pocket inhomogeneity effect. In order to maintain appropriate skin dose within tolerance, the skin surface criterion should be considered as the smallest thickness of the breast tissue located between the air pocket and the skin surface. The thickness should be at least 5 mm. In conclusion, the air pocket outside the balloon had less than 10% inhomogeneity effect based on the situations studied. It is recommended that at least an inverse square correction should be taken into consideration in order to relate clinical outcomes to actual delivered doses to the air pocket and surrounding tissues.

Comparison of different cardiac relaxation indices.

PubMed

Alipov, N N; Izrail'tyan, I M; Sokolov, A V; Trubetskaya, L V; Kuznetsova, T E

2001-05-01

Sensitivity (response to epinephrine infusion) and specificity (response to changes in pre- and afterload) of some cardiac relaxation indices were compared in acute experiments on cats treated with ganglionic blocker arfonad. Some new indices proposed by us provide better characteristics than widely used relaxation time constant (t) and maximum first derivative of the left ventricular pressure (-dP/dt)max.

Implantable control, telemetry, and solar energy system in the moving actuator type total artificial heart.

PubMed

Ahn, J M; Lee, J H; Choi, S W; Kim, W E; Omn, K S; Park, S K; Kim, W G; Roh, J R; Min, B G

1998-03-01

The moving actuator type total artificial heart (TAH) developed in the Seoul National University has numerous design improvements based upon the digital signal processor (DSP). These improvements include the implantability of all electronics, an automatic control algorithm, and extension of the battery run-time in connection with an amorphous silicon solar system (SS). The implantable electronics consist of the motor drive, main processor, intelligent Li ion battery management (LIBM) based upon the DSP, telemetry system, and transcutaneous energy transmission (TET) system. Major changes in the implantable electronics include decreasing the temperature rise by over 21 degrees C on the motor drive, volume reduction (40 x 55 x 33 mm, 7 cell assembly) of the battery pack using a Li ion (3.6 V/cell, 900 mA.h), and improvement of the battery run-time (over 40 min) while providing the cardiac output (CO) of 5 L/min at 100 mm Hg afterload when the external battery for testing is connected with the SS (2.5 W, 192.192, 1 kg) for the external battery recharge or the partial TAH drive. The phase locked loop (PLL) based telemetry system was implemented to improve stability and the error correction DSP algorithm programmed to achieve high accuracy. A field focused light emitting diode (LED) was used to obtain low light scattering along the propagation path, similar to the optical property of the laser and miniature sized, mounted on the pancake type TET coils. The TET operating resonance frequency was self tuned in a range of 360 to 410 kHz to provide enough power even at high afterloads. An automatic cardiac output regulation algorithm was developed based on interventricular pressure analysis and carried out in several animal experiments successfully. All electronics have been evaluated in vitro and in vivo and prepared for implantation of the TAH. Substantial progress has been made in designing a completely implantable TAH at the preclinical stage.

10 CFR 35.615 - Safety precautions for remote afterloader units, teletherapy units, and gamma stereotactic...

Code of Federal Regulations, 2010 CFR

2010-01-01

... room with viewing and intercom systems to permit continuous observation of the patient or the human... treatment room by a door at each entrance. (b) A licensee shall equip each entrance to the treatment room... cycle unless each treatment room entrance door is closed; (2) Cause the source(s) to be shielded when an...

A model to simulate the haemodynamic effects of right heart pulsatile flow after modified Fontan procedure.

PubMed

Tamaki, S; Kawazoe, K; Yagihara, T; Abe, T

1992-02-01

The effect of pulsatile pulmonary flow after the modified Fontan procedure was examined in a model that simulated the right heart. An inlet overflow tank (preload), axial pulsatile pump, Wind-Kessel model (afterload), and an outlet overflow tank were connected in series. The standard conditions were flow 2.00 l/min with 12 mm Hg preload pressure, 3.0 Wood units resistance, and an outlet overflow tank pressure at 6 mm Hg. The pump rate was set at 80 beats/min. The simulated pulmonary arterial pressure and pulmonary flow waves produced by this model closely resembled those obtained from patients who had undergone the modified Fontan procedure. All variables except the preload were fixed and changes in pulmonary flow were examined at preload pressures of 8, 12, 15, and 17 mm Hg. As the peak pulmonary arterial pressure increased so did pulmonary flow, until it was greater than during the non-pulsatile state. Because the afterload of this model was fixed, this result suggests that there was a concomitant decrease in resistance. This model indicates that pulsatile pulmonary blood flow is likely to have a beneficial effect on the pulmonary circulation after the modified Fontan procedure.

Error Analysis of non-TLD HDR Brachytherapy Dosimetric Techniques

NASA Astrophysics Data System (ADS)

Amoush, Ahmad

The American Association of Physicists in Medicine Task Group Report43 (AAPM-TG43) and its updated version TG-43U1 rely on the LiF TLD detector to determine the experimental absolute dose rate for brachytherapy. The recommended uncertainty estimates associated with TLD experimental dosimetry include 5% for statistical errors (Type A) and 7% for systematic errors (Type B). TG-43U1 protocol does not include recommendation for other experimental dosimetric techniques to calculate the absolute dose for brachytherapy. This research used two independent experimental methods and Monte Carlo simulations to investigate and analyze uncertainties and errors associated with absolute dosimetry of HDR brachytherapy for a Tandem applicator. An A16 MicroChamber* and one dose MOSFET detectors† were selected to meet the TG-43U1 recommendations for experimental dosimetry. Statistical and systematic uncertainty analyses associated with each experimental technique were analyzed quantitatively using MCNPX 2.6‡ to evaluate source positional error, Tandem positional error, the source spectrum, phantom size effect, reproducibility, temperature and pressure effects, volume averaging, stem and wall effects, and Tandem effect. Absolute dose calculations for clinical use are based on Treatment Planning System (TPS) with no corrections for the above uncertainties. Absolute dose and uncertainties along the transverse plane were predicted for the A16 microchamber. The generated overall uncertainties are 22%, 17%, 15%, 15%, 16%, 17%, and 19% at 1cm, 2cm, 3cm, 4cm, and 5cm, respectively. Predicting the dose beyond 5cm is complicated due to low signal-to-noise ratio, cable effect, and stem effect for the A16 microchamber. Since dose beyond 5cm adds no clinical information, it has been ignored in this study. The absolute dose was predicted for the MOSFET detector from 1cm to 7cm along the transverse plane. The generated overall uncertainties are 23%, 11%, 8%, 7%, 7%, 9%, and 8% at 1cm, 2cm, 3cm, and 4cm, 5cm, 6cm, and 7cm, respectively. The Nucletron Freiburg flap applicator is used with the Nucletron remote afterloader HDR machine to deliver dose to surface cancers. Dosimetric data for the Nucletron 192Ir source were generated using Monte Carlo simulation and compared with the published data. Two dimensional dosimetric data were calculated at two source positions; at the center of the sphere of the applicator and between two adjacent spheres. Unlike the TPS dose algorithm, The Monte Carlo code developed for this research accounts for the applicator material, secondary electrons and delta particles, and the air gap between the skin and the applicator. *Standard Imaging, Inc., Middleton, Wisconsin USA † OneDose MOSFET, Sicel Technologies, Morrisville NC ‡ Los Alamos National Laboratory, NM USA

Hemodynamic effects of calcium antagonists in cardiac patients.

PubMed

Pozenel, H

1982-01-01

Hemodynamic studies were carried out after cardiac catheterization with a floatation catheter in the pulmonary artery and cannulation of the brachial artery for the calculation of cardiac output by means of the Fick principle. Continuous pressure recordings were carried out at rest and under submaximal treadmill exercise in the supine body position in 5 homogeneous groups of 12 patients, all with disorders due to coronary disease. In a control test, hemodynamic investigations were carried out at rest before medication, under stress and after recovery. Similar tests were performed after intravenous administration of either isotonic saline as placebo, tiapamil (1.1 and 1.6 mg/kg) or verapamil (0.07 and 0.14 mg/kg). It was shown that there was a marked dose-related reduction in peripheral vascular resistance with a maximum effect occurring at 2-5 min after the intravenous administration of tiapamil (1.1 and 1.6 mg/kg) reaching 23 and 39%, respectively, or verapamil (0.07 and 0.14 mg/kg) attaining 28 and 39%, respectively, at rest and, to a similar extent, under stress conditions. In patients with sinus rhythm, the mean arterial pressure was reduced. Cardiac outputs and stroke volumes were increased at rest as well as under stress. There was no evidence of a depressant action of the drug on hemodynamic variables. An interplay of simultaneous changes in preload and afterload seems to be responsible for the effects obtained. The doses used were those commonly employed in the termination of supraventricular tachyarrhythmias. However, a potential depressant effect of tiapamil in patients with markedly reduced ventricular function is not excluded by this study.

Effect of transverse aortic constriction on cardiac structure, function and gene expression in pregnant rats.

PubMed

Songstad, Nils Thomas; Johansen, David; How, Ole-Jacob; Kaaresen, Per Ivar; Ytrehus, Kirsti; Acharya, Ganesh

2014-01-01

There is an increased risk of heart failure and pulmonary edema in pregnancies complicated by hypertensive disorders. However, in a previous study we found that pregnancy protects against fibrosis and preserves angiogenesis in a rat model of angiotensin II induced cardiac hypertrophy. In this study we test the hypothesis that pregnancy protects against negative effects of increased afterload. Pregnant (gestational day 5.5-8.5) and non-pregnant Wistar rats were randomized to transverse aortic constriction (TAC) or sham surgery. After 14.2 ± 0.14 days echocardiography was performed. Aortic blood pressure and left ventricular (LV) pressure-volume loops were obtained using a conductance catheter. LV collagen content and cardiomyocyte circumference were measured. Myocardial gene expression was assessed by real-time polymerase chain reaction. Heart weight was increased by TAC (p<0.001) but not by pregnancy. Cardiac myocyte circumference was larger in pregnant compared to non-pregnant rats independent of TAC (p = 0.01), however TAC per se did not affect this parameter. Collagen content in LV myocardium was not affected by pregnancy or TAC. TAC increased stroke work more in pregnant rats (34.1 ± 2.4 vs 17.5 ± 2.4 mmHg/mL, p<0.001) than in non-pregnant (28.2 ± 1.7 vs 20.9 ± 1.5 mmHg/mL, p = 0.06). However, it did not lead to overt heart failure in any group. In pregnant rats, α-MHC gene expression was reduced by TAC. Increased in the expression of β-MHC gene was higher in pregnant (5-fold) compared to non-pregnant rats (2-fold) after TAC (p = 0.001). Nine out of the 19 genes related to cardiac remodeling were affected by pregnancy independent of TAC. This study did not support the hypothesis that pregnancy is cardioprotective against the negative effects of increased afterload. Some differences in cardiac structure, function and gene expression between pregnant and non-pregnant rats following TAC indicated that afterload increase is less tolerated in pregnancy.

The Achilles' heel of left ventricular assist device therapy: right ventricle.

PubMed

Ranganath, Neel K; Smith, Deane E; Moazami, Nader

2018-06-01

Many patients suffer from either persistent right ventricular failure (RVF) at the time of left ventricular assist device (LVAD) or have ongoing symptoms consistent with RVF during chronic mechanical circulatory support. The lack of long-term right ventricular assist devices (RVADs) has limited the impact that mechanical circulatory support can provide to patients with biventricular failure. We aim to review the entire spectrum of RVF in patients receiving LVADs and reflect on why this entity remains the Achilles' heel of LVAD therapy. In the early postoperative period, LVAD implantation reduces right ventricle (RV) afterload, but RV dysfunction may be exacerbated secondary to increased venous return. With prolonged therapy, the decreased RV afterload leads to improved RV contractile function. Bayesian statistical models outperform previously published preoperative risk scores by considering inter-relationships and conditional probabilities amongst independent variables. Various echocardiographic parameters and the pulmonary artery pulsatility index have shown promise in predicting post-LVAD RVF. Recent publications have delineated the emergence of 'delayed' RVF. Several devices are currently being investigated for use as RVADs. Post-LVAD RVF depends on the RV's ability to adapt to acute hemodynamic changes imposed by the LVAD. Management options are limited due to the lack of an easily implantable, chronic-use RVAD.

Hemodynamic Performance of a Novel Right Ventricular Assist Device (PERKAT).

PubMed

Kretzschmar, Daniel; Schulze, P Christian; Ferrari, Markus W

Acute right ventricular failure (RVF) is an increasing clinical problem and a life-threatening condition. Right ventricular assist devices represent a reasonable treatment option for patients with refractory RVF. We here present a novel percutaneously implantable device for right ventricular support. The PERKAT device is based on a nitinol stent cage, which is covered with valve-carrying foils. A flexible outlet trunk with a pigtail tip is connected to the distal part. The device is driven by an intra-aortic balloon pump (IABP) drive unit, which inflates/deflates a standard IABP-balloon placed within the stent cage. In-vitro evaluation was done in a liquid bath containing water or blood analog. The PERKAT device was tested in different afterload settings using two different IABP-balloons and varying inflation/deflation rates. We detected flow rates ranging from 1.97 to 3.93 L/min depending on the afterload setting, inflation/deflation rate, balloon size, and the medium used. Flow rates between water and blood analog were nearly comparable, and in the higher inflation/deflation rate settings slightly higher with water. Based on this promising in vitro data, the innovative percutaneously implantable PERKAT device has a potential to become a therapeutic option for patients with RVF refractory to medical treatment.

A Physical Heart Failure Simulation System Utilizing the Total Artificial Heart and Modified Donovan Mock Circulation.

PubMed

Crosby, Jessica R; DeCook, Katrina J; Tran, Phat L; Betterton, Edward; Smith, Richard G; Larson, Douglas F; Khalpey, Zain I; Burkhoff, Daniel; Slepian, Marvin J

2017-07-01

With the growth and diversity of mechanical circulatory support (MCS) systems entering clinical use, a need exists for a robust mock circulation system capable of reliably emulating and reproducing physiologic as well as pathophysiologic states for use in MCS training and inter-device comparison. We report on the development of such a platform utilizing the SynCardia Total Artificial Heart and a modified Donovan Mock Circulation System, capable of being driven at normal and reduced output. With this platform, clinically relevant heart failure hemodynamics could be reliably reproduced as evidenced by elevated left atrial pressure (+112%), reduced aortic flow (-12.6%), blunted Starling-like behavior, and increased afterload sensitivity when compared with normal function. Similarly, pressure-volume relationships demonstrated enhanced sensitivity to afterload and decreased Starling-like behavior in the heart failure model. Lastly, the platform was configured to allow the easy addition of a left ventricular assist device (HeartMate II at 9600 RPM), which upon insertion resulted in improvement of hemodynamics. The present configuration has the potential to serve as a viable system for training and research, aimed at fostering safe and effective MCS device use. © 2016 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

Technique of after-loading interstitial implants.

PubMed

Syed, A M; Feder, B H

1977-01-01

Interstitial implants are either removable or permanent (and occasionally a combination of both). Permanent implants are generally utilized where tumors are not accessible enough to permit easy removal of sources or where accurate source distribution is less critical. They are useful for cancers of the lung, pancreas, prostate, bladder, lymph nodes, etc. Radon and gold-198 have been largely replaced by iodine-125. Our major interests are in the removable after-loading iridium-192 implant techniques. Template (steel guide) and non-template (plastic tube) techniques are utilized. Templates are preferred where the tumor volume can only be approached from one side and where accurate positioning of sources would otherwise be difficult. They are useful for cancers of the cervix, vagina, urethra, and rectum. Non-template (plastic tube) techniques are preferred where the tumor volume can be approached from at least two sides and where templates are either not feasible or not essential for accurate positioning of sources. The single needle non-template approach is useful for cancers of lip, nodes, and breast (plastic button) and for cancers of the oral cavity and oropharynx (gold button). The paired needle non-template approach is useful for cancers of the gum, retromolar trigone, and base of tongue (loop technique) and for cancers of the palate (arch technique). Procedures for each technique are described in detail.

Physiological Characterization of the SynCardia Total Artificial Heart in a Mock Circulation System

PubMed Central

Crosby, Jessica R.; DeCook, Katrina J.; Tran, Phat L.; Smith, Richard G.; Larson, Douglas F.; Khalpey, Zain I.; Burkhoff, Daniel; Slepian, Marvin J.

2014-01-01

The SynCardia total artificial heart (TAH) has emerged as an effective, life-saving bi-ventricular replacement system for a wide variety of patients with end-stage heart failure. While the clinical performance of the TAH is established, modern physiologic characterization, in terms of elastance behavior and pressure-volume characterization has not been defined. Herein we examine the TAH in terms of elastance using a non-ejecting left-ventricle, and then characterize the pressure-volume relationship of the TAH by varying preload and afterload parameters using a Donovan Mock Circulatory System. We demonstrate that the TAH does not operate with time-varying elastance, differing from the human heart. Further, we show that the TAH has a pressure-volume relationship behavior that also differs from that of the human heart. The TAH does exhibit Starling-like behavior, with output increasing via preload dependent mechanisms, without reliance on an alteration of inotropic state within the operating window of the TAH. Within our testing range, the TAH is insensitive to variations in afterload, however this insensitivity has a limit, the limit being the maximum driving pressure of the pneumatic driver. Understanding the physiology of the TAH affords insight into the functional parameters that govern artificial heart behavior providing perspective on differences compared to the human heart. PMID:25551416

Physiological characterization of the SynCardia total artificial heart in a mock circulation system.

PubMed

Crosby, Jessica R; DeCook, Katrina J; Tran, Phat L; Smith, Richard G; Larson, Douglas F; Khalpey, Zain I; Burkhoff, Daniel; Slepian, Marvin J

2015-01-01

The SynCardia total artificial heart (TAH) has emerged as an effective, life-saving biventricular replacement system for a wide variety of patients with end-stage heart failure. Although the clinical performance of the TAH is established, modern physiological characterization, in terms of elastance behavior and pressure-volume (PV) characterization has not been defined. Herein, we examine the TAH in terms of elastance using a nonejecting left ventricle, and then characterize the PV relation of the TAH by varying preload and afterload parameters using a Donovan Mock Circulatory System. We demonstrate that the TAH does not operate with time-varying elastance, differing from the human heart. Furthermore, we show that the TAH has a PV relation behavior that also differs from that of the human heart. The TAH does exhibit Starling-like behavior, with output increasing via preload-dependent mechanisms, without reliance on an alteration of inotropic state within the operating window of the TAH. Within our testing range, the TAH is insensitive to variations in afterload; however, this insensitivity has a limit, the limit being the maximum driving pressure of the pneumatic driver. Understanding the physiology of the TAH affords insight into the functional parameters that govern artificial heart behavior providing perspective on differences compared with the human heart.

Bladder Function Preservation With Brachytherapy, External Beam Radiation Therapy, and Limited Surger in Bladder Cancer Patients: Long-Term Results

DOE Office of Scientific and Technical Information (OSTI.GOV)

Aluwini, Shafak, E-mail: s.aluwini@erasmusmc.nl; Rooij, Peter H.E. van; Kirkels, Wim J.

2014-03-01

Purpose: To report long-term results of a bladder preservation strategy for muscle-invasive bladder cancer (MIBC) using external beam radiation therapy and brachytherapy/interstitial radiation therapy (IRT). Methods and Materials: Between May 1989 and October 2011, 192 selected patients with MIBC were treated with a combined regimen of preoperative external beam radiation therapy and subsequent surgical exploration with or without partial cystectomy and insertion of source carrier tubes for afterloading IRT using low dose rate and pulsed dose rate. Data for oncologic and functional outcomes were prospectively collected. The primary endpoints were local recurrence-free survival (LRFS), bladder function preservation survival, and salvage cystectomy-freemore » survival. The endpoints were constructed according to the Kaplan-Meier method. Results: The mean follow-up period was 105.5 months. The LRFS rate was 80% and 73% at 5 and 10 years, respectively. Salvage cystectomy-free survival at 5 and 10 years was 93% and 85%. The 5- and 10-year overall survival rates were 65% and 46%, whereas cancer-specific survival at 5 and 10 years was 75% and 67%. The distant metastases-free survival rate was 76% and 69% at 5 and 10 years. Multivariate analysis revealed no independent predictors of LRFS. Radiation Therapy Oncology Group grade ≥3 late bladder and rectum toxicity were recorded in 11 patients (5.7%) and 2 patients (1%), respectively. Conclusions: A multimodality bladder-sparing regimen using IRT offers excellent long-term oncologic outcome in selected patients with MIBC. The late toxicity rate is low, and the majority of patients preserve their functional bladder.« less

A workshop on developing risk assessment methods for medical use of radioactive material. Volume 1: Summary

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tortorelli, J.P.

1995-08-01

A workshop was held at the Idaho National Engineering Laboratory, August 16--18, 1994 on the topic of risk assessment on medical devices that use radioactive isotopes. Its purpose was to review past efforts to develop a risk assessment methodology to evaluate these devices, and to develop a program plan and a scoping document for future methodology development. This report contains a summary of that workshop. Participants included experts in the fields of radiation oncology, medical physics, risk assessment, human-error analysis, and human factors. Staff from the US Nuclear Regulatory Commission (NRC) associated with the regulation of medical uses of radioactivemore » materials and with research into risk-assessment methods participated in the workshop. The workshop participants concurred in NRC`s intended use of risk assessment as an important technology in the development of regulations for the medical use of radioactive material and encouraged the NRC to proceed rapidly with a pilot study. Specific recommendations are included in the executive summary and the body of this report. An appendix contains the 8 papers presented at the conference: NRC proposed policy statement on the use of probabilistic risk assessment methods in nuclear regulatory activities; NRC proposed agency-wide implementation plan for probabilistic risk assessment; Risk evaluation of high dose rate remote afterloading brachytherapy at a large research/teaching institution; The pros and cons of using human reliability analysis techniques to analyze misadministration events; Review of medical misadministration event summaries and comparison of human error modeling; Preliminary examples of the development of error influences and effects diagrams to analyze medical misadministration events; Brachytherapy risk assessment program plan; and Principles of brachytherapy quality assurance.« less

Cocoa flavanols reduce N‐terminal pro‐B‐type natriuretic peptide in patients with chronic heart failure

PubMed Central

De Palma, Rodney; Sotto, Imelda; Wood, Elizabeth G.; Khan, Noorafza Q.; Butler, Jane; Johnston, Atholl; Rothman, Martin T.

2015-01-01

Abstract Aims Poor prognosis in chronic heart failure (HF) is linked to endothelial dysfunction for which there is no specific treatment currently available. Previous studies have shown reproducible improvements in endothelial function with cocoa flavanols, but the clinical benefit of this effect in chronic HF has yet to be determined. Therefore, the aim of this study was to assess the potential therapeutic value of a high dose of cocoa flavanols in patients with chronic HF, by using reductions in N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) as an index of improved cardiac function. Methods and results Thirty‐two patients with chronic HF, stable on guideline‐directed medical therapy, were randomized to consume 50 g/day of high‐flavanol dark chocolate (HFDC; 1064 mg of flavanols/day) or low‐flavanol dark chocolate (LFDC; 88 mg of flavanols/day) for 4 weeks and then crossed over to consume the alternative dark chocolate for a further 4 weeks. Twenty‐four patients completed the study. After 4 weeks of HFDC, NT‐proBNP (mean decrease % ± standard deviation) was significantly reduced compared with baseline (−44 ± 69%), LFDC (−33 ± 72%), and follow‐up (−41 ± 77%) values. HFDC also reduced diastolic blood pressure compared with values after LFDC (−6.7 ± 10.1 mmHg). Conclusions Reductions in blood pressure and NT‐proBNP after HFDC indicate decreased vascular resistance resulting in reduced left ventricular afterload. These effects warrant further investigation in patients with chronic HF. PMID:27588209

Air kerma strength characterization of a GZP6 Cobalt-60 brachytherapy source

PubMed Central

Toossi, Mohammad Taghi Bahreyni; Ghorbani, Mahdi; Mowlavi, Ali Asghar; Taheri, Mojtaba; Layegh, Mohsen; Makhdoumi, Yasha; Meigooni, Ali Soleimani

2010-01-01

Background Task group number 40 (TG-40) of the American Association of Physicists in Medicine (AAPM) has recommended calibration of any brachytherapy source before its clinical use. GZP6 afterloading brachytherapy unit is a 60Co high dose rate (HDR) system recently being used in some of the Iranian radiotherapy centers. Aim In this study air kerma strength (AKS) of 60Co source number three of this unit was estimated by Monte Carlo simulation and in air measurements. Materials and methods Simulation was performed by employing the MCNP-4C Monte Carlo code. Self-absorption of the source core and its capsule were taken into account when calculating air kerma strength. In-air measurements were performed according to the multiple distance method; where a specially designed jig and a 0.6 cm3 Farmer type ionization chamber were used for the measurements. Monte Carlo simulation, in air measurement and GZP6 treatment planning results were compared for primary air kerma strength (as for November 8th 2005). Results Monte Carlo calculated and in air measured air kerma strength were respectively equal to 17240.01 μGym2 h−1 and 16991.83 μGym2 h−1. The value provided by the GZP6 treatment planning system (TPS) was “15355 μGym2 h−1”. Conclusion The calculated and measured AKS values are in good agreement. Calculated-TPS and measured-TPS AKS values are also in agreement within the uncertainties related to our calculation, measurements and those certified by the GZP6 manufacturer. Considering the uncertainties, the TPS value for AKS is validated by our calculations and measurements, however, it is incorporated with a large uncertainty. PMID:24376948

SU-E-T-255: Development of a Michigan Quality Assurance (MQA) Database for Clinical Machine Operations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Roberts, D

Purpose: A unified database system was developed to allow accumulation, review and analysis of quality assurance (QA) data for measurement, treatment, imaging and simulation equipment in our department. Recording these data in a database allows a unified and structured approach to review and analysis of data gathered using commercial database tools. Methods: A clinical database was developed to track records of quality assurance operations on linear accelerators, a computed tomography (CT) scanner, high dose rate (HDR) afterloader and imaging systems such as on-board imaging (OBI) and Calypso in our department. The database was developed using Microsoft Access database and visualmore » basic for applications (VBA) programming interface. Separate modules were written for accumulation, review and analysis of daily, monthly and annual QA data. All modules were designed to use structured query language (SQL) as the basis of data accumulation and review. The SQL strings are dynamically re-written at run time. The database also features embedded documentation, storage of documents produced during QA activities and the ability to annotate all data within the database. Tests are defined in a set of tables that define test type, specific value, and schedule. Results: Daily, Monthly and Annual QA data has been taken in parallel with established procedures to test MQA. The database has been used to aggregate data across machines to examine the consistency of machine parameters and operations within the clinic for several months. Conclusion: The MQA application has been developed as an interface to a commercially available SQL engine (JET 5.0) and a standard database back-end. The MQA system has been used for several months for routine data collection.. The system is robust, relatively simple to extend and can be migrated to a commercial SQL server.« less

In Vivo Evaluation of Active and Passive Physiological Control Systems for Rotary Left and Right Ventricular Assist Devices.

PubMed

Gregory, Shaun D; Stevens, Michael C; Pauls, Jo P; Schummy, Emma; Diab, Sara; Thomson, Bruce; Anderson, Ben; Tansley, Geoff; Salamonsen, Robert; Fraser, John F; Timms, Daniel

2016-09-01

Preventing ventricular suction and venous congestion through balancing flow rates and circulatory volumes with dual rotary ventricular assist devices (VADs) configured for biventricular support is clinically challenging due to their low preload and high afterload sensitivities relative to the natural heart. This study presents the in vivo evaluation of several physiological control systems, which aim to prevent ventricular suction and venous congestion. The control systems included a sensor-based, master/slave (MS) controller that altered left and right VAD speed based on pressure and flow; a sensor-less compliant inflow cannula (IC), which altered inlet resistance and, therefore, pump flow based on preload; a sensor-less compliant outflow cannula (OC) on the right VAD, which altered outlet resistance and thus pump flow based on afterload; and a combined controller, which incorporated the MS controller, compliant IC, and compliant OC. Each control system was evaluated in vivo under step increases in systemic (SVR ∼1400-2400 dyne/s/cm(5) ) and pulmonary (PVR ∼200-1000 dyne/s/cm(5) ) vascular resistances in four sheep supported by dual rotary VADs in a biventricular assist configuration. Constant speed support was also evaluated for comparison and resulted in suction events during all resistance increases and pulmonary congestion during SVR increases. The MS controller reduced suction events and prevented congestion through an initial sharp reduction in pump flow followed by a gradual return to baseline (5.0 L/min). The compliant IC prevented suction events; however, reduced pump flows and pulmonary congestion were noted during the SVR increase. The compliant OC maintained pump flow close to baseline (5.0 L/min) and prevented suction and congestion during PVR increases. The combined controller responded similarly to the MS controller to prevent suction and congestion events in all cases while providing a backup system in the event of single controller failure. © 2016 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

Combined treatment of inoperable carcinomas of the uterine cervix with radiotherapy and regional hyperthermia. Results of a phase II trial.

PubMed

Dinges, S; Harder, C; Wurm, R; Buchali, A; Blohmer, J; Gellermann, J; Wust, P; Randow, H; Budach, V

1998-10-01

The disappointing results for inoperable, advanced tumors of the uterine cervix after conventional radiotherapy alone necessitates improving of radiation therapy. Simultaneous chemotherapy or altered radiation fractionation, such as accelerated regimen, increase acute toxicity and treatment is often difficult to deliver in the planned manner. The purpose of this phase II study was to investigate the toxicity and effectiveness of a combined approach with radiotherapy and regional hyperthermia. From January 1994 to October 1995 18 patients with advanced carcinomas of the uterine cervix were treated in combination with radiotherapy and hyperthermia. The patients were treated with 6 to 20 MV photons delivered by a linear accelerator in a 4-field-box technique to a total dose of 50.4 Gy in 28 fractions. In the first and fourth week 2 regional hyperthermia treatments were each applied with the Sigma-60 applicator from a BSD-2000 unit. After this a boost to the primary tumor was given with high-dose-rate iridium-192 brachytherapy by an afterloading technique with 4 x 5 Gy at point A to a total of 20 Gy and for the involved parametrium anterioposterior-posterioanterior to 9 Gy in 5 fractions. The acute toxicity was low and similar to an external radiotherapy alone treatment. No Grade III/IV acute toxicity was found. The median age was 47 years (range 34 to 67 years). In 16 of 18 patients a rapid tumor regression was observed during combined thermo-radiotherapy, which allowed the use of intracavitary high-dose-rate brachytherapy in these cases. Complete and partial remission were observed in 13 and 4 cases, respectively. One patient did not respond to the treatment. The median follow-up was 24 months (range 17 to 36 months). The local tumor control rate was 48% at 2 years. Median T20, T50 and T90 values were 41.7 degrees C (range 40.3 to 43.2 degrees C), 41.1 degrees C (range 39.2 to 42.5 degrees C) and 39.9 degrees C (range 37.7 to 41.9 degrees C), respectively. Cumulative minutes of T90 > 40 degrees C (Cum40T90) and cumulative minutes, which were isoeffective to 43 degrees C, were calculated (CEM43T90, CEM43T50, CEM43T20). CEM43T90 was found to be a significant parameter in terms of local tumor control for the 4 hyperthermia treatments (p = 0.019). This treatment modality has proved to be feasible and well tolerable. The rapid tumor shrinkage in the combined approach of radiotherapy with hyperthermia before beginning brachytherapy seems to be a good prerequisite for improving of the disappointing results in cure of advanced cancer of the uterine cervix.

Point-of-Care Ultrasonography to Assess Portal Vein Pulsatility and the Effect of Inhaled Milrinone and Epoprostenol in Severe Right Ventricular Failure: A Report of 2 Cases.

PubMed

Tremblay, Jan-Alexis; Beaubien-Souligny, William; Elmi-Sarabi, Mahsa; Desjardins, Georges; Denault, André Y

2017-10-15

This article describes 2 patients with severe acute right ventricular failure causing circulatory shock. Portal vein pulsatility assessed by bedside ultrasonography suggested clinically relevant venous congestion. Management included cardiac preload reduction and combined inhalation of milrinone and epoprostenol to reduce right ventricular afterload. Portal vein ultrasonography may be useful in assessing right ventricular function in the acutely ill patient.

TU-C-201-01: Clinical Implementation of HDR: A New User’s Perspective

DOE Office of Scientific and Technical Information (OSTI.GOV)

Al-Hallaq, H.

2015-06-15

Recent use of HDR has increased while planning has become more complex often necessitating 3D image-based planning. While many guidelines for the use of HDR exist, they have not kept pace with the increased complexity of 3D image-based planning. Furthermore, no comprehensive document exists to describe the wide variety of current HDR clinical indications. This educational session aims to summarize existing national and international guidelines for the safe implementation of an HDR program. A summary of HDR afterloaders available on the market and their existing applicators will be provided, with guidance on how to select the best fit for eachmore » institution’s needs. Finally, the use of checklists will be discussed as a means to implement a safe and efficient HDR program and as a method by which to verify the quality of an existing HDR program. This session will provide the perspective of expert HDR physicists as well as the perspective of a new HDR user. Learning Objectives: Summarize national and international safety and staffing guidelines for HDR implementation Discuss the process of afterloader and applicator selection for gynecologic, prostate, breast, interstitial, surface treatments Learn about the use of an audit checklist tool to measure of quality control of a new or existing HDR program Describe the evolving use of checklists within an HDR program.« less

TU-C-201-00: Clinical Implementation of HDR Brachytherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

NONE

2015-06-15

Recent use of HDR has increased while planning has become more complex often necessitating 3D image-based planning. While many guidelines for the use of HDR exist, they have not kept pace with the increased complexity of 3D image-based planning. Furthermore, no comprehensive document exists to describe the wide variety of current HDR clinical indications. This educational session aims to summarize existing national and international guidelines for the safe implementation of an HDR program. A summary of HDR afterloaders available on the market and their existing applicators will be provided, with guidance on how to select the best fit for eachmore » institution’s needs. Finally, the use of checklists will be discussed as a means to implement a safe and efficient HDR program and as a method by which to verify the quality of an existing HDR program. This session will provide the perspective of expert HDR physicists as well as the perspective of a new HDR user. Learning Objectives: Summarize national and international safety and staffing guidelines for HDR implementation Discuss the process of afterloader and applicator selection for gynecologic, prostate, breast, interstitial, surface treatments Learn about the use of an audit checklist tool to measure of quality control of a new or existing HDR program Describe the evolving use of checklists within an HDR program.« less

In vitro evaluation of the effect of aortic compliance on pediatric intra-aortic balloon pumping.

PubMed

Minich, L L; Tani, L Y; Hawkins, J A; Bartkowiak, R R; Royall, M L; Pantalos, G M

2001-04-01

OBJECTIVES: To evaluate the effect of aortic compliance on pediatric intra-aortic balloon pumping (IABP). DESIGN: In vitro study using a mechanical model of the pediatric left heart circulation. SETTING: Cardiovascular fluid dynamics research laboratory. SUBJECT: Pulsatile flow system simulating the pediatric left heart circulation and two different aortas with compliances comparable to those of the pediatric aorta (0.12 and 0.07 mL/mm Hg). INTERVENTIONS: Measurements were made at a baseline peak aortic flow of 4 L/min, at simulated shock (1.7 L/min), and with 1:1 IABP (rates, 130 and 150 bpm; balloon volumes, 2.5 and 5.0 mL). MEASUREMENTS AND MAIN RESULTS: Peak flow rates were measured in the ascending aorta, coronary arterial system, and brachiocephalic arterial systems. Aortic pressure was measured in the ascending aorta. For both aortas (0.12 and 0.07 mL/mm Hg), IABP resulted in diastolic augmentation (38 +/- 8 and 43 +/- 16 mm Hg) and afterload reduction (4 +/- 2 and 6 +/- 3 mm Hg). For both aortas, compared to shock, IABP resulted in significant increases in coronary arterial and brachiocephalic arterial flow and aortic pressure for both aortas. Aortic flow significantly increased only in the less-compliant aorta. CONCLUSIONS: In a laboratory model of pediatric left heart circulation, IABP results in diastolic augmentation, afterload reduction, and improved hemodynamics, even in aortas of greater compliance.

Control of a rotary pulsatile cardiac assist pump driven by an electric motor without a pressure sensor to avoid collapse of the pump inlet.

PubMed

Trinkl, J; Havlik, P; Mesana, T; Mitsui, N; Morita, S; Demunck, J L; Tourres, J L; Monties, J R

1993-01-01

Our ventricular assist device uses a valveless volumetric pump operating on the Maillard-Wankel rotary principle. It is driven by an electric motor and provides a semi pulsatile flow. At each cycle, blood is actively aspirated into the device, and overpumping results in collapse at the pump inlet. To prevent overpumping, it is necessary to ensure that pump intake does not exceed venous return. Poor long-term reliability rules out the use of current implantable pressure sensors for this purpose. To resolve this problem, we have developed a method of control based on monitoring of the intensity of electric current consumed by the motor. The method consists of real time monitoring of current intensity at the beginning of each pump cycle. A sudden change in intensity indicates underfilling, and motor speed is reduced to prevent collapse. The current consumed by the motor also depends on the afterload, but the form of the signal remains the same when afterload changes. After demonstrating the feasibility of this technique in a simulator, we are now testing it in animals. We were able to detect and prevent collapse due to overpumping by the cardiac assist device. This system also enables us to know the maximum possible assistance and to thus adapt assistance to the user.

TU-C-201-03: The Use of Checklists and Audit Tools for Safety and QA

DOE Office of Scientific and Technical Information (OSTI.GOV)

Prisciandaro, J.

Recent use of HDR has increased while planning has become more complex often necessitating 3D image-based planning. While many guidelines for the use of HDR exist, they have not kept pace with the increased complexity of 3D image-based planning. Furthermore, no comprehensive document exists to describe the wide variety of current HDR clinical indications. This educational session aims to summarize existing national and international guidelines for the safe implementation of an HDR program. A summary of HDR afterloaders available on the market and their existing applicators will be provided, with guidance on how to select the best fit for eachmore » institution’s needs. Finally, the use of checklists will be discussed as a means to implement a safe and efficient HDR program and as a method by which to verify the quality of an existing HDR program. This session will provide the perspective of expert HDR physicists as well as the perspective of a new HDR user. Learning Objectives: Summarize national and international safety and staffing guidelines for HDR implementation Discuss the process of afterloader and applicator selection for gynecologic, prostate, breast, interstitial, surface treatments Learn about the use of an audit checklist tool to measure of quality control of a new or existing HDR program Describe the evolving use of checklists within an HDR program.« less

Right ventricular sex differences in patients with idiopathic pulmonary arterial hypertension characterised by magnetic resonance imaging: pair-matched case controlled study.

PubMed

Swift, Andrew J; Capener, Dave; Hammerton, Charlotte; Thomas, Steven M; Elliot, Charlie; Condliffe, Robin; Wild, Jim M; Kiely, David G

2015-01-01

Sex differences exist in both the prevalence and survival of patients with idiopathic pulmonary arterial hypertension (IPAH). Men are less frequently affected by the condition but have worse outcome as compared to females. We sought to characterise the sex related differences in right ventricular remodelling in age matched male and female patients with IPAH using cardiac magnetic resonance imaging (MRI). A case controlled pair-matched study was conducted with patients matched by age and sex. Steady state free precession (SSFP) MRI of the heart was performed at 1.5T. Cardiac volume, function and mass measurements were corrected for age, sex and BSA according to reference data. 40 age and sex matched patients with IPAH were identified. The mean age was 57 (SD 17) in both male and female cohorts. Men had proportionally lower right ventricular (RV) ejection fraction, RV stroke volume and LV stroke volume than females, p=0.028, p=0.007 and p=0.013, respectively. However, there was no significant difference in RV mass or haemodynamic indices of mPAP and PVR between males and females. Male patients with IPAH have proportionally worse RV function despite similar afterload. We hypothesise that adaptive remodelling of the RV in response to increased afterload in IPAH is more effective in females.

Right Ventricular Sex Differences in Patients with Idiopathic Pulmonary Arterial Hypertension Characterised by Magnetic Resonance Imaging: Pair-Matched Case Controlled Study

PubMed Central

Swift, Andrew J.; Capener, Dave; Hammerton, Charlotte; Thomas, Steven M.; Elliot, Charlie; Condliffe, Robin; Wild, Jim M.; Kiely, David G.

2015-01-01

Purpose Sex differences exist in both the prevalence and survival of patients with idiopathic pulmonary arterial hypertension (IPAH). Men are less frequently affected by the condition but have worse outcome as compared to females. We sought to characterise the sex related differences in right ventricular remodelling in age matched male and female patients with IPAH using cardiac magnetic resonance imaging (MRI). Methods A case controlled pair-matched study was conducted with patients matched by age and sex. Steady state free precession (SSFP) MRI of the heart was performed at 1.5T. Cardiac volume, function and mass measurements were corrected for age, sex and BSA according to reference data. Results 40 age and sex matched patients with IPAH were identified. The mean age was 57 (SD 17) in both male and female cohorts. Men had proportionally lower right ventricular (RV) ejection fraction, RV stroke volume and LV stroke volume than females, p=0.028, p=0.007 and p=0.013, respectively. However, there was no significant difference in RV mass or haemodynamic indices of mPAP and PVR between males and females. Conclusion Male patients with IPAH have proportionally worse RV function despite similar afterload. We hypothesise that adaptive remodelling of the RV in response to increased afterload in IPAH is more effective in females. PMID:25996939

Load dependence of left ventricular contraction and relaxation. Effects of caffeine.

PubMed

Leite-Moreira, A F; Correia-Pinto, J; Gillebert, T C

1999-08-01

Load dependence of left ventricular (LV) contraction and relaxation was investigated at baseline and after alteration of intracellular calcium handling by caffeine. Afterload was increased by aortic clamp occlusions (n = 281) in anesthetized open-chest dogs (n = 7). Control and first heartbeat after the intervention were considered for analysis. Caffeine (50 mg/kg, iv) had no inotropic effect. The systolic LV pressure (LVP), developed in response to aortic occlusion, decreased as ejection proceeded and this pressure generating capacity was not affected by caffeine. Late-systolic aortic occlusions induced premature onset and accelerated rate of initial LVP fall at baseline and similarly after caffeine. Graded diastolic aortic occlusions induced systolic LVP elevations of various magnitudes. Smaller LVP elevations prolonged ejection and accelerated LVP fall, while larger elevations had opposite effects. The transition from acceleration to deceleration was observed at 83.1 +/- 1.1% of peak isovolumetric LVP at baseline and at lower loads, at 77.6 +/- 1.2%, after caffeine (p < 0.01). Isovolumetric heartbeats prolonged the time constant tau by 238 +/- 70% at baseline and only by 155 +/- 44% after caffeine (p < 0.01). The relaxation-systolic pressure relation, which describes afterload dependence of relaxation, was also modified by caffeine. Caffeine affected LV relaxation without altering contractility. As a consequence contraction-relaxation coupling was modified by caffeine. These results might help to understand load dependence of relaxation in conditions where intracellular calcium handling is altered.

Pulmonary vascular and right ventricular dysfunction in adult critical care: current and emerging options for management: a systematic literature review.

PubMed

Price, Laura C; Wort, Stephen J; Finney, Simon J; Marino, Philip S; Brett, Stephen J

2010-01-01

Pulmonary vascular dysfunction, pulmonary hypertension (PH), and resulting right ventricular (RV) failure occur in many critical illnesses and may be associated with a worse prognosis. PH and RV failure may be difficult to manage: principles include maintenance of appropriate RV preload, augmentation of RV function, and reduction of RV afterload by lowering pulmonary vascular resistance (PVR). We therefore provide a detailed update on the management of PH and RV failure in adult critical care. A systematic review was performed, based on a search of the literature from 1980 to 2010, by using prespecified search terms. Relevant studies were subjected to analysis based on the GRADE method. Clinical studies of intensive care management of pulmonary vascular dysfunction were identified, describing volume therapy, vasopressors, sympathetic inotropes, inodilators, levosimendan, pulmonary vasodilators, and mechanical devices. The following GRADE recommendations (evidence level) are made in patients with pulmonary vascular dysfunction: 1) A weak recommendation (very-low-quality evidence) is made that close monitoring of the RV is advised as volume loading may worsen RV performance; 2) A weak recommendation (low-quality evidence) is made that low-dose norepinephrine is an effective pressor in these patients; and that 3) low-dose vasopressin may be useful to manage patients with resistant vasodilatory shock. 4) A weak recommendation (low-moderate quality evidence) is made that low-dose dobutamine improves RV function in pulmonary vascular dysfunction. 5) A strong recommendation (moderate-quality evidence) is made that phosphodiesterase type III inhibitors reduce PVR and improve RV function, although hypotension is frequent. 6) A weak recommendation (low-quality evidence) is made that levosimendan may be useful for short-term improvements in RV performance. 7) A strong recommendation (moderate-quality evidence) is made that pulmonary vasodilators reduce PVR and improve RV function, notably in pulmonary vascular dysfunction after cardiac surgery, and that the side-effect profile is reduced by using inhaled rather than systemic agents. 8) A weak recommendation (very-low-quality evidence) is made that mechanical therapies may be useful rescue therapies in some settings of pulmonary vascular dysfunction awaiting definitive therapy. This systematic review highlights that although some recommendations can be made to guide the critical care management of pulmonary vascular and right ventricular dysfunction, within the limitations of this review and the GRADE methodology, the quality of the evidence base is generally low, and further high-quality research is needed.

A nursing diagnosis approach to the patient awaiting cardiac transplantation.

PubMed

Cardin, S; Clark, S

1985-09-01

The most common reason to perform cardiac transplantation is dilated cardiomyopathy. Alterations in cardiac output secondary to decreased contractility and increased preload and afterload will, over time, lead to progressive deterioration of the patient with this type of end-stage cardiac disease. Heart transplantation is now an accepted therapy for these patients. This article focused on the patient in the period awaiting cardiac transplantation. Five pertinent nursing diagnoses were identified and discussed. A case study approach was utilized to highlight patient problems and nursing interventions.

Circulatory therapeutics: use of antihypertensive agents and their effects on the vasculature

PubMed Central

Schiffrin, Ernesto L

2010-01-01

Abstract This review addresses the use of the different antihypertensive agents currently available and some in development, and their effects on the vasculature. The different classes of agents used in the treatment of hypertension, and the results of recent large clinical trials, dosing protocols and adverse effects are first briefly summarized. The consequences on blood vessels of the use of antihypertensive drugs and the differential effects on the biology of large and small arteries resulting in modulation of vascular remodelling and dysfunction in hypertensive patients are then described. Large elastic conduit arteries exhibit outward hypertrophic remodelling and increased stiffness, which contributes to raise systolic blood pressure and afterload on the heart. Small resistance arteries undergo eutrophic or hypertrophic inward remodelling, and impair tissue perfusion. By these mechanisms both large and small arteries may contribute to trigger cardiovascular events. Some antihypertensive agents correct these changes, which could contribute to improved outcome. The mechanisms that at the level of the vascular wall lead to remodelling and can be beneficially affected by antihypertensive agents will also be addressed. These include vasoconstriction, growth and inflammation. The molecular pathways contributing to growth and inflammation will be summarily described. Further identification of these signalling pathways should allow identification of novel targets leading to development of new and improved medications for the treatment of hypertension and cardiovascular disease. PMID:20345850

Combination of external beam irradiation and multiple-site perineal applicator (MUPIT) for treatment of locally advanced or recurrent prostatic, anorectal, and gynecologic malignancies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Martinez, A.; Edmundson, G.K.; Cox, R.S.

1985-02-01

The authors have devised a single after-loading applicator, the Martinez Universal Perineal Interstitital Template (MUPIT), which has been used in combination with external beam irradiation to treat 104 patients with either locally advanced or recurrent malignancies of the cervix, vagina, female uretha, prostate, or anorectal region. Twenty-six patients treated for prostate cancer are excluded because of their short follow-up. Local failure developed in 13 of the 78 remaining patients (16.6%) - major complications developed in 4 patients (5.1%). All local recurrences and complications occurred before 18 months. The device consists of two acrylic cyclinders, an acrylic template with an arraymore » of holes that serve as guides for trocars, and a cover plate. In use, the cylinders are placed in the vagina and/or rectum or both and then fastened to the template so that a fixed geometric relationship among the tumor volume, normal structures, and source placement is preserved throughout the course of the implantation. Appropriate computer programs have been developed to calculate the dose from these implants. They conclude that the local control rate (83.4%) with low morbidity (5.1%) achieved with the combination of external beam irradiation and MUPIT applicator in these patients with locally advanced malignancies represents an improvement over previous published results with other applicators.« less

Pediatric Artificial Lung: A Low-Resistance Pumpless Artificial Lung Alleviates an Acute Lamb Model of Increased Right Ventricle Afterload.

PubMed

Alghanem, Fares; Bryner, Benjamin S; Jahangir, Emilia M; Fernando, Uditha P; Trahanas, John M; Hoffman, Hayley R; Bartlett, Robert H; Rojas-Peña, Alvaro; Hirschl, Ronald B

Lung disease in children often results in pulmonary hypertension and right heart failure. The availability of a pediatric artificial lung (PAL) would open new approaches to the management of these conditions by bridging to recovery in acute disease or transplantation in chronic disease. This study investigates the efficacy of a novel PAL in alleviating an animal model of pulmonary hypertension and increased right ventricle afterload. Five juvenile lambs (20-30 kg) underwent PAL implantation in a pulmonary artery to left atrium configuration. Induction of disease involved temporary, reversible occlusion of the right main pulmonary artery. Hemodynamics, pulmonary vascular input impedance, and right ventricle efficiency were measured under 1) baseline, 2) disease, and 3) disease + PAL conditions. The disease model altered hemodynamics variables in a manner consistent with pulmonary hypertension. Subsequent PAL attachment improved pulmonary artery pressure (p = 0.018), cardiac output (p = 0.050), pulmonary vascular input impedance (Z.0 p = 0.028; Z.1 p = 0.058), and right ventricle efficiency (p = 0.001). The PAL averaged resistance of 2.3 ± 0.8 mm Hg/L/min and blood flow of 1.3 ± 0.6 L/min. This novel low-resistance PAL can alleviate pulmonary hypertension in an acute animal model and demonstrates potential for use as a bridge to lung recovery or transplantation in pediatric patients with significant pulmonary hypertension refractory to medical therapies.

Is chronic inhibition of phosphodiesterase type 5 cardioprotective and safe? A meta-analysis of randomized controlled trials.

PubMed

Giannetta, Elisa; Feola, Tiziana; Gianfrilli, Daniele; Pofi, Riccardo; Dall'Armi, Valentina; Badagliacca, Roberto; Barbagallo, Federica; Lenzi, Andrea; Isidori, Andrea M

2014-10-20

The myocardial effects of phosphodiesterase type 5 inhibitors (PDE5i) have recently received consideration in several preclinical studies. The risk/benefit ratio in humans remains unclear. We performed a meta-analysis of randomized, placebo-controlled trials (RCTs) to evaluate the efficacy and safety of PDE5i on cardiac morphology and function. From March 2012 to December 2013 (update: May 2014), we searched English-language studies from MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials and SCOPUS-selecting RCTs of continuous PDE5i administration that reported cardiovascular outcomes: cardiac geometry and performance, afterload, endothelial function and safety. The pooled estimate of a weighted mean difference between treatment and placebo was obtained for all outcomes using a random effects model. A test for heterogeneity was performed and the I2 statistic calculated. Overall, 1,622 subjects were treated, with 954 randomized to PDE5i and 772 to placebo in 24 RCTs. According to our analysis, sustained PDE5 inhibition produced: (1) an anti-remodeling effect by reducing cardiac mass (-12.21 g/m2, 95% confidence interval (CI): -18.85; -5.57) in subjects with left ventricular hypertrophy (LVH) and by increasing end-diastolic volume (5.00 mL/m2; 95% CI: 3.29; 6.71) in non-LVH patients; (2) an improvement in cardiac performance by increasing cardiac index (0.30 L/min/m2, 95% CI: 0.202; 0.406) and ejection fraction (3.56%, 95% CI: 1.79; 5.33). These effects are parallel to a decline of N-terminal-pro brain natriuretic peptide (NT-proBNP) in subjects with severe LVH (-486.7 pg/ml, 95% CI: -712; -261). PDE5i administration also produced: (3) no changes in afterload parameters and (4) an improvement in flow-mediated vasodilation (3.31%, 95% CI: 0.53; 6.08). Flushing, headache, epistaxis and gastric symptoms were the commonest side effects. This meta-analysis suggests for the first time that PDE5i have anti-remodeling properties and improve cardiac inotropism, independently of afterload changes, with a good safety profile. Given the reproducibility of the findings and tolerability across different populations, PDE5i could be reasonably offered to men with cardiac hypertrophy and early stage heart failure. Given the limited gender data, a larger trial on the sex-specific response to long-term PDE5i treatment is required.

Clinical determinants and consequences of left ventricular hypertrophy.

PubMed

Messerli, F H

1983-09-26

The left ventricle adapts to an increased afterload such as that produced by arterial hypertension with concentric left ventricular hypertrophy. However, this adaptive process can be modified by a variety of physiologic and pathophysiologic states. Progressive aging, black race, and perhaps disorders with an increased sympathetic outflow seem to accelerate left ventricular hypertrophy. Obesity and other high cardiac output states predominantly produce dilatation of the left ventricle, and their combination with arterial hypertension results in eccentric left ventricular hypertrophy. Similarly, endurance exercise increases left ventricular volume more than wall thickness, whereas isometric exercise produces an increase in wall thickness only. The presence or absence of some physiologic and pathogenetic factors has direct implication on the assessment of what constitutes a "normal" left ventricular structure and function. Left ventricular hypertrophy has been shown to increase ventricular ectopic impulse generation and to put patients at a high risk of sudden death. Moreover, the increase in myocardial mass lowers coronary reserve and enhances cardiac oxygen requirements. Thus, the presence of left ventricular hypertrophy has to be considered as an ominous sign rather than as a benign adaptive process.

The Critical Role of Pulmonary Arterial Compliance in Pulmonary Hypertension

PubMed Central

Prins, Kurt W.; Pritzker, Marc R.; Scandurra, John; Volmers, Karl; Weir, E. Kenneth

2016-01-01

The normal pulmonary circulation is a low-pressure, high-compliance system. Pulmonary arterial compliance decreases in the presence of pulmonary hypertension because of increased extracellular matrix/collagen deposition in the pulmonary arteries. Loss of pulmonary arterial compliance has been consistently shown to be a predictor of increased mortality in patients with pulmonary hypertension, even more so than pulmonary vascular resistance in some studies. Decreased pulmonary arterial compliance causes premature reflection of waves from the distal pulmonary vasculature, leading to increased pulsatile right ventricular afterload and eventually right ventricular failure. Evidence suggests that decreased pulmonary arterial compliance is a cause rather than a consequence of distal small vessel proliferative vasculopathy. Pulmonary arterial compliance decreases early in the disease process even when pulmonary artery pressure and pulmonary vascular resistance are normal, potentially enabling early diagnosis of pulmonary vascular disease, especially in high-risk populations. With the recognition of the prognostic importance of pulmonary arterial compliance, its impact on right ventricular function, and its contributory role in the development and progression of distal small-vessel proliferative vasculopathy, pulmonary arterial compliance is an attractive target for the treatment of pulmonary hypertension. PMID:26848601

Cardiovascular anatomy and physiology of the fetus, neonate, infant, child, and adolescent.

PubMed

Alyn, I B; Baker, L K

1992-04-01

Practicing cardiovascular nurses are aware that significant differences exist in the cardiac anatomy and physiology of children and adults. Generally, the younger the child the greater these differences are. The cellular anatomy and physiology are markedly different in the fetus, neonate, and infant. As development progresses, cardiac function begins to more closely approximate that of an adult. This article describes the anatomical and physiologic development of the fetus, neonate, infant, child, and adolescent. The developmental differences in preload, afterload, contractility, and heart rate are summarized.

Equine Cardiovascular Therapeutics.

PubMed

Sleeper, Meg M

2017-04-01

Heart disease can be defined as any abnormality of the heart whether it is a cardiac dysrhythmia or structural heart disease, either congenital or acquired. Heart failure occurs when a cardiac abnormality results in the inability of the heart to pump enough blood to meet the body's needs. Heart disease can be present without leading to heart failure. Heart failure, however, is a consequence of heart disease. There are 4 main areas where the clinician can intervene to improve cardiac output with heart failure: preload, afterload, myocardial contractility, and heart rate. Copyright © 2016 Elsevier Inc. All rights reserved.

Positive inotropic and vasodilator actions of milrinone in patients with severe congestive heart failure. Dose-response relationships and comparison to nitroprusside.

PubMed Central

Jaski, B E; Fifer, M A; Wright, R F; Braunwald, E; Colucci, W S

1985-01-01

Milrinone is a potent positive inotropic and vascular smooth muscle-relaxing agent in vitro, and therefore, it is not known to what extent each of these actions contributes to the drug's hemodynamic effects in patients with heart failure. In 11 patients with New York Heart Association class III or IV congestive heart failure, incremental intravenous doses of milrinone were administered to determine the dose-response relationships for heart rate, systemic vascular resistance, and inotropic state, the latter measured by peak positive left ventricular derivative of pressure with respect to time (dP/dt). To clarify further the role of a positive inotropic action, the relative effects of milrinone and nitroprusside on left ventricular stroke work and dP/dt were compared in each patient at doses matched to cause equivalent reductions in mean arterial pressure or systemic vascular resistance, indices of left ventricular afterload. Milrinone caused heart rate, stroke volume, and dP/dt to increase, and systemic vascular resistance to decrease in a concentration-related manner. At the two lowest milrinone doses resulting in serum concentrations of 63 +/- 4 and 156 +/- 5 ng/ml, respectively, milrinone caused significant increases in stroke volume and dP/dt, but no changes in systemic vascular resistance or heart rate. At the maximum milrinone dose administered (mean serum concentration, 427 +/- 11 ng/ml), heart rate increased from 92 +/- 4 to 99 +/- 4 bpm (P less than 0.01), mean aortic pressure fell from 82 +/- 3 to 71 +/- 3 mmHg (P less than 0.01), right atrial pressure fell from 15 +/- 2 to 7 +/- 1 mmHg (P less than 0.005), left ventricular end-diastolic pressure fell from 26 +/- 3 to 18 +/- 3 (P less than 0.005), stroke volume index increased from 20 +/- 2 to 30 +/- 2 ml/m2 (P less than 0.005), stroke work index increased from 14 +/- 2 to 21 +/- 2 g X m/m2 (P less than 0.01), and dP/dt increased from 858 +/- 54 to 1,130 +/- 108 mmHg/s (P less than 0.005). When compared with nitroprusside for a matched reduction in mean aortic pressure or systemic vascular resistance, milrinone caused a significantly greater increase in stroke work index at the same or lower left ventricular end-diastolic pressure. Milrinone caused a concentration-related increase in dP/dt (32% increase at maximum milrinone dose), whereas nitroprusside had no effect. These data in patients with severe heart failure indicate that in addition to a vasodilating effect, milrinone exerts a concentration-related positive inotropic action that contributes significantly to the drug's overall hemodynamic effects. The positive inotropic action occurs at drug levels that do not exert significant chronotropic or vasodilator effects. Images PMID:3973022

Viscous Energy Loss in the Presence of Abnormal Aortic Flow

PubMed Central

Barker, A.J.; van Ooij, P.; Bandi, K.; Garcia, J.; Albaghdadi, M.; McCarthy, P.; Bonow, R. O.; Carr, J.; Collins, J.; Malaisrie, C.; Markl, M.

2014-01-01

Purpose To present a theoretical basis for noninvasively characterizing in vivo fluid-mechanical energy losses, and to apply it in a pilot study of patients known to express abnormal aortic flow patterns. Methods 4D flow MRI was used to characterize laminar viscous energy losses in the aorta of normal controls (n=12, age=37±10), patients with aortic dilation (n=16, age=52±8), and patients with aortic valve stenosis matched for age and aortic size (n=14, age=46±15), using a relationship between the 3D velocity field and viscous energy dissipation. Results Viscous energy loss was significantly elevated in the thoracic aorta for patients with dilated aorta (3.6±1.3 mW, p=0.024) and patients with aortic stenosis (14.3±8.2 mW, p<0.001) compared to healthy volunteers (2.3±0.9 mW). The same pattern of significant differences were seen in the ascending aorta, where viscous energy losses in patients with dilated aortas (2.2±1.1 mW, p=0.021) and patients with aortic stenosis (10.9±6.8 mW, p<0.001) were elevated compared to healthy volunteers (1.2±0.6 mW). Conclusion This technique provides a capability to quantify the contribution of abnormal laminar blood flow to increased ventricular afterload. In this pilot study, viscous energy loss in patient cohorts was significantly elevated and indicates that cardiac afterload is increased due to abnormal flow. PMID:24122967

DOE Office of Scientific and Technical Information (OSTI.GOV)

NONE

Learnings Objectives: Although brachytherapy is the oldest form of radiation therapy, the rapid advancement of the methods of dose calculation, treatment planning and treatment delivery pushes us to keep updating our knowledge and experience to new procedures all the time. Our purpose is to present the newest applicators used in Accelerated Partial Breast Irradiation (APBI) and the techniques of using them for a maximum effective treatment. Our objective will be to get the user familiar with the Savi, Contura and ML Mammosite from the detailed description and measurements to cavity eval and choice or size, to acceptance tests and usemore » of each. At the end of the session the attendants will be able to assist at the scanning of the patient for the first treatment, decide on the proper localization and immobilization devices, import the scans in the treatment planning system, perform the structure segmentation, reconstruct the catheters and develop a treatment plan using inverse planning (IPSA) or volume optimization. The attendant should be able to evaluate the quality of a treatment plan according to the ABS protocols and B39 after this session. Our goal is that all the attendants to gain knowledge of all the quality assurance procedures required to be performed prior to a treatment, at the beginning of a treatment day, weekly, monthly and annualy on the remote afterloader, the treatment planning system and the secondary check system. We will provide tips for a consistent treatment delivery of the 10 fractions in a BID (twice daily) regimen.« less

Calcium as a cardiovascular toxin in CKD-MBD.

PubMed

Moe, Sharon M

2017-07-01

Disordered calcium balance and homeostasis are common in patients with chronic kidney disease. Such alterations are commonly associated with abnormal bone remodeling, directly and indirectly. Similarly, positive calcium balance may also be a factor in the pathogenesis of extra skeletal soft tissue and arterial calcification. Calcium may directly affect cardiac structure and function through direct effects to alter cell signaling due to abnormal intracellular calcium homeostasis 2) extra-skeletal deposition of calcium and phosphate in the myocardium and small cardiac arterioles, 3) inducing cardiomyocyte hypertrophy through calcium and hormone activation of NFAT signaling mechanisms, and 4) increased aorta calcification resulting in chronic increased afterload leading to hypertrophy. Similarly, calcium may alter vascular smooth muscle cell function and affect cell signaling which may predispose to a proliferative phenotype important in arteriosclerosis and arterial calcification. Thus, disorders of calcium balance and homeostasis due to CKD-MBD may play a role in the high cardiovascular burden observed in patients with CKD. Published by Elsevier Inc.

Nasopharyngeal carcinoma with cranial nerve palsy: The importance of MRI for radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chang, Joseph T.-C.; Taipei Chang Gung Head and Neck Oncology Group, Chang Gung Memorial Hospital-Linkou, Taoyuan, Taiwan; Lin, C.-Y.

2005-12-01

Purpose: To evaluate various prognostic factors and the impact of imaging modalities on tumor control in patients with nasopharyngeal cancer (NPC) with cranial nerve (China) palsy. Material and Methods: Between September 1979 and December 2000, 330 NPC patients with CN palsy received radical radiotherapy (RT) by the conventional opposing technique at Chang Gung Memorial Hospital-Linkou. Imaging methods used varied over that period, and included conventional tomography (Tm) for 47 patients, computerized tomography (CT) for 195 patients, and magnetic resonance image (MRI) for 88 patients. Upper CN (II-VI) palsy was found in 268 patients, lower CN (IX-XII) in 13, and 49more » patients had both. The most commonly involved CN were V or VI or both (23%, 12%, and 16%, respectively). All patients had good performance status (World Health Organization <2). The median external RT dose was 70.2 Gy (range, 63-77.5 Gy). Brachytherapy was also given to 156 patients in addition to external RT, delivered by the remote after-loading, high-dose-rate technique. A total of 139 patients received cisplatin-based chemotherapy, in 115 received as neoadjuvant or adjuvant chemotherapy and in 24 concomitant with RT. Recovery from CN palsy occurred in 171 patients during or after radiotherapy. Patients who died without a specific cause identified were regarded as having died with persistent disease. Results: The 3-year, 5-year, and 10-year overall survival was 47.1%, 34.4%, and 22.2%. The 3-year, 5-year, and 10-year disease-specific survival (DSS) rates were 50.4%, 37.8%, and 25.9%. The 5-year DSS for patients staged with MRI, CT, and Tm were 46.9%, 36.7%, and 21.9%, respectively (p = 0.016). The difference between MRI and CT was significant (p = 0.015). The 3-year and 5-year local control rates were 62% and 53%, respectively. The 5-year local control was 68.2% if excluding patients who died without a specific cause. Patients who had an MRI had a significantly better tumor control rate than those evaluated with CT or Tm, with a 15-30% improvement in local tumor control and survival. Patients with extensive CN palsy had worse survival than those with only lower CN or upper CN involvement (5-year DSS 20.4% vs. 43.2% and 40.4%, respectively; p < 0.001). Patients who recovered from CN palsy had better survival than those who did not (47% vs. 26%, p < 0.001). Brachytherapy was associated with poorer local control, whereas a total external dose of more than 70 Gy improved local tumor control and marginally improved DSS. Subgroup analysis in CT and MRI patients group, either DSS or OS was significantly associated with imaging modality, N stage, or location of or remission of CN palsy. Conclusion: The use of MRI was associated with improved tumor control and survival of patients with NPC causing CN palsy. Patients recovering from CN palsy had better survival. A higher radiation dose delivered by external beam may achieve better tumor control than brachytherapy.« less

Right ventricular failure resulting from pressure overload: role of intra-aortic balloon counterpulsation and vasopressor therapy.

PubMed

Liakopoulos, Oliver J; Ho, Jonathan K; Yezbick, Aaron B; Sanchez, Elizabeth; Singh, Vivek; Mahajan, Aman

2010-11-01

Augmentation of coronary perfusion may improve right ventricular (RV) failure following acute increases of RV afterload. We investigated whether intra-aortic balloon counterpulsation (IABP) can improve cardiac function by enhancing myocardial perfusion and reversing compromised biventricular interactions using a model of acute pressure overload. In 10 anesthetized pigs, RV failure was induced by pulmonary artery constriction and systemic hypertension strategies with IABP, phenylephrine (PE), or the combination of both were tested. Systemic and ventricular hemodynamics [cardiac index(CI), ventricular pressures, coronary driving pressures (CDP)] were measured and echocardiography was used to assess tricuspid valve regurgitation, septal positioning (eccentricity index (ECI)), and changes in ventricular and septal dimensions and function [myocardial performance index (MPI), peak longitudinal strain]. Pulmonary artery constriction resulted in doubling of RV systolic pressure (54 ± 4mm Hg), RV distension, severe TR (4+) with decreased RV function (strain: -33%; MPI: +56%), septal flattening (Wt%: -35%) and leftward septal shift (ECI:1.36), resulting in global hemodynamic deterioration (CI: -51%; SvO(2): -26%), and impaired CDP (-30%; P<0.05). IABP support alone failed to improve RV function despite higher CDP (+33%; P<0.05). Systemic hypertension by PE improved CDP (+70%), RV function (strain: +22%; MPI: -21%), septal positioning (ECI:1.12) and minimized TR, but LV dysfunction (strain: -25%; MPI: +31%) occurred after LV afterloading (P<0.05). With IABP, less PE (-41%) was needed to maintain hypertension and CDP was further augmented (+25%). IABP resulted in LV unloading and restored LV function, and increased CI (+46%) and SvO(2) (+29%; P<0.05). IABP with minimal vasopressors augments myocardial perfusion pressure and optimizes RV function after pressure-induced failure. Copyright © 2010 Elsevier Inc. All rights reserved.

Measurement of pulmonary arterial elastance in patients with systolic heart failure using Doppler echocardiography

PubMed Central

Taghavi, Sepideh; Esmaeilzadeh, Maryam; Amin, Ahmad; Naderi, Nasim; Abkenar, Hooman Bakhshandeh; Maleki, Majid; Mitra, Chitsazan

2016-01-01

Objective: A reliable and easy-to-perform method for measuring right ventricular (RV) afterload is desirable when scheduling patients with systolic heart failure to undergo heart transplantation. The present study aimed to investigate the accuracy of echocardiographically-derived pulmonary arterial elastance as a measurement of pulmonary vascular resistance by comparing it with invasive measures. Methods: Thirty-one patients with moderate to severe systolic heart failure, including 22 (71%) male patients, with a mean age of 41.16±15.9 years were enrolled in the study. Right heart catheterization and comprehensive echocardiography during the first hour after completion of cardiac catheterization were performed in all the patients. The pulmonary artery elastance was estimated using the ratio of end-systolic pressure (Pes) over the stroke volume (SV) by both cardiac catheterization [Ea (PV)-C] and echocardiography [Ea (PV)-E]. Results: The mean Ea (PV)-C and Ea (PV)-E were estimated to be 0.73±0.49 mm Hg/mL and 0.67±0.44 mm Hg/mL, respectively. There was a significant relation between Ea (PV)-E and Ea (PV)-C (r=0.897, p<0.001). Agreement between echocardiography and catheterization methods for estimating Ea (PV), investigated by the Bland-Altman method, showed a mean bias of -0.06, with 95% limits of agreement from -0.36 mm Hg/mL to 0.48 mm Hg/mL. Conclusion: Doppler echocardiography is an easy, non-invasive, and inexpensive method for measuring pulmonary arterial elastance, which provides accurate and reliable estimation of RV afterload in patients with systolic heart failure. PMID:26467379

Comparison by Magnetic Resonance Phase Contrast of Pulse Wave Velocity in Patients with Single Ventricle and Reconstructed Aortas versus Those Without

PubMed Central

Fogel, Mark A.; Li, Christine; Nicolson, Susan C; Spray, Thomas L; Gaynor, J William; Fuller, Stephanie; Keller, Marc S.; Harris, Matthew A.; Yoganathan, Ajit P; Whitehead, Kevin K.

2015-01-01

Pulse wave velocity (PWV), a measure of arterial stiffness, is a known independent risk factor for cardiovascular events. Single ventricle patients who undergo aortic to pulmonary anastomosis (recon) have non-compliant patch material inserted into the neo-aorta, possibly increasing vessel stiffness and afterload. The purpose of this study is to determine if PWV differed in single ventricle patients who did and did not undergo aortic reconstruction (no-recon). We retrospectively reviewed cardiac magnetic resonance anatomic, cine and phase contrast evaluations in the ascending (AAo) and descending aorta (DAo) at the level of the diaphragm data from 126 single ventricle patients (8.6±8.0 years) from January 2012 to May, 2013. Significance = P<0.05. Seventy-five underwent recon and 51 did not. PWV in recon were significantly higher than in no-recon (3.9±0.9 m/s vs 3.2±1.0 m/s, P=0.008); in recon, patients > 13 years had a higher PWV than those < 7 years (4.5±0.6 vs 3.5±0.7 m/s, P=0.004). DAo distensibility was similar between both groups. There was no difference in age, body surface area or cardiac index between recon and no-recon. No correlations between various hemodynamic and ventricular function parameters with PWV were noted. In conclusion, PWV in recon is higher than in no-recon with similar DAo distensibility implicating the aortic reconstruction as a possible cause of increased afterload; older recon have stiffer aortas than younger ones possibly imposing an additional cardiovascular risk in the future. Other biomaterials may potentially moderate PWV if clinical outcome is adversely affected. PMID:25432153

Japanese Structure Survey of Radiation Oncology in 2007 Based on Institutional Stratification of Patterns of Care Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Teshima, Teruki, E-mail: teshima@sahs.med.osaka-u.ac.j; Numasaki, Hodaka; Shibuya, Hitoshi

2010-12-01

Purpose: To evaluate the ongoing structure of radiation oncology in Japan in terms of equipment, personnel, patient load, and geographic distribution to identify and improve any deficiencies. Methods and Materials: A questionnaire-based national structure survey was conducted from March to December 2008 by the Japanese Society of Therapeutic Radiology and Oncology (JASTRO). These data were analyzed in terms of the institutional stratification of the Patterns of Care Study. Results: The total numbers of new cancer patients and total cancer patients (new and repeat) treated with radiation in 2007 were estimated at 181,000 and 218,000, respectively. There were 807 linear accelerator,more » 15 telecobalt, 46 Gamma Knife, 45 {sup 60}Co remote-controlled after-loading, and 123 {sup 192}Ir remote-controlled after-loading systems in actual use. The linear accelerator systems used dual-energy function in 539 units (66.8%), three-dimensional conformal radiation therapy in 555 (68.8%), and intensity-modulated radiation therapy in 235 (29.1%). There were 477 JASTRO-certified radiation oncologists, 826.3 full-time equivalent (FTE) radiation oncologists, 68.4 FTE medical physicists, and 1,634 FTE radiation therapists. The number of interstitial radiotherapy (RT) administrations for prostate, stereotactic body radiotherapy, and intensity-modulated radiation therapy increased significantly. Patterns of Care Study stratification can clearly identify the maturity of structures based on their academic nature and caseload. Geographically, the more JASTRO-certified physicians there were in a given area, the more RT tended to be used for cancer patients. Conclusions: The Japanese structure has clearly improved during the past 17 years in terms of equipment and its use, although a shortage of personnel and variations in maturity disclosed by Patterns of Care Study stratification were still problematic in 2007.« less

Cardiovascular response to acute normovolemic hemodilution in patients with coronary artery diseases: Assessment with transesophageal echocardiography.

PubMed

Licker, Marc; Ellenberger, Christoph; Sierra, Jorge; Christenson, Jan; Diaper, John; Morel, Denis

2005-03-01

Preoperative acute normovolemic hemodilution induces an increase in circulatory output that is thought to be limited in patients with cardiac diseases. Using multiple-plane transesophageal echocardiography, we investigated the mechanisms of cardiovascular adaptation during acute normovolemic hemodilution in patients with severe coronary artery disease. Prospective case-control study. Operating theater in a university hospital. Consecutive patients treated with beta-blockers, scheduled to undergo coronary artery bypass (n = 50). After anesthesia induction, blood withdrawal and isovolemic exchange with iso-oncotic starch (1:1.15 ratio) to achieve a hematocrit value of 28%. In addition to heart rate and intravascular pressures, echocardiographic recordings were obtained before and after acute normovolemic hemodilution to assess cardiac preload, afterload, and contractility. In a control group, not subjected to acute normovolemic hemodilution, hemodynamic variables remained stable during a 20-min anesthesia period. Following acute normovolemic hemodilution, increases in cardiac stroke volume (+28 +/- 4%; mean +/- sd) were correlated with increases in central venous pressure (+2.0 +/- 1.3 mm Hg; R = .56) and in left ventricular end-diastolic area (+18 +/- 5%, R = .39). The unchanged left ventricular end-systolic wall stress and preload-adjusted maximal power indicated that neither left ventricular afterload nor contractility was affected by acute normovolemic hemodilution. Diastolic left ventricular filling abnormalities (15 of 22 cases) improved in 11 patients and were stable in the remaining four patients. Despite reduction in systemic oxygen delivery (-20.5 +/- 7%, p < .05), there was no evidence for myocardial ischemia (electrocardiogram, left ventricular wall motion abnormalities). In anesthetized patients with coronary artery disease, moderate acute normovolemic hemodilution did not compromise left ventricular systolic and diastolic function. Lowering blood viscosity resulted in increased stroke volume that was mainly related to increased venous return and higher cardiac preload.

Circadian rhythms in myocardial metabolism and contractile function: influence of workload and oleate.

PubMed

Durgan, David J; Moore, Michael W S; Ha, Ngan P; Egbejimi, Oluwaseun; Fields, Anna; Mbawuike, Uchenna; Egbejimi, Anu; Shaw, Chad A; Bray, Molly S; Nannegari, Vijayalakshmi; Hickson-Bick, Diane L; Heird, William C; Dyck, Jason R B; Chandler, Margaret P; Young, Martin E

2007-10-01

Multiple extracardiac stimuli, such as workload and circulating nutrients (e.g., fatty acids), known to influence myocardial metabolism and contractile function exhibit marked circadian rhythms. The aim of the present study was to investigate whether the rat heart exhibits circadian rhythms in its responsiveness to changes in workload and/or fatty acid (oleate) availability. Thus, hearts were isolated from male Wistar rats (housed during a 12:12-h light-dark cycle: lights on at 9 AM) at 9 AM, 3 PM, 9 PM, and 3 AM and perfused in the working mode ex vivo with 5 mM glucose plus either 0.4 or 0.8 mM oleate. Following 20-min perfusion at normal workload (i.e., 100 cm H(2)O afterload), hearts were challenged with increased workload (140 cm H(2)O afterload plus 1 microM epinephrine). In the presence of 0.4 mM oleate, myocardial metabolism exhibited a marked circadian rhythm, with decreased rates of glucose oxidation, increased rates of lactate release, decreased glycogenolysis capacity, and increased channeling of oleate into nonoxidative pathways during the light phase. Rat hearts also exhibited a modest circadian rhythm in responsiveness to the workload challenge when perfused in the presence of 0.4 mM oleate, with increased myocardial oxygen consumption at the dark-to-light phase transition. However, rat hearts perfused in the presence of 0.8 mM oleate exhibited a markedly blunted contractile function response to the workload challenge during the light phase. In conclusion, these studies expose marked circadian rhythmicities in myocardial oxidative and nonoxidative metabolism as well as responsiveness of the rat heart to changes in workload and fatty acid availability.

Rationale and design of the Transcatheter Aortic Valve Replacement to UNload the Left ventricle in patients with ADvanced heart failure (TAVR UNLOAD) trial.

PubMed

Spitzer, Ernest; Van Mieghem, Nicolas M; Pibarot, Philippe; Hahn, Rebecca T; Kodali, Susheel; Maurer, Mathew S; Nazif, Tamim M; Rodés-Cabau, Josep; Paradis, Jean-Michel; Kappetein, Arie-Pieter; Ben-Yehuda, Ori; van Es, Gerrit-Anne; Kallel, Faouzi; Anderson, William N; Tijssen, Jan; Leon, Martin B

2016-12-01

Coexistence of moderate aortic stenosis (AS) in patients with heart failure (HF) with reduced ejection fraction is not uncommon. Moderate AS increases afterload, whereas pharmacologic reduction of afterload is a pillar of contemporary HF management. Unloading the left ventricle by reducing the transaortic gradient with transfemoral transcatheter aortic valve replacement (TAVR) may improve clinical outcomes in patients with moderate AS and HF with reduced ejection fraction. The TAVR UNLOAD (NCT02661451) is an international, multicenter, randomized, open-label, clinical trial comparing the efficacy and safety of TAVR with the Edwards SAPIEN 3 Transcatheter Heart Valve in addition to optimal heart failure therapy (OHFT) vs OHFT alone in patients with moderate AS (defined by a mean transaortic gradient ≥20 mm Hg and <40 mm Hg, and an aortic valve area >1.0 cm 2 and ≤1.5 cm 2 at rest or after dobutamine stress echocardiography) and reduced ejection fraction. A total of 600 patients will be randomized in a 1:1 fashion. Clinical follow-up is scheduled at 1, 6, and 12 months, and 2 years after randomization. The primary end point is the hierarchical occurrence of all-cause death, disabling stroke, hospitalizations related to HF, symptomatic aortic valve disease or nondisabling stroke, and the change in the Kansas City Cardiomyopathy Questionnaire at 1 year. Secondary end points capture effects on clinical outcome, biomarkers, echocardiographic parameters, and quality of life. The TAVR UNLOAD trial aims to test the hypothesis that TAVR on top of OHFT improves clinical outcomes in patients with moderate AS and HF with reduced ejection fraction. Copyright © 2016 Elsevier Inc. All rights reserved.

Ventricular-Arterial Coupling and Exercise-Induced Pulmonary Hypertension During Low-Level Exercise in Heart Failure With Preserved or Reduced Ejection Fraction.

PubMed

Obokata, Masaru; Nagata, Yasufumi; Kado, Yuichiro; Kurabayashi, Masahiko; Otsuji, Yutaka; Takeuchi, Masaaki

2017-03-01

Exercise-induced pulmonary hypertension (EIPH) may develop even at low workloads in heart failure (HF) patients. Ventricular-arterial stiffening plays an important role in the pathophysiology of HF with preserved ejection fraction (HFpEF). This study aimed to compare the response of ventricular-arterial coupling and PH during low-level exercise between HFpEF and HF with reduced EF (HFrEF). Echocardiography was performed at rest and during 10 W of bicycle exercise in HFpEF (n = 37) and HFrEF (n = 43). Load-independent contractility (end-systolic elastance [Ees], preload recruitable stroke work [PRSW], and peak power index [PWRI]), arterial afterload (arterial elastance [Ea]), and ventricular-arterial interaction (Ea/Ees) were measured with the use of a noninvasive single-beat technique. EIPH was defined as an estimated pulmonary arterial systolic pressure (PASP) of ≥50 mm Hg at 10 W of exercise. PASP was significantly increased during 10 W of exercise in both HF types, and ~50% of HFpEF patients developed EIPH. Arterial afterload was increased significantly during exercise in both groups. HFrEF and HFpEF patients showed a significant increase in LV contractility assessed by Ees, PRSW, and PWRI during exercise. Although Ea/Ees ratio decreased significantly in HFrEF, reduction in Ea/Ees was attenuated because of blunted Ees increases in patients with HFpEF compared with HFrEF. Even at low-level exercise, ~50% of HFpEF patients developed EIPH. Reduction in Ea/Ees was attenuated owing to less Ees increase in HFpEF compared with HFrEF. Further studies are needed to elucidate the association between ventricular-arterial coupling and EIPH in HFpEF. Copyright © 2016 Elsevier Inc. All rights reserved.

Wave energy patterns of counterpulsation: a novel approach with wave intensity analysis.

PubMed

Lu, Pong-Jeu; Yang, Chi-Fu Jeffrey; Wu, Meng-Yu; Hung, Chun-Hao; Chan, Ming-Yao; Hsu, Tzu-Cheng

2011-11-01

In counterpulsation, diastolic augmentation increases coronary blood flow and systolic unloading reduces left ventricular afterload. We present a new approach with wave intensity analysis to revisit and explain counterpulsation principles. In an acute porcine model, a standard intra-aortic balloon pump was placed in descending aorta in 4 pigs. We measured pressure and velocity with probes in left anterior descending artery and aorta during and without intra-aortic balloon pump assistance. Wave intensities of aortic and left coronary waves were derived from pressure and flow measurements with synchronization correction. We identified predominating waves in counterpulsation. In the aorta, during diastolic augmentation, intra-aortic balloon inflation generated a backward compression wave, with a "pushing" effect toward the aortic root that translated to a forward compression wave into coronary circulation. During systolic unloading, intra-aortic balloon pump deflation generated a backward expansion wave that "sucked" blood from left coronary bed into the aorta. While this backward expansion wave translated to reduced left ventricular afterload, the "sucking" effect resulted in left coronary blood steal, as demonstrated by a forward expansion wave in left anterior descending coronary flow. The waves were sensitive to inflation and deflation timing, with just 25 ms delay from standard deflation timing leading to weaker forward expansion wave and less coronary regurgitation. Intra-aortic balloon pumps generate backward-traveling waves that predominantly drive aortic and coronary blood flow during counterpulsation. Wave intensity analysis of arterial circulations may provide a mechanism to explain diastolic augmentation and systolic unloading of intra-aortic balloon pump counterpulsation. Copyright © 2011 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

Acute right ventricular dysfunction: real-time management with echocardiography.

PubMed

Krishnan, Sundar; Schmidt, Gregory A

2015-03-01

In critically ill patients, the right ventricle is susceptible to dysfunction due to increased afterload, decreased contractility, or alterations in preload. With the increased use of point-of-care ultrasonography and a decline in the use of pulmonary artery catheters, echocardiography can be the ideal tool for evaluation and to guide hemodynamic and respiratory therapy. We review the epidemiology of right ventricular failure in critically ill patients; echocardiographic parameters for evaluating the right ventricle; and the impact of mechanical ventilation, fluid therapy, and vasoactive infusions on the right ventricle. Finally, we summarize the principles of management in the context of right ventricular dysfunction and provide recommendations for echocardiography-guided management.

Polymorphism at the 5' end flanking region of the insulin gene is associated with reduced insulin secretion in healthy individuals.

PubMed

Cocozza, S; Riccardi, G; Monticelli, A; Capaldo, B; Genovese, S; Krogh, V; Celentano, E; Farinaro, E; Varrone, S; Avvedimento, V E

1988-12-01

Sixty-four unrelated healthy subjects were studied for the detection of a DNA polymorphism at the 5' end of the insulin gene. No significant difference between the groups was found in blood glucose values at fasting and after an oral glucose load. A significant association was found between fasting (P less than 0.05) and after load plasma C-peptide levels (P less than 0.01) and the presence of a 1.6 Kb insertion at the 5' end of the insulin gene. A gene dose-dependent effect was noted, class 3/3 individuals having the lowest after-load C-peptide concentration and class 1/3 an intermediate level (F for the linear trend: P = 0.007). This might suggest that insulin gene polymorphism affects insulin secretion in healthy individuals. In order to confirm this, a subgroup of six class 3/3 and eight class 1/1 individuals subsequently underwent a hyperglycaemic clamp. The tissue sensitivity to insulin was similar in the two groups but glucose-stimulated insulin secretion was markedly impaired in homozygotes for the class 3 allele. In this group, insulin secretion was, on average, only one-third of that in class 1/1 individuals (P less than 0.02). Similarly impaired in class 3/3 persons was the glucose + arginine-stimulated insulin secretion (P less than 0.05). We conclude that the polymorphism at the 5' end of the insulin gene is associated with variations in insulin secretion in healthy humans.

Interaction between left ventricular twist mechanics and arterial haemodynamics during localised, non-metabolic hyperaemia with and without blood flow restriction.

PubMed

van Mil, Anke C C M; Pearson, James; Drane, Aimee L; Cockcroft, John R; McDonnell, Barry J; Stöhr, Eric J

2016-04-01

What is the central question of this study? Left ventricular (LV) twist is reduced when afterload is increased, but the meaning of this specific heart muscle response and its impact on cardiac output are not well understood. What is the main finding and its importance? This study shows that LV twist responds even when arterial haemodynamics are altered only locally, and without apparent change in metabolic (i.e. heat-induced) demand. The concurrent decline in cardiac output and LV twist during partial arterial occlusion despite the increased peripheral demand caused by heat stress suggests that LV twist may be involved in the protective sensing of heart muscle stress that can override the provision of the required cardiac output. Whether left ventricular (LV) twist and untwisting rate (LV twist mechanics) respond to localised, peripheral, non-metabolic changes in arterial haemodynamics within an individual's normal afterload range is presently unknown. Furthermore, previous studies indicate that LV twist mechanics may override the provision of cardiac output, but this hypothesis has not been examined purposefully. Therefore, we acutely altered local peripheral arterial haemodynamics in 11 healthy humans (women/men n = 3/8; age 26 ± 5 years) by bilateral arm heating (BAH). Ultrasonography was used to examine arterial haemodynamics, LV twist mechanics and the twist-to-shortening ratio (TSR). To determine the arterial function-dependent contribution of LV twist mechanics to cardiac output, partial blood flow restriction to the arms was applied during BAH (BAHBFR ). Bilateral arm heating increased arm skin temperatures [change (Δ) +6.4 ± 0.9°C, P < 0.0001] but not core temperature (Δ -0.0 ± 0.1°C, P > 0.05), concomitant to increases in brachial artery blood flow (Δ 212 ± 77 ml, P < 0.0001), cardiac output (Δ 495 ± 487 l min(-1) , P < 0.05), LV twist (Δ 3.0 ± 3.5 deg, P < 0.05) and TSR (Δ 3.3 ± 1.3, P < 0.05) but maintained carotid artery blood flow (Δ 18 ± 147 ml, P > 0.05). Subsequently, BAHBFR reduced all parameters to preheating levels, except for TSR and heart rate, which remained at BAH levels. In conclusion, LV twist mechanics responded to local peripheral arterial haemodynamics within the normal afterload range, in part independent of TSR and heart rate. The findings suggest that LV twist mechanics may be more closely associated with intrinsic sensing of excessive pressure stress rather than being associated with the delivery of adequate cardiac output. © 2016 The Authors. Experimental Physiology © 2016 The Physiological Society.

Clinical review: Positive end-expiratory pressure and cardiac output

PubMed Central

Luecke, Thomas; Pelosi, Paolo

2005-01-01

In patients with acute lung injury, high levels of positive end-expiratory pressure (PEEP) may be necessary to maintain or restore oxygenation, despite the fact that 'aggressive' mechanical ventilation can markedly affect cardiac function in a complex and often unpredictable fashion. As heart rate usually does not change with PEEP, the entire fall in cardiac output is a consequence of a reduction in left ventricular stroke volume (SV). PEEP-induced changes in cardiac output are analyzed, therefore, in terms of changes in SV and its determinants (preload, afterload, contractility and ventricular compliance). Mechanical ventilation with PEEP, like any other active or passive ventilatory maneuver, primarily affects cardiac function by changing lung volume and intrathoracic pressure. In order to describe the direct cardiocirculatory consequences of respiratory failure necessitating mechanical ventilation and PEEP, this review will focus on the effects of changes in lung volume, factors controlling venous return, the diastolic interactions between the ventricles and the effects of intrathoracic pressure on cardiac function, specifically left ventricular function. Finally, the hemodynamic consequences of PEEP in patients with heart failure, chronic obstructive pulmonary disease and acute respiratory distress syndrome are discussed. PMID:16356246

Pulmonary arterial compliance: How and why should we measure it?

PubMed Central

Ghio, Stefano; Schirinzi, Sandra; Pica, Silvia

2015-01-01

The pulmonary circulation is a high-flow/low-pressure system, coupled with a flow generator chamber–the right ventricle–, which is relatively unable to tolerate increases in afterload. A right heart catheterization, using a fluid-filled, balloon-tipped Swan-Ganz catheter allows the measurement of all hemodynamic parameters characterizing the pulmonary circulation: the inflow pressure, an acceptable estimate the outflow pressure, and the pulmonary blood flow. However, the study of the pulmonary circulation as a continuous flow system is an oversimplification and a thorough evaluation of the pulmonary circulation requires a correct understanding of the load that the pulmonary vascular bed imposes on the right ventricle, which includes static and dynamic components. This is critical to assess the prognosis of patients with pulmonary hypertension or with heart failure. Pulmonary compliance is a measure of arterial distensibility and, either alone or in combination with pulmonary vascular resistance, gives clinicians the possibility of a good prognostic stratification of patients with heart failure or with pulmonary hypertension. The measurement of pulmonary arterial compliance should be included in the routine clinical evaluation of such patients. PMID:26779530

Epidemiology of central sleep apnoea in heart failure.

PubMed

Naughton, Matthew T

2016-03-01

Central sleep apnoea occurs in about a third of patients with reduced systolic heart failure and is a marker of increased mortality. Such patients usually are older males with advanced heart failure (i.e., high pulmonary wedge pressure), often in atrial fibrillation, with evidence of hyperventilation (i.e., low PaCO2) in the absence of hypoxemia. Characteristically, ventilation waxes and wanes in a sinusoidal pattern, with mild hypoxemia, occurring in the lighter levels of sleep usually when supine. Snoring may also occur in central sleep apnoea, often at the peak of hyperventilation, sometimes contributing to the confusion or overlap with obstructive sleep apnoea. Central sleep apnoea is associated with orthopnoea, paroxysmal nocturnal dyspnoea and an oscillatory respiratory pattern with an incremental cardiopulmonary exercise study. Importantly, heart failure therapies (e.g., afterload reduction, diuresis, pacemakers, transplantation) attenuate central sleep apnoea. Night to night variability in severity of central sleep apnoea may occur with changes in patients' posture during sleep (less severe when sleeping on-side or upright). Crown Copyright © 2016. Published by Elsevier Ireland Ltd. All rights reserved.

Protective effect of crataegus extract on the cardiac mechanical dysfunction in isolated perfused working rat heart.

PubMed

Nasa, Y; Hashizume, H; Hoque, A N; Abiko, Y

1993-09-01

The effect of the water-soluble fraction of Crataegus (Crataegus extract) on the cardiac mechanical and metabolic function was studied in the isolated, perfused working rat heart during ischemia and reperfusion. Ischemia (15 min) was produced by removing afterload pressure, and reperfusion (20 min) was produced by returning it to the original pressure. In the control (no drug) heart, ischemia decreased mechanical function to the lowest level, which did not recover even after the end of reperfusion. Crataegus extract (0.01 or 0.05%) was applied to the heart from 5 min before ischemia through the first 10 min after reperfusion. With the high concentration of Crataegus extract (0.05%) the mechanical function recovered during reperfusion incompletely without increasing coronary flow, but the low concentration of Crataegus extract (0.01%) did not. In the heart treated with the high concentration of Crataegus extract, the reperfusion-induced recovery of the energy metabolism was accelerated, and the level of lactate during ischemia was lower than that in the control heart, although the myocardial levels of free fatty acids during ischemia and reperfusion were not greatly affected. These results demonstrate that Crataegus extract (0.05%) has a cardioprotective effect on the ischemic-reperfused heart, and that the cardioprotective effect is not accompanied by an increase in coronary flow.

Pathophysiology of pulmonary hypertension in acute lung injury

PubMed Central

Price, Laura C.; McAuley, Danny F.; Marino, Philip S.; Finney, Simon J.; Griffiths, Mark J.

2012-01-01

Acute lung injury (ALI) and acute respiratory distress syndrome are characterized by protein rich alveolar edema, reduced lung compliance, and acute severe hypoxemia. A degree of pulmonary hypertension (PH) is also characteristic, higher levels of which are associated with increased morbidity and mortality. The increase in right ventricular (RV) afterload causes RV dysfunction and failure in some patients, with associated adverse effects on oxygen delivery. Although the introduction of lung protective ventilation strategies has probably reduced the severity of PH in ALI, a recent invasive hemodynamic analysis suggests that even in the modern era, its presence remains clinically important. We therefore sought to summarize current knowledge of the pathophysiology of PH in ALI. PMID:22246001

Metoprolol Reduces Hemodynamic and Metabolic Overload in Asymptomatic Aortic Valve Stenosis Patients: A Randomized Trial.

PubMed

Hansson, Nils Henrik; Sörensen, Jens; Harms, Hendrik Johannes; Kim, Won Yong; Nielsen, Roni; Tolbod, Lars Poulsen; Frøkiær, Jørgen; Bouchelouche, Kirsten; Dodt, Karen Kaae; Sihm, Inger; Poulsen, Steen Hvitfeldt; Wiggers, Henrik

2017-10-01

Currently, no pharmacological treatment can modify the natural history of aortic valve stenosis (AS). This underlines the critical need to explore novel treatment strategies, which could postpone or prevent the need for aortic valve replacement in patients with asymptomatic AS. The objectives of this study were to investigate whether metoprolol reduce the hemodynamic and metabolic burden imposed by AS. In a double-blinded design, 40 patients with moderate-severe asymptomatic AS (aortic valve area, 0.5±0.1 cm 2 /m 2 ; peak gradient, 53±19 mm Hg) were randomized to placebo or metoprolol treatment for 22 weeks. Patients were evaluated by echocardiography, cardiovascular magnetic resonance, and 11 C-acetate positron emission tomography. Compared with placebo, metoprolol (100±53 mg/d) decreased heart rate; mean difference (95% confidence interval) -8 minute - 1 (-13, -3; P =0.003) and increased ejection time 26 ms (2, 50; P =0.03). Furthermore, metoprolol reduced aortic valve peak -7 mm Hg (-13, 0; P =0.05) and mean -4 mm Hg (-7, -1; P =0.03) gradients, without affecting stroke volume 3 mL/m 2 (-2, 8; P =0.16). Valvuloarterial impedance (ie, global afterload) and myocardial oxygen consumption were reduced by -11% and -12% ( P =0.03 and 0.01), respectively; and decreased heart rate correlated with lower valvuloarterial impedance, myocardial oxygen consumption, and improved myocardial efficiency defined as stroke work/myocardial oxygen consumption ( r =0.63-0.65; all P <0.01). There were 2 adverse cardiovascular events in the metoprolol group and none in the placebo group. In patients with asymptomatic AS, metoprolol increases systolic ejection time and reduces aortic valve gradients, global afterload, and myocardial oxygen requirements. Thus, metoprolol displays favorable hemodynamic and metabolic effects and could improve outcome in patients with asymptomatic AS. URL: http://www.clinicaltrials.gov. Unique identifier: NCT02076711. © 2017 American Heart Association, Inc.

Pulmonary Vascular Input Impedance is a Combined Measure of Pulmonary Vascular Resistance and Stiffness and Predicts Clinical Outcomes Better than PVR Alone in Pediatric Patients with Pulmonary Hypertension

PubMed Central

Hunter, Kendall S.; Lee, Po-Feng; Lanning, Craig J.; Ivy, D. Dunbar; Kirby, K. Scott; Claussen, Lori R.; Chan, K. Chen; Shandas, Robin

2011-01-01

Background Pulmonary vascular resistance (PVR) is the current standard for evaluating reactivity in children with pulmonary arterial hypertension (PAH). However, PVR measures only the mean component of right ventricular afterload and neglects pulsatile effects. We recently developed and validated an method to measure pulmonary vascular input impedance, which revealed excellent correlation between the zero-harmonic impedance value and PVR, and suggested a correlation between higher harmonic impedance values and pulmonary vascular stiffness (PVS). Here we show that input impedance can be measured routinely and easily in the catheterization laboratory, that impedance provides PVR and PVS from a single measurement, and that impedance is a better predictor of disease outcomes compared to PVR. Methods Pressure and velocity waveforms within the main PA were measured during right-heart catheterization of patients with normal PA hemodynamics (n=14) and those with PAH undergoing reactivity evaluation (49 subjects; 95 conditions). A correction factor needed to transform velocity into flow was obtained by calibrating against cardiac output. Input impedance was obtained off-line by dividing Fourier-transformed pressure and flow waveforms. Results Exceptional correlation was found between the indexed zero harmonic of impedance and indexed PVR (y=1.095·x+1.381, R2=0.9620). Additionally, the modulus sum of the first two harmonics of impedance was found to best correlate with indexed pulse pressure over stroke volume (PP/SV) (y=13.39·x-0.8058, R2=0.7962). Amongst a subset of PAH patients (n=25), cumulative logistic regression between outcomes to total indexed impedance was better (RL2=0.4012) than between outcomes and indexed PVR (RL2=0.3131). Conclusions Input impedance can be consistently and easily obtained from PW Doppler and a single catheter pressure measurement, provides comprehensive characterization of the main components of RV afterload, and better predicts patient outcomes compared to PVR alone. PMID:18082509

Pulmonary vascular input impedance is a combined measure of pulmonary vascular resistance and stiffness and predicts clinical outcomes better than pulmonary vascular resistance alone in pediatric patients with pulmonary hypertension.

PubMed

Hunter, Kendall S; Lee, Po-Feng; Lanning, Craig J; Ivy, D Dunbar; Kirby, K Scott; Claussen, Lori R; Chan, K Chen; Shandas, Robin

2008-01-01

Pulmonary vascular resistance (PVR) is the current standard for evaluating reactivity in children with pulmonary arterial hypertension (PAH). However, PVR measures only the mean component of right ventricular afterload and neglects pulsatile effects. We recently developed and validated a method to measure pulmonary vascular input impedance, which revealed excellent correlation between the zero harmonic impedance value and PVR and suggested a correlation between higher-harmonic impedance values and pulmonary vascular stiffness. Here we show that input impedance can be measured routinely and easily in the catheterization laboratory, that impedance provides PVR and pulmonary vascular stiffness from a single measurement, and that impedance is a better predictor of disease outcomes compared with PVR. Pressure and velocity waveforms within the main pulmonary artery were measured during right heart catheterization of patients with normal pulmonary artery hemodynamics (n = 14) and those with PAH undergoing reactivity evaluation (49 subjects, 95 conditions). A correction factor needed to transform velocity into flow was obtained by calibrating against cardiac output. Input impedance was obtained off-line by dividing Fourier-transformed pressure and flow waveforms. Exceptional correlation was found between the indexed zero harmonic of impedance and indexed PVR (y = 1.095x + 1.381, R2 = 0.9620). In addition, the modulus sum of the first 2 harmonics of impedance was found to best correlate with indexed pulse pressure over stroke volume (y = 13.39x - 0.8058, R2 = 0.7962). Among a subset of patients with PAH (n = 25), cumulative logistic regression between outcomes to total indexed impedance was better (R(L)2 = 0.4012) than between outcomes and indexed PVR (R(L)2 = 0.3131). Input impedance can be consistently and easily obtained from pulse-wave Doppler and a single catheter pressure measurement, provides comprehensive characterization of the main components of RV afterload, and better predicts patient outcomes compared with PVR alone.

I-125 seed calibration using the SeedSelectron® afterloader: a practical solution to fulfill AAPM-ESTRO recommendations

PubMed Central

Perez-Calatayud, Jose; Richart, Jose; Guirado, Damián; Pérez-García, Jordi; Rodríguez, Silvia; Santos, Manuel

2012-01-01

Purpose SeedSelectron® v1.26b (Nucletron BV, The Netherlands) is an afterloader system used in prostate interstitial permanent brachytherapy with I-125 selectSeed seeds. It contains a diode array to assay all implanted seeds. Only one or two seeds can be extracted during the surgical procedure and assayed using a well chamber to check the manufacturer air-kerma strength (SK) and to calibrate the diode array. Therefore, it is not feasible to assay 5–10% seeds as required by the AAPM-ESTRO. In this study, we present a practical solution of the SeedSelectron® users to fulfill the AAPM- ESTRO recommendations. Material and methods The method is based on: a) the SourceCheck® well ionization chamber (PTW, Germany) provided with a PTW insert; b) n = 10 selectSeed from the same batch and class as the seeds for the implant; c) the Nucletron insert to accommodate the n = 10 seeds on the SourceCheck® and to measure their averaged SK. Results for 56 implants have been studied comparing the SK value from the manufacturer with the one obtained with the n = 10 seeds using the Nucletron insert prior to the implant and with the SK of just one seed measured with the PTW insert during the implant. Results We are faced with SK deviation for individual seeds up to 7.8%. However, in the majority of cases SK is in agreement with the manufacturer value. With the method proposed using the Nucletron insert, the large deviations of SK are reduced and for 56 implants studied no deviation outside the range of the class were found. Conclusions The new Nucletron insert and the proposed procedure allow to evaluate the SK of the n = 10 seeds prior to the implant, fulfilling the AAPM-ESTRO recommendations. It has been adopted by Nucletron to be extended to seedSelectron® users under request. PMID:23346136

Acute right heart failure after hemorrhagic shock and trauma pneumonectomy-a management approach: A blinded randomized controlled animal trial using inhaled nitric oxide.

PubMed

Lubitz, Andrea L; Sjoholm, Lars O; Goldberg, Amy; Pathak, Abhijit; Santora, Thomas; Sharp, Thomas E; Wallner, Markus; Berretta, Remus M; Poole, Lauren A; Wu, Jichuan; Wolfson, Marla R

2017-02-01

Hemorrhagic shock and pneumonectomy causes an acute increase in pulmonary vascular resistance (PVR). The increase in PVR and right ventricular (RV) afterload leads to acute RV failure, thus reducing left ventricular (LV) preload and output. Inhaled nitric oxide (iNO) lowers PVR by relaxing pulmonary arterial smooth muscle without remarkable systemic vascular effects. We hypothesized that with hemorrhagic shock and pneumonectomy, iNO can be used to decrease PVR and mitigate right heart failure. A hemorrhagic shock and pneumonectomy model was developed using sheep. Sheep received lung protective ventilatory support and were instrumented to serially obtain measurements of hemodynamics, gas exchange, and blood chemistry. Heart function was assessed with echocardiography. After randomization to study gas of iNO 20 ppm (n = 9) or nitrogen as placebo (n = 9), baseline measurements were obtained. Hemorrhagic shock was initiated by exsanguination to a target of 50% of the baseline mean arterial pressure. The resuscitation phase was initiated, consisting of simultaneous left pulmonary hilum ligation, via median sternotomy, infusion of autologous blood and initiation of study gas. Animals were monitored for 4 hours. All animals had an initial increase in PVR. PVR remained elevated with placebo; with iNO, PVR decreased to baseline. Echo showed improved RV function in the iNO group while it remained impaired in the placebo group. After an initial increase in shunt and lactate and decrease in SvO2, all returned toward baseline in the iNO group but remained abnormal in the placebo group. These data indicate that by decreasing PVR, iNO decreased RV afterload, preserved RV and LV function, and tissue oxygenation in this hemorrhagic shock and pneumonectomy model. This suggests that iNO may be a useful clinical adjunct to mitigate right heart failure and improve survival when trauma pneumonectomy is required.

Comparison by magnetic resonance phase contrast imaging of pulse-wave velocity in patients with single ventricle who have reconstructed aortas versus those without.

PubMed

Fogel, Mark A; Li, Christine; Nicolson, Susan C; Spray, Thomas L; Gaynor, J William; Fuller, Stephanie; Keller, Marc S; Harris, Matthew A; Yoganathan, Ajit P; Whitehead, Kevin K

2014-12-15

Pulse-wave velocity (PWV), a measure of arterial stiffness, is a known independent risk factor for cardiovascular events. Patients with single ventricle who undergo aortic to pulmonary anastomosis (recon) have noncompliant patch material inserted into the neoaorta, possibly increasing vessel stiffness and afterload. The purpose of this study is to determine if PWV in patients with single ventricle differed between those who did and those who did not undergo aortic reconstruction (nonrecon). We retrospectively reviewed cardiac magnetic resonance anatomic, cine, and phase contrast evaluations in the ascending aorta and descending aorta (DAo) at the level of the diaphragm data from 126 patients with single ventricle (8.6 ± 8.0 years) from January 2012 to May 2013. Significance = p <0.05. Seventy-five patients underwent recon and 51 did not. PWV in recon was significantly higher than in nonrecon (3.9 ± 0.9 m/s vs 3.2 ± 1.0 m/s, p = 0.008); in recon, patients >13 years old had a higher PWV than those <7 years (4.5 ± 0.6 vs 3.5 ± 0.7 m/s, p = 0.004). Whether <7 or >13 years old, PWV of those with recon was higher than nonrecon DAo distensibility was similar between both groups. There was no difference in age, body surface area, or cardiac index between recon and nonrecon. No correlations between various hemodynamic and ventricular function parameters with PWV were noted. In conclusion, PWV in recon is higher than in nonrecon with similar DAo distensibility implicating the aortic reconstruction as a possible cause of increased afterload; older recon patients have stiffer aortas than younger ones, possibly imposing an additional cardiovascular risk in the future. Other biomaterials may potentially moderate PWV if clinical outcome is adversely affected. Copyright © 2014 Elsevier Inc. All rights reserved.

Further insights into blood pressure induced premature beats: Transient depolarizations are associated with fast myocardial deformation upon pressure decline.

PubMed

Haemers, Peter; Sutherland, George; Cikes, Maja; Jakus, Nina; Holemans, Patricia; Sipido, Karin R; Willems, Rik; Claus, Piet

2015-11-01

An acute increase in blood pressure is associated with the occurrence of premature ventricular complexes (PVCs). We aimed to study the timing of these PVCs with respect to afterload-induced changes in myocardial deformation in a controlled, preclinically relevant, novel closed-chest pig model. An acute left ventricular (LV) afterload challenge was induced by partial balloon inflation in the descending aorta, lasting 5-10 heartbeats (8 pigs; 396 inflations). Balloon inflation enhanced the reflected wave (augmentation index 30% ± 8% vs 59% ± 6%; P < .001), increasing systolic central blood pressure by 35% ± 4%. This challenge resulted in a more abrupt LV pressure decline, which was delayed beyond ventricular repolarization (rate of pressure decline 0.16 ± 0.01 mm Hg/s vs 0.27 ± 0.04 mm Hg/ms; P < .001 and interval T-wave to peak pressure 1 ± 12 ms vs 36 ± 9 ms; P = .008), during which the velocity of myocardial shortening at the basal septum increased abruptly (ie, postsystolic shortening) (peak strain rate -0.6 ± 0.5 s(-1) vs -2.5 ± 0.8 s(-1); P < .001). It is exactly at this time of LV pressure decline, with increased postsystolic shortening, and not at peak pressure, that PVCs occur (22% of inflations). These PVCs preferentially occurred at the basal and apical segments. In the same regions, monophasic action potentials demonstrated the appearance of delayed afterdepolarization-like transient depolarizations as origin of PVCs. An acute blood pressure increase results in a more abrupt LV pressure decline, which is delayed after ventricular repolarization. This has a profound effect on myocardial mechanics with enhanced postsystolic shortening. Coincidence with induced transient depolarizations and PVCs provides support for the mechanoelectrical origin of pressure-induced premature beats. Copyright © 2015 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Japanese Structure Survey of Radiation Oncology in 2005 Based on Institutional Stratification of Patterns of Care Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Teshima, Teruki; Numasaki, Hodaka; Shibuya, Hitoshi

2008-09-01

Purpose: To evaluate the structure of radiation oncology in Japan in terms of equipment, personnel, patient load, and geographic distribution to identify and improve any deficiencies. Methods and Materials: A questionnaire-based national structure survey was conducted between March 2006 and February 2007 by the Japanese Society of Therapeutic Radiology and Oncology. These data were analyzed in terms of the institutional stratification of the Patterns of Care Study. Results: The total numbers of new cancer patients and total cancer patients (new and repeat) treated with radiotherapy in 2005 were estimated at approximately 162,000 and 198,000, respectively. In actual use were 765more » linear accelerators, 11 telecobalt machines, 48 GammaKnife machines, 64 {sup 60}Co remote-controlled after-loading systems, and 119 {sup 192}Ir remote-controlled after-loading systems. The linear accelerator systems used dual-energy function in 498 systems (65%), three-dimensional conformal radiotherapy in 462 (60%), and intensity-modulated radiotherapy in 170 (22%). There were 426 Japanese Society of Therapeutic Radiology and Oncology-certified radiation oncologists, 774 full-time equivalent radiation oncologists, 117 medical physicists, and 1,635 radiation therapists. Geographically, a significant variation was found in the use of radiotherapy, from 0.9 to 2.1 patients/1,000 population. The annual patient load/FTE radiation oncologist was 247, exceeding the Blue Book guidelines level. Patterns of Care Study stratification can clearly discriminate the maturity of structures according to their academic nature and caseload. Conclusions: The Japanese structure has clearly improved during the past 15 years in terms of equipment and its use, although the shortage of manpower and variations in maturity disclosed by this Patterns of Care Study stratification remain problematic. These constitute the targets for nationwide improvement in quality assurance and quality control.« less

Ultracompact, completely implantable permanent use electromechanical ventricular assist device and total artificial heart.

PubMed

Honda, N; Inamoto, T; Nogawa, M; Takatani, S

1999-03-01

An ultracompact, completely implantable permanent use electromechanical ventricular assist device (VAD) and total artificial heart (TAH) intended for 50-60 kg size patients have been developed. The TAH and VAD share a miniature electromechanical actuator that comprises a DC brushless motor and a planetary roller screw. The rotational force of the motor is converted into the rectilinear force of the roller screw to actuate the blood pump. The TAH is a one piece design with left and right pusher plate type blood pumps sandwiching an electromechanical actuator. The VAD is one half of the TAH with the same actuator but a different pump housing and a backplate. The blood contacting surfaces, including those of the flexing diaphragm and pump housing, of both the VAD and TAH were made of biocompatible polyurethane. The diameter, thickness, volume, and weight of the VAD are 90 mm, 56 mm, 285 cc, and 380 g, respectively, while those of the TAH are 90 mm, 73 mm, 400 cc, and 440 g, respectively. The design stroke volume of both the VAD and TAH is 60 cc with the stroke length being 12 mm. The stroke length and motor speed are controlled solely based on the commutation signals of the motor. An in vitro study revealed that a maximum pump flow of 7.5 L/min can be obtained with a pump rate of 140 bpm against a mean afterload of 100 mm Hg. The power requirement ranged from 4 to 6 W to deliver a 4-5 L/min flow against a 100 mm Hg afterload with the electrical-to-hydraulic efficiency being 19-20%. Our VAD and TAH are the smallest of the currently available devices and suitable for bridge to transplant application as well as for permanent circulatory support of 50-60 kg size patients.

The AMORE Protocol for Advanced-Stage and Recurrent Nonorbital Rhabdomyosarcoma in the Head-and-Neck Region of Children: A Radiation Oncology View

DOE Office of Scientific and Technical Information (OSTI.GOV)

Blank, Leo E.C.M.; Koedooder, Kees; Pieters, Bradley R.

2009-08-01

Purpose: A multidisciplinary approach, consisting of consecutive Ablative Surgery, MOld technique with afterloading brachytherapy and immediate surgical REconstruction (AMORE) applied after chemotherapy, was designed for children with rhabdomyosarcoma in the head-and-neck region. Analysis of the first 42 patients was performed. Methods and Materials: After macroscopically radical tumor resection, molds were constructed for each individual to fit into the surgical defect. The molds, made of 5-mm-thick layers of thermoplastic rubber, consisted of different parts. Flexible catheters were positioned between layers. After brachytherapy, the molds were removed. Surgical reconstruction was performed during the same procedure. Results: Dose to the clinical target volumemore » varied from 40 to 50 Gy for the primary treatment (31 patients) and salvage treatment groups (11 patients). There were 18 females and 24 males treated from 1993 until 2007. Twenty-nine tumors were located in the parameningeal region, and 13 were located in the nonparameningeal region. Patient age at the time of AMORE was 1.2-16.9 years (average, 6.5 years). Follow-up was 0.2-14.5 years (average, >5.5 years). Eleven patients died, 3 with local recurrence only, 6 with local and distant disease, 1 died of distant metastases only, and 1 patient died of a second primary tumor. Overall 5-year survival rates were 70% for the primary treatment group and 82% for the salvage group. Treatment was well tolerated, and acute and late toxicity were mild. Conclusions: The AMORE protocol yields good local control and overall survival rates, and side effects are acceptable.« less

Dosimetric characterization of the M−15 high‐dose‐rate Iridium−192 brachytherapy source using the AAPM and ESTRO formalism

PubMed Central

Thanh, Minh‐Tri Ho; Munro, John J.

2015-01-01

The Source Production & Equipment Co. (SPEC) model M−15 is a new Iridium−192 brachytherapy source model intended for use as a temporary high‐dose‐rate (HDR) brachytherapy source for the Nucletron microSelectron Classic afterloading system. The purpose of this study is to characterize this HDR source for clinical application by obtaining a complete set of Monte Carlo calculated dosimetric parameters for the M‐15, as recommended by AAPM and ESTRO, for isotopes with average energies greater than 50 keV. This was accomplished by using the MCNP6 Monte Carlo code to simulate the resulting source dosimetry at various points within a pseudoinfinite water phantom. These dosimetric values next were converted into the AAPM and ESTRO dosimetry parameters and the respective statistical uncertainty in each parameter also calculated and presented. The M−15 source was modeled in an MCNP6 Monte Carlo environment using the physical source specifications provided by the manufacturer. Iridium−192 photons were uniformly generated inside the iridium core of the model M−15 with photon and secondary electron transport replicated using photoatomic cross‐sectional tables supplied with MCNP6. Simulations were performed for both water and air/vacuum computer models with a total of 4×109 sources photon history for each simulation and the in‐air photon spectrum filtered to remove low‐energy photons below δ=10%keV. Dosimetric data, including D(r,θ),gL(r),F(r,θ),Φan(r), and φ¯an, and their statistical uncertainty were calculated from the output of an MCNP model consisting of an M−15 source placed at the center of a spherical water phantom of 100 cm diameter. The air kerma strength in free space, SK, and dose rate constant, Λ, also was computed from a MCNP model with M−15 Iridium−192 source, was centered at the origin of an evacuated phantom in which a critical volume containing air at STP was added 100 cm from the source center. The reference dose rate, D˙(r0,θ0)≡D˙(1cm,π/2), is found to be 4.038±0.064 cGy mCi−1 h−1. The air kerma strength, SK, is reported to be 3.632±0.086 cGy cm2 mCi−1 g−1, and the dose rate constant, Λ, is calculated to be 1.112±0.029 cGy h−1 U−1. The normalized dose rate, radial dose function, and anisotropy function with their uncertainties were computed and are represented in both tabular and graphical format in the report. A dosimetric study was performed of the new M−15 Iridium−192 HDR brachytherapy source using the MCNP6 radiation transport code. Dosimetric parameters, including the dose‐rate constant, radial dose function, and anisotropy function, were calculated in accordance with the updated AAPM and ESTRO dosimetric parameters for brachytherapy sources of average energy greater than 50 keV. These data therefore may be applied toward the development of a treatment planning program and for clinical use of the source. PACS numbers: 87.56.bg, 87.53.Jw PMID:26103489

Right Ventricular Dysfunction in Chronic Lung Disease

PubMed Central

Kolb, Todd M.; Hassoun, Paul M.

2012-01-01

Right ventricular dysfunction arises in chronic lung disease when chronic hypoxemia and disruption of pulmonary vascular beds contribute to increase ventricular afterload, and is generally defined by hypertrophy with preserved myocardial contractility and cardiac output. Although the exact prevalence is unknown, right ventricular hypertrophy appears to be a common complication of chronic lung disease, and more frequently complicates advanced lung disease. Right ventricular failure is rare, except during acute exacerbations of chronic lung disease or when multiple co-morbidities are present. Treatment is targeted at correcting hypoxia and improving pulmonary gas exchange and mechanics. There are presently no convincing data to support the use of pulmonary hypertension-specific therapies in patients with right ventricular dysfunction secondary to chronic lung disease. PMID:22548815

Effects of Additional Intra-aortic Balloon Counter-Pulsation Therapy to Cardiogenic Shock Patients Supported by Extra-corporeal Membranous Oxygenation

PubMed Central

Lin, Lian-Yu; Liao, Che-Wei; Wang, Chih-Hsien; Chi, Nai-Hsin; Yu, Hsi-Yu; Chou, Nai-Kuan; Hwang, Juey-Jen; Lin, Jiunn-Lee; Chiang, Fu-Tien; Chen, Yih-Sharng

2016-01-01

Extra-corporeal membranous oxygenation (ECMO) has been applied in patients with cardiopulmonary failure. One critical drawback of peripheral ECMO is an increase in left ventricular (LV) afterload which could be counterbalanced by the combination of intra-aortic balloon counter-pulsation (IABP) therapy. We hypothesized that an add-on therapy with IABP could improve outcomes in patients receiving ECMO support. We included patients (>18 years old) from 2002 to 2013 requiring ECMO support due to cardiogenic shock in a medical center. A total of 529 patients (227 ECMO alone and 302 combined IABP plus ECMO) were included. The mortality rates at 2 weeks (48.5 vs. 47.7%) after ECMO implantation were not different between the two groups (ECMO vs. combined group). After adjustment for propensity score and potential confounders, the odds ratios of outcomes within 14 days (combined group vs. ECMO) for poor LV systolic function, high preload, multi-organ failure and mortality were not different. The results remained similar for subgroup analysis. Compared with ECMO alone, combined IABP and ECMO treatment did not improve outcomes in patients with circulatory failure. PMID:27032984

β-adrenergic receptor responsiveness in aging heart and clinical implications

PubMed Central

Ferrara, Nicola; Komici, Klara; Corbi, Graziamaria; Pagano, Gennaro; Furgi, Giuseppe; Rengo, Carlo; Femminella, Grazia D.; Leosco, Dario; Bonaduce, Domenico

2014-01-01

Elderly healthy individuals have a reduced exercise tolerance and a decreased left ventricle inotropic reserve related to increased vascular afterload, arterial-ventricular load mismatching, physical deconditioning and impaired autonomic regulation (the so called “β-adrenergic desensitization”). Adrenergic responsiveness is altered with aging and the age-related changes are limited to the β-adrenergic receptor density reduction and to the β-adrenoceptor-G-protein(s)-adenylyl cyclase system abnormalities, while the type and level of abnormalities change with species and tissues. Epidemiological studies have shown an high incidence and prevalence of heart failure in the elderly and a great body of evidence correlate the changes of β-adrenergic system with heart failure pathogenesis. In particular it is well known that: (a) levels of cathecolamines are directly correlated with mortality and functional status in heart failure, (b) β1-adrenergic receptor subtype is down-regulated in heart failure, (c) heart failure-dependent cardiac adrenergic responsiveness reduction is related to changes in G proteins activity. In this review we focus on the cardiovascular β-adrenergic changes involvement in the aging process and on similarities and differences between aging heart and heart failure. PMID:24409150

Systemic Sclerosis-Associated Pulmonary Arterial Hypertension

PubMed Central

Chaisson, Neal F.

2013-01-01

Pulmonary arterial hypertension (PAH) is the leading cause of death in systemic sclerosis (SSc) and affects up to 12% of all patients with SSc, with a 50% mortality rate within 3 years of PAH diagnosis. Compared with the idiopathic form of PAH (IPAH), patients with SSc-associated PAH (SSc-PAH) have a threefold increased risk of death and may receive a diagnosis late in the course of disease because of insidious onset and the high prevalence of cardiac, musculoskeletal, and pulmonary parenchymal comorbidities. Treatment with conventional forms of PAH therapy often yield poor results compared with IPAH cohorts; unfortunately, the exact reasons behind this remain poorly understood but likely include variations in the pathologic mechanisms, differences in cardiovascular response to increasing afterload, and inadequate strategies to detect and treat SSc-PAH early in its course. Current methods for screening and longitudinal evaluation of SSc-PAH, such as the 6-min walk test, transthoracic echocardiography, and MRI, each have notable advantages and disadvantages. We provide an up-to-date, focused review of SSc-PAH and how it differs from IPAH, including pathogenesis, appropriate screening for disease onset, and new approaches to treatment and longitudinal assessment of this disease. PMID:24081346

Determinants and genesis of canine pneumocardiogram.

PubMed

Reitan, J A; Warpinski, M A; Martucci, R W

1978-01-01

The pneumocardiogram measures the to-and-fro movement of gas from the lung with each heartbeat during apnea. Six mongrel dogs were prepared with chronic ascending aortic or pulmonary artery flow probes, corresponding occlusion cuffs and intraventricular pressure transducers. Under halothane anesthesia, the flow pneumocardiogram (PnCG) and its time derivative (acceleration pneumocardiogram or dPn/dt) were transduced during apnea by a small high-gain pneumotachograph. All variables were recorded on paper. The effects on the pneumocardiogram of great vessel occlusion, changes in cardiac loading, small airway patency, and chest wall integrity were investigated. Four of the animals were treated subsequently to produce a chemical cardiac denervation and restudied. The systolic component of the dPn/dt which correlates with myocardial contractility (IJ wave) was dependent primarily on left ventricular (LV) ejection, markedly affected by cardiac preload and modified by afterload changes to a lesser degree. Small airway closure obliterated the wave form, while opening the chest wall attenuated the dPn/dt IJ wave by 25%. This study shows the dPn/dt IJ wave is anatomically related to LV performance and responds to changes in LV function similar to other noninvasive cardiac measurements.

PULMONARY CIRCULATION AT EXERCISE

PubMed Central

NAEIJE, R; CHESLER, N

2012-01-01

The pulmonary circulation is a high flow and low pressure circuit, with an average resistance of 1 mmHg.min.L−1 in young adults, increasing to 2.5 mmHg.min.L−1 over 4–6 decades of life. Pulmonary vascular mechanics at exercise are best described by distensible models. Exercise does not appear to affect the time constant of the pulmonary circulation or the longitudinal distribution of resistances. Very high flows are associated with high capillary pressures, up to a 20–25 mmHg threshold associated with interstitial lung edema and altered ventilation/perfusion relationships. Pulmonary artery pressures of 40–50 mmHg, which can be achieved at maximal exercise, may correspond to the extreme of tolerable right ventricular afterload. Distension of capillaries that decrease resistance may be of adaptative value during exercise, but this is limited by hypoxemia from altered diffusion/perfusion relationships. Exercise in hypoxia is associated with higher pulmonary vascular pressures and lower maximal cardiac output, with increased likelihood of right ventricular function limitation and altered gas exchange by interstitial lung edema. Pharmacological interventions aimed at the reduction of pulmonary vascular tone have little effect on pulmonary vascular pressure-flow relationships in normoxia, but may decrease resistance in hypoxia, unloading the right ventricle and thereby improving exercise capacity. Exercise in patients with pulmonary hypertension is associated with sharp increases in pulmonary artery pressure and a right ventricular limitation of aerobic capacity. Exercise stress testing to determine multipoint pulmonary vascular pressures-flow relationships may uncover early stage pulmonary vascular disease. PMID:23105961

Protective effect of pulmonary hypertension against right-sided tamponade in pericardial effusion.

PubMed

Khan, M Usman; Khouzam, Rami N

2015-01-01

Patients with pericardial effusion are susceptible to cardiac tamponade. A compressing circumferential pericardial effusion typically results in an equalization of intracardiac and pericardial pressure during diastole and a progressive collapse of the right atrium and ventricle. Pulmonary hypertension that increases the afterload of the right ventricle may result in elevated pressures initially in the right ventricle and subsequently in the right atrium. This may lead to right ventricular hypertrophy and a pathologic structural and functional remodeling of both right heart chambers. Conversely, elevated pressures within the right heart chambers caused by longstanding pulmonary hypertension may resist and protect against tamponade of these chambers in the setting of a coexisting pericardial effusion. In such cases, a sudden reduction in pulmonary arterial pressures may result in tamponade of the right heart chambers.

Retreatment of recurrent carcinoma of the head and neck by afterloading interstitial 192Ir implant

DOE Office of Scientific and Technical Information (OSTI.GOV)

Emami, B.; Marks, J.E.

From January 1975 to December 1980, 25 patients with persistent or recurrent carcinomas of the head and neck were retreated for palliation at the Division of Radiation Oncology, Mallinckrodt Institute of Radiology. These patients had all undergone extensive previous treatment by surgery and/or radiation. All were retreated with 192Ir interstitial implant with or without external radiation and/or surgical excision. Of 25 patients, 13 had complete response (CR) and 6 had partial response for a follow-up period of 1 to 7 years. Of 13 patients with CR, 6 are alive with no evidence of disease (NED) and two died NED. Detailedmore » results are presented and the new strategy for such patients is discussed.« less

[Understanding heart failure].

PubMed

Boo, José Fernando Guadalajara

2006-01-01

Heart failure is a disease with several definitions. The term "heart failure" is used by has brougth about confusion in the terminology. For this reason, the value of the ejection fraction (< 0.40 or < 0.35) is used in most meganalyses on the treatment of heart failure, avoiding the term "heart failure" that is a confounding concept. In this paper we carefully analyze the meaning of contractility, ventricular function or performance, preload, afterload, heart failure, compensation mechanisms in heart failure, myocardial oxygen consumption, inadequate, adequate and inappropriate hypertrophy, systole, diastole, compliance, problems of relaxation, and diastolic dysfunction. Their definitions are supported by the original scientific descriptions in an attempt to clarify the concepts about ventricular function and heart failure and, in this way, use the same scientific language about the meaning of ventricular function, heart failure, and diastolic dysfunction.

The cardiovascular system in the ageing patient

PubMed Central

Moore, A; Mangoni, A A; Lyons, D; Jackson, S H D

2003-01-01

The ageing process is associated with important changes in the responses of the cardiovascular system to pharmacological stimuli. They are not limited to the arterial system, involved in the modulation of cardiac afterload and vascular resistance, but they also involve the low-resistance capacitance venous system and the heart. The main changes include loss of large artery compliance, dysfunction of some of the systems modulating resistance vessel tone, increased activity of the sympathetic nervous system, and reduced haemodynamic responses to inotropic agents. This review focuses on the effects of ageing on arterial and venous reactivity to drugs and hormones, the autonomic nervous system, and the cardiovascular responses to inotropic agents. Some of the age-related changes might be at least partially reversible. This may have important therapeutic implications. PMID:12919173

The use of photostimulable phosphor systems for periodic quality assurance in radiotherapy.

PubMed

Conte, L; Bianchi, C; Cassani, E; Monciardini, M; Mordacchini, C; Novario, R; Strocchi, S; Stucchi, P; Tanzi, F

2008-03-01

The fusion of radiological and optical images can be achieved through charging a photostimulable phosphor plate (PSP) with an exposure to a field of X- or gamma-rays, followed by exposure to an optical image which discharges the plate in relation to the amount of incident light. According to this PSP characteristic, we developed a simple method for periodic quality assurance (QA) of light/radiation field coincidence, distance indicator, field size indicators, crosshair centering, coincidence of radiation and mechanical isocenter for linear accelerators. The geometrical accuracy of radiological units can be subjected to the same QA method. Further, the source position accuracy for an HDR remote afterloader can be checked by taking an autoradiography of the radioactive source and simultaneously an optical image of a reference geometrical system.

New estimate of valvuloarterial impedance in aortic valve stenosis: A cardiac magnetic resonance study.

PubMed

Soulat, Gilles; Kachenoura, Nadjia; Bollache, Emilie; Perdrix, Ludivine; Diebold, Benoit; Zhygalina, Valentina; Latremouille, Christian; Laurent, Stephane; Fabiani, Jean-Noel; Mousseaux, Elie

2017-03-01

Valvuloarterial impedance (Z VA ), estimating left ventricle (LV) afterload, has been proposed in transthoracic echocardiography (TTE) as a predictor of mortality in aortic valve stenosis (AVS). However, its calculation differs from arterial characteristic impedance (Z C ). Our aim was to apply the concept of Z C calculation to estimate Z VA from MR with carotid tonometry and to evaluate these indices through their associations with symptoms, LV diastolic function and aortic stiffness. In 40 patients with AVS (76 ± 13 years), Z VA-TI derived from velocity time integral and E/Ea were estimated by TTE. Z VA-INS , based on Z C formula, calculated as the instantaneous pressure gradient to peak flow ratio and aortic compliance were estimated by using MRI at 1.5 Tesla. Both Z VA estimates were higher in symptomatic than asymptomatic patients (707 ± 22 versus 579 ± 53 dyne.s/cm 5 , P = 0.031 for Z VA-INS and 4.35 ± 0.16 versus 3.33 ± 0.38 mmHg.m 2 /mL, P = 0.018 for Z VA-TI ). Although they were both associated with aortic compliance (r = -0.45; P = 0.006 for Z VA-INS and r = -0.43; P = 0.008 for Z VA-TI ) only Z VA-INS was associated with E/Ea (r = 0.50; P < 0.001). In multivariate analysis to identify determinants of E/Ea, a model including age, mean blood pressure, LV ejection fraction, LV mass, and aortic valve area was performed (R 2  = 0.41; P < 0.01). When Z VA-INS was added to the model, its overall significance was higher R 2  = 0.56 (P < 0.01) and Z VA-INS and LV mass were the only significant determinants. Z VA-INS was more strongly associated with diastolic dysfunction than usual parameters quantifying AVS severity. This new Z VA estimate could improve LV afterload evaluation. 1 J. Magn. Reson. Imaging 2017;45:795-803. © 2016 International Society for Magnetic Resonance in Medicine.

Low-Level Laser Application in the Early Myocardial Infarction Stage Has No Beneficial Role in Heart Failure.

PubMed

Manchini, Martha T; Antônio, Ednei L; Silva Junior, José Antônio; de Carvalho, Paulo de Tarso C; Albertini, Regiane; Pereira, Fernando C; Feliciano, Regiane; Montemor, Jairo; Vieira, Stella S; Grandinetti, Vanessa; Yoshizaki, Amanda; Chaves, Marcio; da Silva, Móises P; de Lima, Rafael do Nascimento; Bocalini, Danilo S; de Melo, Bruno L; Tucci, Paulo J F; Serra, Andrey J

2017-01-01

Low-level laser therapy (LLLT) has been targeted as a promising approach that can mitigate post-infarction cardiac remodeling. There is some interesting evidence showing that the beneficial role of the LLLT could persist long-term even after the end of the application, but it remains to be systematically evaluated. Therefore, the present study aimed to test the hypothesis that LLLT beneficial effects in the early post-infarction cardiac remodeling could remain in overt heart failure even with the disruption of irradiations. Female Wistar rats were subjected to the coronary occlusion to induce myocardial infarction or Sham operation. A single LLLT application was carried out after 60 s and 3 days post-coronary occlusion, respectively. Echocardiography was performed 3 days and at the end of the experiment (5 weeks) to evaluate cardiac function. After the last echocardiographic examination, LV hemodynamic evaluation was performed at baseline and on sudden afterload increases. Compared with the Sham group, infarcted rats showed increased systolic and diastolic internal diameter as well as a depressed shortening fraction of LV. The only benefit of the LLLT was a higher shortening fraction after 3 days of infarction. However, treated-LLLT rats show a lower shortening fraction in the 5th week of study when compared with Sham and non-irradiated rats. A worsening of cardiac function was confirmed in the hemodynamic analysis as evidenced by the higher LV end-diastolic pressure and lower +dP/dt and -dP/dt with five weeks of study. Cardiac functional reserve was also impaired by infarction as evidenced by an attenuated response of stroke work index and cardiac output to a sudden afterload stress, without LLLT repercussions. No significant differences were found in the myocardial expression of Akt 1 /VEGF pathway. Collectively, these findings illustrate that LLLT improves LV systolic function in the early post-infarction cardiac remodeling. However, this beneficial effect may be dependent on the maintenance of phototherapy. Long-term studies with LLLT application are needed to establish whether these effects ultimately translate into improved cardiac remodeling.

Time-varying wall stress: an index of ventricular vascular coupling.

PubMed

Dell'Italia, L J; Blackwell, G G; Thorn, B T; Pearce, D J; Bishop, S P; Pohost, G M

1992-08-01

Previous work in the isolated heart and intact circulation has suggested that the relationship between wall stress and time during left ventricular (LV) ejection is linear and that the slope, which will be referred to as time-varying wall stress, increases in response to augmentation in afterload. However, the etiology of the increase in slope has not been determined in an intact animal. Magnetic resonance imaging coupled with high-fidelity LV pressure measurement using a nonferrous catheter-tip manometer generates a detailed assessment of wall stress in an animal model where the thorax and pericardium have never been disturbed. Accordingly, six anesthetized dogs were studied during autonomic blockade with atropine and propranolol during angiotensin infusion, producing three widely disparate left ventricular systolic pressures (87 +/- 7 vs. 124 +/- 13 vs. 152 +/- 10 mmHg, P less than 0.001). Time-varying wall stress did not change from low to medium load (-42.4 +/- 9.5 to -27.3 +/- 22.3 g.cm-2.ms-1) but increased significantly at high load (-21.7 +/- 14.9 g.cm-2.ms-1, P less than 0.05). Analysis of the relative contribution of pressure, chamber radius, wall thickness, and long-axis dimension to the changes in time-varying wall stress demonstrated only the pressure component to change its relative contribution at medium (P less than 0.001) and high load (P less than 0.001). Therefore, we conclude that the increase in time-varying wall stress results from augmentation of pressure in the latter one-half of systole that is incompletely offset by shortening and wall thickening.(ABSTRACT TRUNCATED AT 250 WORDS)

A prospective randomized study of the efficacy and cost-effectiveness of high and low dose regimens of I-131 treatment in hyperthyroidism.

PubMed

Pusuwan, Pawana; Tuntawiroon, Malulee; Sritongkul, Nopamol; Chaudakshetrin, Pachee; Nopmaneejumruslers, Cherdchai; Komoltri, Chulalak; Thepamongkhol, Kullathorn; Khiewvan, Benjapa; Tuchinda, Pongpija; Sriussadaporn, Sutin

2011-03-01

To compare the efficacy and cost-effectiveness of high and low dose regimens of I-131 treatment in patients with hyperthyroidism. One hundred fifty patients with proven hyperthyroidism were randomly allocated into the high (74 patients) and low (76 patients) dose regimen of I-131 treatment. Four patients of the high dose group and one patient of the low dose group were excluded because of lost follow-up. A gland-specific dosage was calculated on the estimated weight of thyroid gland and 24-hour I-131 uptake. The high and low I-131 dose regimens were 150 microCi/gm and 100 microCi/gm, respectively. The first mean radioiodine activity administered to the high and low dose group was 10.2 and 8 mCi, respectively. Repeated treatment was given to 25 patients of the high dose group and 40 patients of the low dose group. Clinical outcome and calculated costs for outpatient attendances, and laboratory tests together with initial and subsequent treatments were evaluated for one year after I-131 treatment. Elimination of hyperthyroidism that resulted in either euthyroidism or hypothyroidism was classified as therapeutic success. The cost effectiveness was also compared. At 6 months after treatment, 45 (64.3%) patients receiving high dose and 59 (78.7%) patients receiving low dose were hyperthyroidism. Clinical outcome at one year showed persistence of hyperthyroidism in 21 (30%) patients of the high dose regimen and 36 (48%) patients of the low dose regimen. At one year post treatment, it was demonstrated that the high dose regimen could eliminate hyperthyroidism in a significantly shorter time than the low dose regimen, i.e., 259.6 days and 305.5 days, respectively, p = 0.008). For the persistent hyperthyroid patients, the average total cost of treatment in the low dose group was significantly higher than that of the high dose group, i.e., 13,422.78 baht and 10,942.79 baht, respectively; p = 0.050). A high dose regimen of radioactive iodine treatment is more effective than the low dose regimen. The successful outcome of a high dose regimen occurred significantly earlier than that of the low dose regimen. For the persistent hyperthyroid patients, the average total cost in the low dose group was significantly higher than that of the high dose group.

Left ventricular mass index as a prognostic factor in patients with severe aortic stenosis and ventricular dysfunction.

PubMed

Fuster, Rafael García; Montero Argudo, José A; Albarova, Oscar Gil; Hornero Sos, Fernando; Cánovas López, Sergio; Bueno Codoñer, María; Buendía Miñano, José A; Rodríguez Albarran, Ignacio

2005-06-01

Ventricular dysfunction and high hypertrophy may influence surgical outcome in aortic stenosis. Our aim was to determine whether an excessive left ventricular mass index (LVMI) discriminates different risk profiles in aortic stenosis with low ventricular ejection fraction (LVEF). Three hundred and thirty-nine patients with severe aortic stenosis underwent valve replacement (Mar-1994 and Nov-2001). LVMI values over the superior quartile were considered increased. Mortality models were constructed in global and LVEF

Comparison of two dose regimens of ibuprofen for the closure of patent ductus arteriosus in preterm newborns.

PubMed

Dornelles, Laura Vargas; Corso, Andréa Lúcia; Silveira, Rita de Cássia; Procianoy, Renato Soibelmann

2016-01-01

To compare the efficacy of intravenous ibuprofen at high (20-10-10mg/kg/dose) and low doses (10-5-5mg/kg/dose) the closure of patent ductus arteriosus in preterm newborns. A cohort study with historical control of newborns that received high- and low-dose intravenous ibuprofen, from 2010 to 2013 in a neonatal intensive care unit, for closure of the patent ductus arteriosus, documented by echocardiography. Secondary outcomes included the number of ibuprofen cycles, incidence of bronchopulmonary dysplasia, necrotizing enterocolitis, changes in renal function, and death. Seventy-seven patients received three doses of ibuprofen for the treatment of patent ductus arteriosus, with 33 receiving high-dose and 44 low-dose therapy. The ductus closed after the first cycle in 25 (56.8%) low-dose patients and in 17 (51.5%) high-dose patients (p>0.99). Sixteen patients received a second cycle of ibuprofen, and the ductus closed in 50% after low-dose and in 60% after high-dose therapy (p>0.99). Seven patients required surgery for ductus closure, 13.6% in the low-dose group and 3% in the high-dose group (p=0.22). Thirty-nine patients developed bronchopulmonary dysplasia, 50% in the low-dose group and 51.5% in the high-dose group (p>0.99). Twenty-two (50%) low-dose patients died vs. 15 (45.5%) high-dose patients (p=0.86). There was no difference in closure of the ductus arteriosus or occurrence of adverse effects between the two dose regimens. Copyright © 2016 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

The impact of the oxygen scavenger on the dose-rate dependence and dose sensitivity of MAGIC type polymer gels

NASA Astrophysics Data System (ADS)

Khan, Muzafar; Heilemann, Gerd; Kuess, Peter; Georg, Dietmar; Berg, Andreas

2018-03-01

Recent developments in radiation therapy aimed at more precise dose delivery along with higher dose gradients (dose painting) and more efficient dose delivery with higher dose rates e.g. flattening filter free (FFF) irradiation. Magnetic-resonance-imaging based polymer gel dosimetry offers 3D information for precise dose delivery techniques. Many of the proposed polymer gels have been reported to exhibit a dose response, measured as relaxation rate ΔR2(D), which is dose rate dependent. A lack of or a reduced dose-rate sensitivity is very important for dosimetric accuracy, especially with regard to the increasing clinical use of FFF irradiation protocols with LINACs at high dose rates. Some commonly used polymer gels are based on Methacrylic-Acid-Gel-Initiated-by-Copper (MAGIC). Here, we report on the dose sensitivity (ΔR2/ΔD) of MAGIC-type gels with different oxygen scavenger concentration for their specific dependence on the applied dose rate in order to improve the dosimetric performance, especially for high dose rates. A preclinical x-ray machine (‘Yxlon’, E  =  200 kV) was used for irradiation to cover a range of dose rates from low \\dot{D} min  =  0.6 Gy min-1 to high \\dot{D} max  =  18 Gy min-1. The dose response was evaluated using R2-imaging of the gel on a human high-field (7T) MR-scanner. The results indicate that all of the investigated dose rates had an impact on the dose response in polymer gel dosimeters, being strongest in the high dose region and less effective for low dose levels. The absolute dose rate dependence \\frac{(Δ R2/Δ D)}{Δ \\dot{D}} of the dose response in MAGIC-type gel is significantly reduced using higher concentrations of oxygen scavenger at the expense of reduced dose sensitivity. For quantitative dose evaluations the relative dose rate dependence of a polymer gel, normalized to its sensitivity is important. Based on this normalized sensitivity the dose rate sensitivity was reduced distinctly using an increased oxygen scavenger concentration with reference to standard MAGIC-type gel formulation at high dose rate levels. The proposed gel composition with high oxygen scavenger concentration exhibits a larger linear active dose response and might be used especially in FFF-radiation applications and preclinical dosimetry at high dose rates. We propose in general to use high dose rates for calibration and evaluation as the change in relative dose sensitivity is reduced at higher dose rates in all of the investigated gel types.

Differential renal effects of candesartan at high and ultra-high doses in diabetic mice–potential role of the ACE2/AT2R/Mas axis

PubMed Central

Callera, Glaucia E.; Antunes, Tayze T.; Correa, Jose W.; Moorman, Danielle; Gutsol, Alexey; He, Ying; Cat, Aurelie Nguyen Dinh; Briones, Ana M.; Montezano, Augusto C.; Burns, Kevin D.; Touyz, Rhian M.

2016-01-01

High doses of Ang II receptor (AT1R) blockers (ARBs) are renoprotective in diabetes. Underlying mechanisms remain unclear. We evaluated whether high/ultra-high doses of candesartan (ARB) up-regulate angiotensin-converting enzyme 2 (ACE2)/Ang II type 2 receptor (AT2R)/Mas receptor [protective axis of the of the renin–angiotensin system (RAS)] in diabetic mice. Systolic blood pressure (SBP), albuminuria and expression/activity of RAS components were assessed in diabetic db/db and control db/+ mice treated with increasing candesartan doses (intermediate, 1 mg/kg/d; high, 5 mg/kg/d; ultra-high, 25 and 75 mg/kg/d; 4 weeks). Lower doses candesartan did not influence SBP, but ultra-high doses reduced SBP in both groups. Plasma glucose and albuminuria were increased in db/db compared with db/+ mice. In diabetic mice treated with intermediate dose candesartan, renal tubular damage and albuminuria were ameliorated and expression of ACE2, AT2R and Mas and activity of ACE2 were increased, effects associated with reduced ERK1/2 phosphorylation, decreased fibrosis and renal protection. Ultra-high doses did not influence the ACE2/AT2R/Mas axis and promoted renal injury with increased renal ERK1/2 activation and exaggerated fibronectin expression in db/db mice. Our study demonstrates dose-related effects of candesartan in diabetic nephropathy: intermediate–high dose candesartan is renoprotective, whereas ultra-high dose candesartan induces renal damage. Molecular processes associated with these effects involve differential modulation of the ACE2/AT2R/Mas axis: intermediate–high dose candesartan up-regulating RAS protective components and attenuating pro-fibrotic processes, and ultra-high doses having opposite effects. These findings suggest novel mechanisms through the protective RAS axis, whereby candesartan may ameliorate diabetic nephropathy. Our findings also highlight potential injurious renal effects of ultra-high dose candesartan in diabetes. PMID:27612496

β-blocker dosage and outcomes after acute coronary syndrome.

PubMed

Allen, Jason E; Knight, Stacey; McCubrey, Raymond O; Bair, Tami; Muhlestein, Joseph Brent; Goldberger, Jeffrey J; Anderson, Jeffrey L

2017-02-01

Although β-blockers increase survival in acute coronary syndrome (ACS) patients, the doses used in trials were higher than doses used in practice, and recent data do not support an advantage of higher doses. We hypothesized that rates of major adverse cardiac events (MACE), all-cause death, myocardial infarction, and stroke are equivalent for patients on low-dose and high-dose β-blocker. Patients admitted to Intermountain Healthcare with ACS and diagnosed with ≥70% coronary stenosis between 1994 and 2013 were studied (N = 7,834). We classified low dose as ≤25% and high dose as ≥50% of an equivalent daily dose of 200 mg of metoprolol. Multivariate analyses were used to test association between low-dose versus high-dose β-blocker dosage and MACE at 0-6 months and 6-24 months. A total of 5,287 ACS subjects were discharged on β-blockers (87% low dose, 12% high dose, and 1% intermediate dose). The 6-month MACE outcomes rates for the β-blocker dosage (low versus high) were not equivalent (P = .18) (hazard ratio [HR] = 0.76; 95% CI, 0.52-1.10). However, subjects on low-dose β-blocker therapy did have a significantly decreased risk of myocardial infarction for 0-6 months (HR = 0.53; 95% CI, 0.33-0.86). The rates of MACE events during the 6-24 months after presentation with ACS were equivalent for the 2 doses (P = .009; HR = 1.03 [95% CI, 0.70-1.50]). In ACS patients, rates of MACE for high-dose and low-dose β-blocker doses are similar. These findings question the importance of achieving a high dose of β-blocker in ACS patients and highlight the need for further investigation of this clinical question. Copyright © 2016 Elsevier Inc. All rights reserved.

Older adults and high-risk medication administration in the emergency department.

PubMed

Kim, Mitchell; Mitchell, Steven H; Gatewood, Medley; Bennett, Katherine A; Sutton, Paul R; Crawford, Carol A; Bentov, Itay; Damodarasamy, Mamatha; Kaplan, Stephen J; Reed, May J

2017-01-01

Older adults are susceptible to adverse effects from opioids, nonsteroidal anti-inflammatory drugs (NSAIDs), and benzodiazepines (BZDs). We investigated factors associated with the administration of elevated doses of these medications of interest to older adults (≥65 years old) in the emergency department (ED). ED records were queried for the administration of medications of interest to older adults at two academic medical center EDs over a 6-month period. Frequency of recommended versus elevated ("High doses" were defined as doses that ranged between 1.5 and 3 times higher than the recommended starting doses; "very high doses" were defined as higher than high doses) starting doses of medications, as determined by geriatric pharmacy/medicine guidelines and expert consensus, was compared by age groups (65-69, 70-74, 75-79, 80-84, and ≥85 years), gender, and hospital. There were 17896 visits representing 11374 unique patients >65 years of age (55.3% men, 44.7% women). A total of 3394 doses of medications of interest including 1678 high doses and 684 very high doses were administered to 1364 different patients. Administration of elevated doses of medications was more common than that of recommended doses. Focusing on opioids and BZDs, the 65-69-year age group was much more likely to receive very high doses (1481 and 412 doses, respectively) than the ≥85-year age groups (relative risk [RR] 5.52, 95% CI 2.56-11.90), mainly reflecting elevated opioid dosing (RR 8.28, 95% CI 3.69-18.57). Men were more likely than women to receive very high doses (RR 1.47, 95% CI 1.26-1.72), primarily due to BZDs (RR 2.12, 95% CI 2.07-2.16). Administration of elevated doses of opioids and BZDs in the older population occurs frequently in the ED, especially to the 65-69-year age group and men. Further attention to potentially unsafe dosing of high-risk medications to older adults in the ED is warranted.

Impact of high- versus low-dose neuromuscular blocking agent administration on unplanned 30-day readmission rates in retroperitoneal laparoscopic surgery.

PubMed

Boon, Martijn; Martini, Chris; Yang, H Keri; Sen, Shuvayu S; Bevers, Rob; Warlé, Michiel; Aarts, Leon; Niesters, Marieke; Dahan, Albert

2018-01-01

Recent data shows that a neuromuscular block (NMB) induced by administration of high doses of rocuronium improves surgical conditions in certain procedures. However, there are limited data on the effect such practices on postoperative outcomes. We performed a retrospective analysis to compare unplanned 30-day readmissions in patients that received high-dose versus low-dose rocuronium administration during general anesthesia for laparoscopic retroperitoneal surgery. This retrospective cohort study was performed in the Netherlands in an academic hospital where routine high-dose rocuronium NMB has been practiced since July 2015. Charts of patients receiving anesthesia between January 2014 and December 2016 were searched for surgical cases receiving high-dose rocuronium and matched with respect to procedure, age, sex and ASA classification to patients receiving low-dose rocuronium. The primary post-operative outcome was unplanned 30-day readmission rate. There were 130 patients in each cohort. Patients in the high- and low-dose rocuronium cohorts received 217 ± 49 versus 37 ± 5 mg rocuronium, respectively. In the high-dose rocuronium group neuromuscular activity was consistently monitored; matched patients were unreliably monitored. All patients receiving high-dose rocuronium were reversed with sugammadex, while just 33% of matched patients were reversed with sugammadex and 20% with neostigmine; the remaining patients were not reversed. Unplanned 30-day readmission rate was significantly lower in the high-dose compared to the low-dose rocuronium cohort (3.8% vs. 12.7%; p = 0.03; odds ratio = 0.33, 95% C.I. 0.12-0.95). This small retrospective study demonstrates a lower incidence of unplanned readmissions within 30-days following laparoscopic retroperitoneal surgery with high-dose relaxant anesthesia and sugammadex reversal in comparison to low-dose relaxant anesthesia. Further prospective studies are needed in larger samples to corroborate our findings and additionally assess the pharmacoeconomics of high-dose relaxant anesthesia taking into account the benefits (reduced readmissions) and harm (cost of relaxants and reversal agents) of such practice.

[Proposing a physiological model for Emergency Department. Operating principles, classification of overcrowding and guidelines for redesign].

PubMed

Herrera Carranza, M; Aguado Correa, F; Padilla Garrido, N; López Camacho, F

2017-04-30

The operation of Emergency Departments (ED) is determined by demand, their own organizational structures and the connection to other medical care levels. When these elements are not simultaneous, it hinders patient flow and decreases capacity, making it necessary to employ a systemic approach to the chain of emergency care as a single operational entity. With this theoretical orientation, we suggest a conceptual model similar to the physiological cardiac output, in which the preload is the demand, the contractile or flow pump is the organizational structure, the afterload is the hospital, the pre-ED valve is primary care and outpatient emergencies, and the post-ED valve is the diagnostic support services and the specialist consultants. Based on this theoretical approach we classify the different types of ED overcrowding and systematise its causes and the different waiting lists that it generates, which can help to redesign the service and avoid its saturation.

Mechanical stimulation in the engineering of heart muscle.

PubMed

Liaw, Norman Yu; Zimmermann, Wolfram-Hubertus

2016-01-15

Recreating the beating heart in the laboratory continues to be a formidable bioengineering challenge. The fundamental feature of the heart is its pumping action, requiring considerable mechanical forces to compress a blood filled chamber with a defined in- and outlet. Ventricular output crucially depends on venous loading of the ventricles (preload) and on the force generated by the preloaded ventricles to overcome arterial blood pressure (afterload). The rate of contraction is controlled by the spontaneously active sinus node and transmission of its electrical impulses into the ventricles. The underlying principles for these physiological processes are described by the Frank-Starling mechanism and Bowditch phenomenon. It is essential to consider these principles in the design and evaluation of tissue engineered myocardium. This review focuses on current strategies to evoke mechanical loading in hydrogel-based heart muscle engineering. Copyright © 2015. Published by Elsevier B.V.

Novel putative pharmacological therapies to protect the right ventricle in pulmonary hypertension: a review of current literature

PubMed Central

Schulz, Rainer; Sliwa, Karen; Schermuly, Ralph Theo; Lecour, Sandrine

2017-01-01

Pulmonary hypertension (PH) is defined by elevated mean pulmonary artery pressure following the pathological remodelling of small pulmonary arteries. An increase in right ventricular (RV) afterload results in RV hypertrophy and RV failure. The pathophysiology of PH, and RV remodelling in particular, is not well understood, thus explaining, at least in part, why current PH therapies have a limited effect. Existing therapies mostly target the pulmonary circulation. Because the remodelled RV fails to support normal cardiac function, patients eventually succumb from RV failure. Developing novel therapies that directly target the function of the RV may therefore benefit patients with PH. In the past decade, several promising studies have investigated novel cardioprotective strategies in experimental models of PH. This review aims to comprehensively discuss and highlight these novel experimental approaches to confer, in the long‐term, greater health benefit in patients with PH. PMID:28099680

Harmony Behind the Trumped-Shaped Vessel: the Essential Role of the Ductus Venosus in Fetal Medicine.

PubMed

Turan, Sifa; Turan, Ozhan M

2018-03-15

The ductus venosus is a fetal vessel that functions importantly in the transfer of oxygen-and nutrient-rich blood from the umbilical vein to vital organs. Its control under active regulation and its anatomy result in a flow-velocity profile that is typically forward throughout the cardiac cycle. This forward cardiac function reflects afterload, cardiac contractility, compliance, and vascular volume changes. Ductus venosus assessment gives valuable information under different fetal conditions. For example, during first trimester screening, an abnormal ductus venosus measurement changes the screening result. Assessment of ductus venosus in twin-to-twin transfusion syndrome is an essential element of staging. In fetal growth restriction, an abnormal waveform mandates imminent delivery. In this review, we will discuss the role of ductus venosus assessment and its role in antenatal management and outcome prediction in certain fetal conditions throughout pregnancy.

Hindlimb immobilization - Length-tension and contractile properties of skeletal muscle

NASA Technical Reports Server (NTRS)

Witzmann, F. A.; Kim, D. H.; Fitts, R. H.

1982-01-01

Casts were placed around rat feet in plantar flexion position to immobilize the soleus muscle in a shortened position, while the other foot was fixed in dorsal flexion to set the extensor digitorum longus in a shortened position. The total muscular atrophy and contractile properties were measured at 1, 2, 4, 7, 14, 21, 28, 35, and 42 days after immobilization, with casts being replaced every two weeks. The slow twitch soleus and the fast-twitch vastus lateralis and longus muscles were excised after termination of the experiment. The muscles were then stretched and subjected to electric shock to elicit peak tetanic tension and peak tetanic tension development. Force velocity features of the three muscles were assayed in a series of afterloaded contractions and fiber lengths were measured from subsequently macerated muscle. All muscles atrophied during immobilization, reaching a new steady state by day 21. Decreases in fiber and sarcomere lengths were also observed.

Harmony Behind the Trumped-Shaped Vessel: the Essential Role of the Ductus Venosus in Fetal Medicine

PubMed Central

Turan, Sifa; Turan, Ozhan M.

2018-01-01

The ductus venosus is a fetal vessel that functions importantly in the transfer of oxygen-and nutrient-rich blood from the umbilical vein to vital organs. Its control under active regulation and its anatomy result in a flow-velocity profile that is typically forward throughout the cardiac cycle. This forward cardiac function reflects afterload, cardiac contractility, compliance, and vascular volume changes. Ductus venosus assessment gives valuable information under different fetal conditions. For example, during first trimester screening, an abnormal ductus venosus measurement changes the screening result. Assessment of ductus venosus in twin-to-twin transfusion syndrome is an essential element of staging. In fetal growth restriction, an abnormal waveform mandates imminent delivery. In this review, we will discuss the role of ductus venosus assessment and its role in antenatal management and outcome prediction in certain fetal conditions throughout pregnancy. PMID:29553462

The clinical pharmacology of alkylating agents in high-dose chemotherapy.

PubMed

Huitema, A D; Smits, K D; Mathôt, R A; Schellens, J H; Rodenhuis, S; Beijnen, J H

2000-08-01

Alkylating agents are widely used in high-dose chemotherapy regimens in combination with hematological support. Knowledge about the pharmacokinetics and pharmacodynamics of these agents administered in high doses is critical for the safe and efficient use of these regimens. The aim of this review is to summarize the clinical pharmacology of the alkylating agents (including the platinum compounds) in high-dose chemotherapy. Differences between conventional and high doses will be discussed.

A first-in-man study of the Reitan catheter pump for circulatory support in patients undergoing high-risk percutaneous coronary intervention.

PubMed

Smith, Elliot J; Reitan, Oyvind; Keeble, Thomas; Dixon, Kerry; Rothman, Martin T

2009-06-01

To investigate the safety of a novel percutaneous circulatory support device during high-risk percutaneous coronary intervention (PCI). The Reitan catheter pump (RCP) consists of a catheter-mounted pump-head with a foldable propeller and surrounding cage. Positioned in the descending aorta the pump creates a pressure gradient, reducing afterload and enhancing organ perfusion. Ten consecutive patients requiring circulatory support underwent PCI; mean age 71 +/- 9; LVEF 34% +/- 11%; jeopardy score 8 +/- 2.3. The RCP was inserted via the femoral artery. Hemostasis was achieved using Perclose sutures. PCI was performed via the radial artery. Outcomes included in-hospital death, MI, stroke, and vascular injury. Hemoglobin (Hb), free plasma Hb (fHb), platelets, and creatinine (cre) were measured pre PCI and post RCP removal. The pump was inserted and operated successfully in 9/10 cases (median 79 min). Propeller rotation at 10,444 +/- 1,424 rpm maintained an aortic gradient of 9.8 +/- 2 mm Hg. Although fHb increased, there was no significant hemolysis (4.7 +/- 2.4 mg/dl pre vs. 11.9 +/- 10.5 post, P = 0.04, reference 20 mg/dl). Platelets were unchanged (pre 257 +/- 74 x 10(9) vs. 245 +/- 63, P = NS). Renal function improved (cre pre 110 +/- 27 micromol/l vs. 99 +/- 28, P = 0.004). The RCP was not used in one patient following femoral introducer sheath related aortic dissection. All PCI procedures were successful with no deaths or strokes, one MI, and no vascular complications following pump removal. The RCP can be used safely in high-risk PCI patients. This device may be an alternative to other percutaneous systems when substantial cardiac support is needed. (c) 2009 Wiley-Liss, Inc.

High doses of S-methylcysteine cause hypoxia-induced cardiomyocyte apoptosis accompanied by engulfment of mitochondaria by nucleus.

PubMed

El-Magd, Mohammed A; Abdo, Walied S; El-Maddaway, Mustafa; Nasr, Nasr M; Gaber, Rasha A; El-Shetry, Eman S; Saleh, Ayman A; Alzahrani, Faisal Abdulrahman Ali; Abdelhady, Doaa H

2017-10-01

Despite its important role as a medicinal plant, some studies reported a toxic effect for garlic (Allium sativum) when given in higher doses. Herein, we investigated the possible cardiotoxic effects of high doses of S-methylcysteine (SMC), a water soluble organosulfur compound present in garlic. Rats were orally administered SMC at a low dose (50mg), high dose (150mg) and very high dose (300mg)/kg body weight, or saline (control) for 10days. High and very high doses of SMC resulted in a significant increase in serum cardiac injury biomarkers [aspartate transaminase (AST), lactate dehydrogenase (LDH), creatine kinase (CK) and cardiac troponin T (cTnT)], as well as oxidative stress marker nitric oxide (NO) concentration in heart and a significant decrease in cardiac superoxide dismutase (SOD) activity. Moreover, ultrastructure findings in myocardium of rats treated by high and very high doses showed inter-bundle vacuolation, loss of myofibrils, and centripetal movement of mitochondria towards nucleus. The mitochondria were partially surrounded by nuclear membrane at high dose SMC, and completely engulfed by nucleus at very high dose. This centripetal movement of mitochondria accompanied by cardiomyocytes hypoxia-induced apoptosis as evident by increasing TUNEL positive cells as well as upregulation of apoptotic genes (caspase3 and Bax), hypoxia inducible factor 1 alpha (HIF1α), dynein light chain 1 (DYNLL1) and downregulation of the anti-apoptotic marker, Bcl2. We conclude that high and very high doses of SMC cause hypoxia induced cardiomyocyte apoptosis accompanied by engulfment of mitochondria by nucleus. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Regulatory Forum Opinion Piece*: Retrospective Evaluation of Doses in the 26-week Tg.rasH2 Mice Carcinogenicity Studies: Recommendation to Eliminate High Doses at Maximum Tolerated Dose (MTD) in Future Studies.

PubMed

Paranjpe, Madhav G; Denton, Melissa D; Vidmar, Tom J; Elbekai, Reem H

2015-07-01

High doses in Tg.rasH2 carcinogenicity studies are usually set at the maximum tolerated dose (MTD), although this dose selection strategy has not been critically evaluated. We analyzed the body weight gains (BWGs), mortality, and tumor response in control and treated groups of 29 Tg.rasH2 studies conducted at BioReliance. Based on our analysis, it is evident that the MTD was exceeded at the high and/or mid-doses in several studies. The incidence of tumors in high doses was lower when compared to the low and mid-doses of both sexes. Thus, we recommend that the high dose in male mice should not exceed one-half of the estimated MTD (EMTD), as it is currently chosen, and the next dose should be one-fourth of the EMTD. Because females were less sensitive to decrements in BWG, the high dose in female mice should not exceed two-third of EMTD and the next dose group should be one-third of EMTD. If needed, a third dose group should be set at one-eighth EMTD in males and one-sixth EMTD in females. In addition, for compounds that do not show toxicity in the range finding studies, a limit dose should be applied for the 26-week carcinogenicity studies. © 2014 by The Author(s).

Analysis of renal impairment in MM-003, a phase III study of pomalidomide + low - dose dexamethasone versus high - dose dexamethasone in refractory or relapsed and refractory multiple myeloma

PubMed Central

Weisel, Katja C.; Dimopoulos, Meletios A.; Moreau, Philippe; Lacy, Martha Q.; Song, Kevin W.; Delforge, Michel; Karlin, Lionel; Goldschmidt, Hartmut; Banos, Anne; Oriol, Albert; Alegre, Adrian; Chen, Christine; Cavo, Michele; Garderet, Laurent; Ivanova, Valentina; Martinez-Lopez, Joaquin; Knop, Stefan; Yu, Xin; Hong, Kevin; Sternas, Lars; Jacques, Christian; Zaki, Mohamed H.; Miguel, Jesus San

2016-01-01

Pomalidomide + low-dose dexamethasone is effective and well tolerated for refractory or relapsed and refractory multiple myeloma after bortezomib and lenalidomide failure. The phase III trial MM-003 compared pomalidomide + low-dose dexamethasone with high-dose dexamethasone. This subanalysis grouped patients by baseline creatinine clearance ≥ 30 − < 60 mL/min (n=93, pomalidomide + low-dose dexamethasone; n=56, high-dose dexamethasone) or ≥ 60 mL/min (n=205, pomalidomide + low-dose dexamethasone; n=93, high-dose dexamethasone). Median progression-free survival was similar for both subgroups and favored pomalidomide + low-dose dexamethasone versus high-dose dexamethasone: 4.0 versus 1.9 months in the group with baseline creatinine clearance ≥ 30 − < 60 mL/min (P<0.001) and 4.0 versus 2.0 months in the group with baseline creatinine clearance ≥ 60 mL/min (P<0.001). Median overall survival for pomalidomide + low-dose dexamethasone versus high-dose dexamethasone was 10.4 versus 4.9 months (P=0.030) and 15.5 versus 9.2 months (P=0.133), respectively. Improved renal function, defined as an increase in creatinine clearance from < 60 to ≥ 60 mL/min, was similar in pomalidomide + low-dose dexamethasone and high-dose dexamethasone patients (42% and 47%, respectively). Improvement in progression-free and overall survival in these patients was comparable with that in patients without renal impairment. There was no increase in discontinuations of therapy, dose modifications, and adverse events in patients with moderate renal impairment. Pomalidomide at a starting dose of 4 mg + low-dose dexamethasone is well tolerated in patients with refractory or relapsed and refractory multiple myeloma, and of comparable efficacy if moderate renal impairment is present. This trial was registered with clinicaltrials.gov identifier 01311687 and EudraCT identifier 2010-019820-30. PMID:27081177

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

PubMed

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

2015-08-01

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

High-dose Versus Low-dose Tranexamic Acid to Reduce Transfusion Requirements in Pediatric Scoliosis Surgery.

PubMed

Johnson, Daniel J; Johnson, Christine C; Goobie, Susan M; Nami, Nina; Wetzler, Joshua A; Sponseller, Paul D; Frank, Steven M

2017-12-01

Our objective was to quantify blood loss and transfusion requirements for high-dose and low-dose tranexamic acid (TXA) dosing regimens in pediatric patients undergoing spinal fusion for correction of idiopathic scoliosis. Previous investigators have established the efficacy of TXA in pediatric scoliosis surgery; however, the dosing regimens vary widely and the optimal dose has not been established. We retrospectively analyzed electronic medical records for 116 patients who underwent spinal fusion surgery for idiopathic scoliosis by a single surgeon and were treated with TXA. In total, 72 patients received a 10 mg/kg loading dose with a 1 mg/kg/h maintenance dose (low-dose) and 44 patients received 50 mg/kg loading dose with a 5 mg/kg/h maintenance dose (high-dose). Estimated blood loss and transfusion requirements were compared between dosing groups. Patient characteristics were nearly identical between the 2 groups. Compared with the low-dose TXA group, the high-dose TXA group had decreased estimated blood loss (695 vs. 968 mL, P=0.01), and a decrease in both intraoperative (0.3 vs. 0.9 units, P=0.01) and whole hospitalization (0.4 vs. 1.0 units, P=0.04) red blood cell transfusion requirements. The higher-dose TXA was associated with decreased intraoperative (P=0.01), and whole hospital transfusion (P=0.01) requirements, even after risk-adjustment for potential confounding variables. High-dose TXA is more effective than low-dose TXA in reducing blood loss and transfusion requirements in pediatric idiopathic scoliosis patients undergoing surgery. Level-III, retrospective cohort study.

Temporal changes in physiology and haematology in response to high- and micro-doses of recombinant human erythropoietin.

PubMed

Clark, Brad; Woolford, Sarah M; Eastwood, Annette; Sharpe, Ken; Barnes, Peter G; Gore, Christopher J

2017-10-01

There is evidence to suggest athletes have adopted recombinant human erythropoietin (rHuEPO) dosing regimens that diminish the likelihood of being caught by direct detection techniques. However, the temporal response in physiology, performance, and Athlete Biological Passport (ABP) parameters to such regimens is not clearly understood. Participants were assigned to a high-dose only group (HIGH, n = 8, six rHuEPO doses of 250 IU/kg over two weeks), a combined high micro-dose group (COMB, n = 8, high-dose plus nine rHuEPO micro-doses over a further three weeks), or one of two placebo control groups who received saline in the same pattern as the HIGH (HIGH-PLACEBO, n = 4) or COMB (COMB-PLACEBO, n = 4) groups. Temporal changes in physiology and performance were tracked by graded exercise test (GXT) and haemoglobin mass assessment at baseline, after high dose, after micro-dose (COMB and COMB-PLACEBO only) and after a four-week washout. Venous blood samples were collected throughout the baseline, rHuEPO administration, and washout periods to determine the haematological and ABP response to each dosing regimen. Physiological adaptations induced by a two-week rHuEPO high-dose were maintained by rHuEPO micro-dosing for at least three weeks. However, all participants administered rHuEPO registered at least one suspicious ABP value during the administration or washout periods. These results indicate there is sufficient sensitivity in the ABP to detect use of high rHuEPO doping regimens in athletic populations and they provide important empirical examples for use by anti-doping experts. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

The effect of perioperative insulin treatment on cardiodepression in mild adiposity in mice.

PubMed

Boly, Chantal A; Eringa, Etto C; Bouwman, R Arthur; van den Akker, Rob F P; de Man, Frances S; Schalij, Ingrid; Loer, Stephan A; Boer, Christa; van den Brom, Charissa E

2016-09-20

While most studies focus on cardiovascular morbidity following anesthesia and surgery in excessive obesity, it is unknown whether these intraoperative cardiovascular alterations also occur in milder forms of adiposity without type 2 diabetes and if insulin is a possible treatment to improve intraoperative myocardial performance. In this experimental study we investigated whether mild adiposity without metabolic alterations is already associated with cardiometabolic dysfunction during anesthesia, mechanical ventilation and surgery and whether these myocardial alterations can be neutralized by intraoperative insulin treatment. Mice were fed a western (WD) or control diet (CD) for 4 weeks. After metabolic profiling, mice underwent general anesthesia, mechanical ventilation and surgery. Cardiac function was determined with echocardiography and left-ventricular pressure-volume analysis. Myocardial perfusion was determined with contrast-enhanced echocardiography. WD-fed mice were subsequently treated with insulin by hyperinsulinemic euglycemic clamping followed by the same measurements of cardiac function and perfusion. Western-type diet feeding led to a 13 % increase in bodyweight, (p < 0.0001) and increased adipose tissue mass, without metabolic alterations. Despite this mild phenotype, WD-fed mice had decreased systolic and diastolic function (end-systolic elastance was 2.0 ± 0.5 versus 4.1 ± 2.4 mmHg/μL, p = 0.01 and diastolic beta was 0.07 ± 0.03 versus 0.04 ± 0.01 mmHg/μL, p = 0.02) compared to CD-fed mice. Ventriculo-arterial coupling and myocardial perfusion were decreased by 48 % (p = 0.003) and 43 % (p = 0.03) respectively. Insulin treatment in WD-fed mice improved echo-derived systolic function (fractional shortening 42 ± 5 % to 46 ± 3, p = 0.05), likely due to decreased afterload, but there was no effect on load-independent measures of systolic function or myocardial perfusion. However, there was a trend towards improved diastolic function after insulin treatment (43 % improvement, p = 0.05) in WD-fed mice. Mild adiposity without metabolic alterations already affected cardiac function and perfusion during anesthesia, mechanical ventilation and surgery in mice. Intraoperative insulin may be beneficial to reduce afterload and enhance intraoperative ventricular relaxation, but not to improve ventricular contractility or myocardial perfusion.

Amiodarone. Haemodynamic profile during intravenous administration and effect on pacing-induced ischaemia in man.

PubMed

Remme, W J; van Hoogenhuyze, D C; Kruyssen, D A; Krauss, X H; Storm, C J

1985-03-01

The haemodynamic changes during intravenous amiodarone administration in laboratory animals and human studies are reviewed and compared with the results from our investigations. While the results of previous human studies have been rather variable, our investigations suggest that the cardiovascular changes following intravenous amiodarone include an early and usually short reduction of systemic and coronary vascular resistance, which may be partially due to the vasodilating properties of the solvent, polysorbate 80. As a result, a decrease in afterload and cardiac work and increases in cardiac output and coronary blood flow occur. Contrary to the observations in the animal experiments, heart rate increases in man, presumably as a result of the relatively greater fall in afterload which occurs. However, in spite of this increase in heart rate, contractility is reduced at the end of amiodarone administration and remains depressed after the infusion, resulting in a significant increase in left ventricular filling pressure. Neither myocardial oxygen demand nor consumption change during amiodarone administration. Although the intrinsic negative inotropic effects of amiodarone warrant a cautious approach in patients with left ventricular dysfunction, worsening of heart failure or the occurrence of myocardial ischaemia has been reported in only very few cases so far. In contrast, the drug was demonstrated to protect against pacing-induced myocardial ischaemia, in patients with both normal and depressed left ventricular function. These anti-ischaemic properties of amiodarone were investigated in a second study using a double pacing stress test protocol. Overall myocardial oxygen consumption did not change during pacing after amiodarone, but it clearly reduced (regional) myocardial ischaemia, as demonstrated by a reduction of ST-segment changes and anginal pain, and in particular by the absence of myocardial lactate production during pacing after amiodarone. These anti-ischaemic properties are mainly based on a reduction of myocardial oxygen demand, rather than on an improvement in coronary flow. It is concluded then, that amiodarone has significant haemodynamic effects as manifested by an early reduction in vascular resistance and a late negative inotropic effect. Although vasodilatation of short duration caused by its solvent, polysorbate 80, also occurs, the overall cardiovascular changes are caused by the direct, intrinsic haemodynamic effects of amiodarone alone. The important anti-ischaemic properties of amiodarone appear to result primarily from these cardiovascular actions and the inherent reduction in myocardial oxygen demand.

Exercise facilitates early recognition of cardiac and vascular remodeling in chronic thromboembolic pulmonary hypertension in swine.

PubMed

Stam, Kelly; van Duin, Richard W B; Uitterdijk, André; Cai, Zongye; Duncker, Dirk J; Merkus, Daphne

2018-03-01

Chronic thromboembolic pulmonary hypertension (CTEPH) develops in 4% of patients after pulmonary embolism and is accompanied by an impaired exercise tolerance, which is ascribed to the increased right ventricular (RV) afterload in combination with a ventilation/perfusion (V/Q) mismatch in the lungs. The present study aimed to investigate changes in arterial Po 2 and hemodynamics in response to graded treadmill exercise during development and progression of CTEPH in a novel swine model. Swine were chronically instrumented and received multiple pulmonary embolisms by 1) microsphere infusion (Spheres) over 5 wk, 2) endothelial dysfunction by administration of the endothelial nitric oxide synthase inhibitor N ω -nitro-l-arginine methyl ester (L-NAME) for 7 wk, 3) combined pulmonary embolisms and endothelial dysfunction (L-NAME + Spheres), or 4) served as sham-operated controls (sham). After a 9 wk followup, embolization combined with endothelial dysfunction resulted in CTEPH, as evidenced by mean pulmonary artery pressures of 39.5 ± 5.1 vs. 19.1 ± 1.5 mmHg (Spheres, P < 0.001), 22.7 ± 2.0 mmHg (L-NAME, P < 0.001), and 20.1 ± 1.5 mmHg (sham, P < 0.001), and a decrease in arterial Po 2 that was exacerbated during exercise, indicating V/Q mismatch. RV dysfunction was present after 5 wk of embolization, both at rest (trend toward increased RV end-systolic lumen area, P = 0.085, and decreased stroke volume index, P = 0.042) and during exercise (decreased stroke volume index vs. control, P = 0.040). With sustained pulmonary hypertension, RV hypertrophy (Fulton index P = 0.022) improved RV function at rest and during exercise, but this improvement was insufficient in CTEPH swine to result in an exercise-induced increase in cardiac index. In conclusion, embolization in combination with endothelial dysfunction results in CTEPH in swine. Exercise increased RV afterload, exacerbated the V/Q mismatch, and unmasked RV dysfunction. NEW & NOTEWORTHY Here, we present the first double-hit chronic thromboembolic pulmonary hypertension swine model. We show that embolization as well as endothelial dysfunction is required to induce sustained pulmonary hypertension, which is accompanied by altered exercise hemodynamics and an exacerbated ventilation/perfusion mismatch during exercise.

IMPACT OF CALCIUM-CHANNEL BLOCKERS ON RIGHT HEART FUNCTION IN A CONTROLLED MODEL OF CHRONIC PULMONARY HYPERTENSION

PubMed Central

Zierer, Andreas; Voeller, Rochus K.; Melby, Spencer J.; Steendijk, Paul; Moon, Marc R.

2009-01-01

Purpose Patients with chronic pulmonary hypertension (CPH) who demonstrate a pulmonary vasodilation following calcium channel blocker (CCB) administration are defined as “responders”. In contrast, “non-responders” are patients who do not show such a pulmonary vasodilation with CCB therapy. The purpose of this investigation was to study the effects of CCB therapy on right heart mechanics in experimental CCB responders versus CCB non-responders. Methods In 12 dogs, right atrial (RA) and ventricular (RV) pressure and volume (conductance catheters) were simultaneously recorded after 3 months of progressive pulmonary artery (PA) banding. Diltiazem was given at 10 mg/hr with the PA constricted (simulated CCB non-responder). Responders were then created by releasing the PA band to unload the ventricle. RA and RV contractility and diastolic stiffness (slope of end-systolic and end-diastolic pressure-volume relations) were calculated and RA reservoir and conduit function were quantified as RA inflow with the tricuspid valve closed versus open, respectively. Results With CCB, RA contractility (p<0.03) and cardiac output (p<0.004) were compromised in simulated non-responders while RA stroke work was pharmacologically depressed in the setting of an unchanged afterload. After simulating a responder by controlled PA band release, the RA became less distensible, causing a shift from reservoir to conduit function (p<0.001) towards physiologic baseline conditions and a recovery in the hyperdynamic compensatory response in both chambers (p<0.007) as evidenced in a declined RA and RV contractility with an improved cardiac output as compared to CPH and simulated non-responders. RA and RV diastolic function in both groups was not affected by CCB. Conclusions CCB did not impact RV function in simulated non-responders, but significantly impaired RA contractility and cardiac output. In simulated responders, afterload fell substantially, thereby allowing the RA and RV to recover from their pathological hyperdynamic contractile response to CPH. This affect was able to outweigh the intrinsic negative effects of CCB therapy on systolic RA function. Current data suggest that the RA in CPH is much more sensitive to CCB therapy than the RV and delineate for the first time why CCB therapy in CPH has been empirically restricted to documented responders. PMID:19237986

Pulmonary arterial hypertension reduces energy efficiency of right, but not left, rat ventricular trabeculae.

PubMed

Pham, Toan; Nisbet, Linley; Taberner, Andrew; Loiselle, Denis; Han, June-Chiew

2018-04-01

Pulmonary arterial hypertension (PAH) triggers right ventricle (RV) hypertrophy and left ventricle (LV) atrophy, which progressively leads to heart failure. We designed experiments under conditions mimicking those encountered by the heart in vivo that allowed us to investigate whether consequent structural and functional remodelling of the ventricles affects their respective energy efficiencies. We found that peak work output was lower in RV trabeculae from PAH rats due to reduced extent and velocity of shortening. However, their suprabasal enthalpy was unaffected due to increased activation heat, resulting in reduced suprabasal efficiency. There was no effect of PAH on LV suprabasal efficiency. We conclude that the mechanism underlying the reduced energy efficiency of hypertrophied RV tissues is attributable to the increased energy cost of Ca 2+ cycling, whereas atrophied LV tissues still maintain normal mechano-energetic performance. Pulmonary arterial hypertension (PAH) greatly increases the afterload on the right ventricle (RV), triggering RV hypertrophy, which progressively leads to RV failure. In contrast, the disease reduces the passive filling pressure of the left ventricle (LV), resulting in LV atrophy. We investigated whether these distinct structural and functional consequences to the ventricles affect their respective energy efficiencies. We studied trabeculae isolated from both ventricles of Wistar rats with monocrotaline-induced PAH and their respective Control groups. Trabeculae were mounted in a calorimeter at 37°C. While contracting at 5 Hz, they were subjected to stress-length work-loops over a wide range of afterloads. They were subsequently required to undergo a series of isometric contractions at various muscle lengths. In both protocols, stress production, length change and suprabasal heat output were simultaneously measured. We found that RV trabeculae from PAH rats generated higher activation heat, but developed normal active stress. Their peak external work output was lower due to reduced extent and velocity of shortening. Despite lower peak work output, suprabasal enthalpy was unaffected, thereby rendering suprabasal efficiency lower. Crossbridge efficiency, however, was unaffected. In contrast, LV trabeculae from PAH rats maintained normal mechano-energetic performance. Pulmonary arterial hypertension reduces the suprabasal energy efficiency of hypertrophied right ventricular tissues as a consequence of the increased energy cost of Ca 2+ cycling. © 2018 The Authors. The Journal of Physiology © 2018 The Physiological Society.

Effects of thyroid hormones on the heart.

PubMed

Vargas-Uricoechea, Hernando; Bonelo-Perdomo, Anilsa; Sierra-Torres, Carlos Hernán

2014-01-01

Thyroid hormones have a significant impact on heart function, mediated by genomic and non-genomic effects. Consequently, thyroid hormone deficiencies, as well as excesses, are expected to result in profound changes in cardiac function regulation and cardiovascular hemodynamics. Thyroid hormones upregulate the expression of the sarcoplasmic reticulum calcium-activated ATPase and downregulate the expression of phospholamban. Overall, hyperthyroidism is characterized by an increase in resting heart rate, blood volume, stroke volume, myocardial contractility, and ejection fraction. The development of "high-output heart failure" in hyperthyroidism may be due to "tachycardia-mediated cardiomyopathy". On the other hand, in a hypothyroid state, thyroid hormone deficiency results in lower heart rate and weakening of myocardial contraction and relaxation, with prolonged systolic and early diastolic times. Cardiac preload is decreased due to impaired diastolic function. Cardiac afterload is increased, and chronotropic and inotropic functions are reduced. Subclinical thyroid dysfunction is relatively common in patients over 65 years of age. In general, subclinical hypothyroidism increases the risk of coronary heart disease (CHD) mortality and CHD events, but not of total mortality. The risk of CHD mortality and atrial fibrillation (but not other outcomes) in subclinical hyperthyroidism is higher among patients with very low levels of thyrotropin. Finally, medications such as amiodarone may induce hypothyroidism (mediated by the Wolff-Chaikoff), as well as hyperthyroidism (mediated by the Jod-Basedow effect). In both instances, the underlying cause is the high concentration of iodine in this medication. Copyright © 2014 Sociedad Española de Arteriosclerosis. Published by Elsevier España. All rights reserved.

Subacute intramuscular toxicity of the acetylcholinesterase reactivating agent Hi-6 in rats and dogs. (Reannouncement with new availability information)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Levine, B.S.; Tomlinson, M.J.

1993-12-31

Studies herein describe the toxicity of HI-6 in Sprague-Dawley rats and Beagle dogs following i.m. injection for 14 days. Dose levels were 0, 50, 150, and 450 mg/kg/day for 10 rats/sex/dose and 0, 35, 70, and 140 mg/kg/day for 4 dogs/sex/dose. Three rats at the high dose, 2 males and 1 female, died prior to scheduled sacrifice. Reduced weight gain, decreased activity, tremors, hunched posture,and poor grooming were seen in high dose survivors. Increased alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities at the mid and high doses suggested hepatotoxicity, although liver weights and histology were normal. Hematology parameters weremore » unaffected except for slight, dose-related increases of platelets in both sexes. Injection site inflammation was seen; however, serum creatine kinase activity was not altered. In dogs, slight weight loss, vomiting, salivation, and diarrhea occurred at the high dose, but no deaths were observed at any of the doses. As with rats, dose-related increases in ALT and AST activities occurred at the mid and high doses, and were, in this case, accompanied at the high dose by hepatomegaly and hepatocellular vacuolization. Cardiotoxicity was evidenced by increased relative heart weights and subtle ECG changes, the latter of which occurred almost exclusively at the highest dose. Injection site inflammation, which was accompanied by dose-related elevations in serum CK-MM2 activity, was also observed.« less

Newly developed ventricular assist device with linear oscillatory actuator.

PubMed

Fukunaga, Kazuyoshi; Funakubo, Akio; Fukui, Yasuhiro

2003-01-01

The goal of this study was to develop a new direct electromagnetic left ventricular assist device (DEM-LVAD) with a linear oscillatory actuator (LOA). The DEM-LVAD is a pulsatile pump with a pusher plate. The pusher plate is driven directly by the mover of the LOA. The LOA provides reciprocating motion without using any movement converter such as a roller screw or a hydraulic system. It consists of a stator with a single winding excitation coil and a mover with two permanent magnets. The simple structure of the LOA is based on fewer parts to bring about high reliability and smaller size. The mover moves back and forth when forward and backward electric current is supplied to the excitation coil. The pump housings have been designed using three-dimensional computer aided design software and fabricated with the aid of computer aided manufacturing technology. Monostrut valves (Bjork-Shiley #21) were used for the prototype. The DEM-LVAD dimension is 96 mm in diameter and 50 mm thick with a mass of 0.62 kg and a volume of 280 ml. An in vitro test (afterload 100 mm Hg; preload 10 mm Hg; input power 10 W) demonstrated more than 6 L/minute maximum output and 15% maximum efficiency at 130 beats per minute (bpm). Dynamic stroke volume ranged between 40 and 60 ml. The feasibility of the DEM-LVAD was confirmed.

Surgical management of a patent ductus arteriosus: Is this still an option?

PubMed

Weisz, Dany E; Giesinger, Regan E

2018-03-07

The evolution of neonatal intensive care over the past decade has seen the role of surgical patent ductus arteriosus (PDA) ligation in preterm infants both decrease in scope and become laden with uncertainty. Associations of ligation with adverse neonatal and neurodevelopmental outcomes have rendered the ligation decision more challenging for clinicians and have been associated with a decline in surgical treatment, but these findings may be due to bias from confounding by indication in observational studies rather than a causal detrimental effect of ligation. Accordingly, ligation may still be indicated for infants with large ductal shunts and moderate-severe respiratory insufficiency in whom the prospect of timely spontaneous closure appears low. Ultimately a randomized trial of surgical ligation versus conservative management is necessary to assess the efficacy of this invasive intervention in a population of extremely preterm infants with large ductal shunts. Simultaneously, the transcatheter approach to ductal closure in the very immature infant represents an exciting therapeutic alternative but which is still in its infancy. Insights into the pathophysiology of postoperative cardiorespiratory deterioration, including the importance of left ventricular afterload, may help clinicians avoid instability and mitigate a potentially injurious aspect of surgical treatment. This review examines the evidence regarding the benefits and risks of PDA surgery in preterm neonates and provides a pathophysiology-based management paradigm to guide perioperative care in high-risk infants. © 2018 Published by Elsevier Ltd.

Efficacy and tolerability of high-dose phenobarbital in children with focal seizures.

PubMed

Okumura, Akihisa; Nakahara, Eri; Ikeno, Mitsuru; Abe, Shinpei; Igarashi, Ayuko; Nakazawa, Mika; Takasu, Michihiko; Shimizu, Toshiaki

2016-04-01

We retrospectively reviewed the outcomes of children with focal epilepsy treated with oral high-dose phenobarbital. We reviewed data on children (aged<15 years) with focal seizures treated with high-dose phenobarbital (>5 mg/kg/day to maintain a target serum level >40 μg/mL) for at least 6 months. Seizure frequency was evaluated after phenobarbital titration, and 1 and 2 years after high-dose phenobarbital treatment commenced. Treatment was judged effective when seizure frequencies fell by ⩾75%. Seven boys and eight girls were treated. The median age at commencement of high-dose phenobarbital therapy was 30 months. The maximal serum phenobarbital level ranged from 36.5 to 62.9 μg/mL. High-dose PB was effective in seven. In two patients, treatment was transiently effective, but seizure frequency later returned to the baseline. High-dose PB was ineffective in six. No significant association between effectiveness and any clinical variable was evident. Drowsiness was recorded in nine patients, but no patient developed a behavioral problem or hypersensitivity. Oral high-dose phenobarbital was effective in 7 of 15 patients with focal epilepsy and well tolerated. High-dose PB may be useful when surgical treatment is difficult. Copyright © 2015 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

[Protection and bidirectional effect of rhubarb anthraquinone and tannins for rats' liver].

PubMed

Qin, Lu-shan; Zhao, Hai-ping; Zhao, Yan-ling; Ma, Zhi-jiel; Zeng, Ling-na; Zhang, Ya-ming; Zhang, Ping; Yan, Dan; Bai, Zhao-fang; Li, Yue; Hao, Qing-xiu; Zhao, Kui-jun; Wang, Jia-bo; Xiao, Xiao-he

2014-06-01

To compare the bidirectional effect of rhubarb total anthraquinone (TA) and total tannins (TT) on rats' liver. One hundred rats were randomly divided into 10 groups, i.e., the blank group, the model group, the blank + high dose TA group, the blank +low dose TA group, the blank + high dose TT group, the blank + low dose TT group, the model + high dose TA group, the model + low dose TA group, the model +high dose TT group, and the model + low dose TT group, 10 in each group. The carbon tetrachloride (CCI4) was used to prepare the acute liver injury rat model. TA and TT of rhubarb (at 5.40 g crude drugs/kg and 14.69 g crude drugs/kg) were intragastrically administrated to rats in all groups except the blank group and the model group, once daily for 6 successive days.The general state of rats, biochemical indices such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), laminin (LN), hyaluronic acid (HA), transforming growth factor beta1 (TGF-beta1), as well pathological results of rat liver tissues. Finally the protection laws of TA and TT for rats' liver were analyzed using factor analysis. Compared with the blank control group, all biochemical indices increased in the blank group (P < 0.05, P < 0.01). HA also increased in the blank + high dose TA group; AST, ALT, and HA also increased in the blank +high dose TT group (P < 0.05). Compared with the model group, AST, ALT, ALP, HA, and TGF-beta1 significantly decreased in the model + low dose TA group, the model + high dose TA group, the model + low dose TT group (P < 0.05, P < 0.01). Serum AST, ALT, and ALP also decreased in the model + high dose TT group (P < 0.05, P < 0.01). Pathological results showed that mild swollen liver cells in the model + high dose TA group. Fatty degeneration and fragmental necrosis around the central veins occurred in the blank + high dose TA group. The pathological injury was inproved in the model +low dose TA group. Two common factors, liver fibrosis and liver cell injury, were extracted by using factor analysis. TA showed stronger improvement of the two common factors than TT. Rhubarb TA and TT showed protective and harmful effects on rats' liver. At an equivalent dosage, TA had better liver protection than TT. High dose TT played a role in liver injury to some extent.

High-Dose Chemotherapy With Autologous Hematopoietic Stem-Cell Transplantation in Metastatic Breast Cancer: Overview of Six Randomized Trials

PubMed Central

Berry, Donald A.; Ueno, Naoto T.; Johnson, Marcella M.; Lei, Xiudong; Caputo, Jean; Smith, Dori A.; Yancey, Linda J.; Crump, Michael; Stadtmauer, Edward A.; Biron, Pierre; Crown, John P.; Schmid, Peter; Lotz, Jean-Pierre; Rosti, Giovanni; Bregni, Marco; Demirer, Taner

2011-01-01

Purpose High doses of effective chemotherapy are compelling if they can be delivered safely. Substantial interest in supporting high-dose chemotherapy with bone marrow or autologous hematopoietic stem-cell transplantation in the 1980s and 1990s led to the initiation of randomized trials to evaluate its effect in the treatment of metastatic breast cancer. Methods We identified six randomized trials in metastatic breast cancer that evaluated high doses of chemotherapy with transplant support versus a control regimen without stem-cell support. We assembled a single database containing individual patient information from these trials. The primary analysis of overall survival was a log-rank test comparing high dose versus control. We also used Cox proportional hazards regression, adjusting for known covariates. We addressed potential treatment differences within subsets of patients. Results The effect of high-dose chemotherapy on overall survival was not statistically different (median, 2.16 v 2.02 years; P = .08). A statistically significant advantage in progression-free survival (median, 0.91 v 0.69 years) did not translate into survival benefit. Subset analyses found little evidence that there are groups of patients who might benefit from high-dose chemotherapy with hematopoietic support. Conclusion Overall survival of patients with metastatic breast cancer in the six randomized trials was not significantly improved by high-dose chemotherapy; any benefit from high doses was small. No identifiable subset of patients seems to benefit from high-dose chemotherapy. PMID:21768454

Effect of high-dose vs standard-dose multivitamin supplementation at the initiation of HAART on HIV disease progression and mortality in Tanzania: a randomized controlled trial.

PubMed

Isanaka, Sheila; Mugusi, Ferdinand; Hawkins, Claudia; Spiegelman, Donna; Okuma, James; Aboud, Said; Guerino, Chalamilla; Fawzi, Wafaie W

2012-10-17

Large randomized trials have previously shown that high-dose micronutrient supplementation can increase CD4 counts and reduce human immunodeficiency virus (HIV) disease progression and mortality among individuals not receiving highly active antiretroviral therapy (HAART); however, the safety and efficacy of such supplementation has not been established in the context of HAART. To test the hypothesis that high-dose multivitamin supplementation vs standard-dose multivitamin supplementation decreases the risk of HIV disease progression or death and improves immunological, virological, and nutritional parameters in patients with HIV initiating HAART. A randomized, double-blind, controlled trial of high-dose vs standard-dose multivitamin supplementation for 24 months in 3418 patients with HIV initiating HAART between November 2006 and November 2008 in 7 clinics in Dar es Salaam, Tanzania. INTERVENTION The provision of daily oral supplements of vitamin B complex, vitamin C, and vitamin E at high levels or standard levels of the recommended dietary allowance. The composite of HIV disease progression or death from any cause. The study was stopped early in March 2009 because of evidence of increased levels of alanine transaminase (ALT) in patients receiving the high-dose multivitamin supplement. At the time of stopping, 3418 patients were enrolled (median follow-up, 15 months), and there were 2374 HIV disease progression events and 453 observed deaths (2460 total combined events). Compared with standard-dose multivitamin supplementation, high-dose supplementation did not reduce the risk of HIV disease progression or death. The absolute risk of HIV progression or death was 72% in the high-dose group vs 72% in the standard-dose group (risk ratio [RR], 1.00; 95% CI, 0.96-1.04). High-dose supplementation had no effect on CD4 count, plasma viral load, body mass index, or hemoglobin level concentration, but increased the risk of ALT elevations (1239 events per 1215 person-years vs 879 events per 1236 person-years; RR, 1.44; 95% CI, 1.11-1.87) vs standard-dose supplementation. CONCLUSION In adults receiving HAART, use of high-dose multivitamin supplements compared with standard-dose multivitamin supplements did not result in a decrease in HIV disease progression or death but may have resulted in an increase in ALT levels. Clinicaltrials.gov Identifier: NCT00383669.

Older adults and high-risk medication administration in the emergency department

PubMed Central

Kim, Mitchell; Mitchell, Steven H; Gatewood, Medley; Bennett, Katherine A; Sutton, Paul R; Crawford, Carol A; Bentov, Itay; Damodarasamy, Mamatha; Kaplan, Stephen J; Reed, May J

2017-01-01

Background Older adults are susceptible to adverse effects from opioids, nonsteroidal anti-inflammatory drugs (NSAIDs), and benzodiazepines (BZDs). We investigated factors associated with the administration of elevated doses of these medications of interest to older adults (≥65 years old) in the emergency department (ED). Patients and methods ED records were queried for the administration of medications of interest to older adults at two academic medical center EDs over a 6-month period. Frequency of recommended versus elevated (“High doses” were defined as doses that ranged between 1.5 and 3 times higher than the recommended starting doses; “very high doses” were defined as higher than high doses) starting doses of medications, as determined by geriatric pharmacy/medicine guidelines and expert consensus, was compared by age groups (65–69, 70–74, 75–79, 80–84, and ≥85 years), gender, and hospital. Results There were 17896 visits representing 11374 unique patients >65 years of age (55.3% men, 44.7% women). A total of 3394 doses of medications of interest including 1678 high doses and 684 very high doses were administered to 1364 different patients. Administration of elevated doses of medications was more common than that of recommended doses. Focusing on opioids and BZDs, the 65–69-year age group was much more likely to receive very high doses (1481 and 412 doses, respectively) than the ≥85-year age groups (relative risk [RR] 5.52, 95% CI 2.56–11.90), mainly reflecting elevated opioid dosing (RR 8.28, 95% CI 3.69–18.57). Men were more likely than women to receive very high doses (RR 1.47, 95% CI 1.26–1.72), primarily due to BZDs (RR 2.12, 95% CI 2.07–2.16). Conclusion Administration of elevated doses of opioids and BZDs in the older population occurs frequently in the ED, especially to the 65–69-year age group and men. Further attention to potentially unsafe dosing of high-risk medications to older adults in the ED is warranted. PMID:29184448

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

PubMed

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

2017-09-01

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

Predictors of Local Control After Single-Dose Stereotactic Image-Guided Intensity-Modulated Radiotherapy for Extracranial Metastases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Greco, Carlo; Zelefsky, Michael J., E-mail: zelefskm@mskcc.or; Lovelock, Michael

2011-03-15

Purpose: To report tumor local control after treatment with single-dose image-guided intensity-modulated radiotherapy (SD-IGRT) to extracranial metastatic sites. Methods and Materials: A total of 126 metastases in 103 patients were treated with SD-IGRT to prescription doses of 18-24 Gy (median, 24 Gy) between 2004 and 2007. Results: The overall actuarial local relapse-free survival (LRFS) rate was 64% at a median follow-up of 18 months (range, 2-45 months). The median time to failure was 9.6 months (range, 1-23 months). On univariate analysis, LRFS was significantly correlated with prescription dose (p = 0.029). Stratification by dose into high (23 to 24 Gy),more » intermediate (21 to 22 Gy), and low (18 to 20 Gy) dose levels revealed highly significant differences in LRFS between high (82%) and low doses (25%) (p < 0.0001). Overall, histology had no significant effect on LRFS (p = 0.16). Renal cell histology displayed a profound dose-response effect, with 80% LRFS at the high dose level (23 to 24 Gy) vs. 37% with low doses ({<=}22 Gy) (p = 0.04). However, for patients who received the high dose level, histology was not a statistically significant predictor of LRFS (p = 0.90). Target organ (bone vs. lymph node vs. soft tissues) (p = 0.5) and planning target volume size (p = 0.55) were not found to be associated with long-term LRFS probability. Multivariate Cox regression analysis confirmed prescription dose to be a significant predictor of LRFS (p = 0.003). Conclusion: High-dose SD-IGRT is a noninvasive procedure resulting in high probability of local tumor control. Single-dose IGRT may be effectively used to locally control metastatic deposits regardless of histology and target organ, provided sufficiently high doses (> 22 Gy) of radiation are delivered.« less

Moderate- vs high-dose methadone in the treatment of opioid dependence: a randomized trial.

PubMed

Strain, E C; Bigelow, G E; Liebson, I A; Stitzer, M L

1999-03-17

Methadone hydrochloride treatment is the most common pharmacological intervention for opioid dependence, and recent interest has focused on expanding methadone treatment availability beyond traditional specially licensed clinics. However, despite recommendations regarding effective dosing of methadone, controlled clinical trials of higher-dose methadone have not been conducted. To compare the relative clinical efficacy of moderate- vs high-dose methadone in the treatment of opioid dependence. A 40-week randomized, double-blind clinical trial starting in June 1992 and ending in October 1995. Outpatient substance abuse treatment research clinic at the Johns Hopkins University Bayview Campus, Baltimore, Md. One hundred ninety-two eligible clinic patients. Daily oral methadone hydrochloride in the dose range of 40 to 50 mg (n = 97) or 80 to 100 mg (n = 95), with concurrent substance abuse counseling. Opioid-positive urinalysis results and retention in treatment. By intent-to-treat analysis through week 30 patients in the high-dose group had significantly lower rates of opioid-positive urine samples compared with patients in the moderate-dose group (53.0% [95% confidence interval [CI], 46.9%-59.2%] vs 61.9% [95% CI, 55.9%-68.0%]; P = .047. These differences persisted during withdrawal from methadone. Through day 210 no significant difference was evident between dose groups in treatment retention (high-dose group mean retention, 159 days; moderate-dose group mean retention, 157 days). Nineteen (33%) of 57 patients in the high-dose group and 11 (20%) of 54 patients in the moderate-dose group completed detoxification. Both moderate- and high-dose methadone treatment resulted in decreased illicit opioid use during methadone maintenance and detoxification. The high-dose group had significantly greater decreases in illicit opioid use.

Comparative transcriptome analysis of rice seedlings induced by different doses of heavy ion radiation

NASA Astrophysics Data System (ADS)

Zhao, Qian; Sun, Yeqing; Wang, Wei

2016-07-01

Highly ionizing radiation (HZE) in space is considered as a main factor causing biological effects on plant seeds. To investigate the different effects on genome-wide gene expression of low-dose and high-dose ion radiation, we carried out ground-base carbon particle HZE experiments with different cumulative doses (0Gy, 0.2Gy, 2Gy) to rice seeds and then performed comparative transcriptome analysis of the rice seedlings. We identified a total of 2551 and 1464 differentially expressed genes (DEGs) in low-dose and high-dose radiation groups, respectively. Gene ontology analyses indicated that low-dose and high-dose ion radiation both led to multiple physiological and biochemical activities changes in rice. By Gene Ontology analyses, the results showed that only one process-oxidation reduction process was enriched in the biological process category after high-dose ion radiation, while more processes such as response to biotic stimulus, heme binding, tetrapyrrole binding, oxidoreductase activity, catalytic activity and oxidoreductase activity were significantly enriched after low-dose ion radiation. The results indicated that the rice plants only focused on the process of oxidation reduction to response to high-dose ion radiation, whereas it was a coordination of multiple biological processes to response to low-dose ion radiation. To elucidate the transcriptional regulation of radiation stress-responsive genes, we identified several DEGs-encoding TFs. AP2/EREBP, bHLH, C2H2, MYB and WRKY TF families were altered significantly in response to ion radiation. Mapman analysis speculated that the biological effects on rice seedlings caused by the radiation stress might share similar mechanisms with the biotic stress. Our findings highlight important alterations in the expression of radiation response genes, metabolic pathways, and TF-encoding genes in rice seedlings exposed to low-dose and high-dose ion radiation.

High- to low-dose extrapolation: critical determinants involved in the dose response of carcinogenic substances.

PubMed

Swenberg, J A; Richardson, F C; Boucheron, J A; Deal, F H; Belinsky, S A; Charbonneau, M; Short, B G

1987-12-01

Recent investigations on mechanism of carcinogenesis have demonstrated important quantitative relationships between the induction of neoplasia, the molecular dose of promutagenic DNA adducts and their efficiency for causing base-pair mismatch, and the extent of cell proliferation in target organ. These factors are involved in the multistage process of carcinogenesis, including initiation, promotion, and progression. The molecular dose of DNA adducts can exhibit supralinear, linear, or sublinear relationships to external dose due to differences in absorption, biotransformation, and DNA repair at high versus low doses. In contrast, increased cell proliferation is a common phenomena that is associated with exposures to relatively high doses of toxic chemicals. As such, it enhances the carcinogenic response at high doses, but has little effect at low doses. Since data on cell proliferation can be obtained for any exposure scenario and molecular dosimetry studies are beginning to emerge on selected chemical carcinogens, methods are needed so that these critical factors can be utilized in extrapolation from high to low doses and across species. The use of such information may provide a scientific basis for quantitative risk assessment.

High- to low-dose extrapolation: critical determinants involved in the dose response of carcinogenic substances.

PubMed Central

Swenberg, J A; Richardson, F C; Boucheron, J A; Deal, F H; Belinsky, S A; Charbonneau, M; Short, B G

1987-01-01

Recent investigations on mechanism of carcinogenesis have demonstrated important quantitative relationships between the induction of neoplasia, the molecular dose of promutagenic DNA adducts and their efficiency for causing base-pair mismatch, and the extent of cell proliferation in target organ. These factors are involved in the multistage process of carcinogenesis, including initiation, promotion, and progression. The molecular dose of DNA adducts can exhibit supralinear, linear, or sublinear relationships to external dose due to differences in absorption, biotransformation, and DNA repair at high versus low doses. In contrast, increased cell proliferation is a common phenomena that is associated with exposures to relatively high doses of toxic chemicals. As such, it enhances the carcinogenic response at high doses, but has little effect at low doses. Since data on cell proliferation can be obtained for any exposure scenario and molecular dosimetry studies are beginning to emerge on selected chemical carcinogens, methods are needed so that these critical factors can be utilized in extrapolation from high to low doses and across species. The use of such information may provide a scientific basis for quantitative risk assessment. PMID:3447904

Comparative trial of low- and high-dose zonisamide as monotherapy for childhood epilepsy.

PubMed

Eun, So-Hee; Kim, Heung Dong; Eun, Baik-Lin; Lee, In Kyu; Chung, Hee Jung; Kim, Joon Sik; Kang, Hoon-Chul; Lee, Young-Mock; Suh, Eun Sook; Kim, Dong Wook; Eom, Soyong; Lee, Joon Soo; Moon, Han Ku

2011-09-01

To evaluate the effectiveness of zonisamide (ZNS) as monotherapy in children with newly diagnosed epilepsy. This randomized, multicenter trial included a 2-4-week titration and a 24-week maintenance phase after randomization to low-(3-4 mg/kg/day) or high-(6-8 mg/kg/day) dose groups as target maintenance dosages. The primary outcome measure was the seizure-free rate over 6 months, while a secondary measure was the change in cognition and behavior from screening to the end of the maintenance phase. Out of 125 patients enrolled, 90 (49 low-dose and 41 high-dose) completed the study. Forty-one patients (63.1%) in the low-dose group and 34(57.6%) in the high-dose group achieved 6 months' freedom from seizures (p=0.66). After treatment, the picture arrangement subtest improved in the low-dose group (p=0.047) while the vocabulary subtest worsened in the high-dose group (p=0.020). Comparing between the two groups, the vocabulary subtest in the high-dose group was significantly worse than that in the low-dose group (p=0.002). Social competence, somatic complaints, depression/anxiety and delinquent and aggressive behavior in the low-dose group were significantly improved (p<0.05). Moreover, total social competence, somatic complaints, delinquent behavior, externalizing, and total behavior problems were significantly more improved in the low-dose group than the high-dose group (p<0.05). ZNS is an effective monotherapy for newly diagnosed childhood epilepsy. Lower doses of ZNS have a similar efficacy and more beneficial neurocognitive effects compared to higher doses. When prescribing higher doses of ZNS, one must be aware of the possible manifestation of problems associated with language development, such as those affecting vocabulary acquisition. Copyright © 2011 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Cost-effectiveness of high-dose versus standard-dose inactivated influenza vaccine in adults aged 65 years and older: an economic evaluation of data from a randomised controlled trial.

PubMed

Chit, Ayman; Becker, Debbie L; DiazGranados, Carlos A; Maschio, Michael; Yau, Eddy; Drummond, Michael

2015-12-01

Adults aged 65 years and older account for most seasonal influenza-related hospital admissions and deaths. Findings from the randomised controlled FIM12 study showed that high-dose inactivated influenza vaccine is more effective than standard-dose vaccine for prevention of laboratory-confirmed influenza in this age group. We aimed to assess the economic impact of high-dose versus standard-dose influenza vaccine in participants in the FIM12 study population. The FIM12 study was a head-to-head randomised controlled trial in which 31,989 participants aged 65 years and older were randomly assigned (1:1) to receive either high-dose or standard-dose trivalent inactivated influenza vaccine over two influenza seasons (2011-12 and 2012-13). Data for health-care resource consumption obtained in the FIM12 study were summarised across vaccine groups. Unit costs obtained from standard US cost sources were applied to each resource item, including to the vaccines (high dose US$31·82, standard dose $12·04). Clinical illness data were mapped to existing quality-of-life data. The time horizon was one influenza season; however, quality-adjusted life-years (QALYs) lost due to death during the study were calculated over a lifetime. We calculated incremental cost-effectiveness ratios (ICERs) for high-dose versus standard-dose vaccine and used QALYs as an outcome in the cost-utility analysis. We undertook a probabilistic sensitivity analysis using bootstrapping to explore the effect of statistical uncertainty on the study results. Mean per-participant medical costs were lower in the high-dose vaccine group ($1376·72 [SD 6857·59]) than in the standard-dose group ($1492·64 [7447·14]; difference -$115·92 [95% CI -264·18 to 35·48]). Mean societal costs were likewise lower in the high-dose versus the standard-dose group ($1506·48 [SD 7305·19] vs $1634·50 [7952·99]; difference -$128·02 [95% CI -286·89 to 33·30]). Hospital admissions contributed 95% of the total health-care-payer cost and 87% of the total societal costs. The mean per-participant number of hospital admissions was 0·0937 (SD 0·3644) in the high-dose group and 0·1017 (0·3708) in the standard-dose group (difference -0·0080, 95% CI -0·0160 to -0·0003). The high-dose vaccine provided a gain in QALYs (mean 8·1502 QALYs gained per participant [SD 0·5693]) compared with the standard-dose vaccine (8·1499 QALYs [0·5697]) and, due to cost savings, dominated standard-dose vaccine in the cost-utility analysis. The probabilistic sensitivity analysis showed that the high-dose vaccine is 93% likely to be cost saving. High-dose trivalent inactivated influenza vaccine is a less costly and more effective alternative to the standard-dose vaccine, driven by a reduction in the number of hospital admissions. These findings are relevant to US health-care beneficiaries, providers, payers, and recommending bodies, especially those seeking to improve outcomes while containing costs. Sanofi Pasteur. Copyright © 2015 Elsevier Ltd. All rights reserved.

Efficacy and safety of high-dose baclofen for the treatment of alcohol dependence: A multicentre, randomised, double-blind controlled trial.

PubMed

Beraha, Esther M; Salemink, Elske; Goudriaan, Anna E; Bakker, Abraham; de Jong, David; Smits, Natasha; Zwart, Jan Willem; Geest, Dick van; Bodewits, Pieter; Schiphof, Tom; Defourny, Harma; van Tricht, Mirjam; van den Brink, Wim; Wiers, Reinout W

2016-12-01

Previous randomised placebo-controlled trials with low-to-medium doses of baclofen (30-60mg) showed inconsistent results, but case studies suggested a dose-response effect and positive outcomes in patients on high doses of baclofen (up to 270mg). Its prescription was temporary permitted for the treatment of alcohol dependence (AD) in France, and baclofen is now widely prescribed. Recently, a small RCT found a strong effect of a mean dose of 180mg baclofen. In the present study the efficacy and safety of high doses of baclofen was examined in a multicentre, double-blind, placebo-controlled trial. 151 patients were randomly assigned to either six weeks titration and ten weeks high-dose baclofen (N=58; up to 150mg), low-dose baclofen (N=31; 30mg), or placebo (N=62). The primary outcome measure was time to first relapse. Nine of the 58 patients (15.5%) in the high-dose group reached 150mg and the mean baclofen dose in this group was 93.6mg (SD=40.3). No differences between the survival distributions for the three groups were found in the time to first relapse during the ten-weeks high-dose phase (χ 2 =0.41; p=0.813) or the 16-weeks complete medication period (χ 2 =0.04; p=0.982). There were frequent dose-related adverse events in terms of fatigue, sleepiness, and dry mouth. One medication related serious adverse event occurred in the high-dose baclofen group. Neither low nor high doses of baclofen were effective in the treatment of AD. Adverse events were frequent, although generally mild and transient. Therefore, large-scale prescription of baclofen for the treatment of AD seems premature and should be reconsidered. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

Different doses of prophylactic platelet transfusion for preventing bleeding in people with haematological disorders after myelosuppressive chemotherapy or stem cell transplantation

PubMed Central

Estcourt, Lise J; Stanworth, Simon; Doree, Carolyn; Trivella, Marialena; Hopewell, Sally; Blanco, Patricia; Murphy, Michael F

2015-01-01

Background Platelet transfusions are used in modern clinical practice to prevent and treat bleeding in people who are thrombocytopenic due to bone marrow failure. Although considerable advances have been made in platelet transfusion therapy in the last 40 years, some areas continue to provoke debate, especially concerning the use of prophylactic platelet transfusions for the prevention of thrombocytopenic bleeding. This is an update of a Cochrane review first published in 2004, and updated in 2012 that addressed four separate questions: prophylactic versus therapeutic-only platelet transfusion policy; prophylactic platelet transfusion threshold; prophylactic platelet transfusion dose; and platelet transfusions compared to alternative treatments. This review has now been split into four smaller reviews; this review compares different platelet transfusion doses. Objectives To determine whether different doses of prophylactic platelet transfusions (platelet transfusions given to prevent bleeding) affect their efficacy and safety in preventing bleeding in people with haematological disorders undergoing myelosuppressive chemotherapy with or without haematopoietic stem cell transplantation (HSCT). Search methods We searched for randomised controlled trials in the Cochrane Central Register of Controlled Trials (CENTRAL) (Cochrane Library 2015, Issue 6), MEDLINE (from 1946), Embase (from 1974), CINAHL (from 1937), the Transfusion Evidence Library (from 1950), and ongoing trial databases to 23 July 2015. Selection criteria Randomised controlled trials involving transfusions of platelet concentrates, prepared either from individual units of whole blood or by apheresis, and given to prevent bleeding in people with malignant haematological disorders or undergoing HSCT that compared different platelet component doses (low dose 1.1 × 1011/m2 ± 25%, standard dose 2.2 × 1011/m2 ± 25%, high dose 4.4 × 1011/m2 ± 25%). Data collection and analysis We used the standard methodological procedures expected by The Cochrane Collaboration. Main results We included seven trials (1814 participants) in this review; six were conducted during one course of treatment (chemotherapy or HSCT). Overall the methodological quality of studies was low to moderate across different outcomes according to GRADE methodology. None of the included studies were at low risk of bias in every domain, and all the included studies had some threats to validity. Five studies reported the number of participants with at least one clinically significant bleeding episode within 30 days from the start of the study. There was no difference in the number of participants with a clinically significant bleeding episode between the low-dose and standard-dose groups (four studies; 1170 participants; risk ratio (RR) 1.04, 95% confidence interval (CI) 0.95 to 1.13; moderate-quality evidence); low-dose and high-dose groups (one study; 849 participants; RR 1.02, 95% CI 0.93 to 1.11; moderate-quality evidence); or high-dose and standard-dose groups (two studies; 951 participants; RR 1.02, 95% CI 0.93 to 1.11; moderate-quality evidence). Three studies reported the number of days with a clinically significant bleeding event per participant. There was no difference in the number of days of bleeding per participant between the low-dose and standard-dose groups (two studies; 230 participants; mean difference −0.17, 95% CI −0.51 to 0.17; low quality evidence). One study (855 participants) showed no difference in the number of days of bleeding per participant between high-dose and standard-dose groups, or between low-dose and high-dose groups (849 participants). Three studies reported the number of participants with severe or life-threatening bleeding. There was no difference in the number of participants with severe or life-threatening bleeding between a low-dose and a standard-dose platelet transfusion policy (three studies; 1059 participants; RR 1.33, 95% CI 0.91 to 1.92; low-quality evidence); low-dose and high-dose groups (one study; 849 participants; RR 1.20, 95% CI 0.82 to 1.77; low-quality evidence); or high-dose and standard-dose groups (one study; 855 participants; RR 1.11, 95% CI 0.73 to 1.68; low-quality evidence). Two studies reported the time to first bleeding episodes; we were unable to perform a meta-analysis. Both studies (959 participants) individually found that the time to first bleeding episode was either the same, or longer, in the low-dose group compared to the standard-dose group. One study (855 participants) found that the time to the first bleeding episode was the same in the high-dose group compared to the standard-dose group. Three studies reported all-cause mortality within 30 days from the start of the study. There was no difference in all-cause mortality between treatment arms (low-dose versus standard-dose: three studies; 1070 participants; RR 2.04, 95% CI 0.70 to 5.93; low-quality evidence; low-dose versus high-dose: one study; 849 participants; RR 1.33, 95% CI 0.50 to 3.54; low-quality evidence; and high-dose versus standard-dose: one study; 855 participants; RR 1.71, 95% CI 0.51 to 5.81; low-quality evidence). Six studies reported the number of platelet transfusions; we were unable to perform a meta-analysis. Two studies (959 participants) out of three (1070 participants) found that a low-dose transfusion strategy led to more transfusion episodes than a standard-dose. One study (849 participants) found that a low-dose transfusion strategy led to more transfusion episodes than a high-dose strategy. One study (855 participants) out of three (1007 participants) found no difference in the number of platelet transfusions between the high-dose and standard-dose groups. One study reported on transfusion reactions. This study’s authors suggested that a high-dose platelet transfusion strategy may lead to a higher rate of transfusion-related adverse events. None of the studies reported quality-of-life. Authors’ conclusions In haematology patients who are thrombocytopenic due to myelosuppressive chemotherapy or HSCT, we found no evidence to suggest that a low-dose platelet transfusion policy is associated with an increased bleeding risk compared to a standard-dose or high-dose policy, or that a high-dose platelet transfusion policy is associated with a decreased risk of bleeding when compared to a standard-dose policy. A low-dose platelet transfusion strategy leads to an increased number of transfusion episodes compared to a standard-dose strategy. A high-dose platelet transfusion strategy does not decrease the number of transfusion episodes per participant compared to a standard-dose regimen, and it may increase the number of transfusion-related adverse events. Findings from this review would suggest a change from current practice, with low-dose platelet transfusions used for people receiving in-patient treatment for their haematological disorder and high-dose platelet transfusion strategies not being used routinely. PMID:26505729

Tumor Control Outcomes Following Hypofractionated and Single-Dose Stereotactic Image-Guided Intensity-Modulated Radiotherapy for Extracranial Metastases from Renal Cell Carcinoma

PubMed Central

Zelefsky, Michael J; Greco, Carlo; Motzer, Robert; Magsanoc, Juan Martin; Pei, Xin; Lovelock, Michael; Mechalakos, Jim; Zatcky, Joan; Fuks, Zvi; Yamada, Yoshiya

2014-01-01

Purpose To report tumor local progression-free outcomes following treatment with single-dose image-guided intensity-modulated radiotherapy (SD-IGRT) and hypofractionated regimens for extracranial metastases from renal cell primary tumors. Methods and Materials Between 2004 and 2010, a total of 105 lesions from renal cell carcinomas were treated with either SD-IGRT to prescription doses of 18–24 Gy (median, 24 Gy) or hypofractionation (3 or 5 fractions) with prescription doses ranging between 20 and 30 Gy. The median follow-up was 12 months (range, 1–48 months). Results The overall 3-year actuarial local progression-free survival (LPFS) for all lesions was 44%. The 3-year LPFS for those who received high single-dose (24 Gy; n = 45), low single-dose (< 24 Gy; n = 14), and hypofractionation regimens (n = 46) were 88%, 21%, and 17%, respectively (high single dose versus low single dose, p = 0.001; high single dose versus hypofractionation, p < 0.001). Multivariate analysis revealed the following variables as significant predictors of improved LPFS: dose of 24 Gy compared with lower dose (p = 0.009), and single dose versus hypofractionation (p = 0.008). Conclusion High-dose SD-IGRT is a non-invasive procedure resulting in high probability of local tumor control for metastatic renal cell cancers, generally considered radioresistant according to classical radiobiological ranking. PMID:21596489

ELDRS Characterization for a Very High Dose Mission

NASA Technical Reports Server (NTRS)

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

2010-01-01

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

SU-E-T-315: The Change of Optically Stimulated Luminescent Dosimeters (OSLDs) Sensitivity by Accumulated Dose and High Dose

DOE Office of Scientific and Technical Information (OSTI.GOV)

Han, S; Jung, H; Kim, M

2014-06-01

Purpose: The objective of this study is to evaluate radiation sensitivity of optical stimulated luminance dosimeters (OSLDs) by accumulated dose and high dose. Methods: This study was carried out in Co-60 unit (Theratron 780, AECL, and Canada) and used InLight MicroStar reader (Landauer, Inc., Glenwood, IL) for reading. We annealed for 30 min using optical annealing system which contained fluorescent lamps (Osram lumilux, 24 W, 280 ∼780 nm). To evaluate change of OSLDs sensitivity by repeated irradiation, the dosimeters were repeatedly irradiated with 1 Gy. And whenever a repeated irradiation, we evaluated OSLDs sensitivity. To evaluate OSLDs sensitivity after accumulatedmore » dose with 5 Gy, We irradiated dose accumulatively (from 1 Gy to 5 Gy) without annealing. And OSLDs was also irradiated with 15, 20, 30 Gy to certify change of OSLDs sensitivity after high dose irradiation. After annealing them, they were irradiated with 1Gy, repeatedly. Results: The OSLDs sensitivity increased up to 3% during irradiating seven times and decreased continuously above 8 times. That dropped by about 0.35 Gy per an irradiation. Finally, after 30 times irradiation, OSLDs sensitivity decreased by about 7%. For accumulated dose from 1 Gy to 5 Gy, OSLDs sensitivity about 1 Gy increased until 4.4% after second times accumulated dose compared with before that. OSLDs sensitivity about 1 Gy decreased by 1.6% in five times irradiation. When OSLDs were irradiated ten times with 1Gy after irradiating high dose (10, 15, 20 Gy), OSLDs sensitivity decreased until 6%, 9%, 12% compared with it before high dose irradiation, respectively. Conclusion: This study certified OSLDs sensitivity by accumulated dose and high dose. When irradiated with 1Gy, repeatedly, OSLDs sensitivity decreased linearly and the reduction rate of OSLDs sensitivity after high dose irradiation had dependence on irradiated dose.« less

Evaluation of Low- Versus High-dose Valganciclovir for Prevention of Cytomegalovirus Disease in High-risk Renal Transplant Recipients.

PubMed

Gabardi, Steven; Asipenko, Natalya; Fleming, James; Lor, Kevin; McDevitt-Potter, Lisa; Mohammed, Anisa; Rogers, Christin; Tichy, Eric M; Weng, Renee; Lee, Ruth-Ann

2015-07-01

Despite proven efficacy of prolonged cytomegalovirus (CMV) prophylaxis using valganciclovir 900 mg/day, some centers use 450 mg/day due to reported success and cost savings. This multicenter, retrospective study compared the efficacy and safety of 6 months of low-dose versus high-dose valganciclovir prophylaxis in high-risk, donor-positive/recipient-negative, renal transplant recipients (RTR). Two hundred thirty-seven high-risk RTR (low-dose group = valganciclovir 450 mg/day [n = 130]; high-dose group = valganciclovir 900 mg/day [n = s7]) were evaluated for 1-year CMV disease prevalence. Breakthrough CMV, resistant CMV, biopsy-proven acute rejection (BPAR), graft loss, opportunistic infections (OI), new-onset diabetes after transplantation (NODAT), premature valganciclovir discontinuation, renal function and myelosuppression were also assessed. Patient demographics and transplant characteristics were comparable. Induction and maintenance immunosuppression were similar, except for more early steroid withdrawal in the high-dose group. Similar proportions of patients developed CMV disease (14.6% vs 24.3%; P = 0.068); however, controlling CMV risk factor differences through multivariate logistic regression revealed significantly lower CMV disease in the low-dose group (P = 0.02; odds ratio, 0.432, 95% confidence interval, 0.211-0.887). Breakthrough and resistant CMV occurred at similar frequencies. There was no difference in renal function or rates of biopsy-proven acute rejection, graft loss, opportunistic infections, or new-onset diabetes after transplantation. The high-dose group had significantly lower mean white blood cell counts at months 5 and 6; however, premature valganciclovir discontinuation rates were similar. Low-dose and high-dose valganciclovir regimens provide similar efficacy in preventing CMV disease in high-risk RTR, with a reduced incidence of leukopenia associated with the low-dose regimen and no difference in resistant CMV. Low-dose valganciclovir may provide a significant cost avoidance benefit.

Severe neuropathy after high dose carboplatin in three patients receiving multidrug chemotherapy

PubMed Central

Heinzlef, O.; Lotz, J.; Roullet, E.

1998-01-01

Three patients are described who developed a severe neuropathy after chemotherapy with high dose cis-diamine-(1,1-cyclobutane dicarboxylato) platinum (carboplatin). This toxic side effect, which is unusual at conventional doses, might become more frequent as increasing doses are administered to overcome drug resistance in cancer treatment, and might limit its use at very high doses before haematopoietic stem cell transplantation. 

 PMID:9598687

Effect of High-Dose vs Standard-Dose Multivitamin Supplementation at the Initiation of HAART on HIV Disease Progression and Mortality in Tanzania

PubMed Central

Isanaka, Sheila; Mugusi, Ferdinand; Hawkins, Claudia; Spiegelman, Donna; Okuma, James; Aboud, Said; Guerino, Chalamilla; Fawzi, Wafaie W.

2013-01-01

Context Large randomized trials have previously shown that high-dose micronutrient supplementation can increase CD4 counts and reduce human immunodeficiency virus (HIV) disease progression and mortality among individuals not receiving highly active antiretroviral therapy (HAART); however, the safety and efficacy of such supplementation has not been established in the context of HAART. Objective To test the hypothesis that high-dose multivitamin supplementation vs standard-dose multivitamin supplementation decreases the risk of HIV disease progression or death and improves immunological, virological, and nutritional parameters in patients with HIV initiating HAART. Design, Setting, and Participants A randomized, double-blind, controlled trial of high-dose vs standard-dose multivitamin supplementation for 24 months in 3418 patients with HIV initiating HAART between November 2006 and November 2008 in 7 clinics in Dar es Salaam, Tanzania. Intervention The provision of daily oral supplements of vitamin B complex, vitamin C, and vitamin E at high levels or standard levels of the recommended dietary allowance. Main Outcome Measure The composite of HIV disease progression or death from any cause. Results The study was stopped early in March 2009 because of evidence of increased levels of alanine transaminase (ALT) in patients receiving the high-dose multivitamin supplement. At the time of stopping, 3418 patients were enrolled (median follow-up, 15 months), and there were 2374 HIV disease progression events and 453 observed deaths (2460 total combined events). Compared with standard-dose multivitamin supplementation, high-dose supplementation did not reduce the risk of HIV disease progression or death. The absolute risk of HIV progression or death was 72% in the high-dose group vs 72% in the standard-dose group (risk ratio [RR], 1.00; 95% CI, 0.96–1.04). High-dose supplementation had no effect on CD4 count, plasma viral load, body mass index, or hemoglobin level concentration, but increased the risk of ALT elevations (1239 events per 1215 person-years vs 879 events per 1236 person-years; RR, 1.44; 95% CI, 1.11–1.87) vs standard-dose supplementation. Conclusion In adults receiving HAART, use of high-dose multivitamin supplements compared with standard-dose multivitamin supplements did not result in a decrease in HIV disease progression or death but may have resulted in an increase in ALT levels. Trial Registration clinicaltrials.gov Identifier: NCT00383669 PMID:23073950

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mwidu, U; Devic, S; Shehadeh, M

Purpose: A retrospective comparison of dose distributions achievable by High dose rate brachytherapy (HDRBT), Helical TomoTherapy (TOMO), CyberKnife (CK) and RapidArc (RA) in locally advanced inoperable cervical cancer patients is presented. Methods: Five patients with advanced stage cervical carcinoma were selected for this study after a full course of external beam radiotherapy (EBRT), chemotherapy and HDR Brachytherapy. To highlight any significant similarities/differences in dose distributions, high-risk clinical target volume (HRCTV) coverage, organs at risk (OAR) sparing, and machine specific delivery limitations, we used D90 (dose received by 90% of the volume) as the parameter for HRCTV coverage as recommended bymore » the GEC-ESTRO Working Group. We also compared both integral and differential dose volume histograms (DVH) between different dose distributions treatment modalities for HRCTV and OAR. Results: TOMO and RA provided the most conformal dose distributions to HRCTV. Median doses (in Gy) to organs at risk were; for rectal wall: 1.7±0.6, 2.5±0.6,1.2±0.3, and 1.5±0.6, and for bladder wall: 1.6±0.1, 2.4±0.4, 0.8±0.6, and 1.5±0.5, for HDRBT, TOMO, CK, and RA, respectively. Conclusion: Contemporary EBRT modalities might be able to replace brachytherapy treatments for cervix cancer. While brachytherapy dose distributions feature high dose gradients, EBRT modalities provide highly conformal dose distributions to the target. However, it is still not clear whether a highly conformal dose or high gradient dose is more clinically relevant for the HRCTV in cervix cancer patients.« less

What dose of tranexamic acid is most effective and safe for adult patients undergoing cardiac surgery?

PubMed

Hodgson, Sam; Larvin, Joseph T; Dearman, Charles

2015-09-01

A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was: what dose of tranexamic acid is most effective and safe for adult patients undergoing cardiac surgery? Altogether 586 papers were found using the reported search, of which 12 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. Current evidence shows clinical benefit of using high-dose tranexamic acid (>80 mg/kg total dose) as opposed to low-dose tranexamic acid (<50 mg/kg total dose) in cardiac surgery with cardiopulmonary bypass. Evidence from a large randomized controlled trial shows that patients receiving high-dose tranexamic acid lose less blood postoperatively than patients receiving low-dose tranexamic acid (590 vs 820 ml, P = 0.01). Patients receiving high-dose tranexamic acid also require fewer units of blood product transfusion (2.5 units vs 4.1 units; P = 0.02) and are less likely to undergo repeat surgery to achieve haemostasis. This effect is larger in those who are at high risk of bleeding. Several prospective studies comparing doses found no difference in clinical outcomes between high- and low-dose regimens, but excluded patients at high risk of bleeding. However, data from numerous observational studies demonstrate that tranexamic acid use is associated with an increased risk of postoperative seizure; one analysis showed tranexamic acid use to be a very strong independent predictor (odds ratio = 14.3, P < 0.001). There is also evidence that this risk of seizure is dose-dependent, with the greatest risk at higher doses of tranexamic acid. We conclude that, in general, patients with a high risk of bleeding should receive high-dose tranexamic acid, while those at low risk of bleeding should receive low-dose tranexamic acid with consideration given to potential dose-related seizure risk. We recommend the regimens of high-dose (30 mg kg(-1) bolus + 16 mg kg(-1) h(-1) + 2 mg kg(-1) priming) and low-dose (10 mg kg(-1) bolus + 1 mg kg(-1) h(-1) + 1 mg kg(-1) priming) tranexamic acid, as these are well established in terms of safety profile and have the strongest evidence for efficacy. © The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Exercise-Induced Dose-Response Alterations in Adiponectin and Leptin Levels Are Dependent on Body Fat Changes in Women at Risk for Breast Cancer.

PubMed

Sturgeon, Kathleen; Digiovanni, Laura; Good, Jerene; Salvatore, Domenick; Fenderson, Desiré; Domchek, Susan; Stopfer, Jill; Galantino, Mary Lou; Bryan, Cathy; Hwang, Wei-Ting; Schmitz, Kathryn

2016-08-01

Dysregulation of adipokines, such as adiponectin and leptin, is associated with a variety of chronic diseases, including cancer. Physical activity protects against breast cancer and one of the mechanisms which may underlie this association is exercise-induced changes in adipokine levels. The WISER Sister Trial was a three-armed randomized controlled trial in premenopausal women (n = 137) with an elevated risk for breast cancer. A 5-menstrual-cycle-long dosed aerobic exercise intervention compared low-dose exercise (150 min/wk; n = 44) or high-dose exercise (300 min/wk; n = 48) with a control group asked to maintain usual activity levels (n = 45). Exercise intensity progressed to and was maintained at 70% to 80% of age predicted heart rate max. Body composition and adipokine levels were measured at baseline and follow-up. We observed significant linear trends for increased fitness capacity (Δ%: -2.0% control, 10.1% low dose, 13.1% high dose), decreased fat tissue-to-total tissue mass (Δ%: 0.7% control, -2.9% low dose, -3.7% high dose), increased body fat adjusted adiponectin (Δ%: -0.6% control, 0.6% low dose, 0.9% high dose), and decreased body fat adjusted leptin (Δ%: 0.7% control, -8.2% low dose, -10.2% high dose). In this randomized clinical trial of premenopausal women at risk for breast cancer, we demonstrate a dose-response effect of exercise on adiponectin and leptin and that dose response is dependent on changes in body fat. Improved adipokine levels, achieved by aerobic exercise training-induced decreases in body fat, may decrease breast cancer risk for high-risk premenopausal women. Cancer Epidemiol Biomarkers Prev; 25(8); 1195-200. ©2016 AACR. ©2016 American Association for Cancer Research.

Comparative dosimetric characterization for different types of detectors in high-energy electron beams

NASA Astrophysics Data System (ADS)

Lee, Chang Yeol; Kim, Woo Chul; Kim, Hun Jeong; Huh, Hyun Do; Park, Seungwoo; Choi, Sang Hyoun; Kim, Kum Bae; Min, Chul Kee; Kim, Seong Hoon; Shin, Dong Oh

2017-02-01

The purpose of this study is to perform a comparison and on analysis of measured dose factor values by using various commercially available high-energy electron beam detectors to measure dose profiles and energy property data. By analyzing the high-energy electron beam data from each detector, we determined the optimal detector for measuring electron beams in clinical applications. The dose linearity, dose-rate dependence, percentage depth dose, and dose profile of each detector were measured to evaluate the dosimetry characteristics of high-energy electron beams. The dose profile and the energy characteristics of high-energy electron beams were found to be different when measured by different detectors. Through comparison with other detectors based on the analyzed data, the microdiamond detector was found to have outstanding dose linearity, a low dose-rate dependency, and a small effective volume. Thus, this detector has outstanding spatial resolution and is the optimal detector for measuring electron beams. Radiation therapy results can be improved and related medical accidents can be prevented by using the procedure developed in this research in clinical practice for all beam detectors when measuring the electron beam dose.

Possible benefit of consolidation therapy with high-dose cytarabine on overall survival of adults with non-promyelocytic acute myeloid leukemia.

PubMed

Azevedo, M C; Velloso, E D R P; Buccheri, V; Chamone, D A F; Dorlhiac-Llacer, P E

2015-02-01

In adults with non-promyelocytic acute myeloid leukemia (AML), high-dose cytarabine consolidation therapy has been shown to influence survival in selected patients, although the appropriate doses and schemes have not been defined. We evaluated survival after calculating the actual dose of cytarabine that patients received for consolidation therapy and divided them into 3 groups according to dose. We conducted a single-center, retrospective study involving 311 non-promyelocytic AML patients with a median age of 36 years (16-79 years) who received curative treatment between 1978 and 2007. The 131 patients who received cytarabine consolidation were assigned to study groups by their cytarabine dose protocol. Group 1 (n=69) received <1.5 g/m2 every 12 h on 3 alternate days for up to 4 cycles. The remaining patients received high-dose cytarabine (≥1.5 g/m2 every 12 h on 3 alternate days for up to 4 cycles). The actual dose received during the entire consolidation period in these patients was calculated, allowing us to divide these patients into 2 additional groups. Group 2 (n=27) received an intermediate-high-dose (<27 g/m2), and group 3 (n=35) received a very-high-dose (≥27 g/m2). Among the 311 patients receiving curative treatment, the 5-year survival rate was 20.2% (63 patients). The cytarabine consolidation dose was an independent determinant of survival in multivariate analysis; age, karyotype, induction protocol, French-American-British classification, and de novo leukemia were not. Comparisons showed that the risk of death was higher in the intermediate-high-dose group 2 (hazard ratio [HR]=4.51; 95% confidence interval [CI]: 1.81-11.21) and the low-dose group 1 (HR=4.43; 95% CI: 1.97-9.96) than in the very-high-dose group 3, with no significant difference between those two groups. Our findings indicated that very-high-dose cytarabine during consolidation in adults with non-promyelocytic AML may improve survival.

Possible benefit of consolidation therapy with high-dose cytarabine on overall survival of adults with non-promyelocytic acute myeloid leukemia

PubMed Central

Azevedo, M.C.; Velloso, E.D.R.P.; Buccheri, V.; Chamone, D.A.F.; Dorlhiac-Llacer, P.E.

2014-01-01

In adults with non-promyelocytic acute myeloid leukemia (AML), high-dose cytarabine consolidation therapy has been shown to influence survival in selected patients, although the appropriate doses and schemes have not been defined. We evaluated survival after calculating the actual dose of cytarabine that patients received for consolidation therapy and divided them into 3 groups according to dose. We conducted a single-center, retrospective study involving 311 non-promyelocytic AML patients with a median age of 36 years (16-79 years) who received curative treatment between 1978 and 2007. The 131 patients who received cytarabine consolidation were assigned to study groups by their cytarabine dose protocol. Group 1 (n=69) received <1.5 g/m2 every 12 h on 3 alternate days for up to 4 cycles. The remaining patients received high-dose cytarabine (≥1.5 g/m2 every 12 h on 3 alternate days for up to 4 cycles). The actual dose received during the entire consolidation period in these patients was calculated, allowing us to divide these patients into 2 additional groups. Group 2 (n=27) received an intermediate-high-dose (<27 g/m2), and group 3 (n=35) received a very-high-dose (≥27 g/m2). Among the 311 patients receiving curative treatment, the 5-year survival rate was 20.2% (63 patients). The cytarabine consolidation dose was an independent determinant of survival in multivariate analysis; age, karyotype, induction protocol, French-American-British classification, and de novo leukemia were not. Comparisons showed that the risk of death was higher in the intermediate-high-dose group 2 (hazard ratio [HR]=4.51; 95% confidence interval [CI]: 1.81-11.21) and the low-dose group 1 (HR=4.43; 95% CI: 1.97-9.96) than in the very-high-dose group 3, with no significant difference between those two groups. Our findings indicated that very-high-dose cytarabine during consolidation in adults with non-promyelocytic AML may improve survival. PMID:25517921

Mutational influences of low-dose and high let ionizing radiation in drosophila melanogaster

NASA Astrophysics Data System (ADS)

Lei, Huang; Fanjun, Kong; Sun, Yeqing

For cosmic environment consists of a varying kinds of radiation particles including high Z and energy ions which was charactered with low-dose and high RBE, it is important to determine the possible biofuctions of high LET radiation on human beings. To analyse the possible effectes of mutational influences of low-dose and high-LET ionizing radiation, wild fruit flies drosophila melanogaster were irradiated by 12C6+ ions in two LET levels (63.3 and 30 keV/µum) with different low doses from 2mGy to 2000mGy (2, 20, 200, 2000mGy) in HIRFL (Heavy ion radiation facility laboratory, lanzhou, China).In the same LET value group, the average polymorphic frequency was elevated along with adding doses of irradation, the frequency in 2000 mGy dose samples was significantly higher than other samples (p<0.01).These results suggest that genomic DNA sequence could be effected by low-dose and high-LET ionizing radiation, the irradiation dose is an important element in genomic mutation frequency origination.

Estimation of the Dose and Dose Rate Effectiveness Factor

NASA Technical Reports Server (NTRS)

Chappell, L.; Cucinotta, F. A.

2013-01-01

Current models to estimate radiation risk use the Life Span Study (LSS) cohort that received high doses and high dose rates of radiation. Transferring risks from these high dose rates to the low doses and dose rates received by astronauts in space is a source of uncertainty in our risk calculations. The solid cancer models recommended by BEIR VII [1], UNSCEAR [2], and Preston et al [3] is fitted adequately by a linear dose response model, which implies that low doses and dose rates would be estimated the same as high doses and dose rates. However animal and cell experiments imply there should be curvature in the dose response curve for tumor induction. Furthermore animal experiments that directly compare acute to chronic exposures show lower increases in tumor induction than acute exposures. A dose and dose rate effectiveness factor (DDREF) has been estimated and applied to transfer risks from the high doses and dose rates of the LSS cohort to low doses and dose rates such as from missions in space. The BEIR VII committee [1] combined DDREF estimates using the LSS cohort and animal experiments using Bayesian methods for their recommendation for a DDREF value of 1.5 with uncertainty. We reexamined the animal data considered by BEIR VII and included more animal data and human chromosome aberration data to improve the estimate for DDREF. Several experiments chosen by BEIR VII were deemed inappropriate for application to human risk models of solid cancer risk. Animal tumor experiments performed by Ullrich et al [4], Alpen et al [5], and Grahn et al [6] were analyzed to estimate the DDREF. Human chromosome aberration experiments performed on a sample of astronauts within NASA were also available to estimate the DDREF. The LSS cohort results reported by BEIR VII were combined with the new radiobiology results using Bayesian methods.

Cyclophosphamide priming reduces intestinal damage in man following high dose melphalan chemotherapy.

PubMed Central

Selby, P. J.; Lopes, N.; Mundy, J.; Crofts, M.; Millar, J. L.; McElwain, T. J.

1987-01-01

A small pre-treatment 'priming' dose of cyclophosphamide will reduce gut damage due to high dose i.v. melphalan in mice and sheep but efforts to demonstrate this effect in man have been hampered by difficulty in the measurement of gut damage. We have evaluated the 51CR EDTA absorption test, a new method for measuring intestinal permeability, as a means of assessing damage due to high dose melphalan. The test was reliable, with a narrow normal range, easy to use and well tolerated. It detected an increase in intestinal permeability after high dose melphalan with a maximum occurring between 9 and 15 days after treatment and subsequently returning to normal. It was shown in 19 patients that a pre-treatment dose of cyclophosphamide was capable of significantly reducing the abnormalities in intestinal permeability which resulted from high dose melphalan. PMID:3111515

Chinese Data of Efficacy of Low- and High-Dose Iodine-131 for the Ablation of Thyroid Remnant.

PubMed

Ma, Chao; Feng, Fang; Wang, Shaoyan; Fu, Hongliang; Wu, Shuqi; Ye, Zhiyi; Chen, Suyun; Wang, Hui

2017-06-01

Chinese data on the efficacy of low- and high-dose radioiodine for thyroid remnant are still absent. The aim of the study was to investigate whether a low dose of radioiodine is as effective as a high dose for remnant ablation in Chinese patients. Patients presenting for radioiodine ablation in the authors' department were included. Inclusion criteria were aged ≥16 years, total or near-total thyroidectomy, tumor-node-metastasis (TNM) stage of pT1-3, any N stage, and M0. All patients were randomly allocated to either the high-dose group of 3700 MBq or the low-dose group of 1850 MBq for remnant ablation. The response to treatment was defined as successful or unsuccessful after a six- to nine-month interval. Ablation was considered to be successful if patients fulfilled the following criteria: no tracer uptake in the thyroid bed on diagnosis whole-body scanning and a negative level of serum thyroglobulin. There were 327 patients enrolled between January 2013 and December 2014. More than 95% had papillary thyroid cancer. Data could be analyzed for 278 cases (M age  = 44 years; 71.6% women), 155 in the low-dose group and 123 in the high-dose group. The rate of initial successful ablation was 84.2% in all patients, 82.6% in the low-dose group, and 86.2% in the high-dose group. There was no difference between the two groups (p = 0.509). In Chinese patients with differentiated thyroid carcinoma, the low dose of 1850 MBq radioiodine activity is as effective as a high dose of 3700 MBq for thyroid remnant ablation.

Comparative toxicity of 4 commonly used intravitreal corticosteroids on rat retina.

PubMed

Citirik, Mehmet; Dilsiz, Nihat; Batman, Cosar; Zilelioglu, Orhan

2009-06-01

To investigate the effects of 4 commonly used steroids (dexamethasone, triamcinolone, betamethasone, and methylprednisolone) on 50 retinas of 25 adult pigmented rats. Experimental animal study. Twenty-five pigmented Long-Evans male rats. Each steroid drug with 2 different doses (0.025 mL and 0.050 mL) was injected into the vitreous of each eye of 5 rats. The low drug dose was injected into the right eye and the high dose was injected into the left eye. Ten eyes of 5 randomly selected rats were used as a control group and intravitreal saline was injected into these eyes. Oxidative damage and intrinsic antioxidative capacity were determined by measuring retinal malondialdehyde (MDA) and glutathione (GSH) levels, respectively. No statistically meaningful difference was observed in retinal GSH and MDA measurements in the low- and high-dose triamcinolone (1 and 2 mg), low-dose betamethasone (0.075 mg), and low-dose dexamethasone (0.1 mg) groups, compared with the control group. Both doses of methylprednisolone (1.6 mg and 3.2 mg), high-dose betamethasone (0.15 mg), and high-dose dexamethasone (0.2 mg) markedly altered retinal GSH and MDA levels. The results of our study show that the toxicity of triamcinolone is not evident even in high doses. It may be used safely. We also suggest that intravitreal use of low doses of betamethasone and dexamethasone is safer than higher doses of these drugs and both doses of methylprednisolone.

Effects of supplementation with higher levels of manganese and magnesium on immune function.

PubMed

Son, Eun-Wha; Lee, Sung-Ryul; Choi, Hye-Sook; Koo, Hyun-Jung; Huh, Jung-Eun; Kim, Mi-Hyun; Pyo, Suhkneung

2007-06-01

The magnesium (Mg) and manganese (Mn) were evaluated for its effectiveness as an immunomodulator in rats. The treatments were as follows: Group 1, AIN-93M diet (0.05% Mg, 0.001% Mn); Group 2, high-dose Mg (0.1% Mg, 0.001% Mn); and Group 3, high dose Mn (0.05% Mg, 0.01% Mn) (n-12/group). After 12 weeks of supplementation, rats were sacrificed to assess the effect on a range of innate responses (tumoricidal activity, oxidative burst and nitric oxide) and the mitogen-stimulated lymphoproliferative response. Immune function was significantly affected in both the high dose Mg and the Mn group. Lymphocyte proliferative responses and NK cell activity were measured in pooled spleen from each group. The mitogen response of lymphocytes to LPS in the spleen was significantly reduced in high dose Mg-treated groups, whereas the response to ConA was not affected in both high dose minerals-treated groups. The reactive oxygen species level of macrophages was decreased in both groups. These effects were more pronounced in high dose Mg-treated group. Nitric oxide production was also decreased in high dose minerals-treated group. In addition, tumoricidal activities of splenic NK cell and peritoneal macrophage in mineral exposed rats were significantly increased. Moreover, percent death of macrophage was reduced in two groups receiving high dose mineral supplements. Taken together, the present data suggest that high dose trace min erals exert a differential effect on the function of immune cells.

Healthcare provider compliance with the 2013 ACC/AHA Adult Cholesterol Guideline recommendation for high-intensity dose statins for patients with coronary artery disease.

PubMed

Housholder-Hughes, Susan D; Martin, Melanie M; McFarland, Marilyn R; Creech, Constance J; Shea, Michael J

Atherosclerotic cardiovascular disease is the foremost cause of death for U.S. adults. The 2013 ACC/AHA Adult Cholesterol Guidelines recommend high-intensity dose statins for individuals with coronary artery disease (CAD). To determine healthcare provider compliance with the Cholesterol Guideline recommendation specific to high-intensity dose statins for patients with CAD. A retrospective chart review was conducted to determine compliance rate. A questionnaire was developed to evaluate healthcare provider beliefs, attitudes, and self-confidence toward this recommendation. Of the 473 patients with CAD, 67% were prescribed a high-intensity dose statin. Patients with non-ST segment myocardial infarction and ST segment myocardial infarction were more likely to be prescribed a high-intensity dose statin versus a moderate or low-intensity dose. Healthcare providers strongly agreed with this guideline recommendation. There exists a dichotomy between intention to prescribe and actual prescribing behaviors of high-intensity dose statin for patients with CAD. Copyright © 2017 Elsevier Inc. All rights reserved.

Progress in high-dose radiation dosimetry. Final report

DOE Office of Scientific and Technical Information (OSTI.GOV)

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

1981-01-01

The last decade has witnessed a deluge of new high-dose dosimetry techniques and expended applications of methods developed earlier. Many of the principal systems are calibrated by means of calorimetry, although production of heat is not always the final radiation effect of interest. Requirements for a stable and reliable transfer dose meters have led to further developments of several important high-dose systems: thermoluminescent materials, radiochromic dyes, ceric-cerous solutions analyzed by high-frequency oscillometry. A number of other prospective dosimeters are also treated in this review. In addition, an IAEA program of high-dose intercomparison and standardization for industrial radiation processing is described.

Progress in high-dose radiation dosimetry. Final report

DOE Office of Scientific and Technical Information (OSTI.GOV)

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

1981-01-01

The last decade has witnessed a deluge of new high-dose dosimetry techniques and expended applications of methods developed earlier. Many of the principal systems are calibrated by means of calorimetry, although production of heat is not always the final radiation effect of interest. Requirements for a stable and reliable transfer dose meters have led to further developments of several important high-dose systems: thermoluminescent materials, radiochromic dyes, ceric-cerous solutions analyzed by high-frequency oscillometry. A number of other prospective dosimeters also treated in this review. In addition, an IAEA programme of high-dose intercomparison and standardization for industrial radiation processing is described.

Typical doses and dose rates in studies pertinent to radiation risk inference at low doses and low dose rates

PubMed Central

Rühm, Werner; Azizova, Tamara; Bouffler, Simon; Cullings, Harry M; Grosche, Bernd; Little, Mark P; Shore, Roy S; Walsh, Linda; Woloschak, Gayle E

2018-01-01

Abstract In order to quantify radiation risks at exposure scenarios relevant for radiation protection, often extrapolation of data obtained at high doses and high dose rates down to low doses and low dose rates is needed. Task Group TG91 on ‘Radiation Risk Inference at Low-dose and Low-dose Rate Exposure for Radiological Protection Purposes’ of the International Commission on Radiological Protection is currently reviewing the relevant cellular, animal and human studies that could be used for that purpose. This paper provides an overview of dose rates and doses typically used or present in those studies, and compares them with doses and dose rates typical of those received by the A-bomb survivors in Japan. PMID:29432579

Comparison of consolidation strategies in acute myeloid leukemia: high-dose cytarabine alone versus intermediate-dose cytarabine combined with anthracyclines.

PubMed

Kim, Dae Sik; Kang, Ka-Won; Lee, Se Ryeon; Park, Yong; Sung, Hwa Jung; Kim, Seok Jin; Choi, Chul Won; Kim, Byung Soo

2015-09-01

We compared the efficacy of high-dose cytarabine alone to that of intermediate-dose cytarabine combined with anthracyclines as consolidation therapy. Patients enrolled in the Korea University acute myeloid leukemia (AML) registry received remission induction chemotherapy with the same standard induction regimen (idarubicin and cytarabine 3 + 7). Postremission therapy was performed for three or four cycles according to one of the following regimens: high-dose cytarabine (3 g/m(2)) or combination of intermediate-dose cytarabine (1 g/m(2)) with anthracyclines (idarubicin or mitoxantrone). Among the 443 AML patients enrolled in the registry, 145 patients received consolidation chemotherapy. The median overall survival (OS) and relapse-free survival (RFS) in the high-dose cytarabine group were significantly longer than those in the anthracycline combination group (OS, not reached vs. 16.6 months, p = 0.045; RFS, 38.6 months vs. 11.0 months, p = 0.011). The median duration of neutropenia was longer in the anthracycline combination group than in the high-dose cytarabine group (8 vs. 10 days, p = 0.001). This study suggests that high-dose cytarabine consolidation may produce superior outcomes than combination treatment with intermediate-dose cytarabine and anthracyclines and that the addition of anthracyclines during AML consolidation has limited value as compared to cytarabine intensification.

END-DIASTOLIC FLOW REVERSAL LIMITS THE EFFICACY OF PEDIATRIC INTRAAORTIC BALLOON PUMP COUNTERPULSATION

PubMed Central

Bartoli, Carlo R.; Rogers, Benjamin D.; Ionan, Constantine E.; Koenig, Steven C.; Pantalos, George M.

2013-01-01

OBJECTIVE Counterpulsation with an intraaortic balloon pump (IABP) has not achieved the same successes or clinical use in pediatric patients as in adults. In a pediatric animal model, IABP efficacy was investigated to determine whether IABP timing with a high-fidelity blood pressure signal may improve counterpulsation therapy versus a low-fidelity signal. METHODS In Yorkshire piglets (n=19, 13.0±0.5 kg) with coronary ligation-induced acute ischemic left ventricular failure, pediatric IABPs (5 or 7cc) were placed in the descending thoracic aorta. Inflation and deflation were timed with traditional criteria from low-fidelity (fluid-filled) and high-fidelity (micromanometer) blood pressure signals during 1:1 support. Aortic, carotid, and coronary hemodynamics were measured with pressure and flow transducers. Myocardial oxygen consumption was calculated from coronary sinus and arterial blood samples. Left ventricular myocardial blood flow and end-organ blood flow were measured with microspheres. RESULTS Despite significant suprasystolic diastolic augmentation and afterload reduction at heart rates of 105±3bmp, left ventricular myocardial blood flow, myocardial oxygen consumption, the myocardial oxygen supply/demand relationship, cardiac output, and end-organ blood flow did not change. Statistically significant end-diastolic coronary, carotid, and aortic flow reversal occurred with IABP deflation. Inflation and deflation timed with a high-fidelity versus low-fidelity signal did not attenuate systemic flow reversal or improve the myocardial oxygen supply/demand relationship. CONCLUSIONS Systemic end-diastolic flow reversal limited counterpulsation efficacy in a pediatric model of acute left ventricular failure. Adjustment of IABP inflation and deflation timing with traditional criteria and a high-fidelity blood pressure waveform did not improve IABP efficacy or attenuate flow reversal. End-diastolic flow reversal may limit the efficacy of IABP counterpulsation therapy in pediatric patients with traditional timing criteria. Investigation of alternative deflation timing strategies is warranted. PMID:24139614

End-diastolic flow reversal limits the efficacy of pediatric intra-aortic balloon pump counterpulsation.

PubMed

Bartoli, Carlo R; Rogers, Benjamin D; Ionan, Constantine E; Pantalos, George M

2014-05-01

Counterpulsation with an intra-aortic balloon pump (IABP) has not achieved the same success or clinical use in pediatric patients as in adults. In a pediatric animal model, IABP efficacy was investigated to determine whether IABP timing with a high-fidelity blood pressure signal may improve counterpulsation therapy versus a low-fidelity signal. In Yorkshire piglets (n = 19; weight, 13.0 ± 0.5 kg) with coronary ligation-induced acute ischemic left ventricular failure, pediatric IABPs (5 or 7 mL) were placed in the descending thoracic aorta. Inflation and deflation were timed with traditional criteria from low-fidelity (fluid-filled) and high-fidelity (micromanometer) blood pressure signals during 1:1 support. Aortic, carotid, and coronary hemodynamics were measured with pressure and flow transducers. Myocardial oxygen consumption was calculated from coronary sinus and arterial blood samples. Left ventricular myocardial blood flow and end-organ blood flow were measured with microspheres. Despite significant suprasystolic diastolic augmentation and afterload reduction at heart rates of 105 ± 3 beats per minute, left ventricular myocardial blood flow, myocardial oxygen consumption, the myocardial oxygen supply/demand relationship, cardiac output, and end-organ blood flow did not change. Statistically significant end-diastolic coronary, carotid, and aortic flow reversal occurred with IABP deflation. Inflation and deflation timed with a high-fidelity versus low-fidelity signal did not attenuate systemic flow reversal or improve the myocardial oxygen supply/demand relationship. Systemic end-diastolic flow reversal limited counterpulsation efficacy in a pediatric model of acute left ventricular failure. Adjustment of IABP inflation and deflation timing with traditional criteria and a high-fidelity blood pressure waveform did not improve IABP efficacy or attenuate flow reversal. End-diastolic flow reversal may limit the efficacy of IABP counterpulsation therapy in pediatric patients with traditional timing criteria. Investigation of alternative deflation timing strategies is warranted. Copyright © 2014 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

Left ventricular midwall mechanics at 24 weeks' gestation in high-risk normotensive pregnant women: relationship to placenta-related complications of pregnancy.

PubMed

Novelli, G P; Vasapollo, B; Gagliardi, G; Tiralongo, G M; Pisani, I; Manfellotto, D; Giannini, L; Valensise, H

2012-04-01

Most studies during pregnancy have assessed maternal left ventricular (LV) function by load-dependent indices, assessing only chamber function. The aim of this study was to assess afterload-adjusted LV myocardial and chamber systolic function at 24 weeks' gestation and 6 months postpartum in high-risk normotensive pregnant women. A group of 118 high-risk women with bilateral notching of the uterine arteries underwent an echocardiographic examination to evaluate midwall mechanics (midwall shortening (mFS%) and stress-corrected midwall shortening (SCmFS%)) of the LV at 24 weeks' gestation and 6 months postpartum. Patients were followed until delivery and pregnancies were classified retrospectively as uneventful (uncomplicated outcome) or complicated. A control group of 54 low-risk women with uneventful pregnancies without bilateral notching was also enrolled. The pregnancy was uneventful in 74 (62.7%) women, whereas 44 (37.3%) developed complications. At 24 weeks' gestation, mFS% and SCmFS% were greater in the uncomplicated-outcome compared with the complicated-outcome group (25.9 ± 4.8 vs 18.8 ± 5.0%, P < 0.001 and 107.9 ± 18.4 vs 77.9 ± 20.7%, P < 0.001, respectively). At 6 months postpartum, SCmFS% remained greater in the uncomplicated-outcome compared with the complicated-outcome group (100.4 ± 21.6 vs 87.8 ± 19.1, P < 0.05). In the uncomplicated-outcome group, SCmFS% was higher during pregnancy than it was postpartum, whereas in the complicated-outcome group, it was lower during pregnancy than it was postpartum (P < 0.05). Maternal cardiac midwall mechanics appear to be enhanced (SCmFS% increased compared with controls) during pregnancy compared with postpartum in high-risk patients with uncomplicated pregnancy, whereas midwall mechanics are depressed both during pregnancy and postpartum in patients with pregnancy complications. Copyright © 2012 ISUOG. Published by John Wiley & Sons, Ltd.

Comparison of high-dose intermittent and low-dose continuous oral artemisinin in dogs with naturally occurring tumors.

PubMed

Hosoya, Kenji; Couto, C Guillermo; London, Cheryl A; Kisseberth, William C; Phelps, Mitchell A; Dalton, James T

2014-01-01

To evaluate the clinical toxicity and activity of orally administered artemisinin in dogs with spontaneous tumors, 24 client-owned dogs were randomly divided into two groups and received either low-continuous dose (3 mg/kg q 24 hr) or high-dose intermittent (three doses of 45 mg/kg q 6 hr repeated q 1 wk) of artemisinin per os. Treatment was continued for 21 days. Dogs were evaluated weekly for clinical effect and at the end of the treatment for hematologic and biochemical adverse events. Whole blood concentrations of artemisinin and dihydroartemisinin were measured by liquid chromatography/tandem mass spectrometry after the first dose of artemisinin in three dogs in each group. Blood concentrations of artemisinin and dihydroartemisinin were <0.1 μM at all time points, and there was no difference in blood concentration between the two dosing groups. The most frequent adverse event was anorexia, which was observed in 11% of the low-dose group and 29% of the high-dose group. Oral artemisinin, both in low-dose continuous and high-dose intermittent, is well tolerated in dogs but results in low bioavailability. Parenteral administration should be considered for future studies.

Accelerated Irradiations for High Dose Microstructures in Fast Reactor Alloys

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jiao, Zhijie

The objective of this project is to determine the extent to which high dose rate, self-ion irradiation can be used as an accelerated irradiation tool to understand microstructure evolution at high doses and temperatures relevant to advanced fast reactors. We will accomplish the goal by evaluating phase stability and swelling of F-M alloys relevant to SFR systems at very high dose by combining experiment and modeling in an effort to obtain a quantitative description of the processes at high and low damage rates.

Cost-effectiveness of Apixaban Compared With Edoxaban for Stroke Prevention in Nonvalvular Atrial Fibrillation.

PubMed

Lip, Gregory Y H; Lanitis, Tereza; Kongnakorn, Thitima; Phatak, Hemant; Chalkiadaki, Corina; Liu, Xianchen; Kuznik, Andreas; Lawrence, Jack; Dorian, Paul

2015-11-01

The purpose of this analysis was to assess the cost-effectiveness of apixaban 5 mg BID versus high- and low-dose edoxaban (60 mg and 30 mg once daily) as intended starting dose strategies for stroke prevention in patients from a UK National Health Service perspective. A previously developed and validated Markov model was adapted to evaluate the lifetime clinical and economic impact of apixaban 5 mg BID versus edoxaban (high and low dose) in patients with nonvalvular atrial fibrillation. A pairwise indirect treatment comparison was conducted for clinical end points, and price parity was assumed between apixaban and edoxaban. Costs in 2012 British pounds, life-years, and quality-adjusted life-years (QALYs) gained, discounted at 3.5% per annum, were estimated. Apixaban was predicted to increase life expectancy and QALYs versus low- and high-dose edoxaban. These gains were achieved at cost-savings versus low-dose edoxaban, thus being dominant and nominal increases in costs versus high-dose edoxaban. The incremental cost-effectiveness ratio of apixaban versus high-dose edoxaban was £6763 per QALY gained. Apixaban was deemed to be dominant (less costly and more effective) versus low-dose edoxaban and a cost-effective alternative to high-dose edoxaban. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Dose measurement using Al2O3 dosimeter in comparison to LiF:Mg,Ti dosimeter and ionization chamber at low and high energy x-ray

NASA Astrophysics Data System (ADS)

Yusof, Mohd Fahmi Mohd; Yahya, Muhammad Hadzmi; Rosnan, Muhammad Syazwan; Abdullah, Reduan; Kadir, Ahmad Bazlie Abdul

2017-01-01

The dose measurement using Al2O3 OSL dosimeter (OSLD) was carried out at low and high energy x-ray. The dose at low energy x-ray was measured at 40, 71 and 125 kVp x-ray energies. The dose ar high energy x-ray was measured at 6 and 10 MV x-ray energies measured at the depth of maximum dose (Zmax). The results were compared to that in ionization chamber and LiF: Mg,Ti thermoluminescent dosimeters (TLD100). The results showed that the dose of OSLD were less in agreement to ionization chamber compared to that in TLD100. The dose of OSLD however was in good agreement to that in ionization chamber at high energy x-ray. The dose measured using OSLD were found to be more consistence at high energy x-ray shown by the standard deviation of the readings. The measurement of x2 showed that the readings of OSLD were close to that in ionization chamber with values of 2.21 and 4.63 for 6 and 10 MV respectively. The results indicated that OSLD is more suitable for dose measurement at high energy x-ray.

Dose Rate Effects in Linear Bipolar Transistors

NASA Technical Reports Server (NTRS)

Johnston, Allan; Swimm, Randall; Harris, R. D.; Thorbourn, Dennis

2011-01-01

Dose rate effects are examined in linear bipolar transistors at high and low dose rates. At high dose rates, approximately 50% of the damage anneals at room temperature, even though these devices exhibit enhanced damage at low dose rate. The unexpected recovery of a significant fraction of the damage after tests at high dose rate requires changes in existing test standards. Tests at low temperature with a one-second radiation pulse width show that damage continues to increase for more than 3000 seconds afterward, consistent with predictions of the CTRW model for oxides with a thickness of 700 nm.

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

PubMed

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 (58 patients) and high-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 <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%. 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.

Improving Low-Dose Blood-Brain Barrier Permeability Quantification Using Sparse High-Dose Induced Prior for Patlak Model

PubMed Central

Fang, Ruogu; Karlsson, Kolbeinn; Chen, Tsuhan; Sanelli, Pina C.

2014-01-01

Blood-brain-barrier permeability (BBBP) measurements extracted from the perfusion computed tomography (PCT) using the Patlak model can be a valuable indicator to predict hemorrhagic transformation in patients with acute stroke. Unfortunately, the standard Patlak model based PCT requires excessive radiation exposure, which raised attention on radiation safety. Minimizing radiation dose is of high value in clinical practice but can degrade the image quality due to the introduced severe noise. The purpose of this work is to construct high quality BBBP maps from low-dose PCT data by using the brain structural similarity between different individuals and the relations between the high- and low-dose maps. The proposed sparse high-dose induced (shd-Patlak) model performs by building a high-dose induced prior for the Patlak model with a set of location adaptive dictionaries, followed by an optimized estimation of BBBP map with the prior regularized Patlak model. Evaluation with the simulated low-dose clinical brain PCT datasets clearly demonstrate that the shd-Patlak model can achieve more significant gains than the standard Patlak model with improved visual quality, higher fidelity to the gold standard and more accurate details for clinical analysis. PMID:24200529

Dose-Response Relationship between Radiation Dose and Loco-regional Control in Patients with Stage II-III Esophageal Cancer Treated with Definitive Chemoradiotherapy.

PubMed

Kim, Hyun Ju; Suh, Yang-Gun; Lee, Yong Chan; Lee, Sang Kil; Shin, Sung Kwan; Cho, Byung Chul; Lee, Chang Geol

2017-07-01

The correlation between radiation dose and loco-regional control (LRC) was evaluated in patients with stage II-III esophageal cancer treated with definitive concurrent chemoradiotherapy (CRT). Medical records of 236 stage II-III esophageal cancer patients treated with definitive CRT at Yonsei Cancer Center between 1994 and 2013 were retrospectively reviewed. Among these, 120 received a radiation dose of < 60 Gy (standard-dose group), while 116 received ≥ 60 Gy (high-dose group). The median doses of radiation in the standard- and high-dose groups were 50.4 and 63 Gy, respectively. Concurrent 5-fluorouracil/cisplatin chemotherapy was administered to most patients. There were no differences in patient characteristics between the two groups except for high Karnofsky performance status and lower-thoracic lesions being more prevalent in the standard-dose group. The median progression-free survival (PFS) and overall survival (OS) times were 13.2 months and 26.2 months, respectively. Patients in the high-dose group had significantly better 2-year LRC (69.1% vs. 50.3%, p=0.002), median PFS (16.7 months vs. 11.7 months, p=0.029), and median OS (35.1 months vs. 22.3 months, p=0.043). Additionally, LRC exhibited a dose-response relationship and the complete response rate was significantly higher in the high-dose group (p=0.006). There were no significant differences in treatment-related toxicities between the groups. A higher radiation dose (> 60 Gy) is associated with increased LRC, PFS, and OS in patients with stage II-III esophageal cancer treated with definitive CRT.

Long-term Pulmonary Responses to Quadweekly Intermittent Intratracheal Spray Instillations of Magnetite (Fe3O4) Nanoparticles for 52 Weeks in Fischer 344 Rats.

PubMed

Tada, Yukie; Yano, Norio; Takahashi, Hiroshi; Yuzawa, Katsuhiro; Ando, Hiroshi; Kubo, Yoshikazu; Nagasawa, Akemichi; Inomata, Akiko; Ogata, Akio; Nakae, Dai

2013-12-01

Information about potential risks of iron nanomaterials is still limited, while a wide variety of applications are expected. We recently reported acute phase responses of male and female Fischer 344 rats after a single intratracheal spray instillation of Fe3O4 nanoparticles (magnetite), clearly showing dose-dependent pulmonary inflammatory changes (Tada et al., J Toxicol Pathol 25, 233-239, 2012). The present study assessed long-term responses of male and female Fischer 344 rats to multiple administrations of magnetite. Ten-week-old male and female Fischer 344 rats (n=20/group) were exposed to a total of 13 quadweekly intermittent intratracheal spray instillations of magnetite during the experimental period of 52 weeks, at doses of 0, 0.2 (low), 1.0 (medium) and 5.0 (high-dose) mg/kg body weight per administration. Absolute and relative lung weights of the high-dose group were significantly higher than those of the control group. Macroscopically, slight enlargement and scattered black patches were recognized in the lungs and the lung-associated lymph nodes of the high-dose group. Histopathologically, infiltration of macrophages phagocytosing magnetite (all dose groups) and of chronic inflammatory cells (medium- and high-dose males and high-dose females), alveolar bronchiolization and granuloma (high-dose group) were observed. In addition, alveolar hyperplasias were observed in some rats of the high-dose group, and cytoplasmic overexpression of β-catenin protein was immunohistochemically found in such lesions. The present results clearly show that instilled magnetite causes chronic inflammatory responses in the lung. These responses occur in a dose-dependent manner without apparent differences among sexes.

Long-term mesalamine maintenance in ulcerative colitis: which is more important? Adherence or daily dose.

PubMed

Khan, Nabeel; Abbas, Ali M; Koleva, Yordanka N; Bazzano, Lydia A

2013-05-01

There are limited data about the long-term follow-up of patients with ulcerative colitis (UC) maintained on high versus low doses of mesalamine. We evaluated the best long-term average daily dose that would keep the disease in remission. Nationwide ulcerative colitis data were obtained from the Veterans Affairs health care system for the period 2001 to 2011. Those who started mesalamine maintenance during this period were included. Average daily dose and the level of adherence were assessed for the period between the first mesalamine dispense and the date of first flare defined as the first filling of 40 mg/day or more of oral prednisone or any dose of intravenous steroids. Patients with ulcerative colitis maintained on an average daily dose 2.4 to 2.8 g/day (low dose) were compared with 4.4 to 4.8 g/day (high dose). Adherence was assessed using continuous single interval medication availability indicator. We included 4452 patients with a median follow-up of 6 years. There was no significant reduction in the risk of flares when comparing high versus low average mesalamine dose among patients with high [hazard ratio = 0.96, P = 0.8)] and medium (hazard ratio = 0.74, P = 0.17) adherence. However, there was a significant reduction in the risk of flares with high dose of mesalamine among patients with low adherence (hazard ratio = 0.28, P = 0.003). Our data show that when starting a patient on mesalamine, there is no difference in the long-term flare risk between low versus high average daily dose as long as the patients have a high to moderate level of adherence.

Low and high dose rate heavy ion radiation-induced intestinal and colonic tumorigenesis in APC1638N/+ mice

NASA Astrophysics Data System (ADS)

Suman, Shubhankar; Kumar, Santosh; Moon, Bo-Hyun; Fornace, Albert J.; Datta, Kamal

2017-05-01

Ionizing radiation (IR) is a recognized risk factor for colorectal cancer (CRC) and astronauts undertaking long duration space missions are expected to receive IR doses in excess of permissible limits with implications for colorectal carcinogenesis. Exposure to IR in outer space occurs at low doses and dose rates, and energetic heavy ions due to their high linear energy transfer (high-LET) characteristics remain a major concern for CRC risk in astronauts. Previously, we have demonstrated that intestinal tumorigenesis in a mouse model (APC1638N/+) of human colorectal cancer was significantly higher after exposure to high dose rate energetic heavy ions relative to low-LET γ radiation. The purpose of the current study was to compare intestinal tumorigenesis in APC1638N/+ mice after exposure to energetic heavy ions at high (50 cGy/min) and relatively low (0.33 cGy/min) dose rate. Male and female mice (6-8 weeks old) were exposed to either 10 or 50 cGy of 28Si (energy: 300 MeV/n; LET: 70 keV/μm) or 56Fe (energy: 1000 MeV/n; LET: 148 keV/μm) ions at NASA Space Radiation Laboratory in Brookhaven National Laboratory. Mice (n = 20 mice/group) were euthanized and intestinal and colon tumor frequency and size were counted 150 days after radiation exposure. Intestinal tumorigenesis in male mice exposed to 56Fe was similar for high and low dose rate exposures. Although male mice showed a decreasing trend at low dose rate relative to high dose rate exposures, the differences in tumor frequency between the two types of exposures were not statistically significant after 28Si radiation. In female mice, intestinal tumor frequency was similar for both radiation type and dose rates tested. In both male and female mice intestinal tumor size was not different after high and low dose rate radiation exposures. Colon tumor frequency in male and female mice after high and low dose rate energetic heavy ions was also not significantly different. In conclusion, intestinal and colonic tumor frequency and size was similar irrespective of energetic heavy ion radiation dose rate suggesting that carcinogenic potential of energetic heavy ions is independent of dose rate.

Effect of different doses of nandrolone decanoate on lipid peroxidation, DNA fragmentation, sperm abnormality and histopathology of testes of male Wister rats.

PubMed

Mohamed, Hanaa Mahmoud; Mohamed, Manal Abdul-Hamid

2015-01-01

The present study aims of to investigate the effects of low and high doses of nandrolone decanoate (ND) on histopathology and apoptosis of the spermatogenic cells as well as lipid peroxidation, antioxidant enzyme activities, sperm abnormality and DNA fragmentation. Eighteen animals were divided into three groups each group contain six animals. The rats were divided into three groups as following: Group 1 was administered saline (control). Group 2, received nandrolone decanoate (3 mg/kg/weekly) (low dose) with intramuscular injection. Group 3, received intramuscular injection dose of nandrolone decanoate (10 mg/kg/weekly) (high dose). After 8 weeks, caspase-3 assay was used to determine the apoptotic cells. The sperm parameters, lipid peroxidation, antioxidant enzyme activities and testosterone concentration were also investigated in the experimental groups of both low and high dose compared to the control groups. Treated group with high dose showed degenerated germinal epithelial cells sloughed in the lumina of seminiferous tubules, where almost seminiferous tubules were devoid of spermatids and spermatozoa compared to control and group treated with low dose. Also, a significant increase of lipid peroxidation levels and heat shock proteins was observed in two groups administrated with two different doses of ND while, antioxidant enzyme activities, and testosterone concentration was significantly decreased in two treated group when compared with control. Administration of ND at high and low doses leads to deteriorated sperm parameters, DNA fragmentation and testicular apoptosis. In conclusion, the administration ND at high doses more effective on lipid peroxidation, antioxidant enzyme activities, sperm abnormality, histopathology, apoptotic and DNA changes compared to low dose group and to control group. Published by Elsevier GmbH.

High-dose versus standard-dose radiotherapy with concurrent chemotherapy in stages II-III esophageal cancer.

PubMed

Suh, Yang-Gun; Lee, Ik Jae; Koom, Wong Sub; Cha, Jihye; Lee, Jong Young; Kim, Soo Kon; Lee, Chang Geol

2014-06-01

In this study, we investigated the effects of radiotherapy ≥60 Gy in the setting of concurrent chemo-radiotherapy for treating patients with Stages II-III esophageal cancer. A total of 126 patients treated with 5-fluorouracilbased concurrent chemo-radiotherapy between January 1998 and February 2008 were retrospectively reviewed. Among these patients, 49 received a total radiation dose of <60 Gy (standard-dose group), while 77 received a total radiation dose of ≥60 Gy (high-dose group). The median doses in the standard- and high-dose groups were 54 Gy (range, 45-59.4 Gy) and 63 Gy (range, 60-81 Gy), respectively. The high-dose group showed significantly improved locoregional control (2-year locoregional control rate, 69 versus 32%, P < 0.01) and progression-free survival (2-year progression-free survival, 47 versus 20%, P = 0.01) than the standard-dose group. Median overall survival in the high- and the standard-dose groups was 28 and 18 months, respectively (P = 0.26). In multivariate analysis, 60 Gy or higher radiotherapy was a significant prognostic factor for improved locoregional control, progression-free survival and overall survival. No significant differences were found in frequencies of late radiation pneumonitis, post-treatment esophageal stricture or treatment-related mortality between the two groups. High-dose radiotherapy of 60 Gy or higher with concurrent chemotherapy improved locoregional control and progression-free survival without a significant increase of in treatment-related toxicity in patients with Stages II-III esophageal cancer. Our study could provide the basis for future randomized clinical trials. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Contribution of adrenal hormones to nicotine-induced inhibition of synovial plasma extravasation in the rat.

PubMed

Miao, F J; Benowitz, N L; Heller, P H; Levine, J D

1997-01-01

1. In this study, we examined the mechanism(s) by which s.c. nicotine inhibits synovial plasma extravasation. We found that nicotine dose-dependently inhibited bradykinin (BK)- and platelet activating factor (PAF)-induced plasma extravasation. 2. The effect of nicotine on both BK- and PAF-induced plasma extravasation was attenuated by adrenal medullectomy. ICI-118,551 (a selective beta 2-adrenoceptor blocker) (30 micrograms ml-1, intra-articularly) significantly attenuated the inhibitory action of high-dose (1 mg kg-1) nicotine on BK-induced plasma extravasation without affecting the inhibition by low- (0.01 microgram kg-1) dose nicotine or that on PAF-induced plasma extravasation by nicotine at any dose. This suggested that beta 2-adrenoceptors mediate the inhibitory actions of high-dose, but not low-dose, nicotine. We also found that systemic naloxone (an opioid receptor antagonist) (two hourly injections of 1 mg kg-1, i.p.) attenuated the inhibitory action produced by all doses of nicotine on BK- or PAF-induced plasma extravasation, suggesting the contribution of endogenous opioids. 3. RU-38,486 (a glucocorticoid receptor antagonist) (30 mg kg-1, s.c.), and metyrapone (a glucocorticoid synthesis inhibitor) (two hourly injections of 100 mg kg-1, i.p.) both attenuated the action of high-dose nicotine without affecting that of low-dose nicotine. 4. Spinal mecamylamine (a nicotinic receptor antagonist) (0.025 mg kg-1, intrathecally, i.t.) attenuated the action of high-dose, but not low-dose, nicotine, suggesting that part of the action of high-dose nicotine is mediated by spinal nicotinic receptors. 5. Combined treatment with ICI-118,551, naloxone and RU-38,486 attenuated the action of low-dose nicotine by an amount similar to that produced by naloxone alone but produced significantly greater attenuation of the effect of high-dose nicotine when compared to the action of any of the three antagonists alone.

Contribution of adrenal hormones to nicotine-induced inhibition of synovial plasma extravasation in the rat

PubMed Central

Jia-Pei Miao, Frederick; Benowitz, Neal L; Heller, Philip H; Levine, Jon D

1997-01-01

In this study, we examined the mechanism(s) by which s.c. nicotine inhibits synovial plasma extravasation. We found that nicotine dose-dependently inhibited bradykinin (BK)- and platelet activating factor (PAF)-induced plasma extravasation. The effect of nicotine on both BK- and PAF-induced plasma extravasation was attenuated by adrenal medullectomy. ICI-118,551 (a selective β2-adrenoceptor blocker) (30 μg ml−1, intra-articularly) significantly attenuated the inhibitory action of high-dose (1 mg kg−1) nicotine on BK-induced plasma extravasation without affecting the inhibition by low- (0.01 μg kg−1) dose nicotine or that on PAF-induced plasma extravasation by nicotine at any dose. This suggested that β2-adrenoceptors mediate the inhibitory actions of high-dose, but not low-dose, nicotine. We also found that systemic naloxone (an opioid receptor antagonist) (two hourly injections of 1 mg kg−1, i.p.) attenuated the inhibitory action produced by all doses of nicotine on BK- or PAF-induced plasma extravasation, suggesting the contribution of endogenous opioids. RU-38,486 (a glucocorticoid receptor antagonist) (30 mg kg−1, s.c.) and metyrapone (a glucocorticoid synthesis inhibitor) (two hourly injections of 100 mg kg−1, i.p.) both attenuated the action of high-dose nicotine without affecting that of low-dose nicotine. Spinal mecamylamine (a nicotinic receptor antagonist) (0.025 mg kg−1, intrathecally, i.t.) attenuated the action of high-dose, but not low-dose, nicotine, suggesting that part of the action of high-dose nicotine is mediated by spinal nicotinic receptors. Combined treatment with ICI-118,551, naloxone and RU-38,486 attenuated the action of low-dose nicotine by an amount similar to that produced by naloxone alone but produced significantly greater attenuation of the effect of high-dose nicotine when compared to the action of any of the three antagonists alone. PMID:9117123

Benefits of High-dose Steroid + Hespander + Mannitol Administration in the Treatment of Bell's Palsy.

PubMed

Furukawa, Takatoshi; Abe, Yasuhiro; Ito, Tsukasa; Kubota, Toshinori; Kakehata, Seiji

2017-02-01

Large-scale investigations have not been recently conducted on the efficacy of high-dose steroid administration of prednisolone (PSL) for Bell's palsy. We compared treatment results between normal-dose steroid (PSL 60 mg/d) and high-dose steroid (PSL 200 mg/d) + Hespander + Mannitol administration. We also investigated the recovery rate for antiviral agents. Retrospective case review. Tertiary referral center. A total of 675 patients with Bell's palsy who had grade V and grade VI on the House-Brackmann (HB) scale were treated in our department between 1995 and 2014. These patients could be divided into a normal-dose group and high-dose group. We separately assessed treatment outcomes for HB grade V patients and HB grade VI patients. Logistic regression analysis was also performed to investigate factors that can impact treatment outcomes, i.e., sex, age, days to start of treatment, PSL dosage, and antiviral drug administration. Recovery rates were significantly better in the high-dose steroid + Hespander + Mannitol group in comparison with the normal-dose steroid group for HB grade V (100% versus 77.7%) and HB grade VI (92.5% versus 68.2%). Additional effects of antiviral agents were only shown in the normal-dose group. Significant factors for treatment outcomes were PSL 200 mg/d administration and early initiation of treatment. Insignificant factors were sex, age, and the antiviral agent. We showed the high-dose steroid + Hespander + Mannitol administration produced significantly better outcomes than normal-dose steroid administration in the treatment of patients with Bell's palsy.

Detection of erythropoietin misuse by the Athlete Biological Passport combined with reticulocyte percentage.

PubMed

Bejder, Jacob; Aachmann-Andersen, Niels Jacob; Bonne, Thomas Christian; Olsen, Niels Vidiendal; Nordsborg, Nikolai Baastrup

2016-10-01

The sensitivity of the adaptive model of the Athlete Biological Passport (ABP) and reticulocyte percentage (ret%) in detection of recombinant human erythropoietin (rHuEPO) misuse was evaluated using both a long-term normal dose and a brief high dose treatment regime. Sixteen subjects received either 65 IU rHuEPO × kg -1 every second day for two weeks (normal-dose), 390 IU rHuEPO × kg -1 on three consecutive days (high-dose), or frequent placebo treatment for 13 days in a randomized, placebo-controlled, double-blind crossover design. Blood variables were measured 4, 11, and 25 days following treatment initiation. The ABP based on haemoglobin concentration ([Hb]) and OFF-hr score ([Hb] - 60 × √ret%) yielded atypical profiles following both normal-dose and high-dose treatment (0 %, 31 %, 13 % vs. 21 %, 33 %, 20 % at days 4, 11, and 25 after normal and high dose, respectively). Including ret% as a stand-alone marker for atypical blood profiles increased (P < 0.05) the sensitivity of the adaptive model at day 11 to 63 % and 67 % for normal-dose and high-dose rHuEPO administration, respectively. In conclusion, ~30 % of subjects injecting a normal-dose rHuEPO for two weeks or a high-dose rHuEPO for three days will present an atypical ABP profile. Including ret% as a stand-alone parameter improves the sensitivity two-fold. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Tumor Control Outcomes After Hypofractionated and Single-Dose Stereotactic Image-Guided Intensity-Modulated Radiotherapy for Extracranial Metastases From Renal Cell Carcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zelefsky, Michael J., E-mail: zelefskm@mskcc.org; Greco, Carlo; Motzer, Robert

2012-04-01

Purpose: To report tumor local progression-free outcomes after treatment with single-dose, image-guided, intensity-modulated radiotherapy and hypofractionated regimens for extracranial metastases from renal cell primary tumors. Patients and Methods: Between 2004 and 2010, 105 lesions from renal cell carcinoma were treated with either single-dose, image-guided, intensity-modulated radiotherapy to a prescription dose of 18-24 Gy (median, 24) or hypofractionation (three or five fractions) with a prescription dose of 20-30 Gy. The median follow-up was 12 months (range, 1-48). Results: The overall 3-year actuarial local progression-free survival for all lesions was 44%. The 3-year local progression-free survival for those who received a highmore » single-dose (24 Gy; n = 45), a low single-dose (<24 Gy; n = 14), or hypofractionation regimens (n = 46) was 88%, 21%, and 17%, respectively (high single dose vs. low single dose, p = .001; high single dose vs. hypofractionation, p < .001). Multivariate analysis revealed the following variables were significant predictors of improved local progression-free survival: 24 Gy dose compared with a lower dose (p = .009) and a single dose vs. hypofractionation (p = .008). Conclusion: High single-dose, image-guided, intensity-modulated radiotherapy is a noninvasive procedure resulting in high probability of local tumor control for metastatic renal cell cancer generally considered radioresistant according to the classic radiobiologic ranking.« less

Novel oxytocin receptor variants in laboring women requiring high doses of oxytocin.

PubMed

Reinl, Erin L; Goodwin, Zane A; Raghuraman, Nandini; Lee, Grace Y; Jo, Erin Y; Gezahegn, Beakal M; Pillai, Meghan K; Cahill, Alison G; de Guzman Strong, Cristina; England, Sarah K

2017-08-01

Although oxytocin commonly is used to augment or induce labor, it is difficult to predict its effectiveness because oxytocin dose requirements vary significantly among women. One possibility is that women requiring high or low doses of oxytocin have variations in the oxytocin receptor gene. To identify oxytocin receptor gene variants in laboring women with low and high oxytocin dosage requirements. Term, nulliparous women requiring oxytocin doses of ≤4 mU/min (low-dose-requiring, n = 83) or ≥20 mU/min (high-dose-requiring, n = 104) for labor augmentation or induction provided consent to a postpartum blood draw as a source of genomic DNA. Targeted-amplicon sequencing (coverage >30×) with MiSeq (Illumina) was performed to discover variants in the coding exons of the oxytocin receptor gene. Baseline relevant clinical history, outcomes, demographics, and oxytocin receptor gene sequence variants and their allele frequencies were compared between low-dose-requiring and high-dose-requiring women. The Scale-Invariant Feature Transform algorithm was used to predict the effect of variants on oxytocin receptor function. The Fisher exact or χ 2 tests were used for categorical variables, and Student t tests or Wilcoxon rank sum tests were used for continuous variables. A P value < .05 was considered statistically significant. The high-dose-requiring women had greater rates of obesity and diabetes and were more likely to have undergone labor induction and required prostaglandins. High-dose-requiring women were more likely to undergo cesarean delivery for first-stage arrest and less likely to undergo cesarean delivery for nonreassuring fetal status. Targeted sequencing of the oxytocin receptor gene in the total cohort (n = 187) revealed 30 distinct coding variants: 17 nonsynonymous, 11 synonymous, and 2 small structural variants. One novel variant (A243T) was found in both the low- and high-dose-requiring groups. Three novel variants (Y106H, A240_A249del, and P197delfs*206) resulting in an amino acid substitution, loss of 9 amino acids, and a frameshift stop mutation, respectively, were identified only in low-dose-requiring women. Nine nonsynonymous variants were unique to the high-dose-requiring group. These included 3 known variants (R151C, G221S, and W228C) and 6 novel variants (M133V, R150L, H173R, A248V, G253R, and I266V). Of these, R150L, R151C, and H173R were predicted by Scale-Invariant Feature Transform algorithm to damage oxytocin receptor function. There was no statistically significant association between the numbers of synonymous and nonsynonymous substitutions in the patient groups. Obesity, diabetes, and labor induction were associated with the requirement for high doses of oxytocin. We did not identify significant differences in the prevalence of oxytocin receptor variants between low-dose-requiring and high-dose-requiring women, but novel oxytocin receptor variants were enriched in the high-dose-requiring women. We also found 3 oxytocin receptor variants (2 novel, 1 known) that were predicted to damage oxytocin receptor function and would likely increase an individual's risk for requiring a high oxytocin dose. Further investigation of oxytocin receptor variants and their effects on protein function will inform precision medicine in pregnant women. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Risperidone dosing in children and adolescents with autistic disorder: a double-blind, placebo-controlled study.

PubMed

Kent, Justine M; Kushner, Stuart; Ning, Xiaoping; Karcher, Keith; Ness, Seth; Aman, Michael; Singh, Jaskaran; Hough, David

2013-08-01

Efficacy and safety of 2 risperidone doses were evaluated in children and adolescents with autism. Patients (N = 96; 5-17 years), received risperidone (low-dose: 0.125 mg/day [20 to <45 kg], 0.175 mg/day [>45 kg] or high-dose: 1.25 mg/day [20 to <45 kg], 1.75 mg/day [>45 kg]) or placebo. Mean baseline (range 27-29) to endpoint change in Aberrant Behavior Checklist-Irritability (primary endpoint) was significantly greater in the high-dose-(-12.4 [6.5]; p < 0.001), but not low-dose (-7.4 [8.1]; p = 0.164) group, versus placebo (-3.5 [10.7]). Clinical Global Impressions-Severity and Children's Yale-Brown Obsessive Compulsive Scale scores improved significantly only in the high-dose group, consistent with ABC-I results. Somnolence, sedation and increased appetite occurred more frequently in high-versus low-dose groups. Overall, increased appetite occurred most frequently.

High dose vitamin D may improve lower urinary tract symptoms in postmenopausal women.

PubMed

Oberg, Johanna; Verelst, Margareta; Jorde, Rolf; Cashman, Kevin; Grimnes, Guri

2017-10-01

Lower urinary tract symptoms (LUTS) are common in postmenopausal women, and have been reported inversely associated with vitamin D intake and serum 25-hydroxyvitamin D (25(OH)D) levels. The aim of this study was to investigate if high dose vitamin D supplementation would affect LUTS in comparison to standard dose. In a randomized controlled study including 297 postmenopausal women with low bone mineral density, the participants were allocated to receive capsules of 20 000IU of vitamin D 3 twice a week (high dose group) or similar looking placebo (standard dose group). In addition, all the participants received 1g of calcium and 800IU of vitamin D daily. A validated questionnaire regarding LUTS was filled in at baseline and after 12 months. At baseline, 76 women in the high dose group and 82 in the standard dose group reported any LUTS. Levels of serum 25(OH)D increased significantly more in the high dose group (from 64.7 to 164.1nmol/l compared to from 64.1 to 81.8nmol/l, p<0.01). No differences between the groups were seen regarding change in LUTS except for a statistically significant reduction in the reported severity of urine incontinence in the high dose group as compared to the standard dose group after one year (p<0.05). The results need confirmation in a study specifically designed for this purpose. Copyright © 2017 Elsevier Ltd. All rights reserved.

Changes in dynamic embryonic heart wall motion in response to outflow tract banding measured using video densitometry

NASA Astrophysics Data System (ADS)

Stovall, Stephanie; Midgett, Madeline; Thornburg, Kent; Rugonyi, Sandra

2016-11-01

Abnormal blood flow during early cardiovascular development has been identified as a key factor in the pathogenesis of congenital heart disease; however, the mechanisms by which altered hemodynamics induce cardiac malformations are poorly understood. This study used outflow tract (OFT) banding to model increased afterload, pressure, and blood flow velocities at tubular stages of heart development and characterized the immediate changes in cardiac wall motion due to banding in chicken embryo models with light microscopy-based video densitometry. Optical videos were used to acquire two-dimensional heart image sequences over the cardiac cycle, from which intensity data were extracted along the heart centerline at several locations in the heart ventricle and OFT. While no changes were observed in the synchronous contraction of the ventricle with banding, the peristaltic-like wall motion in the OFT was significantly affected. Our data provide valuable insight into early cardiac biomechanics and its characterization using a simple light microscopy-based imaging modality.

Connective tissue disease-associated pulmonary arterial hypertension

PubMed Central

Howard, Luke S.

2015-01-01

Although rare in its idiopathic form, pulmonary arterial hypertension (PAH) is not uncommon in association with various associated medical conditions, most notably connective tissue disease (CTD). In particular, it develops in approximately 10% of patients with systemic sclerosis and so these patients are increasingly screened to enable early detection. The response of patients with systemic sclerosis to PAH-specific therapy appears to be worse than in other forms of PAH. Survival in systemic sclerosis-associated PAH is inferior to that observed in idiopathic PAH. Potential reasons for this include differences in age, the nature of the underlying pulmonary vasculopathy and the ability of the right ventricle to cope with increased afterload between patients with systemic sclerosis-associated PAH and idiopathic PAH, while coexisting cardiac and pulmonary disease is common in systemic sclerosis-associated PAH. Other forms of connective tissue-associated PAH have been less well studied, however PAH associated with systemic lupus erythematosus (SLE) has a better prognosis than systemic sclerosis-associated PAH and likely responds to immunosuppression. PMID:25705389

DSC studies on gamma irradiated poly(vinylidene fluoride) applied to high gamma dose dosimetry

NASA Astrophysics Data System (ADS)

Batista, Adriana S. M.; Faria, Luiz O.

2017-11-01

Poly(vinylidene fluoride) homopolymer (PVDF) was investigated for use on high gamma dose dosimetry. Samples were irradiated with gamma doses ranging from 100 kGy to 3000 kGy. Differential scanning calorimetry (DSC) was used to construct an unambiguous relationship between the melting transition latent heat (LM) and the absorbed dose (D). DSC thermograms were taken immediately, 1, 2 and 8 months after the irradiation process revealing that the LMx D relationship presented no change for doses ranging from 100 to 2750 kGy. FTIR and UV-Vis spectroscopy data revealed the radio-induction of C˭O and C˭C bonds. These radio-induced bonds were responsible by the chain stiffening and chain oxidation, respectively. SEM microscopy demonstrates that the spherulitic large crystalline structures present in pristine PVDF are destroyed with doses as low as 100 kGy. The DRX analysis revealed that the main effect of high gamma doses in the crystalline structure of PVDF is to provoke a change from the pristine PVDF α-phase to the γ-phase. Both the ability to detect gamma doses in a large dose range and the low fading features make PVDF homopolymers good candidates to be investigated as high gamma dose dosimeters.

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

PubMed

Charoensri, Suranut; Sriphrapradang, Chutintorn; Nimitphong, Hataikarn

2017-10-01

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

Maximum shortening velocity of lymphatic muscle approaches that of striated muscle.

PubMed

Zhang, Rongzhen; Taucer, Anne I; Gashev, Anatoliy A; Muthuchamy, Mariappan; Zawieja, David C; Davis, Michael J

2013-11-15

Lymphatic muscle (LM) is widely considered to be a type of vascular smooth muscle, even though LM cells uniquely express contractile proteins from both smooth muscle and cardiac muscle. We tested the hypothesis that LM exhibits an unloaded maximum shortening velocity (Vmax) intermediate between that of smooth muscle and cardiac muscle. Single lymphatic vessels were dissected from the rat mesentery, mounted in a servo-controlled wire myograph, and subjected to isotonic quick release protocols during spontaneous or agonist-evoked contractions. After maximal activation, isotonic quick releases were performed at both the peak and plateau phases of contraction. Vmax was 0.48 ± 0.04 lengths (L)/s at the peak: 2.3 times higher than that of mesenteric arteries and 11.4 times higher than mesenteric veins. In cannulated, pressurized lymphatic vessels, shortening velocity was determined from the maximal rate of constriction [rate of change in internal diameter (-dD/dt)] during spontaneous contractions at optimal preload and minimal afterload; peak -dD/dt exceeded that obtained during any of the isotonic quick release protocols (2.14 ± 0.30 L/s). Peak -dD/dt declined with pressure elevation or activation using substance P. Thus, isotonic methods yielded Vmax values for LM in the mid to high end (0.48 L/s) of those the recorded for phasic smooth muscle (0.05-0.5 L/s), whereas isobaric measurements yielded values (>2.0 L/s) that overlapped the midrange of values for cardiac muscle (0.6-3.3 L/s). Our results challenge the dogma that LM is classical vascular smooth muscle, and its unusually high Vmax is consistent with the expression of cardiac muscle contractile proteins in the lymphatic vessel wall.

Effects of acetaldehyde and L-carnitine on morphology and enzyme activity of myocardial mitochondria in rats.

PubMed

Jin, Yuan-Zhe; Wang, Guo-Feng; Wang, Qi; Zhang, Xue-Ying; Yan, Bin; Hu, Wei-Na

2014-12-01

This study aimed to investigate the effects of acetaldehyde (AA) and L-carnitine (LC) on morphology and enzyme activity of myocardial mitochondria in rats. Sixty-five Wistar rats were randomly divided into 4 groups: the control group (n = 20), the AA low-dose group (n = 15), the AA high-dose group (n = 15) and the AA + LC group (n = 15). Different doses (110 mg/kg and 220 mg/kg) AA was injected intraperitoneally once a day for 4 weeks. After 4 weeks administration, transmission electron microscope (TEM) observation of morphology of rat myocardial mitochondria was performed. Serum levels of succinate dehydrogenase (SDH), superoxide dismutase (SOD), malondialdehyde (MDA) and cardiac troponin I (cTnI) were detected to evaluate mitochondrial enzymes activities. Light micrograph of rat myocardiocytes in the control group showing normal architecture of myocytes. The numerical density and number of mitochondria in both low-dose and high-dose AA groups were lower than that of the control group. After administration of LC, the rats in the AA + LC group showed an obvious increase in the numerical density and number of mitochondria. TEM showed that both low-dose and high-dose AA could induce myocardial mitochondrial damage in rats in a dose-dependent manner, such as mitochondrial swelling, disruptions of crest and membrane, mitochondrial deficiency. The degree of mitochondrial damage of the AA + LC group was significantly decreased after administration of LC. Our results showed that serum levels of SDH and SOD in the AA + LC and control groups were also higher than those of the low-dose and high-dose AA groups; while the MDA level in the AA + LC and control groups were lower than that of the low-dose and high-dose AA groups. The low-dose AA, high-dose AA and AA + LC groups exhibited a higher level of serum cTnI than that of the control group. However, there was no significant difference in serum cTnI level among the low-dose AA, high-dose AA and AA + LC groups. Our findings indicate that AA may lead to myocardial mitochondrial damage and the induction of enzyme activity in rats, while administration of LC could alleviate AA-related damage of rat myocardial mitochondria.

Dose of Prophylactic Platelet Transfusions and Prevention of Hemorrhage

PubMed Central

Slichter, Sherrill J.; Kaufman, Richard M.; Assmann, Susan F.; McCullough, Jeffrey; Triulzi, Darrell J.; Strauss, Ronald G.; Gernsheimer, Terry B.; Ness, Paul M.; Brecher, Mark E.; Josephson, Cassandra D.; Konkle, Barbara A.; Woodson, Robert D.; Ortel, Thomas L.; Hillyer, Christopher D.; Skerrett, Donna L.; McCrae, Keith R.; Sloan, Steven R.; Uhl, Lynne; George, James N.; Aquino, Victor M.; Manno, Catherine S.; McFarland, Janice G.; Hess, John R.; Leissinger, Cindy; Granger, Suzanne

2010-01-01

BACKGROUND We conducted a trial of prophylactic platelet transfusions to evaluate the effect of platelet dose on bleeding in patients with hypoproliferative thrombocytopenia. METHODS We randomly assigned hospitalized patients undergoing hematopoietic stem-cell transplantation or chemotherapy for hematologic cancers or solid tumors to receive prophylactic platelet transfusions at a low dose, a medium dose, or a high dose (1.1×1011, 2.2×1011, or 4.4×1011 platelets per square meter of body-surface area, respectively), when morning platelet counts were 10,000 per cubic millimeter or lower. Clinical signs of bleeding were assessed daily. The primary end point was bleeding of grade 2 or higher (as defined on the basis of World Health Organization criteria). RESULTS In the 1272 patients who received at least one platelet transfusion, the primary end point was observed in 71%, 69%, and 70% of the patients in the low-dose group, the medium-dose group, and the high-dose group, respectively (differences were not significant). The incidences of higher grades of bleeding, and other adverse events, were similar among the three groups. The median number of platelets transfused was significantly lower in the low-dose group (9.25×1011) than in the medium-dose group (11.25×1011) or the high-dose group (19.63×1011) (P = 0.002 for low vs. medium, P<0.001 for high vs. low and high vs. medium), but the median number of platelet transfusions given was significantly higher in the low-dose group (five, vs. three in the medium-dose and three in the high-dose group; P<0.001 for low vs. medium and low vs. high). Bleeding occurred on 25% of the study days on which morning platelet counts were 5000 per cubic millimeter or lower, as compared with 17% of study days on which platelet counts were 6000 to 80,000 per cubic millimeter (P<0.001). CONCLUSIONS Low doses of platelets administered as a prophylactic transfusion led to a decreased number of platelets transfused per patient but an increased number of transfusions given. At doses between 1.1×1011 and 4.4×1011 platelets per square meter, the number of platelets in the prophylactic transfusion had no effect on the incidence of bleeding. (ClinicalTrials.gov number, NCT00128713.) PMID:20164484

Development of a high precision dosimetry system for the measurement of surface dose rate distribution for eye applicators.

PubMed

Eichmann, Marion; Flühs, Dirk; Spaan, Bernhard

2009-10-01

The therapeutic outcome of the therapy with ophthalmic applicators is highly dependent on the application of a sufficient dose to the tumor, whereas the dose applied to the surrounding tissue needs to be minimized. The goal for the newly developed apparatus described in this work is the determination of the individual applicator surface dose rate distribution with a high spatial resolution and a high precision in dose rate with respect to time and budget constraints especially important for clinical procedures. Inhomogeneities of the dose rate distribution can be detected and taken into consideration for the treatment planning. In order to achieve this, a dose rate profile as well as a surface profile of the applicator are measured and correlated with each other. An instrumental setup has been developed consisting of a plastic scintillator detector system and a newly designed apparatus for guiding the detector across the applicator surface at a constant small distance. It performs an angular movement of detector and applicator with high precision. The measurements of surface dose rate distributions discussed in this work demonstrate the successful operation of the measuring setup. Measuring the surface dose rate distribution with a small distance between applicator and detector and with a high density of measuring points results in a complete and gapless coverage of the applicator surface, being capable of distinguishing small sized spots with high activities. The dosimetrical accuracy of the measurements and its analysis is sufficient (uncertainty in the dose rate in terms of absorbed dose to water is <7%), especially when taking the surgical techniques in positioning of the applicator on the eyeball into account. The method developed so far allows a fully automated quality assurance of eye applicators even under clinical conditions. These measurements provide the basis for future calculation of a full 3D dose rate distribution, which then can be used as input for a refined clinical treatment planning system. The improved dose rate measurements will facilitate a clinical study, which could correlate the therapeutic outcome of a brachytherapy treatment with an applicator and its individual dose rate distribution.

The impact of low-Z and high-Z metal implants in IMRT: A Monte Carlo study of dose inaccuracies in commercial dose algorithms

DOE Office of Scientific and Technical Information (OSTI.GOV)

Spadea, Maria Francesca, E-mail: mfspadea@unicz.it; Verburg, Joost Mathias; Seco, Joao

2014-01-15

Purpose: The aim of the study was to evaluate the dosimetric impact of low-Z and high-Z metallic implants on IMRT plans. Methods: Computed tomography (CT) scans of three patients were analyzed to study effects due to the presence of Titanium (low-Z), Platinum and Gold (high-Z) inserts. To eliminate artifacts in CT images, a sinogram-based metal artifact reduction algorithm was applied. IMRT dose calculations were performed on both the uncorrected and corrected images using a commercial planning system (convolution/superposition algorithm) and an in-house Monte Carlo platform. Dose differences between uncorrected and corrected datasets were computed and analyzed using gamma index (Pγ{submore » <1}) and setting 2 mm and 2% as distance to agreement and dose difference criteria, respectively. Beam specific depth dose profiles across the metal were also examined. Results: Dose discrepancies between corrected and uncorrected datasets were not significant for low-Z material. High-Z materials caused under-dosage of 20%–25% in the region surrounding the metal and over dosage of 10%–15% downstream of the hardware. Gamma index test yielded Pγ{sub <1}>99% for all low-Z cases; while for high-Z cases it returned 91% < Pγ{sub <1}< 99%. Analysis of the depth dose curve of a single beam for low-Z cases revealed that, although the dose attenuation is altered inside the metal, it does not differ downstream of the insert. However, for high-Z metal implants the dose is increased up to 10%–12% around the insert. In addition, Monte Carlo method was more sensitive to the presence of metal inserts than superposition/convolution algorithm. Conclusions: The reduction in terms of dose of metal artifacts in CT images is relevant for high-Z implants. In this case, dose distribution should be calculated using Monte Carlo algorithms, given their superior accuracy in dose modeling in and around the metal. In addition, the knowledge of the composition of metal inserts improves the accuracy of the Monte Carlo dose calculation significantly.« less

Development of a high precision dosimetry system for the measurement of surface dose rate distribution for eye applicators

DOE Office of Scientific and Technical Information (OSTI.GOV)

Eichmann, Marion; Fluehs, Dirk; Spaan, Bernhard

2009-10-15

Purpose: The therapeutic outcome of the therapy with ophthalmic applicators is highly dependent on the application of a sufficient dose to the tumor, whereas the dose applied to the surrounding tissue needs to be minimized. The goal for the newly developed apparatus described in this work is the determination of the individual applicator surface dose rate distribution with a high spatial resolution and a high precision in dose rate with respect to time and budget constraints especially important for clinical procedures. Inhomogeneities of the dose rate distribution can be detected and taken into consideration for the treatment planning. Methods: Inmore » order to achieve this, a dose rate profile as well as a surface profile of the applicator are measured and correlated with each other. An instrumental setup has been developed consisting of a plastic scintillator detector system and a newly designed apparatus for guiding the detector across the applicator surface at a constant small distance. It performs an angular movement of detector and applicator with high precision. Results: The measurements of surface dose rate distributions discussed in this work demonstrate the successful operation of the measuring setup. Measuring the surface dose rate distribution with a small distance between applicator and detector and with a high density of measuring points results in a complete and gapless coverage of the applicator surface, being capable of distinguishing small sized spots with high activities. The dosimetrical accuracy of the measurements and its analysis is sufficient (uncertainty in the dose rate in terms of absorbed dose to water is <7%), especially when taking the surgical techniques in positioning of the applicator on the eyeball into account. Conclusions: The method developed so far allows a fully automated quality assurance of eye applicators even under clinical conditions. These measurements provide the basis for future calculation of a full 3D dose rate distribution, which then can be used as input for a refined clinical treatment planning system. The improved dose rate measurements will facilitate a clinical study, which could correlate the therapeutic outcome of a brachytherapy treatment with an applicator and its individual dose rate distribution.« less

Accelerated heavy particles and the lens. VII: The cataractogenic potential of 450 MeV/amu iron ions

NASA Technical Reports Server (NTRS)

Worgul, B. V.; Brenner, D. J.; Medvedovsky, C.; Merriam, G. R. Jr; Huang, Y.

1993-01-01

PURPOSE. To determine the cataractogenic potential dose of high velocity iron ions as a fixation of dose administered singly or fractionated. The dose is critical to risk assessment and to theories of radiation action and cataractogenesis. METHODS. Twenty-eight-day-old rats were examined by slit-lamp biomicroscopy on a weekly-bi-weekly basis for more than 2 yr after radiation exposure. For the acute exposure study doses of 1, 2, 5, 25, and 50 cGy were evaluated. The fractionated regimens involved total doses of 2, 25, and 50 cGy. The reference radiation consisted of 50, 100, 200, or 700 cGy of 250 kilovolt (peak) x-rays. RESULTS. In accordance with previous findings in the rat using 570 MeV/amu 40Ar ions, the relative biologic effectiveness increased rapidly with decreasing dose, reaching values as high as 100. Unlike 40Ar ions, fractionation of the 56Fe doses did not produce a consistent enhancement at any of the doses examined. CONCLUSIONS. The data support the previous findings of a high cataractogenic potential for high linear energy transfer (LET) radiation. The effectiveness for the production of cataracts increases with decreasing dose relative to x-rays and is independent of dose protraction. Although the present study did not reveal a consistent enhancement of effect when the ions were applied in fractions, the results are consistent with at least one theory of the inverse dose-rate effect observed for high-LET radiation.

Childhood Central Nervous System Embryonal Tumors Treatment

MedlinePlus

... lower back is numbed. High-dose chemotherapy with stem cell rescue High-dose chemotherapy with stem cell rescue is a way of giving high doses ... blood -forming cells destroyed by the cancer treatment. Stem cells (immature blood cells) are removed from the blood ...

Antipsychotic doses among community-dwelling persons with Alzheimer disease in Finland.

PubMed

Taipale, Heidi; Koponen, Marjaana; Tanskanen, Antti; Tolppanen, Anna-Maija; Tiihonen, Jari; Hartikainen, Sirpa

2014-08-01

Use of antipsychotics for treatment of behavioral and psychological symptoms of dementia is frequent among persons with Alzheimer disease (AD). Doses used in long-term therapy have not been previously reported. We describe antipsychotic doses used among community-dwelling persons with AD and investigate factors associated with high-dose use. The MEDALZ-2005 (Medication use and Alzheimer disease) cohort is a nationwide sample including all persons with clinically diagnosed AD at the end of year 2005 in Finland (n = 28,093). Data including prescriptions, comorbidities, and hospital discharge diagnoses were collected from nationwide registers. Antipsychotic doses in monotherapy were investigated during 2006 to 2009. Among 8920 antipsychotic users, 4% (n = 336) used antipsychotics with high dose. Typical antipsychotics were more often used with high dose than atypical antipsychotics. High-dose use was associated with younger age (<80 years) (odds ratio [OR], 1.71; 95% confidence interval [CI], 1.36-2.15]), male sex (OR, 1.52; CI, 1.21-1.91), history of psychiatric disorder (OR, 3.25; CI, 2.54-4.15), and inversely associated with Charlson Comorbidity Index score (score 1: OR, 0.74; CI, 0.57-0.97; score ≥2: OR, 0.68; CI, 0.47-0.97). In conclusion, the majority of persons with AD used antipsychotics with low or medium dose. Typical antipsychotics were more often used with high dose than atypical antipsychotics, which indicates a need for precise dosing instructions in the treatment of behavioral and psychological symptoms of dementia. Clinicians should regularly assess dosing levels especially among men and those with history of psychiatric disorder.

Safety of low-dose aspirin in endovascular treatment for intracranial atherosclerotic stenosis.

PubMed

Ma, Ning; Xu, Ziqi; Mo, Dapeng; Gao, Feng; Gao, Kun; Sun, Xuan; Xu, Xiaotong; Liu, Lian; Song, Ligang; Wang, Tiejun; Zhao, Xingquan; Wang, Yilong; Wang, Yongjun; Miao, Zhongrong

2014-01-01

To evaluate the safety of low-dose aspirin plus clopidogrel versus high-dose aspirin plus clopidogrel in prevention of vascular risk within 90 days of duration of dual antiplatelet therapy in patients treated with intracranial endovascular treatment. From January 2012 to December 2013, this prospective and observational study enrolled 370 patients with symptomatic intracranial atherosclerotic stenosis of ≥70% with poor collateral undergoing intracranial endovascular treatment. Antiplatelet therapy consists of aspirin, at a low-dose of 100 mg or high-dose of 300 mg daily; clopidogrel, at a dose of 75 mg daily for 5 days before endovascular treatment. The dual antiplatelet therapy continued for 90 days after intervention. The study endpoints include acute thrombosis, subacute thrombosis, stroke or death within 90 days after intervention. Two hundred and seventy three patients received low-dose aspirin plus clopidogrel and 97 patients received high-dose aspirin plus clopidogrel before intracranial endovascular treatment. Within 90 days after intervention, there were 4 patients (1.5%) with acute thrombosis, 5 patients (1.8%) with subacute thrombosis, 17 patients (6.2%) with stroke, and 2 death (0.7%) in low-dose aspirin group, compared with no patient (0%) with acute thrombosis, 2 patient (2.1%) with subacute thrombosis, 6 patients (6.2%) with stroke, and 2 death (2.1%) in high-dose aspirin group, and there were no significant difference in all study endpoints between two groups. Low-dose aspirin plus clopidogrel is comparative in safety with high-dose aspirin plus clopidogrel within 90 days of duration of dual antiplatelet therapy in patients treated with intracranial endovascular treatment.

Impact of cyclophosphamide dose of conditioning on the outcome of allogeneic hematopoietic stem cell transplantation for aplastic anemia from human leukocyte antigen-identical sibling.

PubMed

Mori, Takehiko; Koh, Hideo; Onishi, Yasushi; Kako, Shinichi; Onizuka, Makoto; Kanamori, Heiwa; Ozawa, Yukiyasu; Kato, Chiaki; Iida, Hiroatsu; Suzuki, Ritsuro; Ichinohe, Tatsuo; Kanda, Yoshinobu; Maeda, Tetsuo; Nakao, Shinji; Yamazaki, Hirohito

2016-04-01

The standard conditioning regimen in allogeneic hematopoietic stem cell transplantation (HSCT) for aplastic anemia from a human leukocyte antigen (HLA)-identical sibling has been high-dose cyclophosphamide (CY 200 mg/kg). In the present study, results for 203 patients with aplastic anemia aged 16 years or older who underwent allogeneic HSCT from HLA-identical siblings were retrospectively analyzed using the registry database of Japan Society for Hematopoietic Cell Transplantation. Conditioning regimens were defined as a (1) high-dose CY (200 mg/kg or greater)-based (n = 117); (2) reduced-dose CY (100 mg/kg or greater, but less than 200 mg/kg)-based (n = 38); and (3) low-dose CY (less than 100 mg/kg)-based (n = 48) regimen. Patient age and the proportion of patients receiving fludarabine were significantly higher in the reduced- and low-dose CY groups than the high-dose CY group. Engraftment was comparable among the groups. Five-year overall survival (OS) tended to be higher in the low-dose CY group [93.0 % (95 % CI 85.1-100.0 %)] than the high-dose CY [84.2 % (95 % CI 77.1-91.3 %)] or reduced-dose CY groups [83.8 % (95 % CI 71.8-95.8 %); P = 0.214]. Age-adjusted OS was higher in the low-dose CY group than the high- and reduced-dose CY groups with borderline significance (P = 0.067). These results suggest that CY dose can safely be reduced without increasing graft rejection by adding fludarabine in allogeneic HSCT for aplastic anemia from an HLA-identical sibling.

Plasma Doping—Enabling Technology for High Dose Logic and Memory Applications

NASA Astrophysics Data System (ADS)

Miller, T.; Godet, L.; Papasouliotis, G. D.; Singh, V.

2008-11-01

As logic and memory device dimensions shrink with each generation, there are more high dose implants at lower energies. Examples include dual poly gate (also referred to as counter-doped poly), elevated source drain and contact plug implants. Plasma Doping technology throughput and dopant profile benefits at these ultra high dose and lower energy conditions have been well established [1,2,3]. For the first time a production-worthy plasma doping implanter, the VIISta PLAD tool, has been developed with unique architecture suited for precise and repeatable dopant placement. Critical elements of the architecture include pulsed DC wafer bias, closed-loop dosimetry and a uniform low energy, high density plasma source. In this paper key performance metrics such as dose uniformity, dose repeatability and dopant profile control will be presented that demonstrate the production-worthiness of the VIISta PLAD tool for several high dose applications.

Single high-dose irradiation aggravates eosinophil-mediated fibrosis through IL-33 secreted from impaired vessels in the skin compared to fractionated irradiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, Eun-Jung, E-mail: forejs2@yuhs.ac; Kim, Jun Won, E-mail: JUNWON@yuhs.ac; Yoo, Hyun, E-mail: gochunghee@yuhs.ac

We have revealed in a porcine skin injury model that eosinophil recruitment was dose-dependently enhanced by a single high-dose irradiation. In this study, we investigated the underlying mechanism of eosinophil-associated skin fibrosis and the effect of high-dose-per-fraction radiation. The dorsal skin of a mini-pig was divided into two sections containing 4-cm{sup 2} fields that were irradiated with 30 Gy in a single fraction or 5 fractions and biopsied regularly over 14 weeks. Eosinophil-related Th2 cytokines such as interleukin (IL)-4, IL-5, and C–C motif chemokine-11 (CCL11/eotaxin) were evaluated by quantitative real-time PCR. RNA-sequencing using 30 Gy-irradiated mouse skin and functional assays in amore » co-culture system of THP-1 and irradiated-human umbilical vein endothelial cells (HUVECs) were performed to investigate the mechanism of eosinophil-mediated radiation fibrosis. Single high-dose-per-fraction irradiation caused pronounced eosinophil accumulation, increased profibrotic factors collagen and transforming growth factor-β, enhanced production of eosinophil-related cytokines including IL-4, IL-5, CCL11, IL-13, and IL-33, and reduced vessels compared with 5-fraction irradiation. IL-33 notably increased in pig and mouse skin vessels after single high-dose irradiation of 30 Gy, as well as in irradiated HUVECs following 12 Gy. Blocking IL-33 suppressed the migration ability of THP-1 cells and cytokine secretion in a co-culture system of THP-1 cells and irradiated HUVECs. Hence, high-dose-per-fraction irradiation appears to enhance eosinophil-mediated fibrotic responses, and IL-33 may be a key molecule operating in eosinophil-mediated fibrosis in high-dose-per fraction irradiated skin. - Highlights: • Single high-dose irradiation aggravates eosinophil-mediated fibrosis through IL-33. • Vascular endothelial cells damaged by high-dose radiation secrete IL-33. • Blocking IL-33 suppressed migration of inflammatory cells and cytokine secretion. • IL-33 is a key in eosinophil-mediated fibrosis in high-dose-per-fraction radiation.« less

High-dose MVCT image guidance for stereotactic body radiation therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Westerly, David C.; Schefter, Tracey E.; Kavanagh, Brian D.

Purpose: Stereotactic body radiation therapy (SBRT) is a potent treatment for early stage primary and limited metastatic disease. Accurate tumor localization is essential to administer SBRT safely and effectively. Tomotherapy combines helical IMRT with onboard megavoltage CT (MVCT) imaging and is well suited for SBRT; however, MVCT results in reduced soft tissue contrast and increased image noise compared with kilovoltage CT. The goal of this work was to investigate the use of increased imaging doses on a clinical tomotherapy machine to improve image quality for SBRT image guidance. Methods: Two nonstandard, high-dose imaging modes were created on a tomotherapy machinemore » by increasing the linear accelerator (LINAC) pulse rate from the nominal setting of 80 Hz, to 160 Hz and 300 Hz, respectively. Weighted CT dose indexes (wCTDIs) were measured for the standard, medium, and high-dose modes in a 30 cm solid water phantom using a calibrated A1SL ion chamber. Image quality was assessed from scans of a customized image quality phantom. Metrics evaluated include: contrast-to-noise ratios (CNRs), high-contrast spatial resolution, image uniformity, and percent image noise. In addition, two patients receiving SBRT were localized using high-dose MVCT scans. Raw detector data collected after each scan were used to reconstruct standard-dose images for comparison. Results: MVCT scans acquired using a pitch of 1.0 resulted in wCTDI values of 2.2, 4.7, and 8.5 cGy for the standard, medium, and high-dose modes respectively. CNR values for both low and high-contrast materials were found to increase with the square root of dose. Axial high-contrast spatial resolution was comparable for all imaging modes at 0.5 lp/mm. Image uniformity was improved and percent noise decreased as the imaging dose increased. Similar improvements in image quality were observed in patient images, with decreases in image noise being the most notable. Conclusions: High-dose imaging modes are made possible on a clinical tomotherapy machine by increasing the LINAC pulse rate. Increasing the imaging dose results in increased CNRs; making it easier to distinguish the boundaries of low contrast objects. The imaging dose levels observed in this work are considered acceptable at our institution for SBRT treatments delivered in 3-5 fractions.« less

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

PubMed

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

2012-08-01

Stereotactic body radiation therapy (SBRT) is a potent treatment for early stage primary and limited metastatic disease. Accurate tumor localization is essential to administer SBRT safely and effectively. Tomotherapy combines helical IMRT with onboard megavoltage CT (MVCT) imaging and is well suited for SBRT; however, MVCT results in reduced soft tissue contrast and increased image noise compared with kilovoltage CT. The goal of this work was to investigate the use of increased imaging doses on a clinical tomotherapy machine to improve image quality for SBRT image guidance. Two nonstandard, high-dose imaging modes were created on a tomotherapy machine by increasing the linear accelerator (LINAC) pulse rate from the nominal setting of 80 Hz, to 160 Hz and 300 Hz, respectively. Weighted CT dose indexes (wCTDIs) were measured for the standard, medium, and high-dose modes in a 30 cm solid water phantom using a calibrated A1SL ion chamber. Image quality was assessed from scans of a customized image quality phantom. Metrics evaluated include: contrast-to-noise ratios (CNRs), high-contrast spatial resolution, image uniformity, and percent image noise. In addition, two patients receiving SBRT were localized using high-dose MVCT scans. Raw detector data collected after each scan were used to reconstruct standard-dose images for comparison. MVCT scans acquired using a pitch of 1.0 resulted in wCTDI values of 2.2, 4.7, and 8.5 cGy for the standard, medium, and high-dose modes respectively. CNR values for both low and high-contrast materials were found to increase with the square root of dose. Axial high-contrast spatial resolution was comparable for all imaging modes at 0.5 lp∕mm. Image uniformity was improved and percent noise decreased as the imaging dose increased. Similar improvements in image quality were observed in patient images, with decreases in image noise being the most notable. High-dose imaging modes are made possible on a clinical tomotherapy machine by increasing the LINAC pulse rate. Increasing the imaging dose results in increased CNRs; making it easier to distinguish the boundaries of low contrast objects. The imaging dose levels observed in this work are considered acceptable at our institution for SBRT treatments delivered in 3-5 fractions.

Increased anxiety 3 months after brief exposure to MDMA ("Ecstasy") in rats: association with altered 5-HT transporter and receptor density.

PubMed

McGregor, Iain S; Clemens, Kelly J; Van der Plasse, Geoffrey; Li, Kong M; Hunt, Glenn E; Chen, Feng; Lawrence, Andrew J

2003-08-01

Male Wistar rats were treated with 3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy") using either a high dose (4 x 5 mg/kg over 4 h) or low dose (1 x 5 mg/kg over 4 h) regimen on each of 2 consecutive days. After 10 weeks, rats were tested in the social interaction and emergence tests of anxiety. Rats previously given either of the MDMA dose regimens were significantly more anxious on both tests. After behavioral testing, and 3 months after the MDMA treatment, the rats were killed and their brains examined. Rats given the high-, but not the low-, dose MDMA treatment regimen exhibited significant loss of 5-hydroxytryptamine (5-HT) and 5-HIAA in the amygdala, hippocampus, striatum, and cortex. Quantitative autoradiography showed loss of SERT binding in cortical, hippocampal, thalamic, and hypothalamic sites with the high-dose MDMA regime, while low-dose MDMA only produced significant loss in the medial hypothalamus. Neither high- nor low-dose MDMA affected 5HT(1A) receptor density. High-dose MDMA increased 5HT(1B) receptor density in the nucleus accumbens and lateral septum but decreased binding in the globus pallidus, insular cortex and medial thalamus. Low-dose MDMA decreased 5HT(1B) receptor density in the hippocampus, globus pallidus, and medial thalamus. High-dose MDMA caused dramatic decreases in cortical, striatal, thalamic, and hypothalamic 5HT(2A)/(2C) receptor density, while low-dose MDMA tended to produce similar effects but only significantly in the piriform cortex. These data suggest that even brief, relatively low-dose MDMA exposure can produce significant, long-term changes in 5-HT receptor and transporter function and associated emotional behavior. Interestingly, long-term 5-HT depletion may not be necessary to produce lasting effects on anxiety-like behavior after low-dose MDMA.

Dexamethasone and High-Dose Methotrexate Improve Outcome for Children and Young Adults With High-Risk B-Acute Lymphoblastic Leukemia: A Report From Children’s Oncology Group Study AALL0232

PubMed Central

Devidas, Meenakshi; Chen, Si; Salzer, Wanda L.; Raetz, Elizabeth A.; Loh, Mignon L.; Mattano, Leonard A.; Cole, Catherine; Eicher, Alisa; Haugan, Maureen; Sorenson, Mark; Heerema, Nyla A.; Carroll, Andrew A.; Gastier-Foster, Julie M.; Borowitz, Michael J.; Wood, Brent L.; Willman, Cheryl L.; Winick, Naomi J.; Hunger, Stephen P.; Carroll, William L.

2016-01-01

Purpose Survival for children and young adults with high-risk B-acute lymphoblastic leukemia has improved significantly, but 20% to 25% of patients are not cured. Children’s Oncology Group study AALL0232 tested two interventions to improve survival. Patients and Methods Between January 2004 and January 2011, AALL0232 enrolled 3,154 participants 1 to 30 years old with newly diagnosed high-risk B-acute lymphoblastic leukemia. By using a 2 × 2 factorial design, 2,914 participants were randomly assigned to receive dexamethasone (14 days) versus prednisone (28 days) during induction and high-dose methotrexate versus Capizzi escalating-dose methotrexate plus pegaspargase during interim maintenance 1. Results Planned interim monitoring showed the superiority of the high-dose methotrexate regimens, which exceeded the predefined boundary and led to cessation of enrollment in January 2011. At that time, participants randomly assigned to high-dose methotrexate during interim maintenance 1 versus those randomly assigned to Capizzi methotrexate had a 5-year event-free survival (EFS) of 82% versus 75.4% (P = .006). Mature final data showed 5-year EFS rates of 79.6% for high-dose methotrexate and 75.2% for Capizzi methotrexate (P = .008). High-dose methotrexate decreased both marrow and CNS recurrences. Patients 1 to 9 years old who received dexamethasone and high-dose methotrexate had a superior outcome compared with those who received the other three regimens (5-year EFS, 91.2% v 83.2%, 80.8%, and 82.1%; P = .015). Older participants derived no benefit from dexamethasone during induction and experienced excess rates of osteonecrosis. Conclusion High-dose methotrexate is superior to Capizzi methotrexate for the treatment of high-risk B-acute lymphoblastic leukemia, with no increase in acute toxicity. Dexamethasone given during induction benefited younger children but provided no benefit and was associated with a higher risk of osteonecrosis among participants 10 years and older. PMID:27114587

Axillofemoral Bypass Markedly Improved Acute Decompensated Heart Failure and Kidney Injury in a Patient with Severely Calcified Stenosis of Thoracoabdominal Aorta (Atypical Aortic Coarctation).

PubMed

Ishizuka, Masato; Yamada, Shintaro; Maemura, Sonoko; Yamamoto, Keisuke; Takizawa, Masataka; Uozumi, Hiroki; Minegishi, Sachito; Kobayashi, Jotaro; Ikenouchi, Hiroshi

2017-10-21

Atypical aortic coarctation (AAC) has been reported to occur anywhere along the aorta, except for the ascending aorta. The associated symptoms include hypotension in the lower half of the body, secondary hypertension in the upper half of the body, and heart failure. Here we present an 80-year-old Asian woman complaining of progressive exertional dyspnea. She was diagnosed with acute decompensated heart failure and kidney injury due to severely calcified stenosis of the thoracoabdominal aorta, the so called AAC. She received hemodiafiltration, and pulmonary congestion improved in part. Generally, surgical treatments are quite invasive in elderly patients. Endovascular stent graft placement is less invasive, however, fracture and rupture should be considered at severely calcified lesions like this case. Therefore, we selected extra-anatomical axillofemoral bypass. Her recovery after the surgery was remarkable. In a few days, she became free from hemodiafiltration, intravenous diuretics, and oxygen administration. We thought the contributive factors are the increase in kidney blood flow and the correction of afterload mismatch. The decrease in pulse pressure may reflect the reduction in systemic arterial compliance by axillofemoral bypass. The operative mortality of axillofemoral bypass was reported to be acceptable, although the patency of the axillofemoral bypass graft was not high enough. In conclusion, axillofemoral bypass is effective and feasible for elderly patients with acute decompensated heart failure and kidney injury due to AAC.

Effects of the Mueller maneuver on functional mitral regurgitation and implications for obstructive sleep apnea.

PubMed

Pressman, Gregg S; Orban, Marek; Leinveber, Pavel; Parekh, Kunal; Singh, Manmeet; Kara, Tomas; Somers, Virend K

2015-06-01

Obstructive sleep apnea is prevalent and adversely affects cardiovascular health. However, little is known of the acute effects of an obstructive apnea on cardiovascular physiology. We hypothesized that pre-existing functional mitral regurgitation (MR) would worsen during performance of a Mueller maneuver (MM) used to simulate an obstructive apnea; 15 subjects with an ejection fraction ≤35% and pre-existing functional MR were studied with Doppler echocardiography. The radius of the proximal flow convergence was used as a measure of mitral regurgitant flow. Measurements were made at baseline, during the MM, and post-MM. Areas of all 4 chambers were also measured at these time points, both in systole and diastole. Mean flow convergence radius for the group decreased significantly during the transition from the late-MM to post-MM (0.65 → 0.57 mm, p = 0.001), implying increased MR during the MM. In addition, in 3 subjects, duration of MR increased during the MM. Right atrial (RA) areas, both systolic and diastolic, increased during the maneuver, whereas RA fractional area change decreased, indicating reduced RA emptying. Left ventricular emptying decreased early in the maneuver, probably because of the increased afterload burden, and then recovered. In conclusion, high negative intrathoracic pressure produces changes that, repeated hundreds of times per night in patients with obstructive sleep apnea, have the potential to worsen heart failure and predispose affected subjects to atrial fibrillation. Copyright © 2015 Elsevier Inc. All rights reserved.

Effects of the Mueller Maneuver on Functional Mitral Regurgitation and Implications for Obstructive Sleep Apnea

PubMed Central

Pressman, Gregg S.; Orban, Marek; Leinveber, Pavel; Parekh, Kunal; Singh, Manmeet; Kara, Tomas; Somers, Virend K.

2016-01-01

Obstructive sleep apnea (OSA) is prevalent and adversely impacts cardiovascular health. However, little is known of the acute effects of an obstructive apnea on cardiovascular physiology. We hypothesized that pre-existing functional mitral regurgitation (MR) would worsen during performance of a Mueller maneuver (MM) used to simulate an obstructive apnea. 15 subjects with an ejection fraction ≤35% and pre-existing functional MR were studied with Doppler echocardiography. The radius of the proximal flow convergence was used as a measure of mitral regurgitant flow. Measurements were made at baseline, during the MM, and post-MM. Areas of all 4 chambers were also measured at these time points, both in systole and diastole. Mean flow convergence radius for the group decreased significantly during the transition from the late-MM to post-MM (0.65 mm → 0.57 mm, p = 0.001), implying increased MR during the MM. In addition, in 3 subjects duration of MR increased during the MM. Right atrial (RA) areas, both systolic and diastolic, increased during the maneuver while RA fractional area change decreased, indicating reduced RA emptying. Left ventricular (LV) emptying decreased early in the maneuver, probably due to the increased afterload burden, and then recovered. In conclusion, high negative intrathoracic pressure produces changes which, repeated hundreds of times per night in OSA patients, have the potential to worsen heart failure and predispose affected individuals to atrial fibrillation. PMID:25846766

Altered Redox Balance in the Development of Chronic Hypoxia-induced Pulmonary Hypertension.

PubMed

Jernigan, Nikki L; Resta, Thomas C; Gonzalez Bosc, Laura V

2017-01-01

Normally, the pulmonary circulation is maintained in a low-pressure, low-resistance state with little resting tone. Pulmonary arteries are thin-walled and rely heavily on pulmonary arterial distension and recruitment for reducing pulmonary vascular resistance when cardiac output is elevated. Under pathophysiological conditions, however, active vasoconstriction and vascular remodeling lead to enhanced pulmonary vascular resistance and subsequent pulmonary hypertension (PH). Chronic hypoxia is a critical pathological factor associated with the development of PH resulting from airway obstruction (COPD, sleep apnea), diffusion impairment (interstitial lung disease), developmental lung abnormalities, or high altitude exposure (World Health Organization [WHO]; Group III). The rise in pulmonary vascular resistance increases right heart afterload causing right ventricular hypertrophy that can ultimately lead to right heart failure in patients with chronic lung disease. PH is typically characterized by diminished paracrine release of vasodilators, antimitogenic factors, and antithrombotic factors (e.g., nitric oxide and protacyclin) and enhanced production of vasoconstrictors and mitogenic factors (e.g., reactive oxygen species and endothelin-1) from the endothelium and lung parenchyma. In addition, phenotypic changes to pulmonary arterial smooth muscle cells (PASMC), including alterations in Ca 2+ homeostasis, Ca 2+ sensitivity, and activation of transcription factors are thought to play prominent roles in the development of both vasoconstrictor and arterial remodeling components of hypoxia-associated PH. These changes in PASMC function are briefly reviewed in Sect. 1 and the influence of altered reactive oxygen species homeostasis on PASMC function discussed in Sects. 2-4.

Management of renal artery stenosis - an update.

PubMed

Alhadad, A

2008-06-01

The role of the renal vasculature in eliciting renovascular hypertension (RVH) was established in 1934, when Goldblatt et al. [1] in a classical experimental study demonstrated that partial obstruction of the renal artery increased mean arterial blood pressure (BP). The pathophysiology of renal artery stenosis (RAS) is incompletely understood but has been postulated to be related to increased afterload from neurohormonal activation and cytokine release [2]. Atherosclerotic RAS (ARAS) is increasingly diagnosed in the expanding elderly population, which also has a high prevalence of arterial hypertension. There is still considerable uncertainty concerning the optimal management of patients with RAS. Many hypertensive patients with RAS have co-existing essential hypertension and furthermore, it is often difficult to determine to what degree the RAS is responsible for the impairment of renal function. There are three possible treatment strategies: medical management, surgery, or percutaneous transluminal renal angioplasty (PTRA) with or without stent implantation. The use of stents has improved the technical success rate of PTRA and also led to lower risk of restenosis, in particular for ostial RAS. PTRA with stenting has therefore replaced surgical revascularisation for most patients with RAS and has led to a lower threshold for intervention. The treatment of choice to control hypertension in fibromuscular dysplasia (FMD) is generally accepted to be PTRA [3]. In ARAS, on the other hand, the benefits with PTRA are less clear [4] and the challenge to identify which patients are likely to benefit from revascularisation remains unknown.

Influence of nonylphenol and octylphenol exposure on 5-HT, 5-HT transporter, and 5-HT2A receptor.

PubMed

Liu, Chunhong; Lai, Yuting; Ouyang, Junyan; Yang, Tongwang; Guo, Youting; Yang, Jie; Huang, Shaowen

2017-03-01

Nonylphenol (NP) and octylphenol (OP) are priority environmental contaminants that have a potential role as endocrine disruptors. They can be biomagnified in the food chain and pose an estrogenic health risk to human health. A 28-day oral toxicity study was performed to observe the impact of single and combined exposure to NP and OP on 5-HT transporter (SERT) as well as 5-HT 2A receptor. Results showed that the 5-HT levels in rat plasma increased with exposure to middle-dose and high-dose NP, to high-dose OP, and to low, middle, and high doses of combined NP and OP (P < 0.05), while the 5-HT levels in rat platelets increased when exposed to NP/OP or combined NP and OP of middle or high dose (P < 0.05). The expression levels of SERT in rat platelets decreased when exposed to high-dose NP/OP or high dose of combined NP and OP (P < 0.05). Meanwhile, the expression levels of 5-HT 2A in rat platelets decreased when exposed to high-dose NP/OP as well as combined NP and OP (P < 0.05). These findings suggested that exposure to NP and OP could influence the metabolic network of 5-hydroxytryptamine via transportation and receptor binding pathways.

High-dose prazosin for the treatment of post-traumatic stress disorder

PubMed Central

Koola, Maju Mathew; Fawcett, Jan A.

2014-01-01

Patients with post-traumatic stress disorder (PTSD) are frequently symptomatic despite being on medications currently approved by the US Food and Drug Administration for PTSD. There is evidence to support the notion that prazosin is effective for PTSD nightmares. However, PTSD-related nightmares often do not resolve completely on a low dose of prazosin. The capacity of prazosin to treat daytime symptoms of PTSD which are distressing to patients has not been well studied. Clinicians are reluctant to increase the dose of prazosin due to side effect concerns. To date, the highest reported dose of prazosin used for PTSD is 16 mg daily. We illustrate two case reports using high-dose (up to 30 and 45 mg) prazosin for PTSD with comorbid treatment-resistant mood disorders. We report that high-dose prazosin was safe, tolerable and effective for PTSD in adults. To our knowledge, this is the first case series to highlight the importance of using high-dose prazosin for the treatment of PTSD. In patients with partial response to currently available medications for PTSD, greater utilization of high-dose prazosin for the management of PTSD may lead to better outcomes. PMID:24490030

The susceptibility of TaO x-based memristors to high dose rate ionizing radiation and total ionizing dose

DOE PAGES

McLain, Michael Lee; Sheridan, Timothy J.; Hjalmarson, Harold Paul; ...

2014-11-11

This paper investigates the effects of high dose rate ionizing radiation and total ionizing dose (TID) on tantalum oxide (TaO x) memristors. Transient data were obtained during the pulsed exposures for dose rates ranging from approximately 5.0 ×10 7 rad(Si)/s to 4.7 ×10 8 rad(Si)/s and for pulse widths ranging from 50 ns to 50 μs. The cumulative dose in these tests did not appear to impact the observed dose rate response. Static dose rate upset tests were also performed at a dose rate of ~3.0 ×10 8 rad(Si)/s. This is the first dose rate study on any type ofmore » memristive memory technology. In addition to assessing the tolerance of TaO x memristors to high dose rate ionizing radiation, we also evaluated their susceptibility to TID. The data indicate that it is possible for the devices to switch from a high resistance off-state to a low resistance on-state in both dose rate and TID environments. The observed radiation-induced switching is dependent on the irradiation conditions and bias configuration. Furthermore, the dose rate or ionizing dose level at which a device switches resistance states varies from device to device; the enhanced susceptibility observed in some devices is still under investigation. As a result, numerical simulations are used to qualitatively capture the observed transient radiation response and provide insight into the physics of the induced current/voltages.« less

Lung dose and the potential risk of death in postoperative radiation therapy for non-small cell lung cancer: A study using the method of stratified grouping.

PubMed

Heo, Jaesung; Noh, O Kyu; Kim, Hwan-Ik; Chun, Mison; Cho, Oyeon; Park, Rae Woong; Yoon, Dukyong; Oh, Young-Taek

2018-04-19

Postoperative radiation therapy may have a detrimental effect on survival in patients with non-small cell lung cancer. We investigated the association of the lung radiation dose with the risk of death in patients treated with postoperative radiation therapy. We analyzed 178 patients with non-small cell lung cancer who received postoperative radiation therapy. The mean lung dose was calculated from dose-volume data, and we categorized patients into the high and low lung dose groups using 2 different methods; (1) simple grouping using the median lung dose of all patients, and (2) stratified grouping using the median lung dose of each subgroup sharing the same confounders. We compared clinical variables, and survival between the high and low lung dose groups. In the simple grouping, there were no significant differences in survivals between the high and low lung dose groups. After stratification, the overall survival of low lung dose group was significantly longer than that of high lung dose group (5-year survival, 60.1% vs. 35.3%, p = 0.039). On multivariable analyses, the lung dose remained a significant prognostic factor for overall survival (hazard ratio, HR = 2.08, p = 0.019). The lung dose was associated with the risk of death in patients with non-small cell lung cancer having the same confounders. Further studies evaluating the risk of death according to the lung dose will be helpful to administer more precise and individualized postoperative radiation therapy. Copyright © 2018 Elsevier B.V. All rights reserved.

Iterative reconstruction for CT perfusion with a prior-image induced hybrid nonlocal means regularization: Phantom studies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Bin; Lyu, Qingwen; Ma, Jianhua

2016-04-15

Purpose: In computed tomography perfusion (CTP) imaging, an initial phase CT acquired with a high-dose protocol can be used to improve the image quality of later phase CT acquired with a low-dose protocol. For dynamic regions, signals in the later low-dose CT may not be completely recovered if the initial CT heavily regularizes the iterative reconstruction process. The authors propose a hybrid nonlocal means (hNLM) regularization model for iterative reconstruction of low-dose CTP to overcome the limitation of the conventional prior-image induced penalty. Methods: The hybrid penalty was constructed by combining the NLM of the initial phase high-dose CT inmore » the stationary region and later phase low-dose CT in the dynamic region. The stationary and dynamic regions were determined by the similarity between the initial high-dose scan and later low-dose scan. The similarity was defined as a Gaussian kernel-based distance between the patch-window of the same pixel in the two scans, and its measurement was then used to weigh the influence of the initial high-dose CT. For regions with high similarity (e.g., stationary region), initial high-dose CT played a dominant role for regularizing the solution. For regions with low similarity (e.g., dynamic region), the regularization relied on a low-dose scan itself. This new hNLM penalty was incorporated into the penalized weighted least-squares (PWLS) for CTP reconstruction. Digital and physical phantom studies were performed to evaluate the PWLS-hNLM algorithm. Results: Both phantom studies showed that the PWLS-hNLM algorithm is superior to the conventional prior-image induced penalty term without considering the signal changes within the dynamic region. In the dynamic region of the Catphan phantom, the reconstruction error measured by root mean square error was reduced by 42.9% in PWLS-hNLM reconstructed image. Conclusions: The PWLS-hNLM algorithm can effectively use the initial high-dose CT to reconstruct low-dose CTP in the stationary region while reducing its influence in the dynamic region.« less

Pilot Study: Unique Response of Bone Tissue During an Investigation of Radio-Adaptive Effects in Mice

NASA Technical Reports Server (NTRS)

Sibonga, J. D.; Iwaniec, U.; Wu, H.

2011-01-01

PURPOSE: We obtained bone tissue to evaluate the collateral effects of experiments designed to investigate molecular mechanisms of radio-adaptation in a mouse model. Radio-adaptation describes a process by which the prior exposure to low dose radiation can protect against the toxic effect of a subsequent high dose exposure. In the radio-adaptation experiments, C57Bl/6 mice were exposed to either a Sham or a priming Low Dose (5 cGy) of Cs-137 gamma rays before being exposed to either a Sham or High Dose (6 Gy) 24 hours later. ANALYSIS: Bone tissue were obtained from two experiments where mice were sacrificed at 3 days (n=3/group, 12 total) and at 14 days (n=6/group, 24 total) following high dose exposure. Tissues were analyzed to 1) evaluate a radio-adaptive response in bone tissue and 2) describe cellular and microstructural effects for two skeletal sites with different rates of bone turnover. One tibia and one lumbar vertebrae (LV2), collected at the 3-day time-point, were analyzed by bone histomorphometry and micro-CT to evaluate the cellular response and any evidence of microarchitectural impact. Likewise, tibia and LV2, collected at the 14-day time-point, were analyzed by micro-CT alone to evaluate resulting changes to bone structure and microarchitecture. The data were analyzed by 2-way ANOVA to evaluate the effects of the priming low dose radiation, of the high dose radiation, and of any interaction between the priming low and high doses of radiation. Bone histomorphometry was performed in the cancellous bone (aka trabecular bone) compartments of the proximal tibial metaphysis and of LV2. RESULTS: Cellular Response @ 3 Days The priming Low Dose radiation decreased osteoblast-covered bone perimeter in the proximal tibia and the total cell density in the bone marrow in the LV2. High Dose radiation, regardless of prior exposure to priming dose, dramatically reduced total cell density in bone marrow of both the long bone and vertebra. However, in the proximal tibia, High Dose radiation increased the osteoclast-covered bone perimeters, the density of adipocytes in bone marrow, and the area of bone marrow occupied by fat cells -- while in the LV2, adipocytes were rare and not stimulated by High Dose radiation. In an unexpected response, High Dose radiation dramatically increased (10-fold) osteoblast-covered bone perimeter in the LV2.

Dramatic response to high-dose icotinib in a lung adenocarcinoma patient after erlotinib failure.

PubMed

Guan, Yin; Zhao, Hong; Meng, Jing; Yan, Xiang; Jiao, ShunChang

2014-02-01

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) retreatment is rarely administered for non-small cell lung cancer (NSCLC) patients who did not respond to previous TKI treatment. A high dose of TKI may overcome resistance to the standard dose of TKI and have different effectiveness toward cancer compared with the standard dose of TKI. This manuscript describes a dramatic and durable response to high-dose icotinib in a NSCLC patient who did not respond to a previous standard dose of erlotinib. The treatment extended the life of the patient for one additional year. A higher dose of icotinib deserves further study not only for patients whose therapy failed with the standard dose of TKI but also for newly diagnosed NSCLC patients with a sensitive mutation. Serial mutation testing during disease development is necessary for analysis and evaluation of EGFR TKI treatment. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Comparison in vivo Study of Genotoxic Action of High- Versus Very Low Dose-Rate γ-Irradiation

PubMed Central

Osipov, A. N.; Klokov, D. Y.; Elakov, A. L.; Rozanova, O. M.; Zaichkina, S. I.; Aptikaeva, G. F.; Akhmadieva, A. Kh.

2004-01-01

The aim of the present study was to compare genotoxicity induced by high- versus very low dose-rate exposure of mice to γ-radiation within a dose range of 5 to 61 cGy using the single-cell gel electrophoresis (comet) assay and the micronucleus test. CBA/lac male mice were irradiated at a dose rate of 28.2 Gy/h (high dose rate) or 0.07 mGy/h (very low dose rate). The comet assay study on spleen lymphocytes showed that very low dose-rate irradiation resulted in a statistically significant increase in nucleoid relaxation (DNA breaks), starting from a dose of 20 cGy. Further prolongation of exposure time and, hence, increase of a total dose did not, however, lead to further increase in the extent of nucleoid relaxation. Doses of 20 and 61 cGy were equal in inducing DNA breaks in mouse spleen lymphocytes as assayed by the comet assay. Of note, the level of DNA damage by 20–61 cGy doses of chronic irradiation (0.07 mGy/h) was similar to that an induced by an acute (28.2 Gy/h) dose of 14 cGy. The bone marrow micronucleus test revealed that an increase in polychromatic erythrocytes with micronuclei over a background level was induced by very low-level γ-irradiation with a dose of 61 cGy only, with the extent of the cytogenetic effect being similar to that of 10 cGy high-dose-rate exposure. In summary, presented results support the hypothesis of the nonlinear threshold nature of mutagenic action of chronic low dose-rate irradiation. PMID:19330145

Towards more reliable automated multi-dose dispensing: retrospective follow-up study on medication dose errors and product defects.

PubMed

Palttala, Iida; Heinämäki, Jyrki; Honkanen, Outi; Suominen, Risto; Antikainen, Osmo; Hirvonen, Jouni; Yliruusi, Jouko

2013-03-01

To date, little is known on applicability of different types of pharmaceutical dosage forms in an automated high-speed multi-dose dispensing process. The purpose of the present study was to identify and further investigate various process-induced and/or product-related limitations associated with multi-dose dispensing process. The rates of product defects and dose dispensing errors in automated multi-dose dispensing were retrospectively investigated during a 6-months follow-up period. The study was based on the analysis of process data of totally nine automated high-speed multi-dose dispensing systems. Special attention was paid to the dependence of multi-dose dispensing errors/product defects and pharmaceutical tablet properties (such as shape, dimensions, weight, scored lines, coatings, etc.) to profile the most suitable forms of tablets for automated dose dispensing systems. The relationship between the risk of errors in dose dispensing and tablet characteristics were visualized by creating a principal component analysis (PCA) model for the outcome of dispensed tablets. The two most common process-induced failures identified in the multi-dose dispensing are predisposal of tablet defects and unexpected product transitions in the medication cassette (dose dispensing error). The tablet defects are product-dependent failures, while the tablet transitions are dependent on automated multi-dose dispensing systems used. The occurrence of tablet defects is approximately twice as common as tablet transitions. Optimal tablet preparation for the high-speed multi-dose dispensing would be a round-shaped, relatively small/middle-sized, film-coated tablet without any scored line. Commercial tablet products can be profiled and classified based on their suitability to a high-speed multi-dose dispensing process.

Different dose rate-dependent responses of human melanoma cells and fibroblasts to low dose fast neutrons.

PubMed

Dionet, Claude; Müller-Barthélémy, Melanie; Marceau, Geoffroy; Denis, Jean-Marc; Averbeck, Dietrich; Gueulette, John; Sapin, Vincent; Pereira, Bruno; Tchirkov, Andrei; Chautard, Emmanuel; Verrelle, Pierre

2016-09-01

To analyze the dose rate influence in hyper-radiosensitivity (HRS) of human melanoma cells to very low doses of fast neutrons and to compare to the behaviour of normal human skin fibroblasts. We explored different neutron dose rates as well as possible implication of DNA double-strand breaks (DSB), apoptosis, and energy-provider adenosine-triphosphate (ATP) levels during HRS. HRS in melanoma cells appears only at a very low dose rate (VLDR), while a high dose rate (HDR) induces an initial cell-radioresistance (ICRR). HRS does not seem to be due either to DSB or to apoptosis. Both phenomena (HRS and ICRR) appear to be related to ATP availability for triggering cell repair. Fibroblast survival after neutron irradiation is also dose rate-dependent but without HRS. Melanoma cells or fibroblasts exert their own survival behaviour at very low doses of neutrons, suggesting that in some cases there is a differential between cancer and normal cells radiation responses. Only the survival of fibroblasts at HDR fits the linear no-threshold model. This new insight into human cell responses to very low doses of neutrons, concerns natural radiations, surroundings of accelerators, proton-therapy devices, flights at high altitude. Furthermore, ATP inhibitors could increase HRS during high-linear energy transfer (high-LET) irradiation.

Relationship between high daily erythemal UV doses, total ozone, surface albedo and cloudiness: An analysis of 30 years of data from Switzerland and Austria

NASA Astrophysics Data System (ADS)

Rieder, H. E.; Staehelin, J.; Weihs, P.; Vuilleumier, L.; Maeder, J. A.; Holawe, F.; Blumthaler, M.; Lindfors, A.; Peter, T.; Simic, S.; Spichtinger, P.; Wagner, J. E.; Walker, D.; Ribatet, M.

2010-10-01

This work investigates the occurrence frequency of days with high erythemal UV doses at three stations in Switzerland and Austria (Davos, Hoher Sonnblick and Vienna) for the time period 1974-2003. While several earlier studies have reported on increases in erythemal UV dose up to 10% during the last decades, this study focuses on days with high erythemal UV dose, which is defined as a daily dose at least 15% higher than for 1950s clear-sky conditions (which represent preindustrial conditions with respect to anthropogenic chlorine). Furthermore, the influence of low column ozone, clear-sky/partly cloudy conditions and surface albedo on UV irradiance has been analyzed on annual and seasonal basis. The results of this study show that in the Central Alpine Region the number of days with high UV dose increased strongly in the early 1990s. A large fraction of all days with high UV dose occurring in the period 1974-2003 was found especially during the years 1994-2003, namely 40% at Davos, 54% at Hoher Sonnblick and 65% at Vienna. The importance of total ozone, clear-sky/partly cloudy conditions and surface albedo (e.g. in dependence of snow cover) varies strongly among the seasons. However, overall the interplay of low total ozone and clear-sky/partly cloudy conditions led to the largest fraction of days showing high erythemal UV dose. Furthermore, an analysis of the synoptic weather situation showed that days with high erythemal UV dose, low total ozone and high relative sunshine duration occur at all three stations more frequently during situations with low pressure gradients or southerly advection.

Can we avoid high levels of dose escalation for high-risk prostate cancer in the setting of androgen deprivation?

PubMed Central

Shakespeare, Thomas P; Wilcox, Shea W; Aherne, Noel J

2016-01-01

Aim Both dose-escalated external beam radiotherapy (DE-EBRT) and androgen deprivation therapy (ADT) improve outcomes in patients with high-risk prostate cancer. However, there is little evidence specifically evaluating DE-EBRT for patients with high-risk prostate cancer receiving ADT, particularly for EBRT doses >74 Gy. We aimed to determine whether DE-EBRT >74 Gy improves outcomes for patients with high-risk prostate cancer receiving long-term ADT. Patients and methods Patients with high-risk prostate cancer were treated on an institutional protocol prescribing 3–6 months neoadjuvant ADT and DE-EBRT, followed by 2 years of adjuvant ADT. Between 2006 and 2012, EBRT doses were escalated from 74 Gy to 76 Gy and then to 78 Gy. We interrogated our electronic medical record to identify these patients and analyzed our results by comparing dose levels. Results In all, 479 patients were treated with a 68-month median follow-up. The 5-year biochemical disease-free survivals for the 74 Gy, 76 Gy, and 78 Gy groups were 87.8%, 86.9%, and 91.6%, respectively. The metastasis-free survivals were 95.5%, 94.5%, and 93.9%, respectively, and the prostate cancer-specific survivals were 100%, 94.4%, and 98.1%, respectively. Dose escalation had no impact on any outcome in either univariate or multivariate analysis. Conclusion There was no benefit of DE-EBRT >74 Gy in our cohort of high-risk prostate patients treated with long-term ADT. As dose escalation has higher risks of radiotherapy-induced toxicity, it may be feasible to omit dose escalation beyond 74 Gy in this group of patients. Randomized studies evaluating dose escalation for high-risk patients receiving ADT should be considered. PMID:27274277

Can we avoid high levels of dose escalation for high-risk prostate cancer in the setting of androgen deprivation?

PubMed

Shakespeare, Thomas P; Wilcox, Shea W; Aherne, Noel J

2016-01-01

Both dose-escalated external beam radiotherapy (DE-EBRT) and androgen deprivation therapy (ADT) improve outcomes in patients with high-risk prostate cancer. However, there is little evidence specifically evaluating DE-EBRT for patients with high-risk prostate cancer receiving ADT, particularly for EBRT doses >74 Gy. We aimed to determine whether DE-EBRT >74 Gy improves outcomes for patients with high-risk prostate cancer receiving long-term ADT. Patients with high-risk prostate cancer were treated on an institutional protocol prescribing 3-6 months neoadjuvant ADT and DE-EBRT, followed by 2 years of adjuvant ADT. Between 2006 and 2012, EBRT doses were escalated from 74 Gy to 76 Gy and then to 78 Gy. We interrogated our electronic medical record to identify these patients and analyzed our results by comparing dose levels. In all, 479 patients were treated with a 68-month median follow-up. The 5-year biochemical disease-free survivals for the 74 Gy, 76 Gy, and 78 Gy groups were 87.8%, 86.9%, and 91.6%, respectively. The metastasis-free survivals were 95.5%, 94.5%, and 93.9%, respectively, and the prostate cancer-specific survivals were 100%, 94.4%, and 98.1%, respectively. Dose escalation had no impact on any outcome in either univariate or multivariate analysis. There was no benefit of DE-EBRT >74 Gy in our cohort of high-risk prostate patients treated with long-term ADT. As dose escalation has higher risks of radiotherapy-induced toxicity, it may be feasible to omit dose escalation beyond 74 Gy in this group of patients. Randomized studies evaluating dose escalation for high-risk patients receiving ADT should be considered.

Impact of High-Dose Vitamin D3 Supplementation in Patients with Crohn's Disease in Remission: A Pilot Randomized Double-Blind Controlled Study.

PubMed

Narula, Neeraj; Cooray, Mohan; Anglin, Rebecca; Muqtadir, Zack; Narula, Alisha; Marshall, John K

2017-02-01

To assess the tolerability and efficacy of high-dose vitamin D3 in patients with Crohn's disease (CD). This was a randomized, double-blind placebo-controlled trial of high-dose vitamin D3 at 10,000 IU daily (n = 18) compared to 1000 IU daily (n = 16) for 12 months in patients with CD in remission. The primary outcome was change in serum 25-hydroxy-vitamin D levels. Secondary outcomes included clinical relapse rates and changes in mood scores. High-dose vitamin D3 at 10,000 IU daily significantly improved 25-hydroxy-vitamin D levels from a mean of 73.5 nmol/L [standard deviation (SD) 11.7 nmol/L] to 160.8 nmol/L (SD 43.2 nmol/L) (p = 0.02). On an intention-to-treat basis, the rate of relapse was not significantly different between patients receiving low- and high-dose vitamin D3 (68.8 vs 33.3%, p = 0.0844). In per-protocol analysis, clinical relapse of Crohn's disease was less frequently observed in patients receiving a high dose (0/12 or 0%) compared to those receiving a low dose of 1000 IU daily (3/8 or 37.5%) (p = 0.049). Improvement in anxiety and depression scores and a good safety profile were observed in both groups treated with vitamin D3. Oral supplementation with high-dose vitamin D3 at 10,000 IU daily significantly improved serum 25-hydroxy-vitamin D levels. Rates of clinical relapse were similar between both groups. Larger studies using high-dose vitamin D3 for treatment of inflammatory bowel diseases are warranted. CLINICALTRIALS. NCT02615288.

High-dose octreotide acetate for management of gastroenteropancreatic neuroendocrine tumors.

PubMed

Chadha, Manpreet K; Lombardo, Jeffrey; Mashtare, Terry; Wilding, Gregory E; Litwin, Alan; Raczyk, Cheryl; Gibbs, John F; Kuvshinoff, Boris; Javle, Milind M; Iyer, Renuka V

2009-10-01

Long-acting sandostatin (S-LAR; octreotide acetate) is well tolerated and effective for symptom control and possibly disease control in gastroenteropancreatic neuroendocrine tumors (GEP-NETs). We undertook a retrospective analysis to study the efficacy and tolerability of higher doses (more than 20-30 mg/month) of S-LAR in GEP-NETs. With IRB approval, charts of all patients with GEP-NET who received S-LAR between June 2002 to September 2007 at Roswell Park Cancer Institute were reviewed and their data analyzed. Fifty-four patients with GEP-NET received S-LAR; thirty required dose escalation. Patients received a median of 5 doses of S-LAR at conventional dose followed by up-titration of the dose for symptom control (20) and radiological progression (17). Median high dose of S-LAR was 40 mg (range: 40-90 mg) with a median of 8.5 high doses received. No treatment related toxicities were seen. The estimated 1-year survival for patients on conventional dose alone was 0.77 (95% CI of 0.50 to 0.91) and those on high-dose was 0.88 (95% CI of 0.68 to 0.96) (p=0.4777) while median time to any other intervention was 2.9 months versus 17.7 months (p=0.12). Dose escalation of S-LAR is well tolerated and may provide longer disease control.

Incidence of Hypoglycemia in Patients With Low eGFR Treated With Insulin and Dextrose for Hyperkalemia.

PubMed

Pierce, Dwayne A; Russell, Greg; Pirkle, James L

2015-12-01

Hyperkalemia is a potentially life-threatening condition that is common in kidney disease patients. Insulin is used to treat hyperkalemia, but may cause hypoglycemia, especially in kidney disease when insulin may be metabolized more slowly. We compared the rates of hypoglycemia in patients with low estimated glomerular filtration rate (eGFR) using high versus low doses of insulin for hyperkalemia to determine if lower doses of insulin would decrease the incidence of hypoglycemia. This was a retrospective study of hospitalized patients receiving intravenous insulin for hyperkalemia during a 6-month period. Patients with low eGFR were analyzed based on how much insulin they received: high dose (10 units, n = 78) versus low dose (5 units, n = 71). Postdose nadir blood glucose values were examined for up to 8 hours after the dose. The percentage of hypoglycemia (blood glucose ≤70 mg/dl) and a subset of severe hypoglycemia (blood glucose <50 mg/dl) were then reported for each dose group. A total of 149 doses were identified in patients with low eGFR. The rates of hypoglycemia were 16.7% and 19.7% (P = 0.79), respectively, among high-dose (n = 78) and low-dose (n = 71) groups. Rates of severe hypoglycemia were 8.9% and 7.0%, respectively (P = 0.90). More than 28% of hypoglycemic episodes with high doses occurred after 4 hours (median = 2.5 hours) compared with 14.3% with low doses (median = 2.38 hours). There was no difference in the rate of hypoglycemia or severe hypoglycemia between high or low doses of insulin in patients with low eGFR. We recommend monitoring up to 6 hours after insulin use in hyperkalemia. © The Author(s) 2015.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Berrington de Gonzalez, Amy, E-mail: berringtona@mail.nih.gov; Gilbert, Ethel; Curtis, Rochelle

Rapid innovations in radiation therapy techniques have resulted in an urgent need for risk projection models for second cancer risks from high-dose radiation exposure, because direct observation of the late effects of newer treatments will require patient follow-up for a decade or more. However, the patterns of cancer risk after fractionated high-dose radiation are much less well understood than those after lower-dose exposures (0.1-5 Gy). In particular, there is uncertainty about the shape of the dose-response curve at high doses and about the magnitude of the second cancer risk per unit dose. We reviewed the available evidence from epidemiologic studiesmore » of second solid cancers in organs that received high-dose exposure (>5 Gy) from radiation therapy where dose-response curves were estimated from individual organ-specific doses. We included 28 eligible studies with 3434 second cancer patients across 11 second solid cancers. Overall, there was little evidence that the dose-response curve was nonlinear in the direction of a downturn in risk, even at organ doses of ≥60 Gy. Thyroid cancer was the only exception, with evidence of a downturn after 20 Gy. Generally the excess relative risk per Gray, taking account of age and sex, was 5 to 10 times lower than the risk from acute exposures of <2 Gy among the Japanese atomic bomb survivors. However, the magnitude of the reduction in risk varied according to the second cancer. The results of our review provide insights into radiation carcinogenesis from fractionated high-dose exposures and are generally consistent with current theoretical models. The results can be used to refine the development of second solid cancer risk projection models for novel radiation therapy techniques.« less

Ascorbic acid treatment elevates follicle stimulating hormone and testosterone plasma levels and enhances sperm quality in albino Wistar rats.

PubMed

Okon, Uduak Akpan; Utuk, Ikponoabasi Ibanga

2016-01-01

Infertility issues have been linked to the effect of oxidative reaction in the reproductive system. This study evaluated the effect of ascorbic acid, on fertility parameters of male albino Wistar rats was studied. Eighteen albino Wistar rats weighed between 178 g and 241 g were used, randomly assigned into three groups. Group 1 was the control group; oral gavaged 5 ml of distilled water; Groups 2 and 3 were administered medium dose (250 mg/kg) and high dose of ascorbic acid (400 mg/kg), respectively; twice daily for 21 days. Blood samples were obtained by cardiac puncture, and blood serum was obtained for hormonal assay, and the testes were harvested for sperm analysis. Follicle stimulating hormone levels significantly increased in the high-dose group as compared to both the control and medium dose groups. Luteinizing hormone levels in the medium dose group decreased significantly as compared to the control group. Testosterone significantly increased in both the medium- and high-dose groups as compared to the control group. Sperm motility increased significantly in the high-dose group as compared to both control and medium-dose groups. Percentage sperm concentration decreased significantly in the medium-dose group when compared to the control and increased significantly in the high-dose group as compared to the medium-dose group. For percentage normal morphology, there was a dose-dependent increase in the test groups when compared to control group. These results are indicative of a positive influence of ascorbic acid on male fertility modulators and may therefore, serve as a potential adjuvant treatment for male infertility cases.

High-Dose Vitamin C (PDQ®)—Health Professional Version

Cancer.gov

High-dose vitamin C, with and without conventional cancer therapies, appeared promising in early studies and was well tolerated. However, these studies have several limitations due to lack of rigor in trial design. Get detailed information about high-dose vitamin C in cancer in this clinician summary.

COMPARISON OF THE PERIPHERAL DOSES FROM DIFFERENT IMRT TECHNIQUES FOR PEDIATRIC HEAD AND NECK RADIATION THERAPY.

PubMed

Toyota, Masahiko; Saigo, Yasumasa; Higuchi, Kenta; Fujimura, Takuya; Koriyama, Chihaya; Yoshiura, Takashi; Akiba, Suminori

2017-11-01

Intensity-modulated radiation therapy (IMRT) can deliver high and homogeneous doses to the target area while limiting doses to organs at risk. We used a pediatric phantom to simulate the treatment of a head and neck tumor in a child. The peripheral doses were examined for three different IMRT techniques [dynamic multileaf collimator (DMLC), segmental multileaf collimator (SMLC) and volumetric modulated arc therapy (VMAT)]. Peripheral doses were evaluated taking thyroid, breast, ovary and testis as the points of interest. Doses were determined using a radio-photoluminescence glass dosemeter, and the COMPASS system was used for three-dimensional dose evaluation. VMAT achieved the lowest peripheral doses because it had the highest monitor unit efficiency. However, doses in the vicinity of the irradiated field, i.e. the thyroid, could be relatively high, depending on the VMAT collimator angle. DMLC and SMLC had a large area of relatively high peripheral doses in the breast region. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

High-resolution low-dose scanning transmission electron microscopy.

PubMed

Buban, James P; Ramasse, Quentin; Gipson, Bryant; Browning, Nigel D; Stahlberg, Henning

2010-01-01

During the past two decades instrumentation in scanning transmission electron microscopy (STEM) has pushed toward higher intensity electron probes to increase the signal-to-noise ratio of recorded images. While this is suitable for robust specimens, biological specimens require a much reduced electron dose for high-resolution imaging. We describe here protocols for low-dose STEM image recording with a conventional field-emission gun STEM, while maintaining the high-resolution capability of the instrument. Our findings show that a combination of reduced pixel dwell time and reduced gun current can achieve radiation doses comparable to low-dose TEM.

Identification of Differential Gene Expression Patterns after Acute Exposure to High and Low Doses of Low-LET Ionizing Radiation in a Reconstituted Human Skin Tissue

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tilton, Susan C.; Markillie, Lye Meng; Hays, Spencer

Our goal here was to identify dose and temporal dependent radiation responses in a complex tissue, reconstituted human skin. Direct sequencing of RNA (RNA-seq) was used to quantify altered transcripts following exposure to 0.1, 2 and 10 Gy of ionizing radiation at 3 and 8 hours. These doses include a low dose in the range of some medical diagnostic procedures (0.1 Gy), a dose typically received during radiotherapy (2.0 Gy) and a lethal dose (10 Gy). These doses could be received after an intentional or accidental radiation exposure and biomarkers are needed to rapidly and accurately triage exposed individuals. Amore » total of 1701 genes were deemed to be significantly affected by high dose radiation exposure with the majority of genes affected at 10 Gy. A group of 29 genes including GDF15, BBC3, PPM1D, FDXR, GADD45A, MDM2, CDKN1A, TP53INP1, CYCSP27, SESN1, SESN2, PCNA, and AEN were similarly altered at both 2 and 10 Gy, but not 0.1 Gy, at multiple time points. A much larger group of up regulated genes, including those involved in inflammatory responses, was significantly altered only after a 10 Gy exposure. At high doses, down regulated genes were associated with cell cycle regulation and exhibited an apparent linear response between 2 and 10 Gy. While only a handful of genes were significantly affected by 0.1 Gy exposure using stringent statistical filters, groups of related genes regulating cell cycle progression and inflammatory responses consistently exhibited opposite trends in their regulation compared to the high dose exposures. Differential regulation of PLK1 signaling at low and high doses was confirmed using qRT-PCR. These results indicate that some alterations in gene expression are qualitatively different at low and high doses of radiation in this model system.« less

[Effects of qishenyiqi gutta pills on calcium/calmodulin dependent protein kinase II in rats with renal hypertension].

PubMed

Zhang, Xiao-ying; Wei, Wan-lin; Shu, Chang-cheng; Zhang, Ling; Tian, Guo-xiang

2013-02-05

To explore the effects of qishenyiqi gutta pills on myocardial hypertrophy of left ventricle and calcium/calmodulin dependent protein kinase II (CAMK II) in rats with renal hypertension and elucidate its intervention mechanism for myocardial hypertrophy. A total of 50 Wistar rats were randomly divided into 5 groups of sham-operation, control, high-dose qishenyiqi gutta pills, low-dose qishenyiqi gutta pills and valsartan (n = 10 each). The rat model of myocardial hypertrophy with renal hypertension was established by the 2-kidney 1-clip (2K1C) method. The experimental animals were divided into control, high-dose, low-dose and valsartan groups. At Week 5 postoperation, valsartan group received an oral dose of valsartan (30 mg×kg(-1)×d(-1)), high-dose and low-dose groups took qishenyiqi gutta pills (250 and 125 mg×kg(-1)×d(-1)) while sham-operation and control groups had the same dose of normal saline solution. Tail arterial pressure was detected weekly and continued for 8 weeks. At the end of Week 12, the animals were sacrificed to harvest myocardial tissue of left ventricle for detecting left ventricular mass index (LVMI). The collagen volume fraction (CVF) of myocardium was examined by Van Gieson staining, the activities of superoxide dismutase (SOD) and reactive oxygen species (ROS) were detected by enzyme-linked immunosorbent assay (ELISA) and the expression of CAMK II was detected by immunohistochemistry and Western blot. (1) Blood pressures were significantly higher in high-dose, low-dose and control groups than those in sham-operation and valsartan groups ((167.66 ± 11.48), (166.72 ± 13.51), (174.34 ± 14.52) vs (119.57 ± 6.30), (131.80 ± 12.49) mm Hg, P < 0.01). The changes of blood pressure had no significant difference between high-dose and low-dose groups. (2) LVMI and CVF increased significantly in high-dose, low-dose and valsartan groups versus sham-operation group (LVMI: (1.98 ± 0.16), (2.09 ± 0.14), (1.97 ± 0.17) vs (1.74 ± 0.17) g/kg; CVF: 0.94% ± 0.22%, 2.53% ± 0.61%, 0.81% ± 0.20% vs 0.45% ± 0.13%) (P < 0.01, P < 0.05), but decreased significantly versus control group (LVMI: (1.98 ± 0.16), (2.09 ± 0.14), (1.97 ± 0.17) vs (2.28 ± 0.28) g/kg; CVF: 0.94% ± 0.22%, 2.53% ± 0.61%, 0.81% ± 0.20% vs 4.73% ± 1.04%) (P < 0.01, P < 0.05). (3) The expression of CAMK II was significantly higher in high-dose, low-dose, valsartan and control groups than that in sham-operation group (65.9%, 95.3%, 84.8%, 160.1% vs 67.7%). And it was significantly lower in high-dose, low-dose and valsartan groups than that in control group (65.9%, 95.3%, 84.8% vs 160.1%). There was no statistical difference among high-dose, low-dose and valsartan groups. Qishenyiqi gutta pills may retard myocardial hypertrophy of left ventricle in rats with renal hypertension. And the mechanism is probably be correlated with its antioxidant activity and inhibited expression of myocardial CAMK II.

Phosphoprotein profiles of candidate markers for early cellular responses to low-dose γ-radiation in normal human fibroblast cells

PubMed Central

Yim, Ji-Hye; Yun, Jung Mi; Kim, Ji Young; Lee, In Kyung; Nam, Seon Young

2017-01-01

Abstract Ionizing radiation causes biological damage that leads to severe health effects. However, the effects and subsequent health implications caused by exposure to low-dose radiation are unclear. The objective of this study was to determine phosphoprotein profiles in normal human fibroblast cell lines in response to low-dose and high-dose γ-radiation. We examined the cellular response in MRC-5 cells 0.5 h after exposure to 0.05 or 2 Gy. Using 1318 antibodies by antibody array, we observed ≥1.3-fold increases in a number of identified phosphoproteins in cells subjected to low-dose (0.05 Gy) and high-dose (2 Gy) radiation, suggesting that both radiation levels stimulate distinct signaling pathways. Low-dose radiation induced nucleic acid–binding transcription factor activity, developmental processes, and multicellular organismal processes. By contrast, high-dose radiation stimulated apoptotic processes, cell adhesion and regulation, and cellular organization and biogenesis. We found that phospho-BTK (Tyr550) and phospho-Gab2 (Tyr643) protein levels at 0.5 h after treatment were higher in cells subjected to low-dose radiation than in cells treated with high-dose radiation. We also determined that the phosphorylation of BTK and Gab2 in response to ionizing radiation was regulated in a dose-dependent manner in MRC-5 and NHDF cells. Our study provides new insights into the biological responses to low-dose γ-radiation and identifies potential candidate markers for monitoring exposure to low-dose ionizing radiation. PMID:28122968

Time- and dose-dependent effects of total-body ionizing radiation on muscle stem cells

PubMed Central

Masuda, Shinya; Hisamatsu, Tsubasa; Seko, Daiki; Urata, Yoshishige; Goto, Shinji; Li, Tao-Sheng; Ono, Yusuke

2015-01-01

Exposure to high levels of genotoxic stress, such as high-dose ionizing radiation, increases both cancer and noncancer risks. However, it remains debatable whether low-dose ionizing radiation reduces cellular function, or rather induces hormetic health benefits. Here, we investigated the effects of total-body γ-ray radiation on muscle stem cells, called satellite cells. Adult C57BL/6 mice were exposed to γ-radiation at low- to high-dose rates (low, 2 or 10 mGy/day; moderate, 50 mGy/day; high, 250 mGy/day) for 30 days. No hormetic responses in proliferation, differentiation, or self-renewal of satellite cells were observed in low-dose radiation-exposed mice at the acute phase. However, at the chronic phase, population expansion of satellite cell-derived progeny was slightly decreased in mice exposed to low-dose radiation. Taken together, low-dose ionizing irradiation may suppress satellite cell function, rather than induce hormetic health benefits, in skeletal muscle in adult mice. PMID:25869487

High-Dose Statin Pretreatment Decreases Periprocedural Myocardial Infarction and Cardiovascular Events in Patients Undergoing Elective Percutaneous Coronary Intervention: A Meta-Analysis of Twenty-Four Randomized Controlled Trials

PubMed Central

Wang, Le; Peng, Pingan; Zhang, Ou; Xu, Xiaohan; Yang, Shiwei; Zhao, Yingxin; Zhou, Yujie

2014-01-01

Background Evidence suggests that high-dose statin pretreatment may reduce the risk of periprocedural myocardial infarction (PMI) and major adverse cardiac events (MACE) for certain patients; however, previous analyses have not considered patients with a history of statin maintenance treatment. In this meta-analysis of randomized controlled trials (RCTs), we reevaluated the efficacy of short-term high-dose statin pretreatment to prevent PMI and MACE in an expanded set of patients undergoing elective percutaneous coronary intervention. Methods We searched the PubMed/Medline database for RCTs that compared high-dose statin pretreatment with no statin or low-dose statin pretreatment as a prevention of PMI and MACE. We evaluated the incidence of PMI and MACE, including death, spontaneous myocardial infarction, and target vessel revascularization at the longest follow-up for each study for subgroups stratified by disease classification and prior low-dose statin treatment. Results Twenty-four RCTs with a total of 5,526 patients were identified. High-dose statin pretreatment was associated with 59% relative reduction in PMI (odds ratio [OR]: 0.41; 95% confidence interval [CI]: 0.34–0.49; P<0.00001) and 39% relative reduction in MACE (OR: 0.61; 95% CI: 0.45–0.83; P = 0.002). The benefit of high-dose statin pretreatment on MACE was significant for statin-naive patients (OR: 0.69; 95% CI: 0.50–0.95; P = 0.02) and prior low dose statin-treated patients (OR: 0.28; 95% CI: 0.12–0.65; P = 0.003); and for patients with acute coronary syndrome (OR: 0.52; 95% CI: 0.34–0.79; P = 0.003), but not for patients with stable angina (OR: 0.71; 95% CI 0.45–1.10; P = 0.12). Long-term effects on survival were less obvious. Conclusions High-dose statin pretreatment can result in a significant reduction in PMI and MACE for patients undergoing elective PCI. The positive effect of high-dose statin pretreatment on PMI and MACE is significant for statin-naïve patients and patients with prior treatment. The positive effect of high-dose statin pretreatment on MACE is significant for patients with acute coronary syndrome. PMID:25473831

Dosage effects of histamine-2 receptor antagonist on the primary prophylaxis of non-steroidal anti-inflammatory drug (NSAID)-associated peptic ulcers: a retrospective cohort study.

PubMed

He, Ying; Chan, Esther W; Man, Kenneth K C; Lau, Wallis C Y; Leung, Wai K; Ho, Lai M; Wong, Ian C K

2014-09-01

A histamine-2 receptor antagonist (H2RA) is one of the common gastroprotective co-therapies used with non-steroidal anti-inflammatory drugs (NSAIDs) for the prevention or treatment of peptic ulcers (PUs). To date, no study has directly compared the prophylactic effectiveness between high-dose and low-dose H2RA. Our objective was to compare the effectiveness of high-dose versus low-dose H2RAs in the primary prophylaxis of PUs among short-term NSAID users. A retrospective cohort study was conducted using the Clinical Data Analysis and Reporting System (CDARS) in Hong Kong. Patients aged 18 years or above who received a single prescription of oral NSAID with oral H2RA were identified within the study period (1 January 2009-31 December 2012). Patients with a history of or risk factors for PU in the corresponding 2 years prior to the index date (of the first NSAID prescription) were excluded. Log binomial regression analysis was used to calculate the relative risk of PU among NSAID users with high-dose H2RA versus low-dose H2RA exposure. Among the NSAID cohort (n = 102,042), 77,509 (76 %) were on low-dose H2RA and 24,533 (24 %) were on high-dose H2RA. Of the total 69 PU cases identified during the drug exposure period, 64 (0.08 %) received low-dose-H2RA and five (0.02 %) received high-dose H2RA. The overall absolute risk of PUs for NSAID users whilst on H2RA was approximately 1 per 1,479 patients. The adjusted relative risk for NSAID users receiving high-dose H2RA versus low-dose H2RA was 0.32 (95 % confidence interval [CI] 0.13-0.79). Patients aged ≥65 years, receiving a longer duration of treatment, or with concomitant use of antiplatelet agents were found to be at higher risk of PU. High-dose H2RA showed greater effectiveness than low-dose H2RA in the primary prophylaxis of NSAID-associated PUs in short-term new users.

A randomised controlled trial evaluating IGF1 titration in contrast to current GH dosing strategies in children born small for gestational age: the North European Small-for-Gestational-Age Study.

PubMed

Jensen, Rikke Beck; Thankamony, Ajay; O'Connell, Susan M; Kirk, Jeremy; Donaldson, Malcolm; Ivarsson, Sten-A; Söder, Olle; Roche, Edna; Hoey, Hilary; Dunger, David B; Juul, Anders

2014-10-01

Short children born small for gestational age (SGA) are treated with a GH dose based on body size, but treatment may lead to high levels of IGF1. The objective was to evaluate IGF1 titration of GH dose in contrast to current dosing strategies. In the North European Small-for-Gestational-Age Study (NESGAS), 92 short pre-pubertal children born SGA were randomised after 1 year of high-dose GH treatment (67 μg/kg per day) to three different regimens: high dose (67 μg/kg per day), low dose (35 μg/kg per day) or IGF1 titration. The average dose during the second year of the randomised trial did not differ between the IGF1 titration group (38 μg/kg per day, s.d. 0.019) and the low-dose group (35 μg/kg per day, s.d. 0.002; P=0.46), but there was a wide variation in the IGF1 titration group (range 10-80 μg/kg per day). The IGF1 titration group had significantly lower height gain (0.17 SDS, s.d. 0.18) during the second year of the randomised trial compared with the high-dose group (0.46 SDS, s.d. 0.25), but not significantly lower than the low-dose group (0.23 SDS, s.d. 0.15; P=0.17). The IGF1 titration group had lower IGF1 levels after 2 years of the trial (mean 1.16, s.d. 1.24) compared with both the low-dose (mean 1.76, s.d. 1.48) and the high-dose (mean 2.97, s.d. 1.63) groups. IGF1 titration of GH dose in SGA children proved less effective than current dosing strategies. IGF1 titration resulted in physiological IGF1 levels with a wide range of GH dose and a poorer growth response, which indicates the role of IGF1 resistance and highlights the heterogeneity of short SGA children. © 2014 European Society of Endocrinology.

Medicines and Bone Loss

MedlinePlus

... The doses of thyroid hormone used to treat hypothyroidism (underactive thyroid) don’t harm bone and shouldn’t be cause for concern. Only high doses, used for thyroid cancer treatment, can cause bone loss. High doses or long- ...

Calculation of Dose, Dose Equivalent, and Relative Biological Effectiveness for High Charge and Energy Ion Beams

NASA Technical Reports Server (NTRS)

Wilson, J. W.; Reginatto, M.; Hajnal, F.; Chun, S. Y.

1995-01-01

The Green's function for the transport of ions of high charge and energy is utilized with a nuclear fragmentation database to evaluate dose, dose equivalent, and RBE for C3H1OT1/2 cell survival and neoplastic transformation as a function of depth in soft tissue. Such evaluations are useful to estimates of biological risk for high altitude aircraft, space operations, accelerator operations, and biomedical applications.

Calculation of dose, dose equivalent, and relative biological effectiveness for high charge and energy ion beams

NASA Technical Reports Server (NTRS)

Wilson, J. W.; Chun, S. Y.; Reginatto, M.; Hajnal, F.

1995-01-01

The Green's function for the transport of ions of high charge and energy is utilized with a nuclear fragmentation database to evaluate dose, dose equivalent, and RBE for C3H10T1/2 cell survival and neo-plastic transformation as function of depth in soft tissue. Such evaluations are useful to estimates of biological risk for high altitude aircraft, space operations, accelerator operations, and biomedical application.

High-dose ascorbic acid decreases cholesterolemic factors of an atherogenic diet in guinea pigs.

PubMed

Filis, Konstantinos; Anastassopoulou, Aikaterini; Sigala, Fragiska; Theodorou, Dimitrios; Manouras, Andreas; Leandros, Emanouel; Sigalas, Panagiotis; Hepp, Wolfgang; Bramis, John

2007-03-01

The study evaluates the effect of a high supplemental dose of ascorbic acid (AA) on plasma concentrations of total cholesterol (TC), triglycerides (TG), total lipids (TL), and lipoprotein fractions high-density, very-low-density-, and low-density lipoprotein (HDL, VLDL, LDL) in guinea pigs fed with atherogenic diet. Group I consisted of 5 normally fed guinea pigs plus a low dose of AA (1 mg/100 g/day), group II consisted of 7 guinea pigs fed with food enriched with 2% cholesterol plus a low dose of AA (1 mg/100 g/day), and group III consisted of 7 guinea pigs fed with food enriched with 2% cholesterol plus a high dose of AA (30 mg/100 g/day). Cholesterolemic factors concentrations were determined after nine weeks. Concentrations of TC, TG, TL, LDL, and VLDL were increased in group II compared to group I (p < 0.01 for all differences). Supplementation with a high dose of AA resulted in decreased concentrations of TC (p < 0.01), TG (p < 0.01), TL (p < 0.01), and LDL (p < 0.01) in group III compared to group II. Additionally, concentration of HDL was increased in group III compared to group II (p < 0.01). High-dose AA supplementation to an atherogenic diet decreases concentrations of TC, TG, TL, and LDL and increases concentration of HDL compared to low-dose AA.

Biology of high single doses of IORT: RBE, 5 R's, and other biological aspects.

PubMed

Herskind, Carsten; Ma, Lin; Liu, Qi; Zhang, Bo; Schneider, Frank; Veldwijk, Marlon R; Wenz, Frederik

2017-01-19

Intraoperative radiotherapy differs from conventional, fractionated radiotherapy in several aspects that may influence its biological effect. The radiation quality influences the relative biologic effectiveness (RBE), and the role of the five R's of radiotherapy (reassortment, repair, reoxygenation, repopulation, radiosensitivity) is different. Furthermore, putative special biological effects and the small volume receiving a high single dose may be important. The present review focuses on RBE, repair, and repopulation, and gives an overview of the other factors that potentially contribute to the efficacy. The increased RBE should be taken into account for low-energy X-rays while evidence of RBE < 1 for high-energy electrons at higher doses is presented. Various evidence supports a hypothesis that saturation of the primary DNA double-strand break (DSB) repair mechanisms leads to increasing use of an error-prone backup repair system leading to genomic instability that may contribute to inactivate tumour cells at high single doses. Furthermore, the elimination of repopulation of residual tumour cells in the tumour bed implies that some patients are likely to have very few residual tumour cells which may be cured even by low doses to the tumour bed. The highly localised dose distribution of IORT has the potential to inactivate tumour cells while sparing normal tissue by minimising the volume exposed to high doses. Whether special effects of high single doses also contribute to the efficacy will require further experimental and clinical studies.

Irradiation effects in UO2 and CeO2

NASA Astrophysics Data System (ADS)

Ye, Bei; Oaks, Aaron; Kirk, Mark; Yun, Di; Chen, Wei-Ying; Holtzman, Benjamin; Stubbins, James F.

2013-10-01

Single crystal CeO2, as a surrogate material to UO2, was irradiated with 500 keV xenon ions at 800 °C while being observed using in situ transmission electron microscopy (TEM). Experimental results show the formation and growth of defect clusters including dislocation loops and cavities as a function of increasing atomic displacement dose. At high dose, the dislocation loop structure evolves into an extended dislocation line structure, which appears to remain stable to the high dose levels examined in this study. A high concentration of cavities was also present in the microstructure. Despite high atomic displacement doses, the specimen remained crystalline to a cumulated dose of 5 × 1015 ions/cm2, which is consistent with the known stability of the fluorite structure under high dose irradiation. Kinetic Monte Carlo calculations show that oxygen mobility is substantially higher in hypo-stoichiometric UO2/CeO2 than hyper-stoichiometric systems. This result is consistent with the ability of irradiation damage to recover even at intermediate irradiation temperatures.

Predictive factors of head and neck squamous cell carcinoma patient tolerance to high-dose cisplatin in concurrent chemoradiotherapy

PubMed Central

NAKANO, KENJI; SATO, YASUYOSHI; TOSHIYASU, TAKASHI; SATO, YUKIKO; INAGAKI, LINA; TOMOMATSU, JUNICHI; SASAKI, TORU; SHIMBASHI, WATARU; FUKUSHIMA, HIROFUMI; YONEKAWA, HIROYUKI; MITANI, HIROKI; KAWABATA, KAZUYOSHI; TAKAHASHI, SHUNJI

2016-01-01

Although high-dose cisplatin is the standard regimen of concurrent chemoradiotherapy (CCRT) for locally advanced head and neck squamous cell carcinoma (HNSCC), varying levels of patient tolerance towards cisplatin have been reported, and the predictive factors of cisplatin tolerance remain to be elucidated. The present study retrospectively reviewed newly diagnosed HNSCC patients who received CCRT. Cisplatin (80 mg/m2) was administered every 3 weeks. The proportion of high-dose cisplatin-tolerant patients (cumulative cisplatin dose, ≥200 mg/m2) was determined, and the predictive factors of cisplatin tolerance were analyzed in a logistic regression analysis. Between June 2006 and March 2013, a total of 159 patients were treated with CCRT. The median follow-up time was 36.7 months. A total of 73 patients (46%) tolerated a cumulative cisplatin dose ≥200 mg/m2; male gender [odds ratio (OR), 25.00; P=0.005] and high body surface area (BSA) (>1.80 m2; OR, 2.21; P=0.032) were significantly predictive of high-dose cisplatin tolerance. The high-dose cisplatin-tolerant patients had a significantly higher complete response (CR) rate (82 vs. 67%, P=0.045); however, there were no significant between-group differences in the 3-year OS (79.5 vs. 81.2%, P=0.59) or PFS (70.4 vs. 44.6%, P=0.076) by cisplatin tolerance. In clinical practice, approximately one-half of the patients tolerated high-dose cisplatin in CCRT. Male gender and high BSA could be predictive of cisplatin tolerance. PMID:26893880

Collagenous colitis: Requirement for high-dose budesonide as maintenance treatment.

PubMed

Fernandez-Bañares, Fernando; Piqueras, Marta; Guagnozzi, Danila; Robles, Virginia; Ruiz-Cerulla, Alexandra; Casanova, María José; Gisbert, Javier P; Busquets, David; Arguedas, Yolanda; Pérez-Aisa, Angeles; Fernández-Salazar, Luis; Lucendo, Alfredo J

2017-09-01

Controlled studies show high efficacy of budesonide in inducing short-term clinical remission in collagenous colitis (CC), but relapses are common after its withdrawal. To evaluate the need for high-dose budesonide (≥6mg/d) to maintain clinical remission in CC. Analysis of a multicentre retrospective cohort of 75 patients with CC (62.3±1.5years; 85% women) treated with budesonide in a clinical practice setting between 2013 and 2015. Frequency of budesonide (9mg/d) refractoriness and safety, and the need for high-dose budesonide to maintain clinical remission, were evaluated. Drugs used as budesonide-sparing, including azathioprine and mercaptopurine, were recorded. Logistic regression analysis was performed to evaluate the risk factors associated with the need for high-dose budesonide (≥6mg/d) to maintain clinical remission. Budesonide induced clinical remission in 92% of patients, with good tolerance. Fourteen of 68 patients (21%; 95% CI, 13-32%) needed high-dose budesonide to maintain remission. Only intake of NSAIDs at diagnosis (OR, 8.6; 95% CI, 1.6-44) was associated with the need for high-dose budesonide in the multivariate analysis. with thiopurines was effective in 5 out of 6 patients (83%; 95% CI, 44-97%), allowing for withdrawal from or a dose decrease of budesonide. One fifth of CC patients, especially those with NSAID intake at diagnosis, require high-dose budesonide (≥6mg/d) to maintain clinical remission. In this setting, thiopurines might be effective as budesonide-sparing drugs. Copyright © 2017 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Opioid systems in the response to inflammatory pain: sustained blockade suggests role of kappa- but not mu-opioid receptors in the modulation of nociception, behaviour and pathology.

PubMed

Millan, M J; Colpaert, F C

1991-01-01

One day after intraplantar inoculation of Mycobacterium butyricum into the right hind-paw, unilaterally inflamed and control rats were implanted subcutaneously with osmotic mini-pumps delivering naloxone at 0.16 or 3.0 mg/kg/h or vehicle. As determined three days after implantation, 0.16 mg/kg/h of naloxone completely antagonized the antinociceptive action of the mu-agonist, morphine, but did not affect antinociception evoked by the kappa-agonist, U69,593. In contrast, at 3.0 mg/kg/h, naloxone blocked both morphine- and U69,593-induced antinociception. Thus, 0.16 mg/kg ("low dose") and 3.0 mg/kg ("high dose") of naloxone block mu, or mu- plus kappa-opioid receptors, respectively. Pumps were removed one week following their implantation. Inoculation was associated with a sustained hyperalgesia of the inflamed paw to noxious pressure, and elevation in resting core temperature, a loss of body weight, hypophagia, hypodipsia and a reduction in mobility. These parameters were differentially modified by the high as compared to the low dose of naloxone. Two days following implantation of pumps delivering the high dose of naloxone, the hyperalgesia of the inflamed paw was potentiated: by six days, this effect was lost. Further, one day after removal of pumps yielding the high dose, the inflamed paw showed a normalization of thresholds, that is a "rebound antinociception". One day later, this effect had subsided. In distinction, at no time did the low dose of naloxone modify nociceptive thresholds. The high dose of naloxone enhanced the reduction in body weight and food intake shown by unilaterally inflamed rats whereas the low dose was ineffective. Neither dose affected the reduction in water intake or hypothermia of unilaterally inflamed animals. The high dose of naloxone reduced the mobility of unilaterally inflamed rats whereas the low dose was ineffective. Finally, by 10 days following pump removal, pathology had transferred to the contralateral paw. In rats which had received the high but not the low dose, this transfer was blocked. It is concluded that blockade of kappa-opioid receptors with a high dose of naloxone experts pronounced functional effects in unilaterally inflamed rats. In distinction, selective blockade of mu-receptors with a low dose is ineffective. The changes seen include not only an enhancement of the hyperalgesia of the inflamed tissue, but also an exacerbation of variables (body weight, food intake and motility) which reflect pain states.(ABSTRACT TRUNCATED AT 400 WORDS)

Evaluation of High Ipsilateral Subventricular Zone Radiation Therapy Dose in Glioblastoma: A Pooled Analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, Percy, E-mail: percylee@mednet.ucla.edu; UCLA Jonsson Comprehensive Cancer Center, Los Angeles, California; Eppinga, Wietse

Purpose: Cancer stem cells (CSCs) may play a role in the recurrence of glioblastoma. They are believed to originate from neural stem cells in the subventricular zone (SVZ). Because of their radioresistance, we hypothesized that high doses of radiation (>59.4 Gy) to the SVZ are necessary to control CSCs and improve progression-free survival (PFS) or overall survival (OS) in glioblastoma. Methods and Materials: 173 patients with glioblastoma pooled from 2 academic centers were treated with resection followed by chemoradiation therapy. The SVZ was segmented on computed tomography to calculate radiation doses delivered to the presumptive CSC niches. The relationships betweenmore » high SVZ doses and PFS and OS were examined using Cox proportional hazards models. Five covariates were included to estimate their impact on PFS or OS: ipsilateral and contralateral SVZ doses, clinical target volume dose, age, and extent of resection. Results: Median PFS and OS were 10.4 and 19.6 months for the cohort. The mean ipsilateral SVZ, contralateral SVZ, and clinical target volume doses were 49.2, 35.2, and 60.1 Gy, respectively. Twenty-one patients who received high ipsilateral SVZ dose (>59.4 Gy) had significantly longer median PFS (12.6 vs 9.9 months, P=.042) and longer OS (25.8 vs 19.2 months, P=.173). On multivariate analysis, high radiation therapy doses to ipsilateral SVZ remained a statistically significant independent predictor of improved PFS but not of OS. The extent of surgery affected both PFS and OS on multivariate analysis. Conclusion: High radiation therapy doses to ipsilateral CSC niches are associated with improved PFS in glioblastoma.« less

Dose-dependent effects of vitamin 1,25(OH)2D3 on oxidative stress and apoptosis.

PubMed

Cakici, Cagri; Yigitbasi, Turkan; Ayla, Sule; Karimkhani, Hadi; Bayramoglu, Feyza; Yigit, Pakize; Kilic, Ertugrul; Emekli, Nesrin

2018-02-08

Background The purpose of this study is to examine the dose-dependent effects of vitamin 1,25(OH)2D3 on apoptosis and oxidative stress. Methods In this study, 50 male Balb/c mice were used as control and experiment groups. The mice were divided into 5 groups each consisting of 10 mice. Calcitriol was intraperitoneally administered as low dose, medium dose, medium-high dose and high dose vitamin D groups (at 0.5, 1, 5 and 10 μg/kg, respectively), for three times a week during 14 days. At the end of the study, annexin V was measured by enzyme-linked immunosorbent assay method, and total antioxidant capacity and total oxidant status values were measured by colorimetric method in serum. Hematoxylin eosin staining was performed in liver tissues and periodic acid schiff staining was performed in kidney tissues. Results While comparing the results of medium-high dose (5 μg/kg) and high dose (10 μg/kg) vitamin D administration to that of the control group, it was observed that serum antioxidant status and annexin V levels decreased and glomerular mesenchial matrix ratio increased in kidney (p<0.05). In addition to these findings, in the group receiving high dose vitamin D (10 μg/kg), it was observed that the damage to the liver increased together with the the oxidative stress index values (p<0.05). Conclusions As a result, this study was the first in the literature to report that use of high-dose vitamin D (10 μg/kg) results in oxidant effect, rather than being an antioxidant, and causes severe histopathological toxicity in the liver and kidney.

Tolerance to 3,4-Methylenedioxymethamphetamine (MDMA) in Rats Exposed to Single High-Dose Binges

PubMed Central

Baumann, Michael H.; Clark, Robert D.; Franken, Frederick H.; Rutter, John J.; Rothman, Richard B.

2008-01-01

3,4-Methylenedioxymethamphetamine (MDMA or Ecstasy) stimulates the transporter-mediated release of monoamines, including serotonin (5-HT). High-dose exposure to MDMA causes persistent 5-HT deficits (e.g., depletion of brain 5-HT) in animals, yet the functional and clinical relevance of such deficits are poorly defined. Here we examine functional consequences of MDMA-induced 5-HT depletions in rats. Male rats received binges of 3 ip injections of MDMA or saline, one injection every 2 h; MDMA was given at a threshold pharmacological dose (1.5 mg/kg × 3, low dose) or at a 5-fold higher amount (7.5 mg/kg × 3, high dose). One week later, jugular catheters and intracerebral guide cannulae were implanted. Two weeks after binges, rats received acute iv challenge injections of 1 and 3 mg/kg MDMA. Neuroendocrine effects evoked by iv MDMA (prolactin and corticosterone secretion) were assessed via serial blood sampling, while neurochemical effects (5-HT and dopamine release) were assessed via microdialysis in brain. MDMA binges elevated core temperatures only in the high-dose group, with these same rats exhibiting ~50% loss of forebrain 5-HT two weeks later. Prior exposure to MDMA did not alter baseline plasma hormones or dialysate monoamines, and effects of iv MDMA were similar in saline and low-dose groups. By contrast, rats pretreated with high-dose MDMA displayed significant reductions in evoked hormone secretion and 5-HT release when challenged with iv MDMA. As tolerance developed only in rats exposed to high-dose binges, hyperthermia and 5-HT depletion are implicated in this phenomenon. Our results suggest that MDMA tolerance in humans may reflect 5-HT deficits which could contribute to further dose escalation. PMID:18313226

High- and low-dose oral delayed-release mesalamine in children with mild-to-moderately active ulcerative colitis.

PubMed

Winter, Harland S; Krzeski, Piotr; Heyman, Melvin B; Ibarguen-Secchia, Eduardo; Iwanczak, Barbara; Kaczmarski, Maciej; Kierkus, Jaroslaw; Kolaček, Sanja; Osuntokun, Bankole; Quiros, J Antonio; Shah, Manoj; Yacyshyn, Bruce; Dunnmon, Preston M

2014-12-01

The aim of the study was to assess the safety and efficacy of high- and low-dose oral, delayed-release mesalamine in a randomized, double-blind, active control study of children with mild-to-moderately active ulcerative colitis. Patients ages 5 to 17 years, with a Pediatric Ulcerative Colitis Activity Index (PUCAI) score of ≥ 10 to ≤ 55 and a truncated Mayo Score of ≥ 1 for both rectal bleeding and stool frequency, were enrolled. They received body weight-dependent doses of oral, delayed-release mesalamine for 6 weeks in a low- (27-71 mg · g(-1) · day(-1)) or high-dose group (53-118 mg · g(-1) · day(-1)). The primary endpoint was treatment success, defined as the proportion of patients who achieved remission (PUCAI score <10) or partial response (PUCAI score ≥ 10 with a decrease from baseline by ≥ 20 points). Secondary endpoints included truncated Mayo Score and global assessment of change of disease activity. The modified intent-to-treat population included 81 of 83 patients enrolled. Treatment success by PUCAI was achieved by 23 of 41 (56%) and 22 of 40 (55%) patients in the mesalamine low- and high-dose groups, respectively (P = 0.924). Truncated Mayo Score (low-dose 30 [73%] and high-dose 28 [70%] patients) and other efficacy results did not differ between the groups. The type and severity of adverse events were consistent with those reported in previous studies of adults with ulcerative colitis and did not differ between groups. Both low- and high-dose oral, delayed-release mesalamine doses were equally effective as short-term treatment of mild-to-moderately active ulcerative colitis in children, without a specific benefit or risk to using either dose.

Diazepam dose-dependently increases or decreases implicit priming of alcohol associations in problem drinkers.

PubMed

Zack, Martin; Poulos, Constantine X; Woodford, Tracy M

2006-01-01

Words denoting negative affect (NEG) have been found to prime alcohol-related words (ALC) on semantic priming tasks, and this effect is tied to severity of addiction. Previous research suggested that high doses of benzodiazepines may dampen NEG-ALC priming. The present study tested this possibility and the role of motivation for alcohol in this process. A placebo-controlled, double blind, between-within, counterbalanced design was employed. Two groups of male problem drinkers (n = 6/group) received a high (15-mg) or low (5-mg) dose of diazepam versus placebo on two identical test sessions. A lexical decision task assessed priming. Under placebo, significant NEG-->ALC priming emerged in each group. High-dose diazepam selectively reversed this effect, while low-dose selectively enhanced it. Correlations between NEG-->ALC priming and desire for alcohol provided further support that semantic priming of ALC concepts reflects a motivational process. The bi-directional effects found here parallel the effects of high- versus low-dose benzodiazepines on alcohol self-administration in animals. High-dose diazepam reduces prime-induced activation of ALC concepts in problem drinkers. Low-dose diazepam facilitates this process, and cross-priming of motivation for alcohol appears to explain this effect. Neurochemical modulation of the alcohol memory network may contribute to the motivational effects of benzodiazepines in problem drinkers.

High-Dose Pyridoxine and Magnesium Administration in Children with Autistic Disorder: An Absence of Salutary Effects in a Double-Blind, Placebo-Controlled Study.

ERIC Educational Resources Information Center

Findling, Robert L.; Maxwell, Kathleen; Scotese-Wojtila, Lynette; Huang, Jie; Yamashita, Toyoko; Wiznitzer, Max

1997-01-01

Evaluation of high doses of pyridoxine and magnesium in a 10-week double-blind placebo-controlled trial with 10 patients (mean age 6 years) having autism concluded that the high doses used were ineffective in ameliorating autistic behaviors. (DB)

Characterization of Radiation Hardened Bipolar Linear Devices for High Total Dose Missions

NASA Technical Reports Server (NTRS)

McClure, Steven S.; Harris, Richard D.; Rax, Bernard G.; Thorbourn, Dennis O.

2012-01-01

Radiation hardened linear devices are characterized for performance in combined total dose and displacement damage environments for a mission scenario with a high radiation level. Performance at low and high dose rate for both biased and unbiased conditions is compared and the impact to hardness assurance methodology is discussed.

Efficacy of short-term moderate or high-dose rosuvastatin in preventing contrast-induced nephropathy

PubMed Central

Liang, Min; Yang, Shicheng; Fu, Naikuan

2017-01-01

Abstract Background: The prophylactic efficacy of statin pretreatment for the prevention of contrast-induced nephropathy (CIN) in patients undergoing coronary angiography (CAG) or percutaneous coronary intervention (PCI) remains controversial. The aim of the study was to perform a meta-analysis of randomized controlled trials (RCTs) to assess the effectiveness of short-term moderate or high-dose rosuvastatin pretreatment in preventing CIN. Methods: We included RCTs comparing short-term moderate or high-dose rosuvastatin treatment versus low-dose rosuvastatin treatment or placebo for preventing CIN. The primary endpoint was the incidence of CIN within 2 to 5 days after contrast administration, and related-parameters including serum creatinine (SCr), cystatin C (CysC), hypersensitive C-reactive protein (hs-CRP), urine microalbumin (mALB) were also extracted. Results: Fifteen RCTs with a total of 2673 patients were identified and analyzed. Patients who received moderate or high-dose rosuvastatin pretreatment had a 55% lower risk of CIN compared with low-dose rosuvastatin pretreatment or placebo group based on a fixed effect model (RR = 0.45, 95% CI 0.35–0.58, P < .0001). The benefit of moderate or high-dose rosuvastatin was consistent in both comparisons with low-dose rosuvastatin (RR = 0.40, 95% CI 0.27–0.59, P < .0001) or placebo (RR = 0.45, 95% CI 0.35–0.58, P < .0001). And moderate (20 mg) or high dose (≥40 mg) rosuvastatin significantly reduced the incidence of CIN compared with the control (RR = 0.39, 95% CI 0.29–0.54, P < .0001, RR = 0.56, 95% CI 0.37–0.85, P = .006, respectively). Subgroup analysis showed that moderate or high-dose rosuvastatin pretreatment could decrease the incidence of CIN in patients with chronic kidney disease (CKD) (RR = 0.53, 95% CI 0.30–0.93, P = .03) or diabetes mellitus (DM) (RR = 0.51, 95% CI 0.31–0.86, P = .01) or acute coronary syndrome (ACS) patients undergoing PCI (RR = 0.52, 95% CI 0.35–0.76, P = .0009) or in studies which received mean contrast volume ≥110 mL (RR = 0.43, 95% CI 0.32–0.58, P < .0001). The SCr, CysC, hs-CRP, and mALB after the operation in the moderate or high-dose rosuvastatin group were lower than those of low-dose rosuvastatin group. Conclusion: This meta-analysis demonstrated that moderate or high-dose rosuvastatin treatment could reduce the incidence of CIN in patients undergoing CAG or PCI. Moreover, moderate or high-dose rosuvastatin would be beneficial in high-risk patients with CKD or DM or undergoing PCI. PMID:28682890

Anti-tumor activity of high-dose EGFR tyrosine kinase inhibitor and sequential docetaxel in wild type EGFR non-small cell lung cancer cell nude mouse xenografts

PubMed Central

Tang, Ning; Zhang, Qianqian; Fang, Shu; Han, Xiao; Wang, Zhehai

2017-01-01

Treatment of non-small-cell lung cancer (NSCLC) with wild-type epidermal growth factor receptor (EGFR) is still a challenge. This study explored antitumor activity of high-dose icotinib (an EGFR tyrosine kinase inhibitor) plus sequential docetaxel against wild-type EGFR NSCLC cells-generated nude mouse xenografts. Nude mice were subcutaneously injected with wild-type EGFR NSCLC A549 cells and divided into different groups for 3-week treatment. Tumor xenograft volumes were monitored and recorded, and at the end of experiments, tumor xenografts were removed for Western blot and immunohistochemical analyses. Compared to control groups (negative control, regular-dose icotinib [IcoR], high-dose icotinib [IcoH], and docetaxel [DTX]) and regular icotinib dose (60 mg/kg) with docetaxel, treatment of mice with a high-dose (1200 mg/kg) of icotinib plus sequential docetaxel for 3 weeks (IcoH-DTX) had an additive effect on suppression of tumor xenograft size and volume (P < 0.05). Icotinib-containing treatments markedly reduced phosphorylation of EGFR, mitogen activated protein kinase (MAPK), and protein kinase B (Akt), but only the high-dose icotinib-containing treatments showed an additive effect on CD34 inhibition (P < 0.05), an indication of reduced microvessel density in tumor xenografts. Moreover, high-dose icotinib plus docetaxel had a similar effect on mouse weight loss (a common way to measure adverse reactions in mice), compared to the other treatment combinations. The study indicate that the high dose of icotinib plus sequential docetaxel (IcoH-DTX) have an additive effect on suppressing the growth of wild-type EGFR NSCLC cell nude mouse xenografts, possibly through microvessel density reduction. Future clinical trials are needed to confirm the findings of this study. PMID:27852073

The effect of ezetimibe-statin combination on steroid hormone production in men with coronary artery disease and low cholesterol levels.

PubMed

Krysiak, Robert; Kowalska, Beata; Żmuda, Witold; Okopień, Bogusław

2015-04-01

Aggressive statin treatment was found to slightly reduce testosterone production. The aim of this study was to compare the effects of ezetimibe-statin combination and high-dose statin therapy on testicular and adrenal cortex function in men with LDL cholesterol levels below 70 mg/dL. The study included 26 adult men with coronary artery disease. Twelve of these patients did not tolerate high-dose statin therapy and were treated with lower doses of a statin plus ezetimibe. Fourteen patients tolerating high-dose simvastatin or rosuvastatin treatment continued high-dose statin therapy throughout the study period. Plasma lipids, glucose homeostasis markers and plasma levels of testosterone, cortisol, dehydroepiandrosterone sulphate, sex hormone-binding globulin, gonadotropins and ACTH, as well as urine free cortisol were assessed at baseline and after 16 weeks of treatment. Replacing high-dose statin therapy with ezetimibe/statin combination therapy reduced plasma levels of LH by 32% (p=0.043), as well as increased plasma levels of testosterone by 20% (p=0.038). Ezetimibe/statin combination did not induce any significant changes in plasma levels or urine excretion of the remaining hormones. At the end of the study, plasma LH levels were higher, while plasma testosterone levels were lower in patients receiving the combination therapy than in those treated only with high-dose statin. Our results indicate that ezetimibe combined with moderate statin dose exerts a less pronounced effect on testicular function in comparison with high-dose statin therapy. Copyright © 2014 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

The effects of recombinant activated factor VII dose on the incidence of thromboembolic events in patients with coagulopathic bleeding.

PubMed

Bucklin, Mason H; Acquisto, Nicole M; Nelson, Catherine

2014-05-01

Previous studies have suggested the used of off-label recombinant factor VII (rFVIIa) increases the risk of thromboembolic events, but the effect of the dose of rFVIIa is not well described in the literature. All adult patients that received off-label rFVIIa from 2005-2012 were included in this single-center, retrospective cohort study. The primary endpoint was the incidence of a thromboembolic event in the low dose (<50 mcg/kg) compared to the high dose (≥50 mcg/kg) cohort. Secondary endpoints compared time to thromboembolic event, incidence of arterial compared to venous events, and mortality. There were 152 patients that received rFVIIa during the study period with 66 in the low dose cohort and 86 in the high dose cohort. Mean total dose of rFVIIa was 30.2 mcg/kg (SD ± 9.5 mcg/kg) in the low dose and 99.8 mcg/kg (SD ± 64.7 mcg/kg) in the high dose cohort (p=0.0001). The overall incidence of thromboembolic events was 12.5%. There were 12 (14%) events in the low dose cohort and seven (10.6%) in the high dose cohort, RR=0.76 (95% CI 0.31-1.82). There were no differences in any of the secondary outcomes. A higher incidence of thromboembolic events in cardiothoracic surgery (20.8%) and penetrating trauma patients (21.4%) was seen compared to the remaining cohort (6.7%). No significant difference in the incidence of thromboembolic events was seen between low dose versus high dose rFVIIa over a seven year period at our institution. However, due to the relatively low overall incidence and a small sample size, type II error may be present. Copyright © 2014 Elsevier Ltd. All rights reserved.

Dose-dependent misrejoining of radiation-induced DNA double-strand breaks in human fibroblasts: Experimental and theoretical study for high and low LET radiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rydberg, Bjorn; Cooper, Brian; Cooper, Priscilla K.

2004-11-18

Misrejoining of DNA double-strand breaks (DSBs) was measured in human primary fibroblasts after exposure to X-rays and high LET particles (He, N and Fe) in the dose range 10-80 Gy. To measure joining of wrong DNA ends, the integrity of a 3.2 Mbp restriction fragment was analyzed directly after exposure and after 16 hr of repair incubation. It was found that the misrejoining frequency for X-rays was non-linearly related to dose, with less probability of misrejoining at low doses than at high doses. The dose dependence for the high LET particles, on the other hand, was closer to being linear,more » with misrejoining frequencies higher than for X-rays particularly at the lower doses. These experimental results were simulated with a Monte-Carlo approach that includes a cell nucleus model with all 46 chromosomes present, combined with realistic track structure simulations to calculate the geometrical positions of all DSBs induced for each dose. The model assumes that the main determinant for misrejoining probability is the distance between two simultaneously present DSBs. With a Gaussian interaction probability function with distance, it was found that both the low and high LET data could be fitted with an interaction distance (sigma of the Gaussian curve) of 0.25 {micro}m. This is half the distance previously found to best fit chromosomal aberration data in human lymphocytes using the same methods (Holley et al. Radiat. Res . 158, 568-580 (2002)). The discrepancy may indicate inadequacies in the chromosome model, for example insufficient chromosomal overlap, but may also partly be due to differences between fibroblasts and lymphocytes. Although the experimental data was obtained at high doses, the Monte Carlo calculations could be extended to lower doses. It was found that a linear component of misrejoining versus dose dominated for doses below 1 Gy for all radiations, including X-rays. The calculated relative biological efficiency (RBE) for misrejoining at this low dose region was 31 for the He-ions, 28 for the N-ions and 19 for Fe-ions.« less

Non-Malignant Thyroid Diseases Following a Wide Range of Radiation Exposures

PubMed Central

Ron, Elaine; Brenner, Alina

2013-01-01

Background The thyroid gland is one of the most radiosensitive human organs. While it is well known that radiation exposure increases the risk of thyroid cancer, less is known about its effects in relation to non-malignant thyroid diseases. Objectives The aim of this review is to evaluate the effects of high and low dose radiation on benign structural and functional diseases of the thyroid. Methods We examined the results of major studies from cancer patients treated with high-dose radiotherapy or thyrotoxicosis patients treated with high doses of iodine-131, patients treated with moderate to high dose radiotherapy for benign diseases, persons exposed to low doses from environmental radiation and survivors of the atomic bombings who were exposed to a range of doses. We evaluated radiation effects on structural (tumors, nodules), functional (hyper- and hypothyroidism), and autoimmune thyroid diseases. Results Following a wide range of doses of ionizing radiation, an increased risk of thyroid adenomas and nodules was observed in a variety of populations and settings. The dose response appeared to be linear at low to moderate doses, but in one study there was some suggestion of a reduction in risk above 5 Gy. The elevated risk for benign tumors continues for decades following exposure. Considerably less consistent findings are available regarding functional thyroid diseases including autoimmune diseases. In general, associations for these outcomes were fairly weak and significant radiation effects were most often observed following high doses, particularly for hypothyroidism. Conclusions A significant radiation dose-response relation was demonstrated for benign nodules and follicular adenomas. The effects of radiation on functional thyroid diseases are less clear, partly due to the greater difficulties studying these diseases. PMID:21128812

In vivo safety and tolerability study of QR-441(a) using three dose formulations and three routes of administration in chickens.

PubMed

Cummings, Timothy S; Guralnik, Mario; Rosenbloom, Richard A; Petteruti, Michael P; Digian, Kelly; Lefante, Carolyn

2007-01-01

The current study assessed the safety, tolerability, and palatability of the experimental drug QR-441(a) using three dose formulations and three routes of administration. A 4-day study was carried out using a total of 132 chickens. A total of 11 groups were formed (12 chickens per group) subjected to varying concentrations and routes of administration of QR-441(a). Chickens were given a high, medium, or low dose of QR-441(a) in either feed, water, or both for a period of 4 days. In addition, one group was dosed intranasally, one drop per nostril four times a day. Although no lesions were found to suggest toxicity or irritability, the medium- and high-dose water groups reduced their water intake. This reduction in water intake suggests that chickens may find the medium and high water doses unpalatable. There was no reduction in water intake in the low-dose water groups or in any of the formulated feed groups. There was also no evidence of toxicity or irritability in the nasal-dose group. These data support the use of the low, medium, and high doses in feed and the use of the low-dose concentration in water for the administration of QR-441(a). The data also suggest that QR-441(a) can be administered intranasally without the presence of any adverse events.

Transferring Patients From Methadone to Buprenorphine: The Feasibility and Evaluation of Practice Guidelines.

PubMed

Lintzeris, Nicholas; Monds, Lauren A; Rivas, Consuelo; Leung, Stefanie; Dunlop, Adrian; Newcombe, David; Walters, Carina; Galea, Susanna; White, Nancy; Montebello, Mark; Demirkol, Apo; Swanson, Nicola; Ali, Robert

Transfer from methadone to buprenorphine is problematic for many opioid-dependent patients, with limited documented evidence or practical clinical guidance, particularly for the range of methadone doses routinely prescribed for most patients (>50 mg). This study aimed to implement and evaluate recent national Australian guidelines for transferring patients from methadone to buprenorphine. A multisite prospective cohort study. Participants were patients who transferred from methadone to buprenorphine-naloxone at 1 of 4 specialist addiction centers in Australia and New Zealand. Clinicians were trained in the guidelines, and medical records were reviewed to examine process (eg, transfer setting, doses, and guideline adherence) and safety (precipitated withdrawal) measures. Participants completed research interviews before and after transfer-assessing changes in substance use, health outcomes, and side effects. In all, 33 participants underwent transfer, 9 from low methadone doses (<30 mg), 9 from medium doses (30-50 mg), and 15 from high doses (>50 mg). The majority of high-dose transfers occurred in inpatient settings. There was reasonable guideline adherence, and no complications identified in the low and medium-dose transfers. Three high-dose transfers (20%) experienced precipitated withdrawal, and 7/33 participants (21%) returned to methadone within 1 week of attempted transfer. Transfer is feasible in outpatient settings for those transferring from methadone doses below 50 mg; however, inpatient settings and specialist supervision is recommended for higher-dose transfers. The Australian clinical guidelines appear safe and feasible, although further research is required to optimize high-dose transfer procedures.

Stage III and oestrogen receptor negativity are associated with poor prognosis after adjuvant high-dose therapy in high-risk breast cancer

PubMed Central

Hohaus, S; Funk, L; Martin, S; Schlenk, R F; Abdallah, A; Hahn, U; Egerer, G; Goldschmidt, H; Schneeweiß, A; Fersis, N; Kaul, S; Wallwiener, D; Bastert, G; Haas, R

1999-01-01

We report on the efficacy and toxicity of a sequential high-dose therapy with peripheral blood stem cell (PBSC) support in 85 patients with high-risk stage II/III breast cancer. There were 71 patients with more than nine tumour-positive axillary lymph nodes. An induction therapy of two cycles of ifosfamide (total dose, 7.5 g m−2) and epirubicin (120 mg m−2) was given, and PBSC were harvested during G-CSF-supported leucocyte recovery following the second cycle. The PBSC-supported high-dose chemotherapy consisted of two cycles of ifosfamide (total dose, 12 000 mg m−2), carboplatin (900 mg m−2) and epirubicin (180 mg m−2). Patients were autografted with a median number of 3.7 × 106 CD34+ cells kg−1 (range, 1.9–26.5 × 106) resulting in haematological reconstitution within approximately 2 weeks following high-dose therapy. The toxicity was moderate in general, and there was no treatment-related toxic death. Twenty-one patients relapsed between 3 and 30 months following the last cycle of high-dose therapy (median, 11 months). The probability of disease-free and overall survival at 4 years were 60% and 83%, respectively. According to a multivariate analysis, patients with stage II disease had a significantly better probability of disease-free survival (74%) in comparison to patients with stage III disease (36%). The probability of disease-free survival was also significantly better for patients with oestrogen receptor-positive tumours (70%) compared to patients with receptor-negative ones (40%). Bone marrow samples collected from 52 patients after high-dose therapy were examined to evaluate the prognostic relevance of isolated tumour cells. The proportion of patients presenting with tumour cell-positive samples did not change in comparison to that observed before high-dose therapy (65% vs 71%), but a decrease in the incidence and concentration of tumour cells was observed over time after high-dose therapy. This finding was true for patients with relapse and for those in remission, which argues against a prognostic significance of isolated tumour cells in bone marrow. In conclusion, sequential high-dose chemotherapy with PBSC support can be safely administered to patients with high-risk stage II/III breast cancer. Further intensification of the therapy, including the addition of non-cross resistant drugs or immunological approaches such as the use of antibodies against HER-2/NEU, may be envisaged for patients with stage III disease and hormone receptor-negative tumours. © 1999 Cancer Research Campaign PMID:10188897

Acute cognitive effects of high doses of dextromethorphan relative to triazolam in humans

PubMed Central

Carter, Lawrence P.; Reissig, Chad J.; Johnson, Matthew W.; Klinedinst, Margaret A.; Griffiths, Roland R.

2012-01-01

BACKGROUND Although concerns surrounding high-dose dextromethorphan (DXM) abuse have recently increased, few studies have examined the acute cognitive effects of high doses of DXM. The aim of this study was to compare the cognitive effects of DXM with those of triazolam and placebo. METHODS Single, acute, oral doses of DXM (100, 200, 300, 400, 500, 600, 700, 800 mg/70 kg), triazolam (0.25, 0.5 mg /70 kg), and placebo were administered p.o. to twelve healthy volunteers with histories of hallucinogen use, under double-blind conditions, using an ascending dose run-up design. Effects on cognitive performance were examined at baseline and after drug administration for up to 6 hours. RESULTS Both triazolam and DXM produced acute impairments in attention, working memory, episodic memory, and metacognition. Impairments observed following doses of 100-300 mg/70 kg DXM were generally smaller in magnitude than those observed after 0.5 mg/70 kg triazolam. Doses of DXM that impaired performance to the same extent as triazolam were in excess of 10-30 times the therapeutic dose of DXM. CONCLUSION The magnitude of the doses required for these effects and the absence of effects on some tasks within the 100-300 mg/70 kg dose range of DXM, speak to the relatively broad therapeutic window of over-the-counter DXM preparations when used appropriately. However, the administration of supratherapeutic doses of DXM resulted in acute cognitive impairments on all tasks that were examined. These findings are likely relevant to cases of high-dose DXM abuse. PMID:22989498

Acceleration of atherogenesis in ApoE-/- mice exposed to acute or low-dose-rate ionizing radiation.

PubMed

Mancuso, Mariateresa; Pasquali, Emanuela; Braga-Tanaka, Ignacia; Tanaka, Satoshi; Pannicelli, Alessandro; Giardullo, Paola; Pazzaglia, Simonetta; Tapio, Soile; Atkinson, Michael J; Saran, Anna

2015-10-13

There is epidemiological evidence for increased non-cancer mortality, primarily due to circulatory diseases after radiation exposure above 0.5 Sv. We evaluated the effects of chronic low-dose rate versus acute exposures in a murine model of spontaneous atherogenesis. Female ApoE-/- mice (60 days) were chronically irradiated for 300 days with gamma rays at two different dose rates (1 mGy/day; 20 mGy/day), with total accumulated doses of 0.3 or 6 Gy. For comparison, age-matched ApoE-/- females were acutely exposed to the same doses and sacrificed 300 days post-irradiation. Mice acutely exposed to 0.3 or 6 Gy showed increased atherogenesis compared to age-matched controls, and this effect was persistent. When the same doses were delivered at low dose rate over 300 days, we again observed a significant impact on global development of atherosclerosis, although at 0.3 Gy effects were limited to the descending thoracic aorta. Our data suggest that a moderate dose of 0.3 Gy can have persistent detrimental effects on the cardiovascular system, and that a high dose of 6 Gy poses high risks at both high and low dose rates. Our results were clearly nonlinear with dose, suggesting that lower doses may be more damaging than predicted by a linear dose response.

High-dose boron and silver ion implantation into PMMA probed by slow positrons: Effects of carbonization and formation of metal nanoparticles

NASA Astrophysics Data System (ADS)

Kavetskyy, T.; Iida, K.; Nagashima, Y.; Kuczumow, A.; Šauša, O.; Nuzhdin, V.; Valeev, V.; Stepanov, A. L.

2017-01-01

The Doppler broadening slow positron beam spectroscopy (SPBS) data for the previously observed effect of carbonization in high-dose (>1016 ion/cm2) 40 keV boron-ion-implanted polymethylmethacrylate (B:PMMA) and another one obtained for the effect of formation of metal nanoparticles in high-dose 30 keV silver-ion-implanted polymer (Ag:PMMA) are compared. Following to the Doppler broadening SPBS results, a difference in the high-dose ion-irradiation-induced processes in B:PMMA and Ag:PMMA is detected.

[Development of a perforated peptic ulcer in a child during high dose prednisolone treatment].

PubMed

Moll Harboe, Kirstine; Midtgaard, Helle; Wewer, Vibeke; Cortes, Dina

2012-09-24

Since perforated peptic ulcer is uncommon in children proton pump inhibitor prophylaxis is not routinely recommended when children are treated with high dose steroids. We describe a case of perforated ulcer in a six-year-old patient with nephrotic syndrome treated with high dose prednisolone. Initially, ulcer was not suspected due to uncharacteristic symptoms. The child developed peritoneal signs and surgery revealed a perforated peptic ulcer in the stomach. We recommend treatment with proton pump inhibitors if children, who are treated with high dose steroids develop abdominal symptoms, which can be caused by an ulcus.

Low-, medium- and high-dose steroids with or without aminocaproic acid in adult hematopoietic SCT patients with diffuse alveolar hemorrhage.

PubMed

Rathi, N K; Tanner, A R; Dinh, A; Dong, W; Feng, L; Ensor, J; Wallace, S K; Haque, S A; Rondon, G; Price, K J; Popat, U; Nates, J L

2015-03-01

Diffuse alveolar hemorrhage (DAH) is a poorly understood complication of transplantation carrying a high mortality. Patients commonly deteriorate and require intensive care unit (ICU) admission. Treatment with high-dose steroids and aminocaproic acid (ACA) has been suggested. The current study examined 119 critically ill adult hematopoietic transplant patients treated for DAH. Patients were subdivided into low-, medium- and high-dose steroid groups with or without ACA. All groups had similar baseline characteristics and severity of illness scores. Primary objectives were 30, 60, 100 day, ICU and hospital mortality. Overall mortality (n=119) on day 100 was high at 85%. In the steroids and ACA cohort (n=82), there were no significant differences in 30, 60, 100, day, ICU and hospital mortality between the dosing groups. In the steroids only cohort (n=37), the low-dose steroid group had a lower ICU and hospital mortality (P=0.02). Adjunctive treatment with ACA did not produce differences in outcomes. In the multivariate analysis, medium- and high-dose steroids were associated with a higher ICU mortality (P=0.01) as compared with the low-dose group. Our data suggest that treatment strategies may need to be reanalyzed to avoid potentially unnecessary and potentially harmful therapies.

Comprehensive evaluations of cone-beam CT dose in image-guided radiation therapy via GPU-based Monte Carlo simulations

NASA Astrophysics Data System (ADS)

Montanari, Davide; Scolari, Enrica; Silvestri, Chiara; Jiang Graves, Yan; Yan, Hao; Cervino, Laura; Rice, Roger; Jiang, Steve B.; Jia, Xun

2014-03-01

Cone beam CT (CBCT) has been widely used for patient setup in image-guided radiation therapy (IGRT). Radiation dose from CBCT scans has become a clinical concern. The purposes of this study are (1) to commission a graphics processing unit (GPU)-based Monte Carlo (MC) dose calculation package gCTD for Varian On-Board Imaging (OBI) system and test the calculation accuracy, and (2) to quantitatively evaluate CBCT dose from the OBI system in typical IGRT scan protocols. We first conducted dose measurements in a water phantom. X-ray source model parameters used in gCTD are obtained through a commissioning process. gCTD accuracy is demonstrated by comparing calculations with measurements in water and in CTDI phantoms. Twenty-five brain cancer patients are used to study dose in a standard-dose head protocol, and 25 prostate cancer patients are used to study dose in pelvis protocol and pelvis spotlight protocol. Mean dose to each organ is calculated. Mean dose to 2% voxels that have the highest dose is also computed to quantify the maximum dose. It is found that the mean dose value to an organ varies largely among patients. Moreover, dose distribution is highly non-homogeneous inside an organ. The maximum dose is found to be 1-3 times higher than the mean dose depending on the organ, and is up to eight times higher for the entire body due to the very high dose region in bony structures. High computational efficiency has also been observed in our studies, such that MC dose calculation time is less than 5 min for a typical case.

Efficacy of Low-Dose Corticosteroid Therapy Versus High-Dose Corticosteroid Therapy in Bell's Palsy in Children.

PubMed

Arican, Pinar; Dundar, Nihal Olgac; Gencpinar, Pinar; Cavusoglu, Dilek

2017-01-01

Bell's palsy is the most common cause of acute peripheral facial nerve paralysis, but the optimal dose of corticosteroids in pediatric patients is still unclear. This retrospective study aimed to evaluate the efficacy of low-dose corticosteroid therapy compared with high-dose corticosteroid therapy in children with Bell's palsy. Patients were divided into 2 groups based on the dose of oral prednisolone regimen initiated. The severity of idiopathic facial nerve paralysis was graded according to the House-Brackmann Grading Scale. The patients were re-assessed in terms of recovery rate at the first, third, and sixth months of treatment. There was no significant difference in complete recovery between the 2 groups after 1, 3, and 6 months of treatment. In our study, we concluded that even at a dose of 1 mg/kg/d, oral prednisolone was highly effective in the treatment of Bell's palsy in children.

Evaluation of incidence and risk factors for high-dose methotrexate-induced nephrotoxicity.

PubMed

Wiczer, Tracy; Dotson, Emily; Tuten, Amy; Phillips, Gary; Maddocks, Kami

2016-06-01

High-dose methotrexate (doses ≥1 g/m(2)) is a key component of several chemotherapy regimens used to treat patients with leukemia or lymphoma. Despite appropriate precautions with hydration, urine alkalinization, and leucovorin, nephrotoxicity remains a risk which can lead to significant morbidity and mortality. Current reports of risk factors for nephrotoxicity focus on patients with nephrotoxicity with a lack of comparison to those without toxicity. This study aimed to describe the incidence of high-dose methotrexate-induced nephrotoxicity at our institution and determined risk factors for high-dose methotrexate-induced nephrotoxicity by examining characteristics of patients with and without nephrotoxicity. This was a retrospective, single-center, chart review. Adult patients with a diagnosis of leukemia or lymphoma who received high-dose methotrexate were included. Serum creatinine values were used to evaluate nephrotoxicity according to Common Terminology Criteria for Adverse Events criteria v4.03. Data related to the following proposed risk factors were collected: age, sex, body mass index, methotrexate dose, number of high-dose methotrexate exposures, leucovorin administration route, baseline renal function, albumin, hydration status, Clostridium difficile infection, urine pH, and concomitant interacting and nephrotoxic medications. The primary endpoint was evaluated with exact binomial methods and risk factors were identified using multivariable random-effects logistic regression. Final analyses included 140 patients with 432 high-dose methotrexate exposures. There were no differences in baseline demographical characteristics. Fifty-four patients (38.6%) experienced nephrotoxicity of any grade: 27.9% with grade 1, 5.7% with grade 2, 3.6% grade 3, 0% with grade 4, and 1.4% with grade 5 toxicity. More patients in the toxicity group received doses of methotrexate ≥3 g/m(2) (58.3% versus 57.2%, p < 0.001), had an albumin level <3 g/dL (31.9% versus 15.9%, p = 0.04), and received an interacting medication during high-dose methotrexate clearance (44.4% versus 24.7%, p = 0.003). Male gender (OR 2.3, 95% CI: 1.27-4.18, p = 0.006), albumin (OR 0.44, 95% CI: 0.26-0.75, p = 0.002), number of drug interactions (OR 1.60, 95% CI: 1.15-2.21, p = 0.005), and use of furosemide (OR 2.56, 95% CI 1.46-4.48, p = 0.001) were all independent risk factors for the development of nephrotoxicity. Nephrotoxicity is a possible complication of therapy with high-dose methotrexate with most instances comprising grade 1-2 toxicity. Male gender, low albumin, and administration of interacting drugs or furosemide during high-dose methotrexate clearance may predispose patients to nephrotoxicity. © The Author(s) 2015.

Efficacy and safety of combination therapy of high-dose losartan and hydrochlorothiazide in patients with hypertension.

PubMed

Shiga, Yuhei; Miura, Shin-Ichiro; Norimatsu, Kenji; Hitaka, Yuka; Nagata, Itsuki; Koyoshi, Rie; Morii, Joji; Kuwano, Takashi; Uehara, Yoshinari; Inoue, Asao; Shirotani, Tetsuro; Fujisawa, Kazuaki; Matsunaga, Eiyu; Saku, Keijiro

2015-12-01

We analyzed the efficacy and safety of combination therapy of high-dose losartan (100 mg/day) and hydrochlorothiazide (HCTZ, 12.5 mg/day) compared with those of the combination of high-dose telmisartan (80 mg/day) and HCTZ (12.5 mg/day). Forty hypertensive patients who received a combination of high-dose telmisartan and HCTZ were enrolled. We applied a changeover strategy with switching from a combination of high-dose telmisartan and HCTZ to high-dose losartan and HCTZ. We divided the patients into two groups; those who achieved the target blood pressure (controlled group) and those who did not reach the target blood pressure (uncontrolled group) before the changeover and performed further analysis. The uncontrolled group showed a significant decrease in systolic blood pressure (SBP) (143±12 mmHg to 126±11 mmHg at three months). In addition, serum uric acid significantly decreased in all subjects, and in each of the controlled and uncontrolled groups. There were no significant changes in other biochemical parameters, such as potassium and hemoglobin A1c, at three months after the changeover in all subjects. Combination therapy with high-dose losartan and HCTZ was superior to the combination of telmisartan and HCTZ with respect to significant decreases in systolic blood pressure and serum uric acid in hypertensive patients. © The Author(s) 2014.

Equivalent Noise Dose Obtained through Hearing Aids in the Classrooms of Hearing-Impaired Children.

ERIC Educational Resources Information Center

Wilde, Ronald A.

1990-01-01

A commercial noise dose meter was used to estimate the equivalent noise dose received through high-gain hearing aids worn in four classrooms in a school for deaf children. There were no significant differences among nominal saturation sound pressure level (SSPL) settings, and all SSPL settings produced very high equivalent noise doses. (Author/JDD)

Selective effects of two systemic fungicides on soil fungi.

PubMed

Abdel-Fattah, H M; Abdel-Kader, M I; Hamida, S

1982-08-20

BAS 317 00F was not toxic to the total count of fungi after 2 days but was regularly significantly toxic at the three doses after 5, 20 and 40 days and toxic at the low and the high doses after 80 days. In the agar medium, it was toxic to the counts of total fungi. Aspergillus, A. terreus, Rhizopus oryzae and Mucor racemosus at the high dose. Only the mycelial growth of Trichoderma viride which was significantly inhibited by the three doses when this fungicide was added to the liquid medium. Polyram-Combi induced two effects on the total population of soil fungi. One inhibitory and this was demonstrated almost regularly after 2, 10 and 40 days and the other stimulatory after 80 days of treatment with the low and the high doses. In the agar medium, this fungicide was very toxic to total fungi and to almost all fungal genera and species at the three doses. Several fungi could survive the high dose. In liquid medium, the test fungi showed variable degree of sensitivity and the most sensitive was Gliocladium roseum which was completely eradicated by the three doses.

Evaluation of clinical hypothyroidism risk due to irradiation of thyroid and pituitary glands in radiotherapy of nasopharyngeal cancer patients.

PubMed

Lin, Zhixiong; Wang, Xiaoyan; Xie, Wenjia; Yang, Zhining; Che, Kaijun; Wu, Vincent W C

2013-12-01

Radiation-induced thyroid dysfunction after radiotherapy for nasopharyngeal cancer (NPC) has been reported. This study investigated the radiation effects of the thyroid and pituitary glands on thyroid function after radiotherapy for NPC. Sixty-five NPC patients treated with radiotherapy were recruited. Baseline thyroid hormone levels comprising free triiodothyronine (fT3), free thyroxine (fT4) and thyroid-stimulating hormone (TSH) were taken before treatment and at 3, 6, 12 and 18 months. A seven-beam intensity-modulated radiotherapy plan was generated for each patient. Thyroid and pituitary gland dose volume histograms were generated, dividing the patients into four groups: high (>50 Gy) thyroid and pituitary doses (HTHP group); high thyroid and low pituitary doses (HTLP group); low thyroid and high pituitary doses; and low thyroid and pituitary doses. Incidence of hypothyroidism was analysed. Twenty-two (34%) and 17 patients (26%) received high mean thyroid and pituitary doses, respectively. At 18 months, 23.1% of patients manifested various types of hypothyroidism. The HTHP group showed the highest incidence (83.3%) of hypothyroidism, followed by the HTLP group (50%). NPC patients with high thyroid and pituitary gland doses carried the highest risk of abnormal thyroid physiology. The dose to the thyroid was more influential than the pituitary dose at 18 months after radiotherapy, and therefore more attention should be given to the thyroid gland in radiotherapy planning. © 2013 The Royal Australian and New Zealand College of Radiologists.

In vivo TLD dose measurements in catheter-based high-dose-rate brachytherapy.

PubMed

Adlienė, Diana; Jakštas, Karolis; Urbonavičius, Benas Gabrielis

2015-07-01

Routine in vivo dosimetry is well established in external beam radiotherapy; however, it is restricted mainly to detection of gross errors in high-dose-rate (HDR) brachytherapy due to complicated measurements in the field of steep dose gradients in the vicinity of radioactive source and high uncertainties. The results of in vivo dose measurements using TLD 100 mini rods and TLD 'pin worms' in catheter-based HDR brachytherapy are provided in this paper alongside with their comparison with corresponding dose values obtained using calculation algorithm of the treatment planning system. Possibility to perform independent verification of treatment delivery in HDR brachytherapy using TLDs is discussed. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Micronucleus induction in Vicia faba roots. Part 2. Biological effects of neutrons below 1 cGy.

PubMed

Marshall, I; Bianchi, M

1983-08-01

A dose-effect relationship has been established for high-energy neutrons (maximum energy 600 MeV) within a dose range of 0.2 to 80 cGy and for low-energy neutrons produced by a 252Cf source (mean energy 2.35 MeV) for doses between 0.2 and 5 cGy. The frequency of micronuclei was found to increase linearly with dose. The relative biological effectiveness (r.b.e) values calculated using 60Co radiation as a reference were, in the high-dose region, 4.7 +/- 0.4 and 11.8 +/- 1.3 for the high- and low-energy neutrons, respectively. At doses below 1 cGy constant values of 25.4 +/- 4.4 and 63.7 +/- 12 were reached for the respective neutron energies.

Combination of High-Dose Methylprednisolone and Defibrotide for Veno-Occlusive Disease in Pediatric Hematopoietic Stem Cell Transplant Recipients.

PubMed

Gloude, Nicholas J; Jodele, Sonata; Teusink-Cross, Ashley; Grimley, Michael; Davies, Stella M; Lane, Adam; Myers, Kasiani C

2018-01-01

Veno-occlusive disease (VOD) is a serious complication of hematopoietic stem cell transplant (HSCT), with high mortality in severe cases and until recently very limited therapeutic options consisting largely of supportive care. Defibrotide was recently approved in the United States for the treatment of severe VOD in patients with renal or pulmonary dysfunction after HSCT. Our group previously published on the use of high-dose methylprednisolone (500 mg/m 2 per dose every 12 hours for 6 doses) in patients with VOD, showing good success. A small subset of these individuals were also treated with defibrotide, but additional studies using the combination of high-dose methylprednisolone and defibrotide for the treatment of VOD are lacking. We present a single-institution retrospective chart review of 15 HSCT patients with VOD treated with the combination of high-dose methylprednisolone and defibrotide. VOD developed at a median of 17 days post-HSCT, and combination therapy was initiated within 1 day of VOD diagnosis. Twelve of 15 patients (80%) had multiorgan failure. Our single-center experience using both high-dose methylprednisolone and defibrotide showed a day +100 survival rate of 73% and an overall VOD complete resolution rate of 66.7%, higher than the rates reported in the recent literature using defibrotide alone (40% to 50% day +100 overall survival). These data suggest that the combination of high-dose steroids and defibrotide may be superior to defibrotide alone and warrant further investigation. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Differential Effects of High Dose Magnetic Seizure Therapy (MST) and Electroconvulsive Shock (ECS) on Cognitive Function

PubMed Central

Spellman, Timothy; McClintock, Shawn M.; Terrace, Herbert; Luber, Bruce; Husain, Mustafa M.; Lisanby, Sarah H.

2008-01-01

Background Magnetic seizure therapy (MST) is under investigation as an alternative form of convulsive therapy that induces more focal seizures and spares cortical regions involved in memory. Using a newly expanded version of the Columbia University Primate Cognitive Profile, we compared the cognitive effects of high-dose MST delivered at 100 Hz (6X seizure threshold) with electroconvulsive shock (ECS) delivered at 2.5X seizure threshold. Methods Daily high-dose MST, ECS, and Sham (anesthesia-only) were administered for 4 weeks each in a within-subject cross-over design. Rhesus macaques (n = 3) were trained on five cognitive tasks assessing automatic memory, anterograde learning and memory, combined anterograde and retrograde simultaneous chaining, and spatial and serial working memory. Acutely following each intervention, monkeys were tested on the cognitive battery twice daily, separated by a 3-hour retention interval. Results Subjects were slower to complete criterion tasks (p’s<0.0001) following ECS, compared to sham and high-dose MST. Moreover, time to task-completion following high-dose MST did not differ from sham. Out of 6 measures of accuracy, treatment effects were found in 4; in all of these, ECS, but not MST, fared worse than Sham. On all accuracy and time to completion measurements, subjects performed as well as following high-dose MST as did subjects from a previous study on moderate-dose MST. Conclusion These findings provide evidence that high-dose MST results in benign acute cognitive side-effect profile relative to ECS, and are in line with our previous studies. PMID:18262171

Characteristic miR-24 Expression in Gastric Cancers among Atomic Bomb Survivors.

PubMed

Naito, Yutaka; Oue, Naohide; Pham, Trang T B; Yamamoto, Manabu; Fujihara, Megumu; Ishida, Teruyoshi; Mukai, Shoichiro; Sentani, Kazuhiro; Sakamoto, Naoya; Hida, Eisuke; Sasaki, Hiroki; Yasui, Wataru

2015-01-01

To elucidate the mechanism of radiation-induced cancers, we analyzed the expression profiles of microRNAs extracted from formalin-fixed paraffin-embedded (FFPE) gastric cancer (GC) tissue samples from atomic bomb survivors. The expression levels of miR-21, miR-24, miR-34a, miR-106a, miR-143, and miR-145 were measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR). The expression of microRNAs was measured by qRT-PCR in a Hiroshima University Hospital cohort comprising 32 patients in the high-dose-exposed group and 18 patients in the low-dose-exposed group who developed GC after the bombing. The GC cases showing high expression of miR-24, miR-143, and miR-145 were more frequently found in the high-dose-exposed group than in the low-dose-exposed group. We next performed qRT-PCR of miR-24, miR-143, and miR-145 in a cohort from the Hiroshima Red Cross Hospital and Atomic-Bomb Survivors Hospital comprising 122 patients in the high-dose-exposed group and 48 patients in the low-dose-exposed group who developed GC after the bombing. High expressions of miR-24 and miR-143 were more frequently found in the high-dose-exposed group than in the low-dose-exposed group. Multivariate analysis demonstrated that only high expression of miR-24 was an independent predictor for the exposure status. These results suggest that the measurement of miR-24 expression from FFPE samples is useful to identify radiation-associated GC.

Developmental toxicity study of D-tagatose in rats.

PubMed

Kruger, C L; Whittaker, M H; Frankos, V H; Schroeder, R E

1999-04-01

D-tagatose is a low-calorie sweetener that tastes like sucrose. The developmental toxicity of D-tagatose was investigated in Crl:CD(SD)BR rats administered D-tagatose at three dose levels (4000, 12,000, and 20,000 mg/kg body wt/day) via gastric intubation on days 6-15 of gestation. No compound-related toxicity was seen among any of the maternal groups. No treatment-related clinical effects were seen in the maternal animals at the 4000 mg/kg/day dose level. At the mid- and high-dose levels, most maternal animals had unformed or watery stools; this effect was most prominent early in the treatment period (Gestation Days 6-8). This effect was attributed to the osmotic effect of the large amount of D-tagatose given to the animals at these doses. Since D-tagatose is not digested or absorbed to a large extent, most of the sugar passes into the colon where it absorbs water and is fermented by colonic bacteria. Mean weight gain for the low- and mid-dose animals was comparable to the control; however, the high-dose group experienced a mean weight loss over the Gestation Day 6-9 interval. Over the entire treatment interval, however, mean weight gain for the high-dose animals was comparable to control. The decreased weight gain in the high-dose animals during the Gestation Day 6-9 interval was considered to be a direct result of laxation. In addition to the effect of laxation on body weight, reduced food consumption also contributed to the decreased weight gain. In the low-dose animals, no effect on food consumption was seen; however, both mid- and high-dose animals had food consumption values that were statistically significantly lower than the control. Food consumption was lowest during the Gestation Day 6-9 interval, the period when laxation was most prominent. Food consumption rebounded and was statistically significantly higher than the control for the mid- and high-dose animals during the posttreatment interval. Maternal liver weight for the low-dose animals was comparable to the control. However, a statistically significant increase in mean maternal liver weight was noted for the mid-and high-dose animals. Based on a lack of any corresponding histopathology, the increased liver weights were not considered toxicologically significant. There were no adverse effects on reproductive performance noted in any treatment group. No adverse treatment-related fetal effects on fetal weight, sex distribution, liver weight, or external, skeletal, or visceral malformations were noted at any dose level. Copyright 1999 Academic Press.

Risks Associated with High-Dose Lactobacillus rhamnosus in an Escherichia coli Model of Piglet Diarrhoea: Intestinal Microbiota and Immune Imbalances

PubMed Central

Yue, Yuan; Cai, Zheng-Xing; Lu, Qing-Ping; Zhang, Lu; Weng, Xiao-Gang; Zhang, Fan-Jian; Zhou, Dong; Yang, Jin-Cai; Wang, Jiu-Feng

2012-01-01

Probiotic could be a promising alternative to antibiotics for the prevention of enteric infections; however, further information on the dose effects is required. In this study, weanling piglets were orally administered low- or high-dose Lactobacillus rhamnosus ACTT 7469 (1010 CFU/d or 1012 CFU/d) for 1 week before F4 (K88)-positive Escherichia coli challenge. The compositions of faecal and gastrointestinal microbiota were recorded; gene expression in the intestines was assessed by real-time PCR; serum tumour necrosis factor-α (TNF-α) concentrations and intestinal Toll-like receptor 4 (TLR4) were detected by ELISA and immunohistochemistry, respectively. Unexpectedly, high-dose administration increased the incidence of diarrhoea before F4+ETEC challenge, despite the fact that both doses ameliorated F4+ETEC-induced diarrhoea with increased Lactobacillus and Bifidobacterium counts accompanied by reduced coliform shedding in faeces. Interestingly, L. rhamnosus administration reduced Lactobacillus and Bifidobacterium counts in the colonic contents, and the high-dose piglets also had lower Lactobacillius and Bacteroides counts in the ileal contents. An increase in the concentration of serum TNF-α induced by F4+ETEC was observed, but the increase was delayed by L. rhamnosus. In piglets exposed to F4+ETEC, jejunal TLR4 expression increased at the mRNA and protein levels, while jejunal interleukin (IL)-8 and ileal porcine β-defensins 2 (pBD2) mRNA expression increased; however, these increases were attenuated by administration of L. rhamnosus. Notably, expression of jejunal TLR2, ileal TLR9, Nod-like receptor NOD1 and TNF-α mRNA was upregulated in the low-dose piglets after F4+ETEC challenge, but not in the high-dose piglets. These findings indicate that pretreatment with a low dose of L. rhamnosus might be more effective than a high dose at ameliorating diarrhoea. There is a risk that high-dose L. rhamnosus pretreatment may negate the preventative effects, thus decreasing the prophylactic benefits against potential enteric pathogens. Our data suggest a safe threshold for preventative use of probiotics in clinical practice. PMID:22848393

[Protective effect of pretreatment of Salvia miltiorrhiza Bunge. f. alba plasma against oxygen-glucose deprivation-induced injury of cultured rat hippocampal neurons by inhibiting apoptosis].

PubMed

Li, Mei-Yi; Zhang, Yan-Bo; Zuo, Huan; Liu, Li-Li; Niu, Jing-Zhong

2012-02-25

The present study was to investigate the effect of Salvia miltiorrhiza Bunge. f. alba (SMA) pharmacological pretreatment on apoptosis of cultured hippocampal neurons from neonate rats under oxygen-glucose deprivation (OGD). Cultured hippocampal neurons were randomly divided into five groups (n = 6): normal plasma group, low dose SMA plasma (2.5%) group, middle dose SMA plasma (5%) group, high dose SMA plasma (10%) group and control group. The hippocampal neurons were cultured and treated with plasma from adult Wistar rats intragastrically administered with saline or aqueous extract of SMA. The apoptosis of neurons was induced by glucose-free Earle's solution containing 1 mmol/L Na2S2O4 and labeled by MTT and Annexin V/PI double staining. Moreover, protein expressions of Bcl-2 and Bax were detected by immunofluorescence. The results showed that few apoptotic cells were observed in control group, whereas the number of apoptotic cells was greatly increased in normal plasma group and low dose SMA plasma group. Both middle and high dose SMA plasma could protect cultured hippocampal neurons from apoptosis induced by OGD (P < 0.05). The protective effect of high dose SMA plasma was stronger than that of middle one (P < 0.05). Compared to control, normal plasma and low dose SMA plasma groups, middle and high dose SMA plasma groups both showed significantly higher levels of Bcl-2 (P < 0.05 or 0.01), whereas expressions of Bax was opposite. There were no significant differences of Bcl-2 and Bax expressions between middle and high dose SMA plasma groups. Number of Bcl-2- and Bax-positive cells had similar tendency. Bcl-2/Bax (number of positive cells) ratio was higher in high dose SMA plasma group than those of all the other groups (P < 0.05 or 0.01). These results suggest that pharmacological pretreatment of blood plasma containing middle and high dose SMA could raise viability and inhibit apoptosis of OGD-injured hippocampal neurons by up-regulating the expression of Bcl-2 and down-regulating the expression of Bax.

Booster and higher antigen doses of inactivated influenza vaccine in HIV-infected patients.

PubMed

Johnston, Jessica A; Tincher, Lindsey B; Lowe, Denise K

2013-12-01

To review the literature regarding booster or higher doses of influenza antigen for increasing immunogenicity of inactivated influenza vaccine (IIV) in HIV-infected patients. MEDLINE (1966 to September 2013) was searched using the terms immunize, influenza, vaccine, and HIV or AIDS in combination with two-dose, booster-dose, increased antigen, or high-dose. One trial of booster dosing with standard doses (SDs) of IIV, trivalent (IIV3); 2 trials of booster dosing with intermediate doses (ID) of H1N1 IIV or IIV3; and 1 trial of high-dose (HD) IIV3 were identified. Trials administering 2-dose, booster-dose, or increased antigen of influenza vaccine to patients with HIV were reviewed. Because adjuvanted IIV is not available and IIV, quadrivalent was recently approved in the United States, studies evaluating these vaccines were excluded. HIV-infected individuals are at high risk for influenza-related complications; however, vaccination with SD IIV may not confer optimal protection. It has been postulated that booster or higher doses of influenza antigen may lead to increased immunogenicity. When ID and SD or ID with boosters were evaluated in HIV-infected patients, significant increases in surrogate markers for influenza protection were not achieved. However, HD IIV3 did result in significant increases in seroprotective antibody levels, though 'clinical' influenza was not evaluated. Currently, evidence is insufficient to reach conclusions about the efficacy of booster dosing, ID, or HD influenza vaccine in HIV-infected patients. Trials evaluating booster or higher-antigen doses of IIV for 'clinical' influenza are necessary before routinely recommending for HIV-infected patients.

Pulmonary Venous Anatomy Imaging with Low-Dose, Prospectively ECG-Triggered, High-Pitch 128-Slice Dual Source Computed Tomography

PubMed Central

Thai, Wai-ee; Wai, Bryan; Lin, Kaity; Cheng, Teresa; Heist, E. Kevin; Hoffmann, Udo; Singh, Jagmeet; Truong, Quynh A.

2012-01-01

Background Efforts to reduce radiation from cardiac computed tomography (CT) are essential. Using a prospectively triggered, high-pitch dual source CT (DSCT) protocol, we aim to determine the radiation dose and image quality (IQ) in patients undergoing pulmonary vein (PV) imaging. Methods and Results In 94 patients (61±9 years, 71% male) who underwent 128-slice DSCT (pitch 3.4), radiation dose and IQ were assessed and compared between 69 patients in sinus rhythm (SR) and 25 in atrial fibrillation (AF). Radiation dose was compared in a subset of 19 patients with prior retrospective or prospectively triggered CT PV scans without high-pitch. In a subset of 18 patients with prior magnetic resonance imaging (MRI) for PV assessment, PV anatomy and scan duration were compared to high-pitch CT. Using the high-pitch protocol, total effective radiation dose was 1.4 [1.3, 1.9] mSv, with no difference between SR and AF (1.4 vs 1.5 mSv, p=0.22). No high-pitch CT scans were non-diagnostic or had poor IQ. Radiation dose was reduced with high-pitch (1.6 mSv) compared to standard protocols (19.3 mSv, p<0.0001). This radiation dose reduction was seen with SR (1.5 vs 16.7 mSv, p<0.0001) but was more profound with AF (1.9 vs 27.7 mSv, p=0.039). There was excellent agreement of PV anatomy (kappa 0.84, p<0.0001), and a shorter CT scan duration (6 minutes) compared to MRI (41 minutes, p<0.0001). Conclusions Using a high-pitch DSCT protocol, PV imaging can be performed with minimal radiation dose, short scan acquisition, and excellent IQ in patients with SR or AF. This protocol highlights the success of new cardiac CT technology to minimize radiation exposure, giving clinicians a new low-dose imaging alternative to assess PV anatomy. PMID:22586259

TH-A-9A-04: Incorporating Liver Functionality in Radiation Therapy Treatment Planning

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wu, V; Epelman, M; Feng, M

2014-06-15

Purpose: Liver SBRT patients have both variable pretreatment liver function (e.g., due to degree of cirrhosis and/or prior treatments) and sensitivity to radiation, leading to high variability in potential liver toxicity with similar doses. This work aims to explicitly incorporate liver perfusion into treatment planning to redistribute dose to preserve well-functioning areas without compromising target coverage. Methods: Voxel-based liver perfusion, a measure of functionality, was computed from dynamic contrast-enhanced MRI. Two optimization models with different cost functions subject to the same dose constraints (e.g., minimum target EUD and maximum critical structure EUDs) were compared. The cost functions minimized were EUDmore » (standard model) and functionality-weighted EUD (functional model) to the liver. The resulting treatment plans delivering the same target EUD were compared with respect to their DVHs, their dose wash difference, the average dose delivered to voxels of a particular perfusion level, and change in number of high-/low-functioning voxels receiving a particular dose. Two-dimensional synthetic and three-dimensional clinical examples were studied. Results: The DVHs of all structures of plans from each model were comparable. In contrast, in plans obtained with the functional model, the average dose delivered to high-/low-functioning voxels was lower/higher than in plans obtained with its standard counterpart. The number of high-/low-functioning voxels receiving high/low dose was lower in the plans that considered perfusion in the cost function than in the plans that did not. Redistribution of dose can be observed in the dose wash differences. Conclusion: Liver perfusion can be used during treatment planning potentially to minimize the risk of toxicity during liver SBRT, resulting in better global liver function. The functional model redistributes dose in the standard model from higher to lower functioning voxels, while achieving the same target EUD and satisfying dose limits to critical structures. This project is funded by MCubed and grant R01-CA132834.« less

[High-dose chemotherapy as a strategy to overcome drug resistance in solid tumors].

PubMed

Selle, Frédéric; Gligorov, Joseph; Soares, Daniele G; Lotz, Jean-Pierre

2016-10-01

The concept of high-doses chemotherapy was developed in the 1980s based on in vitro scientific observations. Exposure of tumor cells to increasing concentrations of alkylating agents resulted in increased cell death in a strong dose-response manner. Moreover, the acquired resistance of tumor cells could be overcome by dose intensification. In clinic, dose intensification of alkylating agents resulted in increased therapeutic responses, however associated with significant hematological toxicity. Following the development of autologous stem cells transplantation harvesting from peripheral blood, the high-doses of chemotherapy, initially associated with marked toxic effects, could be more easily tolerated. As a result, the approach was evaluated in different types of solid tumors, including breast, ovarian and germ cell tumors, small cell lung carcinoma, soft tissue sarcomas and Ewing sarcoma. To date, high-doses chemotherapy with hematopoietic stem cells support is only used as a salvage therapy to treat poor prognosis germ cell tumors patients with chemo-sensitive disease. Regarding breast and ovarian cancer, high-doses chemotherapy should be considered only in the context of clinical trials. However, intensive therapy as an approach to overcome resistance to standard treatments is still relevant. Numerous efforts are still ongoing to identify novel therapeutic combinations and active treatments to improve patients' responses. Copyright © 2016 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

Evaluation of growth hormone treatment efficacy in short Japanese children born small for gestational age: Five-year treatment outcome and impact on puberty

PubMed Central

Horikawa, Reiko; Tanaka, Toshiaki; Nishinaga, Hiromi; Ogawa, Yoshihisa; Yokoya, Susumu

2017-01-01

Abstract. Some children born small for gestational age (SGA) have short stature and are at an increased risk of developing psychosocial or behavioral problems. Here we evaluated the efficacy of GH and its effects on the timing of pubertal onset in a 3-yr extension of our previous 2-yr (total 5 yr) multicenter, randomized, double-blind, parallel-group clinical trial of 65 short Japanese children born SGA. Patients received low or high doses of GH (0.033 or 0.067 mg/kg/day, respectively). Age at onset of puberty was not statistically different for male and female patients receiving high- or low-dose GH. After the onset of puberty, no difference in height gain was observed between the two GH dose groups. At the onset of puberty, height standard deviation scores for chronological age of boys and girls improved significantly in both dose groups with evidence of a dose-response effect. Mean bone age/chronological age ratios in the low- and high-dose groups were significantly increased compared with baseline, being significantly greater in the high-dose group at 5 yr after treatment initiation. Delayed bone age at baseline was close to chronological age following GH treatment. GH treatment, especially high-dose GH, induced advanced bone age in short children born SGA. PMID:28458458

Dose uniformity of budesonide Easyhaler® under simulated real-life conditions and with low inspiration flow rates.

PubMed

Haikarainen, Jussi; Rytilä, Paula; Roos, Sirkku; Metsärinne, Sirpa; Happonen, Anita

2017-01-01

Budesonide Easyhaler® multidose dry powder inhaler is approved for the treatment of asthma. Objectives were to determine the delivered dose (DD) uniformity of budesonide Easyhaler® in simulated real-world conditions and with different inspiration flow rates (IFRs). Three dose delivery studies were performed using 100, 200, and 400 µg/dose strengths of budesonide. Dose uniformity was assessed during in-use periods of 4-6 months after exposure to high temperature (30°C) and humidity (60% relative humidity) and after dropping and vibration testing. The influence of various IFRs (31, 43, and 54 L/min) on the DD was also investigated. Acceptable dose uniformity was declared when mean DD were within 80-120% of expected dose; all data reported descriptively. DD was constant (range: 93-109% of expected dose) at all in-use periods and after exposure to high temperature and humidity for a duration of up to 6 months. DD post-dropping and -vibration were unaffected (range 98-105% of expected dose). Similarly, DD was constant and within 10% of expected dose across all IFRs. Results indicate that budesonide Easyhaler® delivers consistently accurate doses in various real-life conditions. Budesonide Easyhaler® can be expected to consistently deliver a uniform dose and improve asthma control regardless of high temperature and humidity or varying IFR.

Hard beta and gamma emissions of 124I. Impact on occupational dose in PET/CT.

PubMed

Kemerink, G J; Franssen, R; Visser, M G W; Urbach, C J A; Halders, S G E A; Frantzen, M J; Brans, B; Teule, G J J; Mottaghy, F M

2011-01-01

The hard beta and gamma radiation of 124I can cause high doses to PET/CT workers. In this study we tried to quantify this occupational exposure and to optimize radioprotection. Thin MCP-Ns thermoluminescent dosimeters suitable for measuring beta and gamma radiation were used for extremity dosimetry, active personal dosimeters for whole-body dosimetry. Extremity doses were determined during dispensing of 124I and oral administration of the activity to the patient, the body dose during all phases of the PET/CT procedure. In addition, dose rates of vials and syringes as used in clinical practice were measured. The procedure for dispensing 124I was optimized using newly developed shielding. Skin dose rates up to 100 mSv/min were measured when in contact with the manufacturer's vial containing 370 MBq of 124I. For an unshielded 5 ml syringe the positron skin dose was about seven times the gamma dose. Before optimization of the preparation of 124I, using an already reasonably safe technique, the highest mean skin dose caused by handling 370 MBq was 1.9 mSv (max. 4.4 mSv). After optimization the skin dose was below 0.2 mSv. The highly energetic positrons emitted by 124I can cause high skin doses if radioprotection is poor. Under optimized conditions occupational doses are acceptable. Education of workers is of paramount importance.

``In Vivo'' Dosimetry in High Dose Rate Brachytherapy for Cervical Cancer Treatments

NASA Astrophysics Data System (ADS)

González-Azcorra, S. A.; Mota-García, A.; Poitevín-Chacón, M. A.; Santamaría-Torruco, B. J.; Rodríguez-Ponce, M.; Herrera-Martínez, F. P.; Gamboa de Buen, I.; Ruíz-Trejo, C.; Buenfil, A. E.

2008-08-01

In this prospective study, rectal dose was measured "in vivo" using TLD-100 crystals (3×3×1 mm3), and it has been compared to the prescribed dose. Measurements were performed in patients with cervical cancer classified in FIGO stages IB-IIIB and treated with high dose rate brachytherapy (HDR BT) at the Instituto Nacional de Cancerología (INCan).

[The role of CYP2E1 in the protection of garlic oil's from n-hexane-induced neurotoxicity].

PubMed

Bi, Ye; Chen, Jing-jing; Li, Yang; Fu, Qiang-qiang; Zeng, Tao; Xie, Ke-qin

2011-11-01

To study the role of CYP2E1 in the protective effects and mechanism of garlic oil (GO) on the peripheral nerve injuries induced by n-hexane. Fifty male Wistar rats were randomly divided into five groups (n = 10): the control, the GO (80 mg/kg) control, the n-hexane (2000 mg/kg) model, the low dose GO (40 mg/kg) plus n-hexane, and the high dose GO (80 mg/kg) plus n-hexane groups. All rats were treated by intragastric administration 6 times a week for 10 weeks. The gait scores were determined every two weeks for monitoring the peripheral neurotrosis. All rats were sacrificed in 10 weeks, the activities and expression levels of hepatic CYP2E1 and 2, 5-HD in serum were examined. As compared with control group, the content and activity of hepatic CYP2E1 in GO control group reduced by 83.1% and 48.3% respectively (P < 0.01), the content and activity of hepatic CYP2E1 in model group increased by 112.5% and 72.2% respectively (P < 0.01). As compared with model group, the contents of hepatic CYP2E1 in low dose and high dose GO groups reduced by 32.9% and 39.1% respectively, the activities of hepatic CYP2E1 in low dose and high dose GO groups reduced by 27.4% and 44.5% respectively (P < 0.01); the contents of serum 2,5-HD in low dose and high dose GO groups reduced by 47.7% and 78.7% respectively (P < 0.01). The gait scores in model, low dose and high dose GO groups were significantly lower than that in control group, but the gait scores in low dose and high dose GO groups were significantly lower than that in model group (P < 0.05). Garlic oil can effectively reduce the peripheral neurotrosis induced by n-hexane due to the decreased content and activity of hepatic CYP2E1, resulting in the reduced formation of 2, 5-HD from n-hexane.

[Effects of soybean isoflavone on born metabolism and morphology in animal model of osteoporosis rats].

PubMed

Yu, Qing; Su, Yi-xiang; Wang, Wen-wei; Li, An-le; Liu, Cun-li; Wang, Yi-long; Hu, Wan-li

2007-07-01

To study the effects of soybean isoflavone (SI) on born metabolism and morphology in animal model of osteoporosis rats. All 70 female Sprague-Dawley (SD) rats were randomly divided into 7 groups according to the levels of total cholesterol (TC) in serum: hyper-lipoid group, estrogen group, low-dose SI group, middle-dose SI group, high-dose SI group, sham group and normal control groups. Bilateral ovaries were extirpated except sham and normal control groups. Except the rats in normal control group, the other rats were fed with high fat diet. Body weight was weighted ad unam vice per week. The estrogen, different dose of SI or deionized water were fed with intragastric administration for 12 weeks. Vena caudalis serum were collected after being ovariectomized, administered for 4 w, 8 w and killed. Serum alkaline phosphatase (AKP) activity and bone density were measured etc. To interfere of estrogen and SI might recover AKP enzyme activity after its being ovariectomized. There almost sowed no differences between high dose SI intervention and estrogen on bone density and microstructure. Bone loss due to being ovariectomized was relieved after SI intervention. SI might protect cardiocyte myofilament and mitochondrial ultramicrostructure. There was mirror image in estrogen, high dose SI group resembling the normal control group, and there was obvious damage in hyper-lipoids group. There should be effects of high dose SI on bone metabolism and morphology in animal model of osteoporosis rats. Serum AKP enzyme activity and bone density should have significantly recovered, the serum level of calcium and phosphorus were maintained after high dose intervened but no significant effects for low dose of SI.

Beneficial effects of Korean red ginseng on lymphocyte DNA damage, antioxidant enzyme activity, and LDL oxidation in healthy participants: a randomized, double-blind, placebo-controlled trial.

PubMed

Kim, Ji Young; Park, Ju Yeon; Kang, Hee Jung; Kim, Oh Yoen; Lee, Jong Ho

2012-07-17

The reported health benefits of Korean red ginseng (KRG) include antioxidant, antitumor, antimutagenic, and immunomodulatory activities; however, the effects on oxidative stress have not yet been evaluated. Therefore, we assessed the effect of KRG on antioxidant enzymes and oxidative stress markers in humans. We conducted a randomized, double-blind, placebo-controlled study with three groups, including placebo, low-dose (3 g/day), and high-dose (6 g/day), which were randomly assigned to healthy subjects aged 20-65 years. Lymphocyte DNA damage, antioxidative enzyme activity, and lipid peroxidation were assessed before and after the 8-week supplementation. Fifty-seven subjects completed the protocol. Plasma superoxide dismutase (SOD) activity after the 8-week KRG supplementation was significantly higher in the low-and high-dose groups compared to baseline. Plasma glutathione peroxidase (GPx) and catalase activities were also increased after the high-dose supplementation. Furthermore, the DNA tail length and tail moment were significantly reduced after the supplementation (low-dose and high-dose), and plasma oxidized low-density lipoprotein (LDL) levels were reduced in low-dose and high-dose groups, but increased in the placebo group. The net changes in oxidized LDL after the supplementation differed significantly between both KRG supplementation groups and the placebo group. Net changes in GPx, SOD and catalase activities, and DNA tail length and tail moment were significantly different between the high-dose group and the placebo group. Additionally, the net changes in urinary 8-epi-PGF(2α) were significantly different between the KRG supplementation groups and the placebo group. KRG supplementation may attenuate lymphocyte DNA damage and LDL oxidation by upregulating antioxidant enzyme activity.

Beneficial effects of Korean red ginseng on lymphocyte DNA damage, antioxidant enzyme activity, and LDL oxidation in healthy participants: a randomized, double-blind, placebo-controlled trial

PubMed Central

2012-01-01

Background The reported health benefits of Korean red ginseng (KRG) include antioxidant, antitumor, antimutagenic, and immunomodulatory activities; however, the effects on oxidative stress have not yet been evaluated. Therefore, we assessed the effect of KRG on antioxidant enzymes and oxidative stress markers in humans. Methods We conducted a randomized, double-blind, placebo-controlled study with three groups, including placebo, low-dose (3 g/day), and high-dose (6 g/day), which were randomly assigned to healthy subjects aged 20–65 years. Lymphocyte DNA damage, antioxidative enzyme activity, and lipid peroxidation were assessed before and after the 8-week supplementation. Results Fifty-seven subjects completed the protocol. Plasma superoxide dismutase (SOD) activity after the 8-week KRG supplementation was significantly higher in the low-and high-dose groups compared to baseline. Plasma glutathione peroxidase (GPx) and catalase activities were also increased after the high-dose supplementation. Furthermore, the DNA tail length and tail moment were significantly reduced after the supplementation (low-dose and high-dose), and plasma oxidized low-density lipoprotein (LDL) levels were reduced in low-dose and high-dose groups, but increased in the placebo group. The net changes in oxidized LDL after the supplementation differed significantly between both KRG supplementation groups and the placebo group. Net changes in GPx, SOD and catalase activities, and DNA tail length and tail moment were significantly different between the high-dose group and the placebo group. Additionally, the net changes in urinary 8-epi-PGF2α were significantly different between the KRG supplementation groups and the placebo group. Conclusions KRG supplementation may attenuate lymphocyte DNA damage and LDL oxidation by upregulating antioxidant enzyme activity. PMID:22805313

Effects of dosage and dosing frequency on the efficacy and safety of high-dose metformin in Japanese patients with type 2 diabetes mellitus.

PubMed

Kanto, Kousei; Ito, Hiroyuki; Noso, Shinsuke; Babaya, Naru; Hiromine, Yoshihisa; Taketomo, Yasunori; Toma, Junko; Niwano, Fumimaru; Yasutake, Sara; Kawabata, Yumiko; Ikegami, Hiroshi

2017-09-30

Differences in the efficacy and safety of antidiabetic drugs among different ethnic groups are well documented. Metformin is widely used in the treatment of type 2 diabetes in Western countries, but high doses of metformin have been approved only recently for clinical use in Japan. The aim of the present study was to investigate the effects of dosage and dosing frequency on the efficacy and safety of high-dose metformin in Japanese patients. A total of 71 Japanese patients with type 2 diabetes were prospectively studied for the effects of dosage and dosing frequency on the efficacy and safety of metformin during hospitalization. Dose effects were studied in 27 patients treated with 0, 500, 1,000, 1,500 and 2,250 mg/day of metformin. The effect of dosing frequency was compared in 56 patients with 1,500 mg/day of metformin administered either two or three times per day. Significant dose-dependent improvement in daily profiles of blood glucose was observed with metformin dosages up to 1,500 mg/day, with a trend towards further improvement observed at 2,250 mg/day. The efficacy of 1,500 mg of metformin was comparable when the drug was administered either two or three times per day. The most frequently reported side-effects were gastrointestinal symptoms, which were not affected by the dosage or dosing frequency of metformin. These results show that the efficacy of high-dose metformin is dose-dependent in Japanese patients. The efficacy and safety of metformin were similar when the drug was administered either two or three times per day. © 2017 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.

Penicillin dosing for pneumococcal pneumonia.

PubMed

Bryan, C S; Talwani, R; Stinson, M S

1997-12-01

Most textbook authors still endorse penicillin G as the specific antibiotic of choice for pneumococcal pneumonia. However, problems with early precise etiologic diagnosis of pneumonia and the emergence of drug-resistant pneumococci cause penicillin to be seldom used for this purpose today. A third explanation for the infrequent use of penicillin is lack of clear consensus dosing guidelines. Emergence of pneumococci resistant to the newer cephalosporins and concerns about overuse of vancomycin, however, have prompted renewed interest in the development of precise, rapid methods for diagnosis of pneumococcal pneumonia with the implication that penicillin might be used more frequently. We review several issues concerning penicillin dosing: intermittent vs continuous therapy, high dose vs low dose, relationship of dose to resistance, and cost-effective pharmacology. An optimum "high-dose" regimen for life-threatening pneumococcal pneumonia in a 70-kg adult consists of a 3 million unit (mu) loading dose followed by continuous infusion of 10 to 12 mu of freshly prepared drug every 12 h. The maintenance dose should be reduced in elderly patients and in patients with renal failure according to the following formula: dose (mu/24 h = 4+[creatinine clearance divided by 7]). This regimen provides a penicillin serum level of 16 to 20 microg/mL, which should suffice for all but the most highly resistant strains (minimum inhibitory concentration > or = 4 microg/mL). Newer cephalosporins and vancomycin can be reserved for patients with suspected meningitis or endocarditis or for localities in which highly resistant pneumococci are known to be prevalent.

High-dose transdermal nicotine replacement for tobacco cessation.

PubMed

Brokowski, Laurie; Chen, Jiahui; Tanner, Sara

2014-04-15

The safety and efficacy of high-dose transdermal nicotine-replacement therapy (NRT) for the treatment of tobacco-use cessation were reviewed. Transdermal nicotine doses of 7, 14, and 21 mg daily are approved by the Food and Drug Administration for use in tobacco cessation. However, studies have suggested that these doses are more adequate for people who smoke fewer than 20 cigarettes per day. A literature search was conducted to identify English-language studies that evaluated the use of transdermal nicotine doses of ≥42 mg daily. A total of 11 articles were identified, representing 10 separate trials. In terms of safety, the majority of the trials had no reports of serious adverse events related to transdermal NRT at doses of ≥42 mg daily. A dose-response relationship with adverse events occurred in most trials. In terms of efficacy, a numerically higher abstinence rate was achieved with high-dose transdermal NRT in all trials but 1. However, none of the studies showed significant differences in final abstinence rates at follow-up. Some reasons why statistical significance was not achieved in these trials may be related to the limitations of these trials, such as their small samples and the lack of a power calculation. A more robust trial is needed to support higher nicotine transdermal doses in tobacco cessation and to help elucidate which patient population would be most suitable for their use. The safety and efficacy of high-dose transdermal NRT for tobacco cessation have not been established in the medical literature.

NEONATAL LOW- AND HIGH-DOSE EXPOSURE TO ESTRADIOL BENZOATE IN THE MALE RAT: I. EFFECTS ON THE PROSTATE GLAND

EPA Science Inventory

Neonatal Low- And High-Dose Exposure To Estradiol Benzoate In The Male Rat: 1. Effects On The Prostate Gland. Oliver Putz, Christian B. Schwartz, Steve Kim, Gerald A. LeBlanc Ralph L. Cooper, Gail S. Prins

ABSTRACT
Brief exposure of rats to high doses of natural estro...

Losartan/hydrochlorothiazide combination vs. high-dose losartan in patients with morning hypertension--a prospective, randomized, open-labeled, parallel-group, multicenter trial.

PubMed

Ueda, Tamenobu; Kai, Hisashi; Imaizumi, Tsutomu

2012-07-01

The treatment of morning hypertension has not been established. We compared the efficacy and safety of a losartan/hydrochlorothiazide (HCTZ) combination and high-dose losartan in patients with morning hypertension. A prospective, randomized, open-labeled, parallel-group, multicenter trial enrolled 216 treated outpatients with morning hypertension evaluated by home blood pressure (BP) self-measurement. Patients were randomly assigned to receive a combination therapy of 50 mg losartan and 12.5 mg HCTZ (n=109) or a high-dose therapy with 100 mg losartan (n=107), each of which were administered once every morning. Primary efficacy end points were morning systolic BP (SBP) level and target BP achievement rate after 3 months of treatment. At baseline, BP levels were similar between the two therapy groups. Morning SBP was reduced from 150.3±10.1 to 131.5±11.5 mm Hg by combination therapy (P<0.001) and from 151.0±9.3 to 142.5±13.6 mm Hg by high-dose therapy (P<0.001). The morning SBP reduction was greater in the combination therapy group than in the high-dose therapy group (P<0.001). Combination therapy decreased evening SBP from 141.6±13.3 to 125.3±13.1 mm Hg (P<0.001), and high-dose therapy decreased evening SBP from 138.9±9.9 to 131.4±13.2 mm Hg (P<0.01). Although both therapies improved target BP achievement rates in the morning and evening (P<0.001 for both), combination therapy increased the achievement rates more than high-dose therapy (P<0.001 and P<0.05, respectively). In clinic measurements, combination therapy was superior to high-dose therapy in reducing SBP and improving the achievement rate (P<0.001 and P<0.01, respectively). Combination therapy decreased urine albumin excretion (P<0.05) whereas high-dose therapy reduced serum uric acid. Both therapies indicated strong adherence and few adverse effects (P<0.001). In conclusion, losartan/HCTZ combination therapy was more effective for controlling morning hypertension and reducing urine albumin than high-dose losartan.

SU-F-P-19: Fetal Dose Estimate for a High-Dose Fluoroscopy Guided Intervention Using Modern Data Tools

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moirano, J

Purpose: An accurate dose estimate is necessary for effective patient management after a fetal exposure. In the case of a high-dose exposure, it is critical to use all resources available in order to make the most accurate assessment of the fetal dose. This work will demonstrate a methodology for accurate fetal dose estimation using tools that have recently become available in many clinics, and show examples of best practices for collecting data and performing the fetal dose calculation. Methods: A fetal dose estimate calculation was performed using modern data collection tools to determine parameters for the calculation. The reference pointmore » air kerma as displayed by the fluoroscopic system was checked for accuracy. A cumulative dose incidence map and DICOM header mining were used to determine the displayed reference point air kerma. Corrections for attenuation caused by the patient table and pad were measured and applied in order to determine the peak skin dose. The position and depth of the fetus was determined by ultrasound imaging and consultation with a radiologist. The data collected was used to determine a normalized uterus dose from Monte Carlo simulation data. Fetal dose values from this process were compared to other accepted calculation methods. Results: An accurate high-dose fetal dose estimate was made. Comparison to accepted legacy methods were were within 35% of estimated values. Conclusion: Modern data collection and reporting methods ease the process for estimation of fetal dose from interventional fluoroscopy exposures. Many aspects of the calculation can now be quantified rather than estimated, which should allow for a more accurate estimation of fetal dose.« less

New botanical drug, HL tablet, reduces hepatic fat as measured by magnetic resonance spectroscopy in patients with nonalcoholic fatty liver disease: A placebo-controlled, randomized, phase II trial.

PubMed

Jeong, Jae Yoon; Sohn, Joo Hyun; Baek, Yang Hyun; Cho, Yong Kyun; Kim, Yongsoo; Kim, Hyeonjin

2017-08-28

To evaluate the efficacy and safety of HL tablet extracted from magnolia officinalis for treating patients with nonalcoholic fatty liver disease (NAFLD). Seventy-four patients with NAFLD diagnosed by ultrasonography were randomly assigned to 3 groups given high dose (400 mg) HL tablet, low dose (133.4 mg) HL tablet and placebo, respectively, daily for 12 wk. The primary endpoint was post-treatment change of hepatic fat content (HFC) measured by magnetic resonance spectroscopy. Secondary endpoints included changes of serum aspartate aminotransferase, alanine aminotransferase (ALT), cholesterol, triglyceride, free fatty acid, homeostasis model assessment-estimated insulin resistance, and body mass index (BMI). The mean HFC of the high dose HL group, but not of the low dose group, declined significantly after 12 wk of treatment (high dose vs placebo, P = 0.033; low dose vs placebo, P = 0.386). The mean changes of HFC from baseline at week 12 were -1.7% ± 3.1% in the high dose group ( P = 0.018), -1.21% ± 4.97% in the low dose group ( P = 0.254) and 0.61% ± 3.87% in the placebo group (relative changes compared to baseline, high dose were: -12.1% ± 23.5%, low dose: -3.2% ± 32.0%, and placebo: 7.6% ± 44.0%). Serum ALT levels also tended to decrease in the groups receiving HL tablet while other factors were unaffected. There were no moderate or severe treatment-related safety issues during the study. HL tablet is effective in reducing HFC without any negative lipid profiles, BMI changes and adverse effects.

New botanical drug, HL tablet, reduces hepatic fat as measured by magnetic resonance spectroscopy in patients with nonalcoholic fatty liver disease: A placebo-controlled, randomized, phase II trial

PubMed Central

Jeong, Jae Yoon; Sohn, Joo Hyun; Baek, Yang Hyun; Cho, Yong Kyun; Kim, Yongsoo; Kim, Hyeonjin

2017-01-01

AIM To evaluate the efficacy and safety of HL tablet extracted from magnolia officinalis for treating patients with nonalcoholic fatty liver disease (NAFLD). METHODS Seventy-four patients with NAFLD diagnosed by ultrasonography were randomly assigned to 3 groups given high dose (400 mg) HL tablet, low dose (133.4 mg) HL tablet and placebo, respectively, daily for 12 wk. The primary endpoint was post-treatment change of hepatic fat content (HFC) measured by magnetic resonance spectroscopy. Secondary endpoints included changes of serum aspartate aminotransferase, alanine aminotransferase (ALT), cholesterol, triglyceride, free fatty acid, homeostasis model assessment-estimated insulin resistance, and body mass index (BMI). RESULTS The mean HFC of the high dose HL group, but not of the low dose group, declined significantly after 12 wk of treatment (high dose vs placebo, P = 0.033; low dose vs placebo, P = 0.386). The mean changes of HFC from baseline at week 12 were -1.7% ± 3.1% in the high dose group (P = 0.018), -1.21% ± 4.97% in the low dose group (P = 0.254) and 0.61% ± 3.87% in the placebo group (relative changes compared to baseline, high dose were: -12.1% ± 23.5%, low dose: -3.2% ± 32.0%, and placebo: 7.6% ± 44.0%). Serum ALT levels also tended to decrease in the groups receiving HL tablet while other factors were unaffected. There were no moderate or severe treatment-related safety issues during the study. CONCLUSION HL tablet is effective in reducing HFC without any negative lipid profiles, BMI changes and adverse effects. PMID:28932090

Postnatal glucocorticoid-induced hypomyelination, gliosis, neurologic deficits are dose-dependent, preparation-specific, and reversible

PubMed Central

Zia, Muhammad TK; Vinukonda, Govindaiah; Vose, Linnea; Bhimavarapu, Bala B.R.; Iacobas, Sanda; Pandey, Nishi K.; Beall, Ann Marie; Dohare, Preeti; LaGamma, Edmund F.; Iacobas, Dumitru A.; Ballabh, Praveen

2014-01-01

Postnatal glucocorticoids (GCs) are widely used in the prevention of chronic lung disease in premature infants. Their pharmacologic use is associated with neurodevelopmental delay and cerebral palsy. However, the effect of GC dose and preparation (dexamethasone versus betamethasone) on short and long-term neurological outcomes remains undetermined, and the mechanisms of GC-induced brain injury are unclear. We hypothesized that postnatal GC would induce hypomyelination and motor impairment in a preparation- and dose-specific manner, and that GC receptor (GR) inhibition might restore myelination and neurological function in GC-treated animals. Additionally, GC-induced hypomyelination and neurological deficit might be transient. To test our hypotheses, we treated prematurely delivered rabbit pups with high (0.5 mg/kg/day) or low (0.2 mg/kg/day) doses of dexamethasone or betamethasone. Myelin basic protein (MBP), oligodendrocyte proliferation and maturation, astrocytes, transcriptomic profile, and neurobehavioral functions were evaluated. We found that high-dose GC treatment, but not low-dose, reduced MBP expression and impaired motor function at postnatal day 14. High-dose dexamethasone induced astrogliosis, betamethasone did not. Mifepristone, a GR antagonist, reversed dexamethasone-induced myelination, but not astrogliosis. Both GCs inhibited oligodendrocyte proliferation and maturation. Moreover, high-dose dexamethasone altered genes associated with myelination, cell-cycle, GR, and Mitogen-activated protein kinase. Importantly, GC-induced hypomyelination, gliosis, and motor-deficit, observed at day 14, completely recovered by day 21. Hence, high-dose, but not low-dose, postnatal GC causes reversible reductions in myelination and motor functions. GC treatment induces hypomyelination by GR-dependent genomic mechanisms, but astrogliosis by non-genomic mechanisms. GC-induced motor impairment and neurodevelopmental delay might be transient and recover spontaneously in premature infants. PMID:25263581

Effects of Different Doses of Irbesartan Combined With Spironolactone on Urinary Albumin Excretion Rate in Elderly Patients With Early Type 2 Diabetic Nephropathy.

PubMed

Chen, Yingying; Liu, Peng; Chen, Xia; Li, Yanan; Zhang, Fengmei; Wang, Yangang

2018-05-01

There is a lack of research on the effect of low dose of angiotensin receptor blockers combined with spironolactone, and the effect of high dose of angiotensin receptor blockers alone on the urinary albumin excretion rate (UAER) in elderly patients with early type 2 diabetic nephropathy (DN). We conducted a prospective, randomized, open-label, parallel-controlled study that included 244 elderly patients with early DN and mild-to-moderate essential hypertension. Patients were randomly divided into 4 groups: low-dose irbesartan (group A), high-dose irbesartan (group B), low-dose irbesartan combined with spironolactone (group C) and high-dose irbesartan combined with spironolactone (group D). Changes in UAER, serum potassium and blood pressure were compared. There were no statistical differences in the baseline characteristics among groups. Furthermore, no significant difference in blood pressure before and after treatment was found among different groups. After 72-week treatment, UAER in group D was lower compared to group A and B (P < 0.05). Meanwhile, compared with group B, UAER in group C decreased significantly (P < 0.05). Additionally, significantly higher serum potassium was found in group D compared to other groups (P < 0.05). Also, group D had the highest count of patients who withdrew from the study due to hyperkalemia compared to other groups (P < 0.05). Our results indicate high-dose irbesartan combined with spironolactone may be more efficient in reducing UAER in elderly patients with early DN, but this treatment could cause hyperkalemia. Low-dose irbesartan combined with spironolactone was shown to be safer and more effective in decreasing UAER compared to high-dose irbesartan. Copyright © 2018 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.

High Dose Atorvastatin Associated with Increased Risk of Significant Hepatotoxicity in Comparison to Simvastatin in UK GPRD Cohort

PubMed Central

Clarke, Alan T.; Johnson, Paul C. D.; Hall, Gillian C.; Ford, Ian; Mills, Peter R.

2016-01-01

Background & Aims Occasional risk of serious liver dysfunction and autoimmune hepatitis during atorvastatin therapy has been reported. We compared the risk of hepatotoxicity in atorvastatin relative to simvastatin treatment. Methods The UK GPRD identified patients with a first prescription for simvastatin [164,407] or atorvastatin [76,411] between 1997 and 2006, but with no prior record of liver disease, alcohol-related diagnosis, or liver dysfunction. Incident liver dysfunction in the following six months was identified by biochemical value and compared between statin groups by Cox regression model adjusting for age, sex, year treatment started, dose, alcohol consumption, smoking, body mass index and comorbid conditions. Results Moderate to severe hepatotoxicity [bilirubin >60μmol/L, AST or ALT >200U/L or alkaline phosphatase >1200U/L] developed in 71 patients on atorvastatin versus 101 on simvastatin. Adjusted hazard ratio [AHR] for all atorvastatin relative to simvastatin was 1.9 [95% confidence interval 1.4–2.6]. High dose was classified as 40–80mg daily and low dose 10–20mg daily. Hepatotoxicity occurred in 0.44% of 4075 patients on high dose atorvastatin [HDA], 0.07% of 72,336 on low dose atorvastatin [LDA], 0.09% of 44,675 on high dose simvastatin [HDS] and 0.05% of 119,732 on low dose simvastatin [LDS]. AHRs compared to LDS were 7.3 [4.2–12.7] for HDA, 1.4 [0.9–2.0] for LDA and 1.5 [1.0–2.2] for HDS. Conclusions The risk of hepatotoxicity was increased in the first six months of atorvastatin compared to simvastatin treatment, with the greatest difference between high dose atorvastatin and low dose simvastatin. The numbers of events in the analyses were small. PMID:26983033

Chronic prazosin attenuates the natriuretic response to a modest saline load in anaesthetized rats.

PubMed Central

Penner, S. B.; Smyth, D. D.

1988-01-01

1. The effect of chronic prazosin pretreatment (3 days) on the ability to excrete a modest saline load (i.v. saline, 0.097 ml min-1) was studied in the anaesthetized rat. Three days before the experiment, the drinking water was replaced with 0.5% dextrose (control), 0.015 mg ml-1 prazosin in 0.5% dextrose (low dose) or 0.15 mg ml-1 prazosin in 0.5% dextrose (high dose). 2. The selectivity of the prazosin for alpha 1-adrenoceptors was evaluated in pithed rats. The pressor response to phenylephrine was partially attenuated by the low dose of prazosin and completely attenuated by the high dose of prazosin. The pressor response to clonidine was slightly decreased by the 3 day prazosin pretreatment indicating a selectivity for alpha 1-adrenoceptors. 3. In rats pretreated with the low dose of prazosin, there was a significant decrease in sodium and water, but not potassium excretion as compared to the control group. Captopril failed to alter these effects of the low dose of prazosin. Blood pressure and creatinine clearance were the same in both groups. In rats pretreated with the high dose of prazosin, there was a further decrease in sodium and water but not potassium excretion. However, this dose of prazosin also significantly decreased blood pressure and increased creatinine clearance. A decrease in renal perfusion pressure with an aortic clamp to the same level as that observed with the high prazosin dose also decreased sodium and water but not potassium excretion. The decrease in sodium and water excretion was not as great as that observed with the high dose of prazosin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2896036

Safety and immunogenicity of a novel recombinant adenovirus type-5 vector-based Ebola vaccine in healthy adults in China: preliminary report of a randomised, double-blind, placebo-controlled, phase 1 trial.

PubMed

Zhu, Feng-Cai; Hou, Li-Hua; Li, Jing-Xin; Wu, Shi-Po; Liu, Pei; Zhang, Gui-Rong; Hu, Yue-Mei; Meng, Fan-Yue; Xu, Jun-Jie; Tang, Rong; Zhang, Jin-Long; Wang, Wen-Juan; Duan, Lei; Chu, Kai; Liang, Qi; Hu, Jia-Lei; Luo, Li; Zhu, Tao; Wang, Jun-Zhi; Chen, Wei

2015-06-06

Up to now, all tested Ebola virus vaccines have been based on the virus strain from the Zaire outbreak in 1976. We aimed to assess the safety and immunogenicity of a novel recombinant adenovirus type-5 vector-based Ebola vaccine expressing the glycoprotein of the 2014 epidemic strain. We did this randomised, double-blind, placebo-controlled, phase 1 clinical trial at one site in Taizhou County, Jiangsu Province, China. Healthy adults (aged 18-60 years) were sequentially enrolled and randomly assigned (2:1), by computer-generated block randomisation (block size of six), to receive placebo, low-dose adenovirus type-5 vector-based Ebola vaccine, or high-dose vaccine. Randomisation was pre-stratified by dose group. All participants, investigators, and laboratory staff were masked to treatment allocation. The primary safety endpoint was occurrence of solicited adverse reactions within 7 days of vaccination. The primary immunogenicity endpoints were glycoprotein-specific antibody titres and T-cell responses at day 28 after the vaccination. Analysis was by intention to treat. The study is registered with ClinicalTrials.gov, number NCT02326194. Between Dec 28, 2014, and Jan 9, 2015, 120 participants were enrolled and randomly assigned to receive placebo (n=40), low-dose vaccine (n=40), or high-dose vaccine. Participants were followed up for 28 days. Overall, 82 (68%) participants reported at least one solicited adverse reaction within 7 days of vaccination (n=19 in the placebo group vs n=27 in the low-dose group vs n=36 in the high-dose group; p=0·0002). The most common reaction was mild pain at the injection site, which was reported in eight (20%) participants in the placebo group, 14 (35%) participants in the low-dose group, and 29 (73%) participants in the high-dose vaccine group (p<0·0001). We recorded no statistical differences in other adverse reactions and laboratory tests across groups. Glycoprotein-specific antibody titres were significantly increased in participants in the low-dose and high-dose vaccine groups at both day 14 (geometric mean titre 421·4 [95% CI 249·7-711·3] and 820·5 [598·9-1124·0], respectively; p<0·0001) and day 28 (682·7 [424·3-1098·5] and 1305·7 [970·1-1757·2], respectively; p<0·0001). T-cell responses peaked at day 14 at a median of 465·0 spot-forming cells (IQR 180·0-1202·5) in participants in the low-dose group and 765·0 cells (400·0-1460·0) in those in the high-dose group. 21 (18%) participants had mild fever (n=9 in the placebo group, n=6 in the low-dose group, and n=6 in the high-dose group). No serious adverse events were recorded. Our findings show that the high-dose vaccine is safe and robustly immunogenic. One shot of the high-dose vaccine could mount glycoprotein-specific humoral and T-cell response against Ebola virus in 14 days. China National Science and Technology, Beijing Institute of Biotechnology, and Tianjin CanSino Biotechnology. Copyright © 2015 Elsevier Ltd. All rights reserved.

Spatial features of dose-surface maps from deformably-registered plans correlate with late gastrointestinal complications

NASA Astrophysics Data System (ADS)

Moulton, Calyn R.; House, Michael J.; Lye, Victoria; Tang, Colin I.; Krawiec, Michele; Joseph, David J.; Denham, James W.; Ebert, Martin A.

2017-05-01

This study investigates the associations between spatial distribution of dose to the rectal surface and observed gastrointestinal toxicities after deformably registering each phase of a combined external beam radiotherapy (EBRT)/high-dose-rate brachytherapy (HDRBT) prostate cancer treatment. The study contains data for 118 patients where the HDRBT CT was deformably-registered to the EBRT CT. The EBRT and registered HDRBT TG43 dose distributions in a reference 2 Gy/fraction were 3D-summed. Rectum dose-surface maps (DSMs) were obtained by virtually unfolding the rectum surface slice-by-slice. Associations with late peak gastrointestinal toxicities were investigated using voxel-wise DSM analysis as well as parameterised spatial patterns. The latter were obtained by thresholding DSMs from 1-80 Gy (increment  =  1) and extracting inferior-superior extent, left-right extent, area, perimeter, compactness, circularity and ellipse fit parameters. Logistic regressions and Mann-Whitney U-tests were used to correlate features with toxicities. Rectal bleeding, stool frequency, diarrhoea and urgency/tenesmus were associated with greater lateral and/or longitudinal spread of the high doses near the anterior rectal surface. Rectal bleeding and stool frequency were also influenced by greater low-intermediate doses to the most inferior 20% of the rectum and greater low-intermediate-high doses to 40-80% of the rectum length respectively. Greater low-intermediate doses to the superior 20% and inferior 20% of the rectum length were associated with anorectal pain and urgency/tenesmus respectively. Diarrhoea, completeness of evacuation and proctitis were also related to greater low doses to the posterior side of the rectum. Spatial features for the intermediate-high dose regions such as area, perimeter, compactness, circularity, ellipse eccentricity and confinement to ellipse fits were strongly associated with toxicities other than anorectal pain. Consequently, toxicity is related to the shape of isodoses as well as dose coverage. The findings indicate spatial constraints on doses to certain sections of the rectum may be important for reducing toxicities and optimising dose.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Matsumoto, Ko; Takahashi, Shoki; Higano, Shuichi

1995-07-15

The main purpose of this study was to determine influential factors related to minor leukoencephalopathy (LEP) caused by moderate-dose methotrexate (MTX) and prophylactic cranial radiotherapy (CRT) in childhood hematopoietic malignancies. We also compared the incidence of LEP following this treatment to that reported in the literature following treatment with high-dose MTX alone. Thirty-eight pediatric patients of hematopoietic malignancies (37 acute lymphoblastic leukemias, 1 non-Hodgkin lymphoma) who were given CRT (18-24 Gy) as well as prophylactic intrathecal and per os MTX were studied for leukoencephalopathy by magnetic resonance (MR) imaging. All the patients were free from grave neuropsychiatric disturbances. The datamore » were examined to elucidate the influential ones of five factors (patients` age, doses of intrathecal and per os MTX, dose of CRT, interval between treatment, and MR study) to develop LEP using multiple regression analysis. To compare the effect of moderate-dose MTX and prophylactic CRT on LEP to that of high-dose MTX alone, we conducted a literature review. Seven out of 38 patients (18%) developed LEP. From multiple regression analysis and partial correlation coefficients, the age and CRT dose seemed influential in the subsequent development of LEP. The incidence of LEP following treatment with moderate-dose MTX and prophylactic CRT appears to be less than that reported in the literature following treatment with intravenous high-dose MTX. However, even moderate-dose MTX in combination with CRT can result in a significant incidence of MR-detectable LEP, particularly in children 6 years of age or younger receiving 24 Gy. Leukoencephalopathy was caused by moderate-dose MTX and prophylactic CRT in pediatric patients, probably less frequently than by high-dose MTX treatment alone. The influential factors were patient`s age and CRT dose. 26 refs., 6 figs., 2 tabs.« less

Low- and high-dose laser irradiation effects on cell migration and destruction

NASA Astrophysics Data System (ADS)

Layton, Elivia; Gallagher, Kyra A.; Zukerman, Sara; Stevens, Brianna; Zhou, Feifan; Liu, Hong; Chen, Wei R.

2018-02-01

Metastases are the cause of more than 90 percent of cancer-related deaths. Current treatment methods, including chemotherapy, radiation, and surgery, fail to target the metastases effectively. One potential treatment for metastatic cancer is laser immunotherapy (LIT). LIT combines the use of a photothermal laser with an immunoadjuvant, Glycated Chitosan (GC). GC combined with single-walled carbon nanotubes (SWNTs) has proven to be a viable alternative to traditional cancer treatment methods, when under irradiation of laser with appropriate wavelength. In this study, the effects of low dose and high dose laser irradiation on metastatic pancreatic cancer cell migration were observed. It was found that low dose irradiation increased the migration rate, but the high dose irradiation significantly decreased the migration rate of the cancer cells. When using LIT, the goal is to kill tumor cells and to prompt the correct immune response. If the tumor were irradiated with a low dose, it would promote metastasis. If the dose of irradiation were too high, it would destroy the entire tumor and the immune response would not recognize the tumor. Therefore, the laser dose plays an important role in LIT, particularly when using SWNT as light absorbing agent. Our results from this study will delineate the optimal laser irradiation dose for destroying tumor cells and at the same time preserve and release tumor antigens as a precursor of antitumor immune response.

Low-Dose Carcinogenicity Studies

EPA Science Inventory

One of the major deficiencies of cancer risk assessments is the lack of low-dose carcinogenicity data. Most assessments require extrapolation from high to low doses, which is subject to various uncertainties. Only 4 low-dose carcinogenicity studies and 5 low-dose biomarker/pre-n...

Low dosing of gonadotropins in in vitro fertilization cycles for women with poor ovarian reserve: systematic review and meta-analysis.

PubMed

Youssef, Mohamed Abdel-Fattah; van Wely, Madelon; Mochtar, Monique; Fouda, Usama Mohamed; Eldaly, Ashraf; El Abidin, Eman Zein; Elhalwagy, Ahmed; Mageed Abdallah, Ahmed Abdel; Zaki, Sherif Sameh; Abdel Ghafar, Mohamed Sayed; Mohesen, Mohamed Nagi; van der Veen, Fulco

2018-02-01

To evaluate the effectiveness of low doses of gonadotropins and gonadotropins combined with oral compounds compared with high doses of gonadotropins in ovarian stimulation regimens in terms of ongoing pregnancy per fresh IVF attempt in women with poor ovarian reserve undergoing IVF/intracytoplasmic sperm injection (ICSI) treatment. A systematic review and meta-analysis of randomized controlled studies that evaluate the effectiveness of low dosing of gonadotropins alone or combined with oral compounds compared with high doses of gonadotropins in women with poor ovarian reserve undergoing IVF/ICSI treatment. Not applicable. Subfertile women with poor ovarian reserve undergoing IVF/ICSI treatment. We searched the PubMed, EMBASE, Web of Science, the Cochrane Library, and the Clinical Trials Registry using medical subject headings and free text terms up to June 2016, without language or year restrictions. We included randomized controlled studies (RCTs) enrolling subfertile women with poor ovarian reserve undergoing IVF/ICSI treatment and comparing low doses of gonadotropins and gonadotropins combined with oral compounds versus high doses of gonadotropins. We assessed the risk of bias using the criteria recommended by the Cochrane Collaboration. We pooled the results by meta-analysis using the fixed and random effects model. The primary outcome was ongoing pregnancy rate (PR) per woman randomized. We retrieved 787 records. Fourteen RCTs (N = 2,104 women) were included in the analysis. Five studies (N = 717 women) compared low doses of gonadotropins versus high doses of gonadotropins. There was no evidence of a difference in ongoing PR (2 RCTs: risk rate 0.98, 95% confidence interval 0.62-1.57, I 2 = 0). Nine studies (N = 1,387 women) compared ovarian stimulation using gonadotropins combined with the oral compounds letrozole (n = 6) or clomiphene citrate (CC) (n = 3) versus high doses of gonadotropins. There was no evidence of a difference in ongoing PR (3 RCTs: risk rate 0.90, 95% confidence interval 0.63-1.27, I 2 = 0). We found no evidence of a difference in pregnancy outcomes between low doses of gonadotropins and gonadotropins combined with oral compounds compared with high doses of gonadotropins in ovarian stimulation regimens. Whether low doses of gonadotropins or gonadotropins combined with oral compounds is to be preferred is unknown, as they have never been compared head to head. A health economic analysis to test the hypothesis that an ovarian stimulation with low dosing is more cost-effective than high doses of gonadotropins is needed. CRD42016041301. Copyright © 2017 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

The Effect of Ezetimibe/Statin Combination and High-Dose Statin Therapy on Thyroid Autoimmunity in Women with Hashimoto's Thyroiditis and Cardiovascular Disease: A Pilot Study.

PubMed

Krysiak, R; Szkróbka, W; Okopień, B

2016-10-01

Background: Intensive statin therapy was found to reduce thyroid autoimmunity in women with Hashimoto's thyroiditis. No similar data are available for other hypolipidemic agents. Methods: The participants of the study were 16 women with Hashimoto's thyroiditis and coronary artery disease. On the basis of statin tolerance, they were divided into 2 groups. 8 patients who did not tolerate high-dose statin therapy were treated with a statin, the dose of which was reduced by half, together with ezetimibe. The remaining 8 patients tolerating the treatment continued high-dose statin therapy. Plasma lipids, serum levels of thyrotropin, free thyroxine and free triiodothyronine, as well as titers of thyroid peroxidase and thyroglobulin antibodies were measured at the beginning of the study and 6 months later. Results: Replacing high-dose statin therapy with ezetimibe/statin combination therapy increased serum titers of thyroid peroxidase as well as led to an insignificant increase in serum titers of thyroglobulin antibodies. At the end of the study, thyroid peroxidase and thyroglobulin antibody titers were higher in patients receiving the combination therapy than in those treated only with high-dose statin. Conclusions: Our study shows that high-dose statin therapy produces a stronger effect on thyroid autoimmunity than ezetimibe/statin combination therapy. © Georg Thieme Verlag KG Stuttgart · New York.

MK-801, but not naloxone, attenuates high-dose dextromethorphan-induced convulsive behavior: Possible involvement of the GluN2B receptor.

PubMed

Tran, Hai-Quyen; Chung, Yoon Hee; Shin, Eun-Joo; Tran, The-Vinh; Jeong, Ji Hoon; Jang, Choon-Gon; Nah, Seung-Yeol; Yamada, Kiyofumi; Nabeshima, Toshitaka; Kim, Hyoung-Chun

2017-11-01

Dextromethorphan (DM) is a dextrorotatory isomer of levorphanol, a typical morphine-like opioid. When administered at supra-antitussive doses, DM produces psychotoxic and neurotoxic effects in humans. Although DM abuse has been well-documented, few studies have examined the effects of high-dose DM. The present study aimed to explore the effects of a single high dose of DM on mortality and seizure occurrence. After intraperitoneal administration with a high dose of DM (80mg/kg), Sprague-Dawley rats showed increased seizure occurrence and intensity. Hippocampal expression levels of N-methyl-d-aspartate (NMDA) receptor subunits (GluN1

Trends in opioid use and dosing among socio-economically disadvantaged patients

PubMed Central

Gomes, Tara; Juurlink, David N; Dhalla, Irfan A; Mailis-Gagnon, Angela; Paterson, J Michael; Mamdani, Muhammad M

2011-01-01

Background Opioid therapy for patients with chronic nonmalignant pain remains controversial, primarily because of safety concerns and the potential for abuse. The objective of this study was to examine trends in opioid utilization for nonmalignant pain among recipients of social assistance and to explore the relation between dose of analgesic and mortality. Methods Using a cross-sectional study design, we characterized annual trends in prescriptions for and daily dose of opioid analgesics between 2003 and 2008 for beneficiaries (aged 15 to 64 years) of Ontario’s public drug plan. We defined moderate, high and very high dose thresholds as daily doses of up to 200, 201 to 400, and more than 400 mg oral morphine (or equivalent), respectively. In an exploratory cohort study, we followed, over a 2-year period, patients who received at least one prescription for an opioid in 2004 to investigate the relation between opioid dose and opioid-related mortality. Results Over the study period, opioid prescribing rates rose by 16.2%, and 180 974 individuals received nearly 1.5 million opioid prescriptions in 2008. Also by 2008, the daily dose dispensed exceeded 200 mg morphine equivalent for almost a third (32.6%) of recipients of long-acting oxycodone but only 20.3% of those treated with fentanyl or other long-acting opioids. Among patients for whom high or very high doses of opioids were dispensed in 2004, 19.3% of deaths during the subsequent 2 years were opioid-related, occurring at a median age of 46 years. Two-year opioid-related mortality rates were 1.63 per 1000 population (95% confidence interval [CI] 1.42–1.85) among people with moderate-dose prescriptions, 7.92 per 1000 population (95% CI 5.25–11.49) among those with high-dose prescriptions, and 9.94 per 1000 population (95% CI 2.78–25.12) among those with very-high-dose prescriptions. Interpretation Among socio-economically disadvantaged patients in Ontario, the use and dose of opioids for nonmalignant pain has increased substantially, driven primarily by the use of long-acting oxycodone and, to a lesser extent, fentanyl. The findings of our exploratory study suggested a strong association between opioid-related mortality and the dose of opioid dispensed. PMID:22046214

Monte-Carlo Simulation of Radiation Track Structure and Calculation of Dose Deposition in Nanovolumes

NASA Technical Reports Server (NTRS)

Plante, I.; Cucinotta, F. A.

2010-01-01

INTRODUCTION: The radiation track structure is of crucial importance to understand radiation damage to molecules and subsequent biological effects. Of a particular importance in radiobiology is the induction of double-strand breaks (DSBs) by ionizing radiation, which are caused by clusters of lesions in DNA, and oxidative damage to cellular constituents leading to aberrant signaling cascades. DSB can be visualized within cell nuclei with gamma-H2AX experiments. MATERIAL AND METHODS: In DSB induction models, the DSB probability is usually calculated by the local dose obtained from a radial dose profile of HZE tracks. In this work, the local dose imparted by HZE ions is calculated directly from the 3D Monte-Carlo simulation code RITRACKS. A cubic volume of 5 micron edge (Figure 1) is irradiated by a (Fe26+)-56 ion of 1 GeV/amu (LET approx.150 keV/micron) and by a fluence of 450 H+ ions, 300 MeV/amu (LET approx. 0.3 keV/micron). In both cases, the dose deposited in the volume is approx.1 Gy. The dose is then calculated into each 3D pixels (voxels) of 20 nm edge and visualized in 3D. RESULTS AND DISCUSSION: The dose is deposited uniformly in the volume by the H+ ions. The voxels which receive a high dose (orange) corresponds to electron track ends. The dose is deposited differently by the 56Fe26+ ion. Very high dose (red) is deposited in voxels with direct ion traversal. Voxels with electron track ends (orange) are also found distributed around the path of the track. In both cases, the appearance of the dose distribution looks very similar to DSBs seen in gammaH2AX experiments, particularly when the visualization threshold is applied. CONCLUSION: The refinement of the dose calculation to the nanometer scale has revealed important differences in the energy deposition between high- and low-LET ions. Voxels of very high dose are only found in the path of high-LET ions. Interestingly, experiments have shown that DSB induced by high-LET radiation are more difficult to repair. Therefore, this new approach may be useful to understand the nature of DSB and oxidative damage induced by ionizing radiation.

High- and Low-Dose Oral Delayed-Release Mesalamine in Children With Mild-to-Moderately Active Ulcerative Colitis

PubMed Central

Winter, Harland S.; Krzeski, Piotr; Heyman, Melvin B.; Ibarguen-Secchia, Eduardo; Iwanczak, Barbara; Kaczmarski, Maciej; Kierkus, Jaroslaw; Kolaček, Sanja; Osuntokun, Bankole; Quiros, J. Antonio; Shah, Manoj; Yacyshyn, Bruce; Dunnmon, Preston M.

2014-01-01

ABSTRACT Objective: The aim of the study was to assess the safety and efficacy of high- and low-dose oral, delayed-release mesalamine in a randomized, double-blind, active control study of children with mild-to-moderately active ulcerative colitis. Methods: Patients ages 5 to 17 years, with a Pediatric Ulcerative Colitis Activity Index (PUCAI) score of ≥10 to ≤55 and a truncated Mayo Score of ≥1 for both rectal bleeding and stool frequency, were enrolled. They received body weight–dependent doses of oral, delayed-release mesalamine for 6 weeks in a low- (27–71 mg · g−1 · day−1) or high-dose group (53–118 mg · g−1 · day−1). The primary endpoint was treatment success, defined as the proportion of patients who achieved remission (PUCAI score <10) or partial response (PUCAI score ≥10 with a decrease from baseline by ≥20 points). Secondary endpoints included truncated Mayo Score and global assessment of change of disease activity. Results: The modified intent-to-treat population included 81 of 83 patients enrolled. Treatment success by PUCAI was achieved by 23 of 41 (56%) and 22 of 40 (55%) patients in the mesalamine low- and high-dose groups, respectively (P = 0.924). Truncated Mayo Score (low-dose 30 [73%] and high-dose 28 [70%] patients) and other efficacy results did not differ between the groups. The type and severity of adverse events were consistent with those reported in previous studies of adults with ulcerative colitis and did not differ between groups. Conclusions: Both low- and high-dose oral, delayed-release mesalamine doses were equally effective as short-term treatment of mild-to-moderately active ulcerative colitis in children, without a specific benefit or risk to using either dose. PMID:25419597

Dose-response study of sajabalssuk ethanol extract from Artemisia princeps Pampanini on blood glucose in subjects with impaired fasting glucose or mild type 2 diabetes.

PubMed

Choi, Ji-Young; Shin, Su-Kyung; Jeon, Seon-Min; Baek, Nam-In; Chung, Hae-Gon; Jeong, Tae-Sook; Lee, Kyung Tae; Lee, Mi-Kyung; Choi, Myung-Sook

2011-01-01

Previously we reported that an ethanol extract from Artemisia princeps Pampanini lowered blood glucose in db/db mice. Here we report a preliminary study in which the blood glucose-lowering effects of two different doses of sajabalssuk ethanol extract (SBE), containing eupatilin and jaseocidin, were examined in hyperglycemic subjects with fasting blood glucose (FBG) levels of 100-150 mg/dL. Subjects were randomized into four groups: negative control (2,000 mg of lactose /day), positive control (1,140 mg of pinitol/day), low-dose SBE (2,000 mg of SBE/day), and high-dose SBE (4,000 mg of SBE/day). After 8 weeks of supplementation, FBG and glycosylated hemoglobin levels were significantly lowered in low-and high-dose SBE groups compared to the baseline values; high-dose SBE also resulted in significantly lower plasma free fatty acid levels and systolic blood pressure. This study demonstrated that supplementation of 2 g or 4 g of SBE daily can significantly reduce blood glucose in hyperglycemic subjects, although high-dose SBE seemed to be more effective than low-dose SBE for lowering plasma free fatty acid level and systolic blood pressure.

MAGIC with formaldehyde applied to dosimetry of HDR brachytherapy source

NASA Astrophysics Data System (ADS)

Marques; T; Fernandes; J; Barbi; G; Nicolucci; P; Baffa; O

2009-05-01

The use of polymer gel dosimeters in brachytherapy can allow the determination of three-dimensional dose distributions in large volumes and with high spatial resolution if an adequate calibration process is performed. One of the major issues in these experiments is the polymer gel response dependence on dose rate when high dose rate sources are used and the doses in the vicinity of the sources are to be determinated. In this study, the response of a modified MAGIC polymer gel with formaldehyde around an Iridium-192 HDR brachytherapy source is presented. Experimental results obtained with this polymer gel were compared with ionization chamber measurements and with Monte Carlo simulation with PENELOPE. A maximum difference of 3.10% was found between gel dose measurements and Monte Carlo simulation at a radial distance of 18 mm from the source. The results obtained show that the gel's response is strongly influenced by dose rate and that a different calibration should be used for the vicinity of the source and for regions of lower dose rates. The results obtained in this study show that, provided the proper calibration is performed, MAGIC with formaldehyde can be successfully used to accurate determinate dose distributions form high dose rate brachytherapy sources.

Chromosomal Aberrations in DNA Repair Defective Cell Lines: Comparisons of Dose Rate and Radiation Quality

NASA Technical Reports Server (NTRS)

George, K. A.; Hada, M.; Patel, Z.; Huff, J.; Pluth, J. M.; Cucinotta, F. A.

2009-01-01

Chromosome aberration yields were assessed in DNA double-strand break repair (DSB) deficient cells after acute doses of gamma-rays or high-LET iron nuclei, or low dose-rate (0.018 Gy/hr) gamma-rays. We studied several cell lines including fibroblasts deficient in ATM (product of the gene that is mutated in ataxia telangiectasia patients) or NBS (product of the gene mutated in the Nijmegen breakage syndrome), and gliomablastoma cells that are proficient or lacking in DNA-dependent protein kinase, DNA-PK activity. Chromosomes were analyzed using the fluorescence in-situ hybridization (FISH) chromosome painting method in cells at the first division post-irradiation and chromosome aberrations were identified as either simple exchanges (translocations and dicentrics) or complex exchanges (involving >2 breaks in 2 or more chromosomes). Gamma radiation induced higher yields of both simple and complex exchanges in the DSB repair defective cells than in the normal cells. The quadratic dose-response terms for both chromosome exchange types were significantly higher for the ATM and NBS defective lines than for normal fibroblasts. However, the linear dose-response term was significantly higher only for simple exchanges in the NBS cells. Large increases in the quadratic dose response terms indicate the important roles of ATM and NBS in chromatin modifications that facilitate correct DSB repair and minimize aberration formation. Differences in the response of AT and NBS deficient cells at lower doses suggests important questions about the applicability of observations of radiation sensitivity at high dose to low dose exposures. For all iron nuclei irradiated cells, regression models preferred purely linear and quadratic dose responses for simple and complex exchanges, respectively. All the DNA repair defective cell lines had lower Relative biological effectiveness (RBE) values than normal cells, the lowest being for the DNA-PK-deficient cells, which was near unity. To further investigate the sensitivity differences for low and low high doses, we performed chronic low dose-rate irradiation, and have begun studies with ATM and Nibrin inhibitors and siRNA knockout of these proteins. Results support the conclusion that for the endpoint of simple chromosomal aberrations (translocation or dicentrics), the increased radiation sensitivity of AT cells found at high doses (>1 Gy) does not carry over to low doses or doserates, while NBS cells show increased sensitivity for both high and low dose exposures.

An evaluation of hyperkalemia and serum creatinine elevation associated with different dosage levels of outpatient trimethoprim-sulfamethoxazole with and without concomitant medications.

PubMed

Gentry, Chris A; Nguyen, Ann T

2013-12-01

Adverse events associated with high-dose trimethoprim-sulfamethoxazole (TMP-SMX) for outpatient infections, particularly those likely caused by community-acquired methicillin-resistant Staphylococcus aureus, have not been adequately characterized. Describe hyperkalemia and acute renal injury associated with high-dose TMP-SMX. An electronic medical record database retrospective study was conducted of outpatients receiving high-dose or low-dose TMP-SMX, comparing the incidences of hyperkalemia and acute renal injury. Of 6162 patients, more developed hyperkalemia (3.06% vs 1.05%, P < .0001) or acute renal injury (1.99% vs 0.700%, P = .0001) in the high-dose TMP-SMX group. Variables independently associated with hyperkalemia included age >58 years (odds ratio [OR] = 3.44; 95% CI = 1.86-7.0; P < .0001), concomitant receipt of an NSAID (OR = 1.71; 95% CI = 1.02-2.79; P = .044) or an ACE inhibitor (OR = 3.27; 95% CI = 2.06-5.14; P < .0001), high-dose TMP-SMX prescribed (OR = 2.92; 95% CI = 1.85-4.60; P < .0001), and baseline elevated serum creatinine (OR = 45.1; 95% CI = 21.7-93.2; P < .0001). Variables independently associated with acute renal injury included concomitant receipt of an ACE inhibitor (OR = 2.36; 95% CI = 1.01-5.24; P = .048) or a potassium supplement (OR = 4.10; 95% CI = 1.45-10.1; P = .010), high-dose TMP-SMX prescribed (OR = 3.70; 95% CI = 1.70-8.12; P = .0012), and baseline elevated serum creatinine (OR = 2110; 95% CI = 724-7980; P < .0001). Serum creatinine and potassium concentrations should be monitored in outpatients receiving high-dose TMP-SMX.

Comparative Effectiveness of Mesalamine, Sulfasalazine, Corticosteroids, and Budesonide for the Induction of Remission in Crohn's Disease: A Bayesian Network Meta-analysis.

PubMed

Coward, Stephanie; Kuenzig, M Ellen; Hazlewood, Glen; Clement, Fiona; McBrien, Kerry; Holmes, Rebecca; Panaccione, Remo; Ghosh, Subrata; Seow, Cynthia H; Rezaie, Ali; Kaplan, Gilaad G

2017-03-01

Induction treatment of mild-to-moderate Crohn's disease is controversial. To compare the induction of remission between different doses of mesalamine, sulfasalazine, corticosteroids, and budesonide for active Crohn's disease. We identified randomized controlled trials from existing Cochrane reviews and an updated literature search in Medline, EMBASE, and CENTRAL to November 2015. We included randomized controlled trials (n = 22) in adult patients with Crohn's disease that compared budesonide, sulfasalazine, mesalamine, or corticosteroids with placebo or each other, for the induction of remission (8-17 wks). Mesalamine (above and below 2.4 g/d) and budesonide (above and below 6 mg/d) were stratified into low and high doses. Our primary outcome was remission, defined as a Crohn's Disease Activity Index score <150. A Bayesian random-effects network meta-analysis was performed on the proportion in remission. Corticosteroids (odds ratio [OR] = 3.80; 95% credible interval [CrI]: 2.48-5.66), high-dose budesonide (OR = 2.96; 95% CrI: 2.06-4.30), and high-dose mesalamine (OR = 2.29; 95% CrI: 1.58-3.33) were superior to placebo. Corticosteroids were similar to high-dose budesonide (OR = 1.21; 95% CrI: 0.84-1.76), but more effective than high-dose mesalamine (OR = 1.83; 95% CrI: 1.16-2.88). Sulfasalazine was not significantly superior to any therapy including placebo. Randomized controlled trials that use a strict definition of induction of remission and disease severity at enrollment to assess effectiveness in treating mild-to-moderate Crohn's disease are limited. Corticosteroids and high-dose budesonide were effective treatments for inducing remission in mild-to-moderate Crohn's disease. High-dose mesalamine is an option among patients preferring to avoid steroids.

Acinetobacter Prosthetic Joint Infection Treated with Debridement and High-Dose Tigecycline.

PubMed

Vila, Andrea; Pagella, Hugo; Amadio, Claudio; Leiva, Alejandro

2016-12-01

Prosthesis retention is not recommended for multidrug-resistant Acinetobacter prosthetic joint infection due to its high failure rate. Nevertheless, replacing the prosthesis implies high morbidity and prolonged hospitalization. Although tigecycline is not approved for the treatment of prosthetic joint infection due to multidrug resistant Acinetobacter baumannii, its appropriate use may preclude prosthesis exchange. Since the area under the curve divided by the minimum inhibitory concentration is the best pharmacodynamic predictor of its efficacy, we used tigecycline at high dose, in order to optimize its efficacy and achieve implant retention in 3 patients who refused prosthesis exchange. All patients with prosthetic joint infections treated at our Institution are prospectively registered in a database. Three patients with early prosthetic joint infection of total hip arthroplasty due to multidrug resistant A. baumannii were treated with debridement, antibiotics and implant retention, using a high maintenance dose of tigecycline (100 mg every 12 hours). The cases were retrospectively reviewed. All patients signed informed consent for receiving off-label use of tigecycline. Tigecycline was well tolerated, allowing its administration at high maintenance dose for a median of 40 days (range 30-60). Two patients were then switched to minocycline at standard doses for a median of 3.3 months in order to complete treatment. Currently, none of the patients showed relapse. Increasing the dose of tigecycline could be considered as a means to better attain pharmacodynamic targets in patients with severe or difficult-to-treat infections. Tigecycline at high maintenance dose might be useful when retention of the implant is attempted for treatment for prosthetic joint infections due to multidrug resistant Acinetobacter. Although this approach might be promising, off-label use of tigecycline should be interpreted cautiously until prospective data are available. Tigecycline is probably under-dosed for the treatment of implant and biofilm associated infections.

High-versus low-dose erythropoietin in extremely low birth weight infants. The European Multicenter rhEPO Study Group.

PubMed

Maier, R F; Obladen, M; Kattner, E; Natzschka, J; Messer, J; Regazzoni, B M; Speer, C P; Fellman, V; Grauel, E L; Groneck, P; Wagner, M; Moriette, G; Salle, B L; Verellen, G; Scigalla, P

1998-05-01

To investigate whether a weekly 1500 IU/kg dose of recombinant human erythropoietin (rhEPO) is more effective than a dose of 750 IU/kg/week in preventing anemia and reducing the transfusion need in infants with birth weights less than 1000 gm. In a randomized, double-blind, multicenter trial, 184 infants with birth weights between 500 and 999 gm were treated with either rhEPO 750 (low-dose group) or 1500 IU/kg/week (high-dose group) from day 3 of life until 37 weeks' corrected age. Thirty-two percent of the infants in each group did not receive any transfusion during the treatment period. The total volume of erythrocytes received was similar in each group. The success rate, defined as no transfusion needed and hematocrit value 0.30 L/L or greater, was 27.6% in the low-dose and 29.5% in the high-dose group (p = 0.96). Doubling the rhEPO dose of 750 IU/kg/week is not indicated in infants with birth weights less than 1000 gm.

Application of TL dosemeters for dose distribution measurements at high temperatures in nuclear reactors.

PubMed

Osvay, M; Deme, S

2006-01-01

Al2O3:Mg,Y ceramic thermoluminescence dosemeters were developed at the Institute of Isotopes for high dose applications at room temperatures. The glow curve of Al2O3:Mg,Y exhibits two peaks--one at 250 degrees C (I) and another peak at approximately 400 degrees C (II). In order to extend the application of these dosemeters to high temperatures, the effect of irradiation temperature was investigated using temperature controlled heating system during high dose irradiation at various temperatures (20-100 degrees C). The new calibration and measuring method has been successfully applied for dose mapping within the hermetic zone of the Paks Nuclear Power Plant even at high temperature parts of blocks.