Memory immune response and safety of a booster dose of Japanese encephalitis chimeric virus vaccine (JE-CV) in JE-CV-primed children

PubMed Central

Feroldi, Emmanuel; Capeding, Maria Rosario; Boaz, Mark; Gailhardou, Sophia; Meric, Claude; Bouckenooghe, Alain

2013-01-01

Japanese encephalitis chimeric virus vaccine (JE-CV) is a licensed vaccine indicated in a single dose administration for primary immunization. This controlled phase III comparative trial enrolled children aged 36–42 mo in the Philippines. 345 children who had received one dose of JE-CV in a study two years earlier, received a JE-CV booster dose. 105 JE-vaccine-naïve children in general good health were randomized to receive JE-CV (JE-vaccine naïve group; 46 children) or varicella vaccine (safety control group; 59 children). JE neutralizing antibody titers were assessed using PRNT50. Immunological memory was observed in children who had received the primary dose of JE-CV before. Seven days after the JE-CV booster dose administration, 96.2% and 66.8% of children were seroprotected and had seroconverted, respectively, and the geometric mean titer (GMT) was 231 1/dil. Twenty-eight days after the JE-CV booster dose seroprotection and seroconversion were achieved in 100% and 95.3% of children, respectively, and the GMT was 2,242 1/dil. In contrast, only 15.4% of JE-CV-vaccine naïve children who had not received any prior JE vaccine were seroprotected seven days after they received JE-CV. One year after receiving the JE-CV booster dose, 99.4% of children remained seroprotected. We conclude that JE-CV is effective and safe, both as a single dose and when administrated as a booster dose. A booster dose increases the peak GMT above the peak level reached after primary immunization and the antibody persistence is maintained at least one year after the JE-CV booster dose administration. Five year follow up is ongoing. PMID:23442823

Memory immune response and safety of a booster dose of Japanese encephalitis chimeric virus vaccine (JE-CV) in JE-CV-primed children.

PubMed

Feroldi, Emmanuel; Capeding, Maria Rosario; Boaz, Mark; Gailhardou, Sophia; Meric, Claude; Bouckenooghe, Alain

2013-04-01

Japanese encephalitis chimeric virus vaccine (JE-CV) is a licensed vaccine indicated in a single dose administration for primary immunization. This controlled phase III comparative trial enrolled children aged 36-42 mo in the Philippines. 345 children who had received one dose of JE-CV in a study two years earlier, received a JE-CV booster dose. 105 JE-vaccine-naïve children in general good health were randomized to receive JE-CV (JE-vaccine naïve group; 46 children) or varicella vaccine (safety control group; 59 children). JE neutralizing antibody titers were assessed using PRNT50. Immunological memory was observed in children who had received the primary dose of JE-CV before. Seven days after the JE-CV booster dose administration, 96.2% and 66.8% of children were seroprotected and had seroconverted, respectively, and the geometric mean titer (GMT) was 231 1/dil. Twenty-eight days after the JE-CV booster dose seroprotection and seroconversion were achieved in 100% and 95.3% of children, respectively, and the GMT was 2,242 1/dil. In contrast, only 15.4% of JE-CV-vaccine naïve children who had not received any prior JE vaccine were seroprotected seven days after they received JE-CV. One year after receiving the JE-CV booster dose, 99.4% of children remained seroprotected. We conclude that JE-CV is effective and safe, both as a single dose and when administrated as a booster dose. A booster dose increases the peak GMT above the peak level reached after primary immunization and the antibody persistence is maintained at least one year after the JE-CV booster dose administration. Five year follow up is ongoing.

Effective Dose Radon 222 of the Tap Water in Children and Adults People; Minab City, Iran.

PubMed

Fakhri, Yadolah; Kargosha, Morteza; Langarizadeh, Ghazaleh; Zandsalimi, Yahya; Rasouli Amirhajeloo, Leila; Moradi, Mahboobeh; Moradi, Bigard; Mirzaei, Maryam

2015-09-01

(222)Rn is a radioactive, odorless, and colorless element which has a half-life of 3.83 days. One of (222)Rn main resources are Groundwater (wells, springs, etc.). Hence, the use of groundwater with high concentration of (222)Rn can increase the risk of lung and stomach cancers. Concentration of (222)Rn in tap water of Minab city in two temperatures 5 and 15 ºC was measured by radon meter model RTM1668-2. The effective dose was calculated by equations proposed by UNSCEAR. Geometric mean concentration of (222)Rn in drinking water was found to be 0.78±0.06 and 0.46±0.04 Bq/l at 5 and 15 ̊C (p value<0.05), respectively. The effective doses were 0.006 and 0.003 mSv/y for adults, and 0.011 and 0.007 mSv/y for the children, respectively (p value<0.05). Besides, the effective dose for adult through inhaling (222)Rn at 5 and 15 ̊C were estimated 0.0021 and 0.0012mSv/y, respectively. Geometric mean concentration in (222)Rn drinking water and effective dose received from drinking water and inhalation of (222)Rn is lower than WHO and EPA standard limits. Increasing temperature of drinking water will decrease the effective dose received. Annual Effective dose received from inhalation and consumption of (222)Rn in drinking water in children is more than adults.

Effective Dose Radon 222 of the Tap Water in Children and Adults People; Minab City, Iran

PubMed Central

Fakhri, Yadolah; Kargosha, Morteza; Langarizadeh, Ghazaleh; Zandsalimi, Yahya; Amirhajeloo, Leila Rasouli; Moradi, Mahboobeh; Moradi, Bigard; Mirzaei, Maryam

2016-01-01

222Rn is a radioactive, odorless, and colorless element which has a half-life of 3.83 days. One of 222Rn main resources are Groundwater (wells, springs, etc.). Hence, the use of groundwater with high concentration of 222Rn can increase the risk of lung and stomach cancers. Concentration of 222Rn in tap water of Minab city in two temperatures 5 and 15 ºC was measured by radon meter model RTM1668-2. The effective dose was calculated by equations proposed by UNSCEAR. Geometric mean concentration of 222Rn in drinking water was found to be 0.78±0.06 and 0.46±0.04 Bq/l at 5 and 15 °C (p value<0.05), respectively. The effective doses were 0.006 and 0.003 mSv/y for adults, and 0.011 and 0.007 mSv/y for the children, respectively (p value<0.05). Besides, the effective dose for adult through inhaling 222Rn at 5 and 15 °C were estimated 0.0021 and 0.0012mSv/y, respectively. Geometric mean concentration in 222Rn drinking water and effective dose received from drinking water and inhalation of 222Rn is lower than WHO and EPA standard limits. Increasing temperature of drinking water will decrease the effective dose received. Annual Effective dose received from inhalation and consumption of 222Rn in drinking water in children is more than adults. PMID:26573047

Lhermitte Sign After Chemo-IMRT of Head-and-Neck Cancer: Incidence, Doses, and Potential Mechanisms

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

Pak, Daniel; Vineberg, Karen; Feng, Felix

2012-08-01

Purpose: We have observed a higher rate of Lhermitte sign (LS) after chemo-intensity-modulated radiotherapy (IMRT) of head-and-neck cancer than the published rates after conventional radiotherapy. We hypothesized that the inhomogeneous spinal cord dose distributions produced by IMRT caused a 'bath-and-shower' effect, characterized by low doses in the vicinity of high doses, reducing spinal cord tolerance. Methods and Materials: Seventy-three patients with squamous cell carcinoma of the oropharynx participated in a prospective study of IMRT concurrent with weekly carboplatin and paclitaxel. Of these, 15 (21%) reported LS during at least 2 consecutive follow-up visits. Mean dose, maximum dose, and partial volumemore » and absolute volume (in milliliters) of spinal cord receiving specified doses ({>=}10 Gy, {>=}20 Gy, {>=}30 Gy, and {>=}40 Gy), as well as the pattern of dose distributions at the 'anatomic' spinal cord (from the base of the skull to the aortic arch) and 'plan-related' spinal cord (from the top through the bottom of the planning target volumes), were compared between LS patients and 34 non-LS patients. Results: LS patients had significantly higher spinal cord mean doses, V{sub 30}, V{sub 40}, and absolute volumes receiving 30 Gy or more and 40 Gy or more compared with the non-LS patients (p < 0.05). The strongest predictors of LS were higher V{sub 40} and higher cord volumes receiving 40 Gy or more (p {<=} 0.007). There was no evidence of larger spinal cord volumes receiving low doses in the vicinity of higher doses (bath-and-shower effect) in LS compared with non-LS patients. Conclusions: Greater mean dose, V{sub 30}, V{sub 40}, and cord volumes receiving 30 Gy or more and 40 Gy or more characterized LS compared with non-LS patients. Bath-and-shower effects could not be validated in this study as a potential contributor to LS. The higher-than-expected rates of LS may be because of the specific concurrent chemotherapy agents or more accurate identification of LS in the setting of a prospective study.« less

Does oral polio vaccine have non-specific effects on all-cause mortality? Natural experiments within a randomised controlled trial of early measles vaccine.

PubMed

Aaby, Peter; Andersen, Andreas; Martins, Cesário L; Fisker, Ane B; Rodrigues, Amabelia; Whittle, Hilton C; Benn, Christine S

2016-12-23

BCG and measles vaccine (MV) may have beneficial non-specific effects (NSEs). If an unplanned intervention with a vaccine (a natural experiment) modifies the estimated effect in a randomised controlled trial (RCT), this suggests NSEs. We used this approach to test NSEs of triple oral polio vaccine (OPV). During an RCT of 2 doses of MV at 4.5 and 9 months versus 1 dose of MV at 9 months of age, we experienced 2 natural experiments with OPV. We assessed whether these OPV experiments modified the effect of 2-dose MV in the MV trial. MV RCT conducted in urban Guinea-Bissau 2003-2009. Natural experiments with OPV due to missing vaccine and the implementation of OPV campaigns. Changes in the mortality rate ratio (MRR) for 2-dose MV versus 1-dose MV. First, the MRR (2-dose/1-dose MV) overall was 0.70 (0.52 to 0.94), but the MRR was 1.04 (0.53 to 2.04) when OPV at birth (OPV0) was not given, suggesting that early priming with OPV was important for the effect of 2-dose MV. The effect of OPV0 depended on age of administration; the MRR (2-dose/1-dose MV) was 0.45 (0.29 to 0.71) for children receiving OPV0 in the first week of life, but 3.63 (0.87 to 15.2) for those receiving OPV0 after the first month of life (p=0.007, test of no interaction). Second, campaign-OPV may have reduced the difference between the randomisation groups since the MRR (2-dose/1-dose MV) was 0.60 (0.42 to 0.85) for children who had not received campaign-OPV before RCT-enrolment versus 0.72 (0.23 to 2.31) and 1.42 (0.70 to 2.90) for children who had received 1 or 2 doses of campaign-OPV-before-enrolment, respectively. Bissau had no polio infection during this trial, so OPV0 and campaign-OPV may have NSEs since they modified the effect of 2-dose MV in an RCT. Different interventions may interact to a much larger effect than usually assumed. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Facial exposure to ultraviolet radiation: Predicted sun protection effectiveness of various hat styles.

PubMed

Backes, C; Religi, A; Moccozet, L; Vuilleumier, L; Vernez, D; Bulliard, J-L

2018-04-23

Solar ultraviolet radiation (UVR) doses received by individuals are highly influenced by behavioural and environmental factors. This study aimed at quantifying hats' sun protection effectiveness in various exposure conditions, by predicting UVR exposure doses and their anatomical distributions. A well-defined three-dimensional head morphology and four hat styles (a cap, a helmet, a middle- and a wide-brimmed hat) were added to a previously published model. Midday (12:00-14:00) and daily (08:00 - 17:00) seasonal UVR doses were estimated at various facial skin zones, with and without hat-wear, accounting for each UVR component. Protection effectiveness was calculated by the relative reduction of predicted UVR dose, expressed as a predictive protection factor (PPF). The unprotected entire face received 2.5 times higher UVR doses during a summer midday compared to a winter midday (3.3 vs. 1.3 SED) with highest doses received at the nose (6.1 SED). During a cloudless summer day, the lowest mean UVR dose is received by the entire face protected by a wide-brimmed hat (1.7 SED). No hat reached 100% protection at any facial skin zone (PPF max : 76%). Hats' sun protection effectiveness varied highly with environmental conditions and were mainly limited by the high contribution of diffuse UVR, irrespective of hat style. Larger brim sizes afforded greater facial protection than smaller brim sizes except around midday when the sun position is high. Consideration of diffuse and reflected UVR in sun educational messages could improve sun protection effectiveness. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Escalation to High Dose Defibrotide in Patients with Hepatic Veno-Occlusive Disease

PubMed Central

Triplett, Brandon M.; Kuttab, Hani I.; Kang, Guolian; Leung, Wing

2015-01-01

Hepatic veno-occlusive disease (VOD) is a serious complication of high-dose chemotherapy regimens, such as those utilized in hematopoietic cell transplantation recipients. Defibrotide is considered a safe and effective treatment when dosed at 25 mg/kg/day. However, patients who develop VOD still have increased mortality despite the use of defibrotide. Data are limited on the use of doses above 60 mg/kg/day for persistent VOD. In this prospective clinical trial, 34 patients received escalating doses of defibrotide. For patients with persistent VOD despite doses of 60 mg/kg/day, doses were increased to a maximum of 110 mg/kg/day. There was no observed increase in toxicity until doses rose beyond 100 mg/kg/day. Patients receiving doses between 10–100 mg/kg/day experienced an average of 3 bleeding episodes per 100 days of treatment, while those receiving doses >100 mg/kg/day experienced 13.2 bleeding episodes per 100 days (p=0.008). Moreover, dose reductions due to toxicity were needed at doses of 110 mg/kg/day more often than at lower doses. Defibrotide may be safely escalated to doses well above the current standard without an increase in bleeding risk. However, the efficacy of this dose escalation strategy remains unclear, as outcomes were similar to published cohorts of patients receiving standard doses of defibrotide for VOD. PMID:26278046

Mumijo attenuates chemically induced inflammatory pain in mice.

PubMed

Malekzadeh, Golnaz; Dashti-Rahmatabadi, Mohammad Hossein; Zanbagh, Samira; Akhavi Mirab-bashii, Atefehsadat

2015-01-01

Mumijo (shilajit) has been well known in traditional medicine as a remedy for a number of diseases, such as bone fractures, wounds, inflammation, and headache. It is also widely used as an analgesic agent in folk medicine, but no scientific documentation exists concerning that effect. The current study was conducted to evaluate the ability of mumijo to reduce sensitivity to painful stimuli when compared with morphine sulfate and sodium diclofenac. A total of 176 animals were randomly and equally divided into 2 groups with 88 mice each-one for formalin test and the other for writhing test. For each test, the animals were allocated into 10 equal groups, based on the dosage of the analgesic, plus a negative control group, with 8 mice in each group. The analgesic effect of mumijo extract in doses of 0.75, 7.5, 75, and 750 mg/kg was assessed and compared witha group receiving distilled water-the negative control group, and that for groups receiving 1, 2, or 4 mg/kg of morphine sulfate or 10, 20, or 30 mg/kg of sodium diclofenac-the positive control groups. The results showed a significant decrease in pain intensity for all mice receiving doses of mumijo extract during a 1-h formalin test when compared with the distilled water group. For all the mumijo groups except the one receiving 750 mg/kg, the analgesic effect was significantly lower than that for the morphine sulfate group receiving 4 mg/kg. No significant differences existed between all mumijo and all diclofenac groups. In a writhing test, a significant inhibition of the pain response induced by acetic acid also occurred in all 4 mumijo-administered groups as opposed to the group receiving distilled water. No significant differences existed between the writhing response in groups receiving 75 and 750 mg/kg of mumijo and any doses of diclofenac or morphine. The comparison among the different doses of mumijo in the formalin test did not show any significant differences, but in the writhing test, the maximum dose showed a more effective analgesic action. The findings indicated a significant analgesic effect for mumijo extract on chronic pain in mice, occurring in a dose-independent manner.

Radiation Doses from the Norwegian Diet.

PubMed

Komperød, Mari; Skuterud, Lavrans

2018-06-13

Ingestion doses between and within countries are expected to vary significantly due to differences in dietary habits and geographical variations in radionuclide concentrations. This paper presents the most comprehensive assessment to date of the effective radiation dose from the Norwegian diet, from natural as well as anthropogenic radionuclides. Ingestion doses to the Norwegian public are calculated using national dietary statistics and the most relevant radionuclide concentration data for the various food products. The age-weighted average effective dose received by the Norwegian population from the diet is estimated at 0.41 mSv y from naturally occurring radionuclides and 0.010 mSv y from anthropogenic radionuclides. This is approximately 50% higher than the estimated world average. Fish and shellfish is the food group that provides the largest dose contribution from the average Norwegian diet. Although the average dose from anthropogenic radionuclides today is low, the exposure may still be significant for certain critical groups-especially persons who consume large amounts of reindeer meat from the regions that received significant radioactive fallout after the Chernobyl accident. Furthermore, persons with high Rn concentrations in their drinking water are among those receiving the highest ingestion doses in Norway.

Influence of exposure and geometric parameters on absorbed doses associated with common neuro-interventional procedures.

PubMed

Safari, Mohammad Javad; Wong, Jeannie Hsiu Ding; Jong, Wei Loong; Thorpe, Nathan; Cutajar, Dean; Rosenfeld, Anatoly; Ng, Kwan Hoong

2017-03-01

The purpose of this study was to investigate the effects of routine exposure parameters on patient's dose during neuro-interventional radiology procedures. We scrutinized the routine radiological exposure parameters during 58 clinical neuro-interventional procedures such as, exposure direction, magnification, frame rate, and distance between image receptor to patient's body and evaluate their effects on patient's dose using an anthropomorphic phantom. Radiation dose received by the occipital region, ears and eyes of the phantom were measured using MOSkin detectors. DSA imaging technique is a major contributor to patient's dose (80.9%) even though they are used sparingly (5.3% of total frame number). The occipital region of the brain received high dose largely from the frontal tube constantly placed under couch (73.7% of the total KAP). When rotating the frontal tube away from under the couch, the radiation dose to the occipital reduced by 40%. The use of magnification modes could increase radiation dose by 94%. Changing the image receptor to the phantom surface distance from 10 to 40cm doubled the radiation dose received by the patient's skin at the occipital region. Our findings provided important insights into the contribution of selected fluoroscopic exposure parameters and their impact on patient's dose during neuro-interventional radiology procedures. This study showed that the DSA imaging technique contributed to the highest patient's dose and judicial use of exposure parameters might assist interventional radiologists in effective skin and eye lens dose reduction for patients undergoing neuro-interventional procedures. Copyright © 2017 Associazione Italiana di Fisica Medica. All rights reserved.

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.

Radiation exposure to nuclear medicine staffs during 18F-FDG PET/CT procedures at Ramathibodi Hospital

NASA Astrophysics Data System (ADS)

Donmoon, T.; Chamroonrat, W.; Tuntawiroon, M.

2016-03-01

The aim of this study is to estimate the whole body and finger radiation doses per study received by nuclear medicine staff involved in dispensing, administration of 18F-FDG and interacting with radioactive patients during PET/CT imaging procedures in a PET/CT facility. The whole-body doses received by radiopharmacists, technologists and nurses were measured by electronic dosimeter and the finger doses by ring dosimeter during a period of 4 months. In 70 PET/CT studies, the mean whole-body dose per study to radiopharmacist, technologist, and nurse were 1.07±0.09, 1.77±0.46, μSv, and not detectable respectively. The mean finger doses per study received by radiopharmacist, technologist, and nurse were 265.65±107.55, 4.84±1.08 and 19.22±2.59 μSv, respectively. The average time in contact with 18F-FDG was 5.88±0.03, 39.06±1.89 and 1.21±0.02 minutes per study for radiopharmacist, technologist and nurse respectively. Technologists received highest mean effective whole- body dose per study and radiopharmacist received the highest finger dose per study. When compared with the ICRP dose limit, each individual worker can work with many more 18F- FDG PET/CT studies for a whole year without exceeding the occupational dose limits. This study confirmed that low levels of radiation does are received by our medical personnel involved in 18F-FDG PET/CT procedures.

Effect of Age at Vaccination on Rotavirus Vaccine Effectiveness in Bolivian Infants.

PubMed

Burke, Rachel M; Tate, Jacqueline E; Pringle, Kimberly D; Patel, Manish; De Oliveira, Lucia H; Parashar, Umesh D

2018-01-16

Rotavirus vaccines are less effective in developing countries versus developed countries. One hypothesis for this difference in performance is that higher levels of maternal antibodies in developing countries may interfere with vaccine response, suggesting that delayed dosing could be beneficial. The present analysis aims to assess whether rotavirus vaccine effectiveness (VE) varies by age at vaccination during routine use in Bolivia. Data were merged from two post-licensure evaluations of monovalent rotavirus vaccine (RV1) in Bolivia, where two doses of RV1 are recommended at two and four months of age. For each dose, children were classified as receiving each dose "early," "on-time," or "late." Stratified unconditional logistic regression models were used to estimate VE, using unvaccinated children as the referent. VE was calculated as (1 - odds ratio) x 100%. Models were adjusted for hospital, age, and time since RV1 introduction (via including terms for month and year of birth). VE for two doses of RV1 tended to be higher in infants receiving the first dose early (VE 92%; 95% confidence interval [CI] [70%, 98%]), when compared to infants receiving their first dose on time (72% [62%, 81%]) or late (68% [51%, 79%]). Estimates of VE were not substantially different when comparing children by age at second dose (early: VE 76% [50%, 89%]; on time: VE 70% [50%, 89%]; late: VE 75% [60%, 84%]), including all children. Our results indicate that early administration may improve VE and support the current WHO recommendations for the RV1 schedule.

Low-dose right unilateral electroconvulsive therapy (ECT): effectiveness of the first treatment.

PubMed

Lapidus, Kyle A B; Shin, Joseph S W; Pasculli, Rosa M; Briggs, Mimi C; Popeo, Dennis M; Kellner, Charles H

2013-06-01

Electroconvulsive therapy (ECT) is a widely used, highly effective antidepressant treatment. Except for the most severely ill patients, right unilateral (RUL) electrode placement is the most frequent initial treatment choice. In current practice, RUL ECT is administered at several multiples of seizure threshold (ST) based on reports that lower stimulus intensity results in lower response/remission rates. Many patients, as part of an initial dose titration to determine ST, will receive a single treatment with low-dose RUL ECT and subsequent treatments with a stimulus at a multiple of ST. To assess response to the first ECT. A retrospective analysis of charts from clinical practice at Mount Sinai Medical Center was performed. A single treatment with low-dose (presumably near ST) RUL ECT had a significant and immediate antidepressant effect in our sample of patients with major depression. We determined that this response is similar to that of patients receiving a single initial treatment with high-dose RUL ECT (at a multiple of ST). These data suggest, contrary to commonly held belief, that RUL ECT may be effective at a low stimulus dose. This argues against restimulating at 6 times ST in the initial session, based on the belief that the near-threshold seizure has no antidepressant efficacy. Our findings suggest a need for further investigation of cases in which low-dose RUL ECT may be an effective antidepressant treatment. Further prospective studies, including larger numbers of patients who receive randomized treatment with low- or high-dose RUL with longer follow-up, are indicated.

Escalation to High-Dose Defibrotide in Patients with Hepatic Veno-Occlusive Disease.

PubMed

Triplett, Brandon M; Kuttab, Hani I; Kang, Guolian; Leung, Wing

2015-12-01

Hepatic veno-occlusive disease (VOD) is a serious complication of high-dose chemotherapy regimens, such as those used in hematopoietic cell transplantation recipients. Defibrotide is considered a safe and effective treatment when dosed at 25 mg/kg/day. However, patients who develop VOD still have increased mortality despite the use of defibrotide. Data are limited on the use of doses above 60 mg/kg/day for persistent VOD. In this prospective clinical trial 34 patients received escalating doses of defibrotide. For patients with persistent VOD despite doses of 60 mg/kg/day, doses were increased to a maximum of 110 mg/kg/day. Increased toxicity was not observed until doses rose beyond 100 mg/kg/day. Patients receiving doses between 10 and 100 mg/kg/day experienced an average of 3 bleeding episodes per 100 days of treatment, whereas those receiving doses >100 mg/kg/day experienced 13.2 bleeding episodes per 100 days (P = .008). Moreover, dose reductions due to toxicity were needed at doses of 110 mg/kg/day more often than at lower doses. Defibrotide may be safely escalated to doses well above the current standard without an increase in bleeding risk. However, the efficacy of this dose-escalation strategy remains unclear, because outcomes were similar to published cohorts of patients receiving standard doses of defibrotide for VOD. Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Side effects of low-dose pyridostigmine bromide are not related to cholinesterase inhibition.

PubMed

Cook, M R; Gerkovich, M M; Sastre, A; Graham, C

2001-12-01

Pretreatment with pyridostigmine bromide (PB) has become part of standard military procedures for protection against the effects of possible chemical warfare attack. The purpose of the work reported here was to quantify the type, intensity and frequency of side effects of low-dose PB, and to examine factors that predict the intensity and frequency of side effects. A double-blind, cross-over, placebo (PL)-controlled design was used. Of the 67 subjects, 33 received 30 mg PB every 8 h for 13 doses, and 34 received 60 mg on the same schedule. Order of PB and PL administration was counterbalanced. Overall, side effects were mild, even at the 60-mg dose level. More side effects were reported when volunteers were taking PB than when they were taking placebo. Women reported more symptoms than men. Neither cholinesterase inhibition nor plasma levels of PB predicted side effect scores during the PB week; the best predictor of side effect scores during the PB week was side effect scores during the PL week. PB is well tolerated by healthy young people, even when twice the recommended military dose is administered.

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.

Prospective Clinical Trial of Bladder Filling and Three-Dimensional Dosimetry in High-Dose-Rate Vaginal Cuff Brachytherapy

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

Stewart, Alexandra J.; Cormack, Robert A.; Lee, Hang

2008-11-01

Purpose: To investigate the effect of bladder filling on dosimetry and to determine the best bladder dosimetric parameter for vaginal cuff brachytherapy. Methods and Materials: In this prospective clinical trial, a total of 20 women underwent vaginal cylinder high-dose-rate brachytherapy. The bladder was full for Fraction 2 and empty for Fraction 3. Dose-volume histogram and dose-surface histogram values were generated for the bladder, rectum, and urethra. The midline maximal bladder point (MBP) and the midline maximal rectal point were recorded. Paired t tests, Pearson correlations, and regression analyses were performed. Results: The volume and surface area of the irradiated bladdermore » were significantly smaller when the bladder was empty than when full. Of the several dose-volume histogram and dose-surface histogram parameters evaluated, the bladder maximal dose received by 2 cm{sup 3} of tissue, volume of bladder receiving {>=}50% of the dose, volume of bladder receiving {>=}70% of the dose, and surface area of bladder receiving {>=}50% of the dose significantly predicted for the difference between the empty vs. full filling state. The volume of bladder receiving {>=}70% of the dose and the maximal dose received by 2 cm{sup 3} of tissue correlated significantly with the MBP. Bladder filling did not alter the volume or surface area of the rectum irradiated. However, an empty bladder did result in the nearest point of bowel being significantly closer to the vaginal cylinder than when the bladder was full. Conclusions: Patients undergoing vaginal cuff brachytherapy treated with an empty bladder have a lower bladder dose than those treated with a full bladder. The MBP correlated well with the volumetric assessments of bladder dose and provided a noninvasive method for reporting the MBP dose using three-dimensional imaging. The MBP can therefore be used as a surrogate for complex dosimetry in the clinic.« less

Immunogenicity of the 9-Valent HPV Vaccine Using 2-Dose Regimens in Girls and Boys vs a 3-Dose Regimen in Women.

PubMed

Iversen, Ole-Erik; Miranda, Maria Jose; Ulied, Angels; Soerdal, Terje; Lazarus, Erica; Chokephaibulkit, Kulkanya; Block, Stan L; Skrivanek, Ales; Nur Azurah, Abdul Ghani; Fong, Siew Moy; Dvorak, Vladimir; Kim, Kyung-Hyo; Cestero, Ramon M; Berkovitch, Matitiahu; Ceyhan, Mehmet; Ellison, Misoo C; Ritter, Michael A; Yuan, Shuai S; DiNubile, Mark J; Saah, Alfred J; Luxembourg, Alain

2016-12-13

Human papillomavirus (HPV) infections cause anogenital cancers and warts. The 9-valent HPV vaccine provides protection against 7 high-risk types of HPV responsible for 90% of cervical cancers and 2 other HPV types accounting for 90% of genital warts. To determine whether HPV type-specific antibody responses would be noninferior among girls and boys aged 9 to 14 years after receiving 2 doses of the 9-valent HPV vaccine compared with adolescent girls and young women aged 16 to 26 years receiving 3 doses. Open-label, noninferiority, immunogenicity trial conducted at 52 ambulatory care sites in 15 countries. The study was initiated on December 16, 2013, with the last participant visit for this report on June 19, 2015. Five cohorts were enrolled: (1) girls aged 9 to 14 years to receive 2 doses 6 months apart (n = 301); (2) boys aged 9 to 14 years to receive 2 doses 6 months apart (n = 301); (3) girls and boys aged 9 to 14 years to receive 2 doses 12 months apart (n = 301); (4) girls aged 9 to 14 years to receive 3 doses over 6 months (n = 301); and (5) a control group of adolescent girls and young women aged 16 to 26 years to receive 3 doses over 6 months (n = 314). Two doses of the 9-valent HPV vaccine administered 6 or 12 months apart or 3 doses administered over 6 months. The primary end point was prespecified as the antibody response against each HPV type assessed 1 month after the last dose using a competitive immunoassay. Each of the three 2-dose regimens was compared with the standard 3-dose schedule in adolescent girls and young women using a noninferiority margin of 0.67 for the ratio of the antibody geometric mean titers. Of the 1518 participants (753 girls [mean age, 11.4 years]; 451 boys [mean age, 11.5 years]; and 314 adolescent girls and young women [mean age, 21.0 years]), 1474 completed the study and data from 1377 were analyzed. At 4 weeks after the last dose, HPV antibody responses in girls and boys given 2 doses were noninferior to HPV antibody responses in adolescent girls and young women given 3 doses (P < .001 for each HPV type). Compared with adolescent girls and young women who received 3 doses over 6 months, the 1-sided 97.5% CIs for the ratio of HPV antibody geometric mean titers at 1 month after the last dose across the 9 HPV subtypes ranged from 1.36 to ∞ to 2.50 to ∞ for girls who received 2 doses 6 months apart; from 1.37 to ∞ to 2.55 to ∞ for boys who received 2 doses 6 months apart; and from 1.61 to ∞ to 5.36 to ∞ for girls and boys who received 2 doses 12 months apart. Among girls and boys aged 9 to 14 years receiving 2-dose regimens of a 9-valent HPV vaccine separated by 6 or 12 months, immunogenicity 4 weeks after the last dose was noninferior to a 3-dose regimen in a cohort of adolescent girls and young women. Further research is needed to assess persistence of antibody responses and effects on clinical outcomes. clinicaltrials.gov Identifier: NCT01984697.

Tailored interventions for screening mammography among a sample of initially non-adherent women: when is a booster dose important?

PubMed

Skinner, Celette Sugg; Kobrin, Sarah C; Monahan, Patrick O; Daggy, Joanne; Menon, Usha; Todora, Helen Smith; Champion, Victoria L

2007-01-01

To assess added value of a booster dose of a tailored mammography intervention. Participants, non-adherent at baseline, were randomly assigned to usual care or one of three tailored interventions. Intervention group members (n=657) were further randomly assigned to receive/not receive a booster intervention dose. Electronic record mammography data were collected following initial intervention and at 6 and 15 months post-booster. Booster had no effect among women not screened after first intervention dose (n=337). Among women screened after initial dose (n=320), booster predicted re-screening at 6 but not 15 months. A boosterxrace interaction showed a booster effect at 6 months for African Americans (OR=4.66, p=.0005) but not Caucasians (OR=0.74, p=.44). Findings suggest if a first-dose intervention does not facilitate screening, neither will a booster dose. However, among women for whom a first dose is effective, boosters can facilitate timely repeat adherence, especially among African Americans. At 6 months booster recipients were less likely to be off-schedule but, by 15 months, the groups were similar. Boosters may effect when, but not whether, women continue screening.

Beneficial effects of low dose Musa paradisiaca on the semen quality of male Wistar rats.

PubMed

Alabi, A S; Omotoso, Gabriel O; Enaibe, B U; Akinola, O B; Tagoe, C N B

2013-03-01

This study aimed at determining the effects of administration of mature green fruits of Musa paradisiaca on the semen quality of adult male Wistar rats. THE ANIMALS USED FOR THE STUDY WERE GROUPED INTO THREE: the control group, given 2 ml of double distilled water, a low dose group given 500 mg/kg/day and a high dose group given 1000 mg/kg/day of the plantain fruits, which was made into flour, and dissolved in 2 ml of double distilled water for easy oral administration. Significant increment in the semen parameters was noticed in animals that received a lower dose of the plantain flour, but those animals who received the high dose had marked and very significant reduction in sperm cell concentration and percentage of morphologically normal spermatozoa. Musa paradisiaca should be consumed in moderate quantities in order to derive its beneficial effects of enhancing male reproductive functions.

Effects of alfaxalone administered intravenously to healthy yearling loggerhead sea turtles (Caretta caretta) at three different doses.

PubMed

Phillips, Brianne E; Posner, Lysa P; Lewbart, Gregory A; Christiansen, Emily F; Harms, Craig A

2017-04-15

OBJECTIVE To compare physiologic and anesthetic effects of alfaxalone administered IV to yearling loggerhead sea turtles (Caretta caretta) at 3 different doses. DESIGN Randomized crossover study. ANIMALS 9 healthy yearling loggerhead sea turtles. PROCEDURES Animals received each of 3 doses of alfaxalone (3 mg/kg [1.4 mg/lb], 5 mg/kg [2.3 mg/lb], or 10 mg/kg [4.5 mg/lb]) administered IV in randomly assigned order, with a minimum 7-day washout period between doses. Endotracheal intubation was attempted following anesthetic induction, and heart rate, sedation depth, cloacal temperature, and respirations were monitored. Times to first effect, induction, first voluntary muscle movement, first respiration, and recovery were recorded. Venous blood gas analysis was performed at 0 and 30 minutes. Assisted ventilation was performed if apnea persisted 30 minutes following induction. RESULTS Median anesthetic induction time for all 3 doses was 2 minutes. Endotracheal intubation was accomplished in all turtles following induction. Heart rate significantly increased after the 3- and 5-mg/kg doses were administered. Median intervals from alfaxalone administration to first spontaneous respiration were 16, 22, and 54 minutes for the 3-, 5-, and 10-mg/kg doses, respectively, and median intervals to recovery were 28, 46, and 90 minutes, respectively. Assisted ventilation was required for 1 turtle after receiving the 5-mg/kg dose and for 5 turtles after receiving the 10-mg/kg dose. The 10-mg/kg dose resulted in respiratory acidosis and marked hypoxemia at 30 minutes. CONCLUSIONS AND CLINICAL RELEVANCE IV alfaxalone administration to loggerhead sea turtles resulted in a rapid anesthetic induction and dose-dependent duration of sedation. Assisted ventilation is recommended if the 10 mg/kg dose is administered.

Effect of simultaneous vaccination with H1N1 and GAD-alum on GAD65-induced immune response.

PubMed

Tavira, Beatriz; Cheramy, Mikael; Axelsson, Stina; Åkerman, Linda; Ludvigsson, Johnny; Casas, Rosaura

2017-07-01

A European Phase III trial of GAD formulated with aluminium hydroxide (GAD-alum) failed to reach its primary endpoint (preservation of stimulated C-peptide secretion from baseline to 15 months in type 1 diabetes patients), but subgroup analysis showed a clinical effect when participants from Nordic countries were excluded, raising concern as to whether the mass vaccination of the Swedish and Finnish populations with the Pandemrix influenza vaccine could have influenced the study outcomes. In the current study, we aimed to assess whether Pandemrix vaccination affects the specific immune responses induced by GAD-alum and the C-peptide response. In this secondary analysis, we analysed data acquired from the Swedish participants in the Phase III GAD-alum trial who received subcutaneous GAD-alum vaccination (two doses, n = 43; four doses, n = 46) or placebo (n = 48). GAD autoantibodies (GADA) and H1N1 autoantibodies, GAD 65 -induced cytokine secretion and change in fasting and stimulated C-peptide levels from baseline to 15 months were analysed with respect to the relative time between H1N1 vaccination and the first injection of GAD-alum. GADA levels at 15 months were associated with the relative time between GAD-alum and Pandemrix administration in participants who received two doses of the GAD-alum vaccine (p = 0.015, r = 0.4). Both in participants treated with two doses and four doses of GAD-alum, GADA levels were higher when the relative time between vaccines was ≥210 days (p < 0.05). In the group that received two doses of GAD-alum, levels of several GAD 65 -induced cytokines were higher in participants who received the H1N1 vaccination and the first GAD-alum injection at least 150 days apart, and the change in fasting and stimulated C-peptide at 15 months was associated with the relative time between vaccines. Neither of these effects were observed in individuals who received four doses of GAD-alum. In individuals who received two doses of GAD-alum, receiving the Pandemrix vaccine closer to the first GAD-alum injection, i.e. <150 days, seemed to affect both GAD 65 -induced immune response and C-peptide preservation. ClinicalTrials.gov NCT00723411.

[Efficacy and safety of vaccination against hepatitis A and B in patients with chronic liver disease].

PubMed

de Artaza Varasa, Tomás; Sánchez Ruano, Juan José; García Vela, Almudena; Gómez Rodríguez, Rafael; Romero Gutiérrez, Marta; de la Cruz Pérez, Gema; Gómez Moreno, Ana Zaida; Carrobles Jiménez, José María

2009-01-01

Vaccination to protect against hepatitis A and B should be part of the routine management of patients with chronic liver disease (CLD). To evaluate the efficacy and safety of hepatitis A virus (HAV) and hepatitis B virus (HBV) vaccination in a group of patients with CLD and to assess the presence of factors predictive of response. We performed a prospective, single-center study in 194 patients (123 men, 71 women; mean age, 48.9+/-10.7 years) with CLD: 107 with chronic hepatitis (CH) and 87 with hepatic cirrhosis (HC), all Child-Pugh class A. The most frequent causes of CLD were HCV infection and alcohol. Patients negative for anti-HAV IgG received the HAV vaccination (1440 ELISA units in two doses) and those with negative HBV serology received the HBV vaccination ( three 20 microg doses). Patients with inadequate response to the latter vaccine received an additional double dose. Thirty patients received a combination vaccine (three doses). Sixty patients (31%) received the HAV vaccine and 150 (77%) patients received the HBV vaccine. Seroconversion was achieved by 91.6% of patients for HAV and by 57% of the patients for HBV. After the additional dose, the response increased to 74%. Efficacy was similar between CH and HC. HBV vaccination was less effective in HC than in CH and the seroconversion rate was significantly lower in patients with HC and previous decompensation. The combination vaccine (30 patients) was highly immunogenic. No adverse effects were registered. HAV vaccination has high efficacy in patients with CLD. Patients with HC respond weakly to HBV vaccination compared with those with CH and especially if there is prior decompensation. The combination vaccine seems particularly effective in patients with CLD. The three vaccines are safe.

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.

Association of adverse drug effects with subjective well-being in patients with schizophrenia receiving stable doses of risperidone.

PubMed

Kim, Jong-Hoon; Kim, Min-Jung

2009-01-01

The purpose of the present study was to examine the association of adverse drug effects with subjective well-being in patients with schizophrenia receiving stable doses of risperidone. Thirty outpatients with schizophrenia receiving stable doses of risperidone were comprehensively evaluated for psychopathology, subjective well-being, and adverse drug effects. Subjective well-being was assessed using the Subjective Well-being Under Neuroleptics Scale (SWN). Adverse drug effects were evaluated using the Liverpool University Neuroleptic Side Effect Rating Scale (LUNSERS) and the Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS). In correlation analysis controlling for relevant variables, the SWN score had significant negative correlations with the following subscale scores of the LUNSERS: extrapyramidal side effect (EPS) (r = -0.54, P < 0.01), akathisia (r = -0.46, P < 0.05), and autonomic adverse effect (r = -0.44, P < 0.05). The SWN score also had a significant negative correlation with the global severity of EPS as measured by the DIEPSS (r = -0.44, P < 0.05). The results of our study suggest that adverse effects, particularly EPS and akathisia, are significantly associated with subjective well-being, implying the necessity to develop rational strategies to control these variables effectively. The results also suggest that EPS and akathisia continue to be major adverse effects associated with a low level of subjective well-being in patients receiving risperidone. Further studies are required to investigate the multidimensional factors associated with subjective well-being in patients receiving atypical antipsychotics and to determine their relative contributions.

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.

Inhalation dose due to radon, thoron, and progenies in dwellings of a hill station.

PubMed

Sivakumar, R

2017-02-01

The general public spends a major portion of their time in an indoor environment and hence receives a considerable amount of radiation. Knowledge about indoor radiation is important in order to arrive at the actual effective dose received by residents. The indoor radon, thoron, and progeny concentrations observed in the present study were found to vary with seasons of a given year. The highest and lowest indoor average radon, thoron, and progeny levels were observed during winter and summer seasons, respectively. The concentrations of indoor radon, thoron, and progenies were found to vary with the type of houses. The highest 222 Rn, 220 Rn, and progeny concentrations were observed in mud houses and the lowest values were recorded in wooden houses. The indoor 222 Rn concentration correlated well with concentration of its grandparent 238 U in underlying soil with a correlation coefficient of 0.87. The correlation between indoor 220 Rn and 232 Th in the underlying soil was found to be 0.64. The estimated effective doses received by the general public in the present study due to indoor radon and thoron were 1.49 ± 0.49 and 1.30 ± 0.53 mSv/year, respectively. The annual effective doses due to radon and thoron progenies were estimated as 0.76 ± 0.27 and 0.47 ± 0.23 mSv/year, respectively. The contributions from 222 Rn, 220 Rn, and corresponding progenies to the annual effective doses received were 37, 32, 19, and 12%, respectively. The general public living in the study area receives an inhalation dose of 4.02 mSv/year due to indoor radon, thoron, and progenies, which were found to be less than the action limit of ICRP 2009.

Double-blind, placebo-controlled immunotherapy with mixed grass-pollen allergoids. IV. Comparison of the safety and efficacy of two dosages of a high-molecular-weight allergoid.

PubMed

Bousquet, J; Hejjaoui, A; Soussana, M; Michel, F B

1990-02-01

Specific immunotherapy is still widely used in grass-pollen allergy, but its side effects may limit its use. We tested the safety and efficacy of a formalinized high-molecular-weight allergoid prepared from a mixed grass-pollen extract with two injection schedules in a double-blind, placebo-controlled study. Eighteen patients received placebo, 19 received the low-dose schedule (maximal dose: 2000 PNU) and 20 received the high-dose schedule (maximal dose: 10,000 PNU). Only one patient presented a systemic reaction of moderate severity for a dose of 1200 PNU. Before the onset of the pollen season, patients had a nasal challenge with orchard grass-pollen grains, a skin test titration, and the titration of serum-specific IgG. Both groups of patients presented a significant reduction in nasal and skin sensitivities and a significant increase in IgG compared to placebo. Symptoms and medications for rhinitis and asthma were studied during the season, and both groups receiving allergoids had a significant reduction of symptom-medication scores for nasal and bronchial symptoms. There was a highly significant correlation between nasal symptom-medication scores during the season and the results of nasal challenges. High-molecular-weight allergoids are safe and effective.

Comparison between the protective effects of vitamin K and vitamin A on the modulation of hypervitaminosis D3 short-term toxicity in adult albino rats.

PubMed

Elshama, Said Said; Osman, Hosam-Eldin Hussein; El-Kenawy, Ayman El-Meghawry; Youseef, Hamdi Mohamed

2016-02-17

Vitamin D3 has increased risk of toxicity due to its common use in multivitamin preparations. Vitamin K and vitamin A play an important role in vitamin D action. The goal of the current study was to compare the protective effects of vitamin K and vitamin A on the modulation of hypervitaminosis D3 toxicity in rats by assessing serum calcium, renal function tests, cardiac enzymes, and related histopathological changes. Eighty adult albino rats were divided into four groups; each group consisted of 20 rats. The first group received water; the second received a toxic dose of vitamin D3; the third received a toxic dose of vitamin D3 with vitamin A; and the fourth received a toxic dose of vitamin D3 with vitamin K. Vitamin D3 toxicity led to significant abnormalities of cardiac enzymes, renal function tests, and serum calcium associated with histopathological changes in the kidney, heart, lung, adrenal gland, and aorta. Individual administration of vitamin A or vitamin K with a toxic dose of vitamin D improved the biochemical and histopathological abnormalities of hypervitaminosis D3. Vitamins A and K showed the same protective effects in the modulation of hypervitaminosis D3 short-term toxicity.

Effects of intrathecal lidocaine on hyperalgesia and allodynia following chronic constriction injury in rats.

PubMed

Tian, Jie; Gu, Yiwen; Su, Diansan; Wu, Yichao; Wang, Xiangrui

2009-02-01

The present study investigated the effects of different doses of intrathecal lidocaine on established thermal hyperalgesia and tactile allodynia in the chronic constriction injury model of neuropathic pain, defined the effective drug dose range, the duration of pain-relief effects, and the influence of this treatment on the body and tissues. Male Sprague-Dawley rats were divided into five groups and received intrathecal saline or lidocaine (2, 6.5, 15, and 35 mg/kg) 7 days after loose sciatic ligation. Respiratory depression and hemodynamic instability were found to become more severe as doses of lidocaine increased during intrathecal therapy. Two animals in the group receiving 35 mg/kg lidocaine developed pulmonary oedema and died. Behavioral tests indicated that 6.5, 15, and 35 mg/kg intrathecal lidocaine showed different degrees of reversal of thermal hyperalgesia, and lasted for 2-8 days, while 2 mg/kg lidocaine did not. The inhibition of tactile allodynia was only observed in rats receiving 15 and 35 mg/kg lidocaine, and the anti-allodynic effects were identical in these two groups. Histopathologic examinations on the spinal cords revealed mild changes in rats receiving 2-15 mg/kg lidocaine. However, lesions were severe after administration of 35 mg/kg lidocaine. These findings indicate that intrathecal lidocaine has prolonged therapeutic effects on established neuropathic pain. The balance between sympathetic and parasympathetic nervous activities could be well preserved in most cases, except for 35 mg/kg. Considering the ratio between useful effects and side effects, doses of 15 mg/kg are suitable for intrathecal injection for relief of neuropathic pain.

Effect of extended-release dexmethylphenidate and mixed amphetamine salts on sleep: a double-blind, randomized, crossover study in youth with attention-deficit hyperactivity disorder.

PubMed

Santisteban, J A; Stein, M A; Bergmame, L; Gruber, R

2014-09-01

We sought to determine the dose-response effects of extended-release (ER) dexmethylphenidate (d-MPH) and ER mixed amphetamine salts (MAS) on objective measures of sleep. This was an 8-week, double-blind, placebo-controlled, randomized, two period, crossover study of youth with attention-deficit hyperactivity disorder (ADHD) as confirmed by the Kiddie Schedule for Affective Disorders for School-Age Children-Present and Lifetime version (K-SADS-PL). Children aged 10-17 years were recruited from clinical practice, colleague referrals, and flyers. Participants were randomized to initially receive either d-MPH or MAS. During each 4-week drug period, children received three dose levels (10, 20, and 25/30 mg) in ascending order, with placebo substituted for active medication in a randomized fashion during 1 week of the study. After 4 weeks, participants were switched to the alternative medication for another 4 weeks of treatment. The main outcome measure was sleep duration as measured by actigraphy. Children, parents, and researchers were blinded to drug, dose, and placebo status. Sixty-five participants met the inclusion criteria and were enrolled in the study. Of these, 37 participants with sufficient sleep data for analysis were included. Sleep schedule measures showed a significant effect for dose on sleep start time (F(1,36) = 6.284; p < 0.05), with a significantly later sleep start time when children were receiving 20- or 30-mg doses, compared with placebo (p < 0.05). A significant dose effect was found on actual sleep duration (F(1,36) = 8.112; p < 0.05), with significantly shorter actual sleep duration for subjects receiving 30 mg compared with those receiving placebo (p < 0.05). There were no significant differences on sleep duration or sleep schedule between the two stimulant medications. The trial is complete and closed to follow-up. Higher stimulant doses were associated with reduced sleep duration and later sleep start times, regardless of medication class. ClinicalTrials.gov: NCT00393042.

Can a single dose of human papillomavirus (HPV) vaccine prevent cervical cancer? Early findings from an Indian study.

PubMed

Sankaranarayanan, Rengaswamy; Joshi, Smita; Muwonge, Richard; Esmy, Pulikottil Okkuru; Basu, Partha; Prabhu, Priya; Bhatla, Neerja; Nene, Bhagwan M; Shaw, Janmesh; Poli, Usha Rani Reddy; Verma, Yogesh; Zomawia, Eric; Pimple, Sharmila; Tommasino, Massimo; Pawlita, Michael; Gheit, Tarik; Waterboer, Tim; Sehr, Peter; Pillai, Madhavan Radhakrishna

2018-03-15

Human papillomavirus (HPV) vaccination is a major strategy for preventing cervical and other ano-genital cancers. Worldwide HPV vaccination introduction and coverage will be facilitated if a single dose of vaccine is as effective as two or three doses or demonstrates significant protective effect compared to 'no vaccination'. In a multi-centre cluster randomized trial of two vs three doses of quadrivalent HPV vaccination (Gardasil™) in India, suspension of the vaccination due to events unrelated to the study led to per protocol and partial vaccination of unmarried 10-18 year old girls leading to four study groups, two by design and two by default. They were followed up for the primary outcomes of immunogenicity in terms of L1 genotype-specific binding antibody titres, neutralising antibody titres, and antibody avidity for the vaccine-targeted HPV types and HPV infections. Analysis was per actual number of vaccine doses received. This study is registered with ISRCTN, number ISRCTN98283094; and with ClinicalTrials.gov, number NCT00923702. Of the 17,729 vaccinated girls, 4348 (25%) received three doses on days 1, 60, 180 or later, 4979 (28%) received two doses on days 1 and 180 or later, 3452 (19%) received two doses on days 1 and 60, and 4950 (28%) received one dose. One dose recipients demonstrated a robust and sustained immune response against HPV 16 and 18, albeit inferior to that of 3- or 2-doses and the antibody levels were stable over a 4 year period. The frequencies of cumulative incident and persistent HPV 16 and 18 infections up to 7 years of follow-up were similar and uniformly low in all the vaccinated study groups; the frequency of HPV 16 and 18 infections were significantly higher in unvaccinated age-matched control women than among vaccine recipients. The frequency of vaccine non-targeted HPV types was similar in the vaccinated groups but higher in the unvaccinated control women. Our results indicate that a single dose of quadrivalent HPV vaccine is immunogenic and provides lasting protection against HPV 16 and 18 infections similar to the three- and two-dose vaccine schedules, although the study suffer from some limitations. Data on long term protection beyond 7 years against HPV infection and cervical precancerous lesions are needed before policy guidelines regarding a single dose can be formulated and implemented. Significant and long-lasting protective effect of a single dose can be a strong argument to introduce one dose of the HPV vaccine in many low income countries where the current standard of care for cervical cancer prevention is 'no intervention'. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

The relationship of body mass index and abdominal fat on the radiation dose received during routine computed tomographic imaging of the abdomen and pelvis.

PubMed

Chan, Victoria O; McDermott, Shaunagh; Buckley, Orla; Allen, Sonya; Casey, Michael; O'Laoide, Risteard; Torreggiani, William C

2012-11-01

To determine the relationship of increasing body mass index (BMI) and abdominal fat on the effective dose acquired from computed tomography (CT) abdomen and pelvis scans. Over 6 months, dose-length product and total milliamp-seconds (mAs) from routine CT abdomen and pelvis scans of 100 patients were recorded. The scans were performed on a 64-slice CT scanner by using an automatic exposure control system. Effective dose (mSv) based on dose-length product, BMI, periumbilical fat thickness, and intra-abdominal fat were documented for each patient. BMI, periumbilical fat thickness, and intra-abdominal fat were compared with effective dose. Thirty-nine men and 61 women were included in the study (mean age, 56.3 years). The mean BMI was 26.2 kg/m(2). The mean effective dose was 10.3 mSv. The mean periumbilical fat thickness was 2.4 cm. Sixty-five patients had a small amount of intra-abdominal fat, and 35 had a large amount of intra-abdominal fat. The effective dose increased with increasing BMI (P < .001) and increasing amounts of intra-abdominal fat (P < .001). For every kilogram of weight, there is a 0.13 mSv increase in effective dose, which is equal to 6.5 chest radiographs per CT examination. For an increase in BMI by 5 kg/m(2), there is a 1.95 mSv increase in effective dose, which is equal to 97.5 chest radiographs per CT examination. Increasing BMI and abdominal fat significantly increases the effective dose received from CT abdomen and pelvis scans. Copyright © 2012 Canadian Association of Radiologists. Published by Elsevier Inc. All rights reserved.

Flucytosine Pharmacokinetics in a Critically Ill Patient Receiving Continuous Renal Replacement Therapy.

PubMed

Kunka, Megan E; Cady, Elizabeth A; Woo, Heejung C; Thompson Bastin, Melissa L

2015-01-01

Purpose. A case report evaluating flucytosine dosing in a critically ill patient receiving continuous renal replacement therapy. Summary. This case report outlines an 81-year-old male who was receiving continuous venovenous hemofiltration (CVVH) for acute renal failure and was being treated with flucytosine for the treatment of disseminated Cryptococcus neoformans infection. Due to patient specific factors, flucytosine was empirically dose adjusted approximately 50% lower than intermittent hemodialysis (iHD) recommendations and approximately 33% lower than CRRT recommendations. Peak and trough levels were obtained, which were supratherapeutic, and pharmacokinetic parameters were calculated. The patient experienced thrombocytopenia, likely due to elevated flucytosine levels, and flucytosine was ultimately discontinued. Conclusion. Despite conservative flucytosine dosing for a patient receiving CVVH, peak and trough serum flucytosine levels were supratherapeutic (120 μg/mL at 2 hours and 81 μg/mL at 11.5 hours), which increased drug-related adverse effects. The results indicate that this conservative dosing regimen utilizing the patient's actual body weight was too aggressive. This case report provides insight into flucytosine dosing in CVVH, a topic that has not been investigated previously. Further pharmacokinetic studies of flucytosine dosing in critically ill patients receiving CVVH are needed in order to optimize pharmacokinetic and pharmacodynamic parameters while avoiding toxic flucytosine exposure.

Immunogenicity and safety of 1 vs 2 doses of quadrivalent meningococcal conjugate vaccine in youth infected with human immunodeficiency virus.

PubMed

Lujan-Zilbermann, Jorge; Warshaw, Meredith G; Williams, Paige L; Spector, Stephen A; Decker, Michael D; Abzug, Mark J; Heckman, Barb; Manzella, Adam; Kabat, Bill; Jean-Philippe, Patrick; Nachman, Sharon; Siberry, George K

2012-10-01

To compare the immunogenicity of 1 vs 2 doses of meningococcal polysaccharide conjugate vaccine (MCV4) in youth infected with human immunodeficiency virus (HIV). P1065 was a phase I/II immunogenicity and safety trial of MCV4 in 324 youth infected with HIV performed at 27 sites of the International Maternal Pediatric Adolescent AIDS Clinical Trials Group network in the US. At entry subjects received 1 dose of MCV4. At 24 weeks, those with screening cluster of differentiation 4 (CD4)% ≥ 15 were randomized to receive a second dose or not, and all with screening CD4% <15 received a second dose. Immunogenicity was evaluated as the proportion of subjects with a ≥ 4-fold rise from entry in serum bactericidal antibody against each meningococcal serogroup (SG) at weeks 28 and 72. Logistic regression models adjusting for HIV disease severity were used to evaluate the effect of 1 vs 2 MCV4 doses among those with screening CD4% ≥ 15. Subjects randomized to receive 2 vs 1 MCV4 dose had significantly higher response rates to all SGs at week 28 and to all except Neisseria meningitidis SG Y at week 72, with adjusted ORs of 2.5-5.6. In 31 subjects with screening CD4% <15 who received 2 MCV4 doses, response rates ranged from 22%-55% at week 28 and 6%-28% at week 72. In youth infected with HIV with a CD4% ≥ 15, a second dose of MCV4 given 6 months after the initial dose significantly improves response rates at 28 and 72 weeks. Subjects with CD4% <15 at entry had lower response rates despite 2 doses of MCV4. Copyright © 2012 Mosby, Inc. All rights reserved.

Safety and reactogenicity of an MSP-1 malaria vaccine candidate: a randomized phase Ib dose-escalation trial in Kenyan children.

PubMed

Withers, Mark R; McKinney, Denise; Ogutu, Bernhards R; Waitumbi, John N; Milman, Jessica B; Apollo, Odika J; Allen, Otieno G; Tucker, Kathryn; Soisson, Lorraine A; Diggs, Carter; Leach, Amanda; Wittes, Janet; Dubovsky, Filip; Stewart, V Ann; Remich, Shon A; Cohen, Joe; Ballou, W Ripley; Holland, Carolyn A; Lyon, Jeffrey A; Angov, Evelina; Stoute, José A; Martin, Samuel K; Heppner, D Gray

2006-11-24

Our aim was to evaluate the safety, reactogenicity, and immunogenicity of an investigational malaria vaccine. This was an age-stratified phase Ib, double-blind, randomized, controlled, dose-escalation trial. Children were recruited into one of three cohorts (dosage groups) and randomized in 2:1 fashion to receive either the test product or a comparator. The study was conducted in a rural population in Kombewa Division, western Kenya. Subjects were 135 children, aged 12-47 mo. Subjects received 10, 25, or 50 microg of falciparum malaria protein 1 (FMP1) formulated in 100, 250, and 500 microL, respectively, of AS02A, or they received a comparator (Imovax (rabies vaccine). We performed safety and reactogenicity parameters and assessment of adverse events during solicited (7 d) and unsolicited (30 d) periods after each vaccination. Serious adverse events were monitored for 6 mo after the last vaccination. Both vaccines were safe and well tolerated. FMP1/AS02A recipients experienced significantly more pain and injection-site swelling with a dose-effect relationship. Systemic reactogenicity was low at all dose levels. Hemoglobin levels remained stable and similar across arms. Baseline geometric mean titers were comparable in all groups. Anti-FMP1 antibody titers increased in a dose-dependent manner in subjects receiving FMP1/AS02A; no increase in anti-FMP1 titers occurred in subjects who received the comparator. By study end, subjects who received either 25 or 50 microg of FMP1 had similar antibody levels, which remained significantly higher than that of those who received the comparator or 10 microg of FMP1. A longitudinal mixed effects model showed a statistically significant effect of dosage level on immune response (F(3,1047) = 10.78, or F(3, 995) = 11.22, p < 0.001); however, the comparison of 25 microg and 50 microg recipients indicated no significant difference (F(1,1047) = 0.05; p = 0.82). The FMP1/AS02A vaccine was safe and immunogenic in malaria-exposed 12- to 47-mo-old children and the magnitude of immune response of the 25 and 50 microg doses was superior to that of the 10 microg dose.

Safety and Reactogenicity of an MSP-1 Malaria Vaccine Candidate: A Randomized Phase Ib Dose-Escalation Trial in Kenyan Children

PubMed Central

Withers, Mark R; McKinney, Denise; Ogutu, Bernhards R; Waitumbi, John N; Milman, Jessica B; Apollo, Odika J; Allen, Otieno G; Tucker, Kathryn; Soisson, Lorraine A; Diggs, Carter; Leach, Amanda; Wittes, Janet; Dubovsky, Filip; Stewart, V. Ann; Remich, Shon A; Cohen, Joe; Ballou, W. Ripley; Holland, Carolyn A; Lyon, Jeffrey A; Angov, Evelina; Stoute, José A; Martin, Samuel K; Heppner, D. Gray

2006-01-01

Objective: Our aim was to evaluate the safety, reactogenicity, and immunogenicity of an investigational malaria vaccine. Design: This was an age-stratified phase Ib, double-blind, randomized, controlled, dose-escalation trial. Children were recruited into one of three cohorts (dosage groups) and randomized in 2:1 fashion to receive either the test product or a comparator. Setting: The study was conducted in a rural population in Kombewa Division, western Kenya. Participants: Subjects were 135 children, aged 12–47 mo. Interventions: Subjects received 10, 25, or 50 μg of falciparum malaria protein 1 (FMP1) formulated in 100, 250, and 500 μL, respectively, of AS02A, or they received a comparator (Imovax® rabies vaccine). Outcome Measures: We performed safety and reactogenicity parameters and assessment of adverse events during solicited (7 d) and unsolicited (30 d) periods after each vaccination. Serious adverse events were monitored for 6 mo after the last vaccination. Results: Both vaccines were safe and well tolerated. FMP1/AS02A recipients experienced significantly more pain and injection-site swelling with a dose-effect relationship. Systemic reactogenicity was low at all dose levels. Hemoglobin levels remained stable and similar across arms. Baseline geometric mean titers were comparable in all groups. Anti-FMP1 antibody titers increased in a dose-dependent manner in subjects receiving FMP1/AS02A; no increase in anti-FMP1 titers occurred in subjects who received the comparator. By study end, subjects who received either 25 or 50 μg of FMP1 had similar antibody levels, which remained significantly higher than that of those who received the comparator or 10 μg of FMP1. A longitudinal mixed effects model showed a statistically significant effect of dosage level on immune response (F3,1047 = 10.78, or F3, 995 = 11.22, p < 0.001); however, the comparison of 25 μg and 50 μg recipients indicated no significant difference (F1,1047 = 0.05; p = 0.82). Conclusions: The FMP1/AS02A vaccine was safe and immunogenic in malaria-exposed 12- to 47-mo-old children and the magnitude of immune response of the 25 and 50 μg doses was superior to that of the 10 μg dose. PMID:17124529

Monitoring Effective Doses Received By Air Crews With A Space Weather Application

NASA Astrophysics Data System (ADS)

Lantos, P.

To fulfil new requirements of the European Community concerning monitoring of effective doses received by air crews, the French Aviation Authority has developed an operational system called Sievert. The SIEVERT system is analysed as an exam- ple of Space Weather application. One of its characteristics is to calculate the dose received on-board each flight on the basis of the specific and detailled flight given by companies. Operational models will be used. As input to the models, the system needs monitoring of galactic cosmic rays and of solar flare particles. The French neu- tron monitors located in Kerguelen Islands (South Indian Ocean) and Terre Adélie (Antarctica) will be used for this purpose. Particular attention will be devoted to evo- lution of the system in conjunction with new measurements available in the frame of a permanent validation process.

Teratogenic effects of retinoic acid on neurulation in mice embryos.

PubMed

Nobakht, M; Zirak, A; Mehdizadeh, M; Tabatabaeei, P

2006-02-21

Retinoic acids (RA) are natural chemicals that exert a hormone-like activity and a variety of biological effects on early development of mouse. In this study, the probable teratogenic effects of RA on CNS have been investigated in pregnant mice (n = 20) divided into four groups: (1) untreated controls, (2) controls which received a single dose of DMSO, (3) a group that received 40 mg/kg, and (4) a group that received 60 mg/kg of all-trans RA in DMSO, respectively on the eighth day of gestation. Embryos whose dams had received 40 and 60 mg/kg doses of RA, showed malformations and decreased size. At 40 mg/kg dosage level, 50% of the embryos had closed neural tubes while at 60 mg/kg dosage level the neural tube failed to close. The neuroblast mantle layers were disorganized in the 40 mg/kg and even more in the 60 mg/kg exposed group compared to the controls. In mitosis, the density of chromatin was increased in the 60 mg/kg dose group. Compared to controls the 40 and 60 mg/kg dose groups of RA treated dams decreases in the luminal longitudinal and internal measures were observed. Also the thickness of ventricular, mantle and marginal layers was smaller. Wide intercellular spaces due to the degenerated cells at high doses of RA as well as an accumulation of intercellular fluid were observed. Therefore, the wedge shape of neuroepithelium was abolished, preventing the elevation of the neural wall.

Dosimetric evaluation of the staff working in a PET/CT department

NASA Astrophysics Data System (ADS)

Dalianis, K.; Malamitsi, J.; Gogou, L.; Pagou, M.; Efthimiadou, R.; Andreou, J.; Louizï, A.; Georgiou, E.

2006-12-01

The dosimetric literature data concerning the medical personnel working in positron emission tomography/computed tomography (PET/CT) departments are limited. Therefore, we measured the radiation dose of the staff working in the first PET/CT department in Greece at the Diagnostic and Therapeutic Center of Athens HYGEIA—Harvard Medical International. As, for the time being, only 2-deoxy-2-[ 18F]fluoro-d-glucose (FDG) PET studies are performed, radiation dose measurements concern those derived from dispensing of the radiopharmaceutical as well as from the patients undergoing FDG-PET imaging. Our aim is to develop more effective protective measures against radionuclide exposure. To estimate the effective dose from external exposure, all seven members of the staff (two nurses, two medical physicists, two technologists, one secretary) had TLD badges worn at the upper pocket of their overall, TLD rings on the right hand and digital dosimeters at their upper side pocket. In addition, isodose curves were measured with thermoluminescence detectors for distances of 20, 50, 70 and 100 cm away from patients who had been injected with 18F-FDG. Dose values of the PET/CT staff were measured with digital detectors, TLD badges and TLD rings over the first 8 months for a total of 160 working days of the department's operation, consisting of a workload of about 10-15 patients/week who received 250-420 MBq of 18F-FDG each. Whole - body collective doses and hand doses for the staff were the following: Nurse #1 received 1.6 mSv as a whole body dose and 2,1 as a hand dose, Nurse #2 received 1.9 and 2.4 mSv respectively. For medical physicist #1 the dose values were 1.45 mSv whole body and 1.7 mSv hand dose, for medical physicist #2 1.67 mSv wholebody dose and 1.55 mSv hand dose and for technologists #1 & #2 the whole body doses were 0.7 and 0.64 mSv respectively. Lastly, the secretary received 0.1 mSv whole body dose. These preliminary data have shown that the dose levels of our PET/CT staff are within acceptable limits.

Enteral Docosahexaenoic Acid Reduces Analgesic Administration in Neonates Undergoing Cardiovascular Surgery.

PubMed

Bernabe-Garcia, Mariela; López-Alarcon, Mardia; Salgado-Sosa, Alfredo; Villegas-Silva, Raul; Maldonado-Hernandez, Jorge; Rodríguez-Cruz, Maricela; Rivas-Ruiz, Rodolfo; Chavez-Sanchez, Luis; Blanco-Favela, Francisco A; Mancilla-Ramirez, Javier; Gordillo-Alvarez, Virginia; Madrigal-Muñiz, Olivia

2016-01-01

Neonates undergoing surgery require analgesic medication to ameliorate acute pain. These medications produce negative side effects. Docosahexaenoic acid (DHA) has an antinociceptive effect in animals, but this has not been evaluated in human neonates. We evaluated the DHA effect on cumulative dose and duration of analgesics administered to neonates undergoing cardiovascular surgery. A secondary analysis was performed with data from a clinical trial, in which enteral DHA was administered perioperatively compared with sunflower oil (SO). Present study assessed the antinociceptive effect of DHA by measuring the cumulative dose and duration of analgesics administered during postoperative stay in a neonatal intensive care unit. Multivariate linear regression models were performed. Seventeen neonates received DHA and 18 received SO in the control group. Compared with the control group, the DHA group received lower cumulative dose (14.6 ± 2.2 vs. 25.2 ± 4.8 μg/kg, p = 0.029) and shorter duration of buprenorphine (2 days (1-8) vs. 4.5 days (1-12); p = 0.053). After adjusting for confounders, the DHA group received significantly lesser buprenorphine (β = -27 μg/kg, p = 0.028; R2 model = 0.90) for shorter duration (β = -9 days, p = 0.003; R2 model = 0.94). No differences in fentanyl or ketorolac were detected. Buprenorphine administration was reduced in neonates who received DHA, suggesting that DHA likely has analgesic effects. © 2016 S. Karger AG, Basel.

Correlation between measles vaccine doses: implications for the maintenance of elimination.

PubMed

McKee, A; Ferrari, M J; Shea, K

2018-03-01

Measles eradication efforts have been successful at achieving elimination in many countries worldwide. Such countries actively work to maintain this elimination by continuing to improve coverage of two routine doses of measles vaccine following measles elimination. While improving measles vaccine coverage is always beneficial, we show, using a steady-state analysis of a dynamical model, that the correlation between populations receiving the first and second routine dose also has a significant impact on the population immunity achieved by a specified combination of first and second dose coverage. If the second dose is administered to people independently of whether they had the first dose, high second-dose coverage improves the proportion of the population receiving at least one dose, and will have a large effect on population immunity. If the second dose is administered only to people who have had the first dose, high second-dose coverage reduces the rate of primary vaccine failure, but does not reach people who missed the first dose; this will therefore have a relatively small effect on population immunity. When doses are administered dependently, and assuming the first dose has higher coverage, increasing the coverage of the first dose has a larger impact on population immunity than does increasing the coverage of the second. Correlation between vaccine doses has a significant impact on the level of population immunity maintained by current vaccination coverage, potentially outweighing the effects of age structure and, in some cases, recent improvements in vaccine coverage. It is therefore important to understand the correlation between vaccine doses as such correlation may have a large impact on the effectiveness of measles vaccination strategies.

Methadone dose increase and abstinence reinforcement for treatment of continued heroin use during methadone maintenance.

PubMed

Preston, K L; Umbricht, A; Epstein, D H

2000-04-01

Although methadone maintenance is an effective therapy for heroin dependence, some patients continue to use heroin and may benefit from therapeutic modifications. This study evaluated a behavioral intervention, a pharmacological intervention, and a combination of both interventions. Throughout the study all patients received daily methadone hydrochloride maintenance (initially 50 mg/d orally) and weekly counseling. Following baseline treatment patients who continued to use heroin were randomly assigned to 1 of 4 interventions: (1) contingent vouchers for opiate-negative urine specimens (n = 29 patients); (2) methadone hydrochloride dose increase to 70 mg/d (n = 31 patients); (3) combined contingent vouchers and methadone dose increase (n = 32 patients); and (4) neither intervention (comparison standard; n = 28 patients). Methadone dose increases were double blind. Vouchers had monetary value and were exchangeable for goods and services. Groups not receiving contingent vouchers received matching vouchers independent of urine test results. Primary outcome measure was opiate-negative urine specimens (thrice weekly urinalysis). Contingent vouchers and a methadone dose increase each significantly increased the percentage of opiate-negative urine specimens during intervention. Contingent vouchers, with or without a methadone dose increase, increased the duration of sustained abstinence as assessed by urine screenings. Methadone dose increase, with or without contingent vouchers, reduced self-reported frequency of use and self-reported craving. In patients enrolled in a methadone-maintainence program who continued to use heroin, abstinence reinforcement and a methadone dose increase were each effective in reducing use. When combined, they did not dramatically enhance each other's effects on any 1 outcome measure, but they did seem to have complementary benefits.

Beneficial effects of low dose Musa paradisiaca on the semen quality of male Wistar rats

PubMed Central

Alabi, A. S.; Omotoso, Gabriel O.; Enaibe, B. U.; Akinola, O. B.; Tagoe, C. N. B.

2013-01-01

Background: This study aimed at determining the effects of administration of mature green fruits of Musa paradisiaca on the semen quality of adult male Wistar rats. Materials and Methods: The animals used for the study were grouped into three: the control group, given 2 ml of double distilled water, a low dose group given 500 mg/kg/day and a high dose group given 1000 mg/kg/day of the plantain fruits, which was made into flour, and dissolved in 2 ml of double distilled water for easy oral administration. Results: Significant increment in the semen parameters was noticed in animals that received a lower dose of the plantain flour, but those animals who received the high dose had marked and very significant reduction in sperm cell concentration and percentage of morphologically normal spermatozoa. Conclusion: Musa paradisiaca should be consumed in moderate quantities in order to derive its beneficial effects of enhancing male reproductive functions. PMID:23798793

The impact of using different doses of progesterone on memory performance.

PubMed

Roozbehi, A; Sharafi, M T; Karimi, F; Kamali, A M

2017-01-01

Progesterone is a sex hormone and its receptors are expressed throughout the hippocampus. This study was aimed at evaluating the effects of different doses of progesterone on memory. Male rats were arbitrarily assigned to nine groups, namely Group I: control, Group II: control-cannula, Group III received 0.5 μl of saline by cannula, Groups IV , V, VI, VII and VIII received progesterone in doses of 0.5, 1, 1.5, 2, and 3 μg/ 0.5 μl by cannula, respectively. Group IX received 0.5 μl almond oil by cannula. Memory performance was tested in form of passive avoidance task. Our results indicated that progesterone at doses of 1.5 and 2 µg (p < 0.05) significantly increased the memory performance while at a dose of 3 µg (p < 0.05), it significantly decreased memory as compared to the control group. The current study revealed that the influence of progesterone on memory is related to its dose (Fig. 1, Ref. 25).

A food effect study and dose proportionality study to assess the pharmacokinetics and safety of bardoxolone methyl in healthy volunteers.

PubMed

Teuscher, Nathan S; Kelley, Richard J; Dumas, Emily O; Klein, Cheri Enders; Awni, Walid M; Meyer, Colin J

2014-07-01

This study investigated the effect of food on the plasma pharmacokinetics of bardoxolone methyl, an antioxidant inflammation modulator, at a 20 mg dose, and the dose proportionality of bardoxolone methyl pharmacokinetics from 20 to 80 mg. It was a single-dose study conducted at a single center in 32 healthy volunteers aged 18-45 years using an amorphous spray-dried dispersion formulation of bardoxolone methyl. In Part A, 16 subjects received single 20 mg doses of bardoxolone methyl under fasting and non-fasting conditions. In Part B, 16 subjects received a single 60 or 80 mg dose of bardoxolone methyl and a matching placebo dose under fasting conditions. Blood samples for pharmacokinetic analysis were taken over 120 hours following dose administration. Single dose administration of 20, 60, and 80 mg bardoxolone methyl was safe and well-tolerated in healthy volunteers. Total bardoxolone methyl exposure was unchanged in the presence of food. However, doses of bardoxolone methyl above 20 mg appear to have a saturated dissolution or absorption process and are associated with less than proportional increases in drug exposure. © 2013, The American College of Clinical Pharmacology.

Hemodialysis patients receiving a greater Kt dose than recommended have reduced mortality and hospitalization risk.

PubMed

Maduell, Francisco; Ramos, Rosa; Varas, Javier; Martin-Malo, Alejandro; Molina, Manuel; Pérez-Garcia, Rafael; Marcelli, Daniele; Moreso, Francesc; Aljama, Pedro; Merello, Jose Ignacio

2016-12-01

Achieving an adequate dialysis dose is one of the key goals for dialysis treatments. Here we assessed whether patients receiving the current cleared plasma volume (Kt), individualized for body surface area per recommendations, had improved survival and reduced hospitalizations at 2 years of follow-up. Additionally, we assessed whether patients receiving a greater dose gained more benefit. This prospective, observational, multicenter study included 6129 patients in 65 Fresenius Medical Care Spanish facilities. Patients were classified monthly into 1 of 10 risk groups based on the difference between achieved and target Kt. Patient groups with a more negative relationship were significantly older with a higher percentage of diabetes mellitus and catheter access. Treatment dialysis time, effective blood flow, and percentage of on-line hemodiafiltration were significantly higher in groups with a higher dose. The mortality risk profile showed a progressive increase when achieved minus target Kt became more negative but was significantly lower in the group with 1 to 3 L clearance above target Kt and in groups with greater increases above target Kt. Additionally, hospitalization risk appeared significantly reduced in groups receiving 9 L or more above the minimum target. Thus, prescribing an additional 3 L or more above the minimum Kt dose could potentially reduce mortality risk, and 9 L or more reduce hospitalization risk. As such, future prospective studies are required to confirm these dose effect findings. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Effects of an injectable trace mineral supplement on first-service conception rate of dairy cows.

PubMed

Vanegas, J A; Reynolds, J; Atwill, E R

2004-11-01

A total of 825 dairy cows from a commercial dairy farm in central California were used to evaluate effects of one or 2 doses of an injectable trace mineral supplement containing 20 mg/mL of zinc, 20 mg/mL of manganese, 5 mg/mL of selenium, and 10 mg/mL of copper on first-service conception rate. Cows were randomly allocated into treatment or control group to either a single dose (experiment 1) or a double dose (experiment 2) of injected supplement. Allocation was based on days in lactation for experiment 1 and the length of gestation periods for experiment 2. In experiment 1, cows 38 to 45 d in lactation (n = 190) received a single dose of 5 mL of injected supplement. Similar cows were used as controls (n = 227). In experiment 2, cows and pregnant heifers received an initial injection of 5 mL of the mineral supplement from 2 to 3 wk precalving (n = 186). An equal dose was repeated 38 to 45 d in lactation. A similar group of cows and pregnant heifers served as controls for experiment 2 (n = 222). Health and reproductive events postcalving were recorded. In experiment 1, the odds of first-service conception were not significantly different for cows receiving a one-dose regimen of minerals compared with untreated control cows; conception rates were 26.8 and 27.5% for experiment 1 treatment and control groups, respectively. In experiment 1, the odds of first-service conception were significantly lower (odds ratio = 0.66) for cows and heifers given the 2-dose regimen of minerals compared with untreated controls; overall conception rates were 21.5 and 31.5% for experiment 2 treatment and control groups, respectively. In this intensively managed dairy herd, a single dose of injected trace minerals before breeding had no beneficial effects on first-service conception rate. However, dairy cows receiving a dose of trace minerals before calving and another dose before breeding had lower conception at first service.

Real-time eye lens dose monitoring during cerebral angiography procedures.

PubMed

Safari, M J; Wong, J H D; Kadir, K A A; Thorpe, N K; Cutajar, D L; Petasecca, M; Lerch, M L F; Rosenfeld, A B; Ng, K H

2016-01-01

To develop a real-time dose-monitoring system to measure the patient's eye lens dose during neuro-interventional procedures. Radiation dose received at left outer canthus (LOC) and left eyelid (LE) were measured using Metal-Oxide-Semiconductor Field-Effect Transistor dosimeters on 35 patients who underwent diagnostic or cerebral embolization procedures. The radiation dose received at the LOC region was significantly higher than the dose received by the LE. The maximum eye lens dose of 1492 mGy was measured at LOC region for an AVM case, followed by 907 mGy for an aneurysm case and 665 mGy for a diagnostic angiography procedure. Strong correlations (shown as R(2)) were observed between kerma-area-product and measured eye doses (LOC: 0.78, LE: 0.68). Lateral and frontal air-kerma showed strong correlations with measured dose at LOC (AKL: 0.93, AKF: 0.78) and a weak correlation with measured dose at LE. A moderate correlation was observed between fluoroscopic time and dose measured at LE and LOC regions. The MOSkin dose-monitoring system represents a new tool enabling real-time monitoring of eye lens dose during neuro-interventional procedures. This system can provide interventionalists with information needed to adjust the clinical procedure to control the patient's dose. Real-time patient dose monitoring helps interventionalists to monitor doses. Strong correlation was observed between kerma-area-product and measured eye doses. Radiation dose at left outer canthus was higher than at left eyelid.

Late effects of intraoperative radiation therapy on retroperitoneal tissues, intestine, and bile duct in a large animal model

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

Sindelar, W.F.; Tepper, J.E.; Kinslla, T.J.

1994-07-01

The late histopathological effects of intraoperative radiotherapy (IORT) on retroperitoneal tissues, intestine, and bile duct were investigated in dogs. Fourteen adult foxhounds were subjected to laparotomy and varying doses (0-45 Gy) of IORT (11 MeV electrons) delivered to retroperitoneal tissues including the great vessels and ureters, to a loop of defunctionalized small bowel, or to the extrahepatic bile duct. One control animal received an aortic transection and reanastomosis at the time of laparotomy; another control received laparotomy alone. This paper describes the late effects of single-fraction IORT occurring 3-5 years following treatment. Dogs receiving IORT to the retroperitoneum through amore » 4 X 15 cm portal showed few gross or histologic abnormalities at 20 Gy. At doses ranging from 30-45 Gy, radiation changes in normal tissues were consistently observed. Retroperitoneal fibrosis with encasement of the ureters and great vessels developed at doses {ge}30 Gy. Radiation changes were present in the aorta and vena cava at doses {ge}40 Gy. A 30 Gy dog developed an in-field malignant osteosarcoma at 3 years which invaded the vertebral column and compressed the spinal cord. A 40 Gy animal developed obstruction of the right ureter with fatal septic hydronephrosis at 4 years. Animals receiving IORT through a 5 cm IORT portal to an upper abdominal field which included a defunctionalized loop of small bowel, showed few gross or histologic abnormalities at a dose of 20 Gy. At 30 Gy, hyaline degeneration of the intestinal muscularis layer of the bowel occurred. At a dose of 45 Gy, internal intestinal fistulae developed. One 30 Gy animal developed right ureteral obstruction and hydronephrosis at 5 years. A dog receiving 30 Gy IORT through a 5 cm portal to the extrahepatic bile duct showed diffuse fibrosis through the gastroduodenal ligament. These canine studies contribute to the area of late tissue tolerance to IORT. 7 refs., 3 figs., 5 tabs.« less

The efficacy of low dose azathioprine/6-mercaptopurine in patients with inflammatory bowel disease.

PubMed

Kim, Dong Uk; Kim, Young-Ho; Kim, Beom Jin; Chang, Dong Kyung; Son, Hee Jung; Rhee, Poong-Lyul; Kim, Jae J; Rhee, Jong Chul

2009-01-01

Azathioprine (AZA) and 6-mercaptopurine (6-MP) have been widely used in patients with ulcerative colitis (UC) and Crohn's disease (CD). However, some patients cannot tolerate standard doses (2-2.5 mg/kg for AZA or 1-1.5 mg/kg for 6-MP) due to side effects such as leukopenialneutropenia. The aim of this study was to evaluate the efficacy of low dose AZA/6-MP compared to the standard dose. From 1995 to 2005, 122 patients with UC or CD treated with AZA/6-MP at Samsung Medical Center in Korea were enrolled. We divided these patients into 2 groups (standard dose group versus low dose group) according to the maintenance dose. Among the 122 patients, 17 received the standard dose and 105 received a low dose. The mean maintenance doses were 2.25 mg/kg for the standard dose group and 1.35mg/kg for the low dose group. The clinical outcomes of remission induction, maintenance of remission and relapse rate showed no significant difference in comparisons between these two groups. Low dose AZA/6-MP was as effective as the standard dose for remission induction and maintenance of remission in patients with UC and CD. For patients that develop leukopenia/neutropenia during dose escalation, maintenance therapy with low dose AZA/6-MP should be considered.

A Phase I Study of Reduced-Intensity Conditioning and Allogeneic Stem Cell Transplantation Followed by Dose Escalation of Targeted Consolidation Immunotherapy with Gemtuzumab Ozogamicin in Children and Adolescents with CD33+ Acute Myeloid Leukemia.

PubMed

Zahler, Stacey; Bhatia, Monica; Ricci, Angela; Roy, Sumith; Morris, Erin; Harrison, Lauren; van de Ven, Carmella; Fabricatore, Sandra; Wolownik, Karen; Cooney-Qualter, Erin; Baxter-Lowe, Lee Ann; Luisi, Paul; Militano, Olga; Kletzel, Morris; Cairo, Mitchell S

2016-04-01

Myeloablative conditioning and allogeneic hematopoietic stem cell transplant (alloHSCT) in children with acute myeloid leukemia (AML) in first complete remission (CR1) may be associated with significant acute toxicity and late effects. Reduced-intensity conditioning (RIC) and alloHSCT in children is safe, feasible, and may be associated with less adverse effects. Gemtuzumab ozogamicin (GO) induces a response in 30% of patients with CD33+ relapsed/refractory AML. The dose of GO is significantly lower when combined with chemotherapy. We examined the feasibility and toxicity of RIC alloHSCT followed by GO targeted immunotherapy in children with CD33+ AML in CR1/CR2. Conditioning consisted of fludarabine 30 mg/m2 × 6 days, busulfan 3.2 to 4 mg/kg × 2 days ± rabbit antithymocyte globulin 2 mg/kg × 4 days followed by alloHSCT from matched related/unrelated donors. GO was administered ≥60 days after alloHSCT in 2 doses (8 weeks apart), following a dose-escalation design (4.5, 6, 7.5, and 9 mg/m2). Fourteen patients with average risk AML received RIC alloHSCT and post-GO consolidation: median age 13.5 years at transplant (range, 1 to 21), male-to-female 8:6, and disease status at alloHSCT 11 CR1 and 3 CR2. Eleven patients received alloHSCT from 5-6/6 HLA-matched family donors: 8 received peripheral blood stem cells, 2 received bone marrow, and 1 received related cord blood transplantation. Three patients received an unrelated allograft (two 4-5/6 and one 9/10) from unrelated cord blood unit and bone marrow, respectively. Neutrophil and platelet engraftment was observed in all assessable patients (100%), achieved at median 15.5 days (range, 7 to 31) and 21 days (range, 10 to 52), respectively. Three patients received GO at dose level 1 (4.5 mg/m2 per dose), 5 at dose level 2 (6 mg/m2 per dose), 3 at dose level 3 (7.5 mg/m2 per dose), and 3 at dose level 4 (9 mg/m2 per dose). Three of 14 patients received only 1 dose of GO after alloHSCT. One patient experienced grade III transaminitis, which resolved; no grade IV transaminitis, no grade III/IV hyperbilirubinemia, or sinusoidal obstructive syndrome were observed. The second dose of GO was given at median of 143 days (range, 120 to 209) after alloHSCT. Probability of grades II to IV acute and chronic graft-versus-host disease were 21% and 33.5%, respectively. Probability of overall survival after RIC alloHSCT and GO consolidation at 1 and 5 years was 78% and 61%, respectively. Probability of 5-year event-free survival after RIC alloHSCT and GO consolidation in patients in CR1 was 78%. No dose-limiting toxicities probably or directly related to GO were observed in this cohort. This preliminary data demonstrate that RIC followed by alloHSCT and consolidation with GO appears to be safe in children and adolescents with CD33+ AML in CR1/CR2. A phase II trial is currently underway investigating this approach with a GO dose of 9 mg/m2 per dose. Copyright © 2016 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Intraoperative Use of Low-Dose Recombinant Activated Factor VII During Thoracic Aortic Operations

PubMed Central

Andersen, Nicholas D.; Bhattacharya, Syamal D.; Williams, Judson B.; Fosbol, Emil L.; Lockhart, Evelyn L.; Patel, Mayur B.; Gaca, Jeffrey G.; Welsby, Ian J.; Hughes, G. Chad

2013-01-01

Background Numerous studies have supported the effectiveness of recombinant activated factor VII (rFVIIa) for the control of bleeding after cardiac procedures; however safety concerns persist. Here we report the novel use of intraoperative low-dose rFVIIa in thoracic aortic operations, a strategy intended to improve safety by minimizing rFVIIa exposure. Methods Between July 2005 and December 2010, 425 consecutive patients at a single referral center underwent thoracic aortic operations with cardiopulmonary bypass (CPB); 77 of these patients received intraoperative low-dose rFVIIa (≤60 μg/kg) for severe coagulopathy after CPB. Propensity matching produced a cohort of 88 patients (44 received intraoperative low-dose rFVIIa and 44 controls) for comparison. Results Matched patients receiving intraoperative low-dose rFVIIa got an initial median dose of 32 μg/kg (interquartile range [IQR], 16–43 μg/kg) rFVIIa given 51 minutes (42–67 minutes) after separation from CPB. Patients receiving intraoperative low-dose rFVIIa demonstrated improved postoperative coagulation measurements (partial thromboplastin time 28.6 versus 31.5 seconds; p = 0.05; international normalized ratio, 0.8 versus 1.2; p < 0.0001) and received 50% fewer postoperative blood product transfusions (2.5 versus 5.0 units; p = 0.05) compared with control patients. No patient receiving intraoperative low-dose rFVIIa required postoperative rFVIIa administration or reexploration for bleeding. Rates of stroke, thromboembolism, myocardial infarction, and other adverse events were equivalent between groups. Conclusions Intraoperative low-dose rFVIIa led to improved postoperative hemostasis with no apparent increase in adverse events. Intraoperative rFVIIa administration in appropriately selected patients may correct coagulopathy early in the course of refractory blood loss and lead to improved safety through the use of smaller rFVIIa doses. Appropriately powered randomized studies are necessary to confirm the safety and efficacy of this approach. PMID:22551846

Intraoperative use of low-dose recombinant activated factor VII during thoracic aortic operations.

PubMed

Andersen, Nicholas D; Bhattacharya, Syamal D; Williams, Judson B; Fosbol, Emil L; Lockhart, Evelyn L; Patel, Mayur B; Gaca, Jeffrey G; Welsby, Ian J; Hughes, G Chad

2012-06-01

Numerous studies have supported the effectiveness of recombinant activated factor VII (rFVIIa) for the control of bleeding after cardiac procedures; however safety concerns persist. Here we report the novel use of intraoperative low-dose rFVIIa in thoracic aortic operations, a strategy intended to improve safety by minimizing rFVIIa exposure. Between July 2005 and December 2010, 425 consecutive patients at a single referral center underwent thoracic aortic operations with cardiopulmonary bypass (CPB); 77 of these patients received intraoperative low-dose rFVIIa (≤60 μg/kg) for severe coagulopathy after CPB. Propensity matching produced a cohort of 88 patients (44 received intraoperative low-dose rFVIIa and 44 controls) for comparison. Matched patients receiving intraoperative low-dose rFVIIa got an initial median dose of 32 μg/kg (interquartile range [IQR], 16-43 μg/kg) rFVIIa given 51 minutes (42-67 minutes) after separation from CPB. Patients receiving intraoperative low-dose rFVIIa demonstrated improved postoperative coagulation measurements (partial thromboplastin time 28.6 versus 31.5 seconds; p=0.05; international normalized ratio, 0.8 versus 1.2; p<0.0001) and received 50% fewer postoperative blood product transfusions (2.5 versus 5.0 units; p=0.05) compared with control patients. No patient receiving intraoperative low-dose rFVIIa required postoperative rFVIIa administration or reexploration for bleeding. Rates of stroke, thromboembolism, myocardial infarction, and other adverse events were equivalent between groups. Intraoperative low-dose rFVIIa led to improved postoperative hemostasis with no apparent increase in adverse events. Intraoperative rFVIIa administration in appropriately selected patients may correct coagulopathy early in the course of refractory blood loss and lead to improved safety through the use of smaller rFVIIa doses. Appropriately powered randomized studies are necessary to confirm the safety and efficacy of this approach. Copyright © 2012 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

TH-AB-207A-03: Skin Dose to Patients Receiving Multiple CTA and CT Exams of the Head

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

Nawfel, RD; Young, G

Purpose: To measure patient skin dose from CT angiography (CTA) and CT exams of the head, and determine if patients having multiple exams could receive cumulative doses that approach or exceed deterministic thresholds. Methods: This study was HIPAA compliant and conducted with IRB approval. Patient skin doses were measured over a 4 month period using nanoDot OSL dosimeters placed on the head of 52 patients for two CT scanners. On each scanner, 26 patients received CT exams (scanner 1: 10 females, 16 males, mean age 64.2 years; scanner 2: 18 females, 8 males, mean age 61.2 years). CT exam dosemore » metrics, CTDIvol and dose-length product (DLP) were recorded for each exam. Additionally, skin dose was measured on an acrylic skull phantom in each scanner and on a neuro-interventional imaging system using clinical protocols. Measured dose data was used to estimate peak skin dose (PSD) for 4 patients receiving multiple exams including CTA, head CT, and cerebral angiography. Results: For scanner 1, the mean PSD for CTA exams (98.9 ± 5.3 mGy) and for routine head CT exams (39.2 ± 3.7 mGy) agreed reasonably well with the PSD measured on the phantom, 105.4 mGy and 40.0 mGy, respectively. Similarly for scanner 2, the mean PSD for CTA exams (98.8 ± 7.4 mGy) and for routine head CT exams (42.9 ± 9.4 mGy) compared well with phantom measurements, 95.2 mGy and 37.6 mGy, respectively. In addition, the mean PSD was comparable between scanners for corresponding patient exams, CTA and routine head CT respectively. PSD estimates ranged from 1.9 – 4.5 Gy among 4 patients receiving multiple exams. Conclusion: Patients having several exams including both CTA and routine head CT may receive cumulative doses approaching or exceeding the threshold for single dose deterministic effects.« less

A randomized phase II trial of personalized peptide vaccine plus low dose estramustine phosphate (EMP) versus standard dose EMP in patients with castration resistant prostate cancer.

PubMed

Noguchi, Masanori; Kakuma, Tatsuyuki; Uemura, Hirotsugu; Nasu, Yasutomo; Kumon, Hiromi; Hirao, Yasuhiko; Moriya, Fukuko; Suekane, Shigetaka; Matsuoka, Kei; Komatsu, Nobukazu; Shichijo, Shigeki; Yamada, Akira; Itoh, Kyogo

2010-07-01

Personalized peptide vaccination (PPV) combined with chemotherapy could be a novel approach for many cancer patients. In this randomized study, we evaluated the anti-tumor effect and safety of PPV plus low-dose estramustine phosphate (EMP) as compared to standard-dose EMP for HLA-A2- or -A24-positive patients with castration resistant prostate cancer. Patients were randomized into groups receiving either PPV plus low-dose EMP (280 mg/day) or standard-dose EMP (560 mg/day). After disease progression, patients were switched to the opposite regime. The primary end point was progression-free survival (PFS). We randomly assigned 28 patients to receive PPV plus low-dose EMP and 29 patients to receive standard-dose EMP. Nineteen events in the PPV group and 20 events in the EMP group occurred during the first treatment. Median PFS for the first treatment was 8.5 months in the PPV group and 2.8 months in the EMP group with a hazard ratio (HR) of 0.28 (95% CI, 0.14-0.61; log-rank P = 0.0012), while there was no difference for median PFS for the second treatment. The HR for overall survival was 0.3 (95% CI, 0.1-0.91) in favor of the PPV plus low-dose EMP group (log-rank, P = 0.0328). The PPV plus low-dose EMP was well tolerated without major adverse effects and with increased levels of IgG and cytotoxic-T cell responses to the vaccinated peptides. PPV plus low-dose EMP was associated with an improvement in PSA-based PFS as compared to the standard-dose EMP alone.

Estradiol promotes the rewarding effects of nicotine in female rats.

PubMed

Flores, Rodolfo J; Pipkin, Joseph A; Uribe, Kevin P; Perez, Adriana; O'Dell, Laura E

2016-07-01

It is presently unclear whether ovarian hormones, such as estradiol (E2), promote the rewarding effects of nicotine in females. Thus, we compared extended access to nicotine intravenous self-administration (IVSA) in intact male, intact female, and OVX female rats (Study 1) as well as OVX females that received vehicle or E2 supplementation (Study 2). The E2 supplementation procedure involved a 4-day injection regimen involving 2 days of vehicle and 2 days of E2 administration. Two doses of E2 (25 or 250μg) were assessed in separate groups of OVX females in order to examine the dose-dependent effects of this hormone on the rewarding effects of nicotine. The rats were given 23-hour access to nicotine IVSA using an escalating dose regimen (0.015, 0.03, and 0.06mg/kg/0.1mL). Each dose was self-administered for 4 days with 3 intervening days of nicotine abstinence. The results revealed that intact females displayed higher levels of nicotine intake as compared to males. Also, intact females displayed higher levels of nicotine intake versus OVX females. Lastly, our results revealed that OVX rats that received E2 supplementation displayed a dose-dependent increase in nicotine intake as compared to OVX rats that received vehicle. Together, our results suggest that the rewarding effects of nicotine are enhanced in female rats via the presence of the ovarian hormone, E2. Copyright © 2016 Elsevier B.V. All rights reserved.

Cumulative effective radiation dose received by blunt trauma patients arriving to a military level I trauma center from point of injury and interhospital transfers.

PubMed

Van Arnem, Kerri A; Supinski, David P; Tucker, Jonathan E; Varney, Shawn

2016-12-01

Trauma patients sustaining blunt injuries are exposed to multiple radiologic studies. Evidence indicates that the risk of cancer from exposure to ionizing radiation rises in direct proportion to the cumulative effective dose (CED) received. The purpose of this study is to quantify the amount of ionizing radiation accumulated when arriving directly from point of injury to San Antonio Military Medical Center (SAMMC), a level I trauma center, compared with those transferred from other facilities. A retrospective record review was conducted from 1st January 2010 through 31st December 2012. The SAMMC trauma registry, electronic medical records, and the digital radiology imaging system were searched for possible candidates. The medical records were then analyzed for sex, age, mechanism of injury, received directly from point of injury (direct group), transfer from another medical facility (transfer group), computed tomographic scans received, dose-length product, CED of radiation, and injury severity score. A diagnostic imaging physicist then calculated the estimated CED each subject received based on the dose-length product of each computed tomographic scan. A total of 300 patients were analyzed, with 150 patients in the direct group and 150 patients in the transfer group. Both groups were similar in age and sex. Patients in the transfer group received a significantly greater CED of radiation compared with the direct group (mean, 37.6 mSv vs 28 mSv; P=.001). The radiation received in the direct group correlates with a lifetime attributable risk (LAR) of 1 in 357 compared with the transfer group with an increase in LAR to 1 in 266. Patients transferred to our facility received a 34% increase in ionizing radiation compared with patients brought directly from the injury scene. This increased dose of ionizing radiation contributes to the LAR of cancer and needs to be considered before repeating imaging studies. III. Published by Elsevier Inc.

High-Dose Ursodeoxycholic Acid Is Associated With the Development of Colorectal Neoplasia in Patients With Ulcerative Colitis and Primary Sclerosing Cholangitis

PubMed Central

Eaton, John E.; Silveira, Marina G.; Pardi, Darrell S.; Sinakos, Emmanouil; Kowdley, Kris V.; Luketic, Velimir A.C.; Harrison, M. Edwyn; McCashland, Timothy; Befeler, Alex S.; Harnois, Denise; Jorgensen, Roberta; Petz, Jan; Lindor, Keith D.

2011-01-01

OBJECTIVES Some studies have suggested that ursodeoxycholic acid (UDCA) may have a chemopreventive effect on the development of colorectal neoplasia in patients with ulcerative colitis (UC) and primary sclerosing cholangitis (PSC). We examined the effects of high-dose (28–30 mg/kg/day) UDCA on the development of colorectal neoplasia in patients with UC and PSC. METHODS Patients with UC and PSC enrolled in a prior, multicenter randomized placebo-controlled trial of high-dose UDCA were evaluated for the development of colorectal neoplasia. Patients with UC and PSC who received UDCA were compared with those who received placebo. We reviewed the pathology and colonoscopy reports for the development of low-grade or high-grade dysplasia or colorectal cancer. RESULTS Fifty-six subjects were followed for a total of 235 patient years. Baseline characteristics (including duration of PSC and UC, medications, patient age, family history of colorectal cancer, and smoking status) were similar for both the groups. Patients who received high-dose UDCA had a significantly higher risk of developing colorectal neoplasia (dysplasia and cancer) during the study compared with those who received placebo (hazard ratio: 4.44, 95% confidence interval: 1.30–20.10, P=0.02). CONCLUSIONS Long-term use of high-dose UDCA is associated with an increased risk of colorectal neoplasia in patients with UC and PSC. PMID:21556038

[Optimization of the dose of radiation in shoulder arthrography].

PubMed

Campos, P A; Redondo, M V; Berná-Serna, J D; Reus, M; Martínez, F

2009-01-01

The aim of this study was to determine whether using a film with radiopaque coordinates placed over the region of interest to guide shoulder arthrography can reduce the dose of radiation received by patients. The entrance dose was obtained in 34 patients (mean age, 44 years; range, 15 to 75 years). The dose received by organs at risk and the effective dose were estimated with Monte Carlo techniques using the following input parameters: patient anatomy, examination geometry, and air kerma at the entrance to the patient without backscattering. Arthrography was performed with a remote controlled device and images were acquired digitally without fluoroscopy. The mean thickness of the shoulders studied was 14.6+/-2.1cm (9-20 cm). Images were obtained with 80+/-10 kVp (60-85 kVp) and 6.5+/-3.5 mAs (1.4-17 mAs). The mean time of irradiation for each patient was 20+/-6 ms (6.9-47.9 ms). The calculated air kerma was 0.41+/-0.19 mGy and the effective dose was 0.79+/-0.40 muSv. The technique described in this study has enabled us to reduce the dose of radiation received by patients undergoing shoulder arthrography in comparison with other techniques described in the literature and to ensure that the radiologist performing the procedure is not irradiated.

Ultraviolet radiation cataract: dose dependence

NASA Astrophysics Data System (ADS)

Soderberg, Per G.; Loefgren, Stefan

1994-07-01

Current safety limits for cataract development after acute exposure to ultraviolet radiation (UVR) are based on experiments analyzing experimental data with a quantal, effect-no effect, dose-response model. The present study showed that intensity of forward light scattering is better described with a continuous dose-response model. It was found that 3, 30 and 300 kJ/m2UVR300nm induces increased light scattering within 6 h. For all three doses the intensity of forward light scattering was constant after 6 h. The intensity of forward light scattering was proportional to the log dose of UVR300nm. There was a slight increase of the intensity of forward light scattering on the contralateral side in animals that received 300 kJ/m2. Altogether 72 Sprague-Dawley male rats were included. Half of the rats were exposed in vivo on one side to UVR300nm. The other half was kept as a control group, receiving the same treatment as exposed rats but without delivery of UVR300nm to the eye. Subgroups of the rats received either of the three doses. Rats were sacrificed at varying intervals after the exposure. The lenses were extracted and the forward light scattering was estimated. It is concluded that intensity of forward light scattering in the lens after exposure to UVR300nm should be described with a continuous dose-reponse model.

Dose to the Developing Dentition During Therapeutic Irradiation: Organ at Risk Determination and Clinical Implications

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

Thompson, Reid F., E-mail: Reid.Thompson@uphs.upenn.edu; Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania; Schneider, Ralf A., E-mail: ralf.schneider@psi.ch

Purpose: Irradiation of pediatric facial structures can cause severe impairment of permanent teeth later in life. We therefore focused on primary and permanent teeth as organs at risk, investigating the ability to identify individual teeth in children and infants and to correlate dose distributions with subsequent dental toxicity. Methods and Materials: We retrospectively reviewed 14 pediatric patients who received a maximum dose >20 Gy(relative biological effectiveness, RBE) to 1 or more primary or permanent teeth between 2003 and 2009. The patients (aged 1-16 years) received spot-scanning proton therapy with 46 to 66 Gy(RBE) in 23 to 33 daily fractions formore » a variety of tumors, including rhabdomyosarcoma (n=10), sarcoma (n=2), teratoma (n=1), and carcinoma (n=1). Individual teeth were contoured on axial slices from planning computed tomography (CT) scans. Dose-volume histogram data were retrospectively obtained from total calculated delivered treatments. Dental follow-up information was obtained from external care providers. Results: All primary teeth and permanent incisors, canines, premolars, and first and second molars were identifiable on CT scans in all patients as early as 1 year of age. Dose-volume histogram analysis showed wide dose variability, with a median 37 Gy(RBE) per tooth dose range across all individuals, and a median 50 Gy(RBE) intraindividual dose range across all teeth. Dental follow-up revealed absence of significant toxicity in 7 of 10 patients but severe localized toxicity in teeth receiving >20 Gy(RBE) among 3 patients who were all treated at <4 years of age. Conclusions: CT-based assessment of dose distribution to individual teeth is feasible, although delayed calcification may complicate tooth identification in the youngest patients. Patterns of dental dose exposure vary markedly within and among patients, corresponding to rapid dose falloff with protons. Severe localized dental toxicity was observed in a few patients receiving the largest doses of radiation at the youngest ages; however, multiple factors including concurrent chemotherapy confounded the dose-effect relationship. Further studies with larger cohorts and appropriate controls will be required.« less

The effects of nandrolone decanoate on nutritional parameters in hemodialysis patients.

PubMed

Barton Pai, A; Chretien, C; Lau, A H

2002-07-01

Malnutrition with hypoalbuminemia is an independent predictor of mortality in end-stage renal disease patients. Anabolic steroids reduce protein catabolism and therefore may improve nutritional parameters. This study was undertaken to determine the effects of the anabolic steroid nandrolone decanoate on the nutritional status of hemodialysis patients. Secondary endpoints were to examine the effects of androgen therapy on hematocrit and erythropoietin (EPO) dose. Medical records of chronic hemodialysis patients who received nandrolone decanoate for greater than 30 days were reviewed. Data collected included: demographics, dose, frequency, duration of treatment and cumulative dose of nandrolone. Baseline albumin, transferrin, dry weight, phosphorus, creatinine, hematocrit and erythropoietin dose were obtained for comparison with values after treatment. Of the 9 patients evaluated (mean +/- SD: age 55+/-28 years, 4/9 male), 2 patients received nandrolone doses of 25 mg intramuscularly (i.m.) every week, while the remaining 7 patients received 100 mg i.m. every 2 weeks. The mean +/- SD duration of treatment was 96+/-43 days, with a mean +/- SD cumulative dose of 656+/-371 mg. The mean +/- SD baseline albumin was 2.9+/-0.6 mg/dl which increased to 3.3+/-0.4 mg/dl after treatment (p = 0.045). Dry weight increased from a mean +/- SD of 64.4+/-11.7 kg to 66.0+/-10.9 kg after nandrolone therapy (p = 0.028). Mean +/- SD hematocrit at baseline was 28.2+/-4.5% and increased to 33.2+/-5.1% (p = 0.033). The dose of EPO was reduced in 4 patients (44%) during nandrolone therapy. Nandrolone significantly improved markers of nutritional status in our hemodialysis patients. This therapy may also enhance the hematopoietic effects of EPO.

Effect of different doses of hexavalent chromium on mandibular growth and tooth eruption in juvenile Wistar rats.

PubMed

De Lucca, Romina C; Dutrey, Patricio L; Villarino, Mariano E; Ubios, Angela M

2009-07-01

Not only workers employed at industrial plants are exposed to intoxication with the element they manipulate, the population at large is also at risk of suffering health problems caused by contaminating wastes inadequately treated for their safe disposal. As a result certain toxic substances, such as hexavalent chromium,has reached the general population including children. The present study sought to evaluate the effect of intoxication with hexavalent chromium on body and mandibular growth and tooth eruption in suckling Wistar rats. Potassium dichromate was administered by gavage in a dose of 6.25 or 12.5mg/kg body weight (b.w.) to one of the two groups of 4-day-old Wistar rats during 10 days. Our results showed that the effects of chromium are dose-dependent. Morphometric studies of body growth showed lower body weight in both experimental groups and shorter tail length in animals receiving 12.5mg/kg b.w. dose of chromium, compared with controls. All parameters of mandibular growth were lower in the experimental group receiving 12.5mg/kg b.w. of chromium. Differences in tooth eruption were observed at the level of the first molar in animals receiving 12.5mg/kg and of the second molar in those receiving 6.25mg/kg b.w. of chromium. Chromium was found to affect all the studied parameters.

Comparison of TID Effects in Space-Like Variable Dose Rates and Constant Dose Rates

NASA Technical Reports Server (NTRS)

Harris, Richard D.; McClure, Steven S.; Rax, Bernard G.; Evans, Robin W.; Jun, Insoo

2008-01-01

The degradation of the LM193 dual voltage comparator has been studied at different TID dose rate profiles, including several different constant dose rates and a variable dose rate that simulates the behavior of a solar flare. A comparison of results following constant dose rate vs. variable dose rates is made to explore how well the constant dose rates used for typical part testing predict the performance during a simulated space-like mission. Testing at a constant dose rate equal to the lowest dose rate seen during the simulated flare provides an extremely conservative estimate of the overall amount of degradation. A constant dose rate equal to the average dose rate is also more conservative than the variable rate. It appears that, for this part, weighting the dose rates by the amount of total dose received at each rate (rather than the amount of time at each dose rate) results in an average rate that produces an amount of degradation that is a reasonable approximation to that received by the variable rate.

The Effects of Nanoparticles Containing Iron on Blood and Inflammatory Markers in Comparison to Ferrous Sulfate in Anemic Rats

PubMed Central

Shafie, Elaheh Honarkar; Keshavarz, Seyed Ali; Kefayati, Mohammad Esmaiel; Taheri, Fatemeh; Sarbakhsh, Parvin; Vafa, Mohammad Reza

2016-01-01

Background: Ferrous sulfate is the most used supplement for treating anemia, but it can result in unfavorable side effects. Nowadays, nanotechnology is used as a way to increase bioavailability and decrease the side effects of drugs and nutrients. This study investigates the effects of nanoparticles containing iron on blood and inflammatory markers in comparison to ferrous sulfate in anemic rats. Methods: To induce the model of hemolytic anemia, 50 mg/kg bw phenylhydrazine was injected intraperitoneally in rats on the 1st day and 25 mg/kg bw for the four following days. Then, rats were randomly divided into five groups. No material was added to the nipple of the Group 1 (control). Group 2 received 0.4 mg/day nanoparticles of iron; Group 3 received 0.4 mg/day ferrous sulfate, and Groups 4 and 5 received double dose of iron nanoparticle and ferrous sulfate, respectively for ten days. Results: Hemoglobin and red blood cell (RBC) in Group 2 were significantly higher than Group 3 (P < 0.05). In addition, hemoglobin and RBC in Group 4 and 5 were significantly higher than Group 3 (P < 0.05). The average level of serum iron in Groups 2 and 4 was remarkably more than the groups received ferrous sulfate with similar doses (P < 0.05). C-reactive protein in Group 3 was more than Group 2 and in Group 5 was more compare to all other groups. Conclusions: Single dose of nanoparticles had more bioavailability compare to ferrous sulfate, but this did not occur for the double dose. Furthermore, both doses of nanoparticles caused lower inflammation than ferrous sulfate. PMID:27857830

An assessment of mumps vaccine effectiveness by dose during an outbreak in Canada

PubMed Central

Deeks, Shelley L.; Lim, Gillian H.; Simpson, Mary Anne; Gagné, Louise; Gubbay, Jonathan; Kristjanson, Erik; Fung, Cecilia; Crowcroft, Natasha S.

2011-01-01

Background This investigation was done to assess vaccine effectiveness of one and two doses of the measles, mumps and rubella (MMR) vaccine during an outbreak of mumps in Ontario. The level of coverage required to reach herd immunity and interrupt community transmission of mumps was also estimated. Methods Information on confirmed cases of mumps was retrieved from Ontario’s integrated Public Health Information System. Cases that occurred between Sept. 1, 2009, and June 10, 2010, were included. Selected health units supplied coverage data from the Ontario Immunization Record Information System. Vaccine effectiveness by dose was calculated using the screening method. The basic reproductive number (R0) represents the average number of new infections per case in a fully susceptile population, and R0 values of between 4 and 10 were considered for varying levels of vaccine effectiveness. Results A total of 134 confirmed cases of mumps were identified. Information on receipt of MMR vaccine was available for 114 (85.1%) cases, of whom 63 (55.3%) reported having received only one dose of vaccine; 32 (28.1%) reported having received two doses. Vaccine effectiveness of one dose of the MMR vaccine ranged from 49.2% to 81.6%, whereas vaccine effectiveness of two doses ranged from 66.3% to 88.0%. If we assume vaccine effectiveness of 85% for two doses of the vaccine, vaccine coverage of 88.2% and 98.0% would be needed to interrupt community transmission of mumps if the corresponding reproductive values were four and six. Interpretation Our estimates of vaccine effectiveness of one and two doses of mumps-containing vaccine were consistent with the estimates that have been reported in other outbreaks. Outbreaks occurring in Ontario and elsewhere serve as a warning against complacency over vaccination programs. PMID:21576295

An assessment of mumps vaccine effectiveness by dose during an outbreak in Canada.

PubMed

Deeks, Shelley L; Lim, Gillian H; Simpson, Mary Anne; Gagné, Louise; Gubbay, Jonathan; Kristjanson, Erik; Fung, Cecilia; Crowcroft, Natasha S

2011-06-14

This investigation was done to assess vaccine effectiveness of one and two doses of the measles, mumps and rubella (MMR) vaccine during an outbreak of mumps in Ontario. The level of coverage required to reach herd immunity and interrupt community transmission of mumps was also estimated. Information on confirmed cases of mumps was retrieved from Ontario's integrated Public Health Information System. Cases that occurred between Sept. 1, 2009, and June 10, 2010, were included. Selected health units supplied coverage data from the Ontario Immunization Record Information System. Vaccine effectiveness by dose was calculated using the screening method. The basic reproductive number (R(0)) represents the average number of new infections per case in a fully susceptible population, and R(0) values of between 4 and 10 were considered for varying levels of vaccine effectiveness. A total of 134 confirmed cases of mumps were identified. Information on receipt of MMR vaccine was available for 114 (85.1%) cases, of whom 63 (55.3%) reported having received only one dose of vaccine; 32 (28.1%) reported having received two doses. Vaccine effectiveness of one dose of the MMR vaccine ranged from 49.2% to 81.6%, whereas vaccine effectiveness of two doses ranged from 66.3% to 88.0%. If we assume vaccine effectiveness of 85% for two doses of the vaccine, vaccine coverage of 88.2% and 98.0% would be needed to interrupt community transmission of mumps if the corresponding reproductive values were four and six. Our estimates of vaccine effectiveness of one and two doses of mumps-containing vaccine were consistent with the estimates that have been reported in other outbreaks. Outbreaks occurring in Ontario and elsewhere serve as a warning against complacency over vaccination programs.

The pharmacological effects of the anesthetic alfaxalone after intramuscular administration to dogs.

PubMed

Tamura, Jun; Ishizuka, Tomohito; Fukui, Sho; Oyama, Norihiko; Kawase, Kodai; Miyoshi, Kenjiro; Sano, Tadashi; Pasloske, Kirby; Yamashita, Kazuto

2015-03-01

The pharmacological effects of the anesthetic alfaxalone were evaluated after intramuscular (IM) administration to 6 healthy beagle dogs. The dogs received three IM doses each of alfaxalone at increasing dose rates of 5 mg/kg (IM5), 7.5 mg/kg (IM7.5) and 10 mg/kg (IM10) every other day. Anesthetic effect was subjectively evaluated by using an ordinal scoring system to determine the degree of neuro-depression and the quality of anesthetic induction and recovery from anesthesia. Cardiorespiratory variables were measured using noninvasive methods. Alfaxalone administered IM produced dose-dependent neuro-depression and lateral recumbency (i.e., 36 ± 28 min, 87 ± 26 min and 115 ± 29 min after the IM5, IM7.5 and IM10 treatments, respectively). The endotracheal tube was tolerated in all dogs for 46 ± 20 and 58 ± 21 min after the IM7.5 and IM10 treatments, respectively. It was not possible to place endotracheal tubes in 5 of the 6 dogs after the IM5 treatment. Most cardiorespiratory variables remained within clinically acceptable ranges, but hypoxemia was observed by pulse oximetry for 5 to 10 min in 2 dogs receiving the IM10 treatment. Dose-dependent decreases in rectal temperature, respiratory rate and arterial blood pressure also occurred. The quality of recovery was considered satisfactory in all dogs receiving each treatment; all the dog exhibited transient muscular tremors and staggering gait. In conclusion, IM alfaxalone produced a dose-dependent anesthetic effect with relatively mild cardiorespiratory depression in dogs. However, hypoxemia may occur at higher IM doses of alfaxalone.

The pharmacological effects of the anesthetic alfaxalone after intramuscular administration to dogs

PubMed Central

TAMURA, Jun; ISHIZUKA, Tomohito; FUKUI, Sho; OYAMA, Norihiko; KAWASE, Kodai; MIYOSHI, Kenjiro; SANO, Tadashi; PASLOSKE, Kirby; YAMASHITA, Kazuto

2014-01-01

The pharmacological effects of the anesthetic alfaxalone were evaluated after intramuscular (IM) administration to 6 healthy beagle dogs. The dogs received three IM doses each of alfaxalone at increasing dose rates of 5 mg/kg (IM5), 7.5 mg/kg (IM7.5) and 10 mg/kg (IM10) every other day. Anesthetic effect was subjectively evaluated by using an ordinal scoring system to determine the degree of neuro-depression and the quality of anesthetic induction and recovery from anesthesia. Cardiorespiratory variables were measured using noninvasive methods. Alfaxalone administered IM produced dose-dependent neuro-depression and lateral recumbency (i.e., 36 ± 28 min, 87 ± 26 min and 115 ± 29 min after the IM5, IM7.5 and IM10 treatments, respectively). The endotracheal tube was tolerated in all dogs for 46 ± 20 and 58 ± 21 min after the IM7.5 and IM10 treatments, respectively. It was not possible to place endotracheal tubes in 5 of the 6 dogs after the IM5 treatment. Most cardiorespiratory variables remained within clinically acceptable ranges, but hypoxemia was observed by pulse oximetry for 5 to 10 min in 2 dogs receiving the IM10 treatment. Dose-dependent decreases in rectal temperature, respiratory rate and arterial blood pressure also occurred. The quality of recovery was considered satisfactory in all dogs receiving each treatment; all the dog exhibited transient muscular tremors and staggering gait. In conclusion, IM alfaxalone produced a dose-dependent anesthetic effect with relatively mild cardiorespiratory depression in dogs. However, hypoxemia may occur at higher IM doses of alfaxalone. PMID:25428797

Sci—Fri PM: Dosimetry—04: Radiation out-of-field dose in the treatment of pediatric central nervous system malignancies

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

Taddei, P J; Tannous, J; Nabha, R

Children diagnosed with central nervous system (CNS) malignancies often receive radiotherapy, which can cause radiogenic late effects. In order to identify and reduce the risk of these late effects, we must understand the radiation doses that these children receive. Modern treatment planning systems accurately estimate the absorbed dose within the treatment fields but poorly estimate the dose outside them. The purpose of our study was to measure the out-of-field dose for children receiving localized radiotherapy for CNS cancer and apply an analytical model for estimating dose as a function of distance from the field edge. Radiation fields designed for amore » 12-year-old boy treated in our clinic were applied to an anthropomorphic phantom containing more than 200 thermoluminescent dosimeters. A double-Gaussian function of absorbed dose versus distance from the field edge (i.e., 50% isodose line) was applied, and parameters were allowed to vary and were fit to the model by minimizing the root mean square deviation, RMSD. The fitted model accurately predicted the dose from distances of 4 cm to 50 cm (RMSD = 0.54 cGy/Gy), but the model was not useful in estimating dose for distances less than 4 cm because of wide variation in measured dose, and the double-Gaussian model failed by systematically underestimating the dose beyond 50 cm. In conclusion, the double-Gaussian model may be applicable for points at distances from the field edge between 4 cm and 50 cm, where most children's radiosensitive tissues are located, but for points beyond 50 cm, an improvement should be investigated.« less

The effects of crude aqueous and alcohol extracts of Aloe vera on growth and abdominal viscera of suckling rats.

PubMed

Beya, Wabeya; Davidson, Bruce; Erlwanger, Kennedy H

2012-01-01

The gastrointestinal tract of neonates is sensitive to dietary manipulations. When nursing mothers use Aloe vera, their babies are at risk of indirect exposure to Aloe vera via breast feeding or directly as health supplements. The effects of orally administered extracts of Aloe vera in unweaned rats were investigated. Six day old Sprague-Dawley rats were gavaged with aqueous or alcohol extracts of Aloe vera (low dose 50mg. kg⁻¹ or high dose 500mg. kg⁻¹) daily for eight days. All data were expressed as mean ± SD and analyzed by one way ANOVA. Pups receiving high doses of either extract had a significantly higher body mass gain than the group receiving lower dose (p < 0.05). Tibial length was significantly increased in the high dose aqueous extract group (15-26%). The differences in growth could not be attributed to circulating insulin-like growth factor-1 as the levels were not significantly different. The caecum was significantly enlarged in the rats that received the high doses of both extracts. Although, there was no significant difference in the non-fasting plasma concentration of glucose and triglycerides, the hepatic lipid and glycogen content were significantly higher (p < 0.001) for the high dose aqueous extract group. The plasma alanine transaminase was not affected by the treatments, however the high doses of the extracts significantly increased plasma alkaline phosphatase activity. Short term administration of Aloe vera extracts resulted in growth promotion, enhanced hepatic storage of metabolic substrates, increased ALP possibly in relation to bone growth and caused hypertrophy of the caecum of neonatal rats. These effects need to be explored further to enhance animal production and health.

The subtle central effect of nutraceuticals: Is it placebo or nocebo?

PubMed Central

Al-Gareeb, Ali I.

2015-01-01

Background: Herbal medicines are often perceived by the general public as a “soft” alternative to Western Medicine, but the use of these substances can be risky since they can induce nocebo effect. Aim: The aim was to evaluate the nocebo effects of Nigella sativa oil, garlic and coenzyme Q10 (CoQ10) on the integrative function of the central nervous system and psychomotor performance. Materials and Methods: This is a randomized, double-blind, controlled, and prospective study conducted in the Department of Pharmacology, College of Medicine, Al-Mustansiriya University, Baghdad, Iraq during February 2013. A total of 160 medical students participated in this study were randomly assigned equally to one of the following groups: Group A: Received single dose of N. sativa oil (500 ml capsule); Group B: Received single dose of garlic (500 mg capsule); Group C: Received single dose of CoQ10 (120 mg capsule) and; Group D: received single dose of matching oral placebo (300 mg starch capsule). For all participants, reaction time and flicker fusion threshold were measured by the Leeds psychomotor performance test battery before and after 3 h of taking the drugs Results: Neither placebo nor nutraceuticals exerted significant effect on total reaction time. Although the recognition reaction time is insignificantly reduced by 2.77% (placebo), 5.83% (Nigella sativa), 7.21% (garlic) and 12.64% (CoQ10) from the pretreatment values, they are adversely affect the motor reaction time to reach the significant level in subjects pretreated with Garlic (P = 0.02). Conclusion: Nutraceuticals are not free from nocebo effect on psychomotor performance. PMID:26401411

The subtle central effect of nutraceuticals: Is it placebo or nocebo?

PubMed

Al-Gareeb, Ali I

2015-01-01

Herbal medicines are often perceived by the general public as a "soft" alternative to Western Medicine, but the use of these substances can be risky since they can induce nocebo effect. The aim was to evaluate the nocebo effects of Nigella sativa oil, garlic and coenzyme Q10 (CoQ10) on the integrative function of the central nervous system and psychomotor performance. This is a randomized, double-blind, controlled, and prospective study conducted in the Department of Pharmacology, College of Medicine, Al-Mustansiriya University, Baghdad, Iraq during February 2013. A total of 160 medical students participated in this study were randomly assigned equally to one of the following groups: Group A: Received single dose of N. sativa oil (500 ml capsule); Group B: Received single dose of garlic (500 mg capsule); Group C: Received single dose of CoQ10 (120 mg capsule) and; Group D: received single dose of matching oral placebo (300 mg starch capsule). For all participants, reaction time and flicker fusion threshold were measured by the Leeds psychomotor performance test battery before and after 3 h of taking the drugs. Neither placebo nor nutraceuticals exerted significant effect on total reaction time. Although the recognition reaction time is insignificantly reduced by 2.77% (placebo), 5.83% (Nigella sativa), 7.21% (garlic) and 12.64% (CoQ10) from the pretreatment values, they are adversely affect the motor reaction time to reach the significant level in subjects pretreated with Garlic (P = 0.02). Nutraceuticals are not free from nocebo effect on psychomotor performance.

Randomized trial of betahistine mesilate tablets as augmentation for oxcarbazepine and carbamazepine in treating vestibular paroxysmia.

PubMed

Xue, Hui; Xiang, Wenping; Yu, Yichuan; Liu, Guorong; Chong, Yi; Zhou, Jiying

2018-01-01

Vestibular paroxysmia (VP) is a rare episodic peripheral vestibular disorder. This study was conducted to compare the efficacy and acceptability of carbamazepine (CBZ) plus betahistine mesilate tablets (BMT) (CBZ+BMT) and oxcarbazepine (OXC) plus BMT (OXC+BMT) in treating VP, and investigated whether the synergistic effect could be increased along with the increased dose of BMT. VP patients were recruited and randomly assigned to receive CBZ+BMT or OXC+BMT. The doses of CBZ and OXC were set to 200 and 300 mg/time, twice daily, respectively. The doses of BMT were set to 12 and 18 mg/time, twice daily. Half of the patients in each group received BMT 12 mg/time and the other half received BMT 18 mg/time. The treatment was continued for 12 weeks. The vertigo frequency, vertigo score, vertigo duration, response rate, and drug-related side effects were analyzed. In total, 92 patients in the CBZ+BMT group and 93 patients in the OXC+BMT group completed this trial. After 12 weeks of treatment, the two groups had similar average vertigo frequency, average vertigo score, average vertigo duration, and response rate. But the incidence of side effects was significantly higher in the CBZ+BMT group than in the OXC+BMT group ( p =0.04). Subgroup analysis found that patients receiving BMT (18 mg) had greater reductions in average vertigo frequency, average vertigo duration, and average vertigo score, and higher response rates than patients receiving BMT (12 mg). These results demonstrated that OXC+BMT may be suitable as an alternative method in VP patients with CBZ hypersensitivity, and the synergistic effect could be increased along with the increased dose of BMT.

Is It All about the Higher Dose? Why Psychoanalytic Therapy Is an Effective Treatment for Major Depression.

PubMed

Zimmermann, Johannes; Löffler-Stastka, Henriette; Huber, Dorothea; Klug, Günther; Alhabbo, Sarah; Bock, Astrid; Benecke, Cord

2015-01-01

Empirical evidence for the effectiveness of long-term psychodynamic psychotherapy (LTPP) in patients with mood disorders is growing. However, it is unclear whether the effectiveness of LTPP is due to distinctive features of psychodynamic/psychoanalytic techniques or to a higher number of sessions. We tested these rival hypotheses in a quasi-experimental study comparing psychoanalytic therapy (i.e., high-dose LTPP) with psychodynamic therapy (i.e., low-dose LTPP) and cognitive-behavioural therapy (CBT) for depression. Analyses were based on a subsample of 77 subjects, with 27 receiving psychoanalytic therapy, 26 receiving psychodynamic therapy and 24 receiving CBT. Depressive symptoms, interpersonal problems and introject affiliation were assessed prior to treatment, after treatment and at the 1-, 2- and 3-year follow-ups. Psychoanalytic techniques were assessed from three audiotaped middle sessions per treatment using the Psychotherapy Process Q-Set. Subjects receiving psychoanalytic therapy reported having fewer interpersonal problems, treated themselves in a more affiliative way directly after treatment and tended to improve in depressive symptoms and interpersonal problems during follow-up as compared with patients receiving psychodynamic therapy and/or CBT. Multilevel mediation analyses suggested that post-treatment differences in interpersonal problems and introject affiliation were mediated by the higher number of sessions, and follow-up differences in depressive symptoms were mediated by the more pronounced application of psychoanalytic techniques. We also found some evidence for indirect treatment effects via psychoanalytic techniques on changes in introject affiliation during follow-up. These results provide support for the prediction that both a high dose and the application of psychoanalytic techniques facilitate therapeutic change in patients with major depression. Psychoanalytic therapy is an effective treatment for major depression, especially in the long run. The differential effectiveness of psychoanalytic therapy cannot be fully explained by its higher dose. Distinctive features of psychoanalytic technique (e.g., focusing on patients' dreams, fantasies, sexual experiences or childhood memories) may play an important role in establishing sustained therapeutic change. Copyright © 2014 John Wiley & Sons, Ltd.

Peri-interventional antibiotic prophylaxis only vs continuous low-dose antibiotic treatment in patients with JJ stents: a prospective randomised trial analysing the effect on urinary tract infections and stent-related symptoms.

PubMed

Moltzahn, Felix; Haeni, Katharina; Birkhäuser, Frédéric D; Roth, Beat; Thalmann, George N; Zehnder, Pascal

2013-02-01

To evaluate the antibiotic treatment regime in patients with indwelling JJ stents, the benefits and disadvantages of a peri-interventional antibiotic prophylaxis were compared with those of a continuous low-dose antibiotic treatment in a prospective randomised trial. In all, 95 patients were randomised to either receive peri-interventional antibiotic prophylaxis during stent insertion only (group A, 44 patients) or to additionally receive a continuous low-dose antibiotic treatment until stent removal (group B, 51). Evaluations for urinary tract infections (UTI), stent-related symptoms (SRSs) and drug side-effects were performed before stent insertion and consecutively after 1, 2 and 4 weeks and/or at stent withdrawal. All patients received a peri-interventional antibiotic prophylaxis with 1.2 g amoxicillin/clavulanic acid. Amoxicillin/clavulanic acid (625 mg) once daily was administered for continuous low-dose treatment (group B). Primary endpoints were the overall rates of UTIs and SRSs. Secondary endpoints were the rates and severity of drug side-effects. Neither the overall UTI rates (group A: 9% vs group B: 10%), nor the rates of febrile UTIs (group A: 7% vs group B: 6%) were different between the groups. Similarly, SRS rates did not differ (group A: 98% vs group B: 96%). Antibiotic side-effect symptoms were to be increased in patients treated with low-dose antibiotics. A continuous antibiotic low-dose treatment during the entire JJ stent-indwelling time does not reduce the quantity or severity of UTIs and has no effect on SRSs either compared with a peri-interventional antibiotic prophylaxis only. © 2012 BJU International.

Primary Prevention of Cervical Cancer: American Society of Clinical Oncology Resource-Stratified Guideline.

PubMed

Arrossi, Silvina; Temin, Sarah; Garland, Suzanne; Eckert, Linda O'Neal; Bhatla, Neerja; Castellsagué, Xavier; Alkaff, Sharifa Ezat; Felder, Tamika; Hammouda, Doudja; Konno, Ryo; Lopes, Gilberto; Mugisha, Emmanuel; Murillo, Rául; Scarinci, Isabel C; Stanley, Margaret; Tsu, Vivien; Wheeler, Cosette M; Adewole, Isaac Folorunso; de Sanjosé, Silvia

2017-10-01

To provide resource-stratified (four tiers), evidence-based recommendations on the primary prevention of cervical cancer globally. The American Society of Clinical Oncology convened a multidisciplinary, multinational panel of oncology, obstetrics/gynecology, public health, cancer control, epidemiology/biostatistics, health economics, behavioral/implementation science, and patient advocacy experts. The Expert Panel reviewed existing guidelines and conducted a modified ADAPTE process and a formal consensus-based process with additional experts (consensus ratings group) for one round of formal ratings. Existing sets of guidelines from five guideline developers were identified and reviewed; adapted recommendations formed the evidence base. Five systematic reviews, along with cost-effectiveness analyses, provided evidence to inform the formal consensus process, which resulted in agreement of ≥ 75%. In all resource settings, two doses of human papillomavirus vaccine are recommended for girls age 9 to 14 years, with an interval of at least 6 months and possibly up to 12 to 15 months. Individuals with HIV positivity should receive three doses. Maximal and enhanced settings: if girls are age ≥ 15 years and received their first dose before age 15 years, they may complete the series; if no doses were received before age 15 years, three doses should be administered; in both scenarios, vaccination may be through age 26 years. Limited and basic settings: if sufficient resources remain after vaccinating girls age 9 to 14 years, girls who received one dose may receive additional doses between age 15 and 26 years. Maximal, enhanced, and limited settings: if ≥ 50% coverage in the priority female target population, sufficient resources, and cost effectiveness, boys may be vaccinated to prevent other noncervical human papillomavirus-related cancers and diseases. Basic settings: vaccinating boys is not recommended. It is the view of the American Society of Clinical Oncology that health care providers and health care system decision makers should be guided by the recommendations for the highest stratum of resources available. The guideline is intended to complement but not replace local guidelines.

Radiation Dose Escalation in Esophageal Cancer Revisited: A Contemporary Analysis of the National Cancer Data Base, 2004 to 2012.

PubMed

Brower, Jeffrey V; Chen, Shuai; Bassetti, Michael F; Yu, Menggang; Harari, Paul M; Ritter, Mark A; Baschnagel, Andrew M

2016-12-01

To evaluate the effect of radiation dose escalation on overall survival (OS) for patients with nonmetastatic esophageal cancer treated with concurrent radiation and chemotherapy. Patients diagnosed with stage I to III esophageal cancer treated from 2004 to 2012 were identified from the National Cancer Data Base. Patients who received concurrent radiation and chemotherapy with radiation doses of ≥50 Gy and did not undergo surgery were included. OS was compared using Cox proportional hazards regression and propensity score matching. A total of 6854 patients were included; 3821 (55.7%) received 50 to 50.4 Gy and 3033 (44.3%) received doses >50.4 Gy. Univariate analysis revealed no significant difference in OS between patients receiving 50 to 50.4 Gy and those receiving >50.4 Gy (P=.53). The dose analysis, binned as 50 to 50.4, 51 to 54, 55 to 60, and >60 Gy, revealed no appreciable difference in OS within any group compared with 50 to 50.4 Gy. Subgroup analyses investigating the effect of dose escalation by histologic type and in the setting of intensity modulated radiation therapy also failed to reveal a benefit. Propensity score matching confirmed the absence of a statistically significant difference in OS among the dose levels. The factors associated with improved OS on multivariable analysis included female sex, lower Charlson-Deyo comorbidity score, private insurance, cervical/upper esophagus location, squamous cell histologic type, lower T stage, and node-negative status (P<.01 for all analyses). In this large national cohort, dose escalation >50.4 Gy did not result in improved OS among patients with stage I to III esophageal cancer treated with definitive concurrent radiation and chemotherapy. These data suggest that despite advanced contemporary treatment techniques, OS for patients with esophageal cancer remains unaltered by escalation of radiation dose >50.4 Gy, consistent with the results of the INT-0123 trial. Furthermore, these data highlight that many radiation oncologists have not embraced the concept that dose escalation does not improve OS. Although local control, not investigated in the present study, might benefit from dose escalation, novel therapies are needed to improve the OS of patients with esophageal cancer. Copyright © 2016 Elsevier Inc. All rights reserved.

Comparison of Levalbuterol and Racemic Albuterol Based on Cardiac Adverse Effects in Children

PubMed Central

Bio, Laura L.; Willey, Vincent J.; Poon, Cathy Y.

2011-01-01

OBJECTIVE To compare the cardiac effects of levalbuterol with those of racemic albuterol based on changes in heart rate (HR) in pediatric patients. METHODS The medical records of hospitalized children ages 1 month to 12 years, who received either levalbuterol or racemic albuterol via nebulizer for 3 consecutive doses between January 2006 and December 2008 were reviewed. The documented HR was collected prior to and after each administered dose of bronchodilator. The primary outcome was the largest percentage of change in HR between groups. Secondary outcomes of comparisons of the number of patients who had more than a 10% change in HR and incidence of tachycardia were included. RESULTS A total of 50 patients, 25 in each group, was included in the study. All patients in the racemic albuterol group received 2.5 mg per dose, while most of the patients in the levalbuterol group received 0.63 mg per dose (19 patients, 76%). Only 6 levalbuterol patients received a dose of 1.25 mg. Nineteen of 25 patients (76%) in the levalbuterol group were tachycardic prior to the first recorded dose compared to 15 patients (60%) in the racemic albuterol group (p = 0.36). The median of the largest percentage of change in HR was 4.1% (interquartile range [IQR], 1.8–8.7) in the levalbuterol group compared to 5% (IQR, 1.9–7.8) in the racemic albuterol group (p = 0.763). Four patients in the levalbuterol group experienced an HR increase of more than 10% compared to 5 patients in the racemic albuterol group (p = 1.0). CONCLUSION Levalbuterol and racemic albuterol bronchodilator therapies produced similar effects on HR. No clinically significant differences were detected in HR changes between the two treatment groups, despite administration of a larger equipotent albuterol dose in the racemic albuterol group than in the levalbuterol group. PMID:22479161

The effect of obesity on pathological complete response and survival in breast cancer patients receiving uncapped doses of neoadjuvant anthracycline-taxane-based chemotherapy.

PubMed

Farr, Alex; Stolz, Myriam; Baumann, Lukas; Bago-Horvath, Zsuzsanna; Oppolzer, Elisabeth; Pfeiler, Georg; Seifert, Michael; Singer, Christian F

2017-06-01

The effect of obesity in breast cancer patients undergoing neoadjuvant chemotherapy (NAC) remains controversial. The aim of this study was to determine the obesity-related effect on pathological complete response (pCR) and survival in women receiving full uncapped doses of NAC. We retrospectively analyzed the data of all consecutive women who underwent anthracycline-taxane-based NAC for primary breast cancer between 2005 and 2015 at the Department of Obstetrics and Gynecology, Medical University of Vienna. Following the WHO criteria, women with a body mass index (BMI) ≥30 kg/m 2 at baseline were considered obese, whereas those with a BMI <30 kg/m 2 were considered non-obese. Those with dose reductions or dose capping were not eligible for study inclusion. Cox regression and logistic regression were performed. The Kaplan-Meier method was used to analyze disease-free, progression-free, and overall survival. The pCR served as the main outcome measure. Among 120 women who received neoadjuvant epirubicin plus cyclophosphamide and docetaxel, 28 (23.3%) were obese and 92 (76.7%) were non-obese. In the multivariate logistic regression model that adjusted for potentially confounding variables, obesity had an independent positive predictive effect on pCR (OR 4.29, 95% CI, 1.42-13.91; p = 0.011), which was significant in the postmenopausal subgroup (OR 4.72, 95% CI, 1.47-15.84; p = 0.01). When comparing non-obese with obese women, we found that obese women experienced longer progression-free survival (HR 0.10, 95% CI, 8.448 × 10 -4 -0.81; p = 0.025). Obese women receiving full uncapped doses of anthracycline-taxane-based NAC have increased pCR and favorable progression-free survival. This could result from increased dose intensity with increased efficacy and toxicity. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effect of Steady-State Faldaprevir on the Pharmacokinetics of Steady-State Methadone and Buprenorphine-Naloxone in Subjects Receiving Stable Addiction Management Therapy

PubMed Central

Joseph, David; Schobelock, Michael J.; Riesenberg, Robert R.; Vince, Bradley D.; Webster, Lynn R.; Adeniji, Abidemi; Elgadi, Mabrouk

2014-01-01

The effects of steady-state faldaprevir on the safety, pharmacokinetics, and pharmacodynamics of steady-state methadone and buprenorphine-naloxone were assessed in 34 healthy male and female subjects receiving stable addiction management therapy. Subjects continued receiving a stable oral dose of either methadone (up to a maximum dose of 180 mg per day) or buprenorphine-naloxone (up to a maximum dose of 24 mg-6 mg per day) and also received oral faldaprevir (240 mg) once daily (QD) for 8 days following a 480-mg loading dose. Serial blood samples were taken for pharmacokinetic analysis. The pharmacodynamics of the opioid maintenance regimens were evaluated by the objective and subjective opioid withdrawal scales. Coadministration of faldaprevir with methadone or buprenorphine-naloxone resulted in geometric mean ratios for the steady-state area under the concentration-time curve from 0 to 24 h (AUC0–24,ss), the steady-state maximum concentration of the drug in plasma (Cmax,ss), and the steady-state concentration of the drug in plasma at 24 h (C24,ss) of 0.92 to 1.18 for (R)-methadone, (S)-methadone, buprenorphine, norbuprenorphine, and naloxone, with 90% confidence intervals including, or very close to including, 1.00 (no effect), suggesting a limited overall effect of faldaprevir. Although individual data showed moderate variability in the exposures between subjects and treatments, there was no evidence of symptoms of opiate overdose or withdrawal either during the coadministration of faldaprevir with methadone or buprenorphine-naloxone or after faldaprevir dosing was stopped. Similar faldaprevir exposures were observed in the methadone- and buprenorphine-naloxone-treated subjects. In conclusion, faldaprevir at 240 mg QD can be coadministered with methadone or buprenorphine-naloxone without dose adjustment, although given the relatively narrow therapeutic windows of these agents, monitoring for opiate overdose and withdrawal may still be appropriate. (This study has been registered at ClinicalTrials.gov under registration no. NCT01637922.) PMID:25385094

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

Mayo, Charles, E-mail: charles.mayo@umassmemorial.or; Yorke, Ellen; Merchant, Thomas E.

Publications relating brainstem radiation toxicity to quantitative dose and dose-volume measures derived from three-dimensional treatment planning were reviewed. Despite the clinical importance of brainstem toxicity, most studies reporting brainstem effects after irradiation have fewer than 100 patients. There is limited evidence relating toxicity to small volumes receiving doses above 60-64 Gy using conventional fractionation and no definitive criteria regarding more subtle dose-volume effects or effects after hypofractionated treatment. On the basis of the available data, the entire brainstem may be treated to 54 Gy using conventional fractionation using photons with limited risk of severe or permanent neurological effects. Smaller volumesmore » of the brainstem (1-10 mL) may be irradiated to maximum doses of 59 Gy for dose fractions <=2 Gy; however, the risk appears to increase markedly at doses >64 Gy.« less

Adolescent mice are less sensitive to the effects of acute nicotine on context pre-exposure than adults.

PubMed

Kutlu, Munir Gunes; Braak, David C; Tumolo, Jessica M; Gould, Thomas J

2016-07-01

Adolescence is a critical developmental period associated with both increased vulnerability to substance abuse and maturation of certain brain regions important for learning and memory such as the hippocampus. In this study, we employed a hippocampus-dependent learning context pre-exposure facilitation effect (CPFE) paradigm in order to test the effects of acute nicotine on contextual processing during adolescence (post-natal day (PND) 38) and adulthood (PND 53). In Experiment 1, adolescent or adult C57BL6/J mice received either saline or one of three nicotine doses (0.09, 0.18, and 0.36mg/kg) prior to contextual pre-exposure and testing. Our results demonstrated that both adolescent and adult mice showed CPFE in the saline groups. However, adolescent mice only showed acute nicotine enhancement of CPFE with the highest nicotine dose whereas adult mice showed the enhancing effects of acute nicotine with all three doses. In Experiment 2, to determine if the lack of nicotine's effects on CPFE shown by adolescent mice is specific to the age when they are tested, mice were either given contextual pre-exposure during adolescence or adulthood and received immediate shock and testing during adulthood after a 15day delay. We found that both adolescent and adult mice showed CPFE in the saline groups when tested during adulthood. However, like Experiment 1, mice that received contextual pre-exposure during adolescence did not show acute nicotine enhancement except at the highest dose (0.36mg/kg) whereas both low (0.09mg/kg) and high (0.36mg/kg) doses enhanced CPFE in adult mice. Finally, we showed that the enhanced freezing response found with 0.36mg/kg nicotine in the 15-day experiment may be a result of decreased locomotor activity as mice that received this dose of nicotine traveled shorter distances in an open field paradigm. Overall, our results indicate that while adolescent mice showed normal contextual processing when tested both during adolescence and adulthood, they are less sensitive to the enhancing effects of nicotine on contextual processing. Copyright © 2016 Elsevier B.V. All rights reserved.

Effect of low-dose atropine administration on dobutamine dose requirement in horses anesthetized with detomidine and halothane.

PubMed

Weil, A B; Keegan, R D; Greene, S A

1997-12-01

To determine whether a low dose of atropine is associated with decreased requirement for cardiovascular supportive treatment in horses given detomidine prior to maintenance of general anesthesia with halothane. 3 groups of 10 healthy horses. Detomidine (20 micrograms/kg of body weight, i.m.) was administered to all 30 horses. Then, 10 horses received atropine (0.006 mg/kg, i.v.) 1 hour after detomidine administration, 10 horses received atropine (0.012 mg/kg, i.m.) at the time of detomidine administration, and 10 horses served as a control group. Heart rate was measured prior to detomidine administration and at fixed intervals throughout anesthesia. The dobutamine infusion rate necessary to maintain mean arterial blood pressure between 70 and 80 mm of Hg was recorded. Systemic blood pressures, end-tidal halothane, end-tidal CO2, and arterial blood gas tensions were measured at fixed intervals. Mean heart rate was higher among horses receiving atropine i.v. or i.m., compared with that in control horses. Horses that received atropine i.v. had higher systemic arterial blood pressure and required a lower dobutamine infusion rate than did horses of the other groups. Detomidine-treated, halothane-anesthetized horses given atropine i.v. required less dobutamine, compared with horses receiving or not receiving atropine i.m. Complications, such as colic and dysrhythmias, from use of higher doses of atropine, were not observed at this lower dose of atropine. i.v. administration of a low dose of atropine prior to induction of general anesthesia may result in improved blood pressure in horses that have received detomidine before anesthesia with halothane.

10 CFR 72.106 - Controlled area of an ISFSI or MRS.

Code of Federal Regulations, 2012 CFR

2012-01-01

... controlled area may not receive from any design basis accident the more limiting of a total effective dose equivalent of 0.05 Sv (5 rem), or the sum of the deep-dose equivalent and the committed dose equivalent to any individual organ or tissue (other than the lens of the eye) of 0.5 Sv (50 rem). The lens dose...

10 CFR 72.106 - Controlled area of an ISFSI or MRS.

Code of Federal Regulations, 2014 CFR

2014-01-01

... controlled area may not receive from any design basis accident the more limiting of a total effective dose equivalent of 0.05 Sv (5 rem), or the sum of the deep-dose equivalent and the committed dose equivalent to any individual organ or tissue (other than the lens of the eye) of 0.5 Sv (50 rem). The lens dose...

10 CFR 72.106 - Controlled area of an ISFSI or MRS.

Code of Federal Regulations, 2011 CFR

2011-01-01

... controlled area may not receive from any design basis accident the more limiting of a total effective dose equivalent of 0.05 Sv (5 rem), or the sum of the deep-dose equivalent and the committed dose equivalent to any individual organ or tissue (other than the lens of the eye) of 0.5 Sv (50 rem). The lens dose...

10 CFR 72.106 - Controlled area of an ISFSI or MRS.

Code of Federal Regulations, 2013 CFR

2013-01-01

... controlled area may not receive from any design basis accident the more limiting of a total effective dose equivalent of 0.05 Sv (5 rem), or the sum of the deep-dose equivalent and the committed dose equivalent to any individual organ or tissue (other than the lens of the eye) of 0.5 Sv (50 rem). The lens dose...

10 CFR 72.106 - Controlled area of an ISFSI or MRS.

Code of Federal Regulations, 2010 CFR

2010-01-01

... controlled area may not receive from any design basis accident the more limiting of a total effective dose equivalent of 0.05 Sv (5 rem), or the sum of the deep-dose equivalent and the committed dose equivalent to any individual organ or tissue (other than the lens of the eye) of 0.5 Sv (50 rem). The lens dose...

Febrile Neutropenia Rates According to Body Mass Index and Dose Capping in Women Receiving Chemotherapy for Early Breast Cancer.

PubMed

Lote, H; Sharp, A; Redana, S; Papadimitraki, E; Capelan, M; Ring, A

2016-09-01

Studies suggest worse outcomes in obese women with breast cancer than in non-obese women. One potential reason may be that oncologists 'dose cap' adjuvant chemotherapy in obese patients in order to avoid excessive toxicity. Reductions from standard dosing may compromise survival outcomes in the curative setting. Here we describe the body mass index (BMI) distribution of patients in a non-trial population, the frequency with which oncologists dose cap and its effect on febrile neutropenia chemotherapy toxicity. In this non-randomised study, electronic patient records retrospectively identified patients with early breast cancer who initiated neoadjuvant or adjuvant chemotherapy at the Royal Marsden Hospital between 1 January and 31 December 2013. Baseline data included age, BMI, performance status, tumour characteristics, granulocyte colony-stimulating factor and comorbidities. Chemotherapy doses, rates of dose capping across BMI groups and rates of febrile neutropenia were reported. In total, 325 patients were eligible: 79 (24.5%) were obese (BMI ≥ 30), 109 (33.5%) were overweight (BMI ≥25 - <30) and 137 (42%) were normal bodyweight (BMI < 25). Sixteen patients (20.5%) in the obese group received dose-capped chemotherapy. Overall, 62 patients (19%) had an episode of febrile neutropenia. Obese patients receiving uncapped chemotherapy did not experience a significant difference in febrile neutropenia rates when compared with overweight or normal bodyweight groups (P = 0.5798). The febrile neutropenia rate in obese patients receiving capped chemotherapy was 6.5%, compared with 24% in obese patients receiving uncapped chemotherapy (P = 0.1216). In a non-trial population of obese patients, dose capping is frequently used. Obese patients receiving uncapped chemotherapy do not experience increased febrile neutropenia rates when compared with uncapped overweight or normal bodyweight patients. Furthermore, dose capping was associated with a trend towards lower rates of febrile neutropenia than in other groups and may indicate relative under-dosing of chemotherapy. This supports international guidelines that state that obese patients should not be dose capped. Copyright © 2016 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

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 Neoadjuvant Radiation Dose on Surgical and Oncological Outcome in Locally Advanced Esophageal Cancer.

PubMed

Van Daele, E; Ceelen, W; Boterberg, T; Varinl, O; Van Nieuwenhove, Y; Putte, D Van de; Geboes, K; Pattyn, P

2015-01-01

Neoadjuvant chemoradiation (CRT) confers a survival benefit in locally advanced esophageal cancer. The optimal dose of radiotherapy remains undefined. From a prospective database, we identified patients who received CRT followed by Ivor Lewis esophagectomy. Surgical complications, pathological response, and oncological outcome were compared between patients who received a radiotherapy (RT) dose of 36 Gy (group1) versus a dose of > 40 Gy (group 1). 147 patients were evaluated: 109 received 36 Gy, while 38 received 41-50Gy. Mean age was 61 ± 9 years (84% male). Median hospital stay was 16 days. Anastomotic leakage occurred in 4.0%. Pulmonary complications occurred in 41.8%, neither being influenced by RT dose. Complete resection (R0) was achieved in 95% (group 1) and 100% (group 2), P = 0.3. Pathological complete response (pCR) was observed in 19% (group 1) and 37% (group 1), P = 0.04. Local recurrence developed in 9% in group 1, and 3% in group 2 (P = 0.3), but regional recurrence developed significantly higher in the low dose group (18% vs 3%, P < 0.001). Metastatic recurrence occurred in 48% in group 1 and 13% in group 1 (P < 0.001). In patients with locally advanced esophageal cancer a higher RT dose does not affect surgical outcome, enhances pCR rate, and reduces the locoregional and metastatic recurrence risk.

Effects of Radiation Exposure From Cardiac Imaging: How Good Are the Data?

PubMed Central

Einstein, Andrew J.

2012-01-01

Concerns about medical exposure to ionizing radiation have become heightened in recent years due to rapid growth in procedure volumes and the high radiation doses incurred from some procedures. This article summarizes the evidence base undergirding concerns about radiation exposure in cardiac imaging. After classifying radiation effects, explaining terminology used to quantify the radiation received by patients, and describing typical doses from cardiac imaging procedures, I address the major epidemiological studies having bearing on radiation effects at doses comparable to those received by patients undergoing cardiac imaging. These include studies of atomic bomb survivors, nuclear industry workers, and children exposed in utero to x-rays, all of which have evidenced increased cancer risks at low doses. Additional higher dose epidemiological studies of cohorts exposed to radiation in the context of medical treatment are described and found to be generally compatible with these cardiac-dose-level studies, albeit with exceptions. Using risk projection models developed by the US National Academies that incorporate these data and reflect several evidence-based assumptions, cancer risk from cardiac imaging can be estimated and compared to benefits from imaging. Several ongoing epidemiological studies will provide better understanding of radiation-associated cancer risks. PMID:22300689

Low-dose caffeine discrimination and self-reported mood effects in normal volunteers.

PubMed Central

Silverman, K; Griffiths, R R

1992-01-01

A caffeine versus placebo discrimination procedure was used to determine the lowest caffeine dose that could produce discrimination and self-reported mood effects in normal volunteers. During daily sessions under double-blind conditions, caffeine-abstinent subjects orally ingested a capsule containing 178 mg caffeine or placebo. Before beginning discrimination training, the compounds were identified to subjects by letter codes. Fifteen, 30, and 45 min after capsule ingestion, subjects guessed the capsule's letter code. Correct guesses at 45 min earned money. After each session, subjects received a supplementary capsule containing caffeine or placebo to ensure that, within each phase of the study, subjects received the same daily dose of caffeine equal to the training dose. Five of the 15 subjects acquired the caffeine versus placebo discrimination within the first 20 sessions (greater than or equal to 75% correct); 6 other subjects acquired the discrimination with additional training. Nine subjects who acquired the discrimination were subsequently trained at progressively lower caffeine doses. In general, the lowest dose to produce discrimination (greater than or equal to 75% correct) was also the lowest dose to produce self-reported mood effects: 4 subjects showed discrimination and self-reported mood effects at 100 mg caffeine, 2 at 56 mg, 1 at 32 mg, and 1 at 18 mg. One of these subjects also showed self-reported mood effects at 10 mg. The present study documents discriminative stimulus and self-reported mood effects of caffeine at doses below those previously shown to affect any behavior in normal volunteers. PMID:1548451

Ocular side effects following intravitreal injection therapy for retinoblastoma: a systematic review.

PubMed

Smith, Stephen J; Smith, Brian D; Mohney, Brian G

2014-03-01

To describe the ocular side effects in patients receiving intravitreal injection therapy (IViT) for retinoblastoma. PubMed (1946-present), Scopus (all years), Science Citation Index (1900-present) and Conference Proceedings Citation Index-Science (1990-present) electronic databases were searched to identify all published reports of therapeutic intravitreal injections for retinoblastoma in humans. Ten studies with original IViT ocular side effect data were included in this systematic review. In these combined reports, a total of 1287 intravitreal injections were given to 306 eyes of 295 patients, with a mean follow-up of 74.1 months. Two hundred sixty-one (88.5%) patients received comparatively standard melphalan IViT doses (8-30 mcg). Ocular side effects occurred in 38 patients (17 significant, 21 minor). The proportion of patients experiencing potentially significant ocular side effects following standard melphalan IViT regimens was 0.031 (8/261; 95% CI 0.013 to 0.06). The side effects of these eight included iris atrophy in three, two each with chorioretinal atrophy and vitreous haemorrhage and one with retinal detachment. Of the other nine patients with significant complications, five experienced sight-threatening complications following dramatic dose escalations (four with melphalan, one with thiotepa), three experienced complications that are commonly associated with concurrent therapies given to these patients and one had a retinal detachment. Of the 61 patients receiving IViT via safety-enhancing injection techniques, all six significant side effects were either attributed to the therapeutic dose or confounded by concurrent treatments. Significant ocular complications following IViT for retinoblastoma are uncommon, and this risk may be reduced further by the use of careful injection technique and standard dosing regimens. Care must be taken in the dosing of intravitreal treatments to avoid potentially irreversible vision loss.

Acute Biological Effects of Simulating the Whole-Body Radiation Dose Distribution from a Solar Particle Event Using a Porcine Model

PubMed Central

Wilson, Jolaine M.; Sanzari, Jenine K.; Diffenderfer, Eric S.; Yee, Stephanie S.; Seykora, John T.; Maks, Casey; Ware, Jeffrey H.; Litt, Harold I.; Reetz, Jennifer A.; McDonough, James; Weissman, Drew; Kennedy, Ann R.; Cengel, Keith A.

2011-01-01

In a solar particle event (SPE), an unshielded astronaut would receive proton radiation with an energy profile that produces a highly inhomogeneous dose distribution (skin receiving a greater dose than internal organs). The novel concept of using megavoltage electron-beam radiation to more accurately reproduce both the total dose and the dose distribution of SPE protons and make meaningful RBE comparisons between protons and conventional radiation has been described previously. Here, Yucatan minipigs were used to determine the effects of a superficial, SPE-like proton dose distribution using megavoltage electrons. In these experiments, dose-dependent increases in skin pigmentation, ulceration, keratinocyte necrosis and pigment incontinence were observed. Five of 18 animals (one each exposed to 7.5 Gy and 12.5 Gy radiation and three exposed to 25 Gy radiation) developed symptomatic, radiation-associated pneumonopathy approximately 90 days postirradiation. The three animals from the highest dose group showed evidence of mycoplasmal pneumonia along with radiation pneumonitis. Moreover, delayed-type hypersensitivity was found to be altered, suggesting that superficial irradiation of the skin with ionizing radiation might cause immune dysfunction or dysregulation. In conclusion, using total doses, patterns of dose distribution, and dose rates that are compatible with potential astronaut exposure to SPE radiation, animals experienced significant toxicities that were qualitatively different from toxicities previously reported in pigs for homogeneously delivered radiation at similar doses. PMID:21859326

A Randomized Double-Blind, Placebo Controlled, Four-Arm Parallel Study Investigating the Effect of a Broad-Spectrum Wellness Beverage on Mood State in Healthy, Moderately Stressed Adults.

PubMed

Evans, Malkanthi; Antony, Joseph; Guthrie, Najla; Landes, Bernie; Aruoma, Okezie I

2018-01-01

The objective of this study was to investigate the effect of a broad-spectrum wellness beverage (Zeal Wellness [ZW]) on standardized measures of mood states, including overall feelings of vitality, in healthy, moderately stressed adults. A randomized, double-blind, placebo-controlled clinical trial was conducted among 99 eligible participants prescreened for moderate stress. Participants were randomized to one of four groups and received ZW once daily (1-dose-ZW; 14 g), ZW twice daily (2-dose-ZW; 28 g), placebo once daily (1-dose-placebo), or placebo twice daily (2-dose-placebo) for 4 weeks. A stress/vitality questionnaire assessed stress and the Profile of Moods (POMS) Questionnaire assessed vigor via mental/physical energy and global mood state. Safety was assessed by clinical chemistry, liver, kidney function, and anthropometric measures and adverse event reporting. Participants receiving 2-dose-ZW reported a 6.6% decrease in scores on POMS-Total Mood Disturbance (TMD; p < 0.05) and a 6.8% decrease in the anger-hostility mood state (p < 0.022) compared to the combined placebo group at day 29. The 2-dose-ZW provided a 12.8% greater improvement in POMS-TMD scores when compared to participants receiving 1-dose-ZW after 28 days of supplementation (p = 0.014). Within groups, there was a 22.4% and a 9.6% decrease in POMS-TMD scores in participants with 2-dose-ZW and 1-dose-ZW, respectively. In addition, participants receiving 2-dose-ZW showed significant improvements (p = 0.001) in the POMS t-score iceberg profile, which represented a shift to a more healthy profile. These data show that daily supplementation with 2-dose-ZW significantly decreased POMS-TMD scores and anger-hostility mood state and shifted the POMS iceberg profile to a healthy profile compared to the combined placebo, reflecting the functional benefit of rice-bran-fruit-vegetable extracts based beverage on health.

Cost-effectiveness of single dose cefotaxime plus metronidazole compared with three doses each of cefuroxime plus metronidazole for the prevention of wound infection after colorectal surgery.

PubMed

Davey, P; Lynch, B; Malek, M; Byrne, D; Thomas, P

1992-12-01

The cost-effectiveness of prophylaxis for colonic surgery with single dose cefotaxime plus metronidazole has been compared with that of three doses each of cefuroxime plus metronidazole, by analysing data from a previously published study supplemented with additional data on the hospital and community costs of wound infection after colonic surgery. The original trial included 942 patients having elective colonic surgery in 14 hospitals. The data on costs of wound infection were collected from a further 124 patients undergoing elective colonic surgery at Ninewells Hospital. All these patients received a three dose regimen of cefuroxime plus metronidazole. The Dundee patients received three injections of 0.75 g cefuroxime at 8-hourly intervals whereas the trial patients received a single dose of 1.5 g followed by two further doses of 0.75 g at 8-hourly intervals. The cefuroxime prophylaxis regimen used in the trial cost 24.16 pounds per patient more than the cefotaxime regimen. The components of the excess cost were drugs (15.18 pounds), equipment (6.14 pounds) and staff time (2.84 pounds). The median cost to the hospital of a wound infection was 978.04 pounds (95% CI 482.04 pounds to 1521.22 pounds). The components of the hospital cost of wound infection were: hotel costs 858 pounds (88%), dressing costs 83.02 pounds (8%) and drug costs (excluding prophylaxis) 37.02 pounds (4%). Only five patients received additional antibiotic treatment in the community, and only one required home visits from the District Nurse. Applying the difference in costs of prophylaxis as 21 pounds (costs of drugs plus equipment) and the cost per wound infection as 1000 pounds to the observed wound infection rate of 7% in the cefuroxime group, the wound infection rate in the cefotaxime group would have to be 2.1% higher for the two regimens to be equally cost-effective. The probability that such a difference in efficacy exists is 0.088. A model was developed to calculate the probability of equal cost-effectiveness over a range of costs of wound infection.

No effect on QT intervals of mipomersen, a 2'-O-methoxyethyl modified antisense oligonucleotide targeting ApoB-100 mRNA, in a phase I dose escalation placebo-controlled study, and confirmed by a thorough QT (tQT) study, in healthy subjects.

PubMed

Yu, Rosie Z; Gunawan, Rudy; Li, Zhaoyang; Mittleman, Robert S; Mahmood, Asif; Grundy, John S; Singleton, Walter; Geary, Richard; Wang, Yanfeng

2016-03-01

The aim of this study to evaluate the effect of mipomersen on QT intervals in a phase I dose escalation, placebo-controlled study, and a thorough QT (tQT) study in healthy subjects. In the initial phase I study, 29 healthy subjects received either single or multiple (for 4 weeks) ascending doses of mipomersen (50-400 mg) administered subcutaneously (SC) or via a 2-h intravenous (IV) infusion, and 7 subjects received placebo. In the confirmative tQT study, 58 healthy subjects received placebo, 400 mg IV moxifloxacin, 200 mg SC, or 200 mg IV of mipomersen in a double-blind, 4-way crossover design with a minimum 5-day washout between treatments. ECG measurements were performed at baseline and selected time points (including Tmax). The correlation between QTcF intervals corrected for baseline and time-matched placebo when available with PK plasma exposure was evaluated by linear regression analysis. In the phase I study, no positive correlation between the PK exposure and ∆QTcF or ∆∆QTcF was observed within the wide dose or exposure range tested. Similar results were observed in the tQT study, where the predicted ΔΔQTcF and its upper bound of the 90% CI at Cmax of therapeutic and supratherapeutic dose were approximately -1.7 and 2.9 ms, respectively. Mipomersen showed no effect on QT intervals in both the phase I dose escalation study and the tQT study. These results support the proposal that QT assessment can be made in a phase I dose escalation study, and no tQT study may be necessary if the phase I dose escalation study showed a negative QT effect.

The radiology informed consent form: recommendations from the European Society of Cardiology position paper.

PubMed

Carpeggiani, Clara; Picano, Eugenio

2016-06-01

Every radiological and nuclear medicine examination confers a definite long-term risk of cancer, but most patients undergoing such examinations receive no or inaccurate information about radiation dose and corresponding risk related to the dose received. Informed consent is a procedure to support (not substitute) the physician/patient dialogue and relationship, facilitating a free, informed and aware expression of the patient's will in the principle of patient autonomy. Physicians are responsible for providing patients with all the information on risks, benefits and alternatives useful to the patient to make the decision. In current radiological practice the information on the radiation dose and long-term cancer risks is difficult to find and not easy to understand. The form using plain language should spell-out the type of examination, the effective dose (mSv), the effective dose expressed in number of chest radiographs and the risk of cancer. The current practice clashes against the guidelines and the law.

Maintenance treatment of duodenal ulceration: ranitidine 300 mg at night is better than 150 mg in cigarette smokers.

PubMed Central

Lee, F I; Hardman, M; Jaderberg, M E

1991-01-01

Two hundred patients received either ranitidine 150 mg or 300 mg at night for 18 months to prevent duodenal ulcer relapse. Recurrence rates were lower in patients receiving the higher dose of ranitidine (3.1% v 9.7%, p = 0.78; 6.5% v 16.7%, p = 0.037; and 8.9% v 17.0%, p = 0.121 at six, 12, and 18 months respectively). In patients receiving ranitidine 150 mg, recurrences were significantly more common in smokers than non-smokers after 12 and 18 months, while in patients receiving ranitidine 300 mg recurrence rates were similar in smokers and non-smokers. Ranitidine 300 mg at night abolishes the adverse effect of smoking observed during maintenance treatment with ranitidine 150 mg at night and may therefore be an appropriate maintenance dose for smokers who relapse during standard dose maintenance treatment. PMID:1864532

Radiation Dose Escalation in Esophageal Cancer Revisited: A Contemporary Analysis of the National Cancer Data Base, 2004 to 2012

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

Brower, Jeffrey V.; Chen, Shuai; Bassetti, Michael F.

Purpose: To evaluate the effect of radiation dose escalation on overall survival (OS) for patients with nonmetastatic esophageal cancer treated with concurrent radiation and chemotherapy. Methods and Materials: Patients diagnosed with stage I to III esophageal cancer treated from 2004 to 2012 were identified from the National Cancer Data Base. Patients who received concurrent radiation and chemotherapy with radiation doses of ≥50 Gy and did not undergo surgery were included. OS was compared using Cox proportional hazards regression and propensity score matching. Results: A total of 6854 patients were included; 3821 (55.7%) received 50 to 50.4 Gy and 3033 (44.3%) received dosesmore » >50.4 Gy. Univariate analysis revealed no significant difference in OS between patients receiving 50 to 50.4 Gy and those receiving >50.4 Gy (P=.53). The dose analysis, binned as 50 to 50.4, 51 to 54, 55 to 60, and >60 Gy, revealed no appreciable difference in OS within any group compared with 50 to 50.4 Gy. Subgroup analyses investigating the effect of dose escalation by histologic type and in the setting of intensity modulated radiation therapy also failed to reveal a benefit. Propensity score matching confirmed the absence of a statistically significant difference in OS among the dose levels. The factors associated with improved OS on multivariable analysis included female sex, lower Charlson-Deyo comorbidity score, private insurance, cervical/upper esophagus location, squamous cell histologic type, lower T stage, and node-negative status (P<.01 for all analyses). Conclusions: In this large national cohort, dose escalation >50.4 Gy did not result in improved OS among patients with stage I to III esophageal cancer treated with definitive concurrent radiation and chemotherapy. These data suggest that despite advanced contemporary treatment techniques, OS for patients with esophageal cancer remains unaltered by escalation of radiation dose >50.4 Gy, consistent with the results of the INT-0123 trial. Furthermore, these data highlight that many radiation oncologists have not embraced the concept that dose escalation does not improve OS. Although local control, not investigated in the present study, might benefit from dose escalation, novel therapies are needed to improve the OS of patients with esophageal cancer.« less

Effect of high doses of 2-CdA on Schwann cells of mouse peripheral nerve.

PubMed

Djaldetti, R; Hart, J; Alexandrova, S; Cohen, S; Beilin, B; Djaldetti, M; Bessler, H

1996-07-01

The present study was undertaken to examine the effect of 2-CdA (Leustatin) on the Schwann cells of myelinated and unmyelinated fibers of peripheral mouse nerve. Two groups of mice were injected intravenously for seven days with 2-CdA: one group received daily doses of 1 mg/kg and the other 0.5 mg/kg. Both doses exceeded those accepted in clinical practice. Mice injected with saline served as controls. The sciatic nerve was then dissected and examined with a transmission electron microscope. The Schwann cells of both the myelinated and unmyelinated nerve fibers of the animals receiving the higher doses of 2-CdA showed nuclear and nucleolus damage, loss of heterochromatin, vacuolization and disorganization of the myelin sheaths. The mesaxons and the axons were also damaged. The Schwann cells of the animals treated with the lower doses appeared undamaged. The results indicate that in contrast to other anticancer drugs known to produce peripheral neuropathy, 2-CdA may cause damage to the Schwann cells only at doses exceeding the therapeutic ones.

Development of a vancomycin dosing approach for critically ill patients receiving hybrid hemodialysis using Monte Carlo simulation.

PubMed

Lewis, Susan J; Mueller, Bruce A

2018-01-01

Prolonged intermittent renal replacement therapy is an increasingly popular treatment for acute kidney injury in critically ill patients that runs at different flow rates and durations than conventional hemodialysis or continuous renal replacement therapies. Pharmacokinetic studies conducted in patients receiving prolonged intermittent renal replacement therapy are scarce; consequently, clinicians are challenged to dose antibiotics effectively. The purpose of this study was to develop vancomycin dosing recommendations for patients receiving prolonged intermittent renal replacement therapy. Monte Carlo simulations were performed in thousands of virtual patients derived from previously published demographic, pharmacokinetic, and dialytic information derived from critically ill patients receiving vancomycin and other forms of renal replacement therapy. We conducted "in silico" vancomycin pharmacokinetic/pharmacodynamics analyses in these patients receiving prolonged intermittent renal replacement therapy to determine what vancomycin dose would achieve vancomycin 24-h area under the curve (AUC 24h ) of 400-700 mg·h/L, a target associated with positive clinical outcomes. Nine different vancomycin dosing regimens were tested using four different, commonly used prolonged intermittent renal replacement therapy modalities. A dosing nomogram based on serum concentration data achieved after the third dose was developed to individualize vancomycin therapy. An initial vancomycin dose of 15 or 20 mg/kg immediately followed by 15 mg/kg after subsequent prolonged intermittent renal replacement therapy treatments achieved AUC 24h of ≥400 mg·h/L for ≥90% of patients regardless of prolonged intermittent renal replacement therapy duration, modality, or time of vancomycin dose relative to prolonged intermittent renal replacement therapy. Many patients experienced AUC 24h of ≥700 mg·h/L, but once the dosing nomogram was applied to serum concentrations obtained after the third vancomycin dose, 67%-88% of patients achieved AUC 24h of 400-700 mg·h/L. An initial loading dose of 15-20 mg/kg followed by a maintenance regimen of 15 mg/kg after every prolonged intermittent renal replacement therapy session coupled with serum concentration monitoring should be used to individualize vancomycin dosing. These predictions need clinical verification.

Inhibition of Interferon-beta Responses in Multiple Sclerosis Immune Cells Associated With High-Dose Statins

PubMed Central

Feng, Xuan; Han, Diana; Kilaru, Bharat K.; Franek, Beverly S.; Niewold, Timothy B.; Reder, Anthony T.

2014-01-01

Objective To determine whether statins affect type 1 interferon responses in relapsing-remitting multiple sclerosis (RRMS). Design Study effects of atorvastatin on type 1 interferon responses in Jurkat cells, mononuclear cells (MNCs) from therapy-naive patients with RRMS in vitro, and MNCs from interferon-treated RRMS patients in vivo in 4 conditions: no drug, statin only, interferon-beta only, and statin added on to interferon-beta therapy. Patients The study examined clinically stable patients with RRMS: 21 therapy-naive patients and 14 patients receiving interferon-beta with a statin. Interventions Statin effects on in vitro and in vivo interferon-beta–induced STAT1 transcription factor activation, expression of interferon-stimulated proteins in MNCs, and serum type 1 interferon activity. Results In vitro, atorvastatin dose dependently inhibited expression of interferon-stimulated P-Y-STAT1 by 44% (P< .001), interferon regulatory factor 1 protein by 30% (P= .006), and myxovirus resistance 1 protein by 32% (P=.004) compared with no-statin control in MNCs from therapy-naive RRMS patients. In vivo, 9 of 10 patients who received high-dose statins (80 mg) had a significant reduction in interferon-beta therapy–induced serum interferon-α/β activity, whereas only 2 of 4 patients who received medium-dose statins (40 mg) had reductions. High-dose add-on statin therapy significantly blocked interferon-beta function, with less P-Y-STAT1 transcription factor activation, and reduced myxovirus resistance 1 protein and viperin protein production. Medium doses of statins did not change STAT1 activation. Conclusions High-dose add-on statin therapy significantly reduces interferon-beta function and type 1 interferon responses in RRMS patients. These data provide a putative mechanism for how statins could counteract the beneficial effects of interferon-beta and worsen disease. PMID:22801747

Proton irradiation of stem cells: Radiation damage and chemical radioprotection

NASA Technical Reports Server (NTRS)

Riley, R. C.; Montour, J. L.; Gurney, C. W.

1972-01-01

Effects of high energy protons on erythropoietic stem cells and radioprotection by chemicals were investigated in NASA Space Radiation Effects Laboratory. The effects of a parallel beam of 600 MeV protons. The fluence, when converted to dose, were referenced to the synchrocyclotron beam monitors which were then used to administer radiation exposures. Mice were given graded doses to 300 rads to determine dose-response curve. Other mice received saline, AET, or 5-hydroxytryptamine 10 to 15 minutes before exposure.

Subgroup effects in a randomised trial of different types and doses of exercise during breast cancer chemotherapy.

PubMed

Courneya, K S; McKenzie, D C; Mackey, J R; Gelmon, K; Friedenreich, C M; Yasui, Y; Reid, R D; Vallerand, J R; Adams, S C; Proulx, C; Dolan, L B; Wooding, E; Segal, R J

2014-10-28

The Combined Aerobic and Resistance Exercise Trial tested different types and doses of exercise in breast cancer patients receiving chemotherapy. Here, we explore potential moderators of the exercise training responses. Breast cancer patients initiating chemotherapy (N=301) were randomly assigned to three times a week, supervised exercise of a standard dose of 25-30 min of aerobic exercise, a higher dose of 50-60 min of aerobic exercise, or a higher dose of 50-60 min of combined aerobic and resistance exercise. Outcomes were patient-reported symptoms and health-related fitness. Moderators were baseline demographic, exercise/fitness, and cancer variables. Body mass index moderated the effects of the exercise interventions on bodily pain (P for interaction=0.038), endocrine symptoms (P for interaction=0.029), taxane/neuropathy symptoms (P for interaction=0.013), aerobic fitness (P for interaction=0.041), muscular strength (P for interaction=0.007), and fat mass (P for interaction=0.005). In general, healthy weight patients responded better to the higher-dose exercise interventions than overweight/obese patients. Menopausal status, age, and baseline fitness moderated the effects on patient-reported symptoms. Premenopausal, younger, and fitter patients achieved greater benefits from the higher-dose exercise interventions. Healthy weight, fitter, and premenopausal/younger breast cancer patients receiving chemotherapy are more likely to benefit from higher-dose exercise interventions.

Long-term effectiveness of plasma-derived hepatitis B vaccine 22-28 years after immunization in a hepatitis B virus endemic rural area: is an adult booster dose needed?

PubMed

Li, H; Li, G J; Chen, Q Y; Fang, Z L; Wang, X Y; Tan, C; Yang, Q L; Wang, F Z; Wang, F; Zhang, S; Bi, S L; Shen, L P

2017-04-01

Longan County is considered a highly endemic area for hepatitis B virus (HBV). The plasma-derived vaccine has been used in newborns in this area since 1987. A cross-sectional survey was conducted to evaluate the long-term effectiveness of this vaccine. In total, 1634 participants born during 1987-1993 and who had received a series of plasma-derived HB vaccinations at ages 0, 1, and 6 months were enrolled. Serological HBV markers were detected and compared with previous survey data. Overall the prevalence of hepatitis B surface antigen (HBsAg) in all participants was 3·79%; 3·47% of subjects who had received the first dose within 24 h were HBsAg positive, and 8·41% of subjects who had received a delayed first dose were also HBsAg positive. There were 1527 subjects identified who had received the first dose within 24 h and whose HBsAg and anti-HBc prevalence increased yearly after immunization, while the anti-HBs-positive rate and vaccine effectiveness declined. The geometric mean concentration of antibody in the anti-HB-positive participants was 55·13 mIU/ml and this declined after immunization. Fewer than 2·0% of participants had anti-HB levels ⩾1000 mIU/ml. The data show that the protective efficacy of the plasma-derived vaccinations declined and administration of HB vaccine within 24 h of birth was very important. To reduce the risk of HBV infection in this highly endemic area, a booster dose might be necessary if anti-HBs levels fall below 10 mIU/ml after age 18 years. Furthermore, studies on the immune memory induced by plasma-derived HB vaccine are needed.

A phase I study of recombinant human leukemia inhibitory factor in patients with advanced cancer.

PubMed

Gunawardana, Dishan H; Basser, Russell L; Davis, Ian D; Cebon, Jonathan; Mitchell, Paul; Underhill, Craig; Kilpatrick, Trevor J; Reardon, Katrina; Green, Michael D; Bardy, Peter; Amor, Pene; Crump, David; Ng, Siobhan; Nation, Roger L; Begley, C Glenn

2003-06-01

Leukemia inhibitory factor (LIF) is a pleiotropic molecule of the interleukin 6 family of cytokines. We aimed to examine the safety, pharmacokinetics, and biological effects of recombinant human LIF (rhLIF, emfilermin) in patients with advanced cancer. In stage 1 of the study, 34 patients received rhLIF or placebo (3:1 ratio) at doses of 0.25-16.0 micro g/kg/day or 4.0 micro g/kg three times daily for 7 days. In stage 2, 40 patients received rhLIF or placebo, either once daily for 14 days commencing the day after chemotherapy (0.25-8.0 micro g/kg/day) or for 7 days commencing the day before chemotherapy (4.0 micro g/kg three times daily). The chemotherapy was cisplatin 75 mg/m(2) and paclitaxel 135 mg/m(2). In stage 1, platelet counts increased in most patients, including those who received placebo. Blood progenitor cells increased in response to rhLIF. In stage 2, platelet recovery to baseline levels was earlier for patients receiving higher doses of rhLIF (>/=4.0 micro g/kg/day; P = 0.02). The neutrophil nadir after chemotherapy was less severe in patients receiving >/=4.0 micro g/kg/day of rhLIF. In stages 1 and 2, increases in C reactive protein were seen at higher doses. Several patients developed evidence of autonomic dysfunction, in particular impotence and episodic hypotension. The dose-limiting toxicities were hypotension and rigors. Pharmacokinetic studies demonstrated a short half-life (1-5 h) independent of dose. We demonstrated a biological effect of rhLIF on blood progenitor cells, C reactive protein levels, and hemopoietic recovery after chemotherapy.

Differences in carbachol dose, pain condition, and sex following lateral hypothalamic stimulation.

PubMed

Holden, J E; Wang, E; Moes, J R; Wagner, M; Maduko, A; Jeong, Y

2014-06-13

Lateral hypothalamic (LH) stimulation produces antinociception in female rats in acute, nociceptive pain. Whether this effect occurs in neuropathic pain or whether male-female sex differences exist is unknown. We examined the effect of LH stimulation in male and female rats using conditions of nociceptive and neuropathic pain. Neuropathic groups received chronic constriction injury (CCI) to induce thermal hyperalgesia, a sign of neuropathic pain. Nociceptive rats were naive for CCI, but received the same thermal stimulus following LH stimulation. To demonstrate that CCI ligation produced thermal hyperalgesia, males and females received either ligation or sham surgery for control. Both males and females demonstrated significant thermal hyperalgesia following CCI ligation (p<0.05), but male sham surgery rats also showed a significant left-right difference not present in female sham rats. In the second experiment, rats randomly assigned to CCI or nociceptive groups were given one of three doses of the cholinergic agonist carbachol (125, 250, or 500 nmol) or normal saline for control, microinjected into the left LH. Paw withdrawal from a thermal stimulus (paw withdrawal latency; PWL) was measured every 5 min for 45 min. Linear mixed models analysis showed that males and females in both pain conditions demonstrated significant antinociception, with the 500-nmol dose producing the greatest effect across groups compared with controls for the left paw (p<0.05). Female CCI rats showed equivalent responses to the three doses, while male CCI rats showed more variability for dose. However, nociceptive females responded only to the 500-nmol dose, while nociceptive males responded to all doses (p<0.05). For right PWL, only nociceptive males showed a significant carbachol dose response. These findings are suggestive that LH stimulation produces antinociception in male and female rats in both nociceptive and neuropathic pain, but dose response differences exist based on sex and pain condition. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

Single and Multiple Ascending-dose Studies of Oral Delafloxacin: Effects of Food, Sex, and Age.

PubMed

Hoover, Randall; Hunt, Thomas; Benedict, Michael; Paulson, Susan K; Lawrence, Laura; Cammarata, Sue; Sun, Eugene

2016-01-01

The objective of this report is describe the results of 2 studies that examined the pharmacokinetic parameters, safety profile, and tolerability of single and multiple ascending doses of oral delafloxacin and the effects of food, sex, and age on oral delafloxacin pharmacokinetic parameters, safety profile, and tolerability. The first study contained 3 parts and used unformulated delafloxacin in a capsule. Part 1 was a randomized, double-blind, placebo-controlled, single (50, 100, 200, 400, 800, 1200, and 1600 mg) ascending-dose study of oral delafloxacin in healthy men. Part 2 was a single-dose crossover study in which 20 men received 250 mg delafloxacin with or without food. Part 2 also included a parallel group, double-blind, placebo-controlled study in 16 women and 16 elderly men and women who were randomized (3:1) to receive 250 mg delafloxacin or placebo. Part 3 was a randomized, double-blind, placebo-controlled, multiple (100, 200, 400, 800, 1200 mg once daily for 5 days) ascending-dose study of oral delafloxacin in healthy men. The second study was a single-dose, randomized, 3-period crossover study in which participants received 900 mg delafloxacin (2 × 450-mg tablets) under fasted conditions, with a high-fat meal, or fasted with a high-fat meal 2 hours after dosing. Serial blood samples were collected, and plasma pharmacokinetic parameters of delafloxacin were determined. Delafloxacin Cmax and AUC0-∞ increased with increasing oral dose over the dose range of 50 to 1600 mg. The increases in delafloxacin AUC0-∞ were dose proportional at doses of ≥200 mg. Steady state was reached by day 3 of dosing with minimal accumulation of delafloxacin. The Cmax of delafloxacin was decreased slightly in the presence of food. No sex difference in delafloxacin pharmacokinetic parameters was observed. In the elderly men and women, mean delafloxacin Cmax and AUC0-∞ were 35% higher than observed for young adults, which could be partially explained by a decrease in the creatinine clearance in the elderly men and women. Delafloxacin was well tolerated at the tested doses, with gastrointestinal adverse effects observed more commonly at doses ≥1200 mg. Delafloxacin exhibits linear pharmacokinetic parameters that reached steady state after 3 days of daily oral dosing with minimal accumulation. Delafloxacin was well tolerated throughout both studies, with gastrointestinal effects observed at the higher doses (≥1200 mg). Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Oral Cryotherapy for Preventing Oral Mucositis in Patients Receiving Cancer Treatment.

PubMed

Riley, Philip; McCabe, Martin G; Glenny, Anne-Marie

2016-10-01

In patients receiving treatment for cancer, does oral cryotherapy prevent oral mucositis? Oral cryotherapy is effective for the prevention of oral mucositis in adults receiving fluorouracil-based chemotherapy for solid cancers, and for the prevention of severe oral mucositis in adults receiving high-dose melphalan-based chemotherapy before hematopoietic stem cell transplantation (HSCT).

Systemic effects of low-dose dopamine during administration of cytarabine.

PubMed

Connelly, James; Benani, Dina J; Newman, Matthew; Burton, Bradley; Crow, Jessica; Levis, Mark

2017-09-01

Purpose Low-dose dopamine has been utilized to improve renal blood flow, urine output, and reduce drug-induced nephrotoxicity. The purpose of this study was to assess changes in renal function, cardiovascular adverse events, and neurologic toxicity in patients receiving cytarabine with or without low-dose dopamine. Methods A retrospective, single-center, cohort study of patients receiving cytarabine at 667 mg/m 2 /dose or greater, with or without dopamine at ≤5 mcg/kg/min. Cohorts were based upon initiation or absence of low-dose dopamine; cytarabine only, cytarabine + pre- and day of low-dose dopamine, and cytarabine + post-low-dose dopamine. Renal outcomes (urine output, serum creatinine, and creatinine clearance) were compared with baseline and between cohorts. Safety endpoints (arrhythmias, tachycardia, and neurotoxicity) were compared between cohorts based on low-dose dopamine exposure. Results There was no difference in urine output from baseline in all cohorts. Comparing cytarabine only and pre- and day of low-dose dopamine cohorts, there was no difference in urine output. In those receiving low-dose dopamine, there was no difference in serum creatinine and creatinine clearance from baseline. No arrhythmias were documented during the study period, and there was no difference in the incidence of tachycardia between groups (P = 0.66). Neurotoxicity was reported in three patients who were on low-dose dopamine. Conclusion Though variation existed in individual patients administered low-dose dopamine, the use of low-dose dopamine did not significantly impact renal function in this small sample at a single institution. In addition, low-dose dopamine did not negatively impact cardiovascular function.

Stray radiation dose and second cancer risk for a pediatric patient receiving craniospinal irradiation with proton beams

PubMed Central

Taddei, Phillip J; Mirkovic, Dragan; Fontenot, Jonas D; Giebeler, Annelise; Zheng, Yuanshui; Kornguth, David; Mohan, Radhe; Newhauser, Wayne D

2014-01-01

Proton beam radiotherapy unavoidably exposes healthy tissue to stray radiation emanating from the treatment unit and secondary radiation produced within the patient. These exposures provide no known benefit and may increase a patient's risk of developing a radiogenic cancer. The aims of this study were to calculate doses to major organs and tissues and to estimate second cancer risk from stray radiation following craniospinal irradiation (CSI) with proton therapy. This was accomplished using detailed Monte Carlo simulations of a passive-scattering proton treatment unit and a voxelized phantom to represent the patient. Equivalent doses, effective dose and corresponding risk for developing a fatal second cancer were calculated for a 10-year-old boy who received proton therapy. The proton treatment comprised CSI at 30.6 Gy plus a boost of 23.4 Gy to the clinical target volume. The predicted effective dose from stray radiation was 418 mSv, of which 344 mSv was from neutrons originating outside the patient; the remaining 74 mSv was caused by neutrons originating within the patient. This effective dose corresponds to an attributable lifetime risk of a fatal second cancer of 3.4%. The equivalent doses that predominated the effective dose from stray radiation were in the lungs, stomach and colon. These results establish a baseline estimate of the stray radiation dose and corresponding risk for a pediatric patient undergoing proton CSI and support the suitability of passively-scattered proton beams for the treatment of central nervous system tumors in pediatric patients. PMID:19305045

Immunogenicity of aluminum-adsorbed hepatitis A vaccine (Havrix®) administered as a third dose after primary doses of Japanese aluminum-free hepatitis A vaccine (Aimmugen®) for Japanese travelers to endemic countries.

PubMed

Fukushima, Shinji; Kiyohara, Tomoko; Ishii, Koji; Nakano, Takashi; Hamada, Atsuo

2017-11-07

Hepatitis A vaccination is recommended for travelers to endemic countries. Several inactivated aluminum-adsorbed hepatitis A vaccines are available worldwide, but only one licensed hepatitis A vaccine is available in Japan. This vaccine is a lyophilized inactivated aluminum-free hepatitis A vaccine (Aimmugen®). The standard schedule of Aimmugen® is three doses (at 0, 2-4 weeks, and 6 months). Japanese people will go abroad after receiving 2 doses of Aimmugen®. Some long-term travelers will receive the third dose of hepatitis A vaccine at their destination, at 6-24 months after 2 doses of Aimmugen®. Aimmugen® is not available in countries other than Japan. They receive inactivated aluminum-adsorbed hepatitis A vaccine instead of a third dose of Aimmugen®. This study was undertaken to determine whether the booster vaccination with an aluminum-adsorbed hepatitis A vaccine is effective following two doses of Aimmugen®. Subjects were healthy Japanese adults aged 20 years or older who had received two doses of Aimmugen®. Subjects received a booster dose of Havrix®1440 intramuscularly as the third dose. Serology samples for hepatitis A virus antibody titers were taken 4-6 weeks later. Anti-hepatitis A virus antibody titers were measured by an inhibition enzyme-linked immunosorbent assay. Subjects were 20 healthy Japanese adults, 6 men and 14 women. The mean age ± standard deviation was 37.2 ± 13.3. The seroprotection rate (SPR, anti-hepatitis A virus antibody titer ≥10 mIU/mL) was 85% at enrollment, and increased to 100% after vaccination with Havrix®. The geometric mean anti-hepatitis A virus antibody titer increased from 39.8 mIU/mL to 2938.2 mIU/mL. The three scheduled doses consisting of two doses of Aimmugen® plus a third dose with Havrix® is more immunogenic than using only two doses of Aimmugen®. The vaccination with Havrix® could be allowed to be used instead of a third dose of Aimmugen®. (UMIN000009351). Copyright © 2017 Elsevier Ltd. All rights reserved.

Acute and Chronic Effects of Cocaine on the Spontaneous Behavior of Pigeons

ERIC Educational Resources Information Center

Pinkston, Jonathan W.; Branch, Marc N.

2010-01-01

The present experiment examined the effects of acute and daily cocaine on spontaneous behavior patterns of pigeons. After determining the acute effects of a range of doses, 9 pigeons were divided into three groups that received one of three doses of cocaine daily, either 1.0, 3.0, or 10.0 mg/kg cocaine. Measures were taken of spontaneous…

Effects of Varenicline Alone and in Combination With Low-dose Naltrexone on Alcohol-primed Smoking in Heavy-drinking Tobacco Users: A Preliminary Laboratory Study.

PubMed

Roberts, Walter; Shi, Julia M; Tetrault, Jeanette M; McKee, Sherry A

Heavy-drinking tobacco users are less likely to successfully quit smoking than their moderate-drinking counterparts, even when they are prescribed smoking cessation medication. One strategy for improving treatment outcomes in this subgroup of tobacco users may be to combine medication therapies to target both alcohol and tobacco use simultaneously. Adding naltrexone to frontline smoking cessation treatments may improve treatment outcomes in this group. This double-blind, placebo-controlled human laboratory study examined the effects of varenicline (2 mg/d) and varenicline (2 mg/d), combined with a low dose of naltrexone (25 mg/d) on alcohol-primed smoking behavior in a laboratory model of smoking relapse in heavy-drinking tobacco users (n = 30). Participants attended a laboratory session and received an alcohol challenge (target breath alcohol concentration = 0.030 g/dL). They completed a smoking delay task that assessed their ability to resist smoking followed by an ad libitum smoking phase (primary outcomes). They also provided ratings of subjective drug effects and craving, and carbon monoxide levels were measured after smoking (secondary outcomes). Participants receiving varenicline monotherapy delayed smoking longer and smoked fewer cigarettes than those on placebo. Participants receiving varenicline + low-dose naltrexone did not delay smoking longer than those receiving varenicline alone. Participants in both active medication arms smoked fewer cigarettes ad libitum than those receiving placebo. Varenicline can improve smoking outcomes even after an alcohol prime, supporting its use in heavy drinkers who wish to quit smoking. Findings did not support increased efficacy of combined varenicline + low-dose naltrexone relative to varenicline monotherapy.

High Dose Cytosine Arabinoside in the consolidation of adult acute myeloid leukemia.

PubMed

Rahman, M H; Khan, M A; Islam, M S; Afrose, S; Ara, T

2012-04-01

This interventional study was done to evaluate the duration of remission with High Dose Cytosine Arabinoside (Ara-C) as post-remission chemotherapy in the consolidation of adult acute myeloid leukemia. A total of 32 patients were included in this study. Among them, 19 were male and 13 were female and the age of the patients ranges from 15-60 years. We use High Dose Cytosine Arabinoside 1.5-2.5 g/m2 i.v, 12 hourly, over 2-3 hours on day 1, 3 and 5 in a 28 days cycle. This study was done during the period of April 2007 to March 2009 in the department of hematology, Dhaka Medical College & Hospital. History, clinical features and laboratory investigations were included. Among 32 patients, 5 patients (15.6%) received one cycle, 20 patients (62.5%) received two cycles and 7 patients (21.9%) received three cycles. The mean ± SD duration of remission (disease free survival) was 5.20 ± 3.83 months who received one cycle, 9.55 ± 3.30 months and 10.71 ± 1.70 months who received two cycles and three cycles respectively. The adverse effects of the therapy were neutropenia and neutropenic fever, purpuric rash, gum bleeding, mucositis and peripheral neuropathy. The supportive materials needed were antibiotics (both prophylactic and treatment) 86.13%, blood and blood products 51.7% and G-CSF 14.9% patients of all cycles. High Dose Ara-C (HiDAC) is a safe and cost effective consolidation treatment for AML patients in complete remission. This therapy merits multi-center control study to define its efficacy and cost-effectiveness in contrast to our socio-economic condition.

OCCUPATIONAL RADIATION DOSES TO OPERATORS PERFORMING FLUOROSCOPICALLY-GUIDED PROCEDURES

PubMed Central

Kim, Kwang Pyo; Miller, Donald L.; de Gonzalez, Amy Berrington; Balter, Stephen; Kleinerman, Ruth A.; Ostroumova, Evgenia; Simon, Steven L.; Linet, Martha S.

2012-01-01

In the past 30 years, the numbers and types of fluoroscopically-guided (FG) procedures have increased dramatically. The objective of the present study is to provide estimated radiation doses to physician specialists, other than cardiologists, who perform FG procedures. We searched Medline to identify English-language journal articles reporting radiation exposures to these physicians. We then identified several primarily therapeutic FG procedures that met specific criteria: well-defined procedures for which there were at least five published reports of estimated radiation doses to the operator, procedures performed frequently in current medical practice, and inclusion of physicians from multiple medical specialties. These procedures were percutaneous nephrolithotomy (PCNL), vertebroplasty, orthopedic extremity nailing for treatment of fractures, biliary tract procedures, transjugular intrahepatic portosystemic shunt creation (TIPS), head/neck endovascular therapeutic procedures, and endoscopic retrograde cholangiopancreatography (ERCP). We abstracted radiation doses and other associated data, and estimated effective dose to operators. Operators received estimated doses per patient procedure equivalent to doses received by interventional cardiologists. The estimated effective dose per case ranged from 1.7 – 56μSv for PCNL, 0.1 – 101 μSv for vertebroplasty, 2.5 – 88μSv for orthopedic extremity nailing, 2.0 – 46μSv for biliary tract procedures, 2.5 – 74μSv for TIPS, 1.8 – 53μSv for head/neck endovascular therapeutic procedures, and 0.2 – 49μSv for ERCP. Overall, mean operator radiation dose per case measured over personal protective devices at different anatomic sites on the head and body ranged from 19 – 800 (median = 113) μSv at eye level, 6 – 1180 (median = 75)μSv at the neck, and 2 – 1600 (median = 302) μSv at the trunk. Operators’ hands often received greater doses than the eyes, neck or trunk. Large variations in operator doses suggest that optimizing procedure protocols and proper use of protective devices and shields might reduce occupational radiation dose substantially. PMID:22647920

Comparison of Immunogenicity Between Inactivated and Live Attenuated Hepatitis A Vaccines Among Young Adults: A 3-Year Follow-up Study.

PubMed

Liu, Xue-en; Chen, Hai-ying; Liao, Zheng; Zhou, Yisheng; Wen, Hairong; Peng, Shihui; Liu, Yan; Li, Rui; Li, Jie; Zhuang, Hui

2015-10-15

A randomized clinical trial of hepatitis A vaccines (1 or 2 doses of inactivated vaccine [Healive] or 1 dose of live attenuated vaccine [Biovac]) was conducted among adults to evaluate seroprotection rates and geometric mean concentrations of antibody against hepatitis A virus for 36 months. High rates of seroprotection persisted for at least 36 months among adults who received 1 or 2 doses of inactivated hepatitis A vaccine but not among adults who received 1 dose of live attenuated hepatitis A vaccine. The long-term serial monitoring of immunogenicity induced by 1 dose of inactivated hepatitis A vaccine is needed to determine an effective alternative to a 2-dose schedule. NCT01865968. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

DOSE COEFFICIENTS FOR LIVER CHEMOEMBOLISATION PROCEDURES USING MONTE CARLO CODE.

PubMed

Karavasilis, E; Dimitriadis, A; Gonis, H; Pappas, P; Georgiou, E; Yakoumakis, E

2016-12-01

The aim of the present study is the estimation of radiation burden during liver chemoembolisation procedures. Organ dose and effective dose conversion factors, normalised to dose-area product (DAP), were estimated for chemoembolisation procedures using a Monte Carlo transport code in conjunction with an adult mathematical phantom. Exposure data from 32 patients were used to determine the exposure projections for the simulations. Equivalent organ (H T ) and effective (E) doses were estimated using individual DAP values. The organs receiving the highest amount of doses during these exams were lumbar spine, liver and kidneys. The mean effective dose conversion factor was 1.4 Sv Gy -1 m -2 Dose conversion factors can be useful for patient-specific radiation burden during chemoembolisation procedures. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

The effect of dose on the safety and immunogenicity of the VSV Ebola candidate vaccine: a randomised double-blind, placebo-controlled phase 1/2 trial.

PubMed

Huttner, Angela; Dayer, Julie-Anne; Yerly, Sabine; Combescure, Christophe; Auderset, Floriane; Desmeules, Jules; Eickmann, Markus; Finckh, Axel; Goncalves, Ana Rita; Hooper, Jay W; Kaya, Gürkan; Krähling, Verena; Kwilas, Steve; Lemaître, Barbara; Matthey, Alain; Silvera, Peter; Becker, Stephan; Fast, Patricia E; Moorthy, Vasee; Kieny, Marie Paule; Kaiser, Laurent; Siegrist, Claire-Anne

2015-10-01

Safe and effective vaccines against Ebola could prevent or control outbreaks. The safe use of replication-competent vaccines requires a careful dose-selection process. We report the first safety and immunogenicity results in volunteers receiving 3 × 10(5) plaque-forming units (pfu) of the recombinant vesicular stomatitis virus-based candidate vaccine expressing the Zaire Ebola virus glycoprotein (rVSV-ZEBOV; low-dose vaccinees) compared with 59 volunteers who had received 1 ×10(7) pfu (n=35) or 5 × 10(7) pfu (n=16) of rVSV-ZEBOV (high-dose vaccinees) or placebo (n=8) before a safety-driven study hold. The Geneva rVSV-ZEBOV study, an investigator-initiated phase 1/2, dose-finding, placebo-controlled, double-blind trial conducted at the University Hospitals of Geneva, Switzerland, enrolled non-pregnant, immunocompetent, and otherwise healthy adults aged 18-65 years. Participants from the low-dose group with no plans to deploy to Ebola-aff5cted regions (non-deployable) were randomised 9:1 in a double-blind fashion using randomly permuted blocks of varying sizes to a single injection of 3 × 10(5) pfu or placebo, whereas deployable participants received single-injection 3 × 10(5) pfu open-label. Primary safety and immunogenicity outcomes were the incidence of adverse events within 14 days of vaccination and day-28 antibody titres, respectively, analysed by intention to treat. After viral oligoarthritis was observed in 11 of the first 51 vaccinees (22%) receiving 10(7) or 5 × 10(7) pfu, 56 participants were given a lower dose (3 × 10(5) pfu, n=51) or placebo (n=5) to assess the effect of dose reduction on safety and immunogenicity. This trial is ongoing with a follow-up period of 12 months; all reported results are from interim databases. This study is registered with ClinicalTrials.gov, number NCT02287480. Between Jan 5 and Jan 26, 2015, 43 non-deployable participants received low-dose rVSV-ZEBOV (3 × 10(5) pfu) or placebo in a double-blind fashion, whereas 13 deployable participants received 3 × 10(5) pfu open-label. Altogether, in the low-dose group, 51 participants received rVSV-ZEBOV and five received placebo. No serious adverse events occurred. At 3 × 10(5) pfu, early-onset reactogenicity remained frequent (45 [88%] of 51 compared with 50 [98%] of 51 high dose and two [15%] of 13 placebo recipients), but mild. Objective fever was present in one (2%) of 51 low-dose versus 13 (25%) of 51 high-dose vaccinees receiving at least 1 ×10(7) pfu (p<0·0001). Subjective fever (p<0·0001), myalgia (p=0·036), and chills (p=0·026) were significantly reduced and their time of onset delayed, reflecting significantly lower viraemia (p<0·0001) and blood monocyte-activation patterns (p=0·0233). Although seropositivity rates remained similarly high (48 [94%] of 51), day-28 EBOV-glycoprotein-binding and neutralising antibody titres were lower in low-dose versus high-dose vaccinees (geometric mean titres 344·5 [95% CI 229·7-516·4] vs 1064·2 [757·6-1495·1]; p<0·0001; and 35·1 [24·7-50·7] vs 127·0 [86·0-187·6]; p<0·0001, respectively). Furthermore, oligoarthritis again occurred on day 10 (median; IQR 9-14) in 13 (25%) of 51 low-dose vaccinees, with maculopapular, vesicular dermatitis, or both in seven (54%) of 13; arthritis was associated with increasing age in low-dose but not high-dose vaccinees. Two vaccinees presented with purpura of the lower legs; histological findings indicated cutaneous vasculitis. The presence of rVSV in synovial fluid and skin lesions confirmed causality. Reducing the dose of rVSV-ZEBOV improved its early tolerability but lowered antibody responses and did not prevent vaccine-induced arthritis, dermatitis, or vasculitis. Like its efficacy, the safety of rVSV-ZEBOV requires further definition in the target populations of Africa. Wellcome Trust through WHO. Copyright © 2015 Elsevier Ltd. All rights reserved.

Hepatoprotective effect of Crocus sativus (saffron) petals extract against acetaminophen toxicity in male Wistar rats

PubMed Central

Omidi, Arash; Riahinia, Narges; Montazer Torbati, Mohammad Bagher; Behdani, Mohammad-Ali

2014-01-01

Objectives: Acetaminophen (APAP) toxicity is known to be common and potentially fatal. This study aims to investigate the protective effects of hydroalcoholic extract, remaining from Crocus sativus petals (CSP) against APAP-induced hepatotoxicity by measuring the blood parameters and studying the histopathology of liver in male rats. Materials and Methods: Wister rats (24) were randomly assigned into four groups including: I) healthy, receiving normal saline; II) Intoxicated, receiving only APAP (600 mg/kg); III) pre-treated with low dose of CSP (10 mg /kg) and receiving APAP (600 mg/kg); IV) pre-treated with high dose of CSP (20 mg/kg) and receiving APAP (600 mg/kg). Results: The APAP treatment resulted in higher levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and bilirubin, along with lower total protein and albumin concentration than the control group. The administration of CSP with a dose of 20 mg/kg was found to result in lower levels of AST, ALT and bilirubin, with a significant higher concentration of total protein and albumin. The histopathological results regarding liver pathology, revealed sever conditions including cell swelling, severe inflammation and necrosis in APAP-exposed rats, which was quiet contrasting compared to the control group. The pre-treated rats with low doses of ‍CSP showed hydropic degeneration with mild necrosis in centrilobular areas of the liver, while the same subjects with high doses of ‍CSP appeared to have only mild hepatocyte degeneration. Conclusions: Doses of 20 mg/kg of CSP ameliorates APAP–induced acute liver injury in rats. It was concluded that the antioxidant property of CSP resulted in reducing the oxidative stress complications of toxic levels of APAP in intoxicated rats. PMID:25386395

Protective effects of selenium on acrylamide toxicity in the liver of the rat. Effects on the oxidative stress.

PubMed

Teodor, V; Cuciureanu, Magdalena; Filip, Cristiana; Zamosteanu, Nina; Cuciureanu, Rodica

2011-01-01

Acrylamide (AA), obtained for the first time by Moureu in Germany in 1893, is presently used as polyacrylamide in water treatment and wastewater treatment, paper and pulp processing, mineral processing, crude-oil production processes. Acrylamide is a chemical product formed when frying, roasting, grilling or baking carbohydrate-rich foods at temperatures above 120 degrees C. Acrylamide is thus found in a number of foods, such as bread, crisps, French fries and coffee. Tobacco smoking also generates substantial amounts of acrylamide. Acrylamide administration is associated with significant increase of oxidative stress parameters; acrylamide caused disturbances in the oxidative status and enzyme activities and the effect was pronounced with the high doses. This study investigates the effect of selenium (as sodium selenite and as a selenium dietary supplements--Celnium) on the oxidative stress in Wistar rats which received high doses of acrylamide. The administration of sodium selenite and selenium dietary supplements (Celnium) significantly increased GSH and GPx levels and decreased MDA compared to group which received only acrylamide. Our results show that sodium selenite and selenium dietary supplements (Celnium) can partially prevent the biochemical changes in the liver of the rats which received high doses of acrylamide.

Laboratory measures of methylphenidate effects in cocaine-dependent patients receiving treatment.

PubMed

Roache, J D; Grabowski, J; Schmitz, J M; Creson, D L; Rhoades, H M

2000-02-01

Two experiments examined the effects of methylphenidate in male and female patients enrolled in an outpatient treatment program for primary cocaine dependence. The first study was a component of a double-blind efficacy trial wherein 57 patients were first tested in a human laboratory for their initial responsiveness to medication. Patients were randomly assigned to receive either placebo or methylphenidate treatment and received their first dose in the human laboratory environment before continuing in outpatient treatment. Methylphenidate was given as a 20-mg sustained-release dose (twice daily) plus an additional 5-mg immediate-release dose combined with the morning dose. Methylphenidate increased heart rate and subjective ratings; however, the subjective effects were primarily of a "dysphoric" nature, and significant effects were limited to increases in anxiety, depression, and anger on the Profile of Mood States; shaky/jittery ratings on a visual analog scale; and dysphoria on the lysergic acid diethylamide (LSD) scale of the Addiction Research Center Inventory. Methylphenidate did not increase cocaine craving nor ratings suggesting abuse potential (i.e., Morphine-Benzedrine Group or drug-liking scores, etc.). None of the drug effects observed in the human laboratory was of clinical concern, and no subject was precluded from continuing in the outpatient study. After outpatient treatment completion, 12 patients were brought back into a second double-blind human laboratory study in which three doses (15, 30, and 60 mg) of immediate-release methylphenidate were administered in an ascending series preceded and followed by placebo. Methylphenidate produced dose-related increases in heart rate, subjective ratings of shaky/jittery, and LSD/dysphoria without significantly altering cocaine craving or stimulant euphoria ratings. These results suggest that stimulant substitution-type approaches to the treatment of cocaine dependence are not necessarily contraindicated because of cardiovascular toxicity or medication abuse potential. However, they also suggest that the subjective effects of methylphenidate may not be positive enough for an adequate replacement approach.

Medical management with diazepam for electrical status epilepticus during slow wave sleep in children.

PubMed

Francois, Densley; Roberts, Jessica; Hess, Stephany; Probst, Luke; Eksioglu, Yaman

2014-03-01

Oral diazepam, administered in varying doses, is among the few proposed treatment options for electrical status epilepticus during slow wave sleep in children. We sought to retrospectively evaluate the long-term efficacy of high-dose oral diazepam in reducing electrographic and clinical evidence of electrical status epilepticus during slow wave sleep in children. Additionally, we surveyed caregivers to assess safety and behavioral outcomes related to ongoing therapy. We collected demographic and clinical data on children treated for electrical status epilepticus during slow wave sleep between October 2010 and March 2013. We sought to identify the number of patients who achieved at least a 50% reduction in spike wave index on electroencephalograph after receiving high-dose oral diazepam. We also administered a questionnaire to caregivers to assess for behavioral problems and side effects. We identified 42 evaluable patients who received high-dose diazepam (range 0.23-2.02 mg/kg per day) to treat electrical status epilepticus during slow wave sleep. Twenty-six patients had spike reduction data and 18/26 (69.2%) children achieved a greater than 50% reduction in spike wave count from an average of 15.54 to 5.05 (P = 0.001). We received 28 responses to the questionnaire. Some patients experienced new onset of difficulties with problem-solving and speech and writing development. Sleep disturbances (50%) and irritability (57.1%) were the most frequent side effects reported. There did not appear to be a dose-related effect with electroencephalograph changes, behavioral effects, or side effects. High-dose oral diazepam significantly reduces the spike wave count on electroencephalograph in children with electrical status epilepticus during slow wave sleep. Although this therapy improves electroencephalograph-related findings, it can be associated with concerning neurological and behavioral side effects in some individuals, so further study is warranted. Copyright © 2014 Elsevier Inc. All rights reserved.

WE-E-BRE-09: Investigation of the Association Between Radiation-Induced Pain and Radiation Dose in Head and Neck Cancer Patients

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

Gay, H; Dyk, P; Mullen, D

Purpose: Patients with head and neck cancer who undergo radiotherapy often experience several undesirable side-effects, including xerostomia, trismus, and pain in the head and neck area, but little is know about the dose-volume predictors of such pain. We investigated the association between radiation dose and both throat and esophagus pain during radiotherapy. Methods: We analyzed 124 head and neck patients who received radiotherapy at the Washington University School of Medicine in Saint Louis. For these patients, weekly PROs were recorded, including 16 pain and anatomical location questions. In addition, 17 observational symptoms were recorded. Patients were asked to describe theirmore » pain at each site according to a four-level scale: none (0), mild (1), moderate (2), and severe (3). We explored the association between throat pain and the mean dose received in oral cavity and between esophageal pain and the mean dose received in the esophagus. The severity of pain was determined by the difference between the baseline (week 1) pain score and the maximum pain score during treatment. The baseline pain score was defined as the first available pain score before receiving 10 Gy because radiotherapy pain originates later during treatment. Dose-volume metrics were extracted from treatment plans using CERR. To evaluate the correlation between pain and radiation dose, Spearman's correlation coefficient (Rs) was used. Results: The associations between throat pain and the mean dose to the oral cavity, and between esophagus pain and the mean dose to the esophagus, were both statistically significant, with Rs=0.320 (p=0.003) and Rs=0.424 (p<0.0001), respectively. Mean dose, for each structure, was a better predictor of pain than total integral dose. Conclusion: We demonstrated that pain during radiotherapy in head and neck patients highly correlates with the dose delivered. We will further investigate the association between other pain locations and relevant normal tissue dose characteristics.« less

Losartan/hydrochlorothiazide combination is safe and effective for morning hypertension in Very-Elderly patients.

PubMed

Uchiwa, Hiroki; Kai, Hisashi; Iwamoto, Yoshiko; Anegawa, Takahiro; Kajimoto, Hidemi; Fukuda, Kenji; Imaizumi, Tsutomu; Fukumoto, Yoshihiro

2018-01-01

Morning hypertension is an independent risk for cerebrovascular and cardiovascular events. Although the prevalence of morning hypertension increases with age, treatment of morning hypertension has not been established, particularly in Very-Elderly patients. We compared the safety and efficacy of a losartan/hydrochlorothiazide (HCTZ) combination in controlling morning hypertension between Very-Elderly (≥75 years) and Young/Elderly patients (<75 years). This study was a subanalysis of the Morning Hypertension and Angiotensin Receptor Blocker/Hydrochlorothiazide Combination Therapy study, in which patients with morning hypertension (≥135/85 mmHg) received a 50-mg losartan/12.5-mg HCTZ combination tablet (combination therapy) or 100-mg losartan (high-dose therapy) for 3 months. High adherence rates and few adverse effects were observed in Very-Elderly patients receiving combination (n = 32) and high-dose (n = 34) therapies and in Young/Elderly patients receiving combination (n = 69) and high-dose (n = 66) therapies. Baseline morning systolic BP (SBP) was similar in both age groups receiving either therapy. Morning SBP was reduced by 20.2 and 18.1 mmHg with combination therapy and by 7.1 and 9.1 mmHg with high-dose therapy in the Very-Elderly and Young/Elderly patients, respectively. Morning BP target (<135/85 mmHg) was achieved in 40.6% and 55.1% by combination therapy and in 14.7% and 24.2% by high-dose therapy in the Very-Elderly and Young/Elderly patients, respectively. Neither therapy changed renal function and serum potassium in Very-Elderly patients. In conclusion, the losartan/HCTZ combination was safe and effective in controlling morning hypertension in Very-Elderly as well as Young/Elderly patients. In addition, combination therapy was also superior to high-dose therapy for lowering morning SBP in Very-Elderly patients.

Comparative effects of vildagliptin and sitagliptin determined by continuous glucose monitoring in patients with type 2 diabetes mellitus.

PubMed

Koyanagawa, Naohide; Miyoshi, Hideaki; Ono, Kota; Nakamura, Akinobu; Cho, Kyu Yong; Yamamoto, Kohei; Takano, Yoshinari; Dan-Noura, Midori; Atsumi, Tatsuya

2016-08-31

The dipeptidyl peptidase-4 inhibitors vildagliptin and sitagliptin are effective in treating patients with type 2 diabetes mellitus. Patients receiving standard doses of sitagliptin plus insulin may require increased doses of sitagliptin or switching to vildagliptin to improve blood glucose control. This study compared the effects of increasing sitagliptin and switching to vildagliptin in type 2 diabetes patients receiving standard doses of sitagliptin plus insulin. This prospective, randomized, parallel-group comparison trial enrolled 33 type 2 diabetes patients receiving 50 mg sitagliptin once daily plus insulin. Seventeen patients were randomized to 50 mg vildagliptin twice daily, and 16 to 100 mg sitagliptin once daily, and evaluated by continuous glucose monitoring at baseline and after 8 weeks. The primary end-point was the change in mean amplitude of glycemic excursions (MAGE). MAGE decreased from baseline in both the vildagliptin (-13.4 ± 35.7 mg/dL) and sitagliptin (-8.4 ± 24.3 mg/dL) groups, but neither within- nor between-group changes were statistically significant. Similarly, the areas under the curve for blood glucose levels ≥180 mg/dL and <70 mg/dL tended to improve in both groups, but these differences were not statistically significant. In contrast, HbA1c was significantly reduced only in the vildagliptin group, from 7.1 ± 0.6% at baseline to 6.8 ± 0.6% at 8 weeks (p=0.006). Increasing sitagliptin dose and switching to vildagliptin had limited effects in improving MAGE in type 2 diabetic patients treated with standard doses of sitagliptin.

Estimated UV doses to psoriasis patients during climate therapy at Gran Canaria in March 2006

NASA Astrophysics Data System (ADS)

Nilsen, L. T. N.; Søyland, E.; Krogstad, A. L.

2008-01-01

Psoriasis is a chronic inflammatory disease involving about 2-3% of the Norwegian population. Sun exposure has a positive effect on most psoriasis lesions, but ultraviolet (UV) radiation also causes a direct DNA damage in the skin cells and comprises a carcinogenic potential. UV exposure on the skin causes a local as well as a systemic immune suppressive effect, but the relation between sun exposure and these biological effects is not well known. In March 2006 a study was carried out to investigate possible therapeutic outcome mechanisms in 20 psoriasis patients receiving climate therapy at Gran Canaria. This paper presents estimates of their individual skin UV-doses based on UV measurements and the patients' diaries with information on time spent in the sun. On the first day of exposure the patients received on average 5.1 Standard Erythema Doses (SED: median=4.0 SED, range 2.6-10.3 SED) estimated to the skin. During the 15 days study they received 165.8 SED (range 104.3-210.1 SED). The reduction in PASI score was 72.8% on average, but there was no obvious relation between the improvement and the UV dose. The UV doses were higher than those found from climate therapy studies at other locations. It seems beneficial to use more strict exposure schedules that consider the available UV irradiance, depending on time of the day, time of the year and weather conditions.

[The radiological situation before and after Chernobyl disaster].

PubMed

Leoniak, Marcin; Zonenberg, Anna; Zarzycki, Wiesław

2006-01-01

The nuclear reactor accident, which occurred on 26 April 1986 at Chernobyl, has been one of the greatest ecological disasters in human history. In our study we discussed the most recent data on the accident, and the natural and synthetic sources of radiation. According to the recent data, the air at Chernobyl had been contaminated with about 5300 PBq radionuclide activity (excluding rare gases), including 1760 PBq (131)I and 85 PBq (137)Cs. The highest radiation received by the liquidators (0.8-16 Gy), lower doses were received by the population which was evacuated or inhabited the contaminated areas (in which the level of (137)Cs activity deposited in the earth was 37 kBq/m(2)). In the European countries the highest mean radiation dose per year for the whole body in the first year after the accident was in Bulgaria (760 microSv), Austria (670 microSv) and Greece (590 microSv), while the lowest radiation dose was observed in Portugal (1.8 microSv) and Spain (4.2 microSv). In Poland the mean effective equivalent dose resulting from Chernobyl accident was 932 microSv and is close to the limited dose permitted in Poland, equalling 1 mSv/year. The highest radiation dose to thyroid was received by inhabitants of the states previously known as Bielskopodlaskie, Nowosadeckie and the north-east region of Poland. Lowest dose was received by inhabitants of the areas previously known as Slupski and Rzeszowski.

Course-, dose-, and stage-dependent toxic effects of prenatal dexamethasone exposure on fetal articular cartilage development.

PubMed

Chen, Ze; Zhao, Zhe; Li, Yunzepeng; Zhang, Xingyu; Li, Bin; Chen, Liaobin; Wang, Hui

2018-04-01

Dexamethasone, a synthetic long-acting glucocorticoid, is routinely used for treating mothers at risk for preterm delivery. However, intrauterine overexposure to glucocorticoids induces low birth weight and cartilage dysplasia in offspring. Also, the "critical window" and safe dose of this treatment are largely unknown. This study investigated the course-, dose-, and stage-dependent toxic effects and the possible mechanisms of prenatal dexamethasone exposure (PDE) on fetal development and articular cartilage development. Pregnant mice (C57BL/6) received subcutaneous injection of dexamethasone (0.8 mg/kg d) once on gestational day (GD) 15 or once a day from GD 15 to 17, or received various doses of dexamethasone (0, 0.2, 0.8, and 1.2 mg/kg d) on GD 15-17, or received dexamethasone (0.8 mg/kg d) at early stage (GD 12-14) or late stage of pregnancy (GD 15-17). Offspring's knee joints were harvested at birth for morphological analyses and detection of gene expression. Repeated PDE significantly suppressed fetal and articular cartilage development, which were characterized by decreased body weight and body length, coarse articular cartilage surfaces, and reduced gene and protein expression of Col2a1 and aggrecan. For those newborns treated with repeated PDE at different doses, the toxic effects on fetal and articular cartilage development were observed at doses of 0.8 and 1.2 mg/kg d, whereas no obvious toxic effects were observed at the dose of 0.2 mg/kg d. Moreover, PDE at 0.8 mg/kg d during the early embryonic stage induced stronger toxic effects on fetal and articular cartilage development, compared with PDE during the late embryonic stage. Detection of gene expression showed that the TGFβ signaling pathway in the articular cartilage was down-regulated after PDE. Taken together, PDE induces fetal developmental toxicity and articular cartilage developmental toxicity in a course-, dose-, and stage-dependent manner. Copyright © 2018 Elsevier B.V. All rights reserved.

76 FR 35672 - Revised Effectiveness Determination; Sunscreen Drug Products for Over-the-Counter Human Use

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-17

... are given ultraviolet (UV) radiation doses produced by a solar simulator (i.e., a UV lamp). Under... increasingly higher UV doses produced by the solar simulator. However, because the solar simulator can produce far higher UV radiation doses than a consumer would ever receive even under the most severe sun...

Radiation exposure of German aircraft crews under the impact of solar cycle 23 and airline business factors.

PubMed

Frasch, Gerhard; Kammerer, Lothar; Karofsky, Ralf; Schlosser, Andrea; Stegemann, Ralf

2014-12-01

The exposure of German aircraft crews to cosmic radiation varies both with solar activity and operational factors of airline business. Data come from the German central dose registry and cover monthly exposures of up to 37,000 German aircraft crewmembers that were under official monitoring. During the years 2004 to 2009 of solar cycle 23 (i.e., in the decreasing phase of solar activity), the annual doses of German aircraft crews increased by an average of 20%. Decreasing solar activity allows more galactic radiation to reach the atmosphere, increasing high-altitude doses. The rise results mainly from the less effective protection from the solar wind but also from airline business factors. Both cockpit and cabin personnel differ in age-dependent professional and social status. This status determines substantially the annual effective dose: younger cabin personnel and the elder pilots generally receive higher annual doses than their counterparts. They also receive larger increases in their annual dose when the solar activity decreases. The doses under this combined influence of solar activity and airline business factors result in a maximum of exposure for German aircrews for this solar cycle. With the increasing solar activity of the current solar cycle 24, the doses are expected to decrease again.

Potentiation of low dose ketamine effects by naltrexone: potential implications for the pharmacotherapy of alcoholism.

PubMed

Krystal, John H; Madonick, Steven; Perry, Edward; Gueorguieva, Ralitza; Brush, Laura; Wray, Yola; Belger, Aysenil; D'Souza, Deepak Cyril

2006-08-01

The interplay of opiate and NMDA glutamate receptors may contribute to psychosis, cognitive function, alcoholism, and substance dependence. Ketamine and ethanol block the NMDA glutamate receptor. The purpose of this randomized double-blind, placebo-controlled human laboratory study was to evaluate whether the interactive effects of drugs acting at opiate and NMDA glutamate receptors might partially explain the efficacy of naltrexone for the treatment of alcoholism, that is, whether naltrexone 25 mg pretreatment would modulate ketamine effects in healthy human subjects. Two groups of healthy subjects were studied. An initial group (n=31) received a perception-altering subanesthetic dose of ketamine (bolus of 0.23 mg/kg over 1 min followed by a 60-min infusion of 0.58 mg/kg or saline bolus and infusion). A second group (n=24) completed the same testing procedures, but received a subperceptual ketamine dose (bolus 0.081 mg/kg over 10 min followed by an infusion of 0.4 mg/kg/h). Ketamine produced positive symptoms, negative symptoms, emotional discomfort, and cognitive effects as measured by the Positive and Negative Syndrome Scale (PANSS) in a dose-related fashion. The lower ketamine dose produced subjective effects similar to two standard ethanol drinks, whereas the higher ketamine dose produced effects similar to five standard drinks. Although naltrexone produced no significant behavioral effects, it significantly magnified the increase in the total PANSS score produced by the lower subperceptual dose of ketamine, but not the higher perception-altering dose of ketamine. These data suggest that the interplay of opiate receptor antagonism and NMDA receptor antagonism may be relevant to the protective effects of naltrexone on alcohol consumption via potentiation of dysphoric effects associated with the NMDA receptor antagonist effects of ethanol. However, these data suggest that at levels of NMDA receptor antagonism associated with heavy drinking, this protective effect of naltrexone on drinking is no longer present.

Contribution of internal exposures to the radiological consequences of the Chernobyl accident.

PubMed

Balonov, M I; Anspaugh, L R; Bouville, A; Likhtarev, I A

2007-01-01

The main pathways leading to exposure of members of the general public due to the Chernobyl accident were external exposure from radionuclides deposited on the ground and ingestion of contaminated terrestrial food products. The collective dose to the thyroid was nearly 1.5 million man Gy in Belarus, Russia and Ukraine with nearly half received by children and adolescents. The collective effective dose received in 1986-2005 by approximately five million residents living in the affected areas of the three countries was approximately 50,000 man Sv with approximately 40% from ingestion. That contribution might have been larger if countermeasures had not been applied. The main radionuclide contributing to both external and internal effective dose is 137Cs with smaller contributions of 134Cs and 90Sr and negligible contribution of transuranic elements. The major demonstrated radiation-caused health effect of the Chernobyl accident has been an elevated incidence of thyroid cancer in children.

Dosimetric Evaluation of Intensity Modulated Radiotherapy and 4-Field 3-D Conformal Radiotherapy in Prostate Cancer Treatment

PubMed Central

Uysal, Bora; Beyzadeoğlu, Murat; Sager, Ömer; Dinçoğlan, Ferrat; Demiral, Selçuk; Gamsız, Hakan; Sürenkök, Serdar; Oysul, Kaan

2013-01-01

Objective: The purpose of this dosimetric study is the targeted dose homogeneity and critical organ dose comparison of 7-field Intensity Modulated Radiotherapy (IMRT) and 3-D 4-field conformal radiotherapy. Study Design: Cross sectional study. Material and Methods: Twenty patients with low and moderate risk prostate cancer treated at Gülhane Military Medical School Radiation Oncology Department between January 2009 and December 2009 are included in this study. Two seperate dosimetric plans both for 7-field IMRT and 3D-CRT have been generated for each patient to comparatively evaluate the dosimetric status of both techniques and all the patients received 7-field IMRT. Results: Dose-comparative evaluation of two techniques revealed the superiority of IMRT technique with statistically significantly lower femoral head doses along with reduced critical organ dose-volume parameters of bladder V60 (the volume receiving 60 Gy) and rectal V40 (the volume receiving 40 Gy) and V60. Conclusion: It can be concluded that IMRT is an effective definitive management tool for prostate cancer with improved critical organ sparing and excellent dose homogenization in target organs of prostate and seminal vesicles. PMID:25207069

Intravenous Nicotine Self-Administration in Smokers: Dose-Response Function and Sex Differences.

PubMed

Jensen, Kevin P; DeVito, Elise E; Valentine, Gerald; Gueorguieva, Ralitza; Sofuoglu, Mehmet

2016-07-01

Sex differences in the sensitivity to nicotine may influence vulnerability to tobacco dependence. The goal of this study was to investigate the dose-response function for the reinforcing and subjective effects of intravenous nicotine in male and female smokers. Tobacco-dependent subjects (12 male and 14 female) participated in four experimental sessions in which they received sample infusions of saline and nicotine (0.1, 0.2, 0.3, or 0.4 mg doses) in a randomized double-blind crossover design. During each session, subjects first received the sample infusions, and heart rate (HR), blood pressure, and subjective stimulatory, pleasurable and aversive responses were monitored. Immediately following the sample infusions, subjects self-administered either nicotine or saline in six double-blind forced-choice trials. A sex by dose interaction was observed in the nicotine choice paradigm. Nicotine self-administration rate was negatively correlated with nicotine dose in males (males displayed choice preference for low doses of nicotine over high doses of nicotine), but no significant relationship between dose and choice preference was evident in females. Relative to placebo, sample doses of nicotine increased heart rate and blood pressure, and induced stimulatory, pleasurable, and aversive subjective effects. Diastolic blood pressure increased dose dependently in males, but not in females. These findings, which demonstrate sex differences in nicotine self-administration for doses that are near to the reinforcement threshold, suggest that male and female smokers may respond differently to the changes in nicotine doses available for self-administration.

Effects of radiation exposure from cardiac imaging: how good are the data?

PubMed

Einstein, Andrew J

2012-02-07

Concerns about medical exposure to ionizing radiation have become heightened in recent years as a result of rapid growth in procedure volumes and the high radiation doses incurred from some procedures. This paper summarizes the evidence base undergirding concerns about radiation exposure in cardiac imaging. After classifying radiation effects, explaining terminology used to quantify the radiation received by patients, and describing typical doses from cardiac imaging procedures, this paper will address the major epidemiological studies having bearing on radiation effects at doses comparable to those received by patients undergoing cardiac imaging. These include studies of atomic bomb survivors, nuclear industry workers, and children exposed in utero to x-rays, all of which have evidenced increased cancer risks at low doses. Additional higher-dose epidemiological studies of cohorts exposed to radiation in the context of medical treatment are described and found to be generally compatible with these cardiac dose-level studies, albeit with exceptions. Using risk projection models developed by the U.S. National Academies that incorporate these data and reflect several evidence-based assumptions, cancer risk from cardiac imaging can be estimated and compared with the benefits from imaging. Several ongoing epidemiological studies will provide better understanding of radiation-associated cancer risks. Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Assessment of dose and DNA damages in individuals exposed to low dose and low dose rate ionizing radiations during computed tomography imaging.

PubMed

Kanagaraj, Karthik; Abdul Syed Basheerudeen, Safa; Tamizh Selvan, G; Jose, M T; Ozhimuthu, Annalakshmi; Panneer Selvam, S; Pattan, Sudha; Perumal, Venkatachalam

2015-08-01

Computed tomography (CT) is a frequently used imaging modality that contributes to a tenfold increase in radiation exposure to the public when compared to other medical imaging modalities. The use of radiation for therapeutic need is always rationalized on the basis of risk versus benefit thereby increasing concerns on the dose received by patients undergoing CT imaging. Therefore, it was of interest to us to investigate the effects of low dose and low dose-rate X-irradiation in patients who underwent CT imaging by recording the doses received by the eye, forehead and thyroid, and to study the levels of damages in the lymphocytes in vivo. Lithium manganese borate doped with terbium (LMB:Tb) thermo luminescence dosimeters (TLD) were used to record the doses in the patient's (n = 27) eye, forehead, and thyroid and compared with the dose length product (DLP) values. The in vivo DNA damages measured were compared before and after CT imaging using chromosomal aberration (CA) and micronucleus (MN) assays. The overall measured organ dose ranged between 2 ± 0.29 and 520 ± 41.63 mGy for the eye, 0.84 ± 0.29 and 210 ± 20.50 mGy for the forehead, and 1.79 ± 0.43 and 185 ± 0.70 mGy for the thyroid. The in vivo damages measured from the blood lymphocytes of the subjects showed an extremely significant (p < 0.0001) increase in CA frequency and significant (p < 0.001) increase in MN frequency after exposure, compared to before exposure. The results suggest that CT imaging delivers a considerable amount of radiation dose to the eye, forehead, and thyroid, and the observed increase in the CA and MN frequencies show low dose radiation effects calling for protective regulatory measures to increase patient's safety. This study is the first attempt to indicate the trend of doses received by the patient's eye, forehead and thyroid and measured directly in contrast to earlier values obtained by extrapolation from phantoms, and to assess the in vivo low dose effects in an Indian patient population undergoing CT procedures. Copyright © 2015 Elsevier B.V. All rights reserved.

Reduced-dose direct oral anticoagulants in the extended treatment of venous thromboembolism: a systematic review and meta-analysis.

PubMed

Vasanthamohan, L; Boonyawat, K; Chai-Adisaksopha, C; Crowther, M

2018-05-17

Essentials In venous thromboembolism (VTE), benefits of extended treatment are balanced by bleeding risks. This is a meta-analysis of reduced-dose direct oral anticoagulants (DOACs) in extended treatment. Reduced-dose DOACs are as effective as full anticoagulation with bleeding risks similar to placebo. Reduced-dose DOACs are an attractive option for patients in the extended phase of VTE treatment. Background Extended-duration anticoagulation is beneficial for preventing recurrent venous thromboembolism (VTE). Reduced-dose direct oral anticoagulants (DOACs) may be preferable if they preserve efficacy and cause less bleeding. We conducted a systematic review and meta-analysis of trials comparing reduced-dose DOACs with full-dose DOACs and aspirin or placebo in the extended phase of VTE treatment. Methods A literature search was conducted by use of the MEDLINE, EMBASE and CINAHL databases, supplemented by hand-searching. One thousand three hundred and ninety-nine titles were screened, with data from accepted studies being extracted by two independent reviewers. Major outcomes analyzed included recurrent VTE and major and clinically relevant non-major bleeding events, presented as risk ratios (RRs) and 95% confidence intervals (CI). Results Two trials met the prespecified inclusion criteria. Data from 5847 patients were analyzed for efficacy outcomes, and from 5842 patients for safety outcomes. Reduced-dose DOACs were as effective as full-dose treatment in preventing recurrent VTE at 1 year (RR 1.12 [95% CI 0.67-1.87]), and more effective than aspirin or placebo (RR 0.26 [95% CI 0.14-0.46]). Rates of major or clinically relevant non-major bleeding events were similar between patients receiving reduced-dose DOACs and and those receiving aspirin or placebo (RR 1.19 [95% CI 0.81-1.77]). There was a trend towards less bleeding when reduced-dose and full-dose DOACs were compared (RR 0.74 [95% CI 0.52-1.05]). Conclusions Extended-duration treatment of VTE with reduced-dose DOACs may be as efficacious as full-dose treatment, with rates of major bleeding being similar to those in patients receiving treatment with aspirin or placebo, but further long-term studies are needed. © 2018 International Society on Thrombosis and Haemostasis.

Captopril in hypertension after renal transplantation.

PubMed Central

Chan, M. K.; Sweny, P.; El Nahas, A. M.; Farrington, K.; Fernando, O. N.; Moorhead, J. F.

1984-01-01

Eight hypertensive renal allograft recipients who had received captopril are presented. Captopril in a maximal daily dose of 250 mg enabled the withdrawal of large doses of beta-blocking agents and vasodilators. Blood pressure was satisfactorily controlled in all except one. No adverse side effects were observed other than the 'first dose' effect which resulted in transient anuria in one patient. Captopril appears to be a useful agent in the management of severe hypertension after renal transplantation. PMID:6369287

A Retrospective Study Evaluating the Effect of Low Doses of Perineural Dexamethasone on Ropivacaine Brachial Plexus Peripheral Nerve Block Analgesic Duration.

PubMed

Schnepper, Gregory D; Kightlinger, Benjamin I; Jiang, Yunyun; Wolf, Bethany J; Bolin, Eric D; Wilson, Sylvia H

2017-09-23

Examination of the effectiveness of perineural dexamethasone administered in very low and low doses on ropivacaine brachial plexus block duration. Retrospective evaluation of brachial plexus block duration in a large cohort of patients receiving peripheral nerve blocks with and without perineural dexamethasone in a prospectively collected quality assurance database. A single academic medical center. A total of 1,942 brachial plexus blocks placed over a 16-month period were reviewed. Demographics, nerve block location, and perineural dexamethasone utilization and dose were examined in relation to block duration. Perineural dexamethasone was examined as none (0 mg), very low dose (2 mg or less), and low dose (greater than 2 mg to 4 mg). Continuous catheter techniques, local anesthetics other than ropivacaine, and block locations with fewer than 15 subjects were excluded. Associations between block duration and predictors of interest were examined using multivariable regression models. A subgroup analysis of the impact of receiving dexamethasone on block duration within each block type was also conducted using a univariate linear regression approach. A total of 1,027 subjects were evaluated. More than 90% of brachial plexus blocks contained perineural dexamethasone (≤4 mg), with a median dose of 2 mg. Increased block duration was associated with receiving any dose of perineural dexamethasone (P < 0.0001), female gender (P = 0.022), increased age (P = 0.048), and increased local anesthetic dose (P = 0.01). In a multivariable model, block duration did not differ with very low- or low-dose perineural dexamethasone after controlling for other factors (P = 0.420). Perineural dexamethasone prolonged block duration compared with ropivacaine alone; however, duration was not greater with low-dose compared with very low-dose perineural dexamethasone. © 2017 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

A double-blind, placebo-controlled, randomised, parallel-group, dose-escalating, repeat dose study in healthy volunteers to evaluate the safety, tolerability, pharmacodynamic effects and pharmacokinetics of the once daily rectal application of NRL001 suppositories for 14 days.

PubMed

Bell, D; Duffin, A; Jacobs, A; Pediconi, C; Gruss, H J

2014-03-01

The 1R,2S stereoisomer of methoxamine hydrochloride, NRL001, is a highly selective α1-adrenoceptor agonist being developed for the local treatment of non-structural faecal incontinence caused by weak internal anal sphincter tone. This study investigated the steady state pharmacokinetics (PK) and safety of 2 g rectal suppositories containing NRL001 in different strengths (7.5, 10, 12.5 or 15 mg). Healthy volunteers aged 18-45 years received 14 daily doses of NRL001 2 g suppositories or matching placebo. In each dose group nine participants received NRL001 and three received placebo. Blood samples to determine NRL001 concentrations were taken on Days 1, 7 and 14. Cardiovascular parameters were collected via electrocardiograms, Holter monitoring (three lead Holter monitor) and vital signs. Forty-eight volunteers were enrolled; 43 completed the study and were included in the PK analysis population. AUC and Cmax broadly increased with increasing dose, Tmax generally occurred between 4.0 and 5.0 h. Although the data did not appear strongly dose proportional, dose proportionality analysis did not provide evidence against dose proportionality as the log(dose) coefficients were not significantly < 1. NRL001 did not accumulate over time for any dose. Increasing NRL001 concentrations were related to changes in vital sign variables, most notably decreased heart rate. The most commonly reported adverse events (AEs) in the active treatment groups were paraesthesia and piloerection. Treatment with NRL001 was generally well tolerated over 14 days once daily dosing and plasma NRL001 did not accumulate over time. Treatment was associated with changes in vital sign variables, most notably decreased heart rate. AEs commonly reported with NRL001 treatment were events indicative of a systemic α-adrenergic effect. Colorectal Disease © 2014 The Association of Coloproctology of Great Britain and Ireland.

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.

Feasibility and Efficacy of Intra‐Arterial Administration of Mesenchymal Stem Cells in an Animal Model of Double Toxin‐Induced Multiple System Atrophy

PubMed Central

Na Kim, Ha; Yeol Kim, Dong; Hee Oh, Se; Sook Kim, Hyung; Suk Kim, Kyung

2017-01-01

Abstract Multiple system atrophy (MSA) is a sporadic neurodegenerative disease of the central and autonomic nervous system. Because no drug treatment consistently benefits MSA patients, neuroprotective strategy using mesenchymal stem cells (MSCs) has a lot of concern for the management of MSA. In this study, we investigated the safety and efficacy of intra‐arterial administration of MSCs via internal carotid artery (ICA) in an animal model of MSA. The study was composed of feasibility test using a ×10 and ×50 of a standard dose of MSCs (4 × 107 MSCs) and efficacy test using a ×0.2, ×2, and ×20 of the standard dose. An ultrasonic flow meter and magnetic resonance imaging (MRI) showed that no cerebral ischemic lesions with patent ICA blood flow was were observed in animals receiving a ×10 of the standard dose of MSCs. However, no MSA animals receiving a ×50 of the standard dose survived. In efficacy test, animals injected with a ×2 of the standard dose increased nigrostriatal neuronal survival relative to a ×0.2 or ×20 of the standard dose. MSA animals receiving MSCs at ×0.2 and ×2 concentrations of the standard dose exhibited a significant reduction in rotation behavior relative to ×20 of the standard dose of MSCs. Cerebral ischemic lesions on MRI were only observed in MSA animals receiving a ×20 of the standard dose. The present study revealed that if their concentration is appropriate, intra‐arterial injection of MSCs is safe and exerts a neuroprotective effect on striatal and nigral neurons with a coincidental improvement in motor behavior. Stem Cells Translational Medicine 2017;6:1424–1433 PMID:28296268

Radiation optic neuropathy after megavoltage external-beam irradiation: Analysis of time-dose factors

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

Parsons, J.T.; Bova, F.J.; Million, R.R.

1994-11-15

To investigate the risk of radiation-induced optic neuropathy according to total radiotherapy dose and fraction size, based on both retrospective and prospectively collected data. Between October 1964 and May 1989, 215 optic nerves in 131 patients received fractionated external-beam irradiation during the treatment of primary extracranial head and neck tumors. All patients had a minimum of 3 years of ophthalmologic follow-up (range, 3 to 21 years). The clinical end point was visual acuity of 20/100 or worse as a result of optic nerve injury. Anterior ischemic optic neuropathy developed in five nerves (at mean and median times of 32 andmore » 30 months, respectively, and a range of 2-4 years). Retrobulbar optic neuropathy developed in 12 nerves (at mean and median times of 47 and 28 months, respectively, and a range of 1-14 years). No injuries were observed in 106 optic nerves that received a total dose of <59 Gy. Among nerves that received doses of {ge} 60 Gy, the dose per fraction was more important than the total dose in producing optic neuropathy. The 15-year actuarial risk of optic compared with 47% when given in fraction sizes {ge}1.9 Gy. The data also suggest an increased risk of optic nerve injury with increasing age. As there is no effective treatment of radiation-induced optic neuropathy, efforts should be directed at its prevention by minimizing the total dose, paying attention to the dose per fraction to the nerve, and using reduced field techniques where appropriate to limit the volume of tissues that receive high-dose irradiation. 32 refs., 5 figs., 5 tabs.« less

Reconstruction of paediatric organ doses from axial CT scans performed in the 1990s - range of doses as input to uncertainty estimates.

PubMed

Olerud, Hilde M; Toft, Benthe; Flatabø, Silje; Jahnen, Andreas; Lee, Choonsik; Thierry-Chef, Isabelle

2016-09-01

To assess the range of doses in paediatric CT scans conducted in the 1990s in Norway as input to an international epidemiology study: the EPI-CT study, http://epi-ct.iarc.fr/ . National Cancer Institute dosimetry system for Computed Tomography (NCICT) program based on pre-calculated organ dose conversion coefficients was used to convert CT Dose Index to organ doses in paediatric CT in the 1990s. Protocols reported from local hospitals in a previous Norwegian CT survey were used as input, presuming these were used without optimization for paediatric patients. Large variations in doses between different scanner models and local scan parameter settings are demonstrated. Small children will receive a factor of 2-3 times higher doses compared with adults if the protocols are not optimized for them. For common CT examinations, the doses to the active bone marrow, breast tissue and brain may have exceeded 30 mGy, 60 mGy and 100 mGy respectively, for the youngest children in the 1990s. The doses children received from non-optimised CT examinations during the 1990s are of such magnitude that they may provide statistically significant effects in the EPI-CT study, but probably do not reflect current practice. • Some organ doses from paediatric CT in the 1990s may have exceeded 100 mGy. • Small children may have received doses 2-3 times higher compared with adults. • Different scanner models varied by a factor of 2-3 in dose to patients. • Different local scan parameter settings gave dose variations of a factor 2-3. • Modern CTs and age-adjusted protocols will give much lower paediatric doses.

Cost-effectiveness and public health impact of alternative influenza vaccination strategies in high-risk adults.

PubMed

Raviotta, Jonathan M; Smith, Kenneth J; DePasse, Jay; Brown, Shawn T; Shim, Eunha; Nowalk, Mary Patricia; Wateska, Angela; France, Glenson S; Zimmerman, Richard K

2017-10-09

High-dose trivalent inactivated influenza vaccine (HD-IIV3) or recombinant trivalent influenza vaccine (RIV) may increase influenza vaccine effectiveness (VE) in adults with conditions that place them at high risk for influenza complications. This analysis models the public health impact and cost-effectiveness (CE) of these vaccines for 50-64year-olds. Markov model CE analysis compared 5 strategies in 50-64year-olds: no vaccination; only standard-dose IIV3 offered (SD-IIV3 only), only quadrivalent influenza vaccine offered (SD-IIV4 only); high-risk patients receiving HD-IIV3, others receiving SD-IIV3 (HD-IIV3 & SD-IIV3); and high-risk patients receiving HD-IIV3, others receiving SD-IIV4 (HD-IIV3 & SD-IIV4). In a secondary analysis, RIV replaced HD-IIV3. Parameters were obtained from U.S. databases, the medical literature and extrapolations from VE estimates. Effectiveness was measured as 3%/year discounted quality adjusted life year (QALY) losses avoided. The least expensive strategy was SD-IIV3 only, with total costs of $99.84/person. The SD-IIV4 only strategy cost an additional $0.91/person, or $37,700/QALY gained. The HD-IIV3 & SD-IIV4 strategy cost $1.06 more than SD-IIV4 only, or $71,500/QALY gained. No vaccination and HD-IIV3 & SD-IIV3 strategies were dominated. Results were sensitive to influenza incidence, vaccine cost, standard-dose VE in the entire population and high-dose VE in high-risk patients. The CE of RIV for high-risk patients was dependent on as yet unknown parameter values. Based on available data, using high-dose influenza vaccine or RIV in middle-aged, high-risk patients may be an economically favorable vaccination strategy with public health benefits. Clinical trials of these vaccines in this population may be warranted. Copyright © 2017 Elsevier Ltd. All rights reserved.

Threshold-type dose response for induction of neoplastic transformation by 1 GeV/nucleon iron ions.

PubMed

Elmore, E; Lao, X-Y; Kapadia, R; Redpath, J L

2009-06-01

Neoplastic transformation of HeLa x skin fibroblast human hybrid cells by doses of 1 GeV/nucleon iron ions in the range 1 cGy to 1 Gy to exposed cultures has been examined. The data indicate a threshold-type dose-response curve with no increase in transformation frequency until doses above 20 cGy. At doses <10 cGy, not all exposed cells receive a direct traversal of an iron-ion track core, but all exposed cells receive up to several mGy of low-LET radiation associated with the delta-ray penumbra. It is proposed that the threshold-type response seen is a consequence of an adaptive response associated with the delta-ray exposure. For comparison purposes, the dose response for (137)Cs gamma rays over the same dose range was examined using the same experimental procedure. As we have shown previously, the dose response for (137)Cs gamma radiation was J-shaped. The iron ions were 1.5 to 1.7 times more biologically effective than the gamma radiation over the dose range examined.

Neuroprotection of dietary virgin olive oil on brain lipidomics during stroke.

PubMed

Rabiei, Zahra; Bigdeli, Mohammad Reza; Rasoulian, Bahram

2013-08-01

Recent studies suggest that dietary virgin olive oil reduces hypoxia-reoxygenation injury in rat brain. This study investigated the effect of pretreatment with different doses of dietary virgin olive oil on brain lipidomics during stroke. In this experimental trial, 60 male Wistar rats were studied in 5 groups of 12 each. The control group received distilled water while three treatment groups received oral virgin olive oil for 30 days (0.25, 0.5 and 0.75 ml/kg/day respectively). Also the sham group received distilled water. Two hours after the last dose, the animals divided two groups. The middle cerebral artery occlusion (MCAO) group subjected to 60 min of middle cerebral artery occlusion (MCAO) and intact groups for brain lipids analysis. The brain phosphatidylcholine, cholesterol ester and cholesterol levels increased significantly in doses of 0.5 and 0.75 ml/kg/day compare with control group. VOO in all three doses increased the brain triglyceride levels. VOO with dose 0.75 ml/kg increased the brain cerebroside levels when compared with control group. VOO pretreatment for 30 days decreased the brain ceramide levels in doses of 0.5 and 0.75 ml/kg/day (p<0.05). Although further studies are needed, the results indicate that the VOO pretreatment improved the injury of ischemia and reperfusion and might be beneficial in patients with these disorders and seems to partly exert their effects via change in brain lipid levels in rat.

[Optimization of ventricular function during anesthesia induction by administering crystalloids and colloids to heart surgery patients].

PubMed

Ballesteros, M; Boldt, J; Zickmann, B; Knothe, C; Hempelmann, G

1995-01-01

To describe the changes in cardiac function after administration of three different solutions infused after anesthetic induction. Thirty-six patients scheduled for elective aortocoronary bypass surgery were randomly distributed into three groups. Over a period of 25 min after anesthetic induction, 12 received 10 ml/kg of Ringer solution (low dose crystalloid group), 12 received 20 ml/kg of Ringer solution (high dose crystalloid group), and 12 received 10 ml/kg of Ringer solution with 10 ml/kg of hydroxi-ethyl-almidon solution 450,000 D, 0.7 substitution grade (group C-HEA). Minute volume, systemic and pulmonary pressures, osmolality of blood and urine, and plasma and urine sodium concentrations were measured before and after infusion of the assigned liquid. In spite of the volume infused, low dose crystalloid group showed a high incidence of oliguria, increased urinary osmolality and decreased sodium in urine. Cardiac and systolic indices and left ventricular work load remained stable after infusion of the assigned liquid in low and high dose crystalloid groups, whereas they increased significantly ion group C-HEA (+23%, +16% and +20%). Administration of restricted doses of crystalloids after anesthetic induction favors the retention of water and sodium. Higher doses of crystalloids weaken this effect. However, neither of these two regimens leads to a more effective cardiac work load. A combination of crystalloids and colloids administered immediately after anesthetic induction temporarily improves cardiac performance during surgery.

Primary Prevention of Cervical Cancer: American Society of Clinical Oncology Resource-Stratified Guideline

PubMed Central

Arrossi, Silvina; Temin, Sarah; Garland, Suzanne; Eckert, Linda O’Neal; Bhatla, Neerja; Castellsagué, Xavier; Alkaff, Sharifa Ezat; Felder, Tamika; Hammouda, Doudja; Konno, Ryo; Lopes, Gilberto; Mugisha, Emmanuel; Murillo, Rául; Scarinci, Isabel C.; Stanley, Margaret; Tsu, Vivien; Wheeler, Cosette M.; Adewole, Isaac Folorunso; de Sanjosé, Silvia

2017-01-01

Purpose To provide resource-stratified (four tiers), evidence-based recommendations on the primary prevention of cervical cancer globally. Methods The American Society of Clinical Oncology convened a multidisciplinary, multinational panel of oncology, obstetrics/gynecology, public health, cancer control, epidemiology/biostatistics, health economics, behavioral/implementation science, and patient advocacy experts. The Expert Panel reviewed existing guidelines and conducted a modified ADAPTE process and a formal consensus-based process with additional experts (consensus ratings group) for one round of formal ratings. Results Existing sets of guidelines from five guideline developers were identified and reviewed; adapted recommendations formed the evidence base. Five systematic reviews, along with cost-effectiveness analyses, provided evidence to inform the formal consensus process, which resulted in agreement of ≥ 75%. Recommendations In all resource settings, two doses of human papillomavirus vaccine are recommended for girls age 9 to 14 years, with an interval of at least 6 months and possibly up to 12 to 15 months. Individuals with HIV positivity should receive three doses. Maximal and enhanced settings: if girls are age ≥ 15 years and received their first dose before age 15 years, they may complete the series; if no doses were received before age 15 years, three doses should be administered; in both scenarios, vaccination may be through age 26 years. Limited and basic settings: if sufficient resources remain after vaccinating girls age 9 to 14 years, girls who received one dose may receive additional doses between age 15 and 26 years. Maximal, enhanced, and limited settings: if ≥ 50% coverage in the priority female target population, sufficient resources, and cost effectiveness, boys may be vaccinated to prevent other noncervical human papillomavirus–related cancers and diseases. Basic settings: vaccinating boys is not recommended. It is the view of the American Society of Clinical Oncology that health care providers and health care system decision makers should be guided by the recommendations for the highest stratum of resources available. The guideline is intended to complement but not replace local guidelines. PMID:29094100

Conditioned pharmacotherapeutic effects: a preliminary study.

PubMed

Ader, Robert; Mercurio, Mary Gail; Walton, James; James, Deborra; Davis, Michael; Ojha, Valerie; Kimball, Alexa Boer; Fiorentino, David

2010-02-01

To test the hypothesize that psoriasis patients treated under a partial schedule of pharmacologic (corticosteroid) reinforcement would show less severe symptoms and relapse than those given the same amount of drug under standard conditions. Behavioral conditioning as an inherent component of many pharmacotherapeutic protocols has never been examined. A double-blind, simple randomization intervention was conducted with 46 patients from California and New York. Initially, lesions were treated with 0.1% acetonide triamcinolone under standard treatment conditions. Thereafter, a Standard Therapy group continued on continuous reinforcement (active drug every treatment) with 100% of the initial dose; Partial Reinforcement patients received a full dose 25% to 50% of the time and placebo medication other times; Dose Control patients received continuous reinforcement with 25% to 50% of the initial dose. Severity of disease scores in California neither supported nor refuted the hypothesis. In New York, where there was no difference between Partial Reinforcement and Dose Control groups at baseline, partial reinforcement effected a greater reduction in lesion severity than Dose Control conditions and did not differ from Standard Therapy patients receiving two to four times more drug. For the entire population, the frequency of relapse under partial reinforcement (26.7%) was lower than in Dose Control patients (61.5%) and did not differ from full-dose treatment (22.2%). A partial schedule of pharmacotherapeutic reinforcement could maintain psoriasis patients with a cumulative amount of corticosteroid that was relatively ineffective when administered under standard treatment conditions. Conceivably, corticosteroid administration only one quarter or half as frequently as currently prescribed is sufficient to treat psoriasis. We posit, however, that these preliminary observations implicate conditioning processes in-and for the design of-regimens of pharmacotherapy.

Evaluation of synergistic effects of resynchronization therapy and a β-blocker up-titration strategy based on a predefined patient-management program: the RESTORE study.

PubMed

Palmisano, Pietro; Ammendola, Ernesto; D'Onofrio, Antonio; Accogli, Michele; Calò, Leonardo; Ruocco, Antonio; Rapacciuolo, Antonio; Del Giorno, Giuseppe; Bianchi, Valter; Malacrida, Maurizio; Valsecchi, Sergio; Gronda, Edoardo

2015-01-01

Prior studies have suggested that a substantial number of eligible heart failure (HF) patients fail to receive β-blocker therapy, or receive it at a suboptimal dose. The aim of this study is to assess the benefit of a predefined management program designed for β-blocker up-titration, evaluating the synergistic effect of cardiac resynchronization therapy (CRT) and β-blockers in a HF population. The Resynchronization Therapy and β-Blocker Titration (RESTORE) study is a prospective, case-control, multicenter cohort study designed to test the hypothesis that a β-blocker up-titration strategy based on a predefined management program maximizes the beneficial effect of CRT, increasing the number of patients reaching the target dose of β-blockers and improving their clinical outcome. All study patients receive an implantable defibrillator for CRT delivery in accordance with current guidelines. Enrollments started in December 2011 and are scheduled to end in December 2014. Approximately 250 consecutive patients will be prospectively enrolled in 6 Italian centers and followed up for 24 months after implantation. The primary endpoint is to demonstrate that CRT may allow titration of β-blockers until the optimal dose, or at least to the effective dose, in patients with HF. This study might provide important information about the benefit of a predefined management program for β-blocker up-titration in patients receiving CRT. Moreover, assessment of health-care utilization and the consumption of resources will allow estimating the potential utility of remote monitoring by means of an automated telemedicine system in facilitating the titration of β-blockers in comparison with a standard in-hospital approach. © 2015 Wiley Periodicals, Inc.

Effects of ethanol on Pavlovian autoshaping in rats.

PubMed

Tomie, A; Cunha, C; Mosakowski, E M; Quartarolo, N M; Pohorecky, L A; Benjamin, D

1998-09-01

Approach responses, consummatory behaviors, and directed motor responses maintained by food reward resemble autoshaping CRs and are increased by lower doses of ethanol. This study evaluated the effects of presession i.p. injections of ethanol doses (0.00, 0.25, 0.50, 0.70. or 1.00 g/kg) on the acquisition of lever-press autoshaping CR performance in groups of male Long-Evans hooded rats. Paired groups received 15 daily sessions of Pavlovian autoshaping procedures, wherein the insertion of a retractable lever for 5 s (CS) was followed by the response-independent presentation of food (US). Ethanol facilitated lever-press autoshaping CR acquisition, as revealed by dose-related increases in the number of trials on which CRs were performed. The form of the dose-effect curve was inverted U-shaped with maximal responding induced during sessions 1-5 by the 0.70 g/kg ethanol dose. A similar dose-effect curve was observed during sessions 11-15, revealing that the effects of ethanol on autoshaping CR performance were relatively stable. A pseudoconditioning control group injected presession with 0.50 g/kg ethanol received training wherein the food US was presented randomly with respect to the lever CS. Few lever-presses were performed by the Random 0.50 group, indicating that ethanol's effects on autoshaping CR acquisition and maintenance observed in the Paired 0.50 group were not due to its psychomotor activating effects. A non-injection control group performed more autoshaping CRs than did the control group injected presession with saline, indicating that daily presession i.p. injections per se suppress autoshaping CR performance. Results reveal that low doses of ethanol enhance Pavlovian conditioning of directed motor and consummatory-like responding maintained by food reward. Implications for autoshaping accounts of impulsivity and drug abuse are considered.

Fixed-dose combination of sitagliptin and metformin for the treatment of type 2 diabetes

PubMed Central

Reynolds, Jonathan K

2009-01-01

JanumetTM, a fixed dose combination of sitagliptin/metformin HCL manufactured by Merck Pharmaceuticals, has received US Food and Drug Administration approval for treatment of patients with type 2 diabetes, that are inadequately controlled, either by sitagliptin or metformin alone or together in free-dose combination form. Sitagliptin, an inhibitor of the enzyme DDP-4, assists patients with type 2 diabetes mellitus to achieve glycemic control. It has been shown to be safe and effective at 100 mg daily doses. The effect of giving sitagliptin in combination with metformin is thought to have a complimentary and possibly additive effect on glycemic control. PMID:21437126

SU-E-T-284: Dose Plan Optimization When Using Hydrogel Prostate-Rectum Spacer: A Single Institution Experience

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

Rajecki, M; Thurber, A; Catalfamo, F

2015-06-15

Purpose: To describe rectal dose reduction achieved and techniques used to take advantage of the increased peri-rectal spacing provided by injected polyethylene-glycol. Methods: Thirty prostate cancer patents were 2:1 randomized during a clinical trial to evaluate the effectiveness of injected poly-ethylene glycol hydrogel (SpaceOAR System) in creating space between the prostate and the anterior rectal wall. All patients received a baseline CT/MR scan and baseline IMRT treatment plan. Patients were randomized to receive hydrogel injection (n=20) or Control (n=10), followed by another CT/MR scan and treatment plan (single arc VMAT, 6 MV photons, 79.2 Gy, 44 fractions). Additional optimization structuresmore » were employed to constrain the dose to the rectum; specifically an avoidance structure to limit V75 <15%, and a control structure to limit the maximum relative dose <105% in the interface region of the anterior rectal wall and the prostate planning target volume. Dose volumetric data was analyzed for rectal volumes receiving 60 through 80 Gy. Results: Rectal dose reduction was observed in all patients who received the hydrogel. Volumetric analysis indicates a median rectal volume and (reduction from baseline plan) following spacer application of 4.9% (8.9%) at V60Gy, 3.8% (8.1%) at V65Gy, 2.5% (7.2%) at V70Gy, 1.6% (5.8%) at V75Gy, and 0.5% (2.5%) at V80Gy. Conclusion: Relative to planning without spacers, rectal dose constraints of 5%, 4%, 3%, 2%, 1% for V60, V65, V70, V75, and V80, should be obtainable when peri-rectal spacers are used. The combined effect of increased peri-rectal space provided by the hydrogel, with strict optimization objectives, resulted in reduced dose to the rectum. To maximize benefit, strict optimization objectives and reduced rectal dose constraints should be employed when creating plans for patients with perirectal spacers. Clinical Trial for SpaceOAR product conducted by Augmenix,Inc. The research site was paid to be a participating site.« less

Protective effect of Ginkgo biloba L. leaf extract against glyphosate toxicity in Swiss albino mice.

PubMed

Cavuşoğlu, Kültiğin; Yapar, Kürşad; Oruç, Ertan; Yalçın, Emine

2011-10-01

The aim of the present study was to investigate the protective role of Ginkgo biloba L. leaf extract against the active agent of Roundup® herbicide (Monsanto, Creve Coeur, MO, USA). The Swiss Albino mice were randomly divided into six groups, with each group consisting of six animals: Group I (control) received an intraperitoneal injection of dimethyl sulfoxide (0.2 mL, once only), Group II received glyphosate at a dose of 50 mg/kg of body weight, Group III received G. biloba at a dose of 50 mg/kg of body weight, Group IV received G. biloba at a dose of 150 mg/kg of body weight, Group V received G. biloba (50 mg/kg of body weight) and glyphosate (50 mg/kg of body weight), and Group VI received G. biloba (150 mg/kg of body weight) and glyphosate (50 mg/kg of body weight). The single dose of glyphosate was given intraperitoneally. Animals from all the groups were sacrificed at the end of 72 hours, and their blood, bone marrow, and liver and kidney tissues were analyzed for aspartate aminotransferase (AST), alanine aminotransferase (ALT), blood urea nitrogen (BUN), creatinine, malondialdehyde (MDA), and glutathione (GSH) levels and the presence of micronucleus (MN), chromosomal aberrations (CAs), and pathological damages. The results indicated that serum AST, ALT, BUN, and creatinine levels significantly increased in mice treated with glyphosate alone compared with the other groups (P<.05). Besides, glyphosate-induced oxidative damage caused a significant decrease in GSH levels and a significant increase in MDA levels of the liver and kidney tissues. Moreover, glyphosate alone-treated mice presented higher frequencies of CAs, MNs, and abnormal metaphases compared with the controls (P<.05). These mice also displayed a lower mean mitotic index than the controls (P<.05). Treatment with G. biloba produced amelioration in indices of hepatotoxicity, nephrotoxicity, lipid peroxidation, and genotoxicity relative to Group II. Each dose of G. biloba provided significant protection against glyphosate-induced toxicity, and the strongest effect was observed at a dose of 150 mg/kg of body weight. Thus, in vivo results showed that G. biloba extract is a potent protector against glyphosate-induced toxicity, and its protective role is dose-dependent.

Ulipristal acetate versus leuprolide acetate for uterine fibroids.

PubMed

Donnez, Jacques; Tomaszewski, Janusz; Vázquez, Francisco; Bouchard, Philippe; Lemieszczuk, Boguslav; Baró, Francesco; Nouri, Kazem; Selvaggi, Luigi; Sodowski, Krzysztof; Bestel, Elke; Terrill, Paul; Osterloh, Ian; Loumaye, Ernest

2012-02-02

The efficacy and side-effect profile of ulipristal acetate as compared with those of leuprolide acetate for the treatment of symptomatic uterine fibroids before surgery are unclear. In this double-blind noninferiority trial, we randomly assigned 307 patients with symptomatic fibroids and excessive uterine bleeding to receive 3 months of daily therapy with oral ulipristal acetate (at a dose of either 5 mg or 10 mg) or once-monthly intramuscular injections of leuprolide acetate (at a dose of 3.75 mg). The primary outcome was the proportion of patients with controlled bleeding at week 13, with a prespecified noninferiority margin of -20%. Uterine bleeding was controlled in 90% of patients receiving 5 mg of ulipristal acetate, in 98% of those receiving 10 mg of ulipristal acetate, and in 89% of those receiving leuprolide acetate, for differences (as compared with leuprolide acetate) of 1.2 percentage points (95% confidence interval [CI], -9.3 to 11.8) for 5 mg of ulipristal acetate and 8.8 percentage points (95% CI, 0.4 to 18.3) for 10 mg of ulipristal acetate. Median times to amenorrhea were 7 days for patients receiving 5 mg of ulipristal acetate, 5 days for those receiving 10 mg of ulipristal acetate, and 21 days for those receiving leuprolide acetate. Moderate-to-severe hot flashes were reported for 11% of patients receiving 5 mg of ulipristal acetate, for 10% of those receiving 10 mg of ulipristal acetate, and for 40% of those receiving leuprolide acetate (P<0.001 for each dose of ulipristal acetate vs. leuprolide acetate). Both the 5-mg and 10-mg daily doses of ulipristal acetate were noninferior to once-monthly leuprolide acetate in controlling uterine bleeding and were significantly less likely to cause hot flashes. (Funded by PregLem; ClinicalTrials.gov number, NCT00740831.).

Randomized dose-ranging study of the safety and efficacy of WR 238605 (Tafenoquine) in the prevention of relapse of Plasmodium vivax malaria in Thailand.

PubMed

Walsh, D S; Looareesuwan, S; Wilairatana, P; Heppner, D G; Tang, D B; Brewer, T G; Chokejindachai, W; Viriyavejakul, P; Kyle, D E; Milhous, W K; Schuster, B G; Horton, J; Braitman, D J; Brueckner, R P

1999-10-01

WR 238605 is an 8-aminoquinoline developed for the radical cure of Plasmodium vivax. Forty-four P. vivax-infected patients were randomly assigned to 1 of 4 treatment regimens: 3 groups received a blood schizonticidal dose of chloroquine followed by WR 238605: group A (n=15) received 300 mg daily for 7 days; group B (n=11), 500 mg daily for 3 days, repeated 1 week after the initial dose; group C (n=9), 1 dose of 500 mg. A fourth group (D; n=9) received chloroquine only. Among patients who completed 2-6 months of follow-up (n=23), there was 1 relapse in group B (day 120) and 1 in group C (day 112). Among patients treated with chloroquine only, there were 4 relapses (days 40, 43, 49, and 84). WR 238605 was safe, well tolerated, and effective in preventing P. vivax relapse.

Effective and safe mannitol administration in patients undergoing supratentorial tumor surgery: A prospective, randomized and double blind study.

PubMed

Akcil, Eren Fatma; Dilmen, Ozlem Korkmaz; Karabulut, Esra Sultan; Koksal, Serdar Selcuk; Altindas, Fatis; Tunali, Yusuf

2017-08-01

Although osmotic diuresis with mannitol is commonly used to provide brain relaxation, there is no consensus regarding its optimal dose and combination with loop diuretics. The aim of the present study is to evaluate the effects of mannitol and combination of furosemide with different doses of mannitol on brain relaxation and on blood electrolytes, lactate level, urine output, fluid balance and blood osmolarity in patients undergoing supratentorial tumor surgery. This prospective, randomized, double blind, placebo-controlled study included 51 patients (ASA I-III) scheduled for elective supratentorial craniotomy. Different doses and combinations of diuretics were administered after the bone flap removal. The Group 1 received mannitol at 0.5gkg -1 and furosemide at 0.5mgkg -1 , the Group 2 received mannitol at 1gkg -1 and furosemide at 0.5mgkg -1 , and the Group 3 received mannitol at 0.5gkg -1 and placebo. The primary end-point of the present study is to evaluate the effects of mannitol and combination of furosemide with different doses of mannitol on brain relaxation and the secondary end-points are to evaluate their effects on blood electrolytes, lactate level, urine output, fluid balance and blood osmolarity. This study shows that mannitol alone (0.5gkg -1 ), and the combinations of furosemide (0.5mgkg -1 ) with different doses of mannitol (0.5gkg -1 -1gkg -1 ) provides adequate brain relaxation. However, administration of furosemide with low or high doses of mannitol may cause reduction in the sodium and chloride levels as well as rise in the lactate level. Moreover it may cause high urine output and negative intra-operative fluid balance. Administration of 0.5gkg -1 mannitol provides adequate brain relaxation without causing systemic side effects in patients undergoing supratentorial tumor surgery. This study is registered to clinical trials (Clinical Trials.gov identifier NCT02712476). Copyright © 2017 Elsevier B.V. All rights reserved.

Clinical tolerability of generic versus brand beta blockers in heart failure with reduced left ventricular ejection fraction: a retrospective cohort from heart failure clinic.

PubMed

Chanchai, Rattanachai; Kanjanavanit, Rungsrit; Leemasawat, Krit; Amarittakomol, Anong; Topaiboon, Paleerat; Phrommintikul, Arintaya

2018-01-01

Background: Beta-blockers have been shown to decrease mortality and morbidity in heart failure with reduced ejection fraction (HFrEF) patients. However, the side effects are also dose-related, leading to the underdosing. Cost constraint may be one of the limitations of appropriate beta-blocker use; this can be improved with generic drugs. However, the effects in real life practice have not been investigated. Methods and results: This study aimed to compare the efficacy and safety of generic and brand beta-blockers in HFrEF patients. We performed a retrospective cohort analysis in HFrEF patients who received either generic or brand beta-blocker in Chiang Mai Heart Failure Clinic. The primary endpoint was the proportion of patients who received at least 50% target dose of beta-blocker between generic and brand beta-blockers. Adverse events were secondary endpoints. 217 patients (119 and 98 patients received generic and brand beta-blocker, respectively) were enrolled. There were no differences between groups regarding age, gender, etiology of heart failure, New York Heart Association (NYHA) functional class, left ventricular ejection fraction (LVEF), rate of receiving angiotensin converting enzyme inhibitor (ACEI), angiotensin recepter blocker (ARB), or spironolactone. Patients receiving brand beta-blockers had lower resting heart rate at baseline (74.9 and 84.2 bpm, p  = .001). Rate of achieved 50% target dose and target daily dose did not differ between groups (40.4 versus 44.5% and 48.0 versus 55.0%, p  > .05, respectively). Rate of side effects was not different between groups (32.3 versus 29.5%, p  > .05) and the most common side effect was hypotension. Conclusion: This study demonstrated that beta-blocker tolerability was comparable between brand and generic formulations. Generic or brand beta-blockers should be prescribed to HFrEF patients who have no contraindications.

Clinical tolerability of generic versus brand beta blockers in heart failure with reduced left ventricular ejection fraction: a retrospective cohort from heart failure clinic

PubMed Central

Chanchai, Rattanachai; Kanjanavanit, Rungsrit; Leemasawat, Krit; Amarittakomol, Anong; Topaiboon, Paleerat; Phrommintikul, Arintaya

2018-01-01

Abstract Background: Beta-blockers have been shown to decrease mortality and morbidity in heart failure with reduced ejection fraction (HFrEF) patients. However, the side effects are also dose-related, leading to the underdosing. Cost constraint may be one of the limitations of appropriate beta-blocker use; this can be improved with generic drugs. However, the effects in real life practice have not been investigated. Methods and results: This study aimed to compare the efficacy and safety of generic and brand beta-blockers in HFrEF patients. We performed a retrospective cohort analysis in HFrEF patients who received either generic or brand beta-blocker in Chiang Mai Heart Failure Clinic. The primary endpoint was the proportion of patients who received at least 50% target dose of beta-blocker between generic and brand beta-blockers. Adverse events were secondary endpoints. 217 patients (119 and 98 patients received generic and brand beta-blocker, respectively) were enrolled. There were no differences between groups regarding age, gender, etiology of heart failure, New York Heart Association (NYHA) functional class, left ventricular ejection fraction (LVEF), rate of receiving angiotensin converting enzyme inhibitor (ACEI), angiotensin recepter blocker (ARB), or spironolactone. Patients receiving brand beta-blockers had lower resting heart rate at baseline (74.9 and 84.2 bpm, p = .001). Rate of achieved 50% target dose and target daily dose did not differ between groups (40.4 versus 44.5% and 48.0 versus 55.0%, p > .05, respectively). Rate of side effects was not different between groups (32.3 versus 29.5%, p > .05) and the most common side effect was hypotension. Conclusion: This study demonstrated that beta-blocker tolerability was comparable between brand and generic formulations. Generic or brand beta-blockers should be prescribed to HFrEF patients who have no contraindications. PMID:29379674

The anticancer estrogen receptor antagonist tamoxifen impairs consolidation of inhibitory avoidance memory through estrogen receptor alpha.

PubMed

Lichtenfels, Martina; Dornelles, Arethuza da Silva; Petry, Fernanda Dos Santos; Blank, Martina; de Farias, Caroline Brunetto; Roesler, Rafael; Schwartsmann, Gilberto

2017-11-01

Over two-thirds of women with breast cancer have positive tumors for hormone receptors, and these patients undergo treatment with endocrine therapy, tamoxifen being the most widely used agent. Despite being very effective in breast cancer treatment, tamoxifen is associated with side effects that include cognitive impairments. However, the specific aspects and mechanisms underlying these impairments remain to be characterized. Here, we have investigated the effects of tamoxifen and interaction with estrogen receptors on formation of memory for inhibitory avoidance conditioning in female rats. In the first experiment, Wistar female rats received a single oral dose of tamoxifen (1, 3, or 10 mg/kg) or saline by gavage immediately after training and were tested for memory consolidation 24 h after training. In the second experiment, rats received a single dose of 1 mg/kg tamoxifen or saline by gavage 3 h after training and were tested 24 h after training for memory consolidation. In the third experiment, rats received a subcutaneous injection with estrogen receptor α agonist or estrogen receptor beta agonist 30 min before the training. After training, rats received a single oral dose of tamoxifen 1 mg/kg or saline and were tested 24 h after training. In the fourth experiment, rats were trained and tested 24 h later. Immediately after test, rats received a single dose of tamoxifen (1 mg/kg) or saline by gavage and were given four additional daily test trials followed by a re-instatement. Tamoxifen at 1 mg/kg impaired memory consolidation when given immediately after training and the estrogen receptor alpha agonist improved the tamoxifen-related memory impairment. Moreover, tamoxifen impairs memory consolidation of the test. These findings indicate that estrogen receptors regulate the early phase of memory consolidation and the effects of tamoxifen on memory consolidation.

In vitro toxicity assay of cisplatin on mouse acute lymphoblastic leukaemia and spermatogonial stem cells.

PubMed

Shabani, R; Ashtari, K; Behnam, B; Izadyar, F; Asgari, H; Asghari Jafarabadi, M; Ashjari, M; Asadi, E; Koruji, M

2016-06-01

Testicular cancer is the most common cancer affecting men in reproductive age, and cisplatin is one of the major helpful chemotherapeutic agents for treatment of this cancer. In addition, exposure of testes cancer cells to cisplatin could potentially eliminate tumour cells from germ cells in patients. The aim of this study was to evaluate the effect of cisplatin on viability of mouse acute lymphoblastic leukaemia cell line (EL-4) and neonatal mouse spermatogonial cells in vitro. In this study, the isolated spermatogonial stem cells (SSC) and EL-4 were divided into six groups including control (received medium), sham (received DMSO in medium) and experimental groups which received different doses of cisplatin (0.5, 5, 10 and 15 μg ml(-1) ). Cells viability was evaluated with MTT assay. The identity of the cultured cells was confirmed by the expression of specific markers. Our finding showed that viability of both SSC and EL-4 cells was reduced with the dose of 15 μg/ml when compared to the control group (P ≤ 0.05). Also, the differences between the IC50 in doses 10 and 15 μg/ml at different time were significant (P ≤ 0.05). The number of TUNEL-positive cells was increased, and the BAX and caspase-3 expressions were upregulated in EL4 cells for group that received an effective dose of cisplatin). In conclusion, despite the dramatic effects of cisplatin on both cells, spermatogonial stem cells could form colony in culture. © 2015 Blackwell Verlag GmbH.

Osteonecrosis of the jaw: effect of bisphosphonate type, local concentration, and acidic milieu on the pathomechanism.

PubMed

Otto, Sven; Pautke, Christoph; Opelz, Christine; Westphal, Ines; Drosse, Inga; Schwager, Joanna; Bauss, Frieder; Ehrenfeld, Michael; Schieker, Matthias

2010-11-01

Osteonecrosis of the jaw has been reported in patients receiving high doses of intravenous nitrogen-containing bisphosphonates (N-BPs) because of malignant disease. The exact pathomechanisms have been elusive and questions of paramount importance remain unanswered. Recent studies have indicated toxic effects of bisphosphonates on different cell types, apart from osteoclast inhibition. Multipotent stem cells play an important role in the processes of wound healing and bone regeneration, which seem to be especially impaired in the jaws of patients receiving high doses of N-BPs. Therefore, the aim of the present study was to investigate the effects of different bisphosphonate derivatives and dose levels combined with varying pH levels on the mesenchymal stem cells in vitro. The effect of 2 N-BPs (zoledronate and ibandronate) and 1 non-N-BP (clodronate) on immortalized mesenchymal stem cells was tested at different concentrations, reflecting 1, 3, and 6 months and 1, 3, 5, and 10 years of exposure to standard oncology doses of the 2 N-BPs and equimolar concentrations of clodronate at different pH values (7.4, 7.0, 6.7, and 6.3). Cell viability and activity were analyzed using a WST assay. Cell motility was investigated using scratch wound assays and visualized using time-lapse microscopy. Both types of bisphosphonates revealed remarkable differences. Zoledronate and ibandronate showed a dose- and pH-dependent cellular toxicity. Increasing concentrations of both N-BPs and an acidic milieu led to a significant decrease in cell viability and activity (P < .01), with more pronounced effects for zoledronate. Equimolar concentrations of clodronate did not affect the cell survival or activity significantly, apart from the effect of pH reduction itself, which was also detectable in the patients in the control group who did not receive bisphosphonates. Our results have shown that high concentrations of N-BPs and a local acidic milieu, which is commonly present in infections of the jaw, might play a key role in the pathogenesis of osteonecrosis of the jaw in patients receiving high doses of N-BPs for malignant diseases. Also the potency of N-BPs might be different, suggesting a greater risk of osteonecrosis of the jaw with zoledronate. Copyright © 2010 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Low-voltage chest CT: another way to reduce the radiation dose in asbestos-exposed patients.

PubMed

Macía-Suárez, D; Sánchez-Rodríguez, E; Lopez-Calviño, B; Diego, C; Pombar, M

2017-09-01

To assess whether low voltage chest computed tomography (CT) can be used to successfully diagnose disease in patients with asbestos exposure. Fifty-six former employees of the shipbuilding industry, who were candidates to receive a standard-dose chest CT due to their occupational exposure to asbestos, underwent a routine CT. Immediately after this initial CT, they underwent a second acquisition using low-dose chest CT parameters, based on a low potential (80 kV) and limited tube current. The findings of the two CT protocols were compared based on typical diseases associated with asbestos exposure. The kappa coefficient for each parameter and for an overall rating (grouping them based on mediastinal, pleural, and pulmonary findings) were calculated in order to test for correlations between the two protocols. A good correlation between routine and low-dose CT was demonstrated for most parameters with a mean radiation dose reduction of up to 83% of the effective dose based on the dose-length product between protocols. Low-dose chest CT, based on a limited tube potential, is useful for patients with an asbestos exposure background. Low-dose chest CT can be successfully used to minimise the radiation dose received by patients, as this protocol produced an estimated mean effective dose similar to that of an abdominal or pelvis plain film. Copyright © 2017 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Impact of Number of Human Papillomavirus Vaccine Doses on Genital Warts Diagnoses Among a National Cohort of U.S. Adolescents.

PubMed

Perkins, Rebecca B; Lin, Mengyun; Wallington, Sherrie F; Hanchate, Amresh

2017-06-01

The impact of fewer than 3 doses of human papillomavirus (HPV) vaccine on genital warts is uncertain. Using the Truven Health Analytics Marketscan administrative database, we compared rates of genital warts among women receiving 0, 1, 2, or 3 doses of HPV vaccine. Females aged 9 to 18 years on January 1, 2007, who were continuously enrolled in the database through December 31, 2013, were included. Patients were assigned an HPV dose state (0, 1, 2, or 3) based on the last recorded dose. The exposure period began on January 1, 2007, or the date of the final HPV dose, and lasted until the first diagnosis of genital warts or December 31, 2013. Multivariable Poisson regression was performed to determine the risk of genital warts associated with vaccine doses. Among 387,906 subjects, mean age and exposure period were 14.73 and 5.64 years, respectively. The proportions of doses received were: 52.1%, 7.8%, 9.4%, and 30.7% for 0, 1, 2, and 3 doses, respectively. The rate of genital warts was 1.97/1000 person-years. Receipt of 0 or 1 dose was associated with more genital warts than 3 doses. The effectiveness of 2 doses following current Centers for Disease Control and Prevention guidelines was similar to 3 doses. The risk of genital warts rose with age. Prevention of genital warts is higher with completion of 3 vaccine doses than with 1 dose, though 2-dose recommendations appear to provide similar protection. Prospective effectiveness studies of recommended 2-dose schedules against clinical endpoints including persistent infection, genital warts, and cervical dysplasia are necessary to ensure long-term protection of vaccinated cohorts.

Effects of Surgery and Proton Therapy on Cerebral White Matter of Craniopharyngioma Patients

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

Uh, Jinsoo, E-mail: jinsoo.uh@stjude.org; Merchant, Thomas E.; Li, Yimei

Purpose: The purpose of this study was to determine radiation dose effect on the structural integrity of cerebral white matter in craniopharyngioma patients receiving surgery and proton therapy. Methods and Materials: Fifty-one patients (2.1-19.3 years of age) with craniopharyngioma underwent surgery and proton therapy in a prospective therapeutic trial. Anatomical magnetic resonance images acquired after surgery but before proton therapy were inspected to identify white matter structures intersected by surgical corridors and catheter tracks. Longitudinal diffusion tensor imaging (DTI) was performed to measure microstructural integrity changes in cerebral white matter. Fractional anisotropy (FA) derived from DTI was statistically analyzed for 51more » atlas-based white matter structures of the brain to determine radiation dose effect. FA in surgery-affected regions in the corpus callosum was compared to that in its intact counterpart to determine whether surgical defects affect radiation dose effect. Results: Surgical defects were seen most frequently in the corpus callosum because of transcallosal resection of tumors and insertion of ventricular or cyst catheters. Longitudinal DTI data indicated reductions in FA 3 months after therapy, which was followed by a recovery in most white matter structures. A greater FA reduction was correlated with a higher radiation dose in 20 white matter structures, indicating a radiation dose effect. The average FA in the surgery-affected regions before proton therapy was smaller (P=.0001) than that in their non–surgery-affected counterparts with more intensified subsequent reduction of FA (P=.0083) after therapy, suggesting that surgery accentuated the radiation dose effect. Conclusions: DTI data suggest that mild radiation dose effects occur in patients with craniopharyngioma receiving surgery and proton therapy. Surgical defects present at the time of proton therapy appear to accentuate the radiation dose effect longitudinally. This study supports consideration of pre-existing surgical defects and their locations in proton therapy planning and studies of treatment effect.« less

Long-term effects of intragastic instillations of BDNPF:BDNPA in male Sprague-Dawley rats and female Swiss-Webster mice

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

Smith, D.M.; Drake, G.A.; London, J.E.

1981-07-01

Young male Sprague-Dawley rats were given a single dose of 1.3 g/kg body weight (BW) bis-dinitro-propyl-formal:bisdinitro-propyl-acetal (BDNPF:BDNPA) intragastrically (IG) and young female Swiss-Webster mice were given BDNPF:BDNPA either as a single dose (800 mg/kg/Bw) IG or a dose (500 mg/kg/BW) IG on each of 5 consecutive days. All animals were then maintained for the durations of their life spans and autopsied at death. The incidence of testicular Leydig cell tumors and subcutaneous fibrosarcomas in rats receiving the material was significantly elevated compared to controls, though treated animals' life spans were not significantly different from those of control animals. No significantmore » effects were seen in any of the mice receiving either a single dose or multiple doses of BDNPF:BDNPA compared to control animals. We suggest that another species of male Laboratory animals be treated with BDNPF:BDNPA to see if these findings can be replicated.« less

Evaluation of computerized decision support for oral anticoagulation management based in primary care.

PubMed

Fitzmaurice, D A; Hobbs, F D; Murray, E T; Bradley, C P; Holder, R

1996-09-01

Increasing indications for oral anticoagulation has led to pressure on general practices to undertake therapeutic monitoring. Computerized decision support (DSS) has been shown to be effective in hospitals for improving clinical management. Its usefulness in primary care has previously not been investigated. To test the effectiveness of using DSS for oral anticoagulation monitoring in primary care by measuring the proportions of patients adequately controlled, defined as within the appropriate therapeutic range of International Normalised Ratio (INR). All patients receiving warfarin from two Birmingham inner city general practices were invited to attend a practice-based anticoagulation clinic. In practice A all patients were managed using DSS. In practice B patients were randomized to receive dosing advice either through DSS or through the local hospital laboratory. Clinical outcomes, adverse events and patient acceptability were recorded. Forty-nine patients were seen in total. There were significant improvements in INR control from 23% to 86% (P > 0.001) in the practice where all patients received dosing through DSS. In the practice where patients were randomized to either DSS or hospital dosing, logistic regression showed a significant trend for improvement in intervention patients which was not apparent in the hospital-dosed patients (P < 0.001). Mean recall times were significantly extended in patients who were dosed by the practice DSS through the full 12 months (24 days to 36 days) (P = 0.033). Adverse events were comparable between hospital and practice-dosed patients, although a number of esoteric events occurred. Patient satisfaction with the practice clinics was high. Computerized DSS enables the safe and effective transfer of anticoagulation management from hospital to primary care and may result in improved patient outcome in terms of the level of control, frequency of review and general acceptability.

Comparison and Efficacy of Low-Dose and Standard-Dose Tamsulosin and Alfuzosin in Medical Expulsive Therapy for Lower Ureteral Calculi: Prospective, Randomized, Comparative Study

PubMed Central

Cha, Woo Heon; Choi, Jae Duck; Seo, Young Jin; Lee, Kyungseop

2012-01-01

Purpose Typically in Korea, for a standard dose (0.4 mg) of tamsulosin, two low doses (0.2 mg) are administered. The aim of this study was to evaluate and compare the efficacy of tamsulosin (0.2 mg and 0.4 mg) and alfuzosin (10 mg) in the treatment of lower ureteral stones. Materials and Methods A total of 141 patients presenting with a single 4- to 10-mm sized lower ureteral stone were randomly assigned to 4 groups. Patients in group 1 (n=41) and group 2 (n=30) received an oral dose of 0.2 mg tamsulosin once and twice daily, respectively, and patients in group 3 (n=36) received a daily oral dose of 10 mg alfuzosin. Patients in group 4 (n=34) received trospium chloride only. The spontaneous passage of stones, the stone expulsion time, and adverse effects were evaluated. Results There were no significant differences in patient background, including age, sex, BMI, stone size, stone side, and symptom duration. The spontaneous stone passage rate through the ureter was higher and the stone expulsion time was faster in groups 1, 2, and 3 than in group 4. There were no statistically different changes in groups 1, 2, and 3. The adverse effects observed in all groups were comparable and were mild. Conclusions Tamsulosin at 0.2 mg and 0.4 mg and alfuzosin (10 mg) proved to be safe and effective. A first cycle of medical expulsive therapy with tamsulosin 0.2 mg could be considered as an option in the management of single lower ureteral stone. PMID:22670195

Dose-dependent effects and reversibility of the injuries caused by nandrolone decanoate in uterine tissue and fertility of rats.

PubMed

Belardin, Larissa Berloffa; Simão, Vinícius Augusto; Leite, Gabriel Adan Araújo; Chuffa, Luiz Gustavo de Almeida; Camargo, Isabel Cristina Cherici

2014-04-01

This study is the first to investigate the effects of different doses of nandrolone decanoate (ND) upon uterine tissue and fertility, and if the reproductive alterations can be restored after cessation of the treatment. Wistar female rats were treated with ND at doses of 1.87, 3.75, 7.5, and 15 mg/kg body weight, diluted in vehicle (n = 30/group), or received only mineral oil (control group, n = 45). The animals were divided into three periods of study: ND-treated receiving a daily subcutaneous injection for 15 consecutive days (1), and treatment with ND followed by 30-day recovery (2), and 60-day recovery (3). At the end of each period, five females per group were induced to death to histopathological analysis and the others were allowed to fertility evaluation (at 19th gestational day). Animals that received ND followed by 30-day recovery exhibited persistent diestrous and marked suppression of reproductive capacity. Conversely, after 60-day recovery, only lowest doses females (1.87 and 3.75 mg/kg) exhibited restoration of normal estrous cyclicity. Uterine weights were increased after ND treatment similarly to that of the controls after 60-day recovery. The ND-treated groups showed histopathological changes in the endometrium, myometrium, and perimetrium, and an increase in the thickness of both muscular and serous layers. Notably, the recovery of uterine tissue after ND treatment was dose- and period-dependent. We reported that administration of ND promoted damage in uterine tissue and fertility of rats, and the recovery periods were insufficient to restore all of the side effects caused by ND under a dose-dependent response. © 2014 Wiley Periodicals, Inc.

Effects of Dose Frequency of Early Communication Intervention in Young Children with and without Down Syndrome

ERIC Educational Resources Information Center

Yoder, Paul; Woynaroski, Tiffany; Fey, Marc; Warren, Steven

2014-01-01

Children with intellectual disability were randomly assigned to receive Milieu Communication Teaching (MCT) at one 1-hr session per week (low dose frequency, LDF) or five 1-hr sessions per week (high dose frequency, HDF) over 9 months (Fey, Yoder, Warren, & Bredin-Oja, 2013. Non-Down syndrome (NDS) and Down syndrome (DS) subgroups were matched…

Comparative effect of atypical and conventional antipsychotic drugs on neurocognition in first-episode psychosis: a randomized, double-blind trial of olanzapine versus low doses of haloperidol.

PubMed

Keefe, Richard S E; Seidman, Larry J; Christensen, Bruce K; Hamer, Robert M; Sharma, Tonmoy; Sitskoorn, Margriet M; Lewine, Richard R J; Yurgelun-Todd, Deborah A; Gur, Ruben C; Tohen, Mauricio; Tollefson, Gary D; Sanger, Todd M; Lieberman, Jeffrey A

2004-06-01

The effect of antipsychotic medication on neurocognitive function remains controversial, especially since most previous work has compared the effects of novel antipsychotic medications with those of high doses of conventional medications. This study compares the neurocognitive effects of olanzapine and low doses of haloperidol in patients with first-episode psychosis. Patients with a first episode of schizophrenia, schizoaffective disorder, or schizophreniform disorder (N=167) were randomly assigned to double-blind treatment with olanzapine (mean modal dose= 9.63 mg/day) or haloperidol (mean modal dose=4.60 mg/day) for the 12-week acute phase of a 2-year study. The patients were assessed with a battery of neurocognitive tests at baseline and 12 weeks after beginning treatment. An unweighted neurocognitive composite score, composed of measures of verbal fluency, motor functions, working memory, verbal memory, and vigilance, improved significantly with both haloperidol and olanzapine treatment (effect sizes of 0.20 and 0.36, respectively, no significant difference between groups). A weighted composite score developed from a principal-component analysis of the same measures improved to a significantly greater degree with olanzapine, compared with haloperidol. Anticholinergic use, extrapyramidal symptoms, and estimated IQ had little effect on the statistical differentiation of the medications, although duration of illness had a modest effect. The correlations of cognitive improvement with changes in clinical characteristics and with side effects of treatment were significant for patients who received haloperidol but not for patients who received olanzapine. Olanzapine has a beneficial effect on neurocognitive function in patients with a first episode of psychosis. However, in a comparison of the effects of olanzapine and low doses of haloperidol, the difference in benefit is small.

Thermal Dose is Related to Duration of Local Control in Canine Sarcomas Undergoing Thermoradiotherapy

PubMed Central

Thrall, Donald E.; LaRue, Susan M.; Yu, Daohai; Samulski, Thaddeus; Sanders, Linda; Case, Beth; Rosner, Gary; Azuma, Chieko; Poulson, Jeannie; Pruitt, Amy F.; Stanley, Wilma; Hauck, Marlene L.; Williams, Laurel; Hess, Paul; Dewhirst, Mark W.

2009-01-01

Purpose To test that prospective delivery of higher thermal dose is associated with longer tumor control duration. Experimental Design 122 dogs with a heatable soft tissue sarcoma were randomized to receive a low (2–5 CEM43°CT90) or high (20–50 CEM43°CT90) thermal dose in combination with radiotherapy. Most dogs (90%) received 4–6 hyperthermia treatments over 5 weeks. Results In the primary analysis, median (95% CI) duration of local control in the low dose group was 1.2 (0.7–2.1) years versus 1.9 (1.4–3.2) years in the high dose group (logrank p=0.28). The probability (95% CI) of tumor control at one year in the low vs. high dose groups was 0.57 (0.43–0.70) vs. 0.74 (0.62–0.86), respectively. Using multivariable procedure, thermal dose group (p=0.023), total duration of heating (p=0.008), tumor volume (p=0.041) and tumor grade (p=0.027) were significantly related to duration of local tumor control. When correcting for volume, grade and duration of heating, dogs in the low dose group were 2.3 times as likely to experience local failure. Conclusions Thermal dose is directly related to local control duration in irradiated canine sarcomas. Longer heating being associated with shorter local tumor control was unexpected. However, the effect of thermal dose on tumor control was stronger than for heating duration. The heating duration effect is possibly mediated through deleterious effects on tumor oxygenation. These results are the first to show the value of prospectively controlled thermal dose in achieving local tumor control with thermoradiotherapy, and they establish a paradigm for prescribing thermoradiotherapy and writing a thermal prescription. PMID:16033838

Platelet Aggregation Inhibitory Effects and Pharmacokinetics of Prasugrel Used in Combination With Aspirin in Healthy Japanese Subjects.

PubMed

Umemura, Kazuo; Ikeda, Yasuhiko; Matsushima, Nobuko; Kondo, Kazunao

2017-07-01

We evaluated the pharmacokinetics and pharmacodynamics of prasugrel used in combination with aspirin in healthy Japanese subjects. All subjects received aspirin 100 mg/day. Subsequently, in the single-administration study, 23 subjects also received prasugrel 20 or 30 mg, and in the multiple-administration study, 20 subjects received a loading dose of prasugrel 20 or 30 mg on day 1, followed by a maintenance dose of prasugrel 5 or 7.5 mg/day, respectively, on days 2-5. In both studies, the plasma concentration of the active metabolite of prasugrel, R-138727, reached a maximum 0.5 hours after administration and rapidly decreased within 4 hours. In the single-administration study, the inhibitory effect on adenosine diphosphate-induced platelet aggregation was significantly higher in the prasugrel 20- and 30-mg groups than in the placebo group at all times (1-144 hours) after administration. In the multiple-administration study, a similar antiplatelet effect was found after both the loading dose and the maintenance dose and was maintained for 3-6 days after the last administration. There were study drug-related adverse events; however, all were mild, and none was clinically significant. © 2016 The Authors. Clinical Pharmacology in Drug Development Published by Wiley Periodicals, Inc. on behalf of The American College of Clinical Pharmacology.

TU-AB-201-06: Evaluation of Electromagnetically Guided High- Dose Rate Brachytherapy for Ablative Treatment of Lung Metastases

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

Pinkham, D.W.; Shultz, D.; Loo, B.W.

Purpose: The advent of electromagnetic navigation bronchoscopy has enabled minimally invasive access to peripheral lung tumors previously inaccessible by optical bronchoscopes. As an adjunct to Stereotactic Ablative Radiosurgery (SABR), implantation of HDR catheters can provide focal treatments for multiple metastases and sites of retreatments. The authors evaluate a procedure to deliver ablative doses via Electromagnetically-Guided HDR (EMG-HDR) to lung metastases, quantify the resulting dosimetry, and assess its role in the comprehensive treatment of lung cancer. Methods: A retrospective study was conducted on ten patients, who, from 2009 to 2011, received a hypo-fractionated SABR regimen with 6MV VMAT to lesions inmore » various lobes ranging from 1.5 to 20 cc in volume. A CT visible pathway was delineated for EM guided placement of an HDR applicator (catheter) and dwell times were optimized to ensure at least 98% prescription dose coverage of the GTV. Normal tissue doses were calculated using inhomogeneity corrections via a grid-based Boltzmann solver (Acuros-BV-1.5.0). Results: With EMG-HDR, an average of 83% (+/−9% standard deviation) of each patient’s GTV received over 200% of the prescription dose, as compared to SABR where the patients received an average maximum dose of 125% (+/−5%). EMG-HDR enabled a 59% (+/−12%) decrease in the aorta maximum dose, a 63% (+/−26%) decrease in the spinal cord max dose, and 57% (+/−23%) and 70% (+/−17%) decreases in the volume of the body receiving over 50% and 25% of the prescription dose, respectively. Conclusion: EMG-HDR enables delivery of higher ablative doses to the GTV, while concurrently reducing surrounding normal tissue doses. The single catheter approach shown here is limited to targets smaller than 20 cc. As such, the technique enables ablation of small lesions and a potentially safe and effective retreatment option in situations where external beam utility is limited by normal tissue constraints.« less

Ultra-low dose of intravitreal bevacizumab in retinopathy of prematurity.

PubMed

Şahin, A; Gürsel-Özkurt, Z; Şahin, M; Türkcü, F M; Yıldırım, A; Yüksel, H

2018-05-01

We aimed to investigate the effectivity of the 0.0625 mg dose of bevacizumab in patients with retinopathy of prematurity (ROP) and compare the results with 0.625 mg dose of intravitreal bevacizumab (IVB) injection. The medical records of the patients with type 1 ROP who received IVB monotherapy were retrospectively reviewed. Demographic and clinical characteristics of the patients were recorded. The patients were classified into two groups with respect to received dose of bevacizumab as follows: group F (n = 46) (full dose of bevacizumab-0.625 mg/0.025 ml) and group L (n = 45) (low dose (one tenth) of bevacizumab-0.0625 mg/0.025 ml). Both treatment dose regimens have similar outcomes. Moreover, the mean retinal vascularization time seemed to be significantly higher in group F compared to group L, 168 ± 65 and 97 ± 29 days, respectively (p < 0.001). Disappearance of plus sign is observed earlier in group F (2.45 ± 1.7 vs 3.66 ± 2.46 days, respectively, p = 0.03). The low dose (0.0625 mg) of IVB treatment was effective as full (0.625 mg) dose in ROP treatment. Moreover, our results showed that low-dose treatment might provide faster retinal vascularization than the regular used dose. On the other hand, disappearance of the plus sign takes longer time in patients treated with low dose compared to eyes treated with full dose of IVB that should be taken into account.

Assessment of Safety, Tolerability, Pharmacokinetics, and Pharmacological Effect of Orally Administered CORT125134: An Adaptive, Double-Blind, Randomized, Placebo-Controlled Phase 1 Clinical Study.

PubMed

Hunt, Hazel; Donaldson, Kirsteen; Strem, Mark; Zann, Vanessa; Leung, Pui; Sweet, Suzanne; Connor, Alyson; Combs, Dan; Belanoff, Joseph

2018-05-01

CORT125134 is an orally active, high-affinity, selective antagonist of the glucocorticoid receptor that is being developed for indications that may benefit from the modulation of cortisol activity. This first-in-human study was conducted to evaluate the dose-related safety, tolerability, pharmacokinetics and pharmacological effects of CORT125134 and its active metabolite CORT125201. Eighty-one healthy male or female subjects received a single dose of 5 to 500 mg CORT125134 or matching placebo across 9 cohorts; 1 cohort received 150 mg CORT125134 after a high-fat breakfast; and 46 subjects received 50 to 500 mg CORT125134 or matching placebo once daily for up to 14 days across 4 cohorts. CORT125134 was well tolerated at doses up to 250 mg per day for 14 days. CORT125134 was absorbed rapidly and eliminated with a mean half-life ranging from 11 to 19 hours. Steady state was achieved by day 7. Exposure increased in a greater than proportional manner, particularly at lower doses. Exposure to CORT125201 at steady state was less than 5% that of parent CORT125134. Evidence for the desired pharmacological effect (glucocorticoid receptor antagonism) was demonstrated by the ability of CORT125134 to prevent several effects of the glucocorticoid receptor agonist prednisone. © 2018 The Authors. Clinical Pharmacology in Drug Development Published by Wiley Periodicals, Inc. on behalf of The American College of Clinical Pharmacology.

Antiosteoporotic effect of Petroselinum crispum, Ocimum basilicum and Cichorium intybus L. in glucocorticoid-induced osteoporosis in rats.

PubMed

Hozayen, Walaa G; El-Desouky, Mohamed A; Soliman, Hanan A; Ahmed, Rasha R; Khaliefa, Amal K

2016-06-02

Glucocorticoid-induced osteoporosis (GIO) is one of the serious side effects which have become the most common secondary osteoporosis. The purpose of this study is to evaluate the effect of aqueous extract of parsley, basil and chicory on glucocorticoid-induced osteoporosis in rats. Fifty Female rats were divided into five groups and treated for 8 weeks as follow: group 1 served as control; group (2) subcutaneously injected with 0.1 mg/kg b. wt. dexamethasone dissolved in saline; group 3 received similar dose of dexamethasone together with aqueous parsley extract in a dose of 2 g/kg b. wt.; group 4 received similar dose of dexamethasone together with 400 mg/kg b. wt. aqueous basil extract and group 5 received similar dose of dexamethasone together with 100 mg/kg b. wt. aqueous chicory extract. The dexamethasone group showed a significant decrease in serum E2, Ca, P levels and significant decrease in total BMD, BMC and a significant increase in serum PTH, ALP and ACP. Bone TBARs was significantly increased while GSH, antioxidant enzymes were significantly decreased. These changes were attenuated by parsley, basil and chicory extracts in the group 3, 4 and 5 respectively. Aqueous extracts of parsley, basil and chicory showed bone protection against glucocorticoid-induced in rats. From our results, we concluded that chicory has a potent protective effect more than parsley and basil due to containing flavonoids and inulin.

High Dose Vitamin D Therapy for Chronic Pain in Children and Adolescents with Sickle Cell Disease: Results of a Randomized Double Blind Pilot Study

PubMed Central

I, Osunkwo; TR, Ziegler; J, Alvarez; C, McCracken; K, Cherry; CE, Osunkwo; SF, Ofori-Acquah; S, Ghosh; A, Ogunbobode; J, Rhodes; JR, Eckman; CD, Dampier; V, Tangpricha

2012-01-01

Summary We report results of a pilot study of high-dose vitamin D in sickle cell disease (SCD). Subjects were followed for 6 months after receiving a six-week course of oral high-dose cholecalciferol or placebo. Vitamin D insufficiency and deficiency was present at baseline in 82.5% and 52.5% of subjects, respectively. Subjects who received high-dose vitamin D achieved higher serum 25-hydroxyvitamin D, experienced fewer pain days per week, and had higher physical activity quality-of-life scores. These findings suggest a potential benefit of vitamin D in reducing the number of pain days in SCD. Larger prospective studies with longer duration are needed to confirm these effects. PMID:22924607

The Effect of Sympathetic Antagonists on the Antidepressant Action of Alprazolam

PubMed Central

Al-Tubuly, RA; Aburawi, SM; Alghzewi, EA; Gorash, ZM; Errwami, S

2008-01-01

Alprazolam is an anti-anxiety drug shown to be effective in the treatment of depression. In this study, the effect of sympathetic receptor antagonists on alprazolam–induced antidepressant action was studied using a mouse model of forced swimming behavioral despair. The interaction of three sympathetic receptor antagonists with benzodiazepines, which may impact the clinical use of alprazolam, was also studied. Behavioral despair was examined in six groups of albino mice. Drugs were administered intraperitoneally. The control group received only a single dose of 1% Tween 80. The second group received a single dose of alprazolam, and the third group received an antagonist followed by alprazolam. The fourth group was treated with imipramine, and the fifth group received an antagonist followed by imipramine. The sixth group was treated with a single dose of an antagonist alone (atenolol, a β1-selective adrenoceptor antagonist; propranolol, a non selective β-adrenoceptor antagonist; and prazocin, an α1-adrenoceptor antagonist). Results confirmed the antidepressant action of alprazolam and imipramine. Prazocin treatment alone produced depression, but it significantly potentiated the antidepressant actions of imipramine and alprazolam. Atenolol alone produced an antidepressant effect and potentiated the antidepressant action of alprazolam. Propranolol treatment alone produced depression, and antagonized the effects of alprazolam and imipramine, even producing depression in combined treatments.In conclusion, our results reveal that alprazolam may produce antidepressant effects through the release of noradrenaline, which stimulates β2 receptors to produce an antidepressant action. Imipramine may act by activating β2 receptors by blocking or down-regulating β1 receptors. PMID:21499463

Effect of a single dose of propofol and lack of dextrose administration in a child with mitochondrial disease: a case report.

PubMed

Mtaweh, Haifa; Bayır, Hülya; Kochanek, Patrick M; Bell, Michael J

2014-08-01

Propofol infusion syndrome is a recognized complication of prolonged propofol use in the pediatric population, but little is reported on other metabolic effects of propofol, especially in children with mitochondrial disorders. We report on a child with metabolic encephalopathy, lactic acidosis, and stroke-like syndrome who received a single dose of propofol for procedural sedation. The patient's initial presentation was consistent with a mild exacerbation of her underlying disease. She received a single dose of propofol and non-dextrose-containing fluids during a magnetic resonance imaging (MRI) study to rule out stroke and progressed to develop severe acidosis, neurologic deterioration, and cardiorespiratory compromise. This is the first case report of severe metabolic disturbances after a single dose of propofol administered for procedural sedation in a patient with metabolic encephalopathy, lactic acidosis, and stroke-like syndrome and it questions the safety of propofol and absence of dextrose infusions during an acute illness in patients with mitochondrial disorders. © The Author(s) 2013.

Health effects from fallout.

PubMed

Gilbert, Ethel S; Land, Charles E; Simon, Steven L

2002-05-01

This paper primarily discusses health effects that have resulted from exposures received as a result of above-ground nuclear tests, with emphasis on thyroid disease from exposure to 131I and leukemia and solid cancers from low dose rate external and internal exposure. Results of epidemiological studies of fallout exposures in the Marshall Islands and from the Nevada Test Site are summarized, and studies of persons with exposures similar to those from fallout are briefly reviewed (including patients exposed to 131I for medical reasons and workers exposed externally at low doses and low dose rates). Promising new studies of populations exposed in countries of the former Soviet Union are also discussed and include persons living near the Semipalatinsk Test Site in Kazakhstan, persons exposed as a result of the Chernobyl accident, and persons exposed as a result of operations of the Mayak Nuclear Plant in the Russian Federation. Very preliminary estimates of cancer risks from fallout doses received by the United States population are presented.

Method for microbeam radiation therapy

DOEpatents

Slatkin, D.N.; Dilmanian, F.A.; Spanne, P.O.

1994-08-16

A method is disclosed of performing radiation therapy on a patient, involving exposing a target, usually a tumor, to a therapeutic dose of high energy electromagnetic radiation, preferably X-ray radiation. The dose is in the form of at least two non-overlapping microbeams of radiation, each microbeam having a width of less than about 1 millimeter. Target tissue exposed to the microbeams receives a radiation dose during the exposure that exceeds the maximum dose that such tissue can survive. Non-target tissue between the microbeams receives a dose of radiation below the threshold amount of radiation that can be survived by the tissue, and thereby permits the non-target tissue to regenerate. The microbeams may be directed at the target from one direction, or from more than one direction in which case the microbeams overlap within the target tissue enhancing the lethal effect of the irradiation while sparing the surrounding healthy tissue. No Drawings

Assessing the use of school public address systems to deliver nutrition messages to children: Shape up Somerville--audio adventures.

PubMed

Folta, Sara C; Goldberg, Jeanne P; Economos, Christina; Bell, Rick; Landers, Stewart; Hyatt, Raymond

2006-11-01

Given the current childhood obesity epidemic, it is especially important to find effective ways to promote healthful foods to children. School public address (PA) systems represent an inexpensive and a replicable way of reaching children with health messages. To test the effectiveness of this channel, messages were created to promote 2 dried bean (legume) dishes that had been added to the school lunch menu. Six elementary schools were pair matched, and 1 school from each pair was randomly chosen to play the messages. The impact of the intervention on choice of the 2 new entrees was assessed. Results indicate that for all schools combined, choice was not significantly affected. However, compared to their matched control schools, choice was significantly higher in the school that received the highest dose of the intervention and was significantly lower in the school that received the lowest dose. Choice was not changed in the school that received an intermediate dose. These results suggest that PA systems show promise as an effective and appropriate communications channel but only in schools that are able to play messages frequently.

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.

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.

Effects of Phone and Text Message Reminders on Completion of the Human Papillomavirus Vaccine Series.

PubMed

Rand, Cynthia M; Vincelli, Phyllis; Goldstein, Nicolas P N; Blumkin, Aaron; Szilagyi, Peter G

2017-01-01

To assess the effect of phone or text message reminders to parents of adolescents on human papillomavirus (HPV) vaccine series completion in Rochester, NY. We performed parallel randomized controlled trials of phone and text reminders for HPV vaccine for parents of 11- to 17-year olds in three urban primary care clinics. The main outcome measures were time to receipt of the third dose of HPV vaccine and HPV vaccination rates. We enrolled 178 phone intervention (180 control) and 191 text intervention (200 control) participants. In multivariate survival analysis controlling for gender, age, practice, insurance, race, and ethnicity, the time from enrollment to receipt of the third HPV dose for those receiving a phone reminder compared with controls was not significant overall (hazard ratio [HR] = 1.30, p = .12) but was for those enrolling at dose 1 (HR = 1.91, p = .007). There was a significant difference in those receiving a text reminder compared with controls (HR = 2.34, p < .0001; an average of 71 days earlier). At the end of the study, 48% of phone intervention versus 40% of phone control (p = .34), and 49% of text intervention versus 30% of text control (p = .001) adolescents had received 3 HPV vaccine doses. In this urban population of parents of adolescents, text message reminders for HPV vaccine completion for those who had already started the series were effective, whereas phone message reminders were only effective for those enrolled at dose 1. Copyright © 2016 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

Anti-radiation damage effect of polyethylenimine as a toll-like receptor 5 targeted agonist

PubMed Central

Hu, Zhiqiang; Xing, Yaling; Qian, Yuanyu; Chen, Xiaojuan; Tu, Jian; Ren, Lening; Wang, Kai; Chen, Zhongbin

2013-01-01

A number of agents are now available for use in protecting against ionizing radiation. These radiation-protective agents, however, have many adverse effects. Efforts have been made to develop new radiation-protective agents for medical application. Here, we investigated whether a compound, polyethylenimine (PEI), which activates Toll-like receptor 5 (TLR5)-mediated NF-kB signaling pathways, could have an anti-radiation effect on a mouse model. First, a cell-based screening model for an agonist of TLR5-mediated NF-kB pathway was established and then validated by activation of TLR5-mediated NF-kB luciferase reporter activity with a known TLR5 agonist, flagellin. We found that PEI induced dose-dependent activation of the TLR5-mediated NF-kB pathway, indicating that PEI is indeed a TLR5 agonist. Furthermore, the anti-radiation effect of polyethylenimine was assessed using a γ-ray total body irradiation (TBI) mouse model. Compared with the irradiation control, both survival time and survival rate were significantly improved in mice that received either a low dose of polyethylenimine (P= 0.019) or a high dose of polyethylenimine (P< 0.001). We also observed a positive correlation between animal body weight and survival time in mice that received a low dose of polyethylenimine, a high dose of polyethylenimine and amifostine, over a period of 30 days, r= 0.42 (P< 0.02), 0.72 (P< 0.0001) and 0.95 (P< 0.0001), respectively, while a negative correlation between animal body weight and survival time was observed in the irradiation control (r= –0.89; P< 0.0001). These results indicate that polyethylenimine is a new TLR5 agonist with potential application in offering protection for patients receiving radiotherapy or in radiation-related accidents. PMID:23104900

Anti-radiation damage effect of polyethylenimine as a toll-like receptor 5 targeted agonist.

PubMed

Hu, Zhiqiang; Xing, Yaling; Qian, Yuanyu; Chen, Xiaojuan; Tu, Jian; Ren, Lening; Wang, Kai; Chen, Zhongbin

2013-03-01

A number of agents are now available for use in protecting against ionizing radiation. These radiation-protective agents, however, have many adverse effects. Efforts have been made to develop new radiation-protective agents for medical application. Here, we investigated whether a compound, polyethylenimine (PEI), which activates Toll-like receptor 5 (TLR5)-mediated NF-kB signaling pathways, could have an anti-radiation effect on a mouse model. First, a cell-based screening model for an agonist of TLR5-mediated NF-kB pathway was established and then validated by activation of TLR5-mediated NF-kB luciferase reporter activity with a known TLR5 agonist, flagellin. We found that PEI induced dose-dependent activation of the TLR5-mediated NF-kB pathway, indicating that PEI is indeed a TLR5 agonist. Furthermore, the anti-radiation effect of polyethylenimine was assessed using a γ-ray total body irradiation (TBI) mouse model. Compared with the irradiation control, both survival time and survival rate were significantly improved in mice that received either a low dose of polyethylenimine (P= 0.019) or a high dose of polyethylenimine (P< 0.001). We also observed a positive correlation between animal body weight and survival time in mice that received a low dose of polyethylenimine, a high dose of polyethylenimine and amifostine, over a period of 30 days, r= 0.42 (P< 0.02), 0.72 (P< 0.0001) and 0.95 (P< 0.0001), respectively, while a negative correlation between animal body weight and survival time was observed in the irradiation control (r= -0.89; P< 0.0001). These results indicate that polyethylenimine is a new TLR5 agonist with potential application in offering protection for patients receiving radiotherapy or in radiation-related accidents.

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

Iatrogenic radiation exposure to patients with early onset spine and chest wall deformities.

PubMed

Khorsand, Derek; Song, Kit M; Swanson, Jonathan; Alessio, Adam; Redding, Gregory; Waldhausen, John

2013-08-01

Retrospective cohort series. Characterize average iatrogenic radiation dose to a cohort of children with thoracic insufficiency syndrome (TIS) during assessment and treatment at a single center with vertically expandable prosthetic titanium rib. Children with TIS undergo extensive evaluations to characterize their deformity. No standardized radiographical evaluation exists, but all reports use extensive imaging. The source and level of radiation these patients receive is not currently known. We evaluated a retrospective consecutive cohort of 62 children who had surgical treatment of TIS at our center from 2001-2011. Typical care included obtaining serial radiographs, spine and chest computed tomographic (CT) scans, ventilation/perfusion scans, and magnetic resonance images. Epochs of treatment were divided into time of initial evaluation to the end of initial vertically expandable prosthetic titanium rib implantation with each subsequent epoch delineated by the next surgical intervention. The effective dose for each examination was estimated within millisieverts (mSv). Plain radiographs were calculated from references. Effective dose was directly estimated for CT scans since 2007 and an average of effective dose from 2007-2011 was used for scans before 2007. Effective dose from fluoroscopy was directly estimated. All doses were reported in mSv. A cohort of 62 children had a total of 447 procedures. There were a total of 290 CT scans, 4293 radiographs, 147 magnetic resonance images, and 134 ventilation/perfusion scans. The average accumulated effective dose was 59.6 mSv for children who had completed all treatment, 13.0 mSv up to initial surgery, and 3.2 mSv for each subsequent epoch of treatment. CT scans accounted for 74% of total radiation dose. Children managed for TIS using a consistent protocol received iatrogenic radiation doses that were on average 4 times the estimated average US background radiation exposure of 3 mSv/yr. CT scans comprised 74% of the total dose. 3.

Comparative electrophysiological study of response to botulinum toxin type B in Japanese and Caucasians.

PubMed

Arimura, Kimiyoshi; Arimura, Yumiko; Takata, Yoshiharu; Nakamura, Tomonori; Kaji, Ryuji

2008-01-30

Ethnic differences in the muscle-relaxing effect of botulinum toxin type B (BTX-B) were examined by means of electrophysiological measurements in Japanese and Caucasian volunteers. This was a randomized, single-blinded, single-center study of 24 Japanese and 24 Caucasian healthy adult male subjects in Japan. BTX-B (20 U, 100 U, or 500 U/0.2 mL) or placebo was administered to the extensor digitorum brevis (EDB) muscle in the left lower limb as a single dose (in each dose group, 6 subjects received the test drug and two received placebo). The inhibitory effect of BTX-B on the M wave amplitude of EDB muscle generated by stimulation of the deep peroneal nerve was measured frequently during 2 weeks after administration, and then at weeks 4 (day 28) and 12 (day 84). The inhibitory effect of BTX-B on the M wave amplitude of EDB muscle was dose-dependent in both Japanese and Caucasian subjects, and the dose-response curves were similar. These findings demonstrate that the muscle-relaxing effect of BTX-B in Japanese subjects is electrophysiologically similar to that in Caucasians. 2007 Movement Disorder Society

Text message reminders to promote human papillomavirus vaccination.

PubMed

Kharbanda, Elyse Olshen; Stockwell, Melissa S; Fox, Harrison W; Andres, Raquel; Lara, Marcos; Rickert, Vaughn I

2011-03-21

To implement and evaluate text message reminders for the second (HPV2) and third (HPV3) vaccine doses. Site-based intervention. Nine pediatric sites (5 academic and 4 private) located in New York City. Parents of adolescents 9-20 years who received HPV1 or HPV2 during the intervention period, January-June 2009. Parents who enrolled received up to three weekly text message reminders that their daughter was due for her next vaccine dose. On-time receipt of the next vaccine dose, within one month of its due date. During the intervention period, of 765 eligible HPV vaccine events, 434 enrollment instructions were distributed to parents (56.7% of doses). Parents of 124 adolescent girls (28.6% of those handed instructions) activated text message reminders. Comparing children of parents who enrolled versus those who did not, on-time receipt of next HPV vaccine dose occurred among 51.6% (95% CI 42.8-60.4%) versus 35.0% (95% CI 29.6-40.2%) of adolescents (p=.001). Similarly, among a historical cohort of adolescents, receiving HPV1 or HPV2 in the six months prior to the intervention period, on-time receipt of next vaccine dose was noted for 38.1% (95% CI 35.2-41.0%) (p=.003). Increases in receipt of next vaccine dose among intervention subjects were sustained at 4 months following the vaccine due date. Using a logistic regression model, after controlling for insurance and site of care, intervention subjects were significantly more likely than either control population to receive their next HPV vaccine dose on-time. Among those choosing to enroll, text message reminders were an effective intervention to increase on-time receipt of HPV2 or HPV3. Copyright © 2011 Elsevier Ltd. All rights reserved.

Effect of vitamin C on male fertility in rats subjected to forced swimming stress.

PubMed

Vijayprasad, Sanghishetti; Bb, Ghongane; Bb, Nayak

2014-07-01

Stress is defined as a general body response to initially threatening external or internal demands, involving the mobilization of physiological and psychological resources to deal with them. Recently, oxidative stress has become the focus of interest as a potential cause of male infertility. Normally, equilibrium exists between reactive oxygen species (ROS) production and antioxidant scavenging activities in the male reproductive organs. The ascorbic acid is a known antioxidant present in the testis with the precise role of protecting the latter from the oxidative damage. It also contributes to the support of spermatogensis at least in part through its capacity to maintain antioxidant in an active state. Group1: Normal Control animal received Distilled water, Group 2: Positive control (Only Stress), Group 3: Normal rats received an intermediate dose of Vitamin C (20mg/kg/day), Group 4: Stress + Low dose Vitamin C (10mg/kg/day), Group 5: Stress+ Intermediate dose Vitamin C (20mg/kg/day), Group 6: High dose Vitamin C (30mg/kg/day). On 16(th) day effect of stress on body weight, Reproductive organ weight, sperm parameters, and hormonal assay was studied. In the present context, in stress group the sperm count, motility, testicular weight declined significantly. The intermediate dose and high dose of vitamin C showed significantly increased effect on the sperm count and motility. Various physiological changes produced force swimming indicates that swimming is an effective model for producing stress in albino rats. The results suggest that Vitamin C supplementation improves the stress induced reproductive infertility due to both their testosterone increase effect and their antioxidant effect.

A pilot study: dose adaptation of capecitabine using mobile phone toxicity monitoring - supporting patients in their homes.

PubMed

Weaver, Andrew; Love, Sharon B; Larsen, Mark; Shanyinde, Milensu; Waters, Rachel; Grainger, Lisa; Shearwood, Vanessa; Brooks, Claire; Gibson, Oliver; Young, Annie M; Tarassenko, Lionel

2014-10-01

Real-time symptom monitoring using a mobile phone is potentially advantageous for patients receiving oral chemotherapy. We therefore conducted a pilot study of patient dose adaptation using mobile phone monitoring of specific symptoms to investigate relative dose intensity of capecitabine, level of toxicity and perceived supportive care. Patients with breast or colorectal cancer receiving capecitabine completed a symptom, temperature and dose diary twice a day using a mobile phone application. This information was encrypted and automatically transmitted in real time to a secure server, with moderate levels of toxicity automatically prompting self-care symptom management messages on the screen of the patient's mobile phone or in severe cases, a call from a specialist nurse to advise on care according to an agreed protocol. Patients (n = 26) completed the mobile phone diary on 92.6 % of occasions. Twelve patients had a maximum toxicity grade of 3 (46.2 %). The average dose intensity for all patients as a percentage of standard dose was 90 %. In eight patients, the dose of capecitabine was reduced, and in eight patients, the dose of capecitabine was increased. Patients and healthcare professionals involved felt reassured by the novel monitoring system, in particular, during out of hours. It is possible to optimise the individual dose of oral chemotherapy safely including dose increase and to manage chemotherapy side effects effectively using real-time mobile phone monitoring of toxicity parameters entered by the patient.

Evaluation of Medicated Gel as a Supplement to Providing Acetaminophen in the Drinking Water of C57BL/6 Mice after Surgery

PubMed Central

Christy, Amanda C; Byrnes, Kimberly R; Settle, Timothy L

2014-01-01

After surgery, rodents frequently receive acetaminophen-treated drinking water for pain relief, but the effectiveness of this practice is often questioned. Gel products are now available to facilitate the delivery of oral medication to rodents after surgery. We sought to compare consumption of flavored medicated gel and medicated water after surgery and to determine whether providing supplemental acetaminophen in gel form ensures the ingestion of a therapeutic dose of an analgesic after surgery. Male C57BL/6 mice were allocated into 3 groups after surgery: those that received acetaminophen-treated water and untreated gel (MW group); those that received medicated gel and untreated water (MG group); and those that received acetaminophen in both forms (MWG group). Total water and gel consumption were monitored daily from the day before surgery until 2 d thereafter. Mice in the MG group consumed significantly less gel than water, and consequently, the total acetaminophen dose per mouse in the MG group (49 mg/kg) was significantly less than that of the MWG group (347 mg/kg). Although the dose consumed by mice in the MW group (158 mg/kg) approached the targeted acetaminophen dose of 200 mg/kg, only mice in the MWG group actually achieved the desired dose. The results of this study indicate that flavored acetaminophen-containing gel can be used in combination with medicated water to ensure that rodents ingest the targeted dose of medication. PMID:24602545

Double-blind, placebo-controlled study of nicergoline in the treatment of pruritus in patients receiving maintenance hemodialysis.

PubMed

Bousquet, J; Rivory, J P; Maheut, M; Michel, F B; Mion, C

1989-04-01

Pruritus is a common symptom among patients undergoing long-term hemodialysis. The effect of nicergoline, an ergoline, on pruritus was studied in products released during dialysis. In a first experiment series, 20 age-matched normal individuals, 25 patients receiving hemodialysis without pruritus, and 15 patients receiving hemodialysis with pruritus had intradermal tests with 500 micrograms of papaverine. All patients with pruritus had a small papaverine skin test response, and mean values were significantly (p less than 0.0001, Mann-Whitney U test) smaller in patients with pruritus. All patients with pruritus entered in a crossover, double-blind trial with nicergoline. In a first period of six dialyses, they received either nicergoline (daily oral dose, 30 mg, and intravenous dose during dialyses, 5 mg) or placebo. In the second period of six dialyses, patients received the crossover treatment. Nicergoline was effective in 13/15 patients, eight of these patients having a complete remission of pruritus. When nicergoline was stopped, patients relapsed within 24 to 48 hours. All patients who improved during the trial were then treated with a daily dose of 30 mg of nicergoline for 6 months. Seven patients had a complete remission, five had moderate symptoms, and one patient relapsed. This study demonstrated that some hemodialyzed patients with pruritus of unknown etiology had improvement with nicergoline.

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

Tucker, Susan L.; Liu, H. Helen; Wang, Shulian

Purpose: The aim of this study was to investigate the effect of radiation dose distribution in the lung on the risk of postoperative pulmonary complications among esophageal cancer patients. Methods and Materials: We analyzed data from 110 patients with esophageal cancer treated with concurrent chemoradiotherapy followed by surgery at our institution from 1998 to 2003. The endpoint for analysis was postsurgical pneumonia or acute respiratory distress syndrome. Dose-volume histograms (DVHs) and dose-mass histograms (DMHs) for the whole lung were used to fit normal-tissue complication probability (NTCP) models, and the quality of fits were compared using bootstrap analysis. Results: Normal-tissue complicationmore » probability modeling identified that the risk of postoperative pulmonary complications was most significantly associated with small absolute volumes of lung spared from doses {>=}5 Gy (VS5), that is, exposed to doses <5 Gy. However, bootstrap analysis found no significant difference between the quality of this model and fits based on other dosimetric parameters, including mean lung dose, effective dose, and relative volume of lung receiving {>=}5 Gy, probably because of correlations among these factors. The choice of DVH vs. DMH or the use of fractionation correction did not significantly affect the results of the NTCP modeling. The parameter values estimated for the Lyman NTCP model were as follows (with 95% confidence intervals in parentheses): n = 1.85 (0.04, {infinity}), m = 0.55 (0.22, 1.02), and D {sub 5} = 17.5 Gy (9.4 Gy, 102 Gy). Conclusions: In this cohort of esophageal cancer patients, several dosimetric parameters including mean lung dose, effective dose, and absolute volume of lung receiving <5 Gy provided similar descriptions of the risk of postoperative pulmonary complications as a function of Radiation dose distribution in the lung.« less

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

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

Eye doses to staff in a nuclear medicine department.

PubMed

Summers, Elizabeth C; Brown, Janis L E; Bownes, Peter J; Anderson, Shona E

2012-05-01

Occupational radiation doses to the Nuclear Medicine Department staff at Mount Vernon Hospital are routinely measured using optically stimulated luminescence dosemeters for whole-body effective dose and ring thermoluminescence dosemeters (TLDs) for finger dose. In 2002, a project was carried out using LiF:Mg,Cu,P Chinese TLDs to measure the dose to the lens of the eye received by staff during normal working procedures. Separate pairs of TLDs were worn by staff on their forehead between their eyes while dispensing and releasing in the radiopharmacy, injecting, and when administering I-131 capsules to patients. The dose received was calculated using calibration data from identical TLDs irradiated with Tc-99m, I-131, and the Ir-192 source of a Gammamed High Dose Rate (HDR) treatment unit. Data were collected over a 5-month period and the mean dose to the eye was calculated for each procedure. Using a typical yearly workload, the annual dose to the eye for a single member of staff was calculated and found to be 4.5 mSv. The occupational eye dose limit was, at the time, 150 mSv; therefore, staff were well below the level (3/10th of this limit) that would have required them to be classified. However, there have been large increases in radiopharmacy production and I-131 therapies administered at Mount Vernon in subsequent years. It is therefore expected that the eye dose received by staff will have increased to be significantly higher than 4.5 mSv and will in fact be greater than 6 mSv, which is 3/10th of the proposed new dose limit and would require these staff to become classified workers.

Management of Venetoclax-Posaconazole Interaction in Acute Myeloid Leukemia Patients: Evaluation of Dose Adjustments.

PubMed

Agarwal, Suresh K; DiNardo, Courtney D; Potluri, Jalaja; Dunbar, Martin; Kantarjian, Hagop M; Humerickhouse, Rod A; Wong, Shekman L; Menon, Rajeev M; Konopleva, Marina Y; Salem, Ahmed Hamed

2017-02-01

The effect of posaconazole, a strong cytochrome P450 3A (CYP3A) inhibitor and commonly used antifungal agent, on the pharmacokinetic properties of venetoclax, a CYP3A substrate, was evaluated in patients with acute myeloid leukemia to determine the dose adjustments needed to manage this potential interaction. Twelve patients received 20- to 200-mg ramp-up treatment with oral venetoclax and 20 mg/m 2 of intravenous decitabine on days 1 through 5, followed by 400 mg of venetoclax alone on days 6 through 20. On days 21 through 28, patients received 300 mg of posaconazole plus reduced doses of venetoclax (50 or 100 mg) to account for expected increases in venetoclax plasma concentrations. Blood samples were collected before dosing and up to 24 hours after the venetoclax dose on days 20 and 28. Compared with a venetoclax dose of 400 mg when administered alone (day 20), coadministration of venetoclax at a 50-mg dose with multiple doses of posaconazole increased mean venetoclax C max and AUC 0-24 by 53% and 76%, respectively, whereas coadministration of venetoclax at a 100-mg dose with posaconazole increased mean venetoclax C max and AUC 0-24 by 93% and 155%, respectively. When adjusted for different doses and nonlinearity, posaconazole was estimated to increase venetoclax C max and AUC 0-24 by 7.1- and 8.8-fold, respectively. Both the 50- and 100-mg venetoclax doses administered with posaconazole were well tolerated. The results are consistent with inhibition of CYP3A-mediated metabolism of venetoclax. Posaconazole can be used for antifungal prophylaxis in patients with acute myeloid leukemia receiving venetoclax after reducing the venetoclax dose by at least 75%. ClinicalTrials.gov identifier: NCT02203773. Copyright © 2017 Elsevier HS Journals, Inc. All rights reserved.

Maximum tolerated dose of nalmefene in patients receiving epidural fentanyl and dilute bupivacaine for postoperative analgesia.

PubMed

Dougherty, T B; Porche, V H; Thall, P F

2000-04-01

This study investigated the ability of the modified continual reassessment method (MCRM) to determine the maximum tolerated dose of the opioid antagonist nalmefene, which does not reverse analgesia in an acceptable number of postoperative patients receiving epidural fentanyl in 0.075% bupivacaine. In the postanesthetic care unit, patients received a single intravenous dose of 0.25, 0.50, 0.75, or 1.00 microg/kg nalmefene. Reversal of analgesia was defined as an increase in pain score of two or more integers above baseline on a visual analog scale from 0 through 10 after nalmefene administration. Patients were treated in cohorts of one, starting with the lowest dose. The maximum tolerated dose of nalmefene was defined as that dose, among the four studied, with a final mean probability of reversal of anesthesia (PROA) closest to 0.20 (ie., a 20% chance of causing reversal). The modified continual reassessment method is an iterative Bayesian statistical procedure that, in this study, selected the dose for each successive cohort as that having a mean PROA closest to the preselected target PROA of 0.20. The modified continual reassessment method repeatedly updated the PROA of each dose level as successive patients were observed for presence or absence of ROA. After 25 patients, the maximum tolerated dose of nalmefene was selected as 0.50 microg/kg (final mean PROA = 0.18). The 1.00-microg/kg dose was never tried because its projected PROA was far above 0.20. The modified continual reassessment method facilitated determination of the maximum tolerated dose ofnalmefene . Operating characteristics of the modified continual reassessment method suggest it may be an effective statistical tool for dose-finding in trials of selected analgesic or anesthetic agents.

High doses of nandrolone decanoate reduce volume of testis and length of seminiferous tubules in rats.

PubMed

Noorafshan, Ali; Karbalay-Doust, Saied; Ardekani, Fakhrodin Mesbah

2005-02-01

Anabolic-androgenic steroid (AAS) compounds rank among the drugs most widely abused with the goal of improving athletic ability, appearance, or muscle mass. It has been shown that these compounds have adverse effects on human and animal physiology and sperm quality, but quantitative structural changes of the testis have received less attention. The present study was conducted to evaluate the effects of nandrolone decanoate, which is one of the AAS compounds, on testis weight and volume, diameter and length of seminiferous tubules in rats by unbiased stereological methods. Adult rats were divided into three groups. The first comprised control rats; the second and third groups received low and high doses of nandrolone decanoate for 14 weeks. The rats were then left untreated for 14 weeks. After removal of the testis, stereological study of these tissues showed that the mean volume of testis and length of the seminiferous tubules in the animals that received high doses of nandrolone decanoate were reduced approximately 32% (p<0.01) and approximately 31% (p<0.04), respectively, in comparison with the control group. It can be concluded that the high doses of nandrolone decanoate produce structural changes in the rat testis that remain 14 weeks after stopping injection of the drug.

Study of UV radiation dose received by the Spanish population.

PubMed

Gurrea, Gonzalo; Cañada, Javier

2007-01-01

Excess exposure to UV radiation can affect our health by causing sunburn, skin cancer, etc. It is therefore useful to determine the UV dosage received by people as a way of protecting them from the possible negative effects that this kind of radiation can cause. In this work, the personal outdoor percentage, which shows the time spent in outdoor activities, as well as personal UV doses, has been calculated by means of global UV radiation on a horizontal plane. A database of average daily UVB radiation on the horizontal plane given by the National Institute of Meteorology has been used. In this work we evaluate the standard erythema dose of the Spanish population throughout the year.

Divergent short- and long-term effects of acute stress in object recognition memory are mediated by endogenous opioid system activation.

PubMed

Nava-Mesa, Mauricio O; Lamprea, Marisol R; Múnera, Alejandro

2013-11-01

Acute stress induces short-term object recognition memory impairment and elicits endogenous opioid system activation. The aim of this study was thus to evaluate whether opiate system activation mediates the acute stress-induced object recognition memory changes. Adult male Wistar rats were trained in an object recognition task designed to test both short- and long-term memory. Subjects were randomly assigned to receive an intraperitoneal injection of saline, 1 mg/kg naltrexone or 3 mg/kg naltrexone, four and a half hours before the sample trial. Five minutes after the injection, half the subjects were submitted to movement restraint during four hours while the other half remained in their home cages. Non-stressed subjects receiving saline (control) performed adequately during the short-term memory test, while stressed subjects receiving saline displayed impaired performance. Naltrexone prevented such deleterious effect, in spite of the fact that it had no intrinsic effect on short-term object recognition memory. Stressed subjects receiving saline and non-stressed subjects receiving naltrexone performed adequately during the long-term memory test; however, control subjects as well as stressed subjects receiving a high dose of naltrexone performed poorly. Control subjects' dissociated performance during both memory tests suggests that the short-term memory test induced a retroactive interference effect mediated through light opioid system activation; such effect was prevented either by low dose naltrexone administration or by strongly activating the opioid system through acute stress. Both short-term memory retrieval impairment and long-term memory improvement observed in stressed subjects may have been mediated through strong opioid system activation, since they were prevented by high dose naltrexone administration. Therefore, the activation of the opioid system plays a dual modulating role in object recognition memory. Copyright © 2013 Elsevier Inc. All rights reserved.

[Estimation of effective doses derived from radon in selected SPA centers that use geothermal waters based on the information of radon concentrations].

PubMed

Walczak, Katarzyna; Zmyślony, Marek

2013-01-01

Geothermal waters contain, among other components, soluble radon gas. Alpha radioactive radon is a health hazard to humans, especially when it gets into the respiratory tract. SPA facilities that use geothermal water can be a source of an increased radiation dose to people who stay there. Based on the available literature concerning radon concentrations, we assessed exposure to radon among people - workers and visitors of Spa centers that use geothermal waters. Radon concentrations were analyzed in 17 geothermal centers: in Greece (3 centers), Iran (5), China (4) and India (5). Doses recived by people in the SPA were estimated using the formula that 1 hour exposure to 1 Bq/m3 of radon concentration and equilibrium factor F = 0.4 corresponds to an effective dose of 3.2 nSv. We have found that radon levels in SPAs are from a few to several times higher than those in confined spaces, where geothermal waters are not used (e.g., residential buildings). In 82% of the analyzed SPAs, workers may receive doses above 1 mSv/year. According to the relevant Polish regulations, people receiving doses higher than 1 mSv/year are included in category B of radiation exposure and require regular dosimetric monitoring. Doses received by SPA visitors are much lower because the time of their exposure to radon released from geothermal water is rather short. The analysis of radon concentration in SPA facilities shows that the radiological protection of people working with geothermal waters plays an important role. It seems reasonable to include SPA workers staying close to geotermal waters into a dosimetric monitoring program.

Modelling the effects of booster dose vaccination schedules and recommendations for public health immunization programs: the case of Haemophilus influenzae serotype b.

PubMed

Charania, Nadia A; Moghadas, Seyed M

2017-09-13

Haemophilus influenzae serotype b (Hib) has yet to be eliminated despite the implementation of routine infant immunization programs. There is no consensus regarding the number of primary vaccine doses and an optimal schedule for the booster dose. We sought to evaluate the effect of a booster dose after receiving the primary series on the long-term disease incidence. A stochastic model of Hib transmission dynamics was constructed to compare the long-term impact of a booster vaccination and different booster schedules after receiving the primary series on the incidence of carriage and symptomatic disease. We parameterized the model with available estimates for the efficacy of Hib conjugate vaccine and durations of both vaccine-induced and naturally acquired immunity. We found that administering a booster dose substantially reduced the population burden of Hib disease compared to the scenario of only receiving the primary series. Comparing the schedules, the incidence of carriage for a 2-year delay (on average) in booster vaccination was comparable or lower than that observed for the scenario of booster dose within 1 year after primary series. The temporal reduction of symptomatic disease was similar in the two booster schedules, suggesting no superiority of one schedule over the other in terms of reducing the incidence of symptomatic disease. The findings underscore the importance of a booster vaccination for continued decline of Hib incidence. When the primary series provides a high level of protection temporarily, delaying the booster dose (still within the average duration of protection conferred by the primary series) may be beneficial to maintain longer-term protection levels and decelerate the decline of herd immunity in the population.

Safety, Pharmacokinetic, and Functional Effects of the Nogo-A Monoclonal Antibody in Amyotrophic Lateral Sclerosis: A Randomized, First-In-Human Clinical Trial

PubMed Central

Meininger, Vincent; Pradat, Pierre-François; Corse, Andrea; Al-Sarraj, Safa; Rix Brooks, Benjamin; Caress, James B.; Cudkowicz, Merit; Kolb, Stephen J.; Lange, Dale; Leigh, P. Nigel; Meyer, Thomas; Milleri, Stefano; Morrison, Karen E.; Orrell, Richard W.; Peters, Gary; Rothstein, Jeffrey D.; Shefner, Jeremy; Lavrov, Arseniy; Williams, Nicola; Overend, Phil; Price, Jeffrey; Bates, Stewart; Bullman, Jonathan; Krull, David; Berges, Alienor; Abila, Bams; Meno-Tetang, Guy; Wurthner, Jens

2014-01-01

The neurite outgrowth inhibitor, Nogo-A, has been shown to be overexpressed in skeletal muscle in amyotrophic lateral sclerosis (ALS); it is both a potential biomarker and therapeutic target. We performed a double-blind, two-part, dose-escalation study, in subjects with ALS, assessing safety, pharmacokinetics (PK) and functional effects of ozanezumab, a humanized monoclonal antibody against Nogo-A. In Part 1, 40 subjects were randomized (3∶1) to receive single dose intravenous ozanezumab (0.01, 0.1, 1, 5, or 15 mg/kg) or placebo. In Part 2, 36 subjects were randomized (3∶1) to receive two repeat doses of intravenous ozanezumab (0.5, 2.5, or 15 mg/kg) or placebo, approximately 4 weeks apart. The primary endpoints were safety and tolerability (adverse events [AEs], vital signs, electrocardiogram (ECG), and clinical laboratory tests). Secondary endpoints included PK, immunogenicity, functional endpoints (clinical and electrophysiological), and biomarker parameters. Overall, ozanezumab treatment (0.01–15 mg/kg) was well tolerated. The overall incidence of AEs in the repeat dose 2.5 mg/kg and 15 mg/kg ozanezumab groups was higher than in the repeat dose placebo group and repeat dose 0.5 mg/kg ozanezumab group. The majority were considered not related to study drug by the investigators. Six serious AEs were reported in three subjects receiving ozanezumab; none were considered related to study drug. No study drug-related patterns were identified for ECG, laboratory, or vital signs parameters. One subject (repeat dose 15 mg/kg ozanezumab) showed a weak, positive anti-ozanezumab-antibody result. PK results were generally consistent with monoclonal antibody treatments. No apparent treatment effects were observed for functional endpoints or muscle biomarkers. Immunohistochemical staining showed dose-dependent co-localization of ozanezumab with Nogo-A in skeletal muscle. In conclusion, single and repeat dose ozanezumab treatment was well tolerated and demonstrated co-localization at the site of action. These findings support future studies with ozanezumab in ALS. Trial Registration ClinicalTrials.gov NCT00875446 GSK-ClinicalStudyRegister.com GSK ID 111330 PMID:24841795

Randomised clinical trial: a phase 1, dose-ranging study of the anti-matrix metalloproteinase-9 monoclonal antibody GS-5745 versus placebo for ulcerative colitis.

PubMed

Sandborn, W J; Bhandari, B R; Fogel, R; Onken, J; Yen, E; Zhao, X; Jiang, Z; Ge, D; Xin, Y; Ye, Z; French, D; Silverman, J A; Kanwar, B; Subramanian, G M; McHutchison, J G; Lee, S D; Shackelton, L M; Pai, R K; Levesque, B G; Feagan, B G

2016-07-01

Matrix metalloproteinase-9 is a proteolytic enzyme whose expression is increased in ulcerative colitis. To evaluate the safety and efficacy of GS-5745, a fully humanised anti-matrix metalloproteinase-9 monoclonal antibody, in moderately-to-severely active ulcerative colitis. We randomised 74 patients with ulcerative colitis to treatment with single or multiple ascending intravenous or subcutaneous doses of GS-5745 or placebo. Multiple-dose cohorts received either IV infusions (0.3, 1.0, 2.5 or 5.0 mg/kg GS-5745 or placebo) every 2 weeks (three total IV infusions) or five weekly SC injections (150 mg GS-5745 or placebo). The primary outcomes were the safety, tolerability and pharmacokinetics of escalating single and multiple doses of GS-5745. Exploratory analyses in the multiple-dose cohorts included clinical response (≥3 points or 30% decrease from baseline in Mayo Clinic score and ≥1 point decrease in the rectal bleeding subscore or a rectal bleeding subscore ≤1) and clinical remission (a complete Mayo Clinic score ≤2 with no subscore >1) at Day 36. Biological effects associated with a clinical response to GS-5745 were explored using histological and molecular approaches. Twenty-three of the 42 patients (55%) receiving multiple doses of GS-5745 had adverse events, compared with 5/8 patients (63%) receiving placebo. GS-5745 showed target-mediated drug disposition, approximately dose-proportional increases in maximum plasma concentration and more than dose-proportional increases in the area under the plasma drug concentration-time curve. Clinical response occurred in 18/42 patients (43%) receiving GS-5745 compared with 1/8 patients (13%) receiving placebo. Clinical remission occurred in 6/42 patients (14%) receiving GS-5745 and 0/8 (0%) receiving placebo. Patients with a clinical response to GS-5745 had reductions in matrix metalloproteinase-9 tissue levels (mean 48.9% decrease from baseline compared with a mean 18.5% increase in nonresponders, P = 0.008) significant improvements in histopathology scores (confirmed with three separate histological disease activity indices), as well as changes in colonic gene expression that were consistent with reduced inflammation. This phase 1 trial provides preliminary evidence for the safety and therapeutic potential of GS-5745 in the treatment of ulcerative colitis. © 2016 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.

Assessing doses to interventional radiologists using a personal dosimeter worn over a protective apron.

PubMed

Stranden, E; Widmark, A; Sekse, T

2008-05-01

Interventional radiologists receive significant radiation doses, and it is important to have simple methods for routine monitoring of their exposure. To evaluate the usefulness of a dosimeter worn outside the protective apron for assessments of dose to interventional radiologists. Assessments of effective dose versus dose to dosimeters worn outside the protective apron were achieved by phantom measurements. Doses outside and under the apron were assessed by phantom measurements and measurements on eight radiologists wearing two routine dosimeters for a 2-month period during ordinary working conditions. Finger doses for the same radiologists were recorded using thermoluminescent dosimeters (TLD; DXT-RAD Extremity dosimeters). Typical values for the ratio between effective dose and dosimeter dose were found to be about 0.02 when the radiologist used a thyroid shield and about 0.03 without. The ratio between the dose to the dosimeter under and outside a protective apron was found to be less than 0.04. There was very good correlation between finger dose and dosimeter dose. A personal dosimeter worn outside a protective apron is a good screening device for dose to the eyes and fingers as well as for effective dose, even though the effective dose is grossly overestimated. Relatively high dose to the fingers and eyes remains undetected by a dosimeter worn under the apron.

Effectiveness of different vaccine schedules for heptavalent and 13-valent conjugate vaccines against pneumococcal disease in the Community of Madrid.

PubMed

Latasa, P; Ordobás, M; Garrido-Estepa, M; Gil de Miguel, A; Sanz, J C; Barranco, M D; Insúa, E; García-Comas, L

2017-09-25

The heptavalent pneumococcal conjugate vaccine (PCV-7) was added to the childhood routine vaccination program in the Community of Madrid in November of 2006 with 3+1 recommended doses and a catch-up for those under 2years old. In June 2010, PCV-7 was replaced by 13-valent vaccine (PCV-13) with 2+1 recommended doses. In July of 2012, the PCV-13 was removed from the funded program and reintroduced again (2+1 recommended doses) in December 2014. In between, children were vaccinated privately with 3+1 recommended doses of PCV-13. The aim of this study was to evaluate the effectiveness of each vaccination schedule used in the Community of Madrid. We included all cases of invasive pneumococcal disease (IPD) reported between 2007 and 2015 to the Notifiable Diseases Surveillance System. Vaccination information was obtained from the Immunization Registry. Vaccine effectiveness (VE) was estimated using the indirect cohort design for cases with serotype information. A total 779 cases were included in the study. Among them 47.6% of the cases were primo-vaccinated with booster, 20% primo-vaccinated, 15.9% incompletely primo-vaccinated and 16.5% not vaccinated. The VE for ≥1 doses of any PCV was 82% (CI 95%: 67.8-89.9%): 91.9% (CI 95%: 76.5-97.2%) for PCV-7 and 77.2% (48.6-89.9%) for PCV-13. VE in those receiving the full 2+1 or 3+1 schedules was 100% for both vaccines. A high number of vaccine failures were reported in children before they had the opportunity to receive the booster dose, especially due to PCV-13-non-PCV-7 serotypes. VE was higher for PCV-7 compared to PCV-13, except for those that received the complete schedule with booster that achieved 100% of VE, which shows the relevance of the vaccines and complying with all doses scheduled. Copyright © 2017 Elsevier Ltd. All rights reserved.

Tolerance of young infants to a single, large dose of vitamin A: a randomized community trial in Nepal.

PubMed

West, K P; Khatry, S K; LeClerq, S C; Adhikari, R; See, L; Katz, J; Shrestha, S R; Pradhan, E K; Pokhrel, R P; Sommer, A

1992-01-01

A randomized, double-masked trial was carried out in rural Nepal to investigate the incidence and severity of acute side-effects among neonates ( < 1 month of age) and infants aged 1-6 months who received a large, oral dose of vitamin A (15,000 retinol equivalents (RE) (50,000 IU) and 30,000 RE (100,000 IU), respectively) or placebo (75 RE (250 IU) and 150 RE (500 IU), respectively) in oil. Infants (vitamin A group, n = 1461; controls, n = 1379) were assessed for vomiting, loose stools, fever, and irritability during the 24 hours before and after dosing. Fontanelles were palpated 24 hours after dosing. Neonates exhibited no excess risk of adverse side-effects after receiving 15,000 RE. Compared with controls the older infants who ingested 30,000 RE had a 1.6% excess rate of vomiting (95% confidence interval (CI): 0.2-3.0%) and a 0.5% excess rate (95% CI: -0.1 to 1.1%) in the occurrence of bulging fontanelles. There were no other significant differences in the older infants. The controlled, periodic distribution of a single 15,000 RE dose of vitamin A therefore confers no apparent acute risk to young infants; a 30,000 RE dose is associated with a minimum risk of transient, acute side-effects.

A Phase 2 Trial of Oral Solithromycin 1200 mg or 1000 mg as Single-Dose Oral Therapy for Uncomplicated Gonorrhea.

PubMed

Hook, Edward W; Golden, Matthew; Jamieson, Brian D; Dixon, Paula B; Harbison, Hanne S; Lowens, Sylvan; Fernandes, Prabhavathi

2015-10-01

Progressive resistance to antimicrobial agents has reduced options for gonorrhea therapy worldwide. Solithromycin (CEM-101) is a novel oral fluoroketolide antimicrobial with substantial in vitro activity against Neisseria gonorrhoeae. We conducted a phase 2 trial of 2 oral doses of solithromycin (1200 and 1000 mg) for treatment of uncomplicated gonorrhea. A total of 59 participants were enrolled and treated in this trial; 28 participants received 1200 mg of solithromycin and 31 received 1000 mg. Forty-six (78%) participants had positive cultures for N. gonorrhoeae at the time of enrollment: 24 of the 28 persons (86%) who received 1200 mg of oral solithromycin, and 22 of 31 (71%) who received 1000 mg. In addition, 8 participants had positive pharyngeal gonococcal cultures, and 4 had positive rectal cultures. All patients with positive cultures for N. gonorrhoeae were cured at all sites of infection. Chlamydia trachomatis and Mycoplasma genitalium coinfections were evaluated using nucleic acid amplification tests and were negative at 1 week of follow-up in 9 of 11 (82%) participants positive for C. trachomatis and 7 of 10 (70%) participants positive for M. genitalium. Mild dose-related gastrointestinal side effects (nausea, loose stools, vomiting) were common but did not limit therapy. Oral single-dose solithromycin, in doses of 1000 mg and 1200 mg, was 100% effective for treatment of culture-proven gonorrhea at genital, oral, and rectal sites of infection and is a promising new agent for gonorrhea treatment. NCT01591447. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Efficacy and Tolerability of High-Dose Escitalopram in Posttraumatic Stress Disorder.

PubMed

Qi, Wei; Gevonden, Martin; Shalev, Arieh

2017-02-01

Open-label trials suggest that escitalopram (up to 20 mg/d) is an effective treatment for some, but not all posttraumatic stress disorder (PTSD) patients. Higher doses of escitalopram effectively reduced major depression symptoms in patients who had not responded to regular doses. The current study examines the efficacy, tolerability, and adherence to high-dose escitalopram in PTSD. Forty-five PTSD patients received 12 weeks of gradually increasing doses of escitalopram reaching 40 mg daily at 4 weeks. Among those, 12 participants received regular doses of antidepressants at study onset including escitalopram (n = 7). The Clinician-Administered PTSD Scale (CAPS) evaluated PTSD symptoms severity before treatment, at 3 months (upon treatment termination), and at 6 months (maintenance effect). A 20% reduction in CAPS scores was deemed clinically significant. Adverse events and medication adherence were monitored at each clinical session. Linear mixed-models analysis showed a significant reduction of mean CAPS scores (11.5 ± 18.1 points) at 3 months and maintenance of gains by 6 months (F2,34.56 = 8.15, P = 0.001). Eleven participants (34.3%) showed clinically significant improvement at 3 months. Only 9 participants (20%) left the study. There were no serious adverse events and few mild ones with only 2 adverse events (diarrhea, 11.1%; drowsiness, 11.1%) reported by more than 10% of participants. High doses of escitalopram are tolerable and well adhered to in PTSD. Their beneficial effect at a group level is due to a particularly good response in a subset of patients.Variability in prior pharmacological treatment precludes a definite attribution of the results to high doses of escitalopram.

Dose- dependent ameliorative effects of quercetin and l-Carnitine against atrazine- induced reproductive toxicity in adult male Albino rats.

PubMed

Abdel Aziz, Rabie L; Abdel-Wahab, Ahmed; Abo El-Ela, Fatma I; Hassan, Nour El-Houda Y; El-Nahass, El-Shaymaa; Ibrahim, Marwa A; Khalil, Abdel-Tawab A Y

2018-06-01

This study aimed to determine the protective effects of co-administration of Quercetin (QT) or l-Carnitine (LC) against the oxidative stress induced by Atrazine (ATZ) in the reproductive system of intact male Albino rats. 36 rats were divided equally into 6 groups. Rats in the control negative "CNT" group received 1.5 ml distilled water for 21 days. All rats in the other groups received ATZ (120 mg/kg bw) through gavage. Groups 3 and 4 were co-administered with either low or high dose of QT (10 "ATZLQT" and 50 "ATZHQT" mg/kg bw, respectively). Groups 5 and 6 were co-administered with either low or high dose of LC (200 "ATZLLC" and 400 "ATZHLC" mg/kg bw, respectively). At the end of the experiment, animals were sacrificed and all samples were collected. ATZ significantly increased serum level of malondialdehyde (MDA) and decreased total antioxidant capacity (TAC). Also, ATZ increased significantly the sperm cell abnormalities and reduced both testicular IgA and serum testosterone levels. Testicular DNA laddering % and CYP17A1 mRNA expression were significantly reduced in ATZ group. Interestingly, co-administration with low dose QT or different doses of LC succeeded to counteract the negative toxic effects of ATZ on serum oxidative stress indicators, serum testosterone levels, testicular IgA level and improved testicular CYP17A1 mRNA expression. In conclusion, QT in low dose and LC in both low and high doses exerted a significant protective action against the reproductive toxicity of ATZ, while higher dose of QT failed induce immune-stimulant effect against ATZ in adult male Albino rats. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

A Comparative Study on the Life-Saving Radioprotective Effects of Vitamins A, E, C and Over-the-Counter Multivitamins.

PubMed

Mortazavi, S M J; Rahimi, S; Mosleh-Shirazi, M A; Arjomandi, M; Soleimani, A; Koohi Hossein-Abadi, O; Haghani, M; Alavi, M

2015-06-01

Oral intake of vitamins which present antioxidant characteristics can protect living organisms against oxidative damage caused by exposure to ionizing radiation. It was previously reported that administration of high levels of vitamin C can lead to increased DNA damage through production of hydroxyl radicals from hydrogen peroxide by the Fenton reaction. However, our early experiments did not confirm this hypothesis. The main goal of this study was to determine if high doses of Vit C can show life-saving radioprotective effects. Phase I: Seventy two male Balb/c mice weighing 20-25g were randomly divided into six groups of 12 animals each. Group I; Vit E for five days, Groups II and III; Vit C and Vit A. Group 4; all three vitamins. Group V; an over-the-counter multivitamin. Group VI; none of the above. Phase II: 120 male BALB/c mice weighing 20-25g were randomly divided into 12 groups of 10 each. Group I; Vit A for five days. Groups II-IV; Vit C 200 mg/kg, 400 mg/kg, 800 mg/kg, respectively. Group V-VII; Vit E at daily doses of 200 iu/kg, 400 iu/kg, 800 iu/kg, respectively. Group VIII and IX; all three vitamins at low and high doses, respectively. Group X; an over-the-counter multivitamin. Group XI; controls group and Group XII; received pure olive oil. All animals (Phases I and II) were exposed to a lethal dose of gamma rays and the survival rates of the animals were monitored and recorded continuously for 16 days after exposure. Phase I: 14 days after irradiation the survival rate for control group was 33.33%, while the survival rates for the 1st to 5th groups were 45.45%, 81.81%, 50%, 57.14%, and 9.09% , respectively. Phase II: The survival rates in the control group and the group that only received pure olive oil, were 50% and 60%, respectively. Survival rate in the animals received Vit C at daily doses of 200 mg/kg, 400 mg/kg, 800 mg/kg, were 90%, 90% and 90%, respectively. Log rank (Mantel-Cox) test showed statistically significant differences between the survival rates in control irradiated mice (no vitamins) and mice received Vit C at daily doses of 200 mg/kg (P=0.042), 400 mg/kg (P=0.042) and 800 mg/kg (P=0.042). Altogether, findings of this study showed that even high doses of Vit C can show life-saving radioprotective effects. The significant radioprotective effect of Vit C at doses used in this study, opens new horizons in developing non-toxic, cost effective, easily available radioprotectors in life-threatening situations such as exposure to lethal doses of ionizing radiation.  The radioprotective effect of Vit A and Vit E seem to be less efficient compared to that of Vit C.

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.

[Improved radiation protection for medical personnel in angiography and interventional radiology using permanent shielding devices in accordance with section 21 of the Radiography Regulation].

PubMed

Eder, H

1995-03-01

Presently examiners using angiographic methods are not accustomed to measure the exposition of parts of the body. This results in a considerable undervaluation of the really received doses (in terms of effective dose). Only a consequent application of dosimetry in parts of the body--demanded by section 35 of the German X-Ray Regulation and also by the corresponding guide-line--demonstrates the real problems i.e. oversteppings of dose limits. The use of practicable installations for permanent shielding will lead to an improvement of the situation and result in a significant decrease of the received doses and--at the same time--a minor physical burden of the examinator. Dosimetry of radiation was performed at the position of the examiner both with and without the application of permanent shielding (acrylic glass (PMMA) containing lead plus shielding of the lower part of the body). It could be demonstrated that a decrease of the received dose can be reached by a rate of 2.5 to 5 concerning the trunk and of 50 concerning the skull, upper arm and hands.

Experimental Clostridium perfringens type D enterotoxemia in goats.

PubMed

Uzal, F A; Kelly, W R

1998-03-01

The effects of intraduodenal administration of Clostridium perfringens cultures and culture products in goats were evaluated to develop a reliable experimental model of enterotoxemia in this species. Five conventionally reared, 11-16-week-old Angora goat kids were dosed intraduodenally with whole cultures of C. perfringens type D; five similar animals were dosed with C. perfringens type D filtered culture supernatant; and a third group of five kids was dosed with C. perfringens type D washed cells. Two kids were used as controls and received sterile, nontoxic culture medium intraduodenally. All animals received starch solution into the abomasum. All five kids inoculated with whole culture and three of five dosed with culture supernatant and with washed cells developed central nervous system signs. Diarrhea was observed in two of five kids inoculated with whole culture, in all five of those dosed with culture supernatant, and in three of five of those that received washed cells. The most striking postmortem findings consisted of lung edema, necrotizing pseudomembranous colitis, and cerebral vasogenic edema. The protocol thus provided a reasonable model of naturally occurring enterotoxemia in goats, producing a range of clinical signs and postmortem changes similar to those observed in the natural disease.

The effect of duration of dose delivery with patient-controlled analgesia on the incidence of nausea and vomiting after hysterectomy

PubMed Central

Woodhouse, Annie; Mather, Laurence E

1998-01-01

Aims Postoperative nausea and vomiting (PONV) may be exacerbated by postoperative opioid analgesics and may limit patients’ successful use of these medications when used with patient controlled analgesia (PCA). We tested the hypothesis that the rapid change in blood morphine concentration associated with PCA bolus delivery contributed to PONV, and that prolonging its delivery to a brief infusion would result in decreased PONV. Methods Patients, who were receiving morphine for pain relief via patient-controlled analgesia (PCA) after total abdominal hysterectomy, received 1 mg morphine sulphate incremental doses either over 40 s with a 5 min lockout interval or over 5 min delivery with a 1 min lockout interval. Episodes of nausea, retching and vomiting, along with the use of morphine and the pain relief obtained, were recorded. Results Data from 20 patients in each group were analysed. Contrary to expectations, most patients in both groups reported nausea postoperatively. Those patients receiving morphine over 5 min experienced more episodes of emesis (36) than those receiving the dose over 40 s (17). Most patients receiving the 40 s doses vomited in the first 12 h (median time 8 h), while those receiving the 5 min doses vomited between 12 and 24 h (median time 19 h) (P=0.01). There were no differences between groups in the visual analogue pain scores or use of morphine between groups. Conclusions Reasons for these unexpected findings remain speculative. The high incidence of PONV appears to be inherently high in gynaecological surgery patients and standard antiemetic medication regimens appear to be poorly efficacious. Reasons for the differences in the time-course of emetic episodes between the two groups may be related to differences in the time-course of central opioid receptor occupancy. PMID:9489595

Effect of contrast media on megavoltage photon beam dosimetry.

PubMed

Rankine, Ashley W; Lanzon, Peter J; Spry, Nigel A

2008-01-01

The purpose of this study was to quantify changes in photon beam dosimetry caused by using contrast media during computed tomography (CT) simulation and determine if the resulting changes are clinically significant. The effect of contrast on dosimetry was first examined for a single 6-MV photon beam incident on a plane phantom with a structure of varying electron densities (rho(e)) and thickness. Patient studies were then undertaken in which CT data sets were collected with and without contrast for 6 typical patients. Three patients received IV contrast (Optiray-240) only and 3 received IV plus oral (Gastrograffin) contrast. Each patient was planned using conformal multifield techniques in accordance with the department standards. Two methods were used to compare the effect of contrast on dosimetry for each patient. The phantom analysis showed that the change in dose at the isocenter for a single 10 x 10 cm2 6-MV photon beam traversing 10 cm of a contrast-enhanced structure with rho(e) 1.22 was 7.0% (1.22 was the highest average rho(e) observed in the patient data). As a result of using contrast, increases in rho(e) were observed in structures for the 6 patients studied. Consequently, when using contrast-enhanced CT data for multifield planning, increases in dose at the isocenter and in critical structures were observed up to 2.1% and 2.5%, respectively. Planning on contrast-enhanced CT images may result in an increase in dose of up to 2.1% at the isocenter, which would generally be regarded as clinically insignificant. If, however, a critical organ is in close proximity to the planning target volume (PTV) and is planned to receive its maximum allowable dose, planning on contrast-enhanced CT images may result in that organ receiving dose beyond the recommended tolerance. In these instances, pre-contrast CT data should be used for dosimetry.

Efficacy and safety of add on low-dose mirtazapine in depression.

PubMed

Matreja, Prithpal S; Badyal, Dinesh K; Deswal, Randhir S; Sharma, Arvind

2012-03-01

Although antidepressant medications are effective, they have a delayed onset of effect. Mirtazapine, an atypical antidepressant is an important option for add-on therapy in major depression. There is insufficient data on mirtazapine in Indian population; hence this study was designed to study the add-on effect of low-dose mirtazapine with selective serotonin reuptake inhibitors (SSRIs) in major depressive disorder (MDD) in Indian population. In an open, randomized study, 60 patients were divided into two groups. In Group A (n=30) patients received conventional SSRIs for 6 weeks. In Group B (n=30) patients received conventional SSRIs with low-dose mirtazapine for 6 weeks. Patients were evaluated at baseline and then at 1, 2, 3, 4, 5, and 6 weeks. There was significant improvement in Hamilton Depression Rating Scale (HDRS), Montgomery and Asberg depression rating scale (MADRS) scores (P<0.05) in both groups. Mirtazapine in low dose as add on therapy showed improvement in scores, had earlier onset of action, and more number of responders and remitters as compared to conventional treatment (P<0.05). No serious adverse event was reported in either of the groups. Low-dose mirtazapine as add-on therapy has shown better efficacy, earlier onset of action and more number of responders and remitters as compared to conventional treatment in MDD in Indian patients.

Gonad dose in AP pelvis radiography: Impact of anode heel orientation.

PubMed

Mraity, H A A B; England, A; Hogg, P

2017-02-01

For antero posterior (AP) pelvis radiographic examination, determine the impact of anode heel orientation on female/male gonad dose. High sensitivity thermo-luminescent dosimeters (TLDs) were used with an ATOM dosimetry phantom; the phantom was positioned for AP pelvis. TLDs were placed into the testes and ovaries. Radiation dose received by these organs was measured with the feet toward anode and feet toward the cathode. kVp, mAs and SID were manipulated to generate a range of exposures. A dose profile was also generated using Unfors Mult-O-Meter 401 along the long axis of the phantom. A decrease in dose from the central ray toward the anode was noted, with a marked increase toward the cathode. A significant reduction in dose was received by the testes with feet towards the anode compared with feet towards cathode (P˂0.001). No difference was seen for ovarian dose (P˃0.05). kVp, mAs and SID all have an effect on male and female gonad dose. For male pelvis imaging, placing feet towards the anode can be used as a simple dose reduction method. Copyright © 2016 The College of Radiographers. Published by Elsevier Ltd. All rights reserved.

Combined effects of methamphetamine and zolpidem on performance and mood during simulated night shift work.

PubMed

Hart, Carl L; Haney, Margaret; Nasser, Jennifer; Foltin, Richard W

2005-07-01

Individuals who work irregular or rotating shifts often use stimulants and sedatives to offset shift-change-related mood and performance decrements. During this simulated shift work study the acute effects of the stimulant, methamphetamine were examined, and the effects of the hypnotic, zolpidem, and the combination were assessed during the shift after drug administration. Eight volunteers completed this 21-day, within-participant, residential laboratory study during which they received a single oral methamphetamine dose (0 or 10 mg) 1 h after waking, i.e., before task performance, and a single oral zolpidem dose (0 or 10 mg) 1 h before bedtime under 2 shift conditions: day shift and night shift. When participants received placebo at both dosing times, performance on some psychomotor tasks (e.g., the digit-symbol substitution task) and on some measures of mood (e.g., ratings of "Energetic") were disrupted during the night shift, relative to the day shift. Methamphetamine alone eliminated virtually all shift-related disruptions, while zolpidem alone and the drug combination produced few effects. These data indicate that shift changes produce performance impairments and mood alterations that are improved by a single low to moderate dose of methamphetamine. Zolpidem, given alone or in combination with methamphetamine, did not alleviate most shift-change mood and performance effects.

Effects of acepromazine and trazodone on anesthetic induction dose of propofol and cardiovascular variables in dogs undergoing general anesthesia for orthopedic surgery.

PubMed

Murphy, Lindsey A; Barletta, Michele; Graham, Lynelle F; Reichl, Lorna J; Duxbury, Margaret M; Quandt, Jane E

2017-02-15

OBJECTIVE To compare the doses of propofol required to induce general anesthesia in dogs premedicated with acepromazine maleate or trazodone hydrochloride and compare the effects of these premedicants on cardiovascular variables in dogs anesthetized for orthopedic surgery. DESIGN Prospective, randomized study. ANIMALS 30 systemically healthy client-owned dogs. PROCEDURES 15 dogs received acepromazine (0.01 to 0.03 mg/kg [0.005 to 0.014 mg/lb], IM) 30 minutes before anesthetic induction and 15 received trazodone (5 mg/kg [2.27 mg/lb] for patients > 10 kg or 7 mg/kg [3.18 mg/lb] for patients ≤ 10 kg, PO) 2 hours before induction. Both groups received morphine sulfate (1 mg/kg [0.45 mg/lb], IM) 30 minutes before induction. Anesthesia was induced with propofol (4 to 6 mg/kg [1.82 to 2.73 mg/lb], IV, to effect) and maintained with isoflurane or sevoflurane in oxygen. Bupivacaine (0.5 mg/kg [0.227 mg/lb]) and morphine (0.1 mg/kg [0.045 mg/lb]) were administered epidurally. Dogs underwent tibial plateau leveling osteotomy (n = 22) or tibial tuberosity advancement (8) and were monitored throughout anesthesia. Propofol induction doses and cardiovascular variables (heart rate and systemic, mean, and diastolic arterial blood pressures) were compared between groups. RESULTS The mean dose of propofol required for anesthetic induction and all cardiovascular variables evaluated did not differ between groups. Intraoperative hypotension developed in 6 and 5 dogs of the acepromazine and trazodone groups, respectively; bradycardia requiring intervention developed in 3 dogs/group. One dog that received trazodone had priapism 24 hours later and was treated successfully. No other adverse effects were reported. CONCLUSIONS AND CLINICAL RELEVANCE At the described dosages, cardiovascular effects of trazodone were similar to those of acepromazine in healthy dogs undergoing anesthesia for orthopedic surgery.

Does Omegaven have beneficial effects on a rat model of ovarian ischemia/reperfusion?

PubMed

Gungor, Ayse N Cakir; Turkon, Hakan; Albayrak, Aynur; Ovali, Mehmet; Islimye, Mine; Gencer, Meryem; Hacivelioglu, Servet; Cevizci, Sibel; Cesur, Ismet; Cosar, Emine

2014-10-01

The beneficial effects of omega-3 fatty acids on an intestinal ischemia/reperfusion (I/R) model was shown previously. Therefore, we aimed to examine the potential beneficial effects of parenteral omega-3 fatty acids, a safe and inexpensive product, on a rat model of ovarian I/R. A group of 39 rats was divided into six groups. Group 1 (Sham Group; n=6) underwent two laparotomies with a 3-h interval and their ovaries were removed 3h later. Group 2 (torsion-detorsion Group; n=7) had their ovaries torsioned clockwise and fixed at 720°; 3h later a detorsion operation was done and after another 3h, their ovaries were removed. Group 3 (n=7) and Group 4 (n=7) received the same treatment as Group 2; however, half an hour prior to detorsion, these rats received Omegaven at 1mL/kg and 5mL/kg, respectively. Group 5 (n=6) and Group 6 (n=6) received the same treatment as Group 1; however, half an hour prior to the second laparotomy, these rats received Omegaven at 1mL/kg and 5mL/kg, respectively. One ovary from each rat was evaluated histologically by hematoxylin and eosin (H&E) staining and the other ovary was homogenized and evaluated for total oxidant status (TOS), total antioxidant status (TAS) and oxidative stress index (OSI). While we failed to show any significant relationship among groups in oxidative parameters, there was a significant worsening in the torsion-detorsion group in histological evaluation. High Omegaven doses, but not low doses, improved tissue injury scores of torsioned and detorsioned ovaries to the levels observed in the control group. Omegaven improves the detrimental effects of ovarian I/R when used in sufficient doses. Its effects and dose adjustment on women with ovarian torsion must be investigated by further studies. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Treatment with acetaminophen/paracetamol or ibuprofen alleviates post-dose symptoms related to intravenous infusion with zoledronic acid 5 mg.

PubMed

Wark, J D; Bensen, W; Recknor, C; Ryabitseva, O; Chiodo, J; Mesenbrink, P; de Villiers, T J

2012-02-01

Patients treated with intravenous zoledronic acid 5 mg for osteoporosis may experience post-dose influenza-like symptoms. Oral acetaminophen/paracetamol or ibuprofen administered 4 h post-infusion reduced the proportion of patients with increased oral temperature and worsening post-infusion symptom scores vs. placebo, thus providing an effective strategy for the treatment of such symptoms. Once-yearly intravenous zoledronic acid 5 mg is a safe and effective treatment for postmenopausal osteoporosis. This study assessed whether transient influenza-like post-dose symptoms associated with intravenous infusion of zoledronic acid can be reduced by post-dose administration of acetaminophen/paracetamol or ibuprofen. In an international, multicenter, randomized, double-blind, double-dummy parallel-group study, bisphosphonate-naïve postmenopausal women with osteopenia (n = 481) were randomized to receive zoledronic acid 5 mg + acetaminophen/paracetamol (n = 135), ibuprofen (n = 137) or placebo (n = 137), or placebo + placebo (n = 72). Acetaminophen/paracetamol and ibuprofen were administered every 6 h for 3 days beginning 4 h post-infusion. The proportion of patients with increased oral temperature (≥1°C above 37.5°C) and with worsening post-infusion symptom scores over 3 days was significantly lower in patients receiving ibuprofen (36.8% and 48.5%) or acetaminophen/paracetamol (37.3% and 46.3%) vs. those receiving placebo (63.5% and 75.9%, respectively; all p < 0.0001) compared with background rates of 11.1% and 16.7%, respectively, in the absence of any active treatment. Overall incidence of adverse events was comparable for patients receiving acetaminophen/paracetamol or ibuprofen. Oral acetaminophen/paracetamol or ibuprofen effectively managed the transient influenza-like symptoms associated with zoledronic acid 5 mg.

Single dose parenteral hyposensitization to poison ivy urushiol in guinea pigs.

PubMed

Walker, L A; Watson, E S; elSohly, M A

1995-08-01

Studies were carried out in guinea pigs to evaluate the potential for single dose hyposensitization to poison ivy urushiol dermatitis. Sensitization was induced by topical application of 1 mg of poison ivy urushiol to the back of the neck. In the first series of studies, three different analogs of poison ivy urushiol were studied: 1) a mixture of pentadecyl and heptadecyl catechols (PDC/HDC), the saturated side chain analog of the natural urushiol mixture; 2) a mixture of the diacetate esters of PDC and HDC (PDC/HDC Ac), the esterified form of the saturated sidechain analogs; 3) 2-n-pentadecyl hydroquinone diacetate (HQ Ac). Each of these compounds was administered as 5 mg of the free catechol i.m. each week for three weeks. A vehicle group received only corn oil injections. Reactivity to poison ivy urushiol (PIU) challenge was evaluated in skin tests at 1 and 5 weeks post-treatment. PDC/HDC Ac induced a marked reduction in both the incidence and the severity of lesions induced by PIU at both 1 and at 5 weeks post-treatment. Other analogs were ineffective at 5 weeks post-treatment, and were less effective than PDC/HDC Ac at 1 week post-treatment. In a second series of experiments, the efficacy of PDC/HDC Ac was evaluated in both single and multiple dose regiments. One treatment group received 5 mg of PDC/HDC Ac intramuscularly each week for 4 weeks, while another treatment group received a single dose of 20 mg PDC/HDC Ac i.m. Corresponding vehicle control groups were also included. At 1 week post-treatment in the single dose group, the PDC/HDC Ac was only modestly effective, with some reduction of severity of lesions at the higher challenge doses of PIU. However, at 4 and 7 weeks post-treatment, both the incidence and the severity of the lesions at all challenge doses were reduced. In the multiple dose group, the incidence and severity of lesions are reduced at 1 week and 4 weeks post-treatment (4 weeks and 7 weeks after the initial dose) but were not significantly different from the single dose group. These findings indicate that the diacetate ester of PDC/HDC is an effective hyposensitizer to poison ivy urushiol, and that this hyposensitization can be reasonably accomplished in a single dose treatment regimen.

Efficacy of transfusion with granulocytes from G-CSF/dexamethasone–treated donors in neutropenic patients with infection

PubMed Central

Boeckh, Michael; Harrison, Ryan W.; McCullough, Jeffrey; Ness, Paul M.; Strauss, Ronald G.; Nichols, W. Garrett; Hamza, Taye H.; Cushing, Melissa M.; King, Karen E.; Young, Jo-Anne H.; Williams, Eliot; McFarland, Janice; Holter Chakrabarty, Jennifer; Sloan, Steven R.; Friedman, David; Parekh, Samir; Sachais, Bruce S.; Kiss, Joseph E.; Assmann, Susan F.

2015-01-01

High-dose granulocyte transfusion therapy has been available for 20 years, yet its clinical efficacy has never been conclusively demonstrated. We report here the results of RING (Resolving Infection in Neutropenia with Granulocytes), a multicenter randomized controlled trial designed to address this question. Eligible subjects were those with neutropenia (absolute neutrophil count <500/μL) and proven/probable/presumed infection. Subjects were randomized to receive either (1) standard antimicrobial therapy or (2) standard antimicrobial therapy plus daily granulocyte transfusions from donors stimulated with granulocyte colony-stimulating factor (G-CSF) and dexamethasone. The primary end point was a composite of survival plus microbial response, at 42 days after randomization. Microbial response was determined by a blinded adjudication panel. Fifty-six subjects were randomized to the granulocyte arm and 58 to the control arm. Transfused subjects received a median of 5 transfusions. Mean transfusion dose was 54.9 × 109 granulocytes. Overall success rates were 42% and 43% for the granulocyte and control groups, respectively (P > .99), and 49% and 41%, respectively, for subjects who received their assigned treatments (P = .64). Success rates for granulocyte and control arms did not differ within any infection type. In a post hoc analysis, subjects who received an average dose per transfusion of ≥0.6 × 109 granulocytes per kilogram tended to have better outcomes than those receiving a lower dose. In conclusion, there was no overall effect of granulocyte transfusion on the primary outcome, but because enrollment was half that planned, power to detect a true beneficial effect was low. RING was registered at www.clinicaltrials.gov as #NCT00627393. PMID:26333778

Effects of arbuscular mycorrhizal inoculation and fertilization on mycorrhizal Statute of Jacaranda mimosifolia D.Don cultivated in nurseries.

PubMed

Zaouchi, Yousr; Bahri, Nada Ben; Rezgui, S; Bettaieb, Taoufik

2013-10-01

The effects of fertilization and the nature of the inoculum as well as the variation of the dose intake of the latter on the level of Jacaranda mimosifolia D.Don mycorhization were tested. Young plants were treated with two inoculums presenting different origins, compositions and modes of application: one is a commercial product containing Glomus irregulare, and the other is a composite indigenous inoculum resulting from trapping five species of genus Glomus and also from multiplication on mycotrophic plants: leek (Allium porrum L.) and vetch (Vicia sativa L.). For each inoculum, two doses were tested and for each dose of inoculum, four levels of fertilization based on a complete commercial fertilizer (Osmocote) were tested: 0 g/plant, 2 g/plant, 4 g/plant, and 6g/plant. Three repetitions were performed for each combination treatment of inoculum/fertilizer. One-year-old young Jacaranda plants, being about 40 cm high, were cultured under greenhouse in 10/12 cm caliber pots. After six months, all the inoculated plants were mycorrhized. According to endomycorrhizal structures found on their roots, plants receiving doses of composite indigenous inoculum reached a more advanced stage of mycorrhization than those treated with the commercial inoculum. The existence of an interaction effect between the inoculum dose and the level of fertilization on Jacaranda mycorhization rate was excluded. These two parameters of variation were studied as simple effects. The increase in commercial inoculum dose had a significant positive influence on the level of Jacaranda plants mycorrhization (P=0.05). The rate of mycorrhization jumped from 12.69% to 21.92%. Nonetheless, for plants receiving increasing doses of composite indigenous inoculum, the level of mycorrhization has varied randomly. In both instances of inoculum treatments, increasing the dose of fertilizer significantly inhibited endomycorrhizal colonization of Jacaranda roots (P=0.01). Thus, the rate of root colonization decreased from 47.43% to 2.41% for plants receiving the composite indigenous inoculums. It decreased from 32.35% to 3.95% for those treated with the commercial inoculum. Mycorrhization had a positive effect on root dry biomass of Jacaranda, as in the case of unfertilize ave the highest rates of colonization. Copyright © 2013. Published by Elsevier SAS.

131I-tositumomab myeloablative radioimmunotherapy for non-Hodgkin’s lymphoma: radiation dose to the testes

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

Hattori, Naoya; Gopal, Ajay K.; Shields, Andrew T.

Purpose: To investigate radiation doses to the testes delivered by a radiolabeled anti-CD20 antibody and its effects on male sex hormone levels. Materials and methods: Testicular uptake and retention of 131I-tositumomab were measured, and testicular absorbed doses were calculated for 67 male patients (54+/-11 years of age) with non-Hodgkin's lymphoma who had undergone myeloablative radioimmunotherapy (RIT) using 131I-tositumomab. Time-activity curves for the major organs, testes, and whole body were generated from planar imaging studies. In a subset of patients, male sex hormones were measured before and 1 year after the therapy. Results: The absorbed dose to the testes showed considerablemore » variability (range=4.4-70.2 Gy). Pretherapy levels of total testosterone were below the lower limit of the reference range, and post-therapy evaluation demonstrated further reduction [4.6+/-1.8 nmol/l (pre-RIT) vs. 3.8+/-2.9 nmol/l (post-RIT), P<0.05]. Patients receiving higher radiation doses to the testes (>=25 Gy) showed a greater reduction [4.7+/-1.6 nmol/l (pre-RIT) vs. 3.3+/-2.7 nmol/l (post-RIT), P<0.05] compared with patients receiving lower doses (<25 Gy), who showed no significant change in total testosterone levels. Conclusion: The testicular radiation absorbed dose varied highly among individual patients. Finally, patients receiving higher doses to the testes were more likely to show post-RIT suppression of testosterone levels.« less

Dosimetric impact in the dose-volume histograms of rectal and vesical wall contouring in prostate cancer IMRT treatments.

PubMed

Gómez, Laura; Andrés, Carlos; Ruiz, Antonio

2017-01-01

The main purpose of this study was to evaluate the differences in dose-volume histograms of IMRT treatments for prostate cancer based on the delineation of the main organs at risk (rectum and bladder) as solid organs or by contouring their wall. Rectum and bladder have typically been delineated as solid organs, including the waste material, which, in practice, can lead to an erroneous assessment of the risk of adverse effects. A retrospective study was made on 25 patients treated with IMRT radiotherapy for prostate adenocarcinoma. 76.32 Gy in 36 fractions was prescribed to the prostate and seminal vesicles. In addition to the delineation of the rectum and bladder as solid organs (including their content), the rectal and bladder wall were also delineated and the resulting dose-volume histograms were analyzed for the two groups of structures. Data analysis shows statistically significant differences in the main parameters used to assess the risk of toxicity of a prostate radiotherapy treatment. Higher doses were received on the rectal and bladder walls compared to doses received on the corresponding solid organs. The observed differences in terms of received doses to the rectum and bladder based on the method of contouring could gain greater importance in inverse planning treatments, where the treatment planning system optimizes the dose in these volumes. So, one should take into account the method of delineating of these structures to make a clinical decision regarding dose limitation and risk assessment of chronic toxicity.

The role of single-shot metronidazole in the prevention of Clostridium difficile infection following ileostomy reversal surgery.

PubMed

Fernandes, Roland; Robinson, Paul; Rangarajan, Karan; Scott, Sophie; Angco, Laura

2017-05-01

Symptomatic infection with Clostridium difficile is strongly linked to antibiotic use and rates are higher for colorectal surgery. In February 2015, trust policy for antibiotic prophylaxis of ileostomy reversal surgery was changed from three doses of metronidazole plus cefuroxime to single-dose metronidazole, in a bid to reduce rates of Clostridium difficile infection. A retrospective cohort study was conducted at a single, large hospital trust between February 2014 and February 2016, before and after change in antimicrobial policy. Theatre data, clinical notes and pathology results were all reviewed. Outcome data, patient age, gender, length of operation and hospital stay were extracted. One hundred three patients underwent ileostomy reversal surgery between February 2014 and February 2015. All received cefuroxime together with metronidazole at induction of anaesthesia followed by two further post-operative doses as operative prophylaxis. Ninety-six patients underwent ileostomy reversal surgery between February 2015 and February 2016. All received single-dose metronidazole at induction as prophylaxis. Post-operative diarrhoea was significantly reduced in patients given single-dose metronidazole compared with patients managed with multiple dose, dual antibiotic therapy (32 vs 12.5%, P 0.001). Rates of CDI were also significantly reduced in patients given single-dose metronidazole (6.8 vs 1%, P 0.038). Single-dose, pre-operative metronidazole is effective at reducing post-operative diarrhoea and CDI in ileostomy reversal surgery compared with multiple-dose cefuroxime plus metronidazole. Metronidazole may be effective as a prophylactic antibiotic against CDI in colonic surgery.

Protective effect of N-acetylcysteine against ethanol-induced gastric ulcer: A pharmacological assessment in mice

PubMed Central

Jaccob, Ausama Ayoob

2015-01-01

Aim: Since there is an increasing need for gastric ulcer therapies with optimum benefit-risk profile. This study was conducted to investigate gastro-protective effects of N-acetylcysteine (NAC) against ethanol-induced gastric ulcer models in mice. Materials and Methods: A total of 41 mice were allocated into six groups consisted of 7 mice each. Groups 1 (normal control) and 2 (ulcer control) received distilled water at a dose of 10 ml/kg, groups 3, 4 and 5 were given NAC at doses 100, 300 and 500 mg/kg, respectively, and the 6th group received ranitidine (50 mg/kg). All drugs administered orally once daily for 7 days, on the 8th day absolute ethanol (7 ml/kg) was administrated orally to all mice to induce the acute ulcer except normal control group. Then 3 h after, all animals were sacrificed then consequently the stomachs were excised for examination. Results: NAC administration at the tested doses showed a dose-related potent gastro-protective effect with significant increase in curative ratio, PH of gastric juice and mucus content viscosity seen with the highest dose of NAC and it is comparable with that observed in ranitidine group. Conclusion: The present findings demonstrate that, oral NAC shows significant gastro-protective effects comparable to ranitidine confirmed by anti-secretory, cytoprotective, histological and biochemical data, but the molecular mechanisms behind such protection are complex. PMID:26401392

Dose-volume parameters predict for the development of chest wall pain after stereotactic body radiation for lung cancer.

PubMed

Mutter, Robert W; Liu, Fan; Abreu, Andres; Yorke, Ellen; Jackson, Andrew; Rosenzweig, Kenneth E

2012-04-01

Chest wall (CW) pain has recently been recognized as an important adverse effect of stereotactic body radiation therapy (SBRT) for non-small-cell lung cancer (NSCLC). We developed a dose-volume model to predict the development of this toxicity. A total of 126 patients with primary, clinically node-negative NSCLC received three to five fractions of SBRT to doses of 40-60 Gy and were prospectively followed. The dose-absolute volume histograms of two different definitions of the CW as an organ at risk (CW3cm and CW2cm) were examined for all 126 patients. With a median follow-up of 16 months, the 2-year estimated actuarial incidence of Grade ≥ 2 CW pain was 39%. The median time to onset of Grade ≥ 2 CW pain (National Cancer Institute Common Terminology Criteria for Adverse Events, Version 3.0) was 9 months. There was no predictive advantage for biologically corrected dose over physical dose. Neither fraction number (p = 0.07) nor prescription dose (p = 0.07) were significantly correlated with the development of Grade ≥ 2 CW pain. Cox Proportional Hazards analysis identified significant correlation with a broad range of dose-volume combinations, with the CW volume receiving 30 Gy (V30) as one of the strongest predictors (p < 0.001). CW2cm consistently enabled better prediction of CW toxicity. When a physical dose of 30 Gy was received by more than 70 cm(3) of CW2cm, there was a significant correlation with Grade ≥ 2 CW pain (p = 0.004). CW toxicity after SBRT is common and long-term follow-up is needed to identify affected patients. A volume of CW ≥ 70 cm(3) receiving 30 Gy is significantly correlated with Grade ≥ 2 CW pain. We are currently applying this constraint at our institution for patients receiving thoracic SBRT. An actuarial atlas of our data is provided as an electronic supplement to facilitate data-sharing and meta-analysis relating to CW pain. Copyright © 2012 Elsevier Inc. All rights reserved.

Dose-Volume Parameters Predict for the Development of Chest Wall Pain After Stereotactic Body Radiation for Lung Cancer

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

Mutter, Robert W.; Liu Fan; Abreu, Andres

Purpose: Chest wall (CW) pain has recently been recognized as an important adverse effect of stereotactic body radiation therapy (SBRT) for non-small-cell lung cancer (NSCLC). We developed a dose-volume model to predict the development of this toxicity. Methods and Materials: A total of 126 patients with primary, clinically node-negative NSCLC received three to five fractions of SBRT to doses of 40-60 Gy and were prospectively followed. The dose-absolute volume histograms of two different definitions of the CW as an organ at risk (CW3cm and CW2cm) were examined for all 126 patients. Results: With a median follow-up of 16 months, themore » 2-year estimated actuarial incidence of Grade {>=} 2 CW pain was 39%. The median time to onset of Grade {>=} 2 CW pain (National Cancer Institute Common Terminology Criteria for Adverse Events, Version 3.0) was 9 months. There was no predictive advantage for biologically corrected dose over physical dose. Neither fraction number (p = 0.07) nor prescription dose (p = 0.07) were significantly correlated with the development of Grade {>=} 2 CW pain. Cox Proportional Hazards analysis identified significant correlation with a broad range of dose-volume combinations, with the CW volume receiving 30 Gy (V30) as one of the strongest predictors (p < 0.001). CW2cm consistently enabled better prediction of CW toxicity. When a physical dose of 30 Gy was received by more than 70 cm{sup 3} of CW2cm, there was a significant correlation with Grade {>=} 2 CW pain (p = 0.004). Conclusions: CW toxicity after SBRT is common and long-term follow-up is needed to identify affected patients. A volume of CW {>=} 70 cm{sup 3} receiving 30 Gy is significantly correlated with Grade {>=} 2 CW pain. We are currently applying this constraint at our institution for patients receiving thoracic SBRT. An actuarial atlas of our data is provided as an electronic supplement to facilitate data-sharing and meta-analysis relating to CW pain.« less

Evaluation of contralateral breast skin doses by thermoluminescent dosimeters of patients receiving adjuvant radiotherapy for breast cancer.

PubMed

Gorken, I B; Kentli, S; Alanyali, H; Karagüler, Z; Kinay, M

2002-01-01

It is reported that low dose radiation received by the contralateral breast (CLB) during adjuvant radiotherapy (RT) is carcinogenic. This trial was planned to evaluate the CLB skin doses received during adjuvant RT of breast carcinoma. Twenty-four breast carcinoma patients treated locally or locoregionally with adjuvant RT were included. RT was performed with only tangential fields (TA) in 6 patients whereas 9 patients had an extra internal mammary (IM) field (TAIM). The remaining 9 patients received 5-field locoregional RT (5FLR). All patients were treated with wedge filters except for 3 TA patients. Of 9 5FLR patients IM fields were treated with Co60 in 5 and with electrons in the remaining 4 patients. LiF(2)-based Ribbon type thermoluminescent dosimeters (TLD) were used for dose evaluation. An average of 10 TLD's, placed with 1 cm gaps beginning from the medial border of the treatment field along the central axis were used to obtain dose measurements. Median measure of TLD's between 2-8 cm and maximum dose point (MDP) values in the same range were used to evaluate the CLB dose. In TA patients the CLB skin received 6.3% of the total dose in patients treated with wedge filters and 7.13% with half-beam blocks. For 6 TAIM patients with IM fields treated with Co60, the CLB dose was 7.24%. In 5 of 9 5FLR patients, whose IM fields were treated with Co60 the CLB skin received 8.8% of the total dose, while for electron beam therapy the CLB dose was 5.44%. CLB median MDP values were as follows: 12.76% in TA patients treated with wedge filters and 11.45% with half-beam blocking; 11.89% in TAIM patients with IM fields treated with Co60 and 7.83% with electron beams; 12.29% in 5FLR patients of whose IM fields were treated with Co60 and 8.94% with electron beams. When compared to wedge filters, halfbeam blocks caused 13% increase in CLB doses. If IM fields were added, 27.5% and 62% increases at CLB doses were established with Co60 when compared to electron beam RT in 3-field and 5-field treatments, respectively. CLB doses increased by 15-40% with the increased number of treatment fields. MDP values were also found to be higher with IM fields treated with Co60, but the number of treatment fields and accessories used seemed to have no effect on MDP doses. We conclude that by using wedge filters instead of half-beam blocks and by increasing the number of fractions treated with electron energies for IM fields, apparent decreases in CLB doses can be obtained. Large number of cases is needed to statistically establish the significant differences between subgroups.

Evaluation of an every-other-day palonosetron schedule to control emesis in multiple-day high-dose chemotherapy.

PubMed

Mirabile, Aurora; Celio, Luigi; Magni, Michele; Bonizzoni, Erminio; Gianni, Alessandro Massimo; Di Nicola, Massimo

2014-12-01

Efficacy of intermittent palonosetron dosing in patients undergoing multiple-day, high-dose chemotherapy (HDC) was investigated. Fifty-eight patients received palonosetron (0.25 mg intravenous [iv.]) every other day plus daily dexamethasone (8 mg iv. twice daily) dosing. The primary end point was complete control (CC; no emesis, no rescue anti-emetics, and no more than mild nausea) in the overall acute-period (until 24 h after chemotherapy completion). Acute-period CC occurred in 81% and 50% of patients receiving palonosetron and ondansetron (historical control cohort), respectively. Palonosetron (odds ratio [OR]: 4.37; p = 0.001) and a longer duration of HDC regimen (OR: 3.47; p = 0.011) independently predicted a better anti-emetic outcome. Palonosetron every other day plus daily dexamethasone is an effective anti-emetic coverage in patients undergoing HDC.

Retrospective Study of 122 Dogs That Were Treated with the Antifibrinolytic Drug Aminocaproic Acid: 2010-2012.

PubMed

Davis, Megan; Bracker, Kiko

2016-01-01

Antifibrinolytic drugs are used to promote hemostasis and decrease the need for red blood cell transfusion. Medical records of 122 dogs that were prescribed either oral or intravenous aminocaproic acid between 2010 and 2012 were evaluated retrospectively. Of the 122 dogs, three experienced possible drug-related adverse effects. No significant differences were identified between dogs that experienced adverse effects and those that did not and the possible adverse effects noted were all minor. All dogs that received packed red blood cell transfusions were evaluated for correlations between baseline packed cell volume or dose of red blood cells and aminocaproic acid dose and no correlation was identified. Dogs that received aminocaproic acid as a treatment for active bleeding were divided by cause of hemorrhage into the following groups: neoplastic, non-neoplastic, and unknown. No significant differences in aminocaproic acid dose or the percentage of patients requiring a blood transfusion were identified between groups.

A phase I study of different doses and frequencies of pegylated recombinant human granulocyte-colony stimulating factor (PEG rhG-CSF) in patients with standard-dose chemotherapy-induced neutropenia

PubMed Central

Qin, Yan; Han, Xiaohong; Wang, Lin; Du, Ping; Yao, Jiarui; Wu, Di; Song, Yuanyuan; Zhang, Shuxiang; Tang, Le; Shi, Yuankai

2017-01-01

Objective The recommended dose of prophylactic pegylated recombinant human granulocyte-colony stimulating factor (PEG rhG-CSF) is 100 μg/kg once per cycle for patients receiving intense-dose chemotherapy. However, few data are available on the proper dose for patients receiving less-intense chemotherapy. The aim of this phase I study is to explore the proper dose and administration schedule of PEG rhG-CSF for patients receiving standard-dose chemotherapy. Methods Eligible patients received 3-cycle chemotherapy every 3 weeks. No PEG rhG-CSF was given in the first cycle. Patients experienced grade 3 or 4 neutropenia would then enter the cycle 2 and 3. In cycle 2, patients received a single subcutaneous injection of prophylactic PEG rhG-CSF on d 3, and received half-dose subcutaneous injection in cycle 3 on d 3 and d 5, respectively. Escalating doses (30, 60, 100 and 200 μg/kg) of PEG rhG-CSF were investigated. Results A total of 26 patients were enrolled and received chemotherapy, in which 24 and 18 patients entered cycle 2 and cycle 3 treatment, respectively. In cycle 2, the incidence of grade 3 or 4 neutropenia for patients receiving single-dose PEG rhG-CSF of 30, 60, 100 and 200 μg/kg was 66.67%, 33.33%, 22.22% and 0, respectively, with a median duration less than 1 (0–2) d. No grade 3 or higher neutropenia was noted in cycle 3 in all dose cohorts. Conclusions The pharmacokinetic and pharmacodynamic profiles of PEG rhG-CSF used in cancer patients were similar to those reported, as well as the safety. Double half dose administration model showed better efficacy result than a single dose model in terms of grade 3 neutropenia and above. The single dose of 60 μg/kg, 100 μg/kg and double half dose of 30 μg/kg were recommended to the phase II study, hoping to find a preferable method for neutropenia treatment. PMID:29142459

A phase I study of different doses and frequencies of pegylated recombinant human granulocyte-colony stimulating factor (PEG rhG-CSF) in patients with standard-dose chemotherapy-induced neutropenia.

PubMed

Qin, Yan; Han, Xiaohong; Wang, Lin; Du, Ping; Yao, Jiarui; Wu, Di; Song, Yuanyuan; Zhang, Shuxiang; Tang, Le; Shi, Yuankai

2017-10-01

The recommended dose of prophylactic pegylated recombinant human granulocyte-colony stimulating factor (PEG rhG-CSF) is 100 μg/kg once per cycle for patients receiving intense-dose chemotherapy. However, few data are available on the proper dose for patients receiving less-intense chemotherapy. The aim of this phase I study is to explore the proper dose and administration schedule of PEG rhG-CSF for patients receiving standard-dose chemotherapy. Eligible patients received 3-cycle chemotherapy every 3 weeks. No PEG rhG-CSF was given in the first cycle. Patients experienced grade 3 or 4 neutropenia would then enter the cycle 2 and 3. In cycle 2, patients received a single subcutaneous injection of prophylactic PEG rhG-CSF on d 3, and received half-dose subcutaneous injection in cycle 3 on d 3 and d 5, respectively. Escalating doses (30, 60, 100 and 200 μg/kg) of PEG rhG-CSF were investigated. A total of 26 patients were enrolled and received chemotherapy, in which 24 and 18 patients entered cycle 2 and cycle 3 treatment, respectively. In cycle 2, the incidence of grade 3 or 4 neutropenia for patients receiving single-dose PEG rhG-CSF of 30, 60, 100 and 200 μg/kg was 66.67%, 33.33%, 22.22% and 0, respectively, with a median duration less than 1 (0-2) d. No grade 3 or higher neutropenia was noted in cycle 3 in all dose cohorts. The pharmacokinetic and pharmacodynamic profiles of PEG rhG-CSF used in cancer patients were similar to those reported, as well as the safety. Double half dose administration model showed better efficacy result than a single dose model in terms of grade 3 neutropenia and above. The single dose of 60 μg/kg, 100 μg/kg and double half dose of 30 μg/kg were recommended to the phase II study, hoping to find a preferable method for neutropenia treatment.

An assessment of the doses received by members of the public in Japan following the nuclear accident at Fukushima Daiichi nuclear power plant.

PubMed

Bedwell, P; Mortimer, K; Wellings, J; Sherwood, J; Leadbetter, S J; Haywood, S M; Charnock, T; Jones, A R; Hort, M C

2015-12-01

The earthquake and tsunami on 11 March 2011, centred off the east coast of Japan, caused considerable destruction and substantial loss of life along large swathes of the Japanese coastline. The tsunami damaged the Fukushima Daiichi nuclear power plant (NPP), resulting in prolonged releases of radioactive material into the environment. This paper assesses the doses received by members of the public in Japan. The assessment is based on an estimated source term and atmospheric dispersion modelling rather than monitoring data. It is evident from this assessment that across the majority of Japan the estimates of dose are very low, for example they are estimated to be less than the annual average dose from natural background radiation in Japan. Even in the regions local to Fukushima Daiichi NPP (and not affected by any form of evacuation) the maximum lifetime effective dose is estimated to be well below the cumulative natural background dose over the same period. The impact of the urgent countermeasures on the estimates of dose was considered. And the relative contribution to dose from the range of exposure pathways and radionuclides were evaluated. Analysis of estimated doses focused on the geographic irregularity and the impact of the meteorological conditions. For example the dose to an infant's thyroid received over the first year was estimated to be greater in Hirono than in the non-evacuated region of Naraha, despite Hirono being further from the release location. A number of factors were identified and thought to contribute towards this outcome, including the local wind pattern which resulted in the recirculation of part of the release. The non-uniform nature of dose estimates strengthens the case for evaluations based on dispersion modelling.

Occupational Radiation Exposure to the Extremities of Medical Staff during Hysterosalpingography and Radionuclide Bone Scan Procedures in Several Nigerian Hospitals.

PubMed

Jibiri, Nnamdi Norbert; Akintunde, Tawakalitu Oluwatoyin; Dambele, Musa Yusuf; Olowookere, Christopher Jimoh

2016-10-05

The practice of regular dose measurement helps to ascertain the level of occupational dose delivered to the staff involved in diagnostic procedures. This study was carried out to evaluate the dose exposed to the hands of radiologists and a radiologic technologist carrying out HSG and radionuclide bone scan examinations in several hospitals in Nigeria. Radiation doses exposed to the hands of radiologists and a technician carrying out hysterosalpingography (HSG) and bone scan procedures were measured using calibrated thermo-luminescent dosimeters. Five radiologists and a radiologic technologist were included in the study for dose measurement. The study indicates that each radiologist carried out approximately 2 examinations per week with the mean dose ranging between 0.49-0.62 mSv per week, resulting in an annual dose of 191 mSv. Similarly, the occupational dose delivered to both the left and right hands of a radiologic technologist administering 99mTc-methylene diphosphonate (MDP) without cannula and with cannula were 10.68 (720.2) and 13.82 (556.4) mSv per week (and per annum), respectively. It was determined that the left hand of the personnel received higher doses than their right hand. The estimated annual dose during HSG is far below the annual dose limit for deterministic effects, however, it is greater than 10% of the applicable annual dose limit. Hence, routine monitoring is required to ensure adequate protection of the personnel. The total annual dose received during the bone scan exceeds the annual dose limit for both hands, and the dose to either left or right hand is greater than the dose limit of 500 mSv/yr. The radiologists monitored are not expected to incur any deterministic effects during HSG examinations, however, accumulated doses arising from the scattered radiation to the eyes, legs, and neck could be substantial and might lead to certain effects. More staff are required to administer 99mTc-MDP in Nigerian institutions to prevent excessive doses to personnel.

Occupational Radiation Exposure to the Extremities of Medical Staff during Hysterosalpingography and Radionuclide Bone Scan Procedures in Several Nigerian Hospitals

PubMed Central

Jibiri, Nnamdi Norbert; Akintunde, Tawakalitu Oluwatoyin; Dambele, Musa Yusuf; Olowookere, Christopher Jimoh

2016-01-01

Objective: The practice of regular dose measurement helps to ascertain the level of occupational dose delivered to the staff involved in diagnostic procedures. This study was carried out to evaluate the dose exposed to the hands of radiologists and a radiologic technologist carrying out HSG and radionuclide bone scan examinations in several hospitals in Nigeria. Methods: Radiation doses exposed to the hands of radiologists and a technician carrying out hysterosalpingography (HSG) and bone scan procedures were measured using calibrated thermo-luminescent dosimeters. Five radiologists and a radiologic technologist were included in the study for dose measurement. Results: The study indicates that each radiologist carried out approximately 2 examinations per week with the mean dose ranging between 0.49-0.62 mSv per week, resulting in an annual dose of 191 mSv. Similarly, the occupational dose delivered to both the left and right hands of a radiologic technologist administering 99mTc-methylene diphosphonate (MDP) without cannula and with cannula were 10.68 (720.2) and 13.82 (556.4) mSv per week (and per annum), respectively. It was determined that the left hand of the personnel received higher doses than their right hand. Conclusion: The estimated annual dose during HSG is far below the annual dose limit for deterministic effects, however, it is greater than 10% of the applicable annual dose limit. Hence, routine monitoring is required to ensure adequate protection of the personnel. The total annual dose received during the bone scan exceeds the annual dose limit for both hands, and the dose to either left or right hand is greater than the dose limit of 500 mSv/yr. The radiologists monitored are not expected to incur any deterministic effects during HSG examinations, however, accumulated doses arising from the scattered radiation to the eyes, legs, and neck could be substantial and might lead to certain effects. More staff are required to administer 99mTc-MDP in Nigerian institutions to prevent excessive doses to personnel. PMID:27751973

Fascia iliaca compartment nerve block versus systemic pain control for acute femur fractures in the pediatric emergency department.

PubMed

Neubrand, Tara L; Roswell, Kelley; Deakyne, Sara; Kocher, Kendra; Wathen, Joseph

2014-07-01

To compare management of acute femur fractures in children who received a fascia iliaca compartment nerve block (FICNB) to those who received systemic intravenously administered analgesics in the pediatric emergency department. The comparison evaluated frequency of use, effectiveness, and associated adverse event profiles. Study population was derived from a retrospective chart review of pediatric patients sustaining acute femur fractures between 2005 and 2009. Cases (received FICNB) were compared with controls (only systemic analgesia) in terms of effectiveness and adverse event. Outcomes included total doses of systemic medications received and comparison of preintervention and postintervention pain scores. Two hundred fifty-nine charts were reviewed: 158 who received FICNB versus 101 who did not. The median dose of systemic medications was 1 dose lower in the FICNB group compared with the systemic medications group. This remained significant after controlling for age and preintervention pain scores (P = 0.02). Median postintervention pain scores in the FICNB group were 1.5 points lower than those in the systemic medications group. This remained significant while controlling for preintervention pain scores and age (P < 0.01). There was no difference in the total adverse events between the FICNB and the control group in either the unadjusted or adjusted analyses (P = 0.08). The FICNB group had 2 seizure episodes, one of which had associated subarachnoid hemorrhage. No patient in either group experienced bradycardia, arrhythmia, visual disturbance, abnormal hearing, mouth numbness, motor tremors, pain or bleeding at injection site, or prolonged nerve block. We report on the largest number of FICNBs administered in a pediatric emergency department for acute femur fractures. Effectiveness, as measured by pain scores and total doses of systemic analgesia, was improved in the FICNB group versus the control. There was no difference in adverse events between the groups.

Acute toxicity of ibogaine and noribogaine.

PubMed

Kubiliene, Asta; Marksiene, Rūta; Kazlauskas, Saulius; Sadauskiene, Ilona; Razukas, Almantas; Ivanov, Leonid

2008-01-01

To evaluate acute toxic effect of ibogaine and noribogaine on the survival of mice and determine median lethal doses of the substances mentioned. White laboratory mice were used for the experiments. Ibogaine and noribogaine were administered intragastrically to mice via a stomach tube. Control animals received the same volume of saline. The median lethal dose was calculated with the help of a standard formula. To determine the median lethal dose of ibogaine, the doses of 100, 300, 400, and 500 mg/kg were administered intragastrically to mice. The survival time of mice after the drug administration was recorded, as well as the number of survived mice in each group. Upon administration of ibogaine at a dose of 500 mg/kg, all mice in this dose group died. Three out of four mice died in the group, which received 300 mg/kg of ibogaine. No mouse deaths were observed in the group, which received 100 mg/kg of ibogaine. The determined LD(50) value of ibogaine equals to 263 mg/kg of body mass. In order to determine the median lethal dose of noribogaine, the doses of 300, 500, 700, and 900 mg/kg were administered to mice intragastrically. Noribogaine given at a dose of 500 mg/kg had no impact on the mouse survival. The increase of noribogaine dose to 700 mg/kg of mouse body mass led to the death of three out of four mice in the group. Upon administration of noribogaine at a dose of 900 mg/kg, all mice in this group died. The LD(50) value of noribogaine in mice determined on the basis of the number of dead mice and the size of the doses used equals to 630 mg/kg of mouse body mass. The behavior of mice was observed upon administration of ibogaine or noribogaine. Low doses of ibogaine and noribogaine had no impact on the mouse behavior. External effects (convulsions, nervous behaviour, limb paralysis) were observed only when substances were administrated at higher doses. It has been determined that the median lethal dose of ibogaine and noribogaine equals to 263 mg and 630 mg/kg of mouse body mass, respectively. The toxicity of ibogaine is 2.4 times higher than that of noribogaine.

Timing of HPV vaccine intervals among United States teens with consideration to the current ACIP schedule and the WHO 2-dose schedule

PubMed Central

Cloessner, Emily A.; Stokley, Shannon; Yankey, David; Markowitz, Lauri E.

2016-01-01

Abstract The current recommendation for human papillomavirus (HPV) vaccination in the United States is for 3 doses to be administered over a 6 month period. In April 2014, the World Health Organization (WHO) recommended adoption of a 2-dose schedule, with doses spaced a minimum of 6 months apart, for teens who begin the series before age 15. We analyzed data from the 2013 National Immunization Survey-Teen to examine the timing of second and third dose receipt among US adolescents. All analyses were restricted to adolescents age 13–17 y who had adequate provider data. The Wilcoxon–Mann–Whitney test measured differences in time to receive vaccine doses among demographic and socioeconomic groups. Logistic regression identified socioeconomic characteristics associated with receiving the second dose of HPV vaccine at least 6 months after the first dose. The median time for teens to receive the second dose of HPV vaccine was 2.6 months after the first dose, and the median time to receive the third dose was 4.9 months after the second dose. Minority teens and teens living below the poverty level took significantly longer to receive doses. Among teens that initiated the HPV vaccine series before age 15 y, 28.6% received the second dose at least 6 months after the first dose. If these teens, who met the WHO criteria for up-to-date HPV vaccination, were classified as having completed the vaccination series, overall coverage in the US would increase 3.9 percentage points, with African American and Hispanic teens having the greatest increases in coverage. PMID:26587886

Timing of HPV vaccine intervals among United States teens with consideration to the current ACIP schedule and the WHO 2-dose schedule.

PubMed

Cloessner, Emily A; Stokley, Shannon; Yankey, David; Markowitz, Lauri E

2016-06-02

The current recommendation for human papillomavirus (HPV) vaccination in the United States is for 3 doses to be administered over a 6 month period. In April 2014, the World Health Organization (WHO) recommended adoption of a 2-dose schedule, with doses spaced a minimum of 6 months apart, for teens who begin the series before age 15. We analyzed data from the 2013 National Immunization Survey-Teen to examine the timing of second and third dose receipt among US adolescents. All analyses were restricted to adolescents age 13-17 y who had adequate provider data. The Wilcoxon-Mann-Whitney test measured differences in time to receive vaccine doses among demographic and socioeconomic groups. Logistic regression identified socioeconomic characteristics associated with receiving the second dose of HPV vaccine at least 6 months after the first dose. The median time for teens to receive the second dose of HPV vaccine was 2.6 months after the first dose, and the median time to receive the third dose was 4.9 months after the second dose. Minority teens and teens living below the poverty level took significantly longer to receive doses. Among teens that initiated the HPV vaccine series before age 15 y, 28.6% received the second dose at least 6 months after the first dose. If these teens, who met the WHO criteria for up-to-date HPV vaccination, were classified as having completed the vaccination series, overall coverage in the US would increase 3.9 percentage points, with African American and Hispanic teens having the greatest increases in coverage.

Effectiveness of a management program for outpatient clinic or remote titration of beta-blockers in CRT patients: The RESTORE study.

PubMed

D'Onofrio, Antonio; Palmisano, Pietro; Rapacciuolo, Antonio; Ammendola, Ernesto; Calò, Leonardo; Ruocco, Antonio; Bianchi, Valter; Maresca, Fabio; Del Giorno, Giuseppe; Martino, Annamaria; Mauro, Ciro; Campari, Monica; Valsecchi, Sergio; Accogli, Michele

2017-06-01

Many patients fail to receive β-blockers before cardiac resynchronization therapy defibrillator (CRT-D) implantation, or receive them at a suboptimal dose, and require optimization after implantation. We assessed the effectiveness of a structured program for β-blocker titration in CRT-D patients followed up by means of conventional in-clinic visits or remote monitoring. 130 patients undergoing CRT implantation and treated according to the standard practice of the centers were included as a control group. A second group of 124 CRT-D candidates (Study Group) underwent up-titration visits every 2weeks after implantation (target dose: 10mg/day of bisoprolol or 50mg/day of carvedilol). In the Study Group, remote monitoring was undertaken in 66 patients, who received additional equipment for daily transmission of weight and blood pressure data, and scheduled titration telephone calls. In the Control Group, the maximal dose of β-blockers was being administered to 12 (9%) patients on implantation and 21 (16%) on 6-month follow-up examination (p>0.05). In the Study Group, 25 (20%) patients were receiving the maximal dose of β-blockers on implantation and 72 (58%) on follow-up examination (p<0.001). The 66 Study Group patients on remote monitoring underwent fewer in-clinic visits (p=0.034). Of these, 50 (76%) were on the maximal dose after remote up-titration (versus 38% of patients followed up conventionally, p<0.001). The decrease in left ventricular end-systolic volume was larger in the Study Group (p=0.040). The program for β-blocker up-titration increased the number of patients reaching the target dose and improved the response to the therapy. The use of remote monitoring and daily transfer of weight and blood pressure data facilitated β-blocker titration. URL: http://clinicaltrials.gov/ Identifier: NCT02173028. Copyright © 2017. Published by Elsevier B.V.

High-pressure liquid chromatography and microbiological assay of serum ofloxacin levels in adults receiving intravenous and oral therapy for skin infections.

PubMed Central

Auten, G M; Preheim, L C; Sookpranee, M; Bittner, M J; Sookpranee, T; Vibhagool, A

1991-01-01

Thirty-two adults hospitalized with skin and skin structure infections received intravenous ofloxacin followed by oral ofloxacin. The standard treatment was 400 mg every 12 h. One patient with renal failure received 400 mg every 24 h. Serum ofloxacin levels were measured (1.5 h postdose and 1 h predose) during intravenous (32 patients) and oral (30 patients) therapy. Levels were assayed by high-pressure liquid chromatography (HPLC) and microbiological assay (MBA). Mean levels +/- standard deviation (in micrograms per milliliter) when measured by MBA after intravenous dosing were (postdose versus predose) 6.23 +/- 2.49 versus 2.42 +/- 1.56, and those after oral dosing were 6.17 +/- 3.25 versus 3.49 +/- 2.77. When measured by HPLC, mean levels +/- standard deviation after intravenous dosing were 5.81 +/- 2.08 versus 2.14 +/- 1.26 and those after oral dosing were 5.63 +/- 2.92 versus 3.41 +/- 2.98. There were no significant differences between levels achieved with oral or intravenous dosing when measured by either MBA or HPLC. Levels in serum did not correlate with side effects. The MICs for 50 and 90% of the 40 aerobic pathogens isolated from 21 patients were 0.5 and 2.0 micrograms/ml, respectively. Cure or improvement was achieved in 30 patients. Intravenous and oral administration of ofloxacin yielded similar levels in serum which were safe and effective in the therapy of skin infections in adult patients. PMID:1810189

Dexmedetomidine oromucosal gel for noise-associated acute anxiety and fear in dogs-a randomised, double-blind, placebo-controlled clinical study.

PubMed

Korpivaara, M; Laapas, K; Huhtinen, M; Schöning, B; Overall, K

2017-04-08

The aim of this randomised, double-blind, placebo-controlled, clinical-field study was to evaluate the effect of dexmedetomidine oromucosal gel at subsedative doses in alleviation of noise-associated acute anxiety and fear in dogs. On New Year's Eve, 182 dogs with a history of acute anxiety and fear associated with fireworks received treatment as needed up to five times: 89 dogs received dexmedetomidine and 93 dogs received placebo. For the primary efficacy variables, dog owners assessed the overall treatment effect as well as signs and extent of anxiety and fear. The overall treatment effect was statistically significant (P<0.0001). An excellent or good treatment effect was reported for a higher proportion of dogs treated with dexmedetomidine (64/89, 72 per cent) than those receiving placebo (34/93, 37 per cent). Additionally, dexmedetomidine-treated dogs expressed significantly (P<0.0314) fewer signs of fear and anxiety despite the noise of fireworks. No local tolerance or clinical safety concerns occurred during the study. This study demonstrated that oromucosal dexmedetomidine at subsedative doses alleviates noise-associated acute anxiety and fear in dogs. British Veterinary Association.

Cysteine reversal of the novel neuromuscular blocking drug CW002 in dogs: pharmacodynamics, acute cardiovascular effects, and preliminary toxicology.

PubMed

Sunaga, Hiroshi; Malhotra, Jaideep K; Yoon, Edward; Savarese, John J; Heerdt, Paul M

2010-04-01

CW002 is a neuromuscular blocking drug that is inactivated by endogenous L-cysteine. This study determined the exogenous L-cysteine dose-response relationship for CW002 reversal along with acute cardiovascular effects and organ toxicity in dogs. Six dogs were each studied four times during isoflurane-nitrous oxide anesthesia and recording of muscle twitch, arterial pressure, and heart rate. CW002 (0.08 mg/kg or 9 x ED95) was injected, and the time to spontaneous muscle recovery was determined. CW002 was then administered again followed 1 min later by 10, 20, 50, or 100 mg/kg L-cysteine (1 dose/experiment). After twitch recovery, CW002 was given a third time to determine whether residual L-cysteine influenced duration. Preliminary toxicology was performed in an additional group of dogs that received CW002 followed by vehicle (n = 8) or 200 mg/kg L-cysteine (n = 8). Animals were awakened and observed for 2 or 14 days before sacrificing and anatomic, biochemical, and histopathologic analyses. L-cysteine at all doses accelerated recovery from CW002, with both 50 and 100 mg/kg decreasing median duration from more than 70 min to less than 5 min. After reversal, duration of a subsequent CW002 dose was also decreased in a dose-dependent manner. Over the studied dose range, L-cysteine had less than 10% effect on blood pressure and heart rate. Animals receiving a single 200-mg/kg dose of L-cysteine showed no clinical, anatomic, biochemical, or histologic evidence of organ toxicity. The optimal L-cysteine dose for rapidly reversing the neuromuscular blockade produced by a large dose of CW002 in dogs is approximately 50 mg/kg, which has no concomitant hemodynamic effect. A dose of 200 mg/kg had no evident organ toxicity.

Profound and Sexually Dimorphic Effects of Clinically-Relevant Low Dose Scatter Irradiation on the Brain and Behavior

PubMed Central

Kovalchuk, Anna; Mychasiuk, Richelle; Muhammad, Arif; Hossain, Shakhawat; Ilnytskyy, Yaroslav; Ghose, Abhijit; Kirkby, Charles; Ghasroddashti, Esmaeel; Kolb, Bryan; Kovalchuk, Olga

2016-01-01

Irradiated cells can signal damage and distress to both close and distant neighbors that have not been directly exposed to the radiation (naïve bystanders). While studies have shown that such bystander effects occur in the shielded brain of animals upon body irradiation, their mechanism remains unexplored. Observed effects may be caused by some blood-borne factors; however they may also be explained, at least in part, by very small direct doses received by the brain that result from scatter or leakage. In order to establish the roles of low doses of scatter irradiation in the brain response, we developed a new model for scatter irradiation analysis whereby one rat was irradiated directly at the liver and the second rat was placed adjacent to the first and received a scatter dose to its body and brain. This work focuses specifically on the response of the latter rat brain to the low scatter irradiation dose. Here, we provide the first experimental evidence that very low, clinically relevant doses of scatter irradiation alter gene expression, induce changes in dendritic morphology, and lead to behavioral deficits in exposed animals. The results showed that exposure to radiation doses as low as 0.115 cGy caused changes in gene expression and reduced spine density, dendritic complexity, and dendritic length in the prefrontal cortex tissues of females, but not males. In the hippocampus, radiation altered neuroanatomical organization in males, but not in females. Moreover, low dose radiation caused behavioral deficits in the exposed animals. This is the first study to show that low dose scatter irradiation influences the brain and behavior in a sex-specific way. PMID:27375442

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.

Spacecraft shielding for a Mars mission

NASA Astrophysics Data System (ADS)

O'Brien, K.

Calculations of the effective radiation dose due to cosmic rays in the interplanetary medium between Earth and Mars show that, as in the atmosphere above the Pfotzer Maximum, the dose rate increases with increasing wall thickness. An unshielded space crew member would receive almost 70 rem (0.70 Sv) a year. The effect of a typically proposed composite space-craft hull of aluminum and polyethylene would increase the dose rate by a few percent. However, 100 g/cm2 of almost any light material would more than double the cosmic radiation exposure of the crew.

10 CFR 835.402 - Individual monitoring.

Code of Federal Regulations, 2010 CFR

2010-01-01

... conditions, are likely to receive one or more of the following: (i) An effective dose of 0.1 rem (0.001 Sv) or more in a year; (ii) An equivalent dose to the skin or to any extremity of 5 rems (0.05 Sv) or more in a year; (iii) An equivalent dose to the lens of the eye of 1.5 rems (0.015 Sv) or more in a...

10 CFR 835.402 - Individual monitoring.

Code of Federal Regulations, 2013 CFR

2013-01-01

... conditions, are likely to receive one or more of the following: (i) An effective dose of 0.1 rem (0.001 Sv) or more in a year; (ii) An equivalent dose to the skin or to any extremity of 5 rems (0.05 Sv) or more in a year; (iii) An equivalent dose to the lens of the eye of 1.5 rems (0.015 Sv) or more in a...

10 CFR 835.402 - Individual monitoring.

Code of Federal Regulations, 2011 CFR

2011-01-01

... conditions, are likely to receive one or more of the following: (i) An effective dose of 0.1 rem (0.001 Sv) or more in a year; (ii) An equivalent dose to the skin or to any extremity of 5 rems (0.05 Sv) or more in a year; (iii) An equivalent dose to the lens of the eye of 1.5 rems (0.015 Sv) or more in a...

10 CFR 835.402 - Individual monitoring.

Code of Federal Regulations, 2012 CFR

2012-01-01

... conditions, are likely to receive one or more of the following: (i) An effective dose of 0.1 rem (0.001 Sv) or more in a year; (ii) An equivalent dose to the skin or to any extremity of 5 rems (0.05 Sv) or more in a year; (iii) An equivalent dose to the lens of the eye of 1.5 rems (0.015 Sv) or more in a...

10 CFR 835.402 - Individual monitoring.

Code of Federal Regulations, 2014 CFR

2014-01-01

... conditions, are likely to receive one or more of the following: (i) An effective dose of 0.1 rem (0.001 Sv) or more in a year; (ii) An equivalent dose to the skin or to any extremity of 5 rems (0.05 Sv) or more in a year; (iii) An equivalent dose to the lens of the eye of 1.5 rems (0.015 Sv) or more in a...

Effects of rebamipide on nephrotoxicity associated with selected NSAIDs in rats.

PubMed

Wood, Robert C; Wyatt, Jarrett E; Bullins, Kenny W; Hanley, Angela V; Hanley, Gregory A; Denham, James W; Panus, Peter C; Harirforoosh, Sam

2013-11-15

Use of nonsteroidal anti-inflammatory drugs (NSAIDs) is primarily limited by renal and gastrointestinal adverse effects. Rebamipide suppresses gastric mucosal injury when administered with NSAIDs. This study aimed to determine rebamipide's influence upon renal effects following concomitant use with celecoxib or diclofenac. On day 0, rats were randomly divided into 6 groups (n≥6). On days 1 and 2, three groups received placebo and three groups were administered rebamipide (30 mg/kg) twice daily. On day 3, the rats treated with placebo received another dose of placebo and ten minutes later a single dose of celecoxib (40 mg/kg), diclofenac (10mg/kg), or placebo, respectively. The rats treated with rebamipide received one more dose of rebamipide and ten minutes later one single dose of celecoxib, diclofenac, or placebo, respectively. Urine and blood samples were collected on days 0, 2, and 3. Sodium and potassium excretion rates decreased significantly in the rats treated with celecoxib, diclofenac, rebamipide plus celecoxib, or rebamipide plus diclofenac on day 3. Blood urea nitrogen (BUN) levels significantly increased in placebo plus diclofenac and rebamipide plus diclofenac groups on day 3. Comparing the two groups, the levels of BUN was significantly higher in the rebamipide plus diclofenac group compared to that of placebo plus diclofenac group. Concomitant administration of rebamipide with either NSAID caused a rise in concentrations of urinary kidney injury molecule-1. Histopathological evaluations revealed an intensified NSAID-induced tubular necrosis by rebamipide. Based upon the results obtained, concomitant administration of rebamipide with NSAIDs enhances the effect of NSAIDs on tubular injury. © 2013 Elsevier B.V. All rights reserved.

Efficacy of a single dose of milbemycin oxime/praziquantel combination tablets, Milpro(®), against adult Echinococcus multilocularis in dogs and both adult and immature E. multilocularis in young cats.

PubMed

Cvejic, Dejan; Schneider, Claudia; Fourie, Josephus; de Vos, Christa; Bonneau, Stephane; Bernachon, Natalia; Hellmann, Klaus

2016-03-01

Two single-site, laboratory, negatively controlled, masked, randomised dose confirmation studies were performed: one in dogs, the other in cats. After a period of acclimatisation, both the dogs and cats were orally infected with Echinococcus multilocularis protoscoleces. In the dog study, 10 dogs received a single dose of Milpro® tablets at a minimum dose of 0.5 mg/kg milbemycin oxime and 5 mg/kg praziquantel 18 days post-infection and 10 dogs received no treatment. In the cat study, 10 cats received a single dose of Milpro® tablets at a minimum dose of 2 mg/kg milbemycin oxime and 5 mg/kg praziquantel 7 days post-infection, 10 cats received a single dose of the treatment 18 days post-infection and 10 cats remained untreated. In both studies, intestinal worm counts were performed 23 days post-infection at necropsy. No worms were retrieved from any of the 30 treated animals. Nine of 10 control dogs had multiple worms (geometric mean 91, arithmetic mean 304) and all 10 control cats had multiple worms (geometric mean 216, arithmetic mean 481). The difference in worm counts between all three treated groups and their controls was highly significant (ANOVA p values of log transformed data <0.0001). Efficacy of 100 % was demonstrated for the elimination of adult E. multilocularis in dogs and cats as well as for elimination of immature E. multilocularis in cats as evidenced by the effectiveness of treatment 7 days post-infection. The treatments were well accepted and tolerated, and there were no adverse drug reactions observed.

Effects of high doses of oxytetracycline on metacarpophalangeal joint kinematics in neonatal foals.

PubMed

Kasper, C A; Clayton, H M; Wright, A K; Skuba, E V; Petrie, L

1995-07-01

Thirteen clinically normal Belgian-type foals were used to study the effects of high doses of oxytetracycline on metacarpophalangeal joint kinematics. Seven foals (treatment group) received 2 doses of oxytetracycline (3 g, IV). The first dose was given when foals were 4 days old; the second dose was given 24 hours later. Six foals (control group) received 2 doses of saline (0.9% NaCl) solution (15 ml, IV) at equivalent time periods. All foals were videotaped at a walk twice: immediately prior to the first treatment and 24 hours after the second treatment. The tapes were digitized, and metacarpophalangeal joint angle was measured along the palmar surface of the limb during 3 strides. The angular data were normalized for time, and data from the 3 strides were averaged to describe a representative stride. Repeated measures ANOVA was used to test for differences between groups and within groups over time. Values for stride duration, stance phase percentage, and minimum metacarpophalangeal joint angle obtained before treatment were not significantly different from values obtained after treatment. Maximum metacarpophalangeal joint angle, which occurred during the stance phase of the stride, and range of joint motion were significantly increased for foals in the treatment group, compared with foals in the control group.

Focal treatment of spasticity using botulinum toxin A in cerebral palsy cases of GMFCS level V: evaluation of adverse effects☆☆☆

PubMed Central

Tedesco, Ana Paula; Martins, Juliana Saccol; Nicolini-Panisson, Renata D’Agostini

2014-01-01

Objective To report on the experience of injections of botulinum toxin A (BTA) in a series of patients with cerebral palsy of Gross Motor Function Classification System (GMFCS) level V. Methods This was a retrospective case series study on 33 patients with cerebral palsy of GMFCS level V who received 89 sessions of BTA application (of which 84 were Botox® and five were other presentations), in which the basic aim was to look for adverse effects. Results The mean number of application sessions per patient was three, and the mean age at the time of each injection was 4 + 6 years (range: 1.6–13 years). The muscles that most frequently received injections were the gastrocnemius, hamstrings, hip adductors, biceps brachii and finger flexors. The mean total dose was 193 U and the mean dose per weight was 12.5 U/kg. Only one patient received anesthesia for the injections and no sedation was used in any case. No local or systemic adverse effects were observed within the minimum follow-up of one month. Conclusion The absence of adverse effects in our series was probably related to the use of low doses and absence of sedation or anesthesia. According to our data, BTA can be safely used for patients with cerebral palsy of GMFCS level V, using low doses and preferably without sedation or anesthesia. PMID:26229827

The usefulness of sLORETA in evaluating the effect of high-dose ARA-C on brain connectivity in patients with acute myeloid leukemia: an exploratory study

PubMed Central

Zarabla, Alessia; Ungania, Sara; Cacciatore, Alessandra; Maialetti, Andrea; Petreri, Gianluca; Mengarelli, Andrea; Spadea, Antonio; Marchesi, Francesco; Renzi, Daniela; Gumenyuk, Svitlana; Strigari, Lidia; Maschio, Marta

2017-01-01

Summary Cytosine arabinoside (Ara-C) is one of the key drugs for treating acute myeloid leukemia (AML). High intravenous doses may produce a number of central nervous system (CNS) toxicities and contribute to modifications in brain functional connectivity. sLORETA is a software used for localizing brain electrical activity and functional connectivity. The aim of this study was to apply sLORETA in the evaluation of possible effects of Ara-C on brain connectivity in patients with AML without CNS involvement. We studied eight patients with AML; four were administered standard doses of Ara-C while the other four received high doses. sLORETA was computed from computerized EEG data before treatment and after six months of treatment. Three regions of interest, corresponding to specific combinations of Brodmann areas, were defined. In the patients receiving high-dose Ara-C, a statistically significant reduction in functional connectivity was observed in the frontoparietal network, which literature data suggest is involved in attentional processes. Our data highlight the possibility of using novel techniques to study potential CNS toxicity of cancer therapy.

Effect of Brain Stem and Dorsal Vagus Complex Dosimetry on Nausea and Vomiting in Head and Neck Intensity-Modulated Radiation Therapy

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

Ciura, Katherine; McBurney, Michelle; Nguyen, Baongoc

Intensity-modulated radiation therapy (IMRT) is becoming the treatment of choice for many head and neck cancer patients. IMRT reduces some toxicities by reducing radiation dose to uninvolved normal tissue near tumor targets; however, other tissues not irradiated using previous 3D techniques may receive clinically significant doses, causing undesirable side effects including nausea and vomiting (NV). Irradiation of the brainstem, and more specifically, the area postrema and dorsal vagal complex (DVC), has been linked to NV. We previously reported preliminary hypothesis-generating dose effects associated with NV in IMRT patients. The goal of this study is to relate brainstem dose to NVmore » symptoms. We retrospectively studied 100 consecutive patients that were treated for oropharyngeal cancer with IMRT. We contoured the brainstem, area postrema, and DVC with the assistance of an expert diagnostic neuroradiologist. We correlated dosimetry for the 3 areas contoured with weekly NV rates during IMRT. NV rates were significantly higher for patients who received concurrent chemotherapy. Post hoc analysis demonstrated that chemoradiation cases exhibited a trend towards the same dose-response relationship with both brainstem mean dose (p = 0.0025) and area postrema mean dose (p = 0.004); however, both failed to meet statistical significance at the p {<=} 0.002 level. Duration of toxicity was also greater for chemoradiation patients, who averaged 3.3 weeks with reported Common Terminology Criteria for Adverse Events (CTC-AE), compared with an average of 2 weeks for definitive RT patients (p = 0.002). For definitive RT cases, no dose-response trend could be ascertained. The mean brainstem dose emerged as a key parameter of interest; however, no one dose parameter (mean/median/EUD) best correlated with NV. This study does not address extraneous factors that would affect NV incidence, including the use of antiemetics, nor chemotherapy dose schedule specifics before and during RT. A prospective study will be required to depict exactly how IMRT dose affects NV.« less

Fractional Dosing of Yellow Fever Vaccine to Extend Supply: A Modeling Study

PubMed Central

Peak, Corey M.; Leung, Gabriel M.

2016-01-01

Background The ongoing yellow fever (YF) epidemic in Angola strains the global vaccine supply, prompting WHO to adopt dose sparing for its vaccination campaign in Kinshasa in July–August 2016. Although a 5-fold fractional-dose vaccine is similar to standard-dose vaccine in safety and immunogenicity, efficacy is untested. There is an urgent need to ensure the robustness of fractional-dose vaccination by elucidating the conditions under which dose fractionation would reduce transmission. Methods We estimate the effective reproductive number for YF in Angola using disease natural history and case report data. With simple mathematical models of YF transmission, we calculate the infection attack rate (IAR, the proportion of population infected over the course of an epidemic) under varying levels of transmissibility and five-fold fractional-dose vaccine efficacy for two vaccination scenarios: (i) random vaccination in a hypothetical population that is completely susceptible; (ii) the Kinshasa vaccination campaign in July–August 2016 with different age cutoff for fractional-dose vaccines. Findings We estimate the effective reproductive number early in the Angola outbreak was between 5·2 and 7·1. If vaccine action is all-or-nothing (i.e. a proportion VE of vaccinees receives complete and the remainder receive no protection), n-fold fractionation can dramatically reduce IAR as long as efficacy VE exceeds 1/n. This benefit threshold becomes more stringent if vaccine action is leaky (i.e. the susceptibility of each vaccinee is reduced by a factor that is equal to the vaccine efficacy VE). The age cutoff for fractional-dose vaccines chosen by the WHO for the Kinshasa vaccination campaign (namely, 2 years) provides the largest reduction in IAR if the efficacy of five-fold fractional-dose vaccines exceeds 20%. Interpretation Dose fractionation is a very effective strategy for reducing infection attack rate that would be robust with a large margin for error in case fractional-dose VE is lower than expected. PMID:27837923

Proof-of-principle evaluation of the efficacy of fewer than three doses of a bivalent HPV16/18 vaccine.

PubMed

Kreimer, Aimée R; Rodriguez, Ana Cecilia; Hildesheim, Allan; Herrero, Rolando; Porras, Carolina; Schiffman, Mark; González, Paula; Solomon, Diane; Jiménez, Silvia; Schiller, John T; Lowy, Douglas R; Quint, Wim; Sherman, Mark E; Schussler, John; Wacholder, Sholom

2011-10-05

Three-dose regimens for human papillomavirus (HPV) vaccines are expensive and difficult to complete, especially in settings where the need for cervical cancer prevention is greatest. We evaluated the vaccine efficacy of fewer than three doses of the HPV16/18 vaccine Cervarix in our Costa Rica Vaccine Trial. Women were randomly assigned to receive three doses of the HPV16/18 vaccine or to a control vaccine and were followed for incident HPV16 or HPV18 infection that persisted in visits that were 10 or more months apart (median follow-up 4.2 years). After excluding women who had no follow-up or who were HPV16 and HPV18 DNA positive at enrollment, 5967 women received three vaccine doses (2957 HPV vaccine vs 3010 control vaccine), 802 received two doses (422 HPV vs. 380 control), and 384 received one dose (196 HPV vs. 188 control). Reasons for receiving fewer doses and other pre- and post-randomization characteristics were balanced within each dosage group between women receiving the HPV and control vaccines. Incident HPV16 or HPV18 infections that persisted for 1 year were unrelated to dosage of the control vaccine. Vaccine efficacy was 80.9% for three doses of the HPV vaccine (95% confidence interval [CI] = 71.1% to 87.7%; 25 and 133 events in the HPV and control arms, respectively), 84.1% for two doses (95% CI = 50.2% to 96.3%; 3 and 17 events), and 100% for one dose (95% CI = 66.5% to 100%; 0 and 10 events). Four years after vaccination of women who appeared to be uninfected, this nonrandomized analysis suggests that two doses of the HPV16/18 vaccine, and maybe even one dose, are as protective as three doses.

Once daily dolutegravir (S/GSK1349572) in combination therapy in antiretroviral-naive adults with HIV: planned interim 48 week results from SPRING-1, a dose-ranging, randomised, phase 2b trial.

PubMed

van Lunzen, Jan; Maggiolo, Franco; Arribas, José R; Rakhmanova, Aza; Yeni, Patrick; Young, Benjamin; Rockstroh, Jürgen K; Almond, Steve; Song, Ivy; Brothers, Cindy; Min, Sherene

2012-02-01

Dolutegravir (S/GSK1349572) is a new HIV-1 integrase inhibitor that has antiviral activity with once daily, unboosted dosing. SPRING-1 is an ongoing study designed to select a dose for phase 3 assessment. We present data from preplanned primary and interim analyses. In a phase 2b, multicentre, dose-ranging study, treatment-naive adults were randomly assigned (1:1:1:1) to receive 10 mg, 25 mg, or 50 mg dolutegravir or 600 mg efavirenz. Dose but not drug allocation was masked. Randomisation was by a central integrated voice-response system according to a computer-generated code. Study drugs were given with either tenofovir plus emtricitabine or abacavir plus lamivudine. Our study was done at 34 sites in France, Germany, Italy, Russia, Spain, and the USA beginning on July 9, 2009. Eligible participants were seropositive for HIV-1, aged 18 years or older, and had plasma HIV RNA viral loads of at least 1000 copies per mL and CD4 counts of at least 200 cells per μL. Our primary endpoint was the proportion of participants with viral load of less than 50 copies per mL at week 16 and we present data to week 48. Analyses were done on the basis of allocation group and included all participants who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, number NCT00951015. 205 patients were randomly allocated and received at least one dose of study drug: 53, 51, and 51 to receive 10 mg, 25 mg, and 50 mg dolutegravir, respectively, and 50 to receive efavirenz. Week 16 response rates to viral loads of at most 50 copies per mL were 93% (144 of 155 participants) for all doses of dolutegravir (with little difference between dose groups) and 60% (30 of 50) for efavirenz; week 48 response rates were 87% (139 of 155) for all doses of dolutegravir and 82% (41 of 50) for efavirenz. Response rates between nucleoside reverse transcriptase inhibitor subgroups were similar. We identified three virological failures in the dolutegravir groups and one in the efavirenz group-we did not identify any integrase inhibitor mutations. We did not identify any dose-related clinical or laboratory toxic effects, with more drug-related adverse events of moderate-or-higher intensity in the efavirenz group (20%) than the dolutegravir group (8%). We did not judge that any serious adverse events were related to dolutegravir. Dolutegravir was effective when given once daily without a pharmacokinetic booster and was well tolerated at all assessed doses. Our findings support the assessment of once daily 50 mg dolutegravir in phase 3 trials. Copyright © 2012 Elsevier Ltd. All rights reserved.

Estimating effective dose to pediatric patients undergoing interventional radiology procedures using anthropomorphic phantoms and MOSFET dosimeters.

PubMed

Miksys, Nelson; Gordon, Christopher L; Thomas, Karen; Connolly, Bairbre L

2010-05-01

The purpose of this study was to estimate the effective doses received by pediatric patients during interventional radiology procedures and to present those doses in "look-up tables" standardized according to minute of fluoroscopy and frame of digital subtraction angiography (DSA). Organ doses were measured with metal oxide semiconductor field effect transistor (MOSFET) dosimeters inserted within three anthropomorphic phantoms, representing children at ages 1, 5, and 10 years, at locations corresponding to radiosensitive organs. The phantoms were exposed to mock interventional radiology procedures of the head, chest, and abdomen using posteroanterior and lateral geometries, varying magnification, and fluoroscopy or DSA exposures. Effective doses were calculated from organ doses recorded by the MOSFET dosimeters and are presented in look-up tables according to the different age groups. The largest effective dose burden for fluoroscopy was recorded for posteroanterior and lateral abdominal procedures (0.2-1.1 mSv/min of fluoroscopy), whereas procedures of the head resulted in the lowest effective doses (0.02-0.08 mSv/min of fluoroscopy). DSA exposures of the abdomen imparted higher doses (0.02-0.07 mSv/DSA frame) than did those involving the head and chest. Patient doses during interventional procedures vary significantly depending on the type of procedure. User-friendly look-up tables may provide a helpful tool for health care providers in estimating effective doses for an individual procedure.

Determining the behavioural dose-response relationship of marine mammals to air gun noise and source proximity.

PubMed

Dunlop, Rebecca A; Noad, Michael J; McCauley, Robert D; Scott-Hayward, Lindsay; Kniest, Eric; Slade, Robert; Paton, David; Cato, Douglas H

2017-08-15

The effect of various anthropogenic sources of noise (e.g. sonar, seismic surveys) on the behaviour of marine mammals is sometimes quantified as a dose-response relationship, where the probability of an animal behaviourally 'responding' (e.g. avoiding the source) increases with 'dose' (or received level of noise). To do this, however, requires a definition of a 'significant' response (avoidance), which can be difficult to quantify. There is also the potential that the animal 'avoids' not only the source of noise but also the vessel operating the source, complicating the relationship. The proximity of the source is an important variable to consider in the response, yet difficult to account for given that received level and proximity are highly correlated. This study used the behavioural response of humpback whales to noise from two different air gun arrays (20 and 140 cubic inch air gun array) to determine whether a dose-response relationship existed. To do this, a measure of avoidance of the source was developed, and the magnitude (rather than probability) of this response was tested against dose. The proximity to the source, and the vessel itself, was included within the one-analysis model. Humpback whales were more likely to avoid the air gun arrays (but not the controls) within 3 km of the source at levels over 140 re. 1 µPa 2  s -1 , meaning that both the proximity and the received level were important factors and the relationship between dose (received level) and response is not a simple one. © 2017. Published by The Company of Biologists Ltd.

A randomized intervention of reminder letter for human papillomavirus vaccine series completion.

PubMed

Chao, Chun; Preciado, Melissa; Slezak, Jeff; Xu, Lanfang

2015-01-01

Completion rate for the three-dose series of the human papillomavirus (HPV) vaccine has generally been low. This study evaluated the effectiveness of a reminder letter intervention on HPV vaccine three-dose series completion. Female members of Kaiser Permanente Southern California Health Plan who received at least one dose, but not more than two doses, of the HPV vaccine by February 13, 2013, and who were between ages 9 and 26 years at the time of first HPV vaccination were included. Eighty percent of these females were randomized to receive the reminder letter, and 20% were randomized to receive standard of care (control). The reminder letters were mailed quarterly to those who had not completed the series. The proportion of series completion at the end of the 12-month evaluation period was compared using chi-square test. A total of 9,760 females were included in the intervention group and 2,445 in the control group. HPV vaccine series completion was 56.4% in the intervention group and 46.6% in the control groups (p < .001). The effect of the intervention appeared to be stronger in girls aged 9-17 years compared with young women aged 18-26 years at the first dose and in blacks compared with whites. Reminder letters scheduled quarterly were effective to enhance HPV vaccine series completion among those who initiated the vaccine. However, a large gap in series completion remained despite the intervention. Future studies should address other barriers to series completion, including those at the providers and the health care system level. Copyright © 2015 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

[Disseminated intravascular coagulation induced by endotoxin in rabbits: effect of treatment with t-PA and urokinase].

PubMed

Paloma, M J; Páramo, J A; Rifón, J; Rocha, E

1992-12-01

To assess the therapeutic efficacy of agents capable of stimulating the fibrinolytic system, such as tissue plasminogen activator (t-PA) and urokinase (UK) on endotoxin-induced disseminated intravascular coagulation (DIC) in the rabbit. DIC was induced by intravenous administration of endotoxin, 20 micrograms/kg/hr during 6 hr. Four different groups were established: a) control group, receiving only saline solution; b) t-PA group receiving 0.2 mg/kg; c) t-PA group receiving 0.7 mg/kg, and d) UK group, which was given 3,000 IU/kg/hr for 6 hr. Blood samples were drawn before and after 2 hr and 6 hr of endotoxin administration. Platelet count, and fibrinogen, factor XII and antithrombin III concentrations, were assessed in each sample. Mean, standard deviation and percentage of increase or decrease with respect to the basal value, this considered 100%, were used to evaluate the findings. For comparison of values, Student's t and Mann Whitney's U were used; the Fisher test was used for mortality studies. No statistical differences appeared for any of the values in the rabbits under basal conditions. The rabbits in the control group developed DIC. No doses of t-PA modified the changes appearing in blood coagulation. UK reduced the fibrinogen and factor XII consumption induced by endotoxin. The mortality rate in the control group reached 70%. High-dose t-PA decreased such figure to 50%, while low-dose t-PA or UK failed to reduce mortality. High-dose t-PA has beneficial effects on endotoxin-induced DIC in rabbits. UK failed to achieve such effect at the doses given in this experimental DIC model.

Combined effects of depleted uranium and ionising radiation on zebrafish embryos.

PubMed

Ng, C Y P; Pereira, S; Cheng, S H; Adam-Guillermin, C; Garnier-Laplace, J; Yu, K N

2015-11-01

In the environment, living organisms are exposed to a mixture of stressors, and the combined effects are deemed as multiple stressor effects. In the present work, the authors studied the multiple stressor effect in embryos of the zebrafish (Danio rerio) from simultaneous exposure to alpha particles and depleted uranium (DU) through quantification of apoptotic signals at 24 h post-fertilisation (hpf) revealed by vital dye acridine orange staining. In each set of experiments, dechorionated zebrafish embryos were divided into 4 groups, each having 10 embryos: Group (C) in which the embryos did not receive any further treatment; Group (IU) in which the embryos received an alpha-particle dose of 0.44 mGy at 5 hpf and were then exposed to 100 µg l(-1) of DU from 5 to 6 hpf; Group (I) in which the embryos received an alpha-particle dose of 0.44 mGy at 5 hpf and Group (U) in which the dechorionated embryos were exposed to 100 µg l(-1) of DU from 5 to 6 hpf. The authors confirmed that an alpha-particle dose of 0.44 mGy and a DU exposure for 1 h separately led to hormetic and toxic effects assessed by counting apoptotic signals, respectively, in the zebrafish. Interestingly, the combined exposure led to an effect more toxic than that caused by the DU exposure alone, so effectively DU changed the beneficial effect (hormesis) brought about by alpha-particle irradiation into an apparently toxic effect. This could be explained in terms of the promotion of early death of cells predisposed to spontaneous transformation by the small alpha-particle dose (i.e. hormetic effect) and the postponement of cell death upon DU exposure. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Long-Term Dose-Dependent Agalsidase Effects on Kidney Histology in Fabry Disease.

PubMed

Skrunes, Rannveig; Tøndel, Camilla; Leh, Sabine; Larsen, Kristin Kampevold; Houge, Gunnar; Davidsen, Einar Skulstad; Hollak, Carla; van Kuilenburg, André B P; Vaz, Frédéric M; Svarstad, Einar

2017-09-07

Dose-dependent clearing of podocyte globotriaosylceramide has previously been shown in patients with classic Fabry disease treated with enzyme replacement. Our study evaluates the dose-dependent effects of agalsidase therapy in serial kidney biopsies of patients treated for up to 14 years. Twenty patients with classic Fabry disease (12 men) started enzyme replacement therapy at a median age of 21 (range =7-62) years old. Agalsidase- α or - β was prescribed for a median of 9.4 (range =5-14) years. The lower fixed dose group received agalsidase 0.2 mg/kg every other week throughout the follow-up period. The higher dose group received a range of agalsidase doses (0.2-1.0 mg/kg every other week). Dose changes were made due to disease progression, suboptimal effect, or agalsidase- β shortage. Serial kidney biopsies were performed along with clinical assessment and biomarkers and scored according to recommendations from the International Study Group of Fabry Nephropathy. No statistical differences were found in baseline or final GFR or albuminuria. Kidney biopsies showed significant reduction of podocyte globotriaosylceramide in both the lower fixed dose group (-1.39 [SD=1.04]; P =0.004) and the higher dose group (-3.16 [SD=2.39]; P =0.002). Podocyte globotriaosylceramide (Gb3) reduction correlated with cumulative agalsidase dose ( r =0.69; P =0.001). Arterial/arteriolar intima Gb3 cleared significantly in the higher dose group, all seven patients with baseline intimal Gb3 cleared the intima, one patient gained intimal Gb3 inclusions ( P =0.03), and medial Gb3 did not change statistically in either group. Residual plasma globotriaosylsphingosine levels remained higher in the lower fixed dose group (20.1 nmol/L [SD=11.9]) compared with the higher dose group (10.4 nmol/L [SD=8.4]) and correlated with cumulative agalsidase dose in men ( r =0.71; P =0.01). Reduction of podocyte globotriaosylceramide was found in patients with classic Fabry disease treated with long-term agalsidase on different dosing regimens, correlating with cumulative dose. Limited clearing of arterial/arteriolar globotriaosylceramide raises concerns regarding long-term vascular effects of current therapy. Residual plasma globotriaosylsphingosine correlated with cumulative dose in men. Copyright © 2017 by the American Society of Nephrology.

Pharmacologic treatment of acute pediatric methamphetamine toxicity.

PubMed

Ruha, Anne-Michelle; Yarema, Mark C

2006-12-01

To report our experience with the use of benzodiazepines and haloperidol for sedation of pediatric patients with acute methamphetamine poisoning. We performed a retrospective chart review of 18 pediatric patients who were admitted to an intensive care unit for methamphetamine toxicity from January 1997 to October 2004 and treated with benzodiazepines or haloperidol. Clinical features, dose of drug received, and laboratory test results were noted. Adverse effects from the use of haloperidol such as prolonged QTc, dystonic reactions, and torsades de pointes were recorded. Eighteen patients received a benzodiazepine, the dose of which varied depending on the agent used. Twelve patients also received parenteral haloperidol. No complications developed from the use of either haloperidol or benzodiazepines. In this case series of pediatric patients poisoned with methamphetamine, parenteral benzodiazepines and haloperidol were used to control agitation. No serious adverse effects were observed from the use of these agents.

Ketamine as an Adjunct to Opioids for Acute Pain in the Emergency Department: A Randomized Controlled Trial.

PubMed

Bowers, Karen J; McAllister, Kelly B; Ray, Meredith; Heitz, Corey

2017-06-01

This study had five objectives: 1) to measure and compare total opioid use and number of opioid doses in patients treated with opioids versus ketamine in conjunction with opioids; 2) to measure pain scores up to 2 hours after presentation in the ED patient with pain, comparing standard opioid pain control to ketamine in conjunction with opioids; 3) to compare patient satisfaction with pain control using opioids alone versus ketamine in conjunction with opioids; 4) to monitor and compare side effects in patients treated with opioids versus ketamine in conjunction with opioids; and 5) to identify effect variation between different subgroups of patients, with the purpose of focusing future research. We hypothesized that low-dose ketamine, compared to placebo, as an adjunctive treatment to opioids would result in better pain control over 2 hours and greater patient satisfaction with pain control; further, this protocol will result in a lower opioid dosage over 2 hours. This was a randomized, double-blinded, placebo-controlled trial at a single academic emergency department evaluating the use of ketamine versus placebo in conjunction with opioids for moderate to severe pain. Subjects with a continued high level of pain after an initial dose of opioid analgesia were randomized to receive either 0.1 mg/kg ketamine or placebo prior to protocol-based dosing of additional opioid analgesia, if required. Over 120 minutes, subjects were assessed for pain level (0-10), satisfaction with pain control (0-4), side effects, sedation level, and need for additional pain medication. Total opioid dose, including the initial dose, was compared between groups. Sixty-three subjects were randomized to the placebo group and 53 to the ketamine group. No significant differences were found in demographics between the groups. Patients receiving ketamine reported lower pain scores over 120 minutes than patients receiving placebo (p = 0.015). Total opioid dose was lower in the ketamine group (mean ± SD = 9.95 ± 4.83 mg) compared to placebo (mean ± SD = 12.81 ± 6.81 mg; p = 0.02). Satisfaction did not differ between groups. Fewer patients in the ketamine group required additional opioid doses. More patients reported light-headedness and dizziness in the ketamine group. Ketamine, as an adjunct to opioid therapy, was more effective at reducing pain over 120 minutes and resulted in a lower total opioid dose as well as fewer repeat doses of analgesia. More side effects were reported in the ketamine group (51% vs. 19%), but the side effect profile appears tolerable. © 2017 by the Society for Academic Emergency Medicine.

Effectiveness of monovalent human rotavirus vaccine against admission to hospital for acute rotavirus diarrhoea in South African children: a case-control study.

PubMed

Groome, Michelle J; Page, Nicola; Cortese, Margaret M; Moyes, Jocelyn; Zar, Heather J; Kapongo, Constant N; Mulligan, Christine; Diedericks, Ralph; Cohen, Cheryl; Fleming, Jessica A; Seheri, Mapaseka; Mphahlele, Jeffrey; Walaza, Sibongile; Kahn, Kathleen; Chhagan, Meera; Steele, A Duncan; Parashar, Umesh D; Zell, Elizabeth R; Madhi, Shabir A

2014-11-01

The effectiveness of the rotavirus vaccine under conditions of routine use in an African setting with a high prevalence of HIV infection needs to be established. We assessed the vaccine effectiveness of monovalent human rotavirus vaccine in preventing admission to hospital for acute rotavirus diarrhoea, after its introduction at age 6 and 14 weeks into South Africa's national immunisation programme. This case-control study was done at seven hospitals in South Africa between April 19, 2010, and Oct 31, 2012. The hospitals were located in a range of urban, peri-urban, and rural settings, with varying rates of population HIV infection. Cases were children aged from 18 weeks to 23 months who were age-eligible to have received at least one dose of the human rotavirus vaccine (ie, those born after June 14, 2009) admitted to hospital with laboratory-confirmed acute rotavirus diarrhoea, and the primary control group was children admitted to hospital with diarrhoea testing negative for rotavirus. A second control group comprised children admitted to a subset of three of the seven hospitals with respiratory illness. The primary endpoint was adjusted vaccine effectiveness (1 - adjusted odds ratio × 100%) in children aged from 18 weeks to 23 months and was calculated by unconditional logistic regression. This study is registered on the South African National Clinical Trial Register, number DOH-27-0512-3247. Of 540 rotavirus-positive cases, 278 children (52%) received two doses, 126 (23%) one dose, and 136 (25%) no doses of human rotavirus vaccine, compared with 1434 rotavirus-negative controls of whom 856 (60%) received two doses, 334 (23%) one dose, and 244 (17%) no doses. Adjusted vaccine effectiveness using rotavirus-negative controls was 57% (95% CI 40-68) for two doses and 40% (16-57) for one dose; estimates were similar when respiratory controls were used as the control group. Adjusted vaccine effectiveness for two doses was similar between age groups 18 weeks-11 months (54%, 95% CI 32-68) and 12-23 months (61%, 35-77), and was similar in HIV-exposed-uninfected (64%, 95% CI 34-80) and HIV-unexposed-uninfected children (54%, 31-69). Human rotavirus vaccine provided sustained protection against admission to hospital for acute rotavirus diarrhoea during the first and second years of life. This finding is encouraging and establishes the public health value of rotavirus vaccine in an African setting, especially as rotavirus vaccines are introduced into an increasing number of African countries. GAVI Alliance (with support from PATH). Copyright © 2014 Elsevier Ltd. All rights reserved.

Intraoperative Methadone in Same-Day Ambulatory Surgery: A Randomized, Double-Blinded, Dose-Finding Pilot Study.

PubMed

Komen, Helga; Brunt, L Michael; Deych, Elena; Blood, Jane; Kharasch, Evan D

2018-05-25

Approximately 50 million US patients undergo ambulatory surgery annually. Postoperative opioid overprescribing is problematic, yet many patients report inadequate pain relief. In major inpatient surgery, intraoperative single-dose methadone produces better analgesia and reduces opioid use compared with conventional repeated dosing of short-duration opioids. This investigation tested the hypothesis that in same-day ambulatory surgery, intraoperative methadone, compared with short-duration opioids, reduces opioid consumption and pain, and determined an effective intraoperative induction dose of methadone for same-day ambulatory surgery. A double-blind, dose-escalation protocol randomized 60 patients (2:1) to intraoperative single-dose intravenous methadone (initially 0.1 then 0.15 mg/kg ideal body weight) or conventional as-needed dosing of short-duration opioids (eg, fentanyl, hydromorphone; controls). Intraoperative and postoperative opioid consumption, pain, and opioid side effects were assessed before discharge. Patient home diaries recorded pain, opioid use, and opioid side effects daily for 30 days postoperatively. Primary outcome was in-hospital (intraoperative and postoperative) opioid use. Secondary outcomes were 30 days opioid consumption, pain intensity, and opioid side effects. Median (interquartile range) methadone doses were 6 (5-6) and 9 (8-9) mg in the 0.1 and 0.15 mg/kg methadone groups, respectively. Total opioid consumption (morphine equivalents) in the postanesthesia care unit was significantly less compared with controls (9.3 mg, 1.3-11.0) in subjects receiving 0.15 mg/kg methadone (0.1 mg, 0.1-3.3; P < .001) but not 0.1 mg/kg methadone (5.0 mg, 3.3-8.1; P = .60). Dose-escalation ended at 0.15 mg/kg methadone. Total in-hospital nonmethadone opioid use after short-duration opioid, 0.1 mg/kg methadone, and 0.15 mg/kg methadone was 35.3 (25.0-44.0), 7.1 (3.7-10.0), and 3.3 (0.1-5.8) mg morphine equivalents, respectively (P < .001 for both versus control). In-hospital pain scores and side effects were not different between groups. In the 30 days after discharge, patients who received methadone 0.15 mg/kg had less pain at rest (P = .02) and used fewer opioid pills than controls (P < .0001), whereas patients who received 0.1 mg/kg had no difference in pain at rest (P = .69) and opioid use compared to controls (P = .08). In same-day discharge surgery, this pilot study identified a single intraoperative dose of methadone (0.15 mg/kg ideal body weight), which decreased intraoperative and postoperative opioid requirements and postoperative pain, compared with conventional intermittent short-duration opioids, with similar side effects.

Digoxin and bepridil: pharmacokinetic and pharmacodynamic interactions.

PubMed

Belz, G G; Wistuba, S; Matthews, J H

1986-01-01

The influence of bepridil on steady-state serum digoxin concentrations (SDCs) and the pharmacodynamic actions of both drugs were tested in 48 healthy subjects in a randomized, double-blind study. Subjects were assigned to one of two groups of 24 subjects each: One group received placebo 1, while the other received digoxin, 0.375 mg/day, loaded with doubled doses on days 1 and 2, for 14 days. After 7 days the groups were subdivided into four groups of 12 subjects each and received concurrent dosing of digoxin with either placebo 2 or bepridil, 300 mg/day, loaded with 900 mg on day 8. Mean (+/- SD) SDCs rose during concurrent bepridil dosing from 0.93 +/- 0.22 to 1.25 +/- 0.25 ng/ml (P less than 0.001). Noninvasive cardiovascular parameters from ECG, systolic time intervals, and electrical impedance cardiography were not influenced by the placebos. Digoxin and bepridil reduced heart rate and prolonged the PQ interval because of negative chronotropic and dromotropic properties. Positive inotropism from digoxin shortened the corrected electromechanical systole (QS2c) and the preejection period and increased impedance cardiography [(dZ/dt)/RZ index]; the opposite effects occurred after bepridil, indicating negative inotropism. The QT interval corrected for heart rate (QTc) showed a similar pattern of changes, as did QS2c for each drug. Concurrent dosing of both drugs resulted in an addition of their chronotropic effects, whereas the dromotropic effects of each drug alone was not intensified. The strengthened digoxin effect from the increased SDC diminished the negative inotropic effect of bepridil. Overall, drug coadministration resulted in a nearly unchanged digoxin-induced positive inotropism.(ABSTRACT TRUNCATED AT 250 WORDS)

Estimating the effective radiation dose imparted to patients by intraoperative cone-beam computed tomography in thoracolumbar spinal surgery.

PubMed

Lange, Jeffrey; Karellas, Andrew; Street, John; Eck, Jason C; Lapinsky, Anthony; Connolly, Patrick J; Dipaola, Christian P

2013-03-01

Observational. To estimate the radiation dose imparted to patients during typical thoracolumbar spinal surgical scenarios. Minimally invasive techniques continue to become more common in spine surgery. Computer-assisted navigation systems coupled with intraoperative cone-beam computed tomography (CT) represent one such method used to aid in instrumented spinal procedures. Some studies indicate that cone-beam CT technology delivers a relatively low dose of radiation to patients compared with other x-ray-based imaging modalities. The goal of this study was to estimate the radiation exposure to the patient imparted during typical posterior thoracolumbar instrumented spinal procedures, using intraoperative cone-beam CT and to place these values in the context of standard CT doses. Cone-beam CT scans were obtained using Medtronic O-arm (Medtronic, Minneapolis, MN). Thermoluminescence dosimeters were placed in a linear array on a foam-plastic thoracolumbar spine model centered above the radiation source for O-arm presets of lumbar scans for small or large patients. In-air dosimeter measurements were converted to skin surface measurements, using published conversion factors. Dose-length product was calculated from these values. Effective dose was estimated using published effective dose to dose-length product conversion factors. Calculated dosages for many full-length procedures using the small-patient setting fell within the range of published effective doses of abdominal CT scans (1-31 mSv). Calculated dosages for many full-length procedures using the large-patient setting fell within the range of published effective doses of abdominal CT scans when the number of scans did not exceed 3. We have demonstrated that single cone-beam CT scans and most full-length posterior instrumented spinal procedures using O-arm in standard mode would likely impart a radiation dose within the range of those imparted by a single standard CT scan of the abdomen. Radiation dose increases with patient size, and the radiation dose received by larger patients as a result of more than 3 O-arm scans in standard mode may exceed the dose received during standard CT of the abdomen. Understanding radiation imparted to patients by cone-beam CT is important for assessing risks and benefits of this technology, especially when spinal surgical procedures require multiple intraoperative scans.

Epidural labour analgesia using Bupivacaine and Clonidine

PubMed Central

Syal, K; Dogra, RK; Ohri, A; Chauhan, G; Goel, A

2011-01-01

Background: To compare the effects of addition of Clonidine (60 μg) to Epidural Bupivacaine (0.125%) for labour analgesia, with regard to duration of analgesia, duration of labour, ambulation, incidence of instrumentation and caesarean section, foetal outcome, patient satisfaction and side effects. Patients & Methods: On demand, epidural labour analgesia was given to 50 nulliparous healthy term parturients (cephalic presentation), divided in two groups randomly. Group I received bupivacaine (0.125%) alone, whereas Group II received bupivacaine (0.125%) along with Clonidine (60 μg). 10 ml of 0.125% bupivacaine was injected as first dose and further doses titrated with patient relief (Numerical Rating Scale <3). Top ups were given whenever Numerical Rating Scale went above 5. Results: There was statistically significant prolongation of duration of analgesia in Group II, with no difference in duration of labour, ambulation, incidence of instrumentation and caesarean section or foetal outcome. Also clonidine gave dose sparing effect to bupivacaine and there was better patient satisfaction without any significant side effects in Group II. Conclusion: Clonidine is a useful adjunct to bupivacaine for epidural labour analgesia and can be considered as alternative to opioids. PMID:21804714

High-dose Carboplatin/Etoposide/Melphalan increases risk of thrombotic microangiopathy and organ injury after autologous stem cell transplantation in patients with neuroblastoma.

PubMed

Jodele, Sonata; Dandoy, Christopher E; Myers, Kasiani; Wallace, Gregory; Lane, Adam; Teusink-Cross, Ashley; Weiss, Brian; Davies, Stella M

2018-04-19

Transplant-associated thrombotic microangiopathy (TA-TMA) is an increasingly recognized complication of hematopoietic cell transplant that can result in multi-organ failure (MOF). Patients undergoing high-dose chemotherapy with autologous stem cell transplant (aHCT) for neuroblastoma require good organ function to receive post-transplant radiation and immunotherapy. We examined TA-TMA incidence and transplant outcomes in patients with neuroblastoma receiving different transplant preparative regimens. Sixty patients underwent aHCT using high-dose chemotherapy: 41 patients received carboplatin/etoposide/melphalan (CEM), 13 patients busulfan/melphalan (Bu/Mel) and six patients received tandem transplant (cyclophosphamide/thiotepa and CEM). TA-TMA with MOF was diagnosed in 13 patients (21.7%) at a median of 18 days after aHCT. TA-TMA occurred in 12 patients receiving CEM and in 1 after cyclophosphamide/thiotepa. There were no incidences of TA-TMA after Bu/Mel regimen. Six of 13 patients with TA-TMA and MOF received terminal complement blocker eculizumab for therapy. They all recovered organ function and received planned post-transplant therapy. Out of seven patients who did not get eculizumab, two died from TA-TMA complications and four progressed to ESRD. We conclude that the CEM regimen is associated with a high incidence of clinically significant TA-TMA after aHCT and eculizumab can be safe and effective treatment option to remediate TA-TMA associated MOF.

No effect of the novel antidiabetic agent nateglinide on the pharmacokinetics and anticoagulant properties of warfarin in healthy volunteers.

PubMed

Anderson, Denise M; Shelley, Sarah; Crick, Nina; Buraglio, Mauro

2002-12-01

The novel hypoglycemic agent nateglinide is pharmacologically distinct from oral hypoglycemic agents such as sulfonylureas and repaglinide. The present study investigated the effects in healthy volunteers of multiple doses of nateglinide on the pharmacokinetics and pharmacodynamics of warfarin. The study comprised a randomized two-group, two-way crossover, open-label design in 12 healthy male subjects. One group of 6 subjects initially received a single oral dose of warfarin 30 mg and then, after a 7- to 14-day washout, received both warfarin and nateglinide (120 mgnateglinide, 10 min before meals for 4 days and a single dose of 30 mg warfarin on the second day). The alternate group of 6 subjects received treatments in the opposite order. Pharmacokinetic profiles were derived from plasma warfarin and nateglinide concentrations. Prothrombin measurements were evaluated in both periods as a measure of warfarin activity. When administered alone or in combination, there were no statistically significant differences in mean warfarin (R- and S-enantiomers) or nateglinide pharmacokinetic parameters. The concurrent administration of nateglinide and warfarin did not affect the maximal change in prothrombin time that follows warfarin administration. In this study, there was no evidence of an effect of coadministration of nateglinide on the pharmacodynamic action of warfarin or any pharmacokinetic interaction between warfarin and nateglinide.

Predicting pneumonitis risk: a dosimetric alternative to mean lung dose.

PubMed

Tucker, Susan L; Mohan, Radhe; Liengsawangwong, Raweewan; Martel, Mary K; Liao, Zhongxing

2013-02-01

To determine whether the association between mean lung dose (MLD) and risk of severe (grade ≥3) radiation pneumonitis (RP) depends on the dose distribution pattern to normal lung among patients receiving 3-dimensional conformal radiation therapy for non-small-cell lung cancer. Three cohorts treated with different beam arrangements were identified. One cohort (2-field boost [2FB]) received 2 parallel-opposed (anteroposterior-posteroanterior) fields per fraction initially, followed by a sequential boost delivered using 2 oblique beams. The other 2 cohorts received 3 or 4 straight fields (3FS and 4FS, respectively), ie, all fields were irradiated every day. The incidence of severe RP was plotted against MLD in each cohort, and data were analyzed using the Lyman-Kutcher-Burman (LKB) model. The incidence of grade ≥3 RP rose more steeply as a function of MLD in the 2FB cohort (N=120) than in the 4FS cohort (N=138), with an intermediate slope for the 3FS group (N=99). The estimated volume parameter from the LKB model was n=0.41 (95% confidence interval, 0.15-1.0) and led to a significant improvement in fit (P=.05) compared to a fit with volume parameter fixed at n=1 (the MLD model). Unlike the MLD model, the LKB model with n=0.41 provided a consistent description of the risk of severe RP in all three cohorts (2FB, 3FS, 4FS) simultaneously. When predicting risk of grade ≥3 RP, the mean lung dose does not adequately take into account the effects of high doses. Instead, the effective dose, computed from the LKB model using volume parameter n=0.41, may provide a better dosimetric parameter for predicting RP risk. If confirmed, these findings support the conclusion that for the same MLD, high doses to small lung volumes ("a lot to a little") are worse than low doses to large volumes ("a little to a lot"). Copyright © 2013 Elsevier Inc. All rights reserved.

Simulation of Dose to Surrounding Normal Structures in Tangential Breast Radiotherapy Due to Setup Error

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

Prabhakar, Ramachandran; Department of Nuclear Medicine, All India Institute of Medical Sciences, New Delhi; Department of Radiology, All India Institute of Medical Sciences, New Delhi

Setup error plays a significant role in the final treatment outcome in radiotherapy. The effect of setup error on the planning target volume (PTV) and surrounding critical structures has been studied and the maximum allowed tolerance in setup error with minimal complications to the surrounding critical structure and acceptable tumor control probability is determined. Twelve patients were selected for this study after breast conservation surgery, wherein 8 patients were right-sided and 4 were left-sided breast. Tangential fields were placed on the 3-dimensional-computed tomography (3D-CT) dataset by isocentric technique and the dose to the PTV, ipsilateral lung (IL), contralateral lung (CLL),more » contralateral breast (CLB), heart, and liver were then computed from dose-volume histograms (DVHs). The planning isocenter was shifted for 3 and 10 mm in all 3 directions (X, Y, Z) to simulate the setup error encountered during treatment. Dosimetric studies were performed for each patient for PTV according to ICRU 50 guidelines: mean doses to PTV, IL, CLL, heart, CLB, liver, and percentage of lung volume that received a dose of 20 Gy or more (V20); percentage of heart volume that received a dose of 30 Gy or more (V30); and volume of liver that received a dose of 50 Gy or more (V50) were calculated for all of the above-mentioned isocenter shifts and compared to the results with zero isocenter shift. Simulation of different isocenter shifts in all 3 directions showed that the isocentric shifts along the posterior direction had a very significant effect on the dose to the heart, IL, CLL, and CLB, which was followed by the lateral direction. The setup error in isocenter should be strictly kept below 3 mm. The study shows that isocenter verification in the case of tangential fields should be performed to reduce future complications to adjacent normal tissues.« less

A single-dose antihelminthic treatment does not influence immunogenicity of a meningococcal and a cholera vaccine in Gabonese school children.

PubMed

Brückner, Sina; Agnandji, Selidji Todagbe; Elias, Johannes; Berberich, Stefan; Bache, Emmanuel; Fernandes, José; Loembe, Marguerite Massinga; Hass, Johanna; Lell, Bertrand; Mordmüller, Benjamin; Adegnika, Ayola Akim; Kremsner, Peter; Esen, Meral

2016-10-17

We recently described the effect of a single-dose antihelminthic treatment on vaccine immunogenicity to a seasonal influenza vaccine. Here we report the effect of antihelminthics on the immunogenicity of a meningococcal vaccine and a cholera vaccine in primary school children living in Lambaréné, Gabon. Since infection with helminths remains a major public health problem and the influence on cognitive and physical development as well as the immunomodulatory effects are well established, we investigated if a single-dose antihelminthic treatment prior to immunization positively influences antibody titers and vaccine-specific memory B-cells. In this placebo-controlled, double-blind trial the effect of a single-dose antihelminthic treatment prior to immunization with a meningococcal as well as with a cholera vaccine was investigated. Anti-meningococcal antibodies were assessed by serum bactericidal assay, cholera vaccine-specific antibody titers by Enzyme-linked Immunosorbent Assay (ELISA) at baseline (Day 0; vaccination), four weeks (Day 28) and 12weeks (Day 84) following vaccination. Meningococcal and cholera vaccine-specific memory B-cells were measured at Day 0 and 84 by vaccine-specific Enzyme-linked Immunospot (ELISpot) assay. The helminth burden of the participants was assessed four weeks before vaccination (Day -28) and at Day 84 by the Merthiolate-Iodine-Formaldehyde technique. Out of 280 screened school children, 96 received a meningococcal vaccine and 89 a cholera vaccine following allocation to either the single-dose antihelminthic treatment group or the placebo group. Bactericidal antibody titers increased following immunization with the meningococcal vaccine at Day 28 and Day 84 in 68 participants for serogroup A, and in 80 participants for serogroup C. The cholera vaccine titers increased in all participants with a peak at Day 28. The number of memory B-cells increased following vaccination compared to baseline. There was no statistically significant difference in antibody and B-cell response between children receiving albendazole compared to those receiving placebo. A single-dose treatment with albendazole prior to immunization had no effect on meningococcal or cholera vaccine immunogenicity in our study population. Copyright © 2016 Elsevier Ltd. All rights reserved.

Age-specific doses of lormetazepam as a night sedative in cases of chronic sleep disturbance.

PubMed

Jovanović, U J; Ott, H; Heidrich, H; Stephan, K; Schratzer, M

1980-01-01

Lormetazepam, a new benzodiazepine derivative, was tested under double blind conditions in order to find the optimal dosage for different age groups of out-patients. 120 patients suffering from chronic sleep disturbance were included in the study: a younger group (age 20 to 55) and an older group (age 56 to 85 years). Four different doses were given to each age group: 0.5, 1.0, 2.0, and 3.0 mg to the younger group and 0.5, 1.0, 1.5, and 2.0 mg to the older group. A pre-placebo week (i.e. when all patients received placebo) in which baseline data were recorded preceded the two verum weeks, and these were followed by a post-placebo or withdrawal week (again all patients receiving placebo). The level of significance accepted for statistical decisions was alpha = 0.05. No differences in effects between the different doses were observed with regard to sleep pattern variables (sleep latency, sleep duration, frequency of awakenings, sleep quality, occurrence of 'bad' dreams) with the exception of sleep quality which was better in the older group than in the younger group after 0.5 mg in week 2. Considerable differences with regard to hangover feelings the next morning and during the next day (morning feelings, tranquility, alertness, and concentration), comparison of the effects of discontinuing therapy upon the above-mentioned sleep pattern variables and small differences in side effects--which were few--led to the following conclusion: --0.5 mg stood out as the best dose for the older group. --None of the dosages given to the younger group emerged clearly as superior. However, it would seem that the 1 mg dose should be the dose recommended, since fewer unfavourable scores and side effects appeared after this dose.

LONG-RANGE RESULTS OF THE RADIOACTIVE PHOSPHORUS THERAPY OF POLYCYTHEMIA VERA

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

Fazekas, S.; Nagy, G.; Petranyi, G.

1963-02-01

The results of P/sup 32/ treatment of 22 patients with polycythemia vera are presented. Some patients received a single dose of P/sup 32/, others repeated doses. In general the therapeutic effect was satisfactory. The average length of remission after the first treatment was 10.8 months. (P.C.H.)

TOXICITY STUDIES OF EPICHLOROHYDRIN IN SPRAGUE-DAWLEY RATS

EPA Science Inventory

Adult male and female Sprague-Dawley rats received epichlorohydrin via gavage in distilled water for 10 consecutive days at dose levels of 3, 7, 19, and 46 mg/kg-day, and for 90 days at dose levels of 1, 5, and 25 mg/kg-day. Epichlorohydrin did not adversely effect mortality, but...

Adequacy of Fixed-Dose Heparin Infusions for Venous Thromboembolism Prevention after Microsurgical Procedures.

PubMed

Bertolaccini, Corinne M; Prazak, Ann Marie B; Agarwal, Jayant; Goodwin, Isak A; Rockwell, W Bradford; Pannucci, Christopher J

2018-05-22

 In microvascular surgery, patients often receive unfractionated heparin infusions to minimize risk for microvascular thrombosis. Patients who receive intravenous (IV) heparin are believed to have adequate prophylaxis against venous thromboembolism (VTE). Whether a fixed dose of IV heparin provides detectable levels of anticoagulation, or whether the "one size fits all" approach provides adequate prophylaxis against VTE remains unknown. This study examined the pharmacodynamics of fixed-dose heparin infusions and the effects of real-time, anti-factor Xa (aFXa) level driven heparin dose adjustments.  This prospective clinical trial recruited adult microvascular surgery patients placed on a fixed-dose (500 units/h) unfractionated heparin infusion during their initial microsurgical procedure. Steady-state aFXa levels, a marker of unfractionated heparin efficacy and safety, were monitored. Patients with out-of-range aFXa levels received protocol-driven real-time dose adjustments. Outcomes of interest included aFXa levels in response to heparin 500 units/h, number of dose adjustments required to achieve goal aFXa levels, time to reach goal aFXa level, and 90-day clinically relevant bleeding and VTE.  Twenty patients were recruited prospectively. None of 20 patients had any detectable level of anticoagulation in response to heparin infusions at 500 units/h. The median number of dose adjustments required to reach goal level was five, and median weight-based dose to reach goal level was 11.8 units/kg/h. Real-time dose adjustments significantly increased the proportion of patients with in-range levels (60 vs. 0%, p  = 0.0001). The 90-day VTE rate was 5% and 90-day clinically relevant bleeding rate was 5%.  Fixed-dose heparin infusions at a rate of 500 units/h do not provide a detectable level of anticoagulation after microsurgical procedures and are insufficient for the majority of patients who require VTE prophylaxis. Weight-based heparin infusions at 10 to 12 units/kg/h deserve future study in patients undergoing microsurgical procedures to increase the proportion of patients receiving adequate VTE prophylaxis. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Optimal precurarizing dose of rocuronium to decrease fasciculation and myalgia following succinylcholine administration.

PubMed

Kim, Kyu Nam; Kim, Kyo Sang; Choi, Hoon Il; Jeong, Ji Seon; Lee, Hee-Jong

2014-06-01

Succinylcholine commonly produces frequent adverse effects, including muscle fasciculation and myalgia. The current study identified the optimal dose of rocuronium to prevent succinylcholine-induced fasciculation and myalgia and evaluated the influence of rocuronium on the speed of onset produced by succinylcholine. This randomized, double-blinded study was conducted in 100 patients randomly allocated into five groups of 20 patients each. Patients were randomized to receive 0.02, 0.03, 0.04, 0.05 and 0.06 mg/kg rocuronium as a precurarizing dose. Neuromuscular monitoring after each precurarizing dose was recorded from the adductor pollicis muscle using acceleromyography with train-of-four stimulation of the ulnar nerve. All patients received succinylcholine 1.5 mg/kg at 2 minutes after the precurarization, and were assessed the incidence and severity of fasciculations, while myalgia was assessed at 24 hours after surgery. The incidence and severity of visible muscle fasciculation was significantly less with increasing the amount of precurarizing dose of rocuronium (P < 0.001). Those of myalgia tend to decrease according to increasing the amount of precurarizing dose of rocuronium, but there was no significance (P = 0.072). The onset time of succinylcholine was significantly longer with increasing the amount of precurarizing dose of rocuronium (P < 0.001). Precurarization with 0.04 mg/kg rocuronium was the optimal dose considering the reduction in the incidence and severity of fasciculation and myalgia with acceptable onset time, and the safe and effective precurarization.

Effect of amphetamine on human macronutrient intake.

PubMed

Foltin, R W; Kelly, T H; Fischman, M W

1995-11-01

Six male subjects participated in a 15-day residential study examining the effects of amphetamine on macronutrient intake. During the first 11 days, carbohydrate intake was manipulated by providing lunch meals high (155 g) or low (25 g) in carbohydrate. Subjects received oral d-amphetamine (5, 10 mg/70 kg, BID) or placebo. Total daily caloric intake was similar under both lunch conditions (approximately 3400/Kcal), but carbohydrate contributed more energy under the high-carbohydrate condition. Both doses of amphetamine decreased total caloric intake to approximately 2600 Kcal, by decreasing the number of eating bouts, without affecting macronutrient selection. During the last four days subjects received a higher daily dose of amphetamine (30 mg/70 kg in four doses) or placebo, and were allowed to self-select lunch. Although 30 mg amphetamine decreased intake of all macronutrients, the relative contribution of carbohydrate to total caloric intake was increased from 54% to 62%, while the contribution of fat was decreased from 32% to 26% and the contribution of protein was decreased from 14% to 12%. Thus, at a high dose, amphetamine altered the relative contribution of specific macronutrients to total caloric intake.

Timeliness and risk factors associated with delay for pneumococcal conjugate 10-valent routine immunization in Brazilian children.

PubMed

Sartori, Ana Lucia; Minamisava, Ruth; Afonso, Eliane Terezinha; Policena, Gabriela Moreira; Pessoni, Grécia Carolina; Bierrenbach, Ana Luiza; Andrade, Ana Lucia

2017-02-15

Vaccination coverage is the usual metrics to evaluate the immunization programs performance. For the 10-valent pneumococcal conjugate (PCV10) vaccine, measuring the delay of vaccination is also important, particularly as younger children are at increased risk of disease. Routinely collected administrative data was used to assess the timeliness of PCV10 vaccination, and the factors associated with delay to receive the first and second doses, and the completion of the PCV10 3+1 schedule. A population-based retrospective cohort study was conducted with children born in 2012 in Central Brazil. Children who received the PCV10 first dose in public health services were followed-up until 23months of age. Timeliness of receiving each PCV10 dose at any given age was defined as receiving the dose within 28days grace period from the recommended age by the National Immunization Program. Log-binomial regression models were used to examine risk factors for delays of the first dose and the completion PCV10 3+1 schedule. In total, 14,282 children were included in the cohort of study. Delayed vaccination occurred in 9.4%, 23.8%, 36.8% and 39.9% children for the first, second, third and the booster doses, respectively. A total of 1912 children (12.8% of the cohort) were not adequately vaccinated at the 6months of life; 1,071 (7%) received the second dose after 6months of age, 784 (5.4%) did not receive the second dose, and 57 (0.4%) received the first dose after six months of life. A considerable delay was found in PCV10 third and booster doses. Almost 2 thousand children had not received the recommended PCV10 doses at 6months of age. Timeliness of vaccination is an issue in Brazil although high vaccination coverages. Copyright © 2017 Elsevier Ltd. All rights reserved.

Cumulative effective dose associated with radiography and CT of adolescents with spinal injuries.

PubMed

Lemburg, Stefan P; Peters, Soeren A; Roggenland, Daniela; Nicolas, Volkmar; Heyer, Christoph M

2010-12-01

The purpose of this study was to analyze the quantity and distribution of cumulative effective doses in diagnostic imaging of adolescents with spinal injuries. At a level 1 trauma center from July 2003 through June 2009, imaging procedures during initial evaluation and hospitalization and after discharge of all patients 10-20 years old with spinal fractures were retrospectively analyzed. The cumulative effective doses for all imaging studies were calculated, and the doses to patients with spinal injuries who had multiple traumatic injuries were compared with the doses to patients with spinal injuries but without multiple injuries. The significance level was set at 5%. Imaging studies of 72 patients (32 with multiple injuries; average age, 17.5 years) entailed a median cumulative effective dose of 18.89 mSv. Patients with multiple injuries had a significantly higher total cumulative effective dose (29.70 versus 10.86 mSv, p < 0.001) mainly owing to the significantly higher CT-related cumulative effective dose to multiple injury patients during the initial evaluation (18.39 versus 2.83 mSv, p < 0.001). Overall, CT accounted for 86% of the total cumulative effective dose. Adolescents with spinal injuries receive a cumulative effective dose equal to that of adult trauma patients and nearly three times that of pediatric trauma patients. Areas of focus in lowering cumulative effective dose should be appropriate initial estimation of trauma severity and careful selection of CT scan parameters.

The effect of ethinyloestradiol and levonorgestrel on the CYP2C19-mediated metabolism of omeprazole in healthy female subjects

PubMed Central

Palovaara, Sanna; Tybring, Gunnel; Laine, Kari

2003-01-01

Aims To study the effect of an oral contraceptive (OC) formulation containing ethinyloestradiol and levonorgestrel (LNG) (combination OC) or LNG alone on the CYP2C19-mediated hydroxylation of omeprazole in healthy females. Methods This was an open crossover study with three phases. In phase one, 10 healthy females received a single 40-mg dose of omeprazole. Thereafter the subjects received in a random order either 40 µg ethinyloestradiol and 75 µg LNG or 60 µg LNG alone once daily for 10 days. On day 10, 1 h after the last OC dose, subjects received a single 40-mg oral dose of omeprazole. The plasma concentrations of omeprazole, 5′-hydroxyomeprazole and omeprazole sulphone were determined for up to 8 h. Results The use of combination OC increased the area under the curve (AUC) of omeprazole by 38% [95% confidence interval (CI) − 3.8, 80; P = 0.040] and caused a 48% increase (95% CI 28, 68) in the AUC ratio of omeprazole/5-hydroxyomeprazole. LNG alone did not effect the 5′-hydroxylation of omeprazole. Neither of the OC preparations seemed to have an inhibitory effect on the formation of omeprazole sulphone by CYP3A4. Conclusions Oral contraceptives containing ethinyloestradiol but not those containing only LNG decrease CYP2C19 activity. PMID:12895199

Multiple Testing, Cumulative Radiation Dose, and Clinical Indications in Patients Undergoing Myocardial Perfusion Imaging

PubMed Central

Einstein, Andrew J.; Weiner, Shepard D.; Bernheim, Adam; Kulon, Michal; Bokhari, Sabahat; Johnson, Lynne L.; Moses, Jeffrey W.; Balter, Stephen

2013-01-01

Context Myocardial perfusion imaging (MPI) is the single medical test with the highest radiation burden to the US population. While many patients undergoing MPI receive repeat MPI testing, or additional procedures involving ionizing radiation, no data are available characterizing their total longitudinal radiation burden and relating radiation burden with reasons for testing. Objective To characterize procedure counts, cumulative estimated effective doses of radiation, and clinical indications, for patients undergoing MPI. Design, Setting, Patients Retrospective cohort study evaluating, for 1097 consecutive patients undergoing index MPI during the first 100 days of 2006 at Columbia University Medical Center, all preceding medical imaging procedures involving ionizing radiation undergone beginning October 1988, and all subsequent procedures through June 2008, at that center. Main Outcome Measures Cumulative estimated effective dose of radiation, number of procedures involving radiation, and indications for testing. Results Patients underwent a median (interquartile range, mean) of 15 (6–32, 23.9) procedures involving radiation exposure; 4 (2–8, 6.5) were high-dose (≥3 mSv, i.e. one year's background radiation), including 1 (1–2, 1.8) MPI studies per patient. 31% of patients received cumulative estimated effective dose from all medical sources >100mSv. Multiple MPIs were performed in 39% of patients, for whom cumulative estimated effective dose was 121 (81–189, 149) mSv. Men and whites had higher cumulative estimated effective doses, and there was a trend towards men being more likely to undergo multiple MPIs than women (40.8% vs. 36.6%, Odds ratio 1.29, 95% confidence interval 0.98–1.69). Over 80% of initial and 90% of repeat MPI exams were performed in patients with known cardiac disease or symptoms consistent with it. Conclusion In this institution, multiple testing with MPI was very common, and in many patients associated with very high cumulative estimated doses of radiation. PMID:21078807

90-Day oral toxicity study of D-tagatose in rats.

PubMed

Kruger, C L; Whittaker, M H; Frankos, V H; Trimmer, G W

1999-04-01

D-tagatose is a ketohexose, tastes like sugar and is useful as a low-calorie sweetener. To assess D-tagatose's safety, an oral 90-day toxicity study was conducted on male and female Crl:CDBR rats at dietary doses of 5, 10, 15, and 20% D-tagatose. One control group (dietary control) received only lab chow; a second control group received 20% cellulose/fructose in the diet. There were no treatment-related effects at 5% D-tagatose in the diet. At higher doses, treatment-related effects included transient soft stools in male and female animals from the 15 and 20% dose groups. This was anticipated as a result of the osmotic effect of a large dose of relatively undigested sugar and was not considered a toxic effect. All treatment groups gained weight over the study period; however, mean body weights were statistically significantly decreased in the 15 and 20% dose-group males and the 20% dose-group females at selected intervals compared to dietary control animals. No significant reduction in mean food consumption was noted in the treatment groups compared to the dietary control. Statistically significantly increased relative liver weights were noted in male and female animals from the 10, 15, and 20% dose groups compared to the dietary control. No gross pathological findings correlated with these increased liver weights. Minimal hepatocellular hypertrophy was observed in male and female animals from the 15 and 20% dose groups. An independent review of the liver slides concluded that histomorphologic changes associated with D-tagatose were restricted hepatocyte hypertrophy and hepatocyte glycogen accumulation. Therefore, it was concluded that increased liver weights and minimal hypertrophy were the result of adaptation to the high dietary levels (greater than 5% in the diet) of D-tagatose. No adverse effects were seen at 5% D-tagatose in the diet. Copyright 1999 Academic Press.

The Impact of Disulfiram Treatment on the Reinforcing Effects of Cocaine: A Randomized Clinical Trial

PubMed Central

Haile, Colin N.; De La Garza, Richard; Mahoney, James J.; Nielsen, David A.; Kosten, Thomas R.; Newton, Thomas F.

2012-01-01

Background Clinical trials indicate that disulfiram (250 mg/d) reduces cocaine use, though one study found that treatment with lower doses of disulfiram (62.5 and 125 mg/d) increased cocaine use. We conducted the present study to better understand how disulfiram alters the reinforcing effects of cocaine in cocaine users. Methods Seventeen non-treatment seeking, cocaine-dependent volunteers participated in this double-blind, placebo-controlled, laboratory-based study. A cross-over design was utilized in which participants received placebo in one phase and disulfiram (250 mg/d) in the other. Following three days of study medication participants completed two choice sessions. In one they made 10 choices between receiving an intravenous infusion of saline or money that increased in value (US$ 0.05–16) and in the other cocaine (20 mg) or money. Results Participants chose cocaine more than saline under both disulfiram and placebo conditions (p<0.05). Unexpectedly, disulfiram increased both the number of cocaine and saline infusion choices (p<0.05). We next examined the relationship between disulfiram dose and cocaine choices. Disulfiram dose (mg/kg bodyweight) was negatively correlated with number of choices for cocaine (p<0.05). Disulfiram also enhanced cocaine-induced increases in cardiovascular measures (p's<0.05–0.01). Conclusions Disulfiram's impact on the reinforcing effects of cocaine depends on dose relative to body weight. Our results suggest that the use of weight-based medication doses would produce more reliable effects, consistent with weight-based dosing used in pediatrics and in preclinical research. Trial Registration Clinicaltrials.gov NCT00729300 PMID:23144826

Mid-way and post-intervention effects on potential determinants of physical activity and sedentary behavior, results of the HEIA study - a multi-component school-based randomized trial.

PubMed

Bergh, Ingunn H; Bjelland, Mona; Grydeland, May; Lien, Nanna; Andersen, Lene F; Klepp, Knut-Inge; Anderssen, Sigmund A; Ommundsen, Yngvar

2012-05-29

There is limited knowledge as to whether obesity prevention interventions are able to produce change in the determinants hypothesized to precede change in energy balance-related behaviors in young people. The aim of this study was to evaluate the effect of a multi-component intervention on a wide range of theoretically informed determinants of physical activity (PA) and sedentary behavior (SB). Moderation effects of gender, weight status and parental education level and whether the perceived intervention dose received influenced the effects were also explored. The HEIA study was a 20-month school-based, randomized controlled trial to promote healthy weight development. In total, 1418 11-year-olds participated at baseline and post-intervention assessment. Enjoyment, self-efficacy, perceived social support from parents, teachers and friends related to PA, perceived parental regulation of TV-viewing and computer/game-use and perceived social inclusion at schools were examined by covariance analyses to assess overall effects and moderation by gender, weight status and parental education, mid-way and post-intervention. Covariance analyses were also used to examine the role of intervention dose received on change in the determinants. At mid-way enjoyment (p = .03), perceived social support from teachers (p = .003) and self-efficacy (p = .05) were higher in the intervention group. Weight status moderated the effect on self-efficacy, with a positive effect observed among the normal weight only. At post-intervention results were sustained for social support from teachers (p = .001), while a negative effect was found for self-efficacy (p = .02). Weight status moderated the effect on enjoyment, with reduced enjoyment observed among the overweight. Moderation effects for parental education level were detected for perceived social support from parents and teachers. Finally, positive effects on several determinants were observed among those receiving a high as opposed to a low intervention dose. The intervention affected both psychological and social-environmental determinants. Results indicate that social support from teachers might be a potential mediator of PA change, and that overweight adolescents might be in need of specially targeted interventions to avoid reducing their enjoyment of PA. Further studies should continue to assess how intervention effectiveness is influenced by the participants' self-reported dose of intervention received.

"Extended" antipsychotic dosing in the maintenance treatment of schizophrenia: a double-blind, placebo-controlled trial.

PubMed

Remington, Gary; Seeman, Philip; Feingold, Alan; Mann, Steve; Shammi, Chekkera; Kapur, Shitij

2011-08-01

In the treatment of schizophrenia, all currently available oral antipsychotics are administered at least once daily, with strict adherence strongly encouraged to minimize risk of relapse. Based on a better understanding of the brain kinetics of antipsychotics, we have proposed a variation of this approach, "extended" dosing, which allows for intermittent but regular dosing. We carried out a randomized, double-blind, placebo-controlled trial evaluating 35 individuals with DSM-IV-defined schizophrenia who had been stabilized on antipsychotic therapy. Over a 6-month interval, 18 subjects received their medication as usual (daily), while 17 received their antipsychotic therapy every second day (extended). Outcome measures included clinical scales to assess symptoms (Brief Psychiatric Rating Scale [the primary outcome measure], Calgary Depression Scale), illness severity (Clinical Global Impressions-Severity of Illness scale), and relapse (ie, rehospitalization) rates. Side effects were also assessed, including movement disorders (Barnes Akathisia Scale, Simpson-Angus Scale, Abnormal Involuntary Movement Scale) and weight. The study was conducted from February 2003 to July 2007. Individuals in the extended dosing group were not at greater risk of symptom exacerbation, relapse, or rehospitalization; indeed, more rehospitalizations occurred in those receiving regular dosing. At the same time, though, there was no indication that side effects were significantly reduced in the extended dosing group. These results challenge the long-standing dogma that oral antipsychotics must be administered daily in stabilized patients with schizophrenia. Further studies with larger samples are needed to replicate these findings, as well as to elucidate whether postulated clinical advantages can be established and determined to outweigh potential risks. clinicaltrials.gov Identifier: NCT00431574. © Copyright 2011 Physicians Postgraduate Press, Inc.

Effect of chronic d-fenfluramine administration on rat hypothalamic serotonin levels and release

NASA Technical Reports Server (NTRS)

Schaechter, Judith D.; Wurtman, Richard J.

1988-01-01

D-fenfluramine, an anorectic agent in rats and man, was administered daily at doses 1.25, 2.5, 5, or 10 mg/kg/day for 10 days, and sacrificed 6 days later. Hypothalamic serotonin (5-HT) levels were unchanged in rats receiving 1.25-5 mg/kg/day of d-fenfluramine but reduced by 22 percent (p less than 0.01) at the highest drug dose (10 mg/kg/day); hypothalamic 5-hydroxyindole acetic acid (5-HIAA) levels were reduced by 15 percent (p less than 0.05) or 28 percent (p less than 0.01) in rats receiving 5 or 10 mg/kg/day of the drug, respectively. Hypothalamic slices prepared from rats which were previously treated with any of the drug doses spontaneously released endogenous 5-HT at rates that did not differ from those of vehicle-treated rats. 5-HT released with electrical field-stimulation was unaffected by prior d-fenfluramine treatment at doses of 1.25-5 mg/kg/day, and was reduced by 20 percent (p less than 0.05) from slices prepared from rats which received 10 mg/kg/day. 5-HIAA efflux was also attenuated by the highest drug dose. These data indicate that chronic administration to rats of customary anorectic doses of d-fenfluramine (i.e. 0.06-1.25 mg/kg) fail to cause long-lasting reductions in brain 5-HT release.

Primate paneth cell degeneration following methylmercury hydroxide ingestion.

PubMed Central

Mottet, N. K.; Body, R. L.

1976-01-01

The effects of methylmercury on the intestinal epithelium were studied in 14 adolescent male Macaca mulatta monkeys weighing 3 to 5 kg. They were divided into three groups: two controls received daily applesauce vehicle without methylmercury. Nine chronic low-dose animals received 0.2 to 1.0 mg of methylmercury per day for 80 to 491 days. Three acute high-dose animals received 2.0 mg methylmercury for 17 to 18 days, when they became terminally ill. Light and electron microscopic observations were made on samples of duodenum and ileum following perfusion and immersion fixation in a glutaraldehyde-paraformaldehyde fixative. Numerous uniquely structured inclusions were prominent in the Paneth cells of the chronic low-dose animals and some necrotic Paneth cells were seen, especially in the most chronic and higher dosed animals of the group. Acute high-dose treatment produced some inclusions in the Paneth cells similar to those of the chronic low-dose group, but degenerative and necrotic cells were more frequently seen. These alterations were not seen in other intestinal epithelial cells. Paneth cells are selectively altered. These findings suggest that a function of Paneth cells may be to eliminate metals from the body. Images Figure 11 Figure 12 Figure 13 Figure 1 Figure 2 Figure 3 Figures 4 and 5 Figure 14 Figure 15 Figures 16-18 Figures 6-10 PMID:820204

Method for microbeam radiation therapy

DOEpatents

Slatkin, Daniel N.; Dilmanian, F. Avraham; Spanne, Per O.

1994-01-01

A method of performing radiation therapy on a patient, involving exposing a target, usually a tumor, to a therapeutic dose of high energy electromagnetic radiation, preferably X-ray radiation, in the form of at least two non-overlapping microbeams of radiation, each microbeam having a width of less than about 1 millimeter. Target tissue exposed to the microbeams receives a radiation dose during the exposure that exceeds the maximum dose that such tissue can survive. Non-target tissue between the microbeams receives a dose of radiation below the threshold amount of radiation that can be survived by the tissue, and thereby permits the non-target tissue to regenerate. The microbeams may be directed at the target from one direction, or from more than one direction in which case the microbeams overlap within the target tissue enhancing the lethal effect of the irradiation while sparing the surrounding healthy tissue.

Efficacy of Common Analgesics for Postsurgical Pain in Rats

PubMed Central

Waite, Megan E; Tomkovich, Ashleigh; Quinn, Tammie L; Schumann, Alan P; Dewberry, L Savannah; Totsch, Stacie K; Sorge, Robert E

2015-01-01

Each year, millions of rats undergo surgery for research purposes and receive analgesics to alleviate pain. We sought to evaluate the efficacy of common analgesics in tests of hot-plate nociception and postsurgical pain by using the Rat Grimace Scale. Rats received a single dose of one of several drug–dose combinations and were tested by using the hot-plate test (acute pain) or after laparotomy (with either prophylactic or intraoperative analgesic). The efficacy of analgesics for hot-plate pain was generally not predictive of efficacy for surgical pain. Carprofen and ketoprofen were rarely effective in any of the conditions tested. With the exception of the opioid buprenorphine, several of the drugs we tested required higher-than-recommended doses to alleviate pain. Taken together, our data suggest that current analgesic use frequently is insufficient, and many rats may experience significant postsurgical pain even when analgesics are used in commonly recommended doses. PMID:26224443

A dose-finding, placebo-controlled study on extended-release felodipine once daily in treatment of hypertension.

PubMed

Cambell, L M; Ross, J R; Goves, J R; Lees, C T; McCullagh, A; Barnes, P; Timerick, S J; Richardson, P D

1989-12-01

Hypertensive patients received a beta-blocker plus placebo once daily for 4 weeks. If their diastolic blood pressure (DBP) was then 95-115 mm Hg, they were randomized to receive, in addition to the beta-blocker, placebo (n = 36), felodipine-extended release (ER) 10 mg (n = 36), or felodipine-ER 20 mg (n = 37) in a 4-week double-blind parallel-group trial. All medication was administered once daily and, when BP was measured 24 h after the last dose, felodipine-ER 10 mg reduced DBP by 14 +/- 9 mm Hg (mean +/- SD) from a mean of 103 mm Hg and felodipine-ER 20 mg reduced DBP by 18 +/- 9 mm Gg from 101 mm Hg. The reductions in DBP with both doses of felodipine were greater than reductions with placebo (5 +/- 8 mm Hg, from 102 mm Hg--both p less than 0.001). At the end of the study, 21% of patients receiving placebo had a DBP less than or equal to 90 mm Hg. In contrast, 69% of patients receiving felodipine-ER 10 mg and 82% receiving 20 mg attained this level. More than 90% of patients receiving 10 mg felodipine-ER once daily had a reduction in DBP greater than 5 mm Hg 24 h postdose. Felodipine-ER was well tolerated. Felodipine-ER once daily is an effective antihypertensive drug for patients who require therapy in addition to a beta-blocker; the tolerability in this study was good, and a starting dose greater than 10 mg once daily is not indicated.

Lack of Effect of Vortioxetine on the Pharmacokinetics and Pharmacodynamics of Ethanol, Diazepam, and Lithium.

PubMed

Chen, Grace; Nomikos, George G; Affinito, John; Zhao, Zhen

2016-09-01

Because the multimodal antidepressant vortioxetine is likely to be coadministered with other central nervous system (CNS)-active drugs, potential drug-drug interactions warrant examination. These studies evaluated whether there are pharmacokinetic and/or pharmacodynamic interactions between vortioxetine and ethanol, diazepam, or lithium. This series of phase I studies included healthy men and women (only men in the lithium study) aged 18-45 years. The ethanol study was a randomized, double-blind, two-parallel group, four-period crossover study in which subjects received a single dose of vortioxetine (20 or 40 mg) or placebo with or without ethanol, and the diazepam study was a randomized, double-blind, placebo-controlled, two-sequence, two-period crossover study in which subjects received a single dose of diazepam following multiple doses of vortioxetine 10 mg/day or placebo. These two studies evaluated the effect of coadministration on standardized psychomotor parameters and on selected pharmacokinetic parameters of each drug. The lithium study was a single-blind, single-sequence study evaluating the effect of multiple doses of vortioxetine 10 mg/day on the steady-state pharmacokinetics of lithium. Concomitant administration of vortioxetine and single doses of either ethanol or diazepam had no significant effect on the psychomotor performance of subjects compared with administration of ethanol or diazepam alone. Vortioxetine had no significant effect on the pharmacokinetics of ethanol, diazepam, or lithium, and ethanol had no significant effect on the pharmacokinetics of vortioxetine. Concomitant administration of these agents with vortioxetine was generally well tolerated, with no clinically relevant drug-drug pharmacokinetic or pharmacodynamic interactions identified.

Volumetric tumor burden and its effect on brachial plexus dosimetry in head and neck intensity-modulated radiotherapy

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

Romesser, Paul B.; Qureshi, Muhammad M.; Kovalchuk, Nataliya

2014-07-01

To determine the effect of gross tumor volume of the primary (GTV-P) and nodal (GTV-N) disease on planned radiation dose to the brachial plexus (BP) in head and neck intensity-modulated radiotherapy (IMRT). Overall, 75 patients underwent definitive IMRT to a median total dose of 69.96 Gy in 33 fractions. The right BP and left BP were prospectively contoured as separate organs at risk. The GTV was related to BP dose using the unpaired t-test. Receiver operating characteristics curves were constructed to determine optimized volumetric thresholds of GTV-P and GTV-N corresponding to a maximum BP dose cutoff of > 66 Gy.more » Multivariate analyses were performed to account for factors associated with a higher maximal BP dose. A higher maximum BP dose (> 66 vs ≤ 66 Gy) correlated with a greater mean GTV-P (79.5 vs 30.8 cc; p = 0.001) and ipsilateral GTV-N (60.6 vs 19.8 cc; p = 0.014). When dichotomized by the optimized nodal volume, patients with an ipsilateral GTV-N ≥ 4.9 vs < 4.9 cc had a significant difference in maximum BP dose (64.2 vs 59.4 Gy; p = 0.001). Multivariate analysis confirmed that an ipsilateral GTV-N ≥ 4.9 cc was an independent predictor for the BP to receive a maximal dose of > 66 Gy when adjusted individually for BP volume, GTV-P, the use of a low anterior neck field technique, total planned radiation dose, and tumor category. Although both the primary and the nodal tumor volumes affected the BP maximal dose, the ipsilateral nodal tumor volume (GTV-N ≥ 4.9 cc) was an independent predictor for high maximal BP dose constraints in head and neck IMRT.« less

Effect of feeding isolates of anaerobic fungus Neocallimastix sp. CF 17 on growth rate and fibre digestion in buffalo calves.

PubMed

Paul, Shyam S; Deb, Sitangshu M; Punia, Balbir S; Das, Kalyan S; Singh, Ghansham; Ashar, Manisha N; Kumar, Rajiv

2011-06-01

In this investigation, the effects of feeding encapsulated cells (rhizomycelia and zoospores) of a fibrolytic isolate from an anaerobic fungus (Neocallimastix sp. CF 17) on nutrient digestion, ruminal fermentation, microbial populations, enzyme profile and growth performance were evaluated in buffaloes. In three in vitro studies, the true digestibility of wheat straw was increased after addition of CF 17 to buffalo rumen fluid (p < 0.05). In Exp. 1, three groups of six buffaloes each (initial BW [body weight] 148 +/- 12.0 kg) were allotted to three dosing regimes: Group 1 received 200 ml of liquid culture of Neocallimastix sp. CF 17 (about 10(6) TFU [thallus-forming units]/ml); Group 2 received an encapsulated culture of the same fungi prepared from 200 ml liquid culture; Group 3: received 200 ml of autoclaved culture (Control). The supplementations were given weekly for four weeks (on days 1,7, 14 and 21). During the dosing period, the average daily gain of Group 2 was higher than in the Control group (444 g/d compared with 264 g/d; p < 0.05). Furthermore, the digestibility of organic matter increased in Group 1 and 2 compared with the Control (64.8, 64.0 and 60.4% respectively; p < 0.05), resulting in an increase in the total digestible nutrient (TDN) percent of ration (p < 0.05). But these effects disappeared post-dosing. There were also an increase in concentration of volatile fatty acids, trichloroacetic acid precipitable N and number of fibrolytic microbes in the rumen during the dosing period (p < 0.05), but these effects declined post-dosing. Results of Exp 2., where the encapsulated culture was applied at intervals of 4 d or 8 d for 120 d, showed that a shorter dosing frequency did not improve growth performance or feed intake. However, independent of the dosing frequency the growth rate of both groups fed the encapsulated culture were about 20% higher than in the Control group (p < 0.05). The present study showed that encapsulated fungi have a high potential to be used as feed additive at the farmers' level and that weekly dosing can increase growth performance of wheat straw based diets.

Reactogenicity of tetanus, diphtheria, 5-component acellular pertussis vaccine administered as a sixth consecutive acellular pertussis vaccine dose to adolescents.

PubMed

Liese, Johannes G; Rieber, Nikolaus; Malzer, Thomas; Ocak, Marion; Johnson, David R; Decker, Michael D

2010-12-01

Safety of a sixth consecutive dose of acellular pertussis vaccine in adolescents was assessed in a 2-armed, randomized study. Adolescents who had received 5 doses of acellular pertussis vaccine combined with diphtheria and tetanus toxoids (6-dose group) received 1 dose of reduced 5-component acellular pertussis vaccine combined with tetanus toxoid and reduced diphtheria toxoid (Tdap). Adolescents who had received a primary series of 3 doses of whole-cell pertussis and 1 acellular or whole-cell pertussis booster received 1 dose of Tdap vaccine (5-dose group). Of 214 participants, 176 (82%) reported an injection-site reaction with pain (80%), erythema (22%), and swelling (19%) most frequently reported. A systemic reaction was reported by 169 of 214 (79%) with myalgia (66%), headache (42%), malaise (39%), and fever (9%) most frequently reported. The overall rate of solicited reactions was lower in the 6-dose group than in the 5-dose group (for injection-site reactions: 76.1% vs. 89.7%; for systemic reactions 72.6% vs. 86.6%). Significant differences were observed for injection-site pain, erythema, and for grade 1 or grade 2 increases in arm circumference. Fever, myalgia, and headache were reported at a significantly lower rate in the 6-dose group. Swelling >10 cm was observed in 5 patients (2%), 4 in the 5-dose group. Tdap vaccine was safe when given to adolescents who had received 5 prior doses of acellular pertussis vaccine.

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.

Measures for curtailment of iatrogenic exposure. Guide to correct x-ray examinations (in Japanese)

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

Misonoo, K.

1973-08-01

Of the coposure dose for humans from various radiation sources, introgenic exposure amounts to 1/2 to twice the natural radiation source. Although the mechanism of induction of malignant tumor by radiation is not clanified, it is evident that it is induced after receiving a dose above 100 rads. However, the presence of a threshold, under which it does not develop, is unknown. Tabulated were ICRP's calculations on the degree of risk of injury and the estimated values of genetic injury due to 1 rad. In order to estimate the harmful effect of exposure in x-ray diagnosis, the dose in themore » critical tissue of the human body and the types and the frequency of radiation examinations are important. The judgment of genetic injury is expressed by the genetically significant dose, which is calculated from the dose in the genital gland received by individuals. The impcrtant criterion for the judgment of physical injury is the mean annual dose per person in the marrow (mean dose in the red marrow). The dose in the genital organ is important as the dose related to the evaluation of the degree of genetic risk. The characteristics of iatrogenic exposure are partial and acute exposure and a high dose rate. Tabulated individually were the frequency of x-ray examinations, the mean dose in the genital organ according urce. The radiation dose during x-ray pelvimetry to 51 patients was estimated, and the cytogenetic response of peripheral lymphocytes was determined in 25 of their newborn babies. The calculations resulted in an average midline fetal dose of 1,035 and 1,860 mrads for the patients receiving 2 projections and more than 2 projections, respectively. There was no evidence of radioinduced chromosomal darnage in the newborn infants following x-ray exposure in utero. (auth)« less

Fourth-ventricle leptin infusions dose-dependently activate hypothalamic signal transducer and activator of transcription 3.

PubMed

Harris, Ruth B S; Desai, Bhavna N

2016-12-01

Previous studies have shown that very low-dose infusions of leptin into the third or the fourth ventricle alone have little effect on energy balance, but simultaneous low-dose infusions cause rapid weight loss and increased phosphorylation of STAT3 (p-STAT3) in hypothalamic sites that express leptin receptors. Other studies show that injecting high doses of leptin into the fourth ventricle inhibits food intake and weight gain. Therefore, we tested whether fourth-ventricle leptin infusions that cause weight loss are associated with increased leptin signaling in the hypothalamus. In a dose response study 14-day infusions of increasing doses of leptin showed significant hypophagia, weight loss, and increased hypothalamic p-STAT3 in rats receiving at least 0.9 μg leptin/day. In a second study 0.6 μg leptin/day transiently inhibited food intake and reduced carcass fat, but had no significant effect on energy expenditure. In a final study, we identified the localization of STAT3 activation in the hypothalamus of rats receiving 0, 0.3, or 1.2 μg leptin/day. The high dose of leptin, which caused weight loss in the first experiment, increased p-STAT3 in the ventromedial, dorsomedial, and arcuate nuclei of the hypothalamus. The low dose that increased brown fat UCP1 but did not affect body composition in the first experiment had little effect on hypothalamic p-STAT3. We propose that hindbrain leptin increases the precision of control of energy balance by lowering the threshold for leptin signaling in the forebrain. Further studies are needed to directly test this hypothesis. Copyright © 2016 the American Physiological Society.

Monte Carlo simulations of the secondary neutron ambient and effective dose equivalent rates from surface to suborbital altitudes and low Earth orbit

NASA Astrophysics Data System (ADS)

El-Jaby, Samy; Richardson, Richard B.

2015-07-01

Occupational exposures from ionizing radiation are currently regulated for airline travel (<20 km) and for missions to low-Earth orbit (∼300-400 km). Aircrew typically receive between 1 and 6 mSv of occupational dose annually, while aboard the International Space Station, the area radiation dose equivalent measured over just 168 days was 106 mSv at solar minimum conditions. It is anticipated that space tourism vehicles will reach suborbital altitudes of approximately 100 km and, therefore, the annual occupational dose to flight crew during repeated transits is expected to fall somewhere between those observed for aircrew and astronauts. Unfortunately, measurements of the radiation environment at the high altitudes reached by suborbital vehicles are sparse, and modelling efforts have been similarly limited. In this paper, preliminary MCNPX radiation transport code simulations are developed of the secondary neutron flux profile in air from surface altitudes up to low Earth orbit at solar minimum conditions and excluding the effects of spacecraft shielding. These secondary neutrons are produced by galactic cosmic radiation interacting with Earth's atmosphere and are among the sources of radiation that can pose a health risk. Associated estimates of the operational neutron ambient dose equivalent, used for radiation protection purposes, and the neutron effective dose equivalent that is typically used for estimates of stochastic health risks, are provided in air. Simulations show that the neutron radiation dose rates received at suborbital altitudes are comparable to those experienced by aircrew flying at 7 to 14 km. We also show that the total neutron dose rate tails off beyond the Pfotzer maximum on ascension from surface up to low Earth orbit.

Monte Carlo simulations of the secondary neutron ambient and effective dose equivalent rates from surface to suborbital altitudes and low Earth orbit.

PubMed

El-Jaby, Samy; Richardson, Richard B

2015-07-01

Occupational exposures from ionizing radiation are currently regulated for airline travel (<20 km) and for missions to low-Earth orbit (∼300-400 km). Aircrew typically receive between 1 and 6 mSv of occupational dose annually, while aboard the International Space Station, the area radiation dose equivalent measured over just 168 days was 106 mSv at solar minimum conditions. It is anticipated that space tourism vehicles will reach suborbital altitudes of approximately 100 km and, therefore, the annual occupational dose to flight crew during repeated transits is expected to fall somewhere between those observed for aircrew and astronauts. Unfortunately, measurements of the radiation environment at the high altitudes reached by suborbital vehicles are sparse, and modelling efforts have been similarly limited. In this paper, preliminary MCNPX radiation transport code simulations are developed of the secondary neutron flux profile in air from surface altitudes up to low Earth orbit at solar minimum conditions and excluding the effects of spacecraft shielding. These secondary neutrons are produced by galactic cosmic radiation interacting with Earth's atmosphere and are among the sources of radiation that can pose a health risk. Associated estimates of the operational neutron ambient dose equivalent, used for radiation protection purposes, and the neutron effective dose equivalent that is typically used for estimates of stochastic health risks, are provided in air. Simulations show that the neutron radiation dose rates received at suborbital altitudes are comparable to those experienced by aircrew flying at 7 to 14 km. We also show that the total neutron dose rate tails off beyond the Pfotzer maximum on ascension from surface up to low Earth orbit. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

Intravenous paracetamol with a lower dose is also effective for the treatment of patent ductus arteriosus in pre-term infants.

PubMed

Tekgündüz, Kadir Şerafettin; Ceviz, Naci; Caner, İbrahim; Olgun, Haşim; Demirelli, Yaşar; Yolcu, Canan; Şahin, İrfan Oğuz; Kara, Mustafa

2015-08-01

Haemodynamically significant patent ductus arteriosus is a significant cause of morbidity and mortality in pre-term infants. This retrospective study was conducted to investigate the usefulness of lower-dose paracetamol for the treatment of patent ductus arteriosus in pre-term infants. A total of 13 pre-term infants who received intravenous paracetamol because of contrindications or side effects to oral ibuprofen were retrospectively enrolled. In the first patient, the dose regimen was 15 mg/kg/dose, every 6 hours. As the patient developed significant elevation in transaminase levels, the dose was decreased to 10 mg/kg/dose, every 8 hours in the following 12 patients. Echocardiographic examination was conducted daily. In case of closure, it was repeated after 2 days and when needed thereafter in terms of reopening. A total of 13 patients received intravenous paracetamol. Median gestational age was 29 weeks ranging from 24 to 31 weeks and birth weight was 950 g ranging from 470 to 1390 g. The median postnatal age at the first intravenous paracetamol dose was 3 days ranging from 2 to 9 days. In 10 of the 13 patients (76.9%), patent ductus arteriosus was closed at the median 2nd day of intravenous paracetamol ranging from 1 to 4 days. When the patient who developed hepatotoxicity was eliminated, the closure rate was found to be 83.3% (10/12). Intravenous paracetamol may be a useful treatment option for the treatment of patent ductus arteriosus in pre-term infants with contrindication to ibuprofen. In our experience, lower-dose paracetamol is effective in closing the patent ductus arteriosus in 83.3% of the cases.

Effects of topical combinations of clonidine and pentoxifylline on capsaicin-induced allodynia and postcapsaicin tourniquet-induced pain in healthy volunteers: a double-blind, randomized, controlled study.

PubMed

Ragavendran, J Vaigunda; Laferrière, André; Bennett, Gary J; Ware, Mark A; Gandhi, Wiebke; Bley, Keith; Schweinhardt, Petra; Coderre, Terence J

2016-10-01

This double-blind randomized controlled study was designed to evaluate the analgesic effects of topical treatments with clonidine (CLON) and pentoxifylline (PTX) tested alone or as low- and high-dose combinations in a human experimental model of pain. Of 69 healthy subjects aged 18 to 60 years, 23 each were randomly allocated to low-dose (0.04% + 2%) and high-dose (0.1% + 5%) CLON + PTX groups. Both of these groups also received their corresponding placebos in one of 2 treatment periods separated by at least 48 hours. Twenty-three additional subjects received either CLON (0.1%) or PTX (5%) as single drug treatments, in each of 2 treatment periods. Assessment of analgesic efficacy was based on allodynic effects of previous intraepidermal capsaicin injection, as well as postcapsaicin tourniquet-induced pain 50 minutes following capsaicin injection. Visual Analogue Scale (VAS) ratings of pain intensity and the area of dynamic mechanical allodynia were the primary outcome measures, whereas area of punctate mechanical allodynia (PMA) served as a secondary outcome measure. Topical treatments with high- or low-dose combinations significantly reduced VAS ratings compared with corresponding placebo treatments throughout the period of postcapsaicin tourniquet-induced pain. Importantly, the high-dose combination produced lower VAS ratings than CLON alone, which were lower than PTX alone. Results also revealed significant inhibition of postcapsaicin dynamic mechanical allodynia and PMA for the high-dose combination compared with placebo, and of PMA for CLON compared with the low-dose combination. Hence, the present data are supportive of further clinical investigation of the high-dose topical combination of CLON + PTX in complex regional pain syndrome and neuropathic pain patients, for which our preclinical data predict efficacy.

A clinical trial of injectable testosterone undecanoate as a potential male contraceptive in normal Chinese men.

PubMed

Zhang, G Y; Gu, Y Q; Wang, X H; Cui, Y G; Bremner, W J

1999-10-01

This is a pilot dose-finding study of spermatogenic suppression using testosterone undecanoate (TU) injections alone in normal Chinese men. Thirty-two healthy men were recruited. Volunteers underwent pretreatment evaluation, then a treatment period in which group I (n = 13) received 500 mg TU, group II (n = 12) received 1000 mg TU, and group III (n = 7) received placebo, respectively, at monthly intervals during the treatment period (or until azoospermia was achieved). Thereafter, they underwent a recovery period until all parameters returned to pretreatment levels. Eleven of 12 volunteers in the 500-mg TU group, and all volunteers in the 1000-mg TU group became azoospermic. Faster suppression of spermatogenesis was achieved in the 1000-mg TU group. Serum testosterone increased significantly in the higher dose group at weeks 8 and 12, but remained within the normal range. Mean serum LH and FSH were profoundly suppressed by both doses to undetectable levels at week 16. TU injections did not cause a significant change in high density lipoprotein cholesterol levels. No serious side-effects were found. We conclude that both dosages of TU can effectively, safely, and reversibly suppress spermatogenesis in normal Chinese men.

Irradiation of members of the general public from radioactive caesium following the Chernobyl reactor accident: Field studies in a highly contaminated area in the Bryansk region, Russia

NASA Astrophysics Data System (ADS)

Thornberg, Charlotte

From 1990 to 1998, estimations of the effective dose due to irradiation from 137Cs and 134Cs were carried out for inhabitants in rural villages in the Bryansk region, Russia. The villages, situated about 180 km from the Chernobyl power plant received deposition of 137Cs in the range 0.9-2.7 MBq m-2 due to the accident in 1986. The body burden of 137,134Cs was estimated from measurements of the urinary concentration of caesium radionuclides, together with in vivo measurements using a portable detector. The external effective dose was estimated from measurements with thermoluminescent (TL)-dosemeters worn by the participants during one month each year. In a case study, the changes in biokinetics of 137Cs during pregnancy was investigated in a woman with an unintended intake of 137Cs via mushrooms grown in the area. During pregnancy the biological half-time of caesium was 54% of that before pregnancy. The ratio of the 137Cs concentration in breast milk (Bq L-1) to that in the mother's body (Bq kg-1) was 15% one month after the child was born. The body burden of 137Cs in the Russian individuals calculated from urine samples showed a good agreement with the body burden estimated from in vivo measurements in the same individuals. Normalisation of the caesium concentration in the urine samples by the use of potassium or creatinine excretion introduced systematic differences and a larger spread in the calculated values of the 137Cs body burden as compared with calculations without normalisation. The yearly effective dose to inhabitants in the Russian villages varied between 1.2 and 2.5 mSv as a mean for all villages between 1991 and 1998 and the internal effective dose was 30-50% of the total effective dose. The external effective dose decreased on average 15% per year, while the internal effective dose varied, depending to a great extent on the availability of mushrooms. The cumulated effective dose for a 70-year period after the accident was calculated to be 100 mSv assuming that the effective dose will decrease by only the physical decay of 137Cs (2% per year) after 1998. Individuals may receive considerably higher effective doses, up to 0.5 Sv during a life-time considering the large spread in dose values among individuals.

Low dose creatine supplementation enhances sprint phase of 400 meters swimming performance.

PubMed

Anomasiri, Wilai; Sanguanrungsirikul, Sompol; Saichandee, Pisut

2004-09-01

This study demonstrated the effect of low dose creatine supplement (10 g. per day) on the sprinting time in the last 50 meters of 400 meters swimming competition, as well as the effect on exertion. Nineteen swimmers in the experimental group received creatine monohydrate 5 g with orange solution 15 g, twice per day for 7 days and nineteen swimmers in the control group received the same quantity of orange solution. The results showed that the swimmers who received creatine supplement lessened the sprinting time in the last 50 meters of 400 meters swimming competition than the control group. (p<0.05). The results of Wingate test (anaerobic power, anaerobic capacity and fatigue index) compared between pre and post supplementation. There was significant difference at p<0.05 in the control group from training effect whereas there was significant difference at p<0.000 from training effect and creatine supplement in the experiment group. Therefore, the creatine supplement in amateur swimmers in the present study enhanced the physical performance up to the maximum capacity.

Folinic acid improves verbal communication in children with autism and language impairment: a randomized double-blind placebo-controlled trial.

PubMed

Frye, R E; Slattery, J; Delhey, L; Furgerson, B; Strickland, T; Tippett, M; Sailey, A; Wynne, R; Rose, S; Melnyk, S; Jill James, S; Sequeira, J M; Quadros, E V

2018-02-01

We sought to determine whether high-dose folinic acid improves verbal communication in children with non-syndromic autism spectrum disorder (ASD) and language impairment in a double-blind placebo control setting. Forty-eight children (mean age 7 years 4  months; 82% male) with ASD and language impairment were randomized to receive 12 weeks of high-dose folinic acid (2 mg kg -1 per day, maximum 50 mg per day; n=23) or placebo (n=25). Children were subtyped by glutathione and folate receptor-α autoantibody (FRAA) status. Improvement in verbal communication, as measured by a ability-appropriate standardized instrument, was significantly greater in participants receiving folinic acid as compared with those receiving placebo, resulting in an effect of 5.7 (1.0,10.4) standardized points with a medium-to-large effect size (Cohen's d=0.70). FRAA status was predictive of response to treatment. For FRAA-positive participants, improvement in verbal communication was significantly greater in those receiving folinic acid as compared with those receiving placebo, resulting in an effect of 7.3 (1.4,13.2) standardized points with a large effect size (Cohen's d=0.91), indicating that folinic acid treatment may be more efficacious in children with ASD who are FRAA positive. Improvements in subscales of the Vineland Adaptive Behavior Scale, the Aberrant Behavior Checklist, the Autism Symptom Questionnaire and the Behavioral Assessment System for Children were significantly greater in the folinic acid group as compared with the placebo group. There was no significant difference in adverse effects between treatment groups. Thus, in this small trial of children with non-syndromic ASD and language impairment, treatment with high-dose folinic acid for 12 weeks resulted in improvement in verbal communication as compared with placebo, particularly in those participants who were positive for FRAAs.

Non-specific effects of standard measles vaccine at 4.5 and 9 months of age on childhood mortality: randomised controlled trial.

PubMed

Aaby, Peter; Martins, Cesário L; Garly, May-Lill; Balé, Carlito; Andersen, Andreas; Rodrigues, Amabelia; Ravn, Henrik; Lisse, Ida M; Benn, Christine S; Whittle, Hilton C

2010-11-30

To examine in a randomised trial whether a 25% difference in mortality exists between 4.5 months and 3 years of age for children given two standard doses of Edmonston-Zagreb measles vaccines at 4.5 and 9 months of age compared with those given one dose of measles vaccine at 9 months of age (current policy). Randomised controlled trial. The Bandim Health Project, Guinea-Bissau, which maintains a health and demographic surveillance system in an urban area. 6648 children aged 4.5 months of age who had received three doses of diphtheria-tetanus-pertussis vaccine at least four weeks before enrolment. A large proportion of the children (80%) had previously taken part in randomised trials of neonatal vitamin A supplementation. Children were randomised to receive Edmonston-Zagreb measles vaccine at 4.5 and 9 months of age (group A), no vaccine at 4.5 months and Edmonston-Zagreb measles vaccine at 9 months of age (group B), or no vaccine at 4.5 months and Schwarz measles vaccine at 9 months of age (group C). Main outcome measure Mortality rate ratio between 4.5 and 36 months of age for group A compared with groups B and C. Secondary outcomes tested the hypothesis that the beneficial effect was stronger in the 4.5 to 9 months age group, in girls, and in the dry season, but the study was not powered to test whether effects differed significantly between subgroups. In the intention to treat analysis of mortality between 4.5 and 36 months of age the mortality rate ratio of children who received two doses of Edmonston-Zagreb vaccine at 4.5 and 9 months of age compared with those who received a single dose of Edmonston-Zagreb vaccine or Schwarz vaccine at 9 months of age was 0.78 (95% confidence interval 0.59 to 1.05). In the analyses of secondary outcomes, the intention to treat mortality rate ratio was 0.67 (0.38 to 1.19) between 4.5 and 9 months and 0.83 (0.83 to 1.16) between 9 and 36 months of age. The effect on mortality between 4.5 and 36 months of age was significant for girls (intention to treat mortality rate ratio 0.64 (0.42 to 0.98)), although this was not significantly different from the effect in boys (0.95 (0.64 to 1.42)) (interaction test, P=0.18). The effect did not differ between the dry season and the rainy season. As neonatal vitamin A supplementation is not WHO policy, the analyses were done separately for the 3402 children who did not receive neonatal vitamin A. In these children, the two dose Edmonston-Zagreb measles vaccine schedule was associated with a significantly lower mortality between 4.5 and 36 months of age (intention to treat mortality rate ratio 0.59 (0.39 to 0.89)). The effect was again significant for girls but not statistically significant from the effect in boys. When measles cases were censored, the intention to treat mortality rate ratio was 0.65 (0.43 to 0.99). Although the overall effect did not reach statistical significance, the results may indicate that a two dose schedule with Edmonston-Zagreb measles vaccine given at 4.5 and 9 months of age has beneficial non-specific effects on children's survival, particularly for girls and for children who have not received neonatal vitamin A. This should be tested in future studies in different locations. Clinical trials NCT00168558.

Relationship between dose of antithyroid drugs and adverse events in pediatric patients with Graves’ disease

PubMed Central

Yasuda, Kie; Miyoshi, Yoko; Tachibana, Makiko; Namba, Noriyuki; Miki, Kazunori; Nakata, Yukiko; Takano, Toru; Ozono, Keiichi

2017-01-01

Abstract. Graves’ disease (GD) accounts for a large proportion of pediatric hyperthyroidism, and the first-line treatment is antithyroid drug (ATD) therapy. Methimazole (MMI) is effective in most patients but is associated with significant adverse events (AEs). We reviewed the medical records of GD patients (n = 56) with onset age of <15 yr and investigated the relationship between MMI dose and AEs. The study population comprised 11 male and 45 female patients and the median age at diagnosis was 11 yr. All patients were initially treated with ATDs. Among the 52 patients initially treated with MMI, 20 received a low dose, and 32 received a high dose of MMI (< 0.7 vs ≥ 0.7 mg/kg/day, respectively). AEs occurred in 20% of the patients in the low-dose MMI group, and in 50% patients in the high-dose MMI group (p = 0.031). A greater variety of AEs was observed in the high-dose group. Neutropenia and rash were observed in both groups. With treatment transition to low-dose MMI according to the Japanese Society for Pediatric Endocrinology guidelines, we expect a decrease in the incidence of AEs in future. However, we should be careful as neutropenia and rash can occur independently of the MMI dose. PMID:28203042

Relationship between dose of antithyroid drugs and adverse events in pediatric patients with Graves' disease.

PubMed

Yasuda, Kie; Miyoshi, Yoko; Tachibana, Makiko; Namba, Noriyuki; Miki, Kazunori; Nakata, Yukiko; Takano, Toru; Ozono, Keiichi

2017-01-01

Graves' disease (GD) accounts for a large proportion of pediatric hyperthyroidism, and the first-line treatment is antithyroid drug (ATD) therapy. Methimazole (MMI) is effective in most patients but is associated with significant adverse events (AEs). We reviewed the medical records of GD patients (n = 56) with onset age of <15 yr and investigated the relationship between MMI dose and AEs. The study population comprised 11 male and 45 female patients and the median age at diagnosis was 11 yr. All patients were initially treated with ATDs. Among the 52 patients initially treated with MMI, 20 received a low dose, and 32 received a high dose of MMI (< 0.7 vs ≥ 0.7 mg/kg/day, respectively). AEs occurred in 20% of the patients in the low-dose MMI group, and in 50% patients in the high-dose MMI group (p = 0.031). A greater variety of AEs was observed in the high-dose group. Neutropenia and rash were observed in both groups. With treatment transition to low-dose MMI according to the Japanese Society for Pediatric Endocrinology guidelines, we expect a decrease in the incidence of AEs in future. However, we should be careful as neutropenia and rash can occur independently of the MMI dose.

Endoscopic Injection of Low Dose Triamcinolone: a Simple, Minimally Invasive and Effective Therapy for Interstitial Cystitis with Hunner Lesions.

PubMed

Funaro, Michael G; King, Alexandra N; Stern, Joel N H; Moldwin, Robert M; Bahlani, Sonia

2018-05-18

To investigate the efficacy of low dose triamcinolone injection for effectiveness and durability in interstitial cystitis/bladder pain syndrome (IC/BPS) patients with Hunner Lesions (HL). Clinical data from patients with HL who underwent endoscopic submucosal injection of triamcinolone were reviewed: Demographics, pre/post operative pain and nocturia scores, and long-term clinical outcomes were assessed. Duration of response was estimated by time to repeat procedure. Kaplan-Meier estimator was used to evaluate time to repeat procedure. 36 patients who received injections of triamcinolone between 2011 and 2015 were included. Median age±SD of patients was 61.5±12.0 years 23; 28 (77.8%) of patients were female and 8 (22.2%) were male. 26 patients (72.2%) received only 1 set of injections, 8 (22.2%) received 2 sets of injections, and 2 (5.56%) received 3 or more sets of injections. Average time between injections in those receiving more than one set of injections was 344.9 days (median: 313.5, range: 77-714). Pre-procedural pain scores were 8.3±1.2 (mean±SD) on Likert pain scale (0-10), and mean post-procedural pain scores at approximately one month were 3.8±2.2 p<0.001. Mean pre-procedural nocturia bother scores were 7.5±2.0 and mean post-procedural nocturia bother scores were 5.1±2.5) p<0.001. Endoscopic submucosal injection of low dose triamcinolone in IC/BPS patients with HL is an effective and durable adjunct to existing treatment modalities. This approach is associated with low morbidity and can be performed on an outpatient basis. Copyright © 2018. Published by Elsevier Inc.

Immediate effects of 33 to 180 rad/min (60)Co exposure on performance and blood pressure in monkeys. Topical report

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

Bruner, A.

1976-09-01

Four groups of monkeys received 1000 rads (60)Co at 33, 50, 75, or 180 rad/min wholebody irradiation while performing a delayed matching-to-sample task. Systematic dose rate effects were observed on performance and blood pressure within the initial 20 min postirradiation. The incidence and severity of performance decrement (PD) increased with higher dose rate. The appearance of postirradiation hypotension was systematically delayed and its rate of fall prolonged as dose rate was lower. The hypotension likewise appeared less deep with lower dose rate exposure. Based on the calculated cumulative dose absorbed at the time of symptom appearance two coactive thresholds weremore » proposed to exist: a total dose threshold of approximately 300 rads (midbody measurement), and a dose rate threshold of about 25 rad/min.« less

Fetal radiation monitoring and dose minimization during intensity modulated radiation therapy for glioblastoma in pregnancy.

PubMed

Horowitz, David P; Wang, Tony J C; Wuu, Cheng-Shie; Feng, Wenzheng; Drassinower, Daphnie; Lasala, Anita; Pieniazek, Radoslaw; Cheng, Simon; Connolly, Eileen P; Lassman, Andrew B

2014-11-01

We examined the fetal dose from irradiation of glioblastoma during pregnancy using intensity modulated radiation therapy (IMRT), and describe fetal dose minimization using mobile shielding devices. A case report is described of a pregnant woman with glioblastoma who was treated during the third trimester of gestation with 60 Gy of radiation delivered via a 6 MV photon IMRT plan. Fetal dose without shielding was estimated using an anthropomorphic phantom with ion chamber and diode measurements. Clinical fetal dose with shielding was determined with optically stimulated luminescent dosimeters and ion chamber. Clinical target volume (CTV) and planning target volume (PTV) coverage was 100 and 98 % receiving 95 % of the prescription dose, respectively. Normal tissue tolerances were kept below quantitative analysis of normal tissue effects in the clinic (QUANTEC) recommendations. Without shielding, anthropomorphic phantom measurements showed a cumulative fetal dose of 0.024 Gy. In vivo measurements with shielding in place demonstrated a cumulative fetal dose of 0.016 Gy. The fetal dose estimated without shielding was 0.04 % and with shielding was 0.026 % of the target dose. In vivo estimation of dose equivalent received by the fetus was 24.21 mSv. Using modern techniques, brain irradiation can be delivered to pregnant patients in the third trimester with very low measured doses to the fetus, without compromising target coverage or normal tissue dose constraints. Fetal dose can further be reduced with the use of shielding devices, in keeping with the principle of as low as reasonably achievable.

The local and systemic side-effects of venom and inhaled-allergen subcutaneous immunotherapy.

PubMed

Adamic, Katja; Zidarn, Mihaela; Bajrovic, Nissera; Erzen, Renato; Kopac, Peter; Music, Ema

2009-01-01

Although immunotherapy is effective in allergic rhinitis, conjunctivitis, asthma and stinging insect hypersensitivity, it carries a risk of anaphylactic reactions. In a 4-year retrospective survey, we investigated 1257 adult patients who had received venom or inhaled-allergen subcutaneous immunotherapy. The dose-increase phase was performed as the 2-day rush protocol for venom immunotherapy and the 6-week protocol for inhaled-allergen immunotherapy. A total of 904 patients received venom immunotherapy and 353 patients inhaled-allergen immunotherapy. The prevalence of systemic reactions was 13.6%. The frequency of systemic reactions was higher during the maintenance phase than in the dose-increase phase (9.6% vs. 5.9%) and was highest in both phases of treatment with honeybee venom (P < 0.001). The majority of systemic reactions were mild. Five (0.4%) patients had reaction with a fall of blood pressure and were treated with adrenaline. There was no fatal outcome. The systemic side-effects during the dose-increase phase of venom immunotherapy occurred at a median dose of 46 microg (range 2-100 microg). Large local reactions occurred in 13.9% of patients without any significant difference between the allergens. We have shown that systemic reactions are not rare even during maintenance phase in patients with a well tolerated dose-increase phase of treatment. The most prominent risk factor for systemic reactions was immunotherapy with honeybee extract.

Modulating Effects of Spirulina platensis against Tilmicosin-Induced Cardiotoxicity in Mice.

PubMed

Ibrahim, Abdelaziz E; Abdel-Daim, Mohamed Mohamed

2015-01-01

Tilmicosin (TIL) is a long-acting macrolide antibiotic used to treat cattle for pathogens that cause bovine respiratory disease. However, overdoses of this medication have been reported to induce cardiac damage. Our experimental objective was to evaluate the protective effects of Spirulina platensis (SP) administration against TIL-induced cardiotoxicity in mice. Our experimental in vivo animal study used 40 male albino mice that were divided into five groups of eight mice per group. The first group served as a control group and was injected with saline. The second group received SP at dose of 1000 mg/kg body weight for five days. The third group received a single dose of TIL (75 mg/kg, subcutaneously). Groups 4 and 5 were given SP at doses of 500 and 1000 mg/kg body weight for five consecutive days just before administration of TIL at the same dose and regimen used for group 3. TIL treated animals showed a significant increase in serum cardiac injury biomarkers as well as cardiac lipid peroxidation, however they had evidence of an inhibition in antioxidant biomarkers. SP normalized elevated serum levels of lactate dehydrogenase (LDH), creatine kinase (CK), and CK-MB. Furthermore, SP reduced TIL-induced lipid peroxidation and oxidative stress in a dose-dependent manner. Administration of SP minimized the toxic effects of TIL by its free radicalscavenging and potent antioxidant activity.

Modulating Effects of Spirulina platensis against Tilmicosin-Induced Cardiotoxicity in Mice

PubMed Central

Ibrahim, Abdelaziz E.; Abdel-Daim, Mohamed Mohamed

2015-01-01

Objective Tilmicosin (TIL) is a long-acting macrolide antibiotic used to treat cattle for pathogens that cause bovine respiratory disease. However, overdoses of this medication have been reported to induce cardiac damage. Our experimental objective was to evaluate the protective effects of Spirulina platensis (SP) administration against TIL-induced cardiotoxicity in mice. Materials and Methods Our experimental in vivo animal study used 40 male albino mice that were divided into five groups of eight mice per group. The first group served as a control group and was injected with saline. The second group received SP at dose of 1000 mg/kg body weight for five days. The third group received a single dose of TIL (75 mg/kg, subcutaneously). Groups 4 and 5 were given SP at doses of 500 and 1000 mg/kg body weight for five consecutive days just before administration of TIL at the same dose and regimen used for group 3. Results TIL treated animals showed a significant increase in serum cardiac injury biomarkers as well as cardiac lipid peroxidation, however they had evidence of an inhibition in antioxidant biomarkers. SP normalized elevated serum levels of lactate dehydrogenase (LDH), creatine kinase (CK), and CK-MB. Furthermore, SP reduced TIL-induced lipid peroxidation and oxidative stress in a dose-dependent manner. Conclusion Administration of SP minimized the toxic effects of TIL by its free radicalscavenging and potent antioxidant activity. PMID:25870843

First-in-man-proof of concept study with molidustat: a novel selective oral HIF-prolyl hydroxylase inhibitor for the treatment of renal anaemia.

PubMed

Böttcher, M; Lentini, S; Arens, E R; Kaiser, A; van der Mey, D; Thuss, U; Kubitza, D; Wensing, G

2018-07-01

Insufficient erythropoietin (EPO) synthesis is a relevant cause of renal anaemia in patients with chronic kidney disease. Molidustat, a selective hypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibitor, increases endogenous EPO levels dose dependently in preclinical models. We examined the pharmacokinetics, safety, tolerability and effect on EPO levels of single oral doses of molidustat in healthy male volunteers. This was a single-centre, randomized, single-blind, placebo-controlled, group-comparison, dose-escalation study. Molidustat was administered at doses of 5, 12.5, 25, 37.5 or 50 mg as a polyethylene glycol-based solution. In total, 45 volunteers received molidustat and 14 received placebo. Molidustat was absorbed rapidly, and the mean maximum plasma concentration and area under the concentration-time curve increased dose dependently. The mean terminal half-life was 4.64-10.40 h. A significant increase in endogenous EPO was observed following single oral doses of molidustat of 12.5 mg and above. Geometric mean peak EPO levels were 14.8 IU l -1 (90% confidence interval 13.0, 16.9) for volunteers who received placebo and 39.8 IU l -1 (90% confidence interval: 29.4, 53.8) for those who received molidustat 50 mg. The time course of EPO levels resembled the normal diurnal variation in EPO. Maximum EPO levels were observed approximately 12 h postdose and returned to baseline after approximately 24-48 h. All doses of molidustat were well tolerated and there were no significant changes in vital signs or laboratory safety parameters. Oral administration of molidustat to healthy volunteers elicited a dose-dependent increase in endogenous EPO. These results support the ongoing development of molidustat as a potential new treatment for patients with renal anaemia. © 2018 The British Pharmacological Society.

Pediatric 131I-MIBG Therapy for Neuroblastoma: Whole-Body 131I-MIBG Clearance, Radiation Doses to Patients, Family Caregivers, Medical Staff, and Radiation Safety Measures.

PubMed

Willegaignon, José; Crema, Karin Paola; Oliveira, Nathaliê Canhameiro; Pelissoni, Rogério Alexandre; Coura-Filho, George Barberio; Sapienza, Marcelo Tatit; Buchpiguel, Carlos Alberto

2018-06-19

I-metaiodobenzylguanidine (I-MIBG) has been used in the diagnosis and therapy of neuroblastoma in adult and pediatric patients for many years. In this study, we evaluated whole-body I-MIBG clearance and radiation doses received by patients, family caregivers, and medical staff to establish appropriate radiation safety measures to be used in therapy applications. Research was focused on 23 children and adolescents with metastatic neuroblastoma, with ages ranging from 1.8 to 13 years, being treated with I-MIBG. Based on measured external dose rates from patients, dosimetric data to patients, family members, and others were calculated. The mean ± SD I-MIBG activity administered was 8.55 ± 1.69 GBq. Percent whole-body retention rates of I-MIBG at 24, 48, and 72 hours after administration were 48% ± 7%, 23% ± 7%, and 12% ± 6%, with a whole-body I-MIBG effective half-life of 23 ± 5 hours for all patients. The mean doses for patients were 0.234 ± 0.096 mGy·MBq to red-marrow and 0.251 ± 0.101 mGy·MBq to whole body. The maximum potential radiation doses transmitted by patients to others at 1.0 m was estimated to be 11.9 ± 3.4 mSv, with 97% of this dose occurring over 120 hours after therapy administration. Measured mean dose received by the 22 family caregivers was 1.88 ± 1.85 mSv, and that received by the 19 pediatric physicians was 43 ± 51 μSv. In this study, we evaluated the whole-body clearance of I-MIBG in 23 pediatric patients, and the radiation doses received by family caregivers and medical staff during these therapy procedures, thus facilitating the establishment of radiation safety measures to be applied in pediatric therapy.

Treatment Patterns and Early Outcomes of ALK-Positive Non-Small Cell Lung Cancer Patients Receiving Ceritinib: A Chart Review Study.

PubMed

Bendaly, Edmond; Dalal, Anand A; Culver, Kenneth; Galebach, Philip; Bocharova, Iryna; Foster, Rebekah; Sasane, Medha; Macalalad, Alexander R; Guérin, Annie

2017-05-01

This study aimed to provide the first real-world description of the characteristics, treatments, dosing patterns, and early outcomes of patients with ALK-positive non-small cell lung cancer (NSCLC) who received ceritinib in US clinical practice. US oncologists provided data from medical charts of adult patients diagnosed with locally advanced or metastatic ALK-positive NSCLC who received ceritinib following crizotinib. Patient characteristics, treatment patterns, ceritinib dosing, early outcomes, and occurrence of gastrointestinal adverse events (AEs) by dose and instructions on food intake were assessed, and Kaplan-Meier analysis was used to describe clinician-defined progression-free survival (PFS) on ceritinib. Medical charts of 58 ALK-positive NSCLC patients treated with ceritinib were reviewed (median age 63 years; 41% male; 21% with prior chemotherapy experience). At ceritinib initiation, 44 patients had multiple distant metastases, most commonly in the liver (60%), bone (53%), and brain (38%). Initial ceritinib dose varied: 71% received 750 mg, 19% 600 mg, and 10% 450 mg. Although median follow-up after ceritinib initiation was short (3.8 months), most patients achieved either a complete or partial response (69%) on ceritinib, regardless of metastatic sites present at initiation or initial dose. Median PFS on ceritinib was 12.9 months. 17% of patients had a gastrointestinal AE reported during follow-up. The majority of events occurred in patients instructed to fast; no patients instructed to take a lower dose of ceritinib with food reported gastrointestinal AEs. These early findings of ceritinib use in clinical practice suggest that ceritinib is effective at treating crizotinib-experienced ALK-positive NSCLC patients, regardless of metastatic sites or initial dose, and dosing ceritinib with food may lead to fewer gastrointestinal AEs. Future studies with larger sample size and longer follow-up are warranted, including an ongoing randomized trial to assess the gastrointestinal tolerability of ceritinib 450 and 600 mg with low-fat meals. Novartis Pharmaceutical Corporation.

The effect of dimethoate and pyrantel on vitamin C concentration in the rat liver.

PubMed

Spodniewska, A; Zasadowski, A

2006-01-01

The aim of this study was to determine the content of vitamin C in the liver of rats exposed to dimethoate or pyrantel embonate as well as co-intoxication with both agents. Investigations were carried out in two stages. At each stage, the rats were divided into three experimental groups (I-III) and a control (C) group. In the first stage, rats from group I were administered pyrantel embonate at a two-week interval at a dose of 1/2 LD50, while the animals from group II received dimethoate for 28 days at a dose of 1/25 LD50, and those from group III - both mentioned compounds in an identical manner as in groups I and II. In the second stage, the rats from group I received pyrantel embonate at a dose of 1/5 LD50 for 3 consecutive days, while the animals from group II received dimethoate at a dose of 1/10 LD50 for 5 consecutive days, and those from III received both compounds, but pyrantel was administered on day 3, 4 and 5 of dimethoate administration. The concentration of vitamin C after pyrantel embonate and dimethoate administration was influenced not only by doses of the compounds used but also by the manner of their application (single or co-administration). Dimethoate delivered at a dose of 1/25 LD50 evoked an increase in vitamin C concentration that was observed to continue up to the 14th day after the exposure, whereas when applied at a dose of 1/10 LD50 it increased the vitamin C level only at the 3rd hour. A considerable decrease in the vitamin C level was reported after pyrantel treatment at a dose of 1/5 LD50. In rats from groups where the compounds were co-administered, increased level of vitamin C was observed at both stages of the experiment only in the first period after intoxication, i.e. up to the 6th hour.

Effect of inhaled corticosteroids on salival composition: a cross-sectional study in patients with bronchial asthma.

PubMed

Navarrete, Bernardino Alcázar; Palacios, Pedro José Romero; Aguilar-Salvatierra, Antonio; Guardia, Javier; Gómez-Moreno, Gerardo

2015-09-01

To date, no evidence exists in the literature as to the effects of inhaled corticosteroids (ICs) on salivary composition in patients with bronchial asthma. The aim of this study was to assess the effect of ICs on salival composition. Adult patients attending an outpatient respiratory clinic who were classified into two groups (controls and patients with bronchial asthma receiving ICs), were recruited in this cross-sectional study. For each participant, data of clinical records, baseline history of asthma, and regular IC dose were recorded. A sample of stimulated saliva was collected and processed for investigation of mucin 5B (MUC5B), lipoxygenase (LPO), total antioxidant capacity, and 8-hydroxydeoxyguanosine (8-OHdG) levels. Overall, 103 patients (49 controls and 54 patients receiving regular treatment with ICs) were recruited. No differences in comorbidities or smoking habits were observed. Patients treated with high-doses of ICs showed lower levels of salival MUC5B compared with those treated with medium IC doses or those not treated with ICs (1.60 vs. 2.20 vs. 2.53 ng/mL; p = 0.042). In patients with asthma, treatment with high-doses of ICs is associated with reduced levels of salivary MUC5B. This effect can explain some of the effects of ICs on oral health.

Impact of Dose Reductions, Delays Between Chemotherapy Cycles, and/or Shorter Courses of Adjuvant Chemotherapy in Stage II and III Colorectal Cancer Patients: a Single-Center Retrospective Study.

PubMed

Sgouros, Joseph; Aravantinos, Gerasimos; Kouvatseas, George; Rapti, Anna; Stamoulis, George; Bisvikis, Anastasios; Res, Helen; Samantas, Epameinondas

2015-12-01

Most stage II or III colorectal cancer patients are receiving nowadays a 4 to 6-month course of adjuvant chemotherapy. However, delays between cycles, reductions in the doses of chemotherapy drugs, or even permanent omissions of chemotherapy cycles might take place due to side effects or patient's preference. We examined the impact of these treatment modifications on recurrence-free survival (RFS) and overall survival (OS). We retrospectively collected data from colorectal cancer patients who had received adjuvant chemotherapy in our Department. Patients were categorized in five groups based on whether they had or not delays between chemotherapy cycles, dose reductions, and permanent omissions of chemotherapy cycles. Three-year RFS and OS of the five different groups were compared using the log-rank test and the Sidak approach. Five hundred and eight patients received treatment. Twenty seven percent of the patients had the full course of chemotherapy; the others had delays, dose reductions, or early termination of the treatment. No statistically significant differences were observed in 3-year RFS and OS between the five groups. A trend for worse RFS was noticed with early termination of treatment. A similar trend was also noticed for OS but only for stage II patients. In colorectal cancer patients, receiving adjuvant chemotherapy, delays between chemotherapy cycles, dose reductions of chemotherapy drugs, or even early termination of the treatment course do not seem to have a negative impact in 3-year RFS and OS; however, due to the trend of worse RFS in patients receiving shorter courses of chemotherapy, further studies are needed.

Comparison of salt with low-dose furosemide and carperitide for treating acute decompensated heart failure: a single-center retrospective cohort study.

PubMed

Okuhara, Yoshitaka; Hirotani, Shinichi; Ando, Tomotaka; Nishimura, Koichi; Orihara, Yoshiyuki; Komamura, Kazuo; Naito, Yoshiro; Mano, Toshiaki; Masuyama, Tohru

2017-04-01

Hypertonic saline with furosemide has been proposed for a long time as an effective therapeutic option for the treatment of acute decompensated heart failure (ADHF). We previously reported the efficacy of continuous infusion of 1.7 % hypertonic saline plus low-dose furosemide in treatment for ADHF. Although this therapeutic strategy can be a useful option for effective decongestion in treatment for ADHF, there is no study that assesses the effect and safety of saline supplementation compared with standard therapy in Japan. The aim of this study was to investigate the efficacy, safety, and cost-effectiveness of 1.7 % hypertonic saline plus low-dose furosemide infusion compared with carperitide. We compared clinical outcomes, adverse events, and cost for patients receiving carperitide (carperitide group) with those for patients receiving 1.7 % hypertonic saline plus low-dose furosemide (salt group) during the initial hospitalization for ADHF. The cost analysis was performed on the basis of the previous report about cost-effectiveness of acute heart failure. A total of 175 ADHF patients received either carperitide (n = 111) or 1.7 % hypertonic saline plus low-dose furosemide infusion (n = 64) as initial treatment. There were no differences in length of hospital stay (27 ± 19 vs. 25 ± 16 day, p = 0.170) and infusion period (7.2 ± 6.1 vs. 8.4 ± 7.5 day, p = 0.474) between the two groups. The incidence of rehospitalization did not differ at 1 month (7.6 vs. 6.6 %, p = 1.000) and 1 year (36.8 vs. 37.7 %, p = 0.907) between the two groups. The Kaplan-Meier curves revealed no significant difference for 1 year all-cause mortality between the two groups (log-rank, p = 0.724). The single hospitalization cost was 95,314 yen lower and the yearly hospitalization cost 125,628 yen lower in the salt group compared with the carperitide group. Thus, intravenous 1.7 % hypertonic saline plus low-dose furosemide infusion is as effective as carperitide in terms of clinical outcome and is a cost-effective therapeutic strategy for the treatment of ADHF.

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

Protective effect of royal jelly on the sperm parameters and testosterone level and lipid peroxidation in adult mice treated with oxymetholone

PubMed Central

Zahmatkesh, Ensieh; Najafi, Gholamreza; Nejati, Vahid; Heidari, Reza

2014-01-01

Objectives : The aim of the present study was to evaluate protective effect of royal jelly on sperm parameters, testosterone level, and malondialdehyde (MDA) production in mice. Materials and Methods: Thirty-two adult male NMRI mice weighing 30±2 g were used. All the animals were divided into 4 groups. Control group: received saline 0.1 ml/mouse/day orally for 30 days. Royal jelly group (RJ): received royal jelly at dose of 100 mg/kg daily for 30 days orally. Oxymetholone group: the received Oxymetholone (OX) at dose of 5 mg/kg daily for 30 days orally. Royal jelly+Oxymetholone group: received royal jelly at dose of 100 mg/kg/day orally concomitant with OX administration. Sperm count, sperm motility, viability, maturity, and DNA integrity were analyzed. Furthermore, serum testosterone and MDA concentrations were determined. Results: In Oxymetholone group, sperm count, motility as well as testosterone concentration reduced significantly (p<0.05), while significant (p<0.05) increases in immature sperm, sperm with DNA damaged, and MDA concentration were announced in Oxymetholone group in comparison with control group and Royal jelly+Oxymetholone group. RJ caused partially amelioration in all of the above- mentioned parameters in Royal Jelly+Oxymetholone group. Conclusion: In conclusion, RJ may be used in combination with OX to improve OX-induced oxidative stress and male infertility. PMID:25050300

Protective effect of royal jelly on the sperm parameters and testosterone level and lipid peroxidation in adult mice treated with oxymetholone.

PubMed

Zahmatkesh, Ensieh; Najafi, Gholamreza; Nejati, Vahid; Heidari, Reza

2014-01-01

Objectives : The aim of the present study was to evaluate protective effect of royal jelly on sperm parameters, testosterone level, and malondialdehyde (MDA) production in mice. Thirty-two adult male NMRI mice weighing 30±2 g were used. All the animals were divided into 4 groups. received saline 0.1 ml/mouse/day orally for 30 days. Royal jelly group (RJ): received royal jelly at dose of 100 mg/kg daily for 30 days orally. Oxymetholone group: the received Oxymetholone (OX) at dose of 5 mg/kg daily for 30 days orally. Royal jelly+Oxymetholone group: received royal jelly at dose of 100 mg/kg/day orally concomitant with OX administration. Sperm count, sperm motility, viability, maturity, and DNA integrity were analyzed. Furthermore, serum testosterone and MDA concentrations were determined. In Oxymetholone group, sperm count, motility as well as testosterone concentration reduced significantly (p<0.05), while significant (p<0.05) increases in immature sperm, sperm with DNA damaged, and MDA concentration were announced in Oxymetholone group in comparison with control group and Royal jelly+Oxymetholone group. RJ caused partially amelioration in all of the above- mentioned parameters in Royal Jelly+Oxymetholone group. In conclusion, RJ may be used in combination with OX to improve OX-induced oxidative stress and male infertility.

A simple 3-day "rush" venom immunotherapy protocol: documentation of safety.

PubMed

Kalogeromitros, D; Makris, M; Koti, I; Chliva, C; Mellios, A; Avgerinou, G; Theoharides, T C

2010-01-01

Venom immunotherapy (VIT) is the only effective treatment for hymenoptera hypersensitivity, but conventional protocols require a few weeks. We present the safety of a 3-day "rush" protocol that requires only 7 injections and 255 mgr cumulative dose before the 100 microg maintenance dose. Forty-nine patients (33 males, 16 females) of mean age 43.57+/-12.9 yrs received "rush" VIT. Only 7 injections were required until the maintenance dose of 100 mgr was reached on Day 5. On Day 1, four injections were administered with initial dose of 5 mgr and total dose of 75 microg. On Day 3 a cumulative dose of 180 mgr was administered in three injections (40 mgr, 60 mgr and 80 mgr). A dose of 100 mgr was administered on Day 5. Twenty-nine individuals were treated with Honey-Bee venom; 18 with Common wasp; 5 with Paper Wasp; while 13 patients received Mixed Vespid preparation. Inclusion criteria were documented IgE-mediated allergy with intradermal sensitivity to < or =0.1 mgr/ml venom concentration and concomitant detection of specific venom IgE > or =0.35 kU/l. All patients reached the maintenance dose. Forty-nine patients received 65 immunotherapy courses, resulting in 1520 injections. Thirty-three systemic reactions: 7 during building phase (1.5%); and 26 in the maintenance dose (2.4%) were observed in 9 patients. The percentage of reactions/total injection number was 2.2%; all reactions were mild-to-moderate. Fourteen patients reported documented field stings at least two months after VIT onset with only one reported mild systemic reaction. We propose a simple "rush" VIT protocol in an outpatient setting as an easy-to-perform alternative option for VIT induction phase. Copyright 2009 SEICAP. Published by Elsevier Espana. All rights reserved.

A retrospective analysis of outcomes of dalteparin use in pediatric patients: a single institution experience.

PubMed

Warad, Deepti; Rao, Amulya Nageswara; Mullikin, Trey; Graner, Kevin; Shaughnessy, William J; Pruthi, Rajiv K; Rodriguez, Vilmarie

2015-08-01

Dalteparin is a commonly used low molecular weight heparin (LMWH) with extensive safety data in adults. With distinct advantages of once daily dosing and relative safety in renal impairment, it has been used off-label in pediatric practice; however, age-based dosing guidelines, safety and efficacy data in children are evolving. To report our institutional experience with the use of dalteparin in the treatment and prophylaxis of venous thromboembolism (VTE) in pediatric patients. Retrospective chart review of all children (0-18years) that received dalteparin from December 1, 2000 through December 31, 2011. Doses per unit body weight per day (units/kg/day) were calculated for age-based group comparisons. Of 166 patients identified, 116 (70%) received prophylactic doses while 50 (30%) received therapeutic doses of dalteparin. Infants (<1year) required significantly higher weight-based dosing to achieve therapeutic anti-Xa levels compared to children (1-10years) or adolescents (>10-18years) (mean dose units/kg/day; 396.6 versus 236.7 and 178.8 respectively, p<0.0001). Overall response rate, including complete and partial thrombus resolution, was 83%. Bleeding complications were minor and the rates were similar in therapeutic and prophylaxis patients. No significant differences in dosing or bleeding events were noted based on obesity or malignancy. In our experience, dalteparin is effective for prophylaxis and therapy of VTE in pediatric patients. Dosing should be customized in an age-based manner with close monitoring of anti-Xa activity in order to achieve optimal levels, prevent bleeding complications, and to allow full benefit of prevention or therapy of thrombotic complications. Copyright © 2015 Elsevier Ltd. All rights reserved.

Pavor nocturnus: a complication of single daily tricyclic or neuroleptic dosage.

PubMed

Flemenbaum, A

1976-05-01

The author tested the hypothesis that a single bedtime dosage schedule of tricyclic or neuroleptic medication produces increased frequency of night terrors by administering a questionnaire to 30 medical patients who were not receiving such medications and 100 psychiatric patients on either multiple- or single-dosage schedules. Psychiatric patients on multiple-dosage schedules reported no more frightening dreams than the medical patients, whereas almost three-fourths of those receiving single bedtime doses had frightening dreams, a significant difference from the medical sample. This preliminary report is presented to call attention to the possible undesirable effects of a single dose schedule.

Two dose Augmentin treatment of acute gonorrhoea in men.

PubMed Central

Lim, K B; Rajan, V S; Giam, Y C; Lui, E O; Sng, E H; Yeo, K L

1984-01-01

We studied 192 men with acute gonococcal urethritis, 97 of whom received two oral doses of Augmentin (amoxycillin 3 g and clavulanic acid 250 mg) separated by a four hour interval; the remaining 95 received 2 g kanamycin in a single intramuscular injection. Of the patients treated with Augmentin, 93 (95.9%) were cured, which was significantly more than the 83 (87.4%) patients treated with kanamycin. Augmentin was equally effective in the treatment of penicillinase producing Neisseria gonorrhoeae (PPNG) and non-PPNG infections, the cure rates for which were 96.6% and 95.6% respectively. PMID:6428699

A Recombinant Vesicular Stomatitis Virus Ebola Vaccine.

PubMed

Regules, Jason A; Beigel, John H; Paolino, Kristopher M; Voell, Jocelyn; Castellano, Amy R; Hu, Zonghui; Muñoz, Paula; Moon, James E; Ruck, Richard C; Bennett, Jason W; Twomey, Patrick S; Gutiérrez, Ramiro L; Remich, Shon A; Hack, Holly R; Wisniewski, Meagan L; Josleyn, Matthew D; Kwilas, Steven A; Van Deusen, Nicole; Mbaya, Olivier Tshiani; Zhou, Yan; Stanley, Daphne A; Jing, Wang; Smith, Kirsten S; Shi, Meng; Ledgerwood, Julie E; Graham, Barney S; Sullivan, Nancy J; Jagodzinski, Linda L; Peel, Sheila A; Alimonti, Judie B; Hooper, Jay W; Silvera, Peter M; Martin, Brian K; Monath, Thomas P; Ramsey, W Jay; Link, Charles J; Lane, H Clifford; Michael, Nelson L; Davey, Richard T; Thomas, Stephen J

2017-01-26

The worst Ebola virus disease (EVD) outbreak in history has resulted in more than 28,000 cases and 11,000 deaths. We present the final results of two phase 1 trials of an attenuated, replication-competent, recombinant vesicular stomatitis virus (rVSV)-based vaccine candidate designed to prevent EVD. We conducted two phase 1, placebo-controlled, double-blind, dose-escalation trials of an rVSV-based vaccine candidate expressing the glycoprotein of a Zaire strain of Ebola virus (ZEBOV). A total of 39 adults at each site (78 participants in all) were consecutively enrolled into groups of 13. At each site, volunteers received one of three doses of the rVSV-ZEBOV vaccine (3 million plaque-forming units [PFU], 20 million PFU, or 100 million PFU) or placebo. Volunteers at one of the sites received a second dose at day 28. Safety and immunogenicity were assessed. The most common adverse events were injection-site pain, fatigue, myalgia, and headache. Transient rVSV viremia was noted in all the vaccine recipients after dose 1. The rates of adverse events and viremia were lower after the second dose than after the first dose. By day 28, all the vaccine recipients had seroconversion as assessed by an enzyme-linked immunosorbent assay (ELISA) against the glycoprotein of the ZEBOV-Kikwit strain. At day 28, geometric mean titers of antibodies against ZEBOV glycoprotein were higher in the groups that received 20 million PFU or 100 million PFU than in the group that received 3 million PFU, as assessed by ELISA and by pseudovirion neutralization assay. A second dose at 28 days after dose 1 significantly increased antibody titers at day 56, but the effect was diminished at 6 months. This Ebola vaccine candidate elicited anti-Ebola antibody responses. After vaccination, rVSV viremia occurred frequently but was transient. These results support further evaluation of the vaccine dose of 20 million PFU for preexposure prophylaxis and suggest that a second dose may boost antibody responses. (Funded by the National Institutes of Health and others; rVSV∆G-ZEBOV-GP ClinicalTrials.gov numbers, NCT02269423 and NCT02280408 .).

First month prednisone dose predicts prednisone burden during the following 11 months: an observational study from the RELES cohort

PubMed Central

Ruiz-Irastorza, G; Garcia, M; Espinosa, G; Caminal, L; Mitjavila, F; González-León, R; Sopeña, B; Canora, J; Villalba, M V; Rodríguez-Carballeira, M; López-Dupla, J M; Callejas, J L; Castro, A; Tolosa, C; Sánchez-García, M E; Pérez-Conesa, M; Navarrete-Navarrete, N; Rodríguez, A P; Herranz, M T; Pallarés, L

2016-01-01

Aim To study the influence of prednisone dose during the first month after systemic lupus erythematosus (SLE) diagnosis (prednisone-1) on glucocorticoid burden during the subsequent 11 months (prednisone-2–12). Methods 223 patients from the Registro Español de Lupus Eritematoso Sistémico inception cohort were studied. The cumulative dose of prednisone-1 and prednisone-2–12 were calculated and recoded into a four-level categorical variable: no prednisone, low dose (up to 7.5 mg/day), medium dose (up to 30 mg/day) and high dose (over 30 mg/day). The association between the cumulative prednisone-1 and prednisone-2–12 doses was tested. We analysed whether the four-level prednisone-1 categorical variable was an independent predictor of an average dose >7.5 mg/day of prednisone-2–12. Adjusting variables included age, immunosuppressives, antimalarials, methyl-prednisolone pulses, lupus nephritis and baseline SLE Disease Activity Index (SLEDAI). Results Within the first month, 113 patients (51%) did not receive any prednisone, 24 patients (11%) received average low doses, 46 patients (21%) received medium doses and 40 patients (18%) received high doses. There was a strong association between prednisone-1 and prednisone-2–12 dose categories (p<0.001). The cumulative prednisone-1 dose was directly associated with the cumulative prednisone-2–12 dose (p<0.001). Compared with patients on no prednisone, patients taking medium (adjusted OR 5.27, 95% CI 2.18 to 12.73) or high-dose prednisone-1 (adjusted OR 10.5, 95% CI 3.8 to 29.17) were more likely to receive prednisone-2–12 doses of >7.5 mg/day, while patients receiving low-dose prednisone-1 were not (adjusted OR 1.4, 95% CI 0. 0.38 to 5.2). If the analysis was restricted to the 158 patients with a baseline SLEDAI of ≥6, the model did not change. Conclusion The dose of prednisone during the first month after the diagnosis of SLE is an independent predictor of prednisone burden during the following 11 months. PMID:27547439

Pharmacokinetics of terbinafine in little brown myotis (Myotis lucifugus) infected with Pseudogymnoascus destructans.

PubMed

Court, Michael H; Robbins, Alison H; Whitford, Anne M; Beck, Erika V; Tseng, Flo S; Reeder, DeeAnn M

2017-01-01

OBJECTIVE To determine the pharmacokinetics of terbinafine in little brown myotis (Myotis lucifugus) infected with Pseudogymnoascus destructans. ANIMALS 123 bats from a P destructans-infected hibernation site in Virginia. PROCEDURES 3 bats were euthanized and necropsied to confirm the presence of P destructans within the population. The remaining 120 bats were systematically assigned to 6 groups (20 bats/group). Bats in each of 3 groups received 6, 20, or 60 mg of terbinafine/kg, SC, once daily for 10 days. Bats in another group received 200 mg of terbinafine/kg, SC, once daily for 5 days. Bats in 1 group received the terbinafine vehicle solution (0.1 mL/kg, SC, once daily for 10 days). Bats in the remaining group did not receive any treatment. Following the treatment period (days 1 through 10), bats were housed in a hibernation chamber and monitored daily until euthanasia on day 42, 75, or 109. Tissue specimens were collected from all bats as soon as possible after death or euthanasia to determine terbinafine concentration. Within each group and tissue type, terbinafine concentration data were pooled, and pharmacokinetic parameters were calculated by noncompartmental methods. RESULTS Adverse neurologic effects and a high mortality rate before day 10 were observed in bats that received the highest terbinafine dose (200 mg/kg) but not those that received lower doses. Presumed therapeutic terbinafine concentrations (≥ 2 μg/g) were maintained in skin and wing for at least 30 and 6 days in bats that received the 60 and 20 mg/kg doses, respectively, but were not achieved in most bats that received the 6 mg/kg dose. Tissue terminal half-life ranged from 14 to 22 days. Terbinafine concentration in hair was positively correlated with that in skin and wing. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated terbinafine doses > 6 but < 200 mg/kg should be further evaluated for the treatment of P destructans-infected bats. Collection of serial hair specimens may represent a noninvasive method for monitoring terbinafine concentration in treated bats.

Cellular and Humoral Responses to a Second Dose of Herpes Zoster Vaccine Administered 10 Years After the First Dose Among Older Adults.

PubMed

Levin, Myron J; Schmader, Kenneth E; Pang, Lei; Williams-Diaz, Angela; Zerbe, Gary; Canniff, Jennifer; Johnson, Michael J; Caldas, Yupanqui; Cho, Alice; Lang, Nancy; Su, Shu-Chih; Parrino, Janie; Popmihajlov, Zoran; Weinberg, Adriana

2016-01-01

Herpes zoster vaccine (ZV) was administered as a second dose to 200 participants ≥ 70 years old who had received a dose of ZV ≥ 10 years previously (NCT01245751). Varicella zoster virus (VZV) antibody titers (measured by a VZV glycoprotein-based enzyme-linked immunosorbent assay [gpELISA]) and levels of interferon γ (IFN-γ) and interleukin 2 (IL-2; markers of VZV-specific cell-mediated immunity [CMI], measured by means of ELISPOT analysis) in individuals aged ≥ 70 years who received a booster dose of ZV were compared to responses of 100 participants aged 50-59 years, 100 aged 60-69 years, and 200 aged ≥ 70 years who received their first dose of ZV. The study was powered to demonstrate noninferiority of the VZV antibody response at 6 weeks in the booster-dose group, compared with the age-matched first-dose group. Antibody responses were similar at baseline and after vaccination across all age and treatment groups. Both baseline and postvaccination VZV-specific CMI were lower in the older age groups. Peak gpELISA titers and their fold rise from baseline generally correlated with higher baseline and postvaccination VZV-specific CMI. IFN-γ and IL-2 results for subjects ≥ 70 years old were significantly higher at baseline and after vaccination in the booster-dose group, compared with the first-dose group, indicating that a residual effect of ZV on VZV-specific CMI persisted for ≥ 10 years and was enhanced by the booster dose. These findings support further investigation of ZV administration in early versus later age and of booster doses for elderly individuals at an appropriate interval after initial immunization against HZ. NCT01245751. © The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Impact of weight-based ribavirin with peginterferon alfa-2b in African Americans with hepatitis C virus genotype 1.

PubMed

Jacobson, Ira M; Brown, Robert S; McCone, Jonathan; Black, Martin; Albert, Clive; Dragutsky, Michael S; Siddiqui, Firdous A; Hargrave, Thomas; Kwo, Paul Y; Lambiase, Louis; Galler, Greg W; Araya, Victor; Freilich, Bradley; Harvey, Joann; Griffel, Louis H; Brass, Clifford A

2007-10-01

WIN-R (Weight-based dosing of pegINterferon alfa-2b and Ribavirin) was a multicenter, randomized, open-label, investigator-initiated trial involving 236 community and academic sites in the United States, comparing response to pegylated interferon (PEG-IFN) alfa-2b plus a flat or weight-based dose of ribavirin (RBV) in treatment-naive patients with chronic hepatitis C and compensated liver disease. Patients were randomized to receive PEG-IFN alfa-2b at 1.5 microg/kg/week plus flat-dose (800 mg/day) or weight-based-dose RBV (800 mg/day for weight <65 kg, 1000 mg/day for 65-85 kg, 1200 mg/day for >85-105 kg, or 1400 mg/day for >105-<125 kg). Sustained virologic response (SVR; undetectable [<125 IU/mL] hepatitis C virus [HCV] RNA at end of follow-up) in patients > or =65 kg was the primary end point. Low SVR rates have been reported among African American individuals, in whom there is a preponderance of HCV genotype 1. This subanalysis of WIN-R was conducted to evaluate the efficacy of weight-based dosing among African American individuals with genotype 1 infection enrolled in the trial. Of 362 African American patients in the primary efficacy analysis, 188 received RBV flat dosing and 174 received weight-based dosing. SVR rates were higher (21% versus 10%; P = 0.0006) and relapse rates were lower (22% versus 30%) in the weight-based-dose group than in the flat-dose group. Safety and rates of drug discontinuation were similar between the 2 groups. Weight-based dosing of RBV is more effective than flat dosing in combination with PEG-IFN alfa-2b in African American individuals with HCV genotype 1. Even with weight-based dosing, response rates in African American individuals are lower than reported in other ethnic groups.

Safety and dose modification for patients receiving niraparib.

PubMed

Berek, J S; Matulonis, U A; Peen, U; Ghatage, P; Mahner, S; Redondo, A; Lesoin, A; Colombo, N; Vergote, I; Rosengarten, O; Ledermann, J; Pineda, M; Ellard, S; Sehouli, J; Gonzalez-Martin, A; Berton-Rigaud, D; Madry, R; Reinthaller, A; Hazard, S; Guo, W; Mirza, M R

2018-05-14

Niraparib is a poly(ADP-ribose) polymerase (PARP) inhibitor approved in the United States and Europe for maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to platinum-based chemotherapy. In the pivotal ENGOT-OV16/NOVA trial, the dose reduction rate due to TEAE was 68.9%, and the discontinuation rate due to TEAE was 14.7%, including 3.3% due to thrombocytopenia. A retrospective analysis was performed to identify clinical parameters that predict dose reductions. All analyses were performed on the safety population, comprising all patients who received at least one dose of study drug. Patients were analyzed according to the study drug consumed (ie, as treated). A predictive modeling method (decision trees) was used to identify important variables for predicting the likelihood of developing grade ≥3 thrombocytopenia within 30 days after the first dose of niraparib and determine cutoff points for chosen variables. Following dose modification, 200 mg was the most commonly administered dose in the ENGOT-OV16/NOVA trial. Baseline platelet count and baseline body weight were identified as risk factors for increased incidence of grade ≥3 thrombocytopenia. Patients with a baseline body weight <77 kg or a baseline platelet count <150,000/μL in effect received an average daily dose approximating 200 mg (median = 207 mg) due to dose interruption and reduction. Progression-free survival in patients who were dose reduced to either 200 mg or 100 mg was consistent with that of patients who remained at the 300 mg starting dose. The analysis presented suggests that patients with baseline body weight of < 77 kg or baseline platelets of < 150,000/μL may benefit from a starting dose of 200 mg per day. (ClinicalTrials.gov ID: NCT01847274).

PUNISHING AND CARDIOVASCULAR EFFECTS OF INTRAVENOUS HISTAMINE IN RATS: PHARMACOLOGICAL SELECTIVITY

PubMed Central

Podlesnik, Christopher A.; Jimenez-Gomez, Corina

2014-01-01

Although drugs may serve as reinforcers or punishers of operant behavior, the punishing function has received much less experimental attention than the reinforcing function. A sensitive method for studying drug-induced punishment is to assess choice for a punished response over an unpunished response. In these experiments, rats chose between pressing one lever and receiving a sucrose pellet or pressing another lever and receiving a sucrose pellet plus an intravenous injection of histamine. When sucrose was delivered equally frequently for either the punished or the unpunished response, rats selected the unpunished lever consistently, but decreases in the punished response did not differ as a function of intravenous histamine dose (0.1–1 mg/kg/inj). Changing the procedure so that sucrose was delivered on the unpunished lever with p = .5 increased the rats’ responding on the punished lever with saline injections. In addition, the same range of histamine doses produced a much larger range of responses on the punished lever that was dose dependent. Using these procedures to assess the receptors mediating histamine’s effects, the histamine H1-receptor antagonists, pyrilamine and ketotifen, antagonized the punishing effect of histamine, but the histamine H2-receptor antagonist ranitidine did not. However, ranitidine pretreatments reduced histamine-induced heart-rate increases to a greater extent than did the histamine H1-receptor antagonists when administered at the same doses examined under conditions of histamine punishment. Overall, the present findings extend the general hypothesis that activation of histamine H1-receptors mediates the punishing effects of histamine. They also introduce methods for rapidly assessing pharmacological mechanisms underlying drug-induced punishment. PMID:23982898

Behavioral and stimulant treatment of hyperactive children: a therapy study with methylphenidate probes in a within-subject design.

PubMed

Pelham, W E; Schnedler, R W; Bologna, N C; Contreras, J A

1980-01-01

Eight hyperactive children were treated with a behavioral intervention focusing on teacher and parent training over a period of 5 months. Three times, before therapy and after 3 weeks and 13 weeks of intervention, children received methylphenidate during 3-week probe periods. Each week in a probe they received either a placebo, .25 mg/kg, or .75 mg/kg methylphenidate. Classroom observation of on-task behavior suggested that effectiveness of the behavioral intervention was between that of the two dosages of medication before therapy. Both dosages resulted in higher levels of on-task behavior when administered after 13 weeks of behavioral intervention than when administered before therapy. Teacher rating data showed equivalent effects of therapy and the low dosage of methylphenidate alone but a stronger effect of the high dose alone; only the high dose resulted in improved behavior after 13 weeks of behavioral intervention. As a group, only when they received the high dose of methylphenidate after 13 weeks of behavioral intervention did children reach the level of appropriate behavior shown by nonhyperactive controls. However, this level was also reached by two children with the low dose and by one child without medication, and it was not reached by one child. The results suggest that the combination of psychostimulant medication and behavior therapy may be more effective in the short-term than either treatment alone for hyperactive children in school settings. In addition, parent ratings and clinic observation of parent-child interactions suggested that children had improved in the home setting, high-lighting the importance of behavioral parent training in the treatment of hyperactivity.

Absorbed organ and effective doses from digital intra-oral and panoramic radiography applying the ICRP 103 recommendations for effective dose estimations

PubMed Central

Thilander-Klang, Anne; Ylhan, Betȕl; Lofthag-Hansen, Sara; Ekestubbe, Annika

2016-01-01

Objective: During dental radiography, the salivary and thyroid glands are at radiation risk. In 2007, the International Commission on Radiological Protection (ICRP) updated the methodology for determining the effective dose, and the salivary glands were assigned tissue-specific weighting factors for the first time. The aims of this study were to determine the absorbed dose to the organs and to calculate, applying the ICRP publication 103 tissue-weighting factors, the effective doses delivered during digital intraoral and panoramic radiography. Methods: Thermoluminescent dosemeter measurements were performed on an anthropomorphic head and neck phantom. The organ-absorbed doses were measured at 30 locations, representing different radiosensitive organs in the head and neck, and the effective dose was calculated according to the ICRP recommendations. Results: The salivary glands and the oral mucosa received the highest absorbed doses from both intraoral and panoramic radiography. The effective dose from a full-mouth intraoral examination was 15 μSv and for panoramic radiography, the effective dose was in the range of 19–75 μSv, depending on the panoramic equipment used. Conclusion: The effective dose from a full-mouth intraoral examination is lower and that from panoramic radiography is higher than previously reported. Clinicians should be aware of the higher effective dose delivered during panoramic radiography and the risk–benefit profile of this technique must be assessed for the individual patient. Advances in knowledge: The effective dose of radiation from panoramic radiography is higher than previously reported and there is large variability in the delivered radiation dosage among the different types of equipment used. PMID:27452261

Pharmacological dose of alpha-tocopherol induces cardiotoxicity in Wistar rats determined by echocardiography and histology

USDA-ARS?s Scientific Manuscript database

The effect of pharmacological dose of alpha-tocopherol on heart health was determined in Wistar rats. Animals were randomly assigned to either C (control, n = 11) or E (alpha-tocopherol, n = 11) group. Animals received corn oil (C) or alpha-tocopherol dissolved in corn oil (250 mg alpha-tocopherol/[...

Intensity-Modulated Radiotherapy of Head and Neck Cancer Aiming to Reduce Dysphagia: Early Dose-Effect Relationships for the Swallowing Structures

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

Feng, Felix Y.; Kim, Hyungjin M.; Lyden, Teresa H.

2007-08-01

Purpose: To present initial results of a clinical trial of intensity-modulated radiotherapy (IMRT) aiming to spare the swallowing structures whose dysfunction after chemoradiation is a likely cause of dysphagia and aspiration, without compromising target doses. Methods and Materials: This was a prospective, longitudinal study of 36 patients with Stage III-IV oropharyngeal (31) or nasopharyngeal (5) cancer. Definitive chemo-IMRT spared salivary glands and swallowing structures: pharyngeal constrictors (PC), glottic and supraglottic larynx (GSL), and esophagus. Lateral but not medial retropharyngeal nodes were considered at risk. Dysphagia endpoints included objective swallowing dysfunction (videofluoroscopy), and both patient-reported and observer-rated scores. Correlations between dosesmore » and changes in these endpoints from pre-therapy to 3 months after therapy were assessed. Results: Significant correlations were observed between videofluoroscopy-based aspirations and the mean doses to the PC and GSL, as well as the partial volumes of these structures receiving 50-65 Gy; the highest correlations were associated with doses to the superior PC (p = 0.005). All patients with aspirations received mean PC doses >60 Gy or PC V{sub 65} >50%, and GSL V{sub 50} >50%. Reduced laryngeal elevation and epiglottic inversion were correlated with mean PC and GSL doses (p < 0.01). All 3 patients with strictures had PC V{sub 70} >50%. Worsening patient-reported liquid swallowing was correlated with mean PC (p = 0.05) and esophageal (p 0.02) doses. Only mean PC doses were correlated with worsening patient-reported solid swallowing (p = 0.04) and observer-rated swallowing scores (p = 0.04). Conclusions: These dose-volume-effect relationships provide initial IMRT optimization goals and motivate further efforts to reduce swallowing structures doses to reduce dysphagia and aspiration.« less

Acute, subacute toxicity and mutagenic effects of anacardic acids from cashew (Anacardium occidentale Linn.) in mice.

PubMed

Carvalho, Ana Laura Nicoletti; Annoni, Raquel; Silva, Paula Regina Pereira; Borelli, Primavera; Fock, Ricardo Ambrósio; Trevisan, Maria Teresa Salles; Mauad, Thais

2011-06-01

Anacardium occidentale Linn. (cashew) is a Brazilian plant that is usually consumed in natura and is used in folk medicine. Anacardic acids (AAs) in the cashew nut shell liquid are biologically active as gastroprotectors, inhibitors of the activity of various deleterious enzymes, antitumor agents and antioxidants. Yet, there are no reports of toxicity testing to guarantee their use in vivo models. We evaluated AAs biosafety by measuring the acute, subacute and mutagenic effects of AAs administration in BALB/c mice. In acute tests, BALB/c mice received a single oral dose of 2000 mg/kg, whereas animals in subacute tests received 300, 600 and 1000 mg/kg for 30 days. Hematological, biochemical and histological analyses were performed in all animals. Mutagenicity was measured with the acute micronucleus test 24h after oral administration of 250 mg/kg AAs. Our results showed that the AAs acute minimum lethal dose in BALB/c mice is higher than 2000 mg/kg since this concentration did not produce any symptoms. In subacute tests, females which received the highest doses (600 or 1000 mg/kg) were more susceptible, which was seen by slightly decreased hematocrit and hemoglobin levels coupled with a moderate increase in urea. Anacardic acids did not produce any mutagenic effects. The data indicate that doses less than 300 mg/kg did not produce biochemical and hematological alterations in BALB/c mice. Additional studies must be conducted to investigate the pharmacological potential of this natural substance in order to ensure their safe use in vivo. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

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

Pirlepesov, F.; Shin, J.; Moskvin, V. P.

Purpose: Dose weighted Linear Energy Transfer (LETd) analysis of critical structures may be useful in understanding the side effects of the proton therapy. The objective is to analyze the differences between LETd and dose distributions in brain tumor patients receiving double scattering proton therapy, to quantify LETd variation in critical organs, and to identify beam arrangements contributing to high LETd in critical organs. Methods: Monte Carlo simulations of 9 pediatric brain tumor patients were performed. The treatment plans were reconstructed with the TOPAS Monte Carlo code to calculate LETd and dose. The beam data were reconstructed proximal to the aperturemore » of the double scattering nozzle. The dose and LETd to target and critical organs including brain stem, optic chiasm, lens, optic nerve, pituitary gland, and hypothalamus were computed for each beam. Results: Greater variability in LETd compared to dose was observed in the brainstem for patients with a variety of tumor types including 5 patients with tumors located in the posterior fossa. Approximately 20%–44% brainstem volume received LETd of 5kev/µm or greater from beams within gantry angles 180°±30° for 5 patients treated with a 3 beam arrangement. Critical organs received higher LETd when located in the vicinity of the beam distal edge. Conclusion: This study presents a novel strategy in the evaluation of the proton treatment impact on critical organs. While the dose to critical organs is confined below the required limits, the LETd may have significant variation. Critical organs in the vicinity of beam distal edge receive higher LETd and depended on beam arrangement, e.g. in posterior fossa tumor treatment, brainstem receive higher LETd from posterior-anterior beams. This study shows importance of the LETd analysis of the radiation impact on the critical organs in proton therapy and may be used to explain clinical imaging observations after therapy.« less

Low-dose D-methionine and N-acetyl-L-cysteine for protection from permanent noise-induced hearing loss in chinchillas.

PubMed

Clifford, Royce E; Coleman, John K M; Balough, Ben J; Liu, Jianzhong; Kopke, Richard D; Jackson, Ronald L

2011-12-01

Despite efforts at public health awareness and stringent industrial standards for hearing protection, noise-induced hearing loss (NIHL) remains a formidable public health concern. Although many antioxidants have proven to be beneficial in the laboratory for prevention of permanent NIHL, low-dose combinations of compounds with different biochemical mechanisms of action may allow long-term administration with fewer side effects and equal efficacy. The mixture of D-methionine and N-acetyl-L-cysteine administered at levels less than 10% of standard dosing has not been previously reported. Twenty-six female adult Chinchilla laniger were placed in 4 study groups, consisting of (1) a group receiving combination 12.5 mg/kg each D-methionine and N-acetyl-L-cysteine (DMET/NAC group), (2) a group receiving 12.5 mg/kg D-methionine (DMET-only group), (3) a group receiving 12.5 mg/kg N-acetyl-L-cysteine (NAC-only group), and (4) saline controls. Laboratory. All groups received twice-daily intraperitoneal injections 2 days prior to noise exposure, 1 hour before and after exposure on day 3, and for 2 days subsequently, totaling 10 doses of 125 mg/kg for each antioxidant over 5 days. Although NAC-only animals paralleled saline control recovery during 3 weeks, the DMET-only group revealed gradual improvement with statistically significant recovery in the middle frequencies. The DMET/NAC group showed significant improvement at most frequencies compared with controls (P < .001 and P < .05). Significant recovery of hearing was observed following continuous noise exposure with either DMET only or a combination of low-dose DMET/NAC, demonstrating a considerably lower dose of antioxidants required than previously reported for hearing recovery following acoustic trauma.

Delta-9-tetrahydrocannabinol (THC) affects forelimb motor map expression but has little effect on skilled and unskilled behavior.

PubMed

Scullion, K; Guy, A R; Singleton, A; Spanswick, S C; Hill, M N; Teskey, G C

2016-04-05

It has previously been shown in rats that acute administration of delta-9-tetrahydrocannabinol (THC) exerts a dose-dependent effect on simple locomotor activity, with low doses of THC causing hyper-locomotion and high doses causing hypo-locomotion. However the effect of acute THC administration on cortical movement representations (motor maps) and skilled learned movements is completely unknown. It is important to determine the effects of THC on motor maps and skilled learned behaviors because behaviors like driving place people at a heightened risk. Three doses of THC were used in the current study: 0.2mg/kg, 1.0mg/kg and 2.5mg/kg representing the approximate range of the low to high levels of available THC one would consume from recreational use of cannabis. Acute peripheral administration of THC to drug naïve rats resulted in dose-dependent alterations in motor map expression using high resolution short duration intracortical microstimulation (SD-ICMS). THC at 0.2mg/kg decreased movement thresholds and increased motor map size, while 1.0mg/kg had the opposite effect, and 2.5mg/kg had an even more dramatic effect. Deriving complex movement maps using long duration (LD)-ICMS at 1.0mg/kg resulted in fewer complex movements. Dosages of 1.0mg/kg and 2.5mg/kg THC reduced the number of reach attempts but did not affect percentage of success or the kinetics of reaching on the single pellet skilled reaching task. Rats that received 2.5mg/kg THC did show an increase in latency of forelimb removal on the bar task, while dose-dependent effects of THC on unskilled locomotor activity using the rotorod and horizontal ladder tasks were not observed. Rats may be employing compensatory strategies after receiving THC, which may account for the robust changes in motor map expression but moderate effects on behavior. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Effect of stimulus intensity and number of treatments on ECS-related seizure duration and retrograde amnesia in rats.

PubMed

Andrade, Chittaranjan; Thyagarajan, S; Vinod, P S; Srikanth, S N; Rao, N S K; Chandra, J Suresh

2002-12-01

Animal models are frequently used to generate and test hypotheses about amnesia resulting from electroconvulsive therapy (ECT). Although many predictors of ECT-induced amnesia are known, their relative effects have been inadequately researched in the context of the animal models. We sought to determine the relative retrograde amnestic effects of electroconvulsive shock (ECS) stimulus intensity (dose) and number on strong memories in rats. We also sought to identify dose-dependent ceiling amnestic effects, if any. Adult rats (n = 144) were overtrained in a passive avoidance task using a step down apparatus. The rats were then randomized in a factorial design to receive one, two, or three once-daily bilateral ECS at 0-mC (sham ECS), 30-mC, 60-mC, 120-mC, or 180-mC doses. Recall of the pre-ECS training was assessed 1 day after the last ECS. Retrograde amnesia was observed only in rats that received 3 ECS; dose-dependent amnestic effects did not emerge. Higher stimulus intensity was associated with a small (13%) but significant increase in motor seizure duration, but only at the first ECS; stimulus intensity did not influence the attenuation of seizure duration across repeated occasions of ECS. With bilateral ECS, the number of ECSs administered is a more important variable than the ECS dose in weakening a strong, recently acquired, noxious memory; this finding may have important clinical implications. Higher stimulus intensity marginally increases motor seizure duration at the first ECS but does not influence the decrease in seizure duration across repeated ECSs.

Analysis of Dose at the Site of Second Tumor Formation After Radiotherapy to the Central Nervous System

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

Galloway, Thomas J.; University of Florida Proton Therapy Institute, Jacksonville, FL; Indelicato, Daniel J., E-mail: dindelicato@floridaproton.org

Purpose: Second tumors are an uncommon complication of multimodality treatment of childhood cancer. The present analysis attempted to correlate the dose received as a component of primary treatment and the site of the eventual development of a second tumor. Methods and Materials: We retrospectively identified 16 patients who had received radiotherapy to sites in the craniospinal axis and subsequently developed a second tumor. We compared the historical fields and port films of the primary treatment with the modern imaging of the second tumor locations. We classified the location of the second tumors as follows: in the boost field; marginal tomore » the boost field, but in a whole-brain field; in a whole-brain field; marginal to the whole brain/primary treatment field; and distant to the field. We divided the dose received into 3 broad categories: high dose (>45 Gy), moderate dose (20-36 Gy), and low dose (<20 Gy). Results: The most common location of the second tumor was in the whole brain field (57%) and in the moderate-dose range (81%). Conclusions: Our data contradict previous publications that suggested that most second tumors develop in tissues that receive a low radiation dose. Almost all the second tumors in our series occurred in tissue within a target volume in the cranium that had received a moderate dose (20-36 Gy). These findings suggest that a major decrease in the brain volume that receives a moderate radiation dose is the only way to substantially decrease the second tumor rate after central nervous system radiotherapy.« less

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.

Timing of two versus three doses of quadrivalent HPV vaccine and associated effectiveness against condyloma in Sweden: a nationwide cohort study

PubMed Central

F, Lamb; E, Herweijer; A, Ploner; I, Uhnoo; K, Sundström; P, Sparén; L, Arnheim-Dahlström

2017-01-01

Objective To assess incidence of condyloma after two doses of quadrivalent human papillomavirus (qHPV) vaccine, by time since first vaccine dose, in girls and women initiating vaccination before age 20 years. Design Register-based nationwide open cohort study. Setting Sweden. Participants Girls and women initiating qHPV vaccination before age 20 years between 2006 and 2012. The study cohort included 264 498 girls, of whom 72 042 had received two doses of qHPV vaccine and 185 456 had received all three doses. Main outcome measure Incidence rate ratios (IRRs) of condyloma estimated by time between first and second doses of qHPV in months (m) and age at vaccination, adjusted for attained age. Results For girls first vaccinated with two doses before the age of 17 years, the IRR of condyloma for 0–3 months between the first and second doses was 1.96 (95% CI 1.43 to 2.68) as compared with the standard three-dose schedule. The IRRs were 1.27 (95% CI 0.63 to 2.58) and 4.36 (95% CI 2.05 to 9.28) after receipt of two doses with 4–7 months and 8+ months between doses, respectively. For women first vaccinated after the age of 17 years, vaccination with two doses of qHPV vaccine and 0–3 months between doses was associated with an IRR of 2.12 (95% CI 1.62 to 2.77). For an interval of 4–7 months between doses, the IRR did not statistically significantly differ to the standard three-dose schedule (IRR=0.81, 95% CI 0.36 to 1.84). For women with 8+ months between dose 1 and dose 2 the IRR was 3.16 (95% CI 1.40 to 7.14). Conclusion A two-dose schedule for qHPV vaccine with 4–7 months between the first and second doses may be as effective against condyloma in girls and women initiating vaccination under 20 years as a three-dose schedule. Results from this nationwide study support immunogenicity data from clinical trials. PMID:28600369

Use of remifentanil to reduce propofol injection pain and the required propofol dose in upper digestive tract endoscopy diagnostic tests.

PubMed

Uliana, Gustavo Nadal; Tambara, Elizabeth Milla; Baretta, Giorgio Alfredo Pedroso

2015-01-01

The introduction of propofol (2,6-diisopropylphenol) as a sedative agent has transformed the area of sedation for endoscopic procedures. However, a major drawback of sedation with the use of propofol is its high incidence of injection pain. The most widely used technique in reducing propofol injection pain is through the association of other drugs. The aim of this study was to evaluate the effect of remifentanil-propofol combination on the incidence of propofol injection pain and its influence on the total dose of propofol required for sedation in upper digestive tract endoscopy (UDE) diagnostic tests. One hundred and five patients undergoing upper digestive tract endoscopy were evaluated and randomly divided into 3 groups of 35 patients each. The Control Group received propofol alone; Study-group 1 received remifentanil at a fixed dose of 0.2mg/kg combined with propofol; Study-group 2 received remifentanil at a fixed dose of 0.3mg/kg combined with propofol. The incidence of propofol injection pain and the total dose of propofol required for the test were evaluated. The sample was very similar regarding age, weight, height, sex, and physical status. Statistical analysis was performed according to the nature of the evaluated data. Student's t-test was used to compare the mean of age, weight, height (cm), and dose (mg/kg) variables between groups. The χ(2) test was used to compare sex, physical status, and propofol injection pain between groups. The significance level was α<0.05. There was significant statistical difference between the study groups and the control group regarding the parameters of propofol injection pain and total dose of propofol (mg/kg) used. However, there were no statistical differences between the two study groups for these parameters. We conclude that the use of remifentanil at doses of 0.2mg/kg and 0.3mg/kg was effective for reducing both the propofol injection pain and the total dose of propofol used. Copyright © 2015 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.

Leukemia risk associated with chronic external exposure to ionizing radiation in a French cohort of nuclear workers.

PubMed

Metz-Flamant, C; Samson, E; Caër-Lorho, S; Acker, A; Laurier, D

2012-11-01

Leukemia is one of the earliest cancer effects observed after acute exposure to relatively high doses of ionizing radiation. Leukemia mortality after external exposure at low doses and low-dose rates has been investigated at the French Atomic Energy Commission (CEA) and Nuclear Fuel Company (AREVA NC) after an additional follow-up of 10 years. The cohort included radiation-monitored workers employed for at least one year during 1950-1994 at CEA or AREVA NC and followed during 1968-2004. Association between external exposure and leukemia mortality was estimated with excess relative risk (ERR) models and time-dependent modifying factors were investigated with time windows. The cohort included 36,769 workers, followed for an average of 28 years, among whom 73 leukemia deaths occurred. Among the workers with a positive recorded dose, the mean cumulative external dose was 21.7 mSv. Results under a 2-year lag assumption suggested that the risk of leukemia (except chronic lymphatic leukemia) increased significantly by 8% per 10 mSv. The magnitude of the association for myeloid leukemia was larger. The higher ERR/Sv for doses received 2-14 years earlier suggest that time since exposure modifies the effect. The ERR/Sv also appeared higher for doses received at exposure rates ≥20 mSv per year. These results are consistent with those found in other studies of nuclear workers. However, confidence intervals are still wide. Further analyses should be conducted in pooled cohorts of nuclear workers.

Vaccination response to tetanus toxoid and 23-valent pneumococcal vaccines following administration of a single dose of abatacept: a randomized, open-label, parallel group study in healthy subjects

PubMed Central

Tay, Lee; Leon, Francisco; Vratsanos, George; Raymond, Ralph; Corbo, Michael

2007-01-01

The effect of abatacept, a selective T-cell co-stimulation modulator, on vaccination has not been previously investigated. In this open-label, single-dose, randomized, parallel-group, controlled study, the effect of a single 750 mg infusion of abatacept on the antibody response to the intramuscular tetanus toxoid vaccine (primarily a memory response to a T-cell-dependent peptide antigen) and the intramuscular 23-valent pneumococcal vaccine (a less T-cell-dependent response to a polysaccharide antigen) was measured in 80 normal healthy volunteers. Subjects were uniformly randomized to receive one of four treatments: Group A (control group), subjects received vaccines on day 1 only; Group B, subjects received vaccines 2 weeks before abatacept; Group C, subjects received vaccines 2 weeks after abatacept; and Group D, subjects received vaccines 8 weeks after abatacept. Anti-tetanus and anti-pneumococcal (Danish serotypes 2, 6B, 8, 9V, 14, 19F and 23F) antibody titers were measured 14 and 28 days after vaccination. While there were no statistically significant differences between the dosing groups, geometric mean titers following tetanus or pneumococcal vaccination were generally lower in subjects who were vaccinated 2 weeks after receiving abatacept, compared with control subjects. A positive response (defined as a twofold increase in antibody titer from baseline) to tetanus vaccination at 28 days was seen, however, in ≥ 60% of subjects across all treatment groups versus 75% of control subjects. Similarly, over 70% of abatacept-treated subjects versus all control subjects (100%) responded to at least three pneumococcal serotypes, and approximately 25–30% of abatacept-treated subjects versus 45% of control subjects responded to at least six serotypes. PMID:17425783

Comparison of platelet count recovery with use of vincristine and prednisone or prednisone alone for treatment for severe immune-mediated thrombocytopenia in dogs.

PubMed

Rozanski, Elizabeth A; Callan, Mary Beth; Hughes, Dez; Sanders, Nancy; Giger, Urs

2002-02-15

To evaluate the effect of prednisone alone, compared with a combination of prednisone and vincristine, on platelet counts in bleeding dogs with severe primary immune-mediated thrombocytopenia (IMT). Prospective case study. 24 dogs with severe primary IMT PROCEDURE: All dogs received immunosuppressive doses of prednisone (1.5 to 2 mg/kg [0.7 to 0.9 mg/lb] of body weight, PO, q 12 h). In addition, 12 dogs received a single dose of vincristine (0.02 mg/kg [0.01 mg/lb], IV). Platelet count, transfusion requirement, and outcome were monitored. A response was defined as an increase in platelet count to > or = 40,000/microl. Dogs in the prednisone group that failed to respond received 1 dose of vincristine on day 7. Dogs that received prednisone and vincristine had a significantly faster increase in platelet count to > or = 40,000 platelets/microl than dogs that received prednisone alone (mean +/- SD, 4.9 +/- 1.1 vs 6.8 +/- 4.5 days, respectively). A similarly rapid response was observed in dogs that received vincristine on day 7 after treatment with prednisone alone failed. Furthermore, duration of hospitalization was reduced in the vincristine group, compared with the prednisone group (5.4 +/- 0.3 vs 7.3 +/- 0.5 days, respectively). No adverse effects attributable to vincristine were observed in any dog. Administration of combined vincristine and prednisone is associated with more rapid increase in platelet numbers and shortened duration of hospitalization in dogs with IMT, compared with use of prednisone alone. Early use of vincristine seems warranted in dogs with severe primary IMT.

Process evaluation of a randomised controlled trial of a diabetes prevention intervention in Dutch primary health care: the SLIMMER study.

PubMed

van Dongen, Ellen Ji; Duijzer, Geerke; Jansen, Sophia C; Ter Beek, Josien; Huijg, Johanna M; Leerlooijer, Joanne N; Hiddink, Gerrit J; Feskens, Edith Jm; Haveman-Nies, Annemien

2016-11-01

To investigate (i) how the SLIMMER intervention was delivered and received in Dutch primary health care and (ii) how this could explain intervention effectiveness. A randomised controlled trial was conducted and subjects were randomly allocated to the intervention (10-month combined dietary and physical activity intervention) or the control group. A process evaluation including quantitative and qualitative methods was conducted. Data on process indicators (recruitment, reach, dose received, acceptability, implementation integrity and applicability) were collected via semi-structured interviews with health-care professionals (n 45) and intervention participant questionnaires (n 155). SLIMMER was implemented in Dutch primary health care in twenty-five general practices, eleven dietitians, nine physiotherapist practices and fifteen sports clubs. Subjects at increased risk of developing type 2 diabetes were included. It was possible to recruit the intended high-risk population (response rate 54 %) and the SLIMMER intervention was very well received by both participants and health-care professionals (mean acceptability rating of 82 and 80, respectively). The intervention programme was to a large extent implemented as planned and was applicable in Dutch primary health care. Higher dose received and participant acceptability were related to improved health outcomes and dietary behaviour, but not to physical activity behaviour. The present study showed that it is feasible to implement a diabetes prevention intervention in Dutch primary health care. Higher dose received and participant acceptability were associated with improved health outcomes and dietary behaviour. Using an extensive process evaluation plan to gain insight into how an intervention is delivered and received is a valuable way of identifying intervention components that contribute to implementation integrity and effective prevention of type 2 diabetes in primary health care.

Reduction in radiation-induced brain injury by use of pentobarbital or lidocaine protection

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

Oldfield, E.H.; Friedman, R.; Kinsella, T.

1990-05-01

To determine if barbiturates would protect brain at high doses of radiation, survival rates in rats that received whole-brain x-irradiation during pentobarbital- or lidocaine-induced anesthesia were compared with those of control animals that received no medication and of animals anesthetized with ketamine. The animals were shielded so that respiratory and digestive tissues would not be damaged by the radiation. Survival rates in rats that received whole-brain irradiation as a single 7500-rad dose under pentobarbital- or lidocaine-induced anesthesia was increased from between from 0% and 20% to between 45% and 69% over the 40 days of observation compared with the othermore » two groups (p less than 0.007). Ketamine anesthesia provided no protection. There were no notable differential effects upon non-neural tissues, suggesting that pentobarbital afforded protection through modulation of ambient neural activity during radiation exposure. Neural suppression during high-dose cranial irradiation protects brain from acute and early delayed radiation injury. Further development and application of this knowledge may reduce the incidence of radiation toxicity of the central nervous system (CNS) and may permit the safe use of otherwise unsafe doses of radiation in patients with CNS neoplasms.« less

Effective doses in children: association with common complex imaging techniques used during interventional radiology procedures.

PubMed

Lai, Priscilla; McNeil, Sarah M; Gordon, Christopher L; Connolly, Bairbre L

2014-12-01

The purpose of this study was to determine the range of effective doses associated with imaging techniques used during interventional radiology procedures on children. A pediatric phantom set (1, 5, and 10 years) coupled with high-sensitivity metal oxide semiconductor field effect transistor (MOSFET) dosimeters was used to calculate effective doses. Twenty MOSFETs were inserted into each phantom at radiosensitive organ locations. The phantoms were exposed to mock head, chest, and abdominal interventional radiology procedures performed with different geometries and magnifications. Fluoroscopy, digital subtraction angiography (DSA), and spin angiography were simulated on each phantom. Road mapping was conducted only on the 5-year-old phantom. International Commission on Radiological Protection publication 103 tissue weights were applied to the organ doses recorded with the MOSFETs to determine effective dose. For easy application to clinical cases, doses were normalized per minute of fluoroscopy and per 10 frames of DSA or spin angiography. Effective doses from DSA, angiography, and fluoroscopy were higher for younger ages because of magnification use and were largest for abdominal procedures. DSA of the head, chest, and abdomen (normalized per 10 frames) imparted doses 2-3 times as high as corresponding doses per minute of fluoroscopy while all other factors remained unchanged (age, projection, collimation, magnification). Three to five frames of DSA imparted an effective dose equal to doses from 1 minute of fluoroscopy. Doses from spin angiography were almost one-half the doses received from an equivalent number of frames of DSA. Patient effective doses during interventional procedures vary substantially depending on procedure type but tend to be higher because of magnification use in younger children and higher in the abdomen.

Evaluation of Emergency Department Management of Opioid-Tolerant Cancer Patients With Acute Pain.

PubMed

Patel, Pina M; Goodman, Lauren F; Knepel, Sheri A; Miller, Charles C; Azimi, Asma; Phillips, Gary; Gustin, Jillian L; Hartman, Amber

2017-10-01

There are no previously published studies examining opioid doses administered to opioid-tolerant cancer patients during emergency department (ED) encounters. To determine if opioid-tolerant cancer patients presenting with acute pain exacerbations receive adequate initial doses of as needed (PRN) opioids during ED encounters based on home oral morphine equivalent (OME) use. We performed a retrospective cohort study of opioid-tolerant cancer patients who received opioids in our ED over a two-year period. The percentage of patients who received an adequate initial dose of PRN opioid (defined as ≥10% of total 24-hour ambulatory OME) was evaluated. Logistic regression was used to establish the relationship between 24-hour ambulatory OME and initial ED OME to assess whether higher home usage was associated with higher likelihood of being undertreated. Out of 216 patients, 61.1% of patients received an adequate initial PRN dose of opioids in the ED. Of patients taking <200 OMEs per day at home, 77.4% received an adequate initial dose; however, only 3.2% of patients taking >400 OMEs per day at home received an adequate dose. Patients with ambulatory 24-hour OME greater than 400 had 99% lower odds of receiving an adequate initial dose of PRN opioid in the ED compared to patients with ambulatory 24-hour OME less than 100 (OR <0.01, CI 0.00-0.02, P < 0.001). Patients with daily home use less than 200 OMEs generally received adequate initial PRN opioid doses during their ED visit. However, patients with higher home opioid usage were at increased likelihood of being undertreated. Copyright © 2017 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

Cumulative doses analysis in young trauma patients: a single-centre experience.

PubMed

Salerno, Sergio; Marrale, Maurizio; Geraci, Claudia; Caruso, Giuseppe; Lo Re, Giuseppe; Lo Casto, Antonio; Midiri, Massimo

2016-02-01

Multidetector computed tomography (MDCT) represents the main source of radiation exposure in trauma patients. The radiation exposure of young patients is a matter of considerable medical concern due to possible long-term effects. Multiple MDCT studies have been observed in the young trauma population with an increase in radiation exposure. We have identified 249 young adult patients (178 men and 71 women; age range 14-40 years) who had received more than one MDCT study between June 2010 and June 2014. According to the International Commission on Radiological Protection publication, we have calculated the cumulative organ dose tissue-weighting factors by using CT-EXPO software(®). We have observed a mean cumulative dose of about 27 mSv (range from 3 to 297 mSv). The distribution analysis is characterised by low effective dose, below 20 mSv, in the majority of the patients. However, in 29 patients, the effective dose was found to be higher than 20 mSv. Dose distribution for the various organs analysed (breasts, ovaries, testicles, heart and eye lenses) shows an intense peak for lower doses, but in some cases high doses were recorded. Even though cumulative doses may have long-term effects, which are still under debate, high doses are observed in this specific group of young patients.

Abdominal Pediatric Cancer Surveillance using Serial CT: Evaluation of Organ Absorbed Dose and Effective Dose

PubMed Central

Lam, Diana; Wootton-Gorges, Sandra L.; McGahan, John P.; Stern, Robin; Boone, John M.

2012-01-01

Computed tomography (CT) is used extensively in cancer diagnosis, staging, evaluation of response to treatment, and in active surveillance for cancer reoccurrence. A review of CT technology is provided, at a level of detail appropriate for a busy clinician to review. The basis of x-ray CT dosimetry is also discussed, and concepts of absorbed dose and effective dose are distinguished. Absorbed dose is a physical quantity (measured in milliGray) equal to the x-ray energy deposited in a mass of tissue, whereas effective dose utilizes an organ-specific weighting method which converts organ doses to effective dose measured in milliSieverts. The organ weighting values carry with them a measure of radiation risk, and so effective dose (in mSv) is not a physical dose metric but rather is one that conveys radiation risk. The use of CT in a cancer surveillance protocol was used as an example of a pediatric patient who had kidney cancer, with surgery and radiation therapy. The active use of CT for cancer surveillance along with diagnostic CT scans led to a total of 50 CT scans performed on this child in a 7 year period. It was estimated that the patient received an average organ dose of 431 mGy from these CT scans. By comparison, the radiation therapy was performed and delivered 50.4 Gy to the patient’s abdomen. Thus, the total dose from CT represented only 0.8% of the patients radiation dose. PMID:21362521

Choleretic activity of Gentiana lutea ssp. symphyandra in rats.

PubMed

Oztürk, N; Herekman-Demir, T; Oztürk, Y; Bozan, B; Başer, K H

1998-08-01

Effects of an ethanolic extract prepared from G. lutea ssp. symphyandra roots on the bile production and liver in rats were investigated. Bile flows of rats which were treated by a single i.p. dose of CCl(4) 24 h prior to experiments were measured after the cannulation of bile duct under urethane anaesthesia. After an equilibration period of 1 h, the lyophilized extract were administered intraduodenally (500 mg/kg i.p.), while control animals received physiological saline only. To monitor the effect of multiple dose therapy, rats received the same dose of G. lutea ssp. symphyandra extract for 3 days (2 days prior to CCl(4) administration) and their bile flows were measured after the cannulation. In all groups, bile samples were collected for 3 h with 15 min intervals. After the completion of bile flow experiment, rat livers were removed and put in neutral formaldehyde solution (10%) for the histological examination. According to results obtained, multiple dose treatment of rats with the plant extract normalized the decreased bile flow due CCl(4), whereas single dose therapy was ineffective on the impaired bile flow. These data indicate that the extract prepared from Gentiana lutea ssp. symphyandra roots has a hepatoprotective activity. Copyright © 1998 Gustav Fischer Verlag. Published by Elsevier GmbH.. All rights reserved.

Measurement of radiation exposure in relatives of thyroid cancer patients treated with (131)I.

PubMed

Ramírez-Garzón, Y T; Ávila, O; Medina, L A; Gamboa-deBuen, I; Rodríguez-Laguna, A; Buenfil, A E; Ruíz-Trejo, C; Estrada, E; Brandan, M E

2014-11-01

This work evaluates the radiological risk that patients treated with I for differentiated thyroid cancer could present to relatives and occupationally exposed workers. Recently, the International Atomic Energy Agency issued document K9010241, which recommends that patient discharge from the hospital must be based on the particular status of each patient. This work measures effective dose received by caregivers of patients treated with I at the Instituto Nacional de Cancerología, Mexico City. Thermoluminescent dosimeters were carried during a 15-d period by 40 family caregivers after patient release from hospital. Relatives were classified into two groups, ambulatory and hospitalized, according to the release mode of the patient, and three categories according to the individual patient home and transport facilities. Categories A, B, and C were defined going from most to least adequate concerning public exposure risk. Measurements were performed for 20 family caregivers in each group. The effective dose received by all caregivers participating in this study was found to be less than 5 mSv, the recommended limit per event for caregivers suggested by ICRP 103. In addition, 70 and 90% of ambulatory and hospitalized groups, respectively, received doses lower than 1 mSv. Caregivers belonging to category C, with home situations that are not appropriate for immediate release, received the highest average doses; i.e., 2.2 ± 1.3 and 3.1 ± 1.0 mSv for hospitalized and ambulatory patients, respectively. Results of this work have shown that the proper implementation of radiation protection instructions for relatives and patients can reduce significantly the risk that differentiated thyroid cancer patients treated with I can represent for surrounding individuals. The results also stress the relevance of the patient's particular lifestyle and transport conditions as the prevailing factors related to the dose received by the caregiver. Therefore, the patient's status should be the criterion used to decide his/her release modality. This work provides support to recommend the implementation of the "patient specific release criteria" in accordance with ICRP 94, IAEA Safety Report No. 63, and IAE document K9010241 A for patients treated with radiopharmaceuticals.

10 CFR 20.1301 - Dose limits for individual members of the public.

Code of Federal Regulations, 2014 CFR

2014-01-01

... Section 20.1301 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Radiation..., exclusive of the dose contributions from background radiation, from any medical administration the....75, to receive a radiation dose greater than 0.1 rem (1 mSv) if— (1) The radiation dose received does...

10 CFR 20.1301 - Dose limits for individual members of the public.

Code of Federal Regulations, 2010 CFR

2010-01-01

... Section 20.1301 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Radiation..., exclusive of the dose contributions from background radiation, from any medical administration the....75, to receive a radiation dose greater than 0.1 rem (1 mSv) if— (1) The radiation dose received does...

10 CFR 20.1301 - Dose limits for individual members of the public.

Code of Federal Regulations, 2013 CFR

2013-01-01

... Section 20.1301 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Radiation..., exclusive of the dose contributions from background radiation, from any medical administration the....75, to receive a radiation dose greater than 0.1 rem (1 mSv) if— (1) The radiation dose received does...

10 CFR 20.1301 - Dose limits for individual members of the public.

Code of Federal Regulations, 2011 CFR

2011-01-01

... Section 20.1301 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Radiation..., exclusive of the dose contributions from background radiation, from any medical administration the....75, to receive a radiation dose greater than 0.1 rem (1 mSv) if— (1) The radiation dose received does...

10 CFR 20.1301 - Dose limits for individual members of the public.

Code of Federal Regulations, 2012 CFR

2012-01-01

... Section 20.1301 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Radiation..., exclusive of the dose contributions from background radiation, from any medical administration the....75, to receive a radiation dose greater than 0.1 rem (1 mSv) if— (1) The radiation dose received does...

Efficacy and Safety of Fixed-Dose Perindopril Arginine/Amlodipine in Hypertensive Patients Not Adequately Controlled with Amlodipine 5 mg or Perindopril tert-Butylamine 4 mg Monotherapy.

PubMed

Hu, Dayi; Sun, Yihong; Liao, Yuhua; Huang, Jing; Zhao, Ruiping; Yang, Kan

2016-01-01

To assess the blood pressure-lowering efficacy and tolerability of perindopril/amlodipine fixed-dose combinations in Chinese patients with mild-to-moderate essential hypertension not adequately controlled with monotherapy alone. In 2 separate double-blind studies, patients received a 4-week run-in monotherapy of amlodipine 5 mg or perindopril 4 mg, respectively. Those whose blood pressure was uncontrolled were then randomized to receive the fixed-dose combination of perindopril 5 mg/amlodipine 5 mg (Per/Amlo group) or remain on the monotherapy for 8 weeks. Patients who were uncontrolled at the week 8 (W8) visit were up-titrated for the Per/Amlo combination, or received additional treatment if on monotherapy, for a further 4 weeks. The main efficacy assessment was at 8 weeks. After 8 weeks, systolic blood pressure (SBP; primary criterion) was statistically significantly lower in the Per/Amlo group (vs. Amlo 5 mg, p = 0.0095; vs. Per 4 mg, p < 0.0001). Uncontrolled patients at W8 who received an up-titration of the Per/Amlo combination showed a further SBP reduction. These changes were mirrored by reassuring reductions in diastolic blood pressure. The fixed-dose combinations were well tolerated. Single-pill combinations of perindopril and amlodipine provide hypertensive patients with a convenient and effective method of reducing blood pressure. © 2016 S. Karger AG, Basel.

Furosemide Prescription During the Dry State Is a Predictor of Long-Term Survival of Stable, Optimally Medicated Patients With Systolic Heart Failure.

PubMed

Sargento, Luis; Simões, Andre Vicente; Longo, Susana; Lousada, Nuno; Reis, Roberto Palma Dos

2017-05-01

Furosemide is associated with poor prognosis in patients with heart failure and reduced ejection fraction (HFrEF). To evaluate the association between daily furosemide dose prescribed during the dry state and long-term survival in stable, optimally medicated outpatients with HFrEF. Two hundred sixty-six consecutive outpatients with left ventricular ejection fraction <40%, clinically stable in the dry state and on optimal heart failure therapy, were followed up for 3 years in a heart failure unit. The end point was all-cause death. There were no changes in New York Heart Association class and therapeutics, including diuretics, and no decompensation or hospitalization during 6 months. Furosemide doses were categorized as low or none (0-40 mg/d), intermediate (41-80 mg/d), and high (>80 mg). Cox regression was adjusted for significant confounders. The 3-year mortality rate was 33.8%. Mean dose of furosemide was 57.3 ± 21.4 mg/d. A total of 47.6% of patients received the low dose, 42.1% the intermediate dose, and 2.3% the high dose. Receiver operating characteristics for death associated with furosemide dose showed an area under the curve of 0.74 (95% confidence interval [CI]: 0.68-0.79; P < .001), and the best cutoff was >40 mg/d. An increasing daily dose of furosemide was associated with worse prognosis. Those receiving the intermediate dose (hazard ratio [HR] = 4.1; 95% CI: 2.57-6.64; P < .001) or high dose (HR = 19.8; 95% CI: 7.9-49.6; P < .001) had a higher risk of mortality compared to those receiving a low dose. Patients receiving >40 mg/d, in a propensity score-matched cohort, had a greater risk of mortality than those receiving a low dose (HR = 4.02; 95% CI: 1.8-8.8; P = .001) and those not receiving furosemide (HR = 3.9; 95% CI: 0.07-14.2; P = .039). Furosemide administration during the dry state in stable, optimally medicated outpatients with HFrEF is unfavorably associated with long-term survival. The threshold dose was 40 mg/d.

Immune response in pigs treated with therapeutic doses of enrofloxacin at the time of vaccination against Aujeszky's disease.

PubMed

Pomorska-Mól, Małgorzata; Czyżewska-Dors, Ewelina; Kwit, Krzysztof; Rachubik, Jarosław; Lipowski, Andrzej; Pejsak, Zygmunt

2015-06-01

The effect of treatment with enrofloxacin was studied on the postvaccinal immune response in pigs. Forty pigs were used (control not vaccinated (C), control vaccinated (CV), vaccinated, received enrofloxacin (ENRO)). From day -1 to day 3 pigs from ENRO group received enrofloxacin at the recommended dose. Pigs from ENRO and CV groups were vaccinated twice against Aujeszky's disease virus (ADV). There was a significant delay in the production of humoral response of enrofloxacin dosed pigs when compared with CV group. Moreover, in ENRO group the significant decrease in IFN-γ production and significantly lower values of stimulation index after ADV restimulation was noted, as compared with CV group. The secretion of IL-6, IL-10 and TNF-α by PBMC after recall stimulation was also affected in ENRO group. The results indicate that enrofloxacin, in addition to its antimicrobial properties, possess significant immunomodulatory effects and may alter the immune response to vaccines. Copyright © 2015 Elsevier Ltd. All rights reserved.

Evaluation of genotype-guided acenocoumarol dosing algorithms in Russian patients.

PubMed

Sychev, Dmitriy Alexeyevich; Rozhkov, Aleksandr Vladimirovich; Ananichuk, Anna Viktorovna; Kazakov, Ruslan Evgenyevich

2017-05-24

Acenocoumarol dose is normally determined via step-by-step adjustment process based on International Normalized Ratio (INR) measurements. During this time, the risk of adverse reactions is especially high. Several genotype-based acenocoumarol dosing algorithms have been created to predict ideal doses at the start of anticoagulant therapy. Nine dosing algorithms were selected through a literature search. These were evaluated using a cohort of 63 patients with atrial fibrillation receiving acenocoumarol therapy. None of the existing algorithms could predict the ideal acenocoumarol dose in 50% of Russian patients. The Wolkanin-Bartnik algorithtm based on European population was the best-performing one with the highest correlation values (r=0.397), mean absolute error (MAE) 0.82 (±0.61). EU-PACT also managed to give an estimate within the ideal range in 43% of the cases. The two least accurate results were yielded by the Indian population-based algorithms. Among patients receiving amiodarone, algorithms by Schie and Tong proved to be the most effective with the MAE of 0.48±0.42 mg/day and 0.56±0.31 mg/day, respectively. Patient ethnicity and amiodarone intake are factors that must be considered when building future algorithms. Further research is required to find the perfect dosing formula of acenocoumarol maintenance doses in Russian patients.

Immunogenicity of 2 doses of HPV vaccine in younger adolescents vs 3 doses in young women: a randomized clinical trial.

PubMed

Dobson, Simon R M; McNeil, Shelly; Dionne, Marc; Dawar, Meena; Ogilvie, Gina; Krajden, Mel; Sauvageau, Chantal; Scheifele, David W; Kollmann, Tobias R; Halperin, Scott A; Langley, Joanne M; Bettinger, Julie A; Singer, Joel; Money, Deborah; Miller, Dianne; Naus, Monika; Marra, Fawziah; Young, Eric

2013-05-01

Global use of human papillomavirus (HPV) vaccines to prevent cervical cancer is impeded by cost. A 2-dose schedule for girls may be possible. To determine whether mean antibody levels to HPV-16 and HPV-18 among girls receiving 2 doses was noninferior to women receiving 3 doses. Randomized, phase 3, postlicensure, multicenter, age-stratified, noninferiority immunogenicity study of 830 Canadian females from August 2007 through February 2011. Follow-up blood samples were provided by 675 participants (81%). Girls (9-13 years) were randomized 1:1 to receive 3 doses of quadrivalent HPV vaccine at 0, 2, and 6 months (n = 261) or 2 doses at 0 and 6 months (n = 259). Young women (16-26 years) received 3 doses at 0, 2, and 6 months (n = 310). Antibody levels were measured at 0, 7, 18, 24, and 36 months. Primary outcome was noninferiority (95% CI, lower bound >0.5) of geometric mean titer (GMT) ratios for HPV-16 and HPV-18 for girls (2 doses) compared with young women (3 doses) 1 month after last dose. Secondary outcomes were noninferiority of GMT ratios of girls receiving 2 vs 3 doses of vaccine; and durability of noninferiority to 36 months. The GMT ratios were noninferior for girls (2 doses) to women (3 doses): 2.07 (95% CI, 1.62-2.65) for HPV-16 and 1.76 (95% CI, 1.41-2.19) for HPV-18. Girls (3 doses) had GMT responses 1 month after last vaccination for HPV-16 of 7736 milli-Merck units per mL (mMU/mL) (95% CI, 6651-8999) and HPV-18 of 1730 mMU/mL (95% CI, 1512-1980). The GMT ratios were noninferior for girls (2 doses) to girls (3 doses): 0.95 (95% CI, 0.73-1.23) for HPV-16 and 0.68 (95% CI, 0.54-0.85) for HPV-18. The GMT ratios for girls (2 doses) to women (3 doses) remained noninferior for all genotypes to 36 months. Antibody responses in girls were noninferior after 2 doses vs 3 doses for all 4 vaccine genotypes at month 7, but not for HPV-18 by month 24 or HPV-6 by month 36. Among girls who received 2 doses of HPV vaccine 6 months apart, responses to HPV-16 and HPV-18 one month after the last dose were noninferior to those among young women who received 3 doses of the vaccine within 6 months. Because of the loss of noninferiority to some genotypes at 24 to 36 months in girls given 2 doses vs 3 doses, more data on the duration of protection are needed before reduced-dose schedules can be recommended. clinicaltrials.gov Identifier: NCT00501137.

Preventive Effect of Cashew-Derived Protein Hydrolysate with High Fiber on Cerebral Ischemia

PubMed Central

Thukham-mee, Wipawee; Wannanon, Panakaporn; Tiamkao, Somsak

2017-01-01

This study aimed to determine the protective effect of cashew nut-derived protein hydrolysate with high dietary fiber (AO) in cerebral ischemic rats induced by the occlusion of right middle cerebral artery (Rt.MCAO). Acute toxicity was determined and data showed that LD50 of AO > 5000 mg/kg BW. To determine the cerebroprotective effect of AO, male Wistar rats were orally given AO at doses of 2, 10, and 50 mg/kg for 14 days and subjected to Rt.MCAO. Brain infarction volume, neurological score, spatial memory, serum lipid profiles, and C-reactive protein together with the brain oxidative stress status were assessed. All doses of AO significantly decreased brain infarction in cortex, hippocampus, and striatum together with the decreased oxidative stress status. The improvement of spatial memory and serum C-reactive protein were also observed in MCAO rats which received AO at all doses. In addition, the decreased serum cholesterol, TG, and LDL but increased HDL were observed in MCAO rats which received high dose of AO. Taken all together, AO is the potential protectant against cerebral ischemia. The improvement of oxidative stress, inflammation, and dyslipidemia might play roles in the actions. However, further researches are required to understand the precise underlying mechanism. PMID:29457029

A randomized, double-blinded, placebo-controlled phase II trial of recombinant human leukemia inhibitory factor (rhuLIF, emfilermin, AM424) to prevent chemotherapy-induced peripheral neuropathy.

PubMed

Davis, Ian D; Kiers, Lynette; MacGregor, Lachlan; Quinn, Michael; Arezzo, Joseph; Green, Michael; Rosenthal, Mark; Chia, Michael; Michael, Michael; Bartley, Peter; Harrison, Leonie; Daly, Michael

2005-03-01

To determine whether recombinant human leukemia inhibitory factor (rhuLIF, AM424, emfilermin) can prevent or ameliorate the development of chemotherapy-induced peripheral neuropathy (CIPN) after treatment with carboplatin (AUC 6) and paclitaxel (175 mg/m(2) over 3 hours). Randomized double-blind placebo-controlled phase II clinical trial. Eligible patients had solid tumors for which treatment with carboplatin/paclitaxel was appropriate. The primary end point was a standardized composite peripheral nerve electrophysiology (CPNE) score, based on nerve velocities and amplitudes, measured at baseline and after four cycles of chemotherapy. Secondary efficacy end points included CPNE score at last cycle and at exit evaluation, vibration perception threshold, H-reflex latency, symptom scores, and quantitative assessment of neurologic signs. Study drug was given s.c. daily for 7 days starting the day before chemotherapy. Patients were randomized to receive low-dose rhuLIF (2 microg/kg), high-dose rhuLIF (4 microg/kg), or placebo. Patients (n = 117) were randomized across seven neurology test centers. Thirty-six patients received low dose rhuLIF (2 microg/kg), 39 received high dose rhuLIF (4 microg/kg) and 42 received placebo. rhuLIF was well tolerated with 95% compliance and no adverse effects on quality of life. No differences between groups in CPNE or any of the individual neurologic testing variables were observed between baseline and cycle 4 or by the secondary efficacy variables. rhuLIF is not effective in preventing CIPN caused by carboplatin and paclitaxel. CPNE is a reliable and valid tool that was sensitive to the onset and progression of CIPN.

Patterns of zolpidem use among Iraq and Afghanistan veterans: A retrospective cohort analysis.

PubMed

Shayegani, Ramona; Song, Kangwon; Amuan, Megan E; Jaramillo, Carlos A; Eapen, Blessen C; Pugh, Mary Jo

2018-01-01

Although concern exists regarding the adverse effects and rate of zolpidem use, especially long-term use, limited information is available concerning patterns of zolpidem use. To examine the prevalence and correlates of zolpidem exposure in Iraq and Afghanistan Veterans (IAVs). A retrospective cohort study of zolpidem prescriptions was performed with National Veterans Health Administration (VHA) data. We gathered national VA inpatient, outpatient, and pharmacy data files for IAV's who received VA care between fiscal years (FY) 2013 and 2014. The VA pharmacy database was used to identify the prevalence of long term (>30 days), high-dose zolpidem exposure (>10mg immediate-release; >12.5mg extended-release) and other medications received in FY14. Baseline characteristics (demographics, diagnoses) were identified in FY13. Bivariate and multivariable analyses were used to examine the demographic, clinical, and medication correlates of zolpidem use. Of 493,683 IAVs who received VHA care in FY 2013 and 2014, 7.6% (n = 37,422) were prescribed zolpidem in FY 2014. Women had lower odds of high-dose zolpidem exposure than men. The majority (77.3%) of IAVs who received zolpidem prescriptions had long-term use with an average days' supply of 189.3 days and a minority (0.9%) had high-dose exposure. In multivariable analyses, factors associated with long-term zolpidem exposure included age greater than 29 years old, PTSD, insomnia, Selim Index, physical 2-3 conditions, opioids, antidepressants, benzodiazepines, atypical antipsychotics, and stimulants. High dose exposure was associated with PTSD, depression, substance use disorder, insomnia, benzodiazepines, atypical antipsychotics, and stimulant prescriptions. The current practices of insomnia pharmacotherapy in IAVs fall short of the clinical guidelines and may reflect high-risk zolpidem prescribing practices that put Iraq and Afghanistan Veterans at risk for adverse effects of zolpidem and poor health outcomes.

Immediate breast reconstruction with anatomical implants following mastectomy: The radiation perspective

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

Ben-David, Merav, E-mail: Merav.ben-david@sheba.health.gov.il; Sackler School of Medicine, Tel Aviv University, Tel Aviv; Granot, Hila

2016-07-01

Immediate implant-based breast reconstruction followed by postmastectomy radiation therapy (PMRT) is controversial because of the risk of compromised treatment plans and concerns regarding cosmetic outcomes. We evaluated the effects of immediate direct-to-implant breast reconstruction with anatomical implants on the quality of PMRT delivered by 3-dimensional conformal radiotherapy (3D-CRT). In this retrospective, single-institution study, patients who had undergone reconstruction with direct anatomic implant, performed by a single surgeon, received 3D-CRT between 2008 and 2013. For each patient, 2 plans (including or excluding internal mammary nodes [IMN]) were created and calculated. The primary end point was the dose distribution among reconstructed breasts,more » heart, lungs, and IMNs, and between right and left breasts. Of 29 consecutive patients, 11 received right-sided and 18 received left-sided PMRT to a total dose of 50 Gy. For plans excluding IMN coverage, mean D{sub mean} for right and left reconstructed breasts was 49.09 Gy (98.2% of the prescribed dose) and 48.51 Gy (97.0%), respectively. For plans including IMNs, mean D{sub mean} was 49.15 Gy (98.3%) for right and 48.46 Gy (96.9%) for left reconstructed breasts; the mean IMN D{sub mean} was 47.27 Gy (right) and 47.89 Gy (left). Heart D{sub mean} was below 1.56 Gy for all plans. Mean total lung volume receiving a dose of ≥ 20 Gy was 13.80% to 19.47%. PMRT can be delivered effectively and safely by 3D-CRT after direct-to-implant breast reconstruction with anatomical implants, even if patients require IMN treatment.« less

Combined extracts of Urtica dioica and Pygeum africanum in the treatment of benign prostatic hyperplasia: double-blind comparison of two doses.

PubMed

Krzeski, T; Kazón, M; Borkowski, A; Witeska, A; Kuczera, J

1993-01-01

The 134 patients (aged 53 to 84 years) with symptoms of benign prostatic hyperplasia were drawn from two medical centers in Warsaw. The patients were randomly assigned to receive two capsules of the standard dose of an urtica/pygeum preparation (300 mg of Urtica dioica root extract combined with 25 mg of Pygeum africanum bark extract) or two capsules containing half the standard dose twice daily for 8 weeks. After 28 days' treatment, urine flow, residual urine, and nycturia were significantly reduced in both treatment groups. After 56 days' treatment, further significant decreases were found in residual urine (half-dose group) and in nycturia (both groups). There were no between-group differences in these measures of efficacy. Five patients reported adverse effects of treatment; treatment was not discontinued in any patient because of side effects. It is concluded that half doses of the urtica/pygeum extract are as safe and effective as the recommended full doses.

Safety and immunogenicity of ricin vaccine, RVEc™, in a Phase 1 clinical trial.

PubMed

Pittman, Phillip R; Reisler, Ronald B; Lindsey, Changhong Y; Güereña, Fernando; Rivard, Robert; Clizbe, Denise P; Chambers, Matthew; Norris, Sarah; Smith, Leonard A

2015-12-16

Ricin is a potent toxin and potential bioterrorism weapon for which no specific licensed countermeasures are available. We report the safety and immunogenicity of the ricin vaccine RVEc™ in a Phase 1 (N=30) multiple-dose, open-label, non-placebo-controlled, dose-escalating (20, 50, and 100μg), single-center study. Each subject in the 20- and 50-μg dose groups (n=10 for each group) received three injections at 4-week intervals and was observed carefully for untoward effects of the vaccine; blood was drawn at predetermined intervals after each dose for up to 1 year. RVEc™ was safe and well tolerated at the 20- and 50-μg doses. The most common adverse events were pain at the injection site and headache. Of the 10 subjects who received a single 100-μg dose, two developed elevated creatine phosphokinase levels, which resolved without sequelae. No additional doses were administered to subjects in the 100-μg group. Immunogenicity of the vaccine was evaluated by measuring antibody response using the well standardized enzyme-linked immunosorbent assay (ELISA) and toxin neutralization assay (TNA). Of the subjects in the 20- and 50-μg dose groups, 100% achieved ELISA anti-ricin IgG titers of 1:500 to 1:121,500 and 50% produced neutralizing anti-ricin antibodies measurable by TNA. Four subjects in the 50-μg group received a single booster dose of RVEc™ 20-21 months after the initial dose. The single booster was safe and well tolerated, resulting in no serious adverse events, and significantly enhanced immunogenicity of the vaccine in human subjects. Each booster recipient developed a robust anamnestic response with ELISA anti-ricin IgG titers of 1:13,500 to 1:121,500 and neutralizing antibody titers of 1:400 to 1:3200. Future studies will attempt to optimize dose, scheduling, and route of administration. This study is registered at clinicaltrials.gov (NCT01317667 and NCT01846104). Published by Elsevier Ltd.

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.

The pharmacokinetics of colistin in patients with cystic fibrosis.

PubMed

Reed, M D; Stern, R C; O'Riordan, M A; Blumer, J L

2001-06-01

The safety and pharmacokinetics of colistin were determined after first dose (n = 30) and again under steady-state conditions (n = 27) in 31 patients with cystic fibrosis receiving the drug as a component of their treatment for an acute pulmonary exacerbation of their disease. Patients ranged in age from 14 to 53 years and received colistin for 6 to 35 days. Each patient was started on colistin 5 to 7 mg/kg/day administered intravenously in three equally divided doses. Elimination half-life (t1/2), mean residence time (MRT), steady-state volume of distribution (Vdss), total body clearance (Cl), and renal clearance (Clr) after first-dose administration averaged 3.4 hours, 4.4 hours, 0.09 l/kg, and 0.35 and 0.24 ml/min/kg, respectively. No differences in colistin disposition characteristics between first-dose and steady-state evaluations were observed. Sputum sampling was incomplete and confounded by previous aerosol administration but revealed colistin concentrations that markedly exceeded observed plasma concentrations. Twenty-one patients experienced one or more side effects attributed to colistin administration. The most common reactions involved reversible neurologic manifestations, including oral and perioral paresthesias (n = 16), headache (n = 5), and lower limb weakness (n = 5). All of these apparent colistin-induced neurologic adverse effects, though bothersome, were benign and reversible. Intermittent proteinuria was observed on urinalysis in 14 patients, and 1 patient developed reversible, colistin-induced nephrotoxicity. No relationship between the occurrence of any colistin-associated adverse effect and plasma colistin concentration or colistin pharmacokinetic parameter estimate was observed. These data provide no basis for routine monitoring of colistin plasma concentrations to guide dosing for patient safety and suggest slow upward dose titration to minimize the incidence and severity of associated side effects.

Effect of two prophylactic bolus vitamin D dosing regimens (1000 IU/day vs. 400 IU/day) on bone mineral content in new-onset and infrequently-relapsing nephrotic syndrome: a randomised clinical trial.

PubMed

Muske, Sravani; Krishnamurthy, Sriram; Kamalanathan, Sadish Kumar; Rajappa, Medha; Harichandrakumar, K T; Sivamurukan, Palanisamy

2018-02-01

To examine the efficacy of two vitamin D dosages (1000 vs. 400 IU/day) for osteoprotection in children with new-onset and infrequently-relapsing nephrotic syndrome (IFRNS) receiving corticosteroids. This parallel-group, open label, randomised clinical trial enrolled 92 children with new-onset nephrotic syndrome (NS) (n = 28) or IFRNS (n = 64) to receive 1000 IU/day (Group A, n = 46) or 400 IU/day (Group B, n = 46) vitamin D (administered as a single bolus initial supplemental dose) by block randomisation in a 1:1 allocation ratio. In Group A, vitamin D (cholecalciferol in a Calcirol® sachet) was administered in a single stat dose of 84,000 IU on Day 1 of steroid therapy (for new-onset NS), calculated for a period of 12 weeks@1000 IU/day) and 42,000 IU on Day 1 of steroid therapy (for IFRNS, calculated for a period of 6 weeks@1000 IU/day). In Group B, vitamin D (cholecalciferol in a Calcirol® sachet) was administered as a single stat dose of 33,600 IU on Day 1 of steroid therapy (for new-onset NS, calculated for a period of 12 weeks@400 IU/day) and 16,800 IU on Day 1 of steroid therapy (for IFRNS, calculated for a period of 6 weeks@400 IU/day). The proportionate change in bone mineral content (BMC) was analysed in both groups after vitamin D supplementation. Of the 92 children enrolled, 84 (n = 42 new onset, n = 42 IFRNS) completed the study and were included in the final analysis. Baseline characteristics including initial BMC, bone mineral density, cumulative prednisolone dosage and serum 25-hydroxycholecalciferol levels were comparable in the two groups. There was a greater median proportionate change in BMC in the children who received 1000 IU/day vitamin D (3.25%, IQR -1.2 to 12.4) than in those who received 400 IU/day vitamin D (1.2%, IQR -2.5 to 3.8, p = 0.048). The difference in proportionate change in BMC was only statistically significant in the combined new-onset and IFRNS, but not for IFRNS alone. There was a greater median proportionate change in serum 25-hydroxycholecalciferol, in the children who received 1000 IU/day vitamin D (20.6%, IQR 14.9-36.75) than in those who received 400 IU/day vitamin D (7.7%, IQR 3.5-18.5, p < 0.01). There was a greater median proportionate change in serum calcium in the children who received 1000 IU/day vitamin D (20%, IQR 13.1-29.0) than in those who received 400 IU/day vitamin D (11.3%, IQR 2.8-25.0, p = 0.03). Despite vitamin D therapy, BMC decreased from the baseline in 15 (32.6%) children receiving 1000 IU/day vitamin D and in 17 (36.9%) children receiving 400 IU/day vitamin D. There were no adverse effects attributable to vitamin D. The 1000 IU/day dose is marginally more effective than 400 IU/day and it is likely than an even larger dose is required. Further research is required to assess the efficacy and safety of vitamin D doses higher than 1000 IU/day.

Efficacy of fewer than three doses of an HPV-16/18 AS04-adjuvanted vaccine: combined analysis of data from the Costa Rica Vaccine and PATRICIA Trials.

PubMed

Kreimer, Aimée R; Struyf, Frank; Del Rosario-Raymundo, Maria Rowena; Hildesheim, Allan; Skinner, S Rachel; Wacholder, Sholom; Garland, Suzanne M; Herrero, Rolando; David, Marie-Pierre; Wheeler, Cosette M; González, Paula; Jiménez, Silvia; Lowy, Douglas R; Pinto, Ligia A; Porras, Caroline; Rodriguez, Ana Cecilia; Safaeian, Mahboobeh; Schiffman, Mark; Schiller, John T; Schussler, John; Sherman, Mark E; Bosch, F Xavier; Castellsague, Xavier; Chatterjee, Archana; Chow, Song-Nan; Descamps, Dominique; Diaz-Mitoma, Francisco; Dubin, Gary; Germar, Maria Julieta; Harper, Diane M; Lewis, David J M; Limson, Genara; Naud, Paulo; Peters, Klaus; Poppe, Willy A J; Ramjattan, Brian; Romanowski, Barbara; Salmeron, Jorge; Schwarz, Tino F; Teixeira, Julio C; Tjalma, Wiebren A A

2015-07-01

There is some evidence to suggest that one or two doses of the HPV vaccine provides similar protection to the three-dose regimen. The main aim of the study was to ascertain HPV-16/18 vaccine efficacy in both full and naive cohorts and to explore protection conferred against non-vaccine HPV types, by number of doses received. Summary data from the Costa Rica Vaccine Trial (CVT; NCT00128661) and ~the PATRICIA trial (NCT001226810), two phase 3, double-blind, randomised controlled clinical trials of the HPV-16/18 AS04-adjuvanted vaccine in young women, were combined in a post-hoc analysis (GlaxoSmithKline [GSK] e-track number 202142) to investigate the efficacy of fewer than three doses of the HPV-16/18 vaccine after 4 years of follow-up. Women were randomly assigned to receive three doses of the HPV-16/18 vaccine or to a control vaccine; yet, some received fewer doses. After exclusion of women with less than 12 months of follow-up or those who were HPV-16/18 DNA-positive at enrolment (for the HPV-16/18 endpoint), we calculated vaccine efficacy against one-time detection of incident HPV infections after three, two, and one dose(s). The primary study endpoint was one-time detection of first incident HPV-16/18 infections accumulated during the follow-up phase. We assessed vaccine efficacy against incident HPV-16/18 infection in the modified total vaccinated cohort (22 327 received three doses, 1185 two doses, 543 one dose). Vaccine efficacy against incident HPV-16/18 infections for three doses was 77·0% (95% CI 74·7-79·1), two doses was 76·0% (62·0-85·3), and one dose was 85·7% (70·7-93·7). Vaccine efficacy against incident HPV-31/33/45 infections for three doses was 59·7% (56·0-63·0), two doses was 37·7% (12·4-55·9), and one dose was 36·6% (-5·4 to 62·2). Vaccine efficacy against incident HPV-16/18 infection for two-dose women who received their second dose at 1 month was 75·3% (54·2-87·5) and 82·6% (42·3-96·1) for those who received the second dose at 6 months (CVT data only). Vaccine efficacy against HPV-31/33/45 for two-dose women who received their second dose at 6 months (68·1%, 27·0-87·0; CVT data only), but not those receiving it at one month (10·1%, -42·0 to 43·3), was similar to the three-dose group. 4 years after vaccination of women aged 15-25 years, one and two doses of the HPV-16/18 vaccine seem to protect against cervical HPV-16/18 infections, similar to the protection provided by the three-dose schedule. Two doses separated by 6 months additionally provided some cross-protection. These data argue for a direct assessment of one-dose efficacy of the HPV-16/18 vaccine. US National Cancer Institute, National Institutes of Health Office of Research on Women's Health, and Ministry of Health of Costa Rica (CVT); GlaxoSmithKline Biologicals SA (PATRICIA). Copyright © 2015 Elsevier Ltd. All rights reserved.

Local Control With Reduced-Dose Radiotherapy for Low-Risk Rhabdomyosarcoma: A Report From the Children's Oncology Group D9602 Study

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

Breneman, John, E-mail: john.breneman@uchealth.com; Meza, Jane; Donaldson, Sarah S.

2012-06-01

Purpose: To analyze the effect of reduced-dose radiotherapy on local control in children with low-risk rhabdomyosarcoma (RMS) treated in the Children's Oncology Group D9602 study. Methods and Materials: Patients with low-risk RMS were nonrandomly assigned to receive radiotherapy doses dependent on the completeness of surgical resection of the primary tumor (clinical group) and the presence of involved regional lymph nodes. After resection, most patients with microscopic residual and uninvolved nodes received 36 Gy, those with involved nodes received 41.4 to 50.4 Gy, and those with orbital primary tumors received 45 Gy. All patients received vincristine and dactinomycin, with cyclophosphamide addedmore » for patient subsets with a higher risk of relapse in Intergroup Rhabdomyosarcoma Study Group III and IV studies. Results: Three hundred forty-two patients were eligible for analysis; 172 received radiotherapy as part of their treatment. The cumulative incidence of local/regional failure was 15% in patients with microscopic involved margins when cyclophosphamide was not part of the treatment regimen and 0% when cyclophosphamide was included. The cumulative incidence of local/regional failure was 14% in patients with orbital tumors. Protocol-specified omission of radiotherapy in girls with Group IIA vaginal tumors (n = 5) resulted in three failures for this group. Conclusions: In comparison with Intergroup Rhabdomyosarcoma Study Group III and IV results, reduced-dose radiotherapy does not compromise local control for patients with microscopic tumor after surgical resection or with orbital primary tumors when cyclophosphamide is added to the treatment program. Girls with unresected nonbladder genitourinary tumors require radiotherapy for postsurgical residual tumor for optimal local control to be achieved.« less

Zinc Sulfate and/or Growth Hormone Administration for the Prevention of Radiation-Induced Dermatitis: a Placebo-Controlled Rat Model Study.

PubMed

Kandaz, Mustafa; Ertekin, Mustafa Vecdi; Karslıoğlu, İhsan; Erdoğan, Fazlı; Sezen, Orhan; Gepdiremen, Akçahan; Gündoğdu, Cemal

2017-09-01

Growth hormone (GH) and zinc (Zn) were evaluated for their potential to prevent radiation injury using a rat model of radiation-induced skin injury. Sprague-Dawley rats were divided into five groups: a control group not receiving Zn, GH, or irradiation: a radiation (RT) group receiving a single 30 Gy dose of gamma irradiation to the right hind legs; a radiation + GH group (RT + GH) receiving a single 30 Gy dose of gamma irradiation plus the subcutaneous administration of 0.01 IU kg d -1 GH; a radiation + Zn group (RT + Zn) receiving a single 30 Gy dose plus 5 mg kg d -1 Zn po; and a radiation + GH + Zn group (RT + GH + Zn) group receiving a single 30 Gy dose plus subcutaneous 0.01 IU kg d -1 GH and 5 mg kg d -1 Zn po. Acute skin reactions were assessed every 3 days by two radiation oncologists grouping. Light microscopic findings were assessed blindly by two pathologists. Groups receiving irradiation were associated with dermatitis as compared to the control group (P < 0.05). The severity of radiodermatitis in the RT + GH, RT + Zn, and RT + GH + Zn groups was significantly lower than that in the RT group (P < 0.05). Furthermore, radiodermatitis was observed earlier in the RT group than in the other treatment groups (P < 0.05). GH and Zn effectively prevented epidermal atrophy, dermal degeneration, and hair follicle atrophy. The highest level of protection against radiation dermatitis was observed in the combination group.

Modulating effect of the nootropic drug, piracetam on stress- and subsequent morphine-induced prolactin secretion in male rats.

PubMed Central

Matton, A.; Engelborghs, S.; Bollengier, F.; Finné, E.; Vanhaeist, L.

1996-01-01

1. The effect of the nootropic drug, piracetam on stress- and subsequent morphine-induced prolactin (PRL) secretion was investigated in vivo in male rats, by use of a stress-free blood sampling and drug administration method by means of a permanent indwelling catheter in the right jugular vein. 2. Four doses of piracetam were tested (20, 100, 200 and 400 mg kg-1), being given intraperitoneally 1 h before blood sampling; control rats received saline instead. After a first blood sample, rats were subjected to immobilization stress and received morphine, 6 mg kg-1, 90 min later. 3. Piracetam had no effect on basal plasma PRL concentration. 4. While in the non-piracetam-treated rats, stress produced a significant rise in plasma PRL concentration, in the piracetam-pretreated rats PRL peaks were attenuated, especially in the group given 100 mg kg-1 piracetam, where plasma PRL concentration was not significantly different from basal values. The dose-response relationship showed a U-shaped curve; the smallest dose had a minor inhibitory effect and the highest dose had no further effect on the PRL rise. 5. In unrestrained rats, morphine led to a significant elevation of plasma PRL concentration. After the application of immobilization stress it lost its ability to raise plasma PRL concentration in the control rats, but not in the piracetam-treated rats. This tolerance was overcome by piracetam in a significant manner but with a reversed dose-response curve; i.e. the smaller the dose of piracetam, the higher the subsequent morphine-induced PRL peak. 6. There is no simple explanation for the mechanism by which piracetam induces these contradictory effects. Interference with the excitatory amino acid system, which is also involved in opiate action, is proposed speculatively as a possible mediator of the effects of piracetam. PMID:8821540

Optimal timing and frequency of bone marrow soup therapy for functional restoration of salivary glands injured by single-dose or fractionated irradiation.

PubMed

Fang, Dongdong; Shang, Sixia; Liu, Younan; Bakkar, Mohammed; Sumita, Yoshinori; Seuntjens, Jan; Tran, Simon D

2018-02-01

Injections of bone marrow (BM) cell extract, known as 'BM soup', were previously reported to mitigate ionizing radiation (IR) injury to salivary glands (SGs). However, the optimal starting time and frequency to maintain BM soup therapeutic efficacy remains unknown. This study tested the optimal starting time and frequency of BM soup injections in mice radiated with either a single dose or a fractionated dose. First, BM soup treatment was started at 1, 3 or 7 weeks post-IR; positive (non-IR) and negative (IR) control mice received injections of saline (vehicle control). Second, BM soup-treated mice received injections at different frequencies (1, 2, 3 and 5 weekly injections). Third, a 'fractionated-dose radiation' model to injure mouse SGs was developed (5 Gy × 5 days) and compared with the single high dose radiation model. All mice (n = 65) were followed for 16 weeks post-IR. The results showed that starting injections of BM soup between 1 and 3 weeks mitigated the effect of IR-induced injury to SGs and improved the restoration of salivary function. Although the therapeutic effect of BM soup lessens after 8 weeks, it can be sustained by increasing the frequency of weekly injections. Moreover, both single-dose and fractionated-dose radiation models are efficient and comparable in inducing SG injury and BM soup treatments are effective in restoring salivary function in both radiation models. In conclusion, starting injections of BM soup within 3 weeks post-radiation, with 5 weekly injections, maintains 90-100% of saliva flow in radiated mice. Copyright © 2017 John Wiley & Sons, Ltd.

Radon exposure assessment for underground workers: a case of Seoul Subway Police officers in Korea.

PubMed

Song, Myeong Han; Chang, Byung-Uck; Kim, Yongjae; Cho, Kun-Woo

2011-11-01

The objective of this study is the systematic and individual assessment of the annual effective dose due to inhaled radon for the Seoul Subway Police officers, Korea. The annual average radon concentrations were found to be in the range of 18.9-114 Bq·m(-3) in their workplaces. The total annual effective doses which may likely to be received on duty were assessed to be in the range of 0.41-1.64 mSv·y(-1). These were well below the recommended action level 10 mSv·y(-1) by ICRP. However, the effective doses were higher than subway station staff in Seoul, Korea.

Prevention of febrile neutropenia: use of prophylactic antibiotics.

PubMed

Cullen, M; Baijal, S

2009-09-01

Febrile neutropenia (FN) causes significant morbidity and mortality in patients receiving cytotoxic chemotherapy and can lead to reduced chemotherapy dose intensity and increased overall treatment costs. Antibiotic prophylaxis reduces the incidence of FN. Recent research and meta-analyses confirm that prophylactic fluoroquinolones decrease FN and infection-related mortality in patients with acute leukaemia and those receiving high-dose chemotherapy. Fluoroquinolone prophylaxis also lowers the incidence of FN and all-cause mortality following the first cycle of myelosuppressive chemotherapy for solid tumours. Levofloxacin has been the agent studied most thoroughly in this context. Although there is no convincing evidence that colonisation of individuals with resistant organisms due to antibiotic prophylaxis increases FN or mortality, such concerns must be taken seriously and the use of prophylaxis should be limited responsibly for patients with the greatest chance of benefit. Fluoroquinolone prophylaxis is well tolerated and cost-effective and should be offered to patients receiving chemotherapy for haematological malignancies and high-dose chemotherapy for solid tumours in which prolonged (>7 days) neutropenia is expected. It should also be considered for those receiving chemotherapy for solid tumours and lymphomas during the first cycle of chemotherapy when grade 4 neutropenia is anticipated.

Prevention of febrile neutropenia: use of prophylactic antibiotics

PubMed Central

Cullen, M; Baijal, S

2009-01-01

Febrile neutropenia (FN) causes significant morbidity and mortality in patients receiving cytotoxic chemotherapy and can lead to reduced chemotherapy dose intensity and increased overall treatment costs. Antibiotic prophylaxis reduces the incidence of FN. Recent research and meta-analyses confirm that prophylactic fluoroquinolones decrease FN and infection-related mortality in patients with acute leukaemia and those receiving high-dose chemotherapy. Fluoroquinolone prophylaxis also lowers the incidence of FN and all-cause mortality following the first cycle of myelosuppressive chemotherapy for solid tumours. Levofloxacin has been the agent studied most thoroughly in this context. Although there is no convincing evidence that colonisation of individuals with resistant organisms due to antibiotic prophylaxis increases FN or mortality, such concerns must be taken seriously and the use of prophylaxis should be limited responsibly for patients with the greatest chance of benefit. Fluoroquinolone prophylaxis is well tolerated and cost-effective and should be offered to patients receiving chemotherapy for haematological malignancies and high-dose chemotherapy for solid tumours in which prolonged (>7 days) neutropenia is expected. It should also be considered for those receiving chemotherapy for solid tumours and lymphomas during the first cycle of chemotherapy when grade 4 neutropenia is anticipated. PMID:19756000

Maternal Tetanus Toxoid Vaccination and Neonatal Mortality in Rural North India

PubMed Central

Singh, Abhishek; Pallikadavath, Saseendran; Ogollah, Reuben; Stones, William

2012-01-01

Objectives Preventable neonatal mortality due to tetanus infection remains common. We aimed to examine antenatal vaccination impact in a context of continuing high neonatal mortality in rural northern India. Methods and Findings Using the third round of the Indian National Family Health Survey (NFHS) 2005–06, mortality of most recent singleton births was analysed in discrete-time logistic model with maternal tetanus vaccination, together with antenatal care utilisation and supplementation with iron and folic acid. 59% of mothers reported receiving antenatal care, 48% reported receiving iron and folic acid supplementation and 68% reported receiving two or more doses of tetanus toxoid (TT) vaccination. The odds of all-cause neonatal death were reduced following one or more antenatal dose of TT with odds ratios (OR) of 0.46 (95% CI 0.26 to 0.78) after one dose and 0.45 (95% CI 0.31 to 0.66) after two or more doses. Reported utilisation of antenatal care and iron-folic acid supplementation did not influence neonatal mortality. In the statistical model, 16% (95% CI 5% to 27%) of neonatal deaths could be attributed to a lack of at least two doses of TT vaccination during pregnancy, representing an estimated 78,632 neonatal deaths in absolute terms. Conclusions Substantial gains in newborn survival could be achieved in rural North India through increased coverage of antenatal TT vaccination. The apparent substantial protective effect of a single antenatal dose of TT requires further study. It may reflect greater population vaccination coverage and indicates that health programming should prioritise universal antenatal coverage with at least one dose. PMID:23152814

Maternal tetanus toxoid vaccination and neonatal mortality in rural north India.

PubMed

Singh, Abhishek; Pallikadavath, Saseendran; Ogollah, Reuben; Stones, William

2012-01-01

Preventable neonatal mortality due to tetanus infection remains common. We aimed to examine antenatal vaccination impact in a context of continuing high neonatal mortality in rural northern India. Using the third round of the Indian National Family Health Survey (NFHS) 2005-06, mortality of most recent singleton births was analysed in discrete-time logistic model with maternal tetanus vaccination, together with antenatal care utilisation and supplementation with iron and folic acid. 59% of mothers reported receiving antenatal care, 48% reported receiving iron and folic acid supplementation and 68% reported receiving two or more doses of tetanus toxoid (TT) vaccination. The odds of all-cause neonatal death were reduced following one or more antenatal dose of TT with odds ratios (OR) of 0.46 (95% CI 0.26 to 0.78) after one dose and 0.45 (95% CI 0.31 to 0.66) after two or more doses. Reported utilisation of antenatal care and iron-folic acid supplementation did not influence neonatal mortality. In the statistical model, 16% (95% CI 5% to 27%) of neonatal deaths could be attributed to a lack of at least two doses of TT vaccination during pregnancy, representing an estimated 78,632 neonatal deaths in absolute terms. Substantial gains in newborn survival could be achieved in rural North India through increased coverage of antenatal TT vaccination. The apparent substantial protective effect of a single antenatal dose of TT requires further study. It may reflect greater population vaccination coverage and indicates that health programming should prioritise universal antenatal coverage with at least one dose.

The effect of sulforaphane on oxidative stress and inflammation in rats with toxic hepatitis induced by acetaminophene.

PubMed

Dokumacioglu, E; Iskender, H; Aktas, M S; Hanedan, B; Dokumacioglu, A; Sen, T M; Musmul, A

2017-01-01

The aim of the present study was to reveal the possible effect of sulforaphane on oxidative stress and inflammation in rats liver with toxic hepatitis induced by acetaminophene. Sulforaphane is a compound with high antioxidant properties. Acetaminophen, which is a para-aminophenol derivative, can lead to fatal hepatic necrosis with direct hepatotoxic effects at high doses. Thirty six male Sprague-Dawley rats were randomly divided into four groups. Control group (n = 9) was fed with standard rat chow and water for 3 days. Group APAP (n = 9) received a single dose acetaminophen 1 g/kg by oral gavage in addition to standard chow and water. Group SFN (n = 9) received sulforaphane 500 μg/kg by oral gavage in addition to standard chow and water for 3 days. Group APAP+SFN (n = 9) received sulforaphane 500 μg/kg and a single dose acetaminophen 1 g/kg by oral gavage in addition to standard chow and water. Acetaminophen was administered three hours after SFN administration. Neopterin, MDA, AST, ALT and CRP levels of group APAP were significantly increased compared to control group. GSH level of group APAP was significantly lower than in the control group. Sulforaphane is a protective agent against acetaminophen-induced liver damage and it can be added in the treatment protocol (Tab. 1, Fig. 5, Ref. 51).

Radiological protection and medical dosimetry for the Skylab crewmen

NASA Technical Reports Server (NTRS)

Bailey, J. V.; Hoffman, R. A.; English, R. A.

1977-01-01

Dosimetry results for Skylab crewmembers show that the Skylab 4 crewmen received the highest dose equivalents but remained well within the established limits for Skylab missions below the threshold of significant clinical effects. These dose equivalents apply specificially to long term effects such as general life shortening, increased neoplasm incidence, and cataract production. A Skylab crewman could fly a mission comparable to one 84-day Skylab 4 mission per year for 50 years before exceeding these career limits.

Cytogenetic effects of space radiation in lymphocytes of MIR-18 crews

NASA Technical Reports Server (NTRS)

Yang, T. C.; George, K.; Johnson, A. S.; Tavakoli, A.; Durante, M.; Fedorenko, B. S.

1997-01-01

For assessing health risk, the measurement of physical dose received during a space mission, as well as the LETs, energies and charges of particles is important. It is also important to obtain quantitative information regarding the effectiveness of space radiation in causing damage to critical biological targets, e.g., chromosomes, since at present the estimated uncertainty of biological effects of space radiation is more than a factor of two. Such large uncertainty makes accurate health risk assessment very difficult. For this very reason, a study on cytogenetic effects of space radiation in human lymphocytes was proposed and done for MIR-18 mission. This study used FISH technique to score chromosomal translocations and C-banding method to determine dicentrics. Growth kinetics of cells and SCE were examined to ensure that chromosomal aberrations were scored in first mitosis and were induced not by chemical mutagens. Our results showed that chromosomal aberration frequency of post-flight samples was significantly higher than that of pre-flight ones and that SCE frequency was similar between pre- and post-flight samples. Based on a dose-response curve of preflight samples exposed to gamma rays, the absorbed dose received by crews during the mission was estimated to be about 14.5 cSv. Because the absorbed dose measured by physical dosimeters is 4.16 cGy for the entire mission, the RBE is about 3.5.

Aripiprazole maintenance increases smoked cocaine self-administration in humans

PubMed Central

Rubin, Eric; Foltin, Richard W.

2011-01-01

Rationale Partial dopamine receptor agonists have been proposed as candidate pharmacotherapies for cocaine dependence. Objective This 42-day, within-subject, human laboratory study assessed how maintenance on aripiprazole, a partial D2 receptor agonist, influenced smoked cocaine self-administration, cardiovascular measures, subjective effects, and cocaine craving in nontreatment-seeking, cocaine-dependent volunteers. Methods In order to achieve steady-state concentrations, participants (n=8 men) were administered placebo and aripiprazole (15 mg/day) capsules in counter-balanced order for 21 days. A smoked cocaine dose–response curve (0, 12, 25, 50 mg) was determined twice under placebo and aripiprazole maintenance. Sessions comprised a “sample” trial, when participants smoked the cocaine dose available that session, and five choice trials, when they responded on a progressive-ratio schedule of reinforcement to receive the cocaine dose or receive $5.00. Results Cocaine’s reinforcing, subjective, and cardiovascular effects were dose-dependent. Aripiprazole significantly increased cocaine (12, 25 mg) self-administration. Following a single administration of cocaine (25 mg), aripiprazole decreased ratings of how much participants would pay for that dose. Following repeated cocaine (50 mg) self-administration, aripiprazole decreased ratings of cocaine quality, craving, and good drug effect as compared to placebo. Conclusions These data suggest that aripiprazole may have increased self-administration to compensate for a blunted subjective cocaine effect. Overall, the findings do not suggest aripiprazole would be useful for treating cocaine dependence. PMID:21373790

Effect of Ranitidine on Acetaminophen-Induced Hepatotoxicity in Dogs

PubMed Central

Panella, C.; Makowka, L.; Barone, M.; Polimeno, L.; Rizzi, S.; Demetris, J.; Bell, S.; Guglielmi, F. W.; Prelich, J. G.; Van Thiel, D. H.; Starzl, T. E.; Francavilla, A.

2010-01-01

The effect of ranitidine administration upon the hepatotoxic effect produced by a multidose acetaminophen administration regimen was examined. Seventy-two dogs received three subcutaneous injections of acetaminophen (750, 200, 200 mg/kg body wt) in DMSO (600 mg/ml) at time zero, 9 hr later, and 24 hr after the first dose. Ten control animals (group I) were not given ranitidine, the remaining 62 dogs received an intramuscular injection of ranitidine 30 min before each acetaminophen dose. Three different doses of ranitidine were used (mg/kg body wt): 50 mg, group II (33 dogs); 75 mg, group III (14 dogs); 120 mg, group IV (15 dogs). Ranitidine reduced the expected acetaminophen-induced hepatoxicity in a dose–response manner. Moreover, a significant correlation was found between the ranitidine dose and the survival rate, as evidenced by transaminase levels in the serum and histology of the liver. This model of fulminant hepatic failure induced by acetaminophen and its modulation with ranitidine provides clinical investigators with a research tool that will be useful in the future investigation of putative medical and surgical therapies being investigated for use in the clinical management of fulminant hepatic failure. Because of the size of the animal used in this model, frequent and serial analyses of blood and liver were available for study to determine the effect of therapy within a given animal as opposed to within groups of animals. PMID:2307085

Occupational radiation doses during interventional procedures

NASA Astrophysics Data System (ADS)

Nuraeni, N.; Hiswara, E.; Kartikasari, D.; Waris, A.; Haryanto, F.

2016-03-01

Digital subtraction angiography (DSA) is a type of fluoroscopy technique used in interventional radiology to clearly visualize blood vessels in a bony or dense soft tissue environment. The use of DSA procedures has been increased quite significantly in the Radiology departments in various cities in Indonesia. Various reports showed that both patients and medical staff received a noticeable radiation dose during the course of this procedure. A study had been carried out to measure these doses among interventionalist, nurse and radiographer. The results show that the interventionalist and the nurse, who stood quite close to the X-ray beams compared with the radiographer, received radiation higher than the others. The results also showed that the radiation dose received by medical staff were var depending upon the duration and their position against the X-ray beams. Compared tothe dose limits, however, the radiation dose received by all these three medical staff were still lower than the limits.

Effect of low-dose versus higher-dose antenatal iron supplementation on child health outcomes at 36 months of age in Viet Nam: longitudinal follow-up of a cluster randomised controlled trial.

PubMed

Hanieh, Sarah; Ha, Tran T; Simpson, Julie A; Braat, Sabine; Thuy, Tran T; Tran, Thach D; King, Janet; Tuan, Tran; Fisher, Jane; Biggs, Beverley-Ann

2017-01-01

Intermittent iron-folic acid supplementation (IFA) is currently recommended for pregnant women in populations where anaemia prevalence among pregnant women is <20% or if daily iron is not acceptable. The effect of providing lower doses of antenatal elemental iron through intermittent regimes on longer-term health outcomes in childhood is unclear. A prospective cohort study conducted between May 2012 and May 2014 in Viet Nam among children of 36 months of age, born to women previously enrolled in a cluster randomised controlled trial of antenatal micronutrient supplementation (daily IFA (60 mg elemental iron) vs twice-weekly IFA (60 mg elemental iron) vs twice-weekly multiple micronutrient (MMN) supplementation (60 mg elemental iron)). Primary outcomes were height-for-age z-scores (HAZ), according to WHO growth standards and cognitive composite scores (Bayley Scales of Infant and Toddler Development, third edition) at 36 months of age. A total of 1017 children born to mothers enrolled in the cluster randomised trial were assessed at 36 months of age. Adjusted mean differences (MDs) in HAZ were -0.14 (95% CI -0.28 to -0.01) and -0.15 (95% CI -0.29 to -0.01) in children born to mothers who received twice-weekly IFA or MMN compared with those who received daily IFA. Children born to mothers who received twice-weekly MMN had lower composite motor scores compared with those who received daily IFA (MD -2.07, 95% CI -4.11 to -0.03). There were no differences in composite cognitive scores in the twice-weekly compared with daily regimens. Low-dose antenatal IFA supplementation (120 mg elemental iron per week) resulted in lower HAZ and motor composite scores in children compared with higher-dose antenatal IFA supplementation (420 mg elemental iron per week). This highlights the importance of adequate iron stores during pregnancy and the need for careful monitoring when lower-dose antenatal iron regimens are used. Australia New Zealand Clinical Trials Registry: 12610000944033.

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

Gomez, Daniel R., E-mail: dgomez@mdanderson.org; Gillin, Michael; Liao, Zhongxing

Background: Many patients with locally advanced non-small cell lung cancer (NSCLC) cannot undergo concurrent chemotherapy because of comorbidities or poor performance status. Hypofractionated radiation regimens, if tolerable, may provide an option to these patients for effective local control. Methods and Materials: Twenty-five patients were enrolled in a phase 1 dose-escalation trial of proton beam therapy (PBT) from September 2010 through July 2012. Eligible patients had histologically documented lung cancer, thymic tumors, carcinoid tumors, or metastatic thyroid tumors. Concurrent chemotherapy was not allowed, but concurrent treatment with biologic agents was. The dose-escalation schema comprised 15 fractions of 3 Gy(relative biological effectivenessmore » [RBE])/fraction, 3.5 Gy(RBE)/fraction, or 4 Gy(RBE)/fraction. Dose constraints were derived from biologically equivalent doses of standard fractionated treatment. Results: The median follow-up time for patients alive at the time of analysis was 13 months (range, 8-28 months). Fifteen patients received treatment to hilar or mediastinal lymph nodes. Two patients experienced dose-limiting toxicity possibly related to treatment; 1 received 3.5-Gy(RBE) fractions and experienced an in-field tracheoesophageal fistula 9 months after PBT and 1 month after bevacizumab. The other patient received 4-Gy(RBE) fractions and was hospitalized for bacterial pneumonia/radiation pneumonitis 4 months after PBT. Conclusion: Hypofractionated PBT to the thorax delivered over 3 weeks was well tolerated even with significant doses to the lungs and mediastinal structures. Phase 2/3 trials are needed to compare the efficacy of this technique with standard treatment for locally advanced NSCLC.« less

Effectiveness of esophagectomy in patients with thoracic esophageal squamous cell carcinoma receiving definitive radiotherapy or concurrent chemoradiotherapy through intensity-modulated radiation therapy techniques.

PubMed

Yen, Yu-Chun; Chang, Jer-Hwa; Lin, Wei-Cheng; Chiou, Jeng-Fong; Chang, Yin-Chun; Chang, Chia-Lun; Hsu, Han-Lin; Chow, Jyh-Ming; Yuan, Kevin Sheng-Po; Wu, Alexander T H; Wu, Szu-Yuan

2017-06-01

Few large, prospective, randomized studies have investigated the effectiveness of esophagectomy in patients with thoracic esophageal squamous cell carcinoma (TESCC) who receive definitive radiotherapy (RT) or concurrent chemoradiotherapy (CCRT) through modern, intensity modulated-RT (IMRT) techniques. The therapeutic effects of esophagectomy in patients with TESCC were evaluated using modern clinical staging and RT techniques and suitable RT doses. The authors analyzed data from patients with TESCC from the Taiwan Cancer Registry database. Patients were categorized into the following groups on the basis of treatment modality to compare their outcomes: group 1 received definitive CCRT, group 2 received neoadjuvant RT followed by esophagectomy (total IMRT dose, ≥50 grays [Gy]), and group 3 receiving neoadjuvant CCRT followed by esophagectomy (total IMRT dose, ≥ 50 Gy). The median total RT dose and fraction size were 50.4 Gy and 1.8 Gy per fraction, respectively. Group 1 was used as the control arm for investigating the risk of mortality after treatment. In total, 3123 patients who had TESCC without distant metastasis were enrolled. Patient ages 65 years and older, Charlson comorbidity index scores ≥3, advanced clinical stages (IIA-IIIC), alcohol consumption, and cigarette smoking were identified as significant, independent poor prognostic risk factors for overall survival in multivariate Cox regression analyses. In group 3, after adjustment for confounders, the adjusted hazard ratios (95% confidence intervals [CIs]) for overall mortality were 0.62 (95% CI, 0.41-0.93) for patients with clinical stage IIA disease, 0.61 (95% CI, 0.41-0.91) for those with clinical stage IIB disease, 0.47 (95% CI, 0.38-0.55) for those with clinical stage IIIA disease, 0.47 (95% CI, 0.39-0.56) for those with clinical stage IIIB disease, and 0.46 (95% CI, 0.37-0.57) for those with clinical stage IIIC disease. Esophagectomy can be beneficial in patients with TESCC after definitive CCRT, especially in those who have advanced-stage disease. Cancer 2017;123:2043-2053. © 2017 American Cancer Society. © 2017 American Cancer Society.

Prevention of Rectal SHIV Transmission in Macaques by Daily or Intermittent Prophylaxis with Emtricitabine and Tenofovir

PubMed Central

García-Lerma, J. Gerardo; Otten, Ron A; Qari, Shoukat H; Jackson, Eddie; Cong, Mian-er; Masciotra, Silvina; Luo, Wei; Kim, Caryn; Adams, Debra R; Monsour, Michael; Lipscomb, Jonathan; Johnson, Jeffrey A; Delinsky, David; Schinazi, Raymond F; Janssen, Robert; Folks, Thomas M; Heneine, Walid

2008-01-01

Background In the absence of an effective vaccine, HIV continues to spread globally, emphasizing the need for novel strategies to limit its transmission. Pre-exposure prophylaxis (PrEP) with antiretroviral drugs could prove to be an effective intervention strategy if highly efficacious and cost-effective PrEP modalities are identified. We evaluated daily and intermittent PrEP regimens of increasing antiviral activity in a macaque model that closely resembles human transmission. Methods and Findings We used a repeat-exposure macaque model with 14 weekly rectal virus challenges. Three drug treatments were given once daily, each to a different group of six rhesus macaques. Group 1 was treated subcutaneously with a human-equivalent dose of emtricitabine (FTC), group 2 received orally the human-equivalent dosing of both FTC and tenofovir-disoproxil fumarate (TDF), and group 3 received subcutaneously a similar dosing of FTC and a higher dose of tenofovir. A fourth group of six rhesus macaques (group 4) received intermittently a PrEP regimen similar to group 3 only 2 h before and 24 h after each weekly virus challenge. Results were compared to 18 control macaques that did not receive any drug treatment. The risk of infection in macaques treated in groups 1 and 2 was 3.8- and 7.8-fold lower than in untreated macaques (p = 0.02 and p = 0.008, respectively). All six macaques in group 3 were protected. Breakthrough infections had blunted acute viremias; drug resistance was seen in two of six animals. All six animals in group 4 that received intermittent PrEP were protected. Conclusions This model suggests that single drugs for daily PrEP can be protective but a combination of antiretroviral drugs may be required to increase the level of protection. Short but potent intermittent PrEP can provide protection comparable to that of daily PrEP in this SHIV/macaque model. These findings support PrEP trials for HIV prevention in humans and identify promising PrEP modalities. PMID:18254653

Bone mineral density in relation to efficacy and side effects of budesonide and prednisolone in Crohn's disease.

PubMed

Schoon, Erik J; Bollani, Simona; Mills, Peter R; Israeli, Eran; Felsenberg, Dieter; Ljunghall, Sverker; Persson, Tore; Haptén-White, Louise; Graffner, Hans; Bianchi Porro, Gabriele; Vatn, Morten; Stockbrügger, Reinhold W

2005-02-01

Osteoporosis frequently occurs in Crohn's disease, often because of corticosteroids. Budesonide as controlled release capsules is a locally acting corticosteroid with low systemic bioavailability. We investigated its effects on bone compared with prednisolone. In 34 international centers, 272 patients with Crohn's disease involving ileum and/or colon ascendens were randomized to once daily treatment with budesonide or prednisolone for 2 years at doses adapted to disease activity. One hundred eighty-one corticosteroid-free patients had active disease (98 had never received corticosteroids, corticosteroid naive; 83 had received corticosteroids previously, corticosteroid exposed), and 90 had quiescent disease, receiving long-term low doses of corticosteroids, corticosteroid-dependent; in 1 patient, no efficacy data were obtained. Bone mineral density and fractures were assessed in a double-blinded fashion; disease activity, side effects, and quality of life were monitored. Neither the corticosteroid-free nor the corticosteroid-dependent patients treated with budesonide differed significantly in bone mineral density from those receiving prednisolone. However, corticosteroid-naive patients receiving budesonide had smaller reductions in bone mineral density than those on prednisolone (mean, -1.04% vs -3.84%; P = .0084). Treatment-emergent corticosteroid side effects were less frequent with budesonide. Efficacy was similar in both groups. Treatment with budesonide is associated with better preserved bone mass compared with prednisolone in only the corticosteroid-naive patients with active ileocecal Crohn's disease. In both the corticosteroid-free and corticosteroid-dependent groups, budesonide and prednisolone were equally effective for up to 2 years, but budesonide caused fewer corticosteroid side effects.

L-Boronophenylalanine-Mediated Boron Neutron Capture Therapy for Malignant Glioma Progressing After External Beam Radiation Therapy: A Phase I Study

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

Kankaanranta, Leena; Seppaelae, Tiina; Koivunoro, Hanna

Purpose: To investigate the safety of boronophenylalanine-mediated boron neutron capture therapy (BNCT) in the treatment of malignant gliomas that progress after surgery and conventional external beam radiation therapy. Methods and Materials: Adult patients who had histologically confirmed malignant glioma that had progressed after surgery and external beam radiotherapy were eligible for this Phase I study, provided that >6 months had elapsed from the last date of radiation therapy. The first 10 patients received a fixed dose, 290 mg/kg, of L-boronophenylalanine-fructose (L-BPA-F) as a 2-hour infusion before neutron irradiation, and the remaining patients were treated with escalating doses of L-BPA-F, eithermore » 350 mg/kg, 400 mg/kg, or 450 mg/kg, using 3 patients on each dose level. Adverse effects were assessed using National Cancer Institute Common Toxicity Criteria version 2.0. Results: Twenty-two patients entered the study. Twenty subjects had glioblastoma, and 2 patients had anaplastic astrocytoma, and the median cumulative dose of prior external beam radiotherapy was 59.4 Gy. The maximally tolerated L-BPA-F dose was reached at the 450 mg/kg level, where 4 of 6 patients treated had a grade 3 adverse event. Patients who were given >290 mg/kg of L-BPA-F received a higher estimated average planning target volume dose than those who received 290 mg/kg (median, 36 vs. 31 Gy [W, i.e., a weighted dose]; p = 0.018). The median survival time following BNCT was 7 months. Conclusions: BNCT administered with an L-BPA-F dose of up to 400 mg/kg as a 2-hour infusion is feasible in the treatment of malignant gliomas that recur after conventional radiation therapy.« less

Evaluation of the dose received in the tissues of the neck during quantification of iodine in the thyroid by X-ray fluorescence spectrometry

NASA Astrophysics Data System (ADS)

Portararo, Antonio; Licour, Caroline; Gerardy, Isabelle; Pozuelo Navarro, Fausto

2018-04-01

The determination of the iodine content in the thyroid is of great interest for many investigations of this gland. The conventional scintigraphic method, using radionuclides, is efficient but delivers a significant dose to the patient. The X-ray fluorescence spectrometry could give information about the iodine content in the thyroid. The measured signal is obtained after stimulation of the stable iodine contained in the gland by X-rays. The advantage of this technique is the complete absence of radioactive isotope injected into the patient body. By applying this, a decrease in effective dose to the patient should be obtained. In this work, the study of the dose received by a thyroid phantom (surrounded by the different tissues of the neck) was performed. The phantom is made of PLA. The dose is measured in optimised conditions defined for the analytical technique. A total head-neck phantom was also used in order to consider the absorbed dose in each different tissues and organs as spinal cord or eyes. Thermo-luminescence dosimeters were chosen for their small size, their sensitivity and the easy positioning on the surface of the phantom but also inside of it to evaluate dose to internal organs. Those LiF 100 dosimeters have been calibrated within the X-ray beam also used for the analysis of iodine. The repeatability and reproducibility of the method has been evaluated. The influence of parameters as concentration of iodine in the thyroid, distance between the X-ray generator and the neck, thickness of the tissues surrounding the thyroid, has been investigated in terms of modifying parameters of the dose received by different tissues situated in the neck and the head.

Multiple-, But Not Single-, Dose of Parecoxib Reduces Shoulder Pain after Gynecologic Laparoscopy

PubMed Central

Zhang, Hufei; Shu, Haihua; Yang, Lu; Cao, Minghui; Zhang, Jingjun; Liu, Kexuan; Xiao, Liangcan; Zhang, Xuyu

2012-01-01

Background: The aim of this study was to investigate effect of single- and multiple-dose of parecoxib on shoulder pain after gynecologic laparoscopy. Methods: 126 patients requiring elective gynecologic laparoscopy were randomly allocated to three groups. Group M (multiple-dose): receiving parecoxib 40mg at 30min before the end of surgery, at 8 and 20hr after surgery, respectively; Group S (single-dose): receiving parecoxib 40mg at 30min before the end of surgery and normal saline at the corresponding time points; Group C (control): receiving normal saline at the same three time points. The shoulder pain was evaluated, both at rest and with motion, at postoperative 6, 24 and 48hr. The impact of shoulder pain on patients' recovery (activity, mood, walking and sleep) was also evaluated. Meanwhile, rescue analgesics and complications were recorded. Results: The overall incidence of shoulder pain in group M (37.5%) was lower than that in group C (61.9%) (difference=-24.4%; 95% CI: 3.4~45.4%; P=0.023). Whereas, single-dose regimen (61.0%) showed no significant reduction (difference with control=-0.9%; 95% CI: -21.9~20.0%; P=0.931). Moreover, multiple-dose regimen reduced the maximal intensity of shoulder pain and the impact for activity and mood in comparison to the control. Multiple-dose of parecoxib decreased the consumption of rescue analgesics. The complications were similar among all groups and no severe complications were observed. Conclusions: Multiple-, but not single-, dose of parecoxib may attenuate the incidence and intensity of shoulder pain and thereby improve patients' quality of recovery following gynecologic laparoscopy. PMID:23136538

Rifapentine Pharmacokinetics and Tolerability in Children and Adults Treated Once Weekly With Rifapentine and Isoniazid for Latent Tuberculosis Infection.

PubMed

Weiner, Marc; Savic, Radojka M; Kenzie, William R Mac; Wing, Diane; Peloquin, Charles A; Engle, Melissa; Bliven, Erin; Prihoda, Thomas J; Gelfond, Jonathan A L; Scott, Nigel A; Abdel-Rahman, Susan M; Kearns, Gregory L; Burman, William J; Sterling, Timothy R; Villarino, M Elsa

2014-06-01

In a phase 3, randomized clinical trial (PREVENT TB) of 8053 people with latent tuberculosis infection, 12 once-weekly doses of rifapentine and isoniazid had good efficacy and tolerability. Children received higher rifapentine milligram per kilogram doses than adults. In the present pharmacokinetic study (a component of the PREVENT TB trial), rifapentine exposure was compared between children and adults. Rifapentine doses in children ranged from 300 to 900 mg, and adults received 900 mg. Children who could not swallow tablets received crushed tablets. Sparse pharmacokinetic sampling was performed with 1 rifapentine concentration at 24 hours after drug administration (C24). Rifapentine area under concentration-time curve (AUC) was estimated from a nonlinear, mixed effects regression model (NLME). There were 80 children (age: median, 4.5 years; range, 2-11 years) and 77 adults (age: median, 40 years; all ≥18 years) in the study. The geometric mean rifapentine milligram per kilogram dose was greater in children than in adults (children, 23 mg/kg; adults, 11 mg/kg). Rifapentine geometric mean AUC and C24 were 1.3-fold greater in children (all children combined) than in adults. Children who swallowed whole tablets had 1.3-fold higher geometric mean AUC than children who received crushed tablets, and children who swallowed whole tablets had a 1.6-fold higher geometric mean AUC than adults. The higher rifapentine doses in children were well tolerated. To obtain rifapentine exposures comparable in children to adults, dosing algorithms modeled by NLME were developed. A 2-fold greater rifapentine dose for all children resulted in a 1.3-fold higher AUC compared to adults administered a standard dose. Use of higher weight-adjusted rifapentine doses for young children are warranted to achieve systemic exposures that are associated with successful treatment of latent tuberculosis infection in adults. Published by Oxford University Press on behalf of the Pediatric Infectious Diseases Society 2014. This work is written by US Government employees and is in the public domain in the US.

Effectiveness of an oral cholera vaccine campaign to prevent clinically-significant cholera in Odisha State, India.

PubMed

Wierzba, Thomas F; Kar, Shantanu K; Mogasale, Vijayalaxmi V; Kerketta, Anna S; You, Young Ae; Baral, Prameela; Khuntia, Hemant K; Ali, Mohammad; Kim, Yang Hee; Rath, Shyam Bandhu; Bhattachan, Anuj; Sah, Binod

2015-05-15

A clinical trial conducted in India suggests that the oral cholera vaccine, Shanchol, provides 65% protection over five years against clinically-significant cholera. Although the vaccine is efficacious when tested in an experimental setting, policymakers are more likely to use this vaccine after receiving evidence demonstrating protection when delivered to communities using local health department staff, cold chain equipment, and logistics. We used a test-negative, case-control design to evaluate the effectiveness of a vaccination campaign using Shanchol and validated the results using a cohort approach that addressed disparities in healthcare seeking behavior. The campaign was conducted by the local health department using existing resources in a cholera-endemic area of Puri District, Odisha State, India. All non-pregnant residents one year of age and older were offered vaccine. Over the next two years, residents seeking care for diarrhea at one of five health facilities were asked to enroll following informed consent. Cases were patients seeking treatment for laboratory-confirmed V. cholera-associated diarrhea. Controls were patients seeking treatment for V. cholerae negative diarrhea. Of 51,488 eligible residents, 31,552 individuals received one dose and 23,751 residents received two vaccine doses. We identified 44 V. cholerae O1-associated cases and 366 non V. cholerae diarrhea controls. The adjusted protective effectiveness for persons receiving two doses was 69.0% (95% CI: 14.5% to 88.8%), which is similar to the adjusted estimates obtained from the cohort approach. A statistical trend test suggested a single dose provided a modicum of protection (33%, test for trend, p=0.0091). This vaccine was found to be as efficacious as the results reported from a clinical trial when administered to a rural population using local health personnel and resources. This study provides evidence that this vaccine should be widely deployed by public health departments in cholera endemic areas. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Treatment of Endometriosis-Associated Pain with Elagolix, an Oral GnRH Antagonist.

PubMed

Taylor, Hugh S; Giudice, Linda C; Lessey, Bruce A; Abrao, Mauricio S; Kotarski, Jan; Archer, David F; Diamond, Michael P; Surrey, Eric; Johnson, Neil P; Watts, Nelson B; Gallagher, J Chris; Simon, James A; Carr, Bruce R; Dmowski, W Paul; Leyland, Nicholas; Rowan, Jean P; Duan, W Rachel; Ng, Juki; Schwefel, Brittany; Thomas, James W; Jain, Rita I; Chwalisz, Kristof

2017-07-06

Endometriosis is a chronic, estrogen-dependent condition that causes dysmenorrhea and pelvic pain. Elagolix, an oral, nonpeptide, gonadotropin-releasing hormone (GnRH) antagonist, produced partial to nearly full estrogen suppression in previous studies. We performed two similar, double-blind, randomized, 6-month phase 3 trials (Elaris Endometriosis I and II [EM-I and EM-II]) to evaluate the effects of two doses of elagolix - 150 mg once daily (lower-dose group) and 200 mg twice daily (higher-dose group) - as compared with placebo in women with surgically diagnosed endometriosis and moderate or severe endometriosis-associated pain. The two primary efficacy end points were the proportion of women who had a clinical response with respect to dysmenorrhea and the proportion who had a clinical response with respect to nonmenstrual pelvic pain at 3 months. Each of these end points was measured as a clinically meaningful reduction in the pain score and a decreased or stable use of rescue analgesic agents, as recorded in a daily electronic diary. A total of 872 women underwent randomization in Elaris EM-I and 817 in Elaris EM-II; of these women, 653 (74.9%) and 632 (77.4%), respectively, completed the intervention. At 3 months, a significantly greater proportion of women who received each elagolix dose met the clinical response criteria for the two primary end points than did those who received placebo. In Elaris EM-I, the percentage of women who had a clinical response with respect to dysmenorrhea was 46.4% in the lower-dose elagolix group and 75.8% in the higher-dose elagolix group, as compared with 19.6% in the placebo group; in Elaris EM-II, the corresponding percentages were 43.4% and 72.4%, as compared with 22.7% (P<0.001 for all comparisons). In Elaris EM-I, the percentage of women who had a clinical response with respect to nonmenstrual pelvic pain was 50.4% in the lower-dose elagolix group and 54.5% in the higher-dose elagolix group, as compared with 36.5% in the placebo group (P<0.001 for all comparisons); in Elaris EM-II, the corresponding percentages were 49.8% and 57.8%, as compared with 36.5% (P=0.003 and P<0.001, respectively). The responses with respect to dysmenorrhea and nonmenstrual pelvic pain were sustained at 6 months. Women who received elagolix had higher rates of hot flushes (mostly mild or moderate), higher levels of serum lipids, and greater decreases from baseline in bone mineral density than did those who received placebo; there were no adverse endometrial findings. Both higher and lower doses of elagolix were effective in improving dysmenorrhea and nonmenstrual pelvic pain during a 6-month period in women with endometriosis-associated pain. The two doses of elagolix were associated with hypoestrogenic adverse effects. (Funded by AbbVie; Elaris EM-I and EM-II ClinicalTrials.gov numbers, NCT01620528 and NCT01931670 .).

Cardiac systolic dysfunction in doxorubicin-challenged rats is associated with upregulation of MuRF2 and MuRF3 E3 ligases

PubMed Central

da Silva, Marcia Gracindo; Mattos, Elisabete; Camacho-Pereira, Juliana; Domitrovic, Tatiana; Galina, Antonio; Costa, Mauro W; Kurtenbach, Eleonora

2012-01-01

Doxorubicin (DOXO) is an efficient and low-cost chemotherapeutic agent. The use of DOXO is limited by its side effects, including cardiotoxicity, that may progress to cardiac failure as a result of multifactorial events that have not yet been fully elucidated. In the present study, the effects of DOXO at two different doses were analyzed to identify early functional and molecular markers of cardiac distress. One group of rats received 7.5 mg/kg of DOXO (low-dose group) and was followed for 20 weeks. A subset of these animals was then subjected to an additional cycle of DOXO treatment, generating a cumulative dose of 20 mg/kg (high-dose group). Physiological and biochemical parameters were assessed in both treatment groups and in a control group that received saline. Systolic dysfunction was observed only in the high-dose group. Mitochondrial function analysis showed a clear reduction in oxidative cellular respiration for animals in both DOXO treatment groups, with evidence of complex I damage being observed. Transcriptional analysis by quantitative polymerase chain reaction revealed an increase in atrial natriuretic peptide transcript in the high-dose group, which is consistent with cardiac failure. Analysis of transcription levels of key components of the cardiac ubiquitin-proteasome system found that the ubiquitin E3 ligase muscle ring finger 1 (MuRF1) was upregulated in both the low- and high-dose DOXO groups. MuRF2 and MuRF3 were also upregulated in the high-dose group but not in the low-dose group. This molecular profile may be useful as an early physiological and energetic cardiac failure indicator for testing therapeutic interventions in animal models. PMID:23620696

Fractional dosing of yellow fever vaccine to extend supply: a modelling study.

PubMed

Wu, Joseph T; Peak, Corey M; Leung, Gabriel M; Lipsitch, Marc

2016-12-10

The ongoing yellow fever epidemic in Angola strains the global vaccine supply, prompting WHO to adopt dose sparing for its vaccination campaign in Kinshasa, Democratic Republic of the Congo, in July-August, 2016. Although a 5-fold fractional-dose vaccine is similar to standard-dose vaccine in safety and immunogenicity, efficacy is untested. There is an urgent need to ensure the robustness of fractional-dose vaccination by elucidation of the conditions under which dose fractionation would reduce transmission. We estimate the effective reproductive number for yellow fever in Angola using disease natural history and case report data. With simple mathematical models of yellow fever transmission, we calculate the infection attack rate (the proportion of population infected over the course of an epidemic) with various levels of transmissibility and 5-fold fractional-dose vaccine efficacy for two vaccination scenarios, ie, random vaccination in a hypothetical population that is completely susceptible, and the Kinshasa vaccination campaign in July-August, 2016, with different age cutoff for fractional-dose vaccines. We estimate the effective reproductive number early in the Angola outbreak was between 5·2 and 7·1. If vaccine action is all-or-nothing (ie, a proportion of vaccine recipients receive complete protection [VE] and the remainder receive no protection), n-fold fractionation can greatly reduce infection attack rate as long as VE exceeds 1/n. This benefit threshold becomes more stringent if vaccine action is leaky (ie, the susceptibility of each vaccine recipient is reduced by a factor that is equal to the vaccine efficacy). The age cutoff for fractional-dose vaccines chosen by WHO for the Kinshasa vaccination campaign (2 years) provides the largest reduction in infection attack rate if the efficacy of 5-fold fractional-dose vaccines exceeds 20%. Dose fractionation is an effective strategy for reduction of the infection attack rate that would be robust with a large margin for error in case fractional-dose VE is lower than expected. NIH-MIDAS, HMRF-Hong Kong. Copyright © 2016 Elsevier Ltd. All rights reserved.

Effects of the Chemical Defense Antidote Atropine Sulfate on Helicopter Pilot Performance: An In-Flight Study

DTIC Science & Technology

1991-06-01

reported minor hallucinations . Digging ;,rt -,-,7in -e wis degraded overall and number facility was impaired en the aiernoon of the atropine day...at higher doses; 4) loss of coordination with doses higher than 10 mg; and 5) hallucinations with very large doses of atropine. Longo’s (1966) review...diopter of refractive error, possessed normal hearing , and was between the ages of 24 and 32 (mean=29.1). Each one received a complete physical

Increasing Use of Dose-Escalated External Beam Radiation Therapy for Men With Nonmetastatic Prostate Cancer

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

Swisher-McClure, Samuel, E-mail: Swisher-Mcclure@uphs.upenn.edu; Leonard Davis Institute of Health Economics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA; Mitra, Nandita

Purpose: To examine recent practice patterns, using a large national cancer registry, to understand the extent to which dose-escalated external beam radiation therapy (EBRT) has been incorporated into routine clinical practice for men with prostate cancer. Methods and Materials: We conducted a retrospective observational cohort study using the National Cancer Data Base, a nationwide oncology outcomes database in the United States. We identified 98,755 men diagnosed with nonmetastatic prostate cancer between 2006 and 2011 who received definitive EBRT and classified patients into National Comprehensive Cancer Network (NCCN) risk groups. We defined dose-escalated EBRT as total prescribed dose of ≥75.6 Gy. Usingmore » multivariable logistic regression, we examined the association of patient, clinical, and demographic characteristics with the use of dose-escalated EBRT. Results: Overall, 81.6% of men received dose-escalated EBRT during the study period. The use of dose-escalated EBRT did not vary substantially by NCCN risk group. Use of dose-escalated EBRT increased from 70.7% of patients receiving treatment in 2006 to 89.8% of patients receiving treatment in 2011. On multivariable analysis, year of diagnosis and use of intensity modulated radiation therapy were significantly associated with receipt of dose-escalated EBRT. Conclusions: Our study results indicate that dose-escalated EBRT has been widely adopted by radiation oncologists treating prostate cancer in the United States. The proportion of patients receiving dose-escalated EBRT increased nearly 20% between 2006 and 2011. We observed high utilization rates of dose-escalated EBRT within all disease risk groups. Adoption of intensity modulated radiation therapy was strongly associated with use of dose-escalated treatment.« less

Estimation of Second Primary Cancer Risk After Treatment with Radioactive Iodine for Differentiated Thyroid Carcinoma.

PubMed

Corrêa, Nilton Lavatori; de Sá, Lidia Vasconcellos; de Mello, Rossana Corbo Ramalho

2017-02-01

An increase in the incidence of second primary cancers is the late effect of greatest concern that could occur in differentiated thyroid carcinoma (DTC) patients treated with radioactive iodine (RAI). The decision to treat a patient with RAI should therefore incorporate a careful risk-benefit analysis. The objective of this work was to adapt the risk-estimation models developed by the Biological Effects of Ionizing Radiation Committee to local epidemiological characteristics in order to assess the carcinogenesis risk from radiation in a population of Brazilian DTC patients treated with RAI. Absorbed radiation doses in critical organs were also estimated to determine whether they exceeded the thresholds for deterministic effects. A total of 416 DTC patients treated with RAI were retrospectively studied. Four organs were selected for absorbed dose estimation and subsequent calculation of carcinogenic risk: the kidney, stomach, salivary glands, and bone marrow. Absorbed doses were calculated by dose factors (absorbed dose per unit activity administered) previously established and based on standard human models. The lifetime attributable risk (LAR) of incidence of cancer as a function of age, sex, and organ-specific dose was estimated, relating it to the activity of RAI administered in the initial treatment. The salivary glands received the greatest absorbed doses of radiation, followed by the stomach, kidney, and bone marrow. None of these, however, surpassed the threshold for deterministic effects for a single administration of RAI. Younger patients received the same level of absorbed dose in the critical organs as older patients did. The lifetime attributable risk for stomach cancer incidence was by far the highest, followed in descending order by salivary-gland cancer, leukemia, and kidney cancer. RAI in a single administration is safe in terms of deterministic effects because even high-administered activities do not result in absorbed doses that exceed the thresholds for significant tissue reactions. The Biological Effects of Ionizing Radiation Committee mathematical models are a practical method of quantifying the risks of a second primary cancer, demonstrating a marked decrease in risk for younger patients with the administration of lower RAI activities and suggesting that only the smallest activities necessary to promote an effective ablation should be administered in low-risk DTC patients.

Proarrhythmic potential of halofantrine, terfenadine and clofilium in a modified in vivo model of torsade de pointes

PubMed Central

Batey, Andrew J; Coker, Susan J

2002-01-01

This study was designed to compare the proarrhythmic activity of the antimalarial drug, halofantrine and the antihistamine, terfenadine, with that of clofilium a K+ channel blocking drug that can induce torsade de pointes. Experiments were performed in pentobarbitone-anaesthetized, open-chest rabbits. Each rabbit received intermittent, rising dose i.v. infusions of the α-adrenoceptor agonist phenylephrine. During these infusions rabbits also received increasing i.v. doses of clofilium (20, 60 and 200 nmol kg−1 min−1), terfenadine (75, 250 and 750 nmol kg−1 min−1), halofantrine (6, 20 and 60 μmol kg−1) or vehicle. Clofilium and halofantrine caused dose-dependent increases in the rate-corrected QT interval (QTc), whereas terfenadine prolonged PR and QRS intervals rather than prolonging cardiac repolarization. Progressive bradycardia occurred in all groups. After administration of the highest dose of each drug halofantrine caused a modest decrease in blood pressure, but terfenadine had profound hypotensive effects resulting in death of most rabbits. The total number of ventricular premature beats was highest in the clofilium group. Torsade de pointes occurred in 6 out of 8 clofilium-treated rabbits and 4 out of 6 of those which received halofantrine, but was not seen in any of the seven terfenadine-treated rabbits. These results show that, like clofilium, halofantrine can cause torsade de pointes in a modified anaesthetized rabbit model whereas the primary adverse effect of terfenadine was cardiac contractile failure. PMID:11861329

Effects of a reduced dose of injected iron on health, iron status and growth of suckling piglets with access to iron enriched soil.

PubMed

Thanner, S; Gutzwiller, A

2018-02-01

The effects of the recommended dose of 200 mg iron and of half that dose injected on the first day of life on health, iron status and performance during the 4 week suckling period were studied in 2'123 piglets. All piglets received creep feed and soil which was supplemented with 14 g iron per kg. Neither mortality nor the prevalence of arthritis, meningitis and foot abscess (each disease affecting about 1% of the piglets) differed between the two groups. The low dose of 100 mg iron decreased blood haemoglobin concentration at weaning (110 ± 19 vs.120 ± 15 g/l), but did not affect growth rate.

An Open-Label Trial of Escitalopram in Pervasive Developmental Disorders.

ERIC Educational Resources Information Center

Owley, Thomas; Walton, Laura; Salt, Jeff; Guter, Stephen J., Jr.; Winnega, Marrea; Leventhal, Bennett L.; Cook, Edwin H., Jr.

2005-01-01

Objective: To assess the effect of escitalopram in the treatment of pervasive developmental disorders (PDDs). Method: This 10-week study had a forced titration, open-label design. Twenty-eight subjects (mean age 125.1 [+ or -] 33.5 months) with a PDD received escitalopram at a dose that increased weekly to a maximum dose of 20 mg as tolerated. The…

The Nightly Use of Sodium Oxybate Is Associated with a Reduction in Nocturnal Sleep Disruption: A Double-Blind, Placebo-Controlled Study in Patients with Narcolepsy

PubMed Central

Black, Jed; Pardi, Daniel; Hornfeldt, Carl S.; Inhaber, Neil

2010-01-01

Objective: To further explore the effects of sodium oxybate (SXB) administration on nocturnal sleep in narcolepsy patients during a double-blind, placebo-controlled, parallel group study conducted with 228 adult patients with narcolepsy/cataplexy in the United States, Canada, and Europe. Method: Patients were withdrawn from antidepressants and sedative/hypnotics, and then randomized to receive 4.5, 6, or 9 g SXB or placebo nightly for 8 weeks. Patients receiving 6 and 9 g/night doses were titrated to their final dose in weekly 1.5 g increments, while patients receiving placebo were randomized to undergo a similar mock dose titration. The use of stimulant therapy continued unchanged. Changes in sleep architecture were measured using centrally scored nocturnal polysomnograms. Daily diaries were used to record changes in narcolepsy symptoms and adverse events. Results: Following 8 weeks of SXB treatment, study patients demonstrated significant dose-related increases in the duration of stage 3 and 4 sleep, reaching a median increase of 52.5 minutes in patients receiving 9 g nightly. Compared to placebo-treated patients, delta power was significantly increased in all dose groups. Stage 1 sleep and the frequency of nocturnal awakenings were each significantly decreased at the 6 and 9 g/night doses. The changes in nocturnal sleep coincided with significant decreases in the severity and frequency of narcolepsy symptoms. Conclusions: The nightly administration of SXB to narcolepsy patients significantly impacts measures of slow wave sleep, wake after sleep onset, awakenings, total sleep time, and stage 1 sleep in a dose-related manner. The frequency and severity of narcolepsy symptoms decreased with treatment. Citation: Black J; Pardi D; Hornfeldt CS; Inhaber N. The nightly use of sodium oxybate is associated with a reduction in nocturnal sleep disruption: a double-blind, placebo-controlled study in patients with narcolepsy. J Clin Sleep Med 2010;6(6):596-602. PMID:21206549

The effect of intraoperative administration of dexamethasone for PONV prophylaxis on perioperative blood glucose level in obese and normal weight children.

PubMed

Gnatzy, Richard; Hempel, Gunther; Kaisers, Udo X; Höhne, Claudia

2015-11-01

The incidence of postoperative nausea and vomiting (PONV) can be reduced by dexamethasone. Single-dose administration may cause elevated blood glucose levels in obese adults. No data are available for children. The aim was to evaluate perioperative blood glucose changes related to body weight in children who received dexamethasone. This prospective observational study included 62 children. All patients received total intravenous anesthesia and a single dose of dexamethasone (0.15 mg/kg, maximum 8 mg). Blood glucose levels were measured up to 6 h. Standard deviation scores (SDS) were calculated using age- and gender-specific body mass index (BMI) percentiles, p<0.05. A total of 62 children (11.5±2.9 years, median SDS 0.43, 29% overweight/obese) were included. Blood glucose levels increased from 5.52±0.52 to 6.74±0.84 mmol/L 6 h after dexamethasone without correlation to the BMI-SDS. This study showed an increase of perioperative blood glucose (normoglycemic ranges) after single dose of dexamethasone, but no BMI-dependent effect was observed in children. Therefore, low-dose dexamethasone may be used in obese children for PONV prophylaxis.

Pharmacokinetic and pharmacodynamic profile of supratherapeutic oral doses of Δ9-THC in cannabis users

PubMed Central

Lile, Joshua A.; Kelly, Thomas H.; Charnigo, Richard J.; Stinchcomb, Audra L.; Hays, Lon R.

2013-01-01

Oral Δ9-tetrahydrocannabinol (Δ9-THC) has been evaluated as a medication for cannabis dependence, but repeated administration of acute oral doses up to 40 mg has not been effective at reducing drug-taking behavior. Larger doses might be necessary to affect cannabis use. The purpose of the present study was therefore to determine the physiological and behavioral effects of oral Δ9-THC at acute doses higher than those tested previously. The pharmacokinetic and pharmacodynamic profile of oral Δ9-THC, administered in ascending order in 15 mg increments across separate sessions, up to a maximum of 90 mg, was determined in seven cannabis users. Five subjects received all doses and two experienced untoward side effects at lower doses. Δ9-THC produced a constellation of effects consistent with previous clinical studies. Low cannabinoid concentrations were associated with significant effects on drug- sensitive measures, although progressively greater levels did not lead to proportionately larger drug effects. Considerable variability in Cmax and tmax was observed. Doses of oral Δ9-THC larger than those tested previously can be administered to individuals with a history of cannabis use, although given the pharmacokinetic variability of oral Δ9-THC and individual differences in sensitivity, individualized dose adjustment is needed to avoid side effects and maximize therapeutic response. PMID:23754596

SU-E-T-580: Comparison of Cervical Carcinoma IMRT Plans From Four Commercial Treatment Planning Systems (TPS)

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

Cao, Y; Li, R; Chi, Z

2014-06-01

Purpose: Different treatment planning systems (TPS) use different treatment optimization and leaf sequencing algorithms. This work compares cervical carcinoma IMRT plans optimized with four commercial TPSs to investigate the plan quality in terms of target conformity and delivery efficiency. Methods: Five cervical carcinoma cases were planned with the Corvus, Monaco, Pinnacle and Xio TPSs by experienced planners using appropriate optimization parameters and dose constraints to meet the clinical acceptance criteria. Plans were normalized for at least 95% of PTV to receive the prescription dose (Dp). Dose-volume histograms and isodose distributions were compared. Other quantities such as Dmin(the minimum dose receivedmore » by 99% of GTV/PTV), Dmax(the maximum dose received by 1% of GTV/PTV), D100, D95, D90, V110%, V105%, V100% (the volume of GTV/PTV receiving 110%, 105%, 100% of Dp), conformity index(CI), homogeneity index (HI), the volume of receiving 40Gy and 50 Gy to rectum (V40,V50) ; the volume of receiving 30Gy and 50 Gy to bladder (V30,V50) were evaluated. Total segments and MUs were also compared. Results: While all plans meet target dose specifications and normal tissue constraints, the maximum GTVCI of Pinnacle plans was up to 0.74 and the minimum of Corvus plans was only 0.21, these four TPSs PTVCI had significant difference. The GTVHI and PTVHI of Pinnacle plans are all very low and show a very good dose distribution. Corvus plans received the higer dose of normal tissue. The Monaco plans require significantly less segments and MUs to deliver than the other plans. Conclusion: To deliver on a Varian linear-accelerator, the Pinnacle plans show a very good dose distribution. Corvus plans received the higer dose of normal tissue. The Monaco plans have faster beam delivery.« less

Tranexamic acid use during total hip arthroplasty: A single center retrospective analysis.

PubMed

Stoicea, Nicoleta; Moran, Kenneth; Mahmoud, Abdel-Rasoul; Glassman, Andrew; Ellis, Thomas; Ryan, John; Granger, Jeffrey; Joseph, Nicholas; Salon, Nathan; Ackermann, Wiebke; Rogers, Barbara; Niermeyer, Weston; Bergese, Sergio D

2018-05-01

Tranexamic acid (TXA) is an antifibrinolytic agent that has shown promise in reducing blood loss during total hip arthroplasty (THA). Several studies have reported side effects of high-dose TXA administration, including myocardial infarction (MI), thromboembolic events, and seizures. These possible side effects have prevented the widespread adoption of TXA in the surgical community. We conducted a retrospective chart review of 564 primary and revision THAs performed at a single academic center. Surgical patients received either no TXA or 1 g IV TXA at the beginning of surgery followed by a second bolus just before the surgical wound closure, at the surgeon's discretion. We analyzed differences in hemoglobin (Hb), hematocrit (Hct), estimated blood loss (EBL), and adverse events in patients receiving TXA versus patients not receiving TXA up to 2 days following surgery. Significantly higher Hb and Hct values were found across all time points among patients undergoing primary posterior or revision THA who had received TXA. In addition, transfusion rates were significantly decreased in both primary posterior THAs and revision THAs when TXA was administered. Patients who received TXA experienced significantly fewer adverse events than those who did not for all surgery types. Administration of low-dose intravenous (IV) and intra-articular (IA) TXA does not appear to increase rates of adverse events and may be effective in minimizing blood loss, as reflected by Hb and Hct values following THA.

Application of the Extended Health Control Belief Model to Predict Hepatitis A and B Vaccinations.

PubMed

Reynolds, Grace L; Nguyen, Hannah H; Singh-Carlson, Savitri; Fisher, Dennis G; Odell, Anne; Xandre, Pamela

2016-09-01

Adult vaccination compliance rates vary according to sample and type of vaccine administered (influenza, pneumococcal). This study looked at vaccination of a community sample of low-income, minority adults. Nurses offered free vaccination for hepatitis A and B in the form of the combined Twinrix vaccine to adults on a walk-in basis. In addition to dosing information, participants completed the Risk Behavior Assessment, the Coping Strategies Indicator and the Cardiovascular Risk Assessment. Skaff's extended Health Belief Model was used as the theoretical framework. Count regression was used to model receipt of one, two, or three doses. The majority of participants were male with a mean age of 40 years. The distribution of doses was: 173 individuals (27.6%) received one dose only, 261 (41.7%) received two doses, and 191 (30.5%) received three doses of vaccine. The multivariate count regression model including being male, having previously been told by a health care provider that one has syphilis, having severe negative emotions, and perceived social support were associated with participants' receiving fewer doses of hepatitis vaccine. A greater problem-solving score was associated with a higher number of vaccine doses received. Despite free vaccinations offered in an easily accessible community setting, the majority of participants failed to complete the hepatitis vaccine series. More effort is needed to get adult men to participate in hepatitis vaccination clinics. Additional research is necessary to understand barriers other than cost to adults receiving vaccination. © 2016 Wiley Periodicals, Inc.

A rapid enhancement of locomotor sensitization to amphetamine by estradiol in female rats.

PubMed

Zovkic, Iva B; McCormick, Cheryl M

2017-11-14

Estradiol moderates the effects of drugs of abuse in both humans and rodents. Estradiol's enhancement of behavioral effects resulting from high (>2.5mg/kg) doses of amphetamine is established in rats; there is less evidence for the role of estradiol in locomotor effects elicited by lower doses, which are less aversive, increase incentive motivation, involve different neural mechanisms than higher doses, and often more readily reveal group differences than do higher doses. Further, the extent to which estradiol is required for the induction versus the expression of sensitization is unknown. To establish a protocol, we replicated the effects of estradiol on locomotor sensitization to amphetamine reported in a previous study that involved a high locomotor-activating dose (1.5mg/kg) of amphetamine, but with a lower dose. Ovariectomized female rats received 5μg of estradiol benzoate (EB) or OIL 30min before each of 5 treatments of 1.0mg/kg amphetamine or saline; all received a 0.5mg/kg challenge dose three days later. Compared with results for OIL, EB enhanced the locomotor-activating effects of repeated 1.0mg/kg amphetamine across treatment days. In contrast, on challenge day, there was no difference between EB-saline and EB-amphetamine to the lower dose (i.e., no sensitization). Experiments 2 and 3 involved a shorter induction (2days) and a lengthier withdrawal (9days) before the challenge test for the expression of sensitization to better differentiate the induction phase from the expression phase. In Expt2, EB-, and not OIL-, treated rats showed sensitization to 0.5mg/kg amphetamine; neither group showed sensitization to 1.5mg/kg amphetamine (ceiling effect?). In Expt3, rats were treated with EB either in both the induction and expression phases, in one of the phases only, or in neither phase. There was an effect of hormone treatment on challenge day and not on induction day; rats given EB on Challenge day showed sensitization to 0.5mg/kg amphetamine; OIL rats did not. The results suggest rapid effects of estradiol on amphetamine sensitization consistent with rapid effects of estradiol reported for other behaviours. Copyright © 2017. Published by Elsevier Inc.

Comparison of organ doses for patients undergoing balloon brachytherapy of the breast with HDR 192Ir or electronic sources using Monte Carlo simulations in a heterogeneous human phantom1

PubMed Central

Mille, Matthew M.; Xu, X. George; Rivard, Mark J.

2010-01-01

Purpose: Accelerated partial breast irradiation via interstitial balloon brachytherapy is a fast and effective treatment method for certain early stage breast cancers. The radiation can be delivered using a conventional high-dose rate (HDR) 192Ir gamma-emitting source or a novel electronic brachytherapy (eBx) source which uses lower energy x rays that do not penetrate as far within the patient. A previous study [A. Dickler, M. C. Kirk, N. Seif, K. Griem, K. Dowlatshahi, D. Francescatti, and R. A. Abrams, “A dosimetric comparison of MammoSite high-dose-rate brachytherapy and Xoft Axxent electronic brachytherapy,” Brachytherapy 6, 164–168 (2007)] showed that the target dose is similar for HDR 192Ir and eBx. This study compares these sources based on the dose received by healthy organs and tissues away from the treatment site. Methods: A virtual patient with left breast cancer was represented by a whole-body, tissue-heterogeneous female voxel phantom. Monte Carlo methods were used to calculate the dose to healthy organs in a virtual patient undergoing balloon brachytherapy of the left breast with HDR 192Ir or eBx sources. The dose-volume histograms for a few organs which received large doses were also calculated. Additional simulations were performed with all tissues in the phantom defined as water to study the effect of tissue inhomogeneities. Results: For both HDR 192Ir and eBx, the largest mean organ doses were received by the ribs, thymus gland, left lung, heart, and sternum which were close to the brachytherapy source in the left breast. eBx yielded mean healthy organ doses that were more than a factor of ∼1.4 smaller than for HDR 192Ir for all organs considered, except for the three closest ribs. Excluding these ribs, the average and median dose-reduction factors were ∼28 and ∼11, respectively. The volume distribution of doses in nearby soft tissue organs that were outside the PTV were also improved with eBx. However, the maximum dose to the closest rib with the eBx source was 5.4 times greater than that of the HDR 192Ir source. The ratio of tissue-to-water maximum rib dose for the eBx source was ∼5. Conclusions: The results of this study indicate that eBx may offer lower toxicity to most healthy tissues, except nearby bone. TG-43 methods have a tendency to underestimate dose to bone, especially the ribs. Clinical studies evaluating the negative health effects caused by irradiating healthy organs are needed so that physicians can better understand when HDR 192Ir or eBx might best benefit a patient. PMID:20229875

Effect of esomeprazole and rabeprazole on intragastric pH in healthy Chinese: an open, randomized crossover trial.

PubMed

Li, Zhao-Shen; Zhan, Xian-Bao; Xu, Guo-Ming; Cheng, Neng-Neng; Liao, Zhuan

2007-06-01

Esomeprazole is the S-isomer of omeprazole, with a stronger acid suppressive effect than omeprazole. This open, randomized crossover study was designed to evaluate the effect of esomeprazole and another proton-pump inhibitor, rabeprazole, on intragastric pH in healthy Chinese. Thirty-six healthy volunteers (26 men and 10 women, aged between 20 and 31 years) were enrolled. Subjects were given either esomeprazole 40 mg (n = 18) or rabeprazole 10 mg (n = 18) orally once daily for 5 days during the first dosing period, then the other medicine at the set dosage for the second dosing period. The two periods were separated by a 14-day washout phase. The doses were chosen according to the State Food and Drug Administration of China for the treatment of acid-related diseases. Intragastric pH was continuously monitored for 24 h on days 1 and 5 of each dosing period. CYP2C19 genotypes were analyzed to identify the extensive metabolizers (EM) and poor metabolizers (PM). The percentage of time with intragastric pH >4 was significantly higher (P < 0.001) in subjects receiving esomeprazole than in those receiving rabeprazole in the first 4 h after administration of the first dose (70.65% vs 44.87%), at 24 h on day 1 (73.7% vs 54.8%) and at 24 h on day 5 (84.2% vs 76.2%). The median intragastric pH was also higher in subjects receiving esomeprazole than in those receiving rabeprazole in the first 6 h, day 1 and day 5 (P 4 for at least 16 h on day 1 (63.9% vs 33.3%) and on day 5 (88.9% vs 61.1%) was higher after administration of esomeprazole than after rabeprazole (both P < 0.05). On genotype analysis, 28 of the subjects were EM and eight were PM. Those who were PM tended to have a higher, albeit not statistically significant, percentage of time with intragastric pH >4 and the median 24-h intragastric pH than those who were EM. Both drugs were well tolerated. Esomeprazole 40 mg orally once daily is more effective and faster in increasing intragastric pH than rabeprazole 10 mg orally once daily, and thus offers a potential for improved efficacy in acid-related diseases.

Effectiveness of hepatitis A vaccination as post-exposure prophylaxis

PubMed Central

Parrón, Ignasi; Planas, Caritat; Manzanares-Laya, Sandra; Martínez, Ana; Sala, Maria Rosa; Minguell, Sofia; Jané, Mireia

2017-01-01

ABSTRACT Hepatitis A (HA) has been a vaccine-preventable disease since 1995. In Catalonia, a universal combined hepatitis A+B vaccination program of preadolescents was initiated at the end of 1998. However, outbreaks are reported each year and post-exposure prophylaxis (PEP) with hepatitis A virus (HAV) vaccine or immunoglobulin (IG) is recommended to avoid cases. The aim of this study was to assess the effectiveness of HAV vaccine and IG in preventing hepatitis A cases in susceptible exposed people. A retrospective cohort study of contacts of HA cases involved in outbreaks reported in Catalonia between January 2006 and December 2012 was made. The rate ratios and 95% confidence intervals (CI) of HA in susceptible contacts receiving HAV or IG versus those without PEP were calculated. There were 3550 exposed persons in the outbreaks studied: 2381 received one dose of HAV vaccine (Hepatitis A or hepatitis A+B), 190 received IG, and 611 received no PEP. 368 exposed subjects received one dose of HAV vaccine and IG simultaneously and were excluded from the study. The effectiveness of PEP was 97.6% (95% CI 96.2–98.6) for HAV vaccine and 98.3% (95% CI 91.3–99.9) for IG; the differences were not statistically significant (p = 0.36). The elevated effectiveness of HAV vaccination for PEP in HA outbreaks, similar to that of IG, and the long-term protection of active immunization, supports the preferential use of vaccination to avoid secondary cases. PMID:27925847

Effectiveness of hepatitis A vaccination as post-exposure prophylaxis.

PubMed

Parrón, Ignasi; Planas, Caritat; Godoy, Pere; Manzanares-Laya, Sandra; Martínez, Ana; Sala, Maria Rosa; Minguell, Sofia; Torner, Nuria; Jané, Mireia; Domínguez, Angela

2017-02-01

Hepatitis A (HA) has been a vaccine-preventable disease since 1995. In Catalonia, a universal combined hepatitis A+B vaccination program of preadolescents was initiated at the end of 1998. However, outbreaks are reported each year and post-exposure prophylaxis (PEP) with hepatitis A virus (HAV) vaccine or immunoglobulin (IG) is recommended to avoid cases. The aim of this study was to assess the effectiveness of HAV vaccine and IG in preventing hepatitis A cases in susceptible exposed people. A retrospective cohort study of contacts of HA cases involved in outbreaks reported in Catalonia between January 2006 and December 2012 was made. The rate ratios and 95% confidence intervals (CI) of HA in susceptible contacts receiving HAV or IG versus those without PEP were calculated. There were 3550 exposed persons in the outbreaks studied: 2381 received one dose of HAV vaccine (Hepatitis A or hepatitis A+B), 190 received IG, and 611 received no PEP. 368 exposed subjects received one dose of HAV vaccine and IG simultaneously and were excluded from the study. The effectiveness of PEP was 97.6% (95% CI 96.2-98.6) for HAV vaccine and 98.3% (95% CI 91.3-99.9) for IG; the differences were not statistically significant (p = 0.36). The elevated effectiveness of HAV vaccination for PEP in HA outbreaks, similar to that of IG, and the long-term protection of active immunization, supports the preferential use of vaccination to avoid secondary cases.

Single ascending oral dose pharmacokinetics and pharmacodynamics study of EV-077: the specific inhibitor of prostanoid- and isoprostane-induced cellular activation.

PubMed

Richardson, A; Sakariassen, K S; Meyer, J-P; Alberts, P; Sorensen, A S

2013-03-01

This study was performed to determine the oral pharmacokinetics (PK) of EV-077 and its effects on pharmacodynamic (PD) markers. EV-077 blocks prostanoid-induced and isoprostane-induced cellular activation, and is in development for the treatment of vascular inflammation and associated complications of type-2 diabetes.. This single-ascending-dose mono-centre study was randomised, placebo-controlled, and double-blinded within each dose group. Seven EV-077 doses were administered sequentially as an oral solution: 0.0125, 0.125, 0.375, 0.75, 1.25, 1.875 and 2.5 mg/kg body weight. PK, platelet aggregation, bleeding time and safety parameters were measured. Seven to eight healthy male subjects were dosed per group: five to six subjects received EV-077 and two subjects received placebo. Tmax was reached rapidly between 0.5 h and 1.0 h. Both Cmax and AUC increased linearly with the dose. The apparent terminal half-life (t½z) increased with the dose, most likely reflecting the increasing last quantifiable concentration with increasing dose; at 2.5 mg/kg, it was 2.7-6.9 h. Measurement of platelet aggregation showed no effect at 0.0125 mg/kg, and a full and reversible inhibition at doses of 0.125-2.5 mg/kg. The average bleeding time was dose-dependently prolonged, but was always below 9 min. The PK/PD profile showed that at plasma concentrations above 20 ng/ml, EV-077 platelet aggregation was completely inhibited (>90 %). All tested doses were well tolerated. Orally administered EV-077 was well tolerated, readily absorbed, reached Cmax within 1 h, with a linear PK based on Cmax and AUC. The inhibition of platelet aggregation was complete and reversible at doses of 0.125 mg/kg and higher, and average bleeding time was below 9 min.

An estimation of Canadian population exposure to cosmic rays from air travel.

PubMed

Chen, Jing; Newton, Dustin

2013-03-01

Based on air travel statistics in 1984, it was estimated that less than 4 % of the population dose from cosmic ray exposure would result from air travel. In the present study, cosmic ray doses were calculated for more than 3,000 flights departing from more than 200 Canadian airports using actual flight profiles. Based on currently available air travel statistics, the annual per capita effective dose from air transportation is estimated to be 32 μSv for Canadians, about 10 % of the average cosmic ray dose received at ground level (310 μSv per year).

Effect of delayed anthrax vaccine dose on Bacillus anthracis protective antigen IgG response and lethal toxin neutralization activity.

PubMed

Pittman, Phillip R; Fisher, Diana; Quinn, Xiaofei; Schmader, Trevor; Barrera-Oro, Julio G

2013-10-17

We describe the Bacillus anthracis protective antigen IgG antibody response and the B. anthracis lethal toxin neutralization activity to a delayed dose of anthrax vaccine adsorbed (AVA, BioThrax(®)) using validated assays. 373 individuals received 1, 2, or 3 priming doses, 18-24 months afterward, they received a delayed dose of AVA. Overall, 23.6% of subjects showed detectable anti-PA IgG before the boost, compared to 99.2% (P<0.0001) 28 days after the boost. Geometric mean anti-PA IgG concentration (GMC) was 1.66 μg/mL before and 887.82 μg/mL after the boost (P<0.0001). The proportion of individuals with four-fold increase in GMC following the boost ranged from 93.8% to 100%. Robust anti-PA IgG levels and B. anthracis lethal toxin neutralization activity are induced when an AVA dose is delayed as long as two years. These data support continuing with the vaccination schedule when a dose is delayed as long as two years rather than restarting the series. Published by Elsevier Ltd.

Effects of β-blockers and anxiety on complication rates after acute myocardial infarction.

PubMed

Abu Ruz, Mohannad E; Lennie, Terry A; Moser, Debra K

2011-01-01

Anxiety is common after acute myocardial infarction and increases the number of complications and the length of stay in the hospital. Anxiety-induced activation of the sympathetic nervous system is hypothesized to be an underlying cause of increased complication rates. Little is known about whether use of β-blockers eliminates the effects of anxiety on complication rate and length of stay. To compare number of complications and length of stay among nonanxious and anxious patients receiving β-blockers during hospitalization. A total of 322 patients with acute myocardial infarction participated in this study within 48 hours of hospital admission. Patients completed the Brief Symptom Inventory to assess anxiety level. After discharge, medical records were reviewed to determine use of β-blockers, type and number of complications, and length of stay. Most patients (96%) were treated with less than 200 mg daily of metoprolol. Anxious patients had more complications (mean [SD], 1.43 [0.15] vs 0.73 [.09], P ≤ .01) and longer stays (7.0 [0.49] vs 5.7 [0.36] days, P < .05) than did nonanxious patients. To test whether the dose of β-blocker made a difference, the interaction between daily dose and anxiety score was tested. No interaction was found between metoprolol dose and anxiety score, and no main effect was found for metoprolol dose. Anxious patients had more complications and longer stays than did nonanxious patients. The administration of metoprolol did not eliminate this relationship, perhaps because patients did not receive a sufficient dose of metoprolol to counter the effect of anxiety.

Effect of heterogeneity correction on dosimetric parameters of radiotherapy planning for thoracic esophageal cancer

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

Nakayama, Masao, E-mail: naka2008@med.kobe-u.ac.jp; Yoshida, Kenji; Nishimura, Hideki

2014-04-01

The present study aimed to investigate the effect of heterogeneity correction (HC) on dosimetric parameters in 3-dimensional conformal radiotherapy planning for patients with thoracic esophageal cancer. We retrospectively analyzed 20 patients. Two treatment plans were generated for each patient using a superposition algorithm on the Xio radiotherapy planning system. The first plan was calculated without HC. The second was a new plan calculated with HC, using identical beam geometries and maintaining the same number of monitor units as the first. With regard to the planning target volume (PTV), the overall mean differences in the prescription dose, maximum dose, mean dose,more » and dose that covers 95% of the PTV between the first and second plans were 1.10 Gy (1.8%), 1.35 Gy (2.2%), 1.10 Gy (1.9%), and 0.56 Gy (1.0%), respectively. With regard to parameters related to the organs at risk (OARs), the mean differences in the absolute percentages of lung volume receiving greater than 5, 10, 20, and 30 Gy (lung V{sub 5}, V{sub 10}, V{sub 20}, and V{sub 30}) between the first and second plans were 7.1%, 2.7%, 0.4%, and 0.5%, respectively. These results suggest that HC might have a more pronounced effect on the percentages of lung volume receiving lower doses (e.g., V{sub 5} and V{sub 10}) than on the dosimetric parameters related to the PTV and other OARs.« less

High dose of antacid (Mylanta II) reduces bioavailability of ranitidine.

PubMed Central

Mihaly, G W; Marino, A T; Webster, L K; Jones, D B; Louis, W J; Smallwood, R A

1982-01-01

To investigate the effect of antacid on the bioavailability and disposition of ranitidine six healthy volunteers were studied on two occasions one week apart. In the first study the received ranitidine 150 mg with 60 ml water, and in the second study they received ranitidine 150 mg plus 30 ml of an aluminium/magnesium hydroxide mixture (Mylanta II) and 30 ml water. Giving antacid reduced both the maximum plasma ranitidine concentration and the area under the curve by one-third; elimination of the drug was not changed. Thus giving a high dose of antacid significantly diminished the bioavailability of ranitidine. PMID:6289961

Effects of temperature during the irradiation of calcium carbonate.

PubMed

Negrón-Mendoza, Alicia; Camargo-Raya, Claudia; Gómez-Vidales, Virginia; Uribe, Roberto M; Ramos-Bernal, Sergio

2016-05-01

Calcium carbonate received gamma irradiation at different doses (0-309kGy) and temperature regimes (77-298K) to study the effects of irradiation temperature. The changes were followed by EPR spectroscopy. We observed the formation of a composite EPR spectrum, even at low radiation doses and temperature. There was a strong effect on the evaluation of the radicals formed as a function of irradiation temperature, probably due to the diffusion in the frozen powder and the recombination of some radicals at room temperature. Copyright © 2016 Elsevier Ltd. All rights reserved.

Efficacy and Safety of Escalation of Adalimumab Therapy to Weekly Dosing in Pediatric Patients with Crohn's Disease.

PubMed

Dubinsky, Marla C; Rosh, Joel; Faubion, William A; Kierkus, Jaroslaw; Ruemmele, Frank; Hyams, Jeffrey S; Eichner, Samantha; Li, Yao; Huang, Bidan; Mostafa, Nael M; Lazar, Andreas; Thakkar, Roopal B

2016-04-01

The efficacy of adalimumab in inducing and maintaining remission in children with moderately to severely active Crohn's disease was shown in the IMAgINE 1 trial (NCT00409682). As per protocol, nonresponders or patients experiencing flare(s) on every other week (EOW) maintenance dosing could escalate to weekly dosing; we aimed to determine the therapeutic benefits of weekly dose escalation in this subpopulation. Week 52 remission and response rates were assessed in patients who escalated to weekly dosing from their previous EOW schedule, which was according to randomized treatment dose (higher dose [HD] adalimumab [≥40 kg, 40 mg EOW; <40 kg, 20 mg EOW] or lower dose [LD; ≥40 kg, 20 mg EOW; <40 kg, 10 mg EOW]). Adverse events were reported for patients remaining on EOW dosing and patients receiving weekly dosing. Escalation to weekly dosing occurred in 48/95 (50.5%) patients randomized to LD and 35/93 (37.6%) patients randomized to HD adalimumab (P = 0.076). Week 52 remission and response rates were 18.8% and 47.9% for patients receiving LD adalimumab weekly and 31.4% and 57.1% for patients receiving HD adalimumab weekly, respectively (LD versus HD, P = 0.19 for remission; P = 0.41 for response). Adverse event rates were similar for patients receiving EOW and weekly adalimumab. Weekly adalimumab dosing was clinically beneficial for children with Crohn's disease who experienced nonresponse or flare on EOW dosing. No increased safety risks were observed with weekly dosing.

Effects of intra-aortic balloon counterpulsation in a model of septic shock.

PubMed

Solomon, Steven B; Minneci, Peter C; Deans, Katherine J; Feng, Jing; Eichacker, Peter Q; Banks, Steven M; Danner, Robert L; Natanson, Charles; Solomon, Michael A

2009-01-01

Fluid refractory septic shock can develop into a hypodynamic cardiovascular state in both children and adults. Despite management of these patients with empirical inotropic therapy (with or without a vasodilator), mortality remains high. The effect of cardiovascular support using intra-aortic balloon counterpulsation was investigated in a hypodynamic, mechanically ventilated canine sepsis model in which cardiovascular and pulmonary support were titrated based on treatment protocols. Each week, three animals (n = 33, 10-12 kg) were administered intrabronchial Staphylococcus aureus challenge and then randomized to receive intra-aortic balloon counterpulsation for 68 hrs or no intra-aortic balloon counterpulsation (control). Bacterial doses were increased over the study (4-8 x 10(9) cfu/kg) to assess the effects of intra-aortic balloon counterpulsation during sepsis with increasing risk of death. Compared with lower bacterial doses (4-7 x 10(9) colony-forming units/kg), control animals challenged with the highest dose (8 x 10(9) colony-forming units/kg) had a greater risk of death (mortality rate 86% vs. 17%), with worse lung injury ([A - a]O2), and renal dysfunction (creatinine). These sicker animals required higher norepinephrine infusion rates to maintain blood pressure (and higher FIO2) and positive end-expiratory pressure levels to maintain oxygenation (p < or = 0.04 for all). In animals receiving the highest bacterial dose, intra-aortic balloon counterpulsation improved survival time (23.4 +/- 10 hrs longer; p = 0.003) and lowered norepinephrine requirements (0.43 +/- 0.17 microg/kg/min; p = 0.002) and systemic vascular resistance index (1.44 +/- 0.57 dynes/s/cm5/kg; p = 0.0001) compared with controls. Despite these beneficial effects, intra-aortic balloon counterpulsation was associated with an increase in blood urea nitrogen (p = 0.002) and creatinine (p = 0.12). In animals receiving lower doses of bacteria, intra-aortic balloon counterpulsation had no significant effects on survival or renal function. In a canine model of severe septic shock with a low cardiac index, intra-aortic balloon counterpulsation prolongs survival time and lowers vasopressor requirements.

Clinical Pharmacokinetics of IPX066: Evaluation of Dose Proportionality and Effect of Food in Healthy Volunteers

PubMed Central

Yao, Hsuan-Ming; Hsu, Ann; Gupta, Suneel; Modi, Nishit B.

2016-01-01

Objectives IPX066 is an oral, extended-release capsule formulation of carbidopa-levodopa (CD-LD) available in 4 strengths. The goals of this investigation were to assess the dose proportionality of IPX066 and to study the effects of a high-fat, high-calorie meal and of sprinkling the capsule contents on applesauce on the pharmacokinetics of IPX066 in healthy volunteers. Methods Three open-label studies were conducted. In the first study, subjects received 1 capsule of each IPX066 strength (23.75–95, 36.25–145, 48.75–195, and 61.25–245 mg of CD-LD). In the second study, subjects received 1 and 2 capsules of IPX066 245-mg LD under fasting conditions. In the third study, subjects received 2 capsules of IPX066 245-mg LD under 3 conditions: fasting; following a high-fat, high-calorie breakfast; and with the capsule contents sprinkled on applesauce under fasting conditions. Results Peak plasma concentrations (Cmax) and systemic exposure (AUCt, AUCinf) for LD and CD increased dose-proportionally over the range of the IPX066 capsule strengths. Comparison of 1 and 2 IPX066 245-mg LD capsules showed dose-proportional pharmacokinetics for Cmax and AUCt. Sprinkling the capsule contents on applesauce did not affect the pharmacokinetics. A high-fat, high-calorie meal delayed the initial increase in LD concentration by approximately 1 to 2 hours, reduced Cmax by 21%, and increased AUCinf by 13% compared with the fasted state. Conclusions IPX066 shows dose-proportional pharmacokinetics. Sprinkling the capsule contents on applesauce does not affect the pharmacokinetics; a high-fat, high-calorie meal delayed absorption by 1 to 2 hours, slightly reduced Cmax, and slightly increased extent of absorption. PMID:26626430

Comparing Pain and Depressive Symptoms of Chronic Opioid Therapy Patients Receiving Dose Reduction and Risk Mitigation Initiatives With Usual Care.

PubMed

Thakral, Manu; Walker, Rod L; Saunders, Kathleen; Shortreed, Susan M; Parchman, Michael; Hansen, Ryan N; Ludman, Evette; Sherman, Karen J; Dublin, Sascha; Von Korff, Michael

2018-01-01

Dose reduction and risk mitigation initiatives have been recommended to reduce opioid-related risks among patients receiving chronic opioid therapy (COT), but questions remain over whether these initiatives worsen pain control and quality of life. In 2014 to 2015, we interviewed 1,588 adult COT patients within a health care system in Washington State and compared those who received dose reduction and risk mitigation initiatives in primary care clinics (intervention) with patients in comparable health care settings without initiatives (control). The primary outcomes were pain assessed using the pain, enjoyment, and general activity (PEG) scale, a 3-item scale to assess global pain intensity and interference, with secondary measures including depression (Patient Health Questionnaire-8 scale). Generalized estimating equations for linear regression models were used to estimate differences in mean scores between intervention and control sites. Estimated differences, adjusted for patient characteristics and weighted for nonresponse, between patients at intervention and control clinics were not clinically significant for the PEG (-.03, 95% confidence interval = -.25 to .19) or Patient Health Questionnaire-8 (-.64, 95% confidence interval = -1.19 to -.08). We found no evidence that COT patients in clinics with dose reduction and risk mitigation initiatives had clinically meaningful differences in pain intensity, interference with activities and enjoyment of life, or depressive symptoms compared with control health care settings. This article evaluates the effect of dose reduction and risk mitigation initiatives, such as those recently recommended by the Centers for Disease Control and Prevention, to reduce risks associated with COT on global pain and interference, depressive symptoms, and perceived pain relief and bothersomeness of side effects. Copyright © 2017 The American Pain Society. Published by Elsevier Inc. All rights reserved.

Clinical Pharmacokinetics of IPX066: Evaluation of Dose Proportionality and Effect of Food in Healthy Volunteers.

PubMed

Yao, Hsuan-Ming; Hsu, Ann; Gupta, Suneel; Modi, Nishit B

2016-01-01

IPX066 is an oral, extended-release capsule formulation of carbidopa-levodopa (CD-LD) available in 4 strengths. The goals of this investigation were to assess the dose proportionality of IPX066 and to study the effects of a high-fat, high-calorie meal and of sprinkling the capsule contents on applesauce on the pharmacokinetics of IPX066 in healthy volunteers. Three open-label studies were conducted. In the first study, subjects received 1 capsule of each IPX066 strength (23.75-95, 36.25-145, 48.75-195, and 61.25-245 mg of CD-LD). In the second study, subjects received 1 and 2 capsules of IPX066 245-mg LD under fasting conditions. In the third study, subjects received 2 capsules of IPX066 245-mg LD under 3 conditions: fasting; following a high-fat, high-calorie breakfast; and with the capsule contents sprinkled on applesauce under fasting conditions. Peak plasma concentrations (Cmax) and systemic exposure (AUCt, AUCinf) for LD and CD increased dose-proportionally over the range of the IPX066 capsule strengths. Comparison of 1 and 2 IPX066 245-mg LD capsules showed dose-proportional pharmacokinetics for Cmax and AUCt. Sprinkling the capsule contents on applesauce did not affect the pharmacokinetics. A high-fat, high-calorie meal delayed the initial increase in LD concentration by approximately 1 to 2 hours, reduced Cmax by 21%, and increased AUCinf by 13% compared with the fasted state. IPX066 shows dose-proportional pharmacokinetics. Sprinkling the capsule contents on applesauce does not affect the pharmacokinetics; a high-fat, high-calorie meal delayed absorption by 1 to 2 hours, slightly reduced Cmax, and slightly increased extent of absorption.

Use of tailored loading-dose clopidogrel in patients undergoing selected percutaneous coronary intervention based on adenosine diphosphate-mediated platelet aggregation.

PubMed

Meng, Kang; Lü, Shu-Zheng; Zhu, Hua-Gang; Chen, Xin; Ge, Chang-Jiang; Song, Xian-Tao

2010-12-01

Adenosine phosphate-mediated platelet aggregation is a prognostic factor for major adverse cardiac events in patients who have undergone selective percutaneous coronary interventions. This study aimed to assess whether an adjusted loading dose of clopidogrel could more effectively inhibit platelet aggregation in patients undergoing selected percutaneous coronary intervention. A total of 205 patients undergoing selected percutaneous coronary intervention were enrolled in this multicenter, prospective, randomized study. Patients receiving domestic clopidogrel (n = 104) served as the Talcom (Taijia) group; others (n = 101) received Plavix, the Plavix group. Patients received up to 3 additional 300-mg loading doses of clopidogrel to decrease the adenosine phosphate-mediated platelet aggregation index by more than 50% (the primary endpoint) compared with the baseline. The secondary endpoint was major adverse cardiovascular events at 12 months. Compared with the rational loading dosage, the tailored loading dosage better inhibited platelet aggregation based on a > 50% decrease in adenosine phosphate-mediated platelet aggregation (rational loading dosage vs. tailored loading dosage, 48% vs. 73%, P = 0.028). There was no significant difference in the eligible index between the Talcom and Plavix groups (47% vs. 49% at 300 mg; 62% vs. 59% at 600 mg; 74% vs. 72% at 900 mg; P > 0.05) based on a standard adenosine diphosphate-mediated platelet aggregation decrease of > 50%. After 12 months of follow-up, there were no significant differences in major adverse cardiac events (2.5% vs. 2.9%, P = 5.43). No acute or subacute stent thrombosis events occurred. An adjusted loading dose of clopidogrel could have significant effects on antiplatelet aggregation compared with a rational dose, decreasing 1-year major adverse cardiac events in patients undergoing percutaneous coronary interventions based on adenosine phosphate-mediated platelet aggregation with no increase in bleeding.

Primary cancers of extrahepatic biliary passages.

PubMed

Mittal, B; Deutsch, M; Iwatsuki, S

1985-04-01

We analyzed the records of 22 patients with cancers of extrahepatic biliary passages (EHBP) to understand their natural histories and patterns of failure and to evaluate the effectiveness of various treatments. None of the preoperative investigations consistently defined the entire extent of tumor. Percutaneous transhepatic cholangiography (PTHC) was the most helpful (100%) in accurately defining the site of ductal obstruction. Computed tomography was helpful in diagnosing liver metastases in 53% and primary tumor mass in 23% of patients. The most common sites of tumor failure or persistence were: liver (67%), tumor bed (56%), peritoneum (22%), porta hepatis and lymph nodes (17%). The median survival for the entire group was 6.8 months. Surgery plays an important role in managing these tumors and in defining tumor extent for subsequent adjuvant irradiation. Patients receiving radiation doses greater than or equal to 70 TDF had a longer median survival (11 months) than patients receiving less than 70 TDF (4.4 months). All three patients, who were alive and free of disease greater than 1 year, received radiation doses greater than or equal to 70 TDF. From our data, it is difficult to comment on the effectiveness of chemotherapy. We have made suggestions regarding radiation volume and doses to various structures. The need for entering these patients into multi-institutional clinical trials is stressed.

SU-E-T-56: A Novel Approach to Computing Expected Value and Variance of Point Dose From Non-Gated Radiotherapy Delivery

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

Zhou, S; Zhu, X; Zhang, M

Purpose: Randomness in patient internal organ motion phase at the beginning of non-gated radiotherapy delivery may introduce uncertainty to dose received by the patient. Concerns of this dose deviation from the planned one has motivated many researchers to study this phenomenon although unified theoretical framework for computing it is still missing. This study was conducted to develop such framework for analyzing the effect. Methods: Two reasonable assumptions were made: a) patient internal organ motion is stationary and periodic; b) no special arrangement is made to start a non -gated radiotherapy delivery at any specific phase of patient internal organ motion.more » A statistical ensemble was formed consisting of patient’s non-gated radiotherapy deliveries at all equally possible initial organ motion phases. To characterize the patient received dose, statistical ensemble average method is employed to derive formulae for two variables: expected value and variance of dose received by a patient internal point from a non-gated radiotherapy delivery. Fourier Series was utilized to facilitate our analysis. Results: According to our formulae, the two variables can be computed from non-gated radiotherapy generated dose rate time sequences at the point’s corresponding locations on fixed phase 3D CT images sampled evenly in time over one patient internal organ motion period. The expected value of point dose is simply the average of the doses to the point’s corresponding locations on the fixed phase CT images. The variance can be determined by time integration in terms of Fourier Series coefficients of the dose rate time sequences on the same fixed phase 3D CT images. Conclusion: Given a non-gated radiotherapy delivery plan and patient’s 4D CT study, our novel approach can predict the expected value and variance of patient radiation dose. We expect it to play a significant role in determining both quality and robustness of patient non-gated radiotherapy plan.« less

What is the optimal radiation dose for non-operable esophageal cancer? Dissecting the evidence in a meta-analysis.

PubMed

Chen, Yong; Zhu, Hui-Ping; Wang, Tao; Sun, Chang-Jiang; Ge, Xiao-Lin; Min, Ling-Feng; Zhang, Xian-Wen; Jia, Qing-Qing; Yu, Jie; Yang, Jian-Qi; Allgayer, Heike; Abba, Mohammed L; Zhang, Xi-Zhi; Sun, Xin-Chen

2017-10-24

The standard radiation dose 50.4 Gy with concurrent chemotherapy for localized inoperable esophageal cancer as supported by INT-0123 trail is now being challenged since a radiation dose above 50 Gy has been successfully administered with an observable dose-response relationship and insignificant untoward effects. Therefore, to ascertain the treatment benefits of different radiation doses, we performed a meta-analysis with 18 relative publications. According to our findings, a dose between 50 and 70 Gy appears optimal and patients who received ≥ 60 Gy radiation had a significantly better prognosis (pooled HR = 0.78, P = 0.004) as compared with < 60 Gy, especially in Asian countries (pooled HR = 0.75, P = 0.003). However, contradictory results of treatment benefit for ≥ 60 Gy were observed in two studies from Western countries, and the pooled treatment benefit of ≥ 60 Gy radiation was inconclusive (pooled HR = 0.86, P = 0.64). There was a marginal benefit in locoregional control in those treated with high dose (> 50.4/51 Gy) radiation when compared with those treated with low dose (≤ 50.4/51 Gy) radiation (pooled OR = 0.71, P = 0.06). Patients that received ≥ 60 Gy radiation had better locoregional control (OR = 0.29, P = 0.001), and for distant metastasis control, neither the > 50.4 Gy nor the ≥ 60 Gy treated group had any treatment benefit as compared to the groups that received ≤ 50.4 Gy and < 60 Gy group respectively. Taken together, a dose range of 50 to 70 Gy radiation with CCRT is recommended for non-operable EC patients. A dose of ≥ 60 Gy appears to be better in improving overall survival and locoregional control, especially in Asian countries, while the benefit of ≥ 60 Gy radiation in Western countries still remains controversial.

Limited Impact of Setup and Range Uncertainties, Breathing Motion, and Interplay Effects in Robustly Optimized Intensity Modulated Proton Therapy for Stage III Non-small Cell Lung Cancer.

PubMed

Inoue, Tatsuya; Widder, Joachim; van Dijk, Lisanne V; Takegawa, Hideki; Koizumi, Masahiko; Takashina, Masaaki; Usui, Keisuke; Kurokawa, Chie; Sugimoto, Satoru; Saito, Anneyuko I; Sasai, Keisuke; Van't Veld, Aart A; Langendijk, Johannes A; Korevaar, Erik W

2016-11-01

To investigate the impact of setup and range uncertainties, breathing motion, and interplay effects using scanning pencil beams in robustly optimized intensity modulated proton therapy (IMPT) for stage III non-small cell lung cancer (NSCLC). Three-field IMPT plans were created using a minimax robust optimization technique for 10 NSCLC patients. The plans accounted for 5- or 7-mm setup errors with ±3% range uncertainties. The robustness of the IMPT nominal plans was evaluated considering (1) isotropic 5-mm setup errors with ±3% range uncertainties; (2) breathing motion; (3) interplay effects; and (4) a combination of items 1 and 2. The plans were calculated using 4-dimensional and average intensity projection computed tomography images. The target coverage (TC, volume receiving 95% of prescribed dose) and homogeneity index (D2 - D98, where D2 and D98 are the least doses received by 2% and 98% of the volume) for the internal clinical target volume, and dose indexes for lung, esophagus, heart and spinal cord were compared with that of clinical volumetric modulated arc therapy plans. The TC and homogeneity index for all plans were within clinical limits when considering the breathing motion and interplay effects independently. The setup and range uncertainties had a larger effect when considering their combined effect. The TC decreased to <98% (clinical threshold) in 3 of 10 patients for robust 5-mm evaluations. However, the TC remained >98% for robust 7-mm evaluations for all patients. The organ at risk dose parameters did not significantly vary between the respective robust 5-mm and robust 7-mm evaluations for the 4 error types. Compared with the volumetric modulated arc therapy plans, the IMPT plans showed better target homogeneity and mean lung and heart dose parameters reduced by about 40% and 60%, respectively. In robustly optimized IMPT for stage III NSCLC, the setup and range uncertainties, breathing motion, and interplay effects have limited impact on target coverage, dose homogeneity, and organ-at-risk dose parameters. Copyright © 2016 Elsevier Inc. All rights reserved.

Sirolimus and tacrolimus trough concentrations and dose requirements after kidney transplantation in relation to CYP3A5 and MDR1 polymorphisms and steroids.

PubMed

Mourad, Michel; Mourad, Georges; Wallemacq, Pierre; Garrigue, Valérie; Van Bellingen, Christophe; Van Kerckhove, Valérie; De Meyer, Martine; Malaise, Jacques; Eddour, Djamila Chaib; Lison, Dominique; Squifflet, Jean Paul; Haufroid, Vincent

2005-10-15

CYP3A5 and MDR1 polymorphisms have been shown to influence tacrolimus blood concentrations and dose requirements. The aim is to determine whether these polymorphisms also affect sirolimus trough concentrations and dose requirements after kidney transplantation. Eighty-five renal transplant recipients receiving sirolimus were included. Twenty-four were treated with a combined sirolimus-tacrolimus regimen. Eighty-one patients received steroids. Sirolimus and tacrolimus were adjusted to a target therapeutic window. CYP3A5 (intron 3) and MDR1 (exons 12, 21, 26) genotypes were correlated to the adjusted trough concentrations and dose requirements for both sirolimus and tacrolimus. There were no significant correlation between adjusted sirolimus trough concentrations or dose requirements and genetic polymorphisms. In a multiple regression model, adjusted-prednisone dose was involved with a positive or negative effect when considering sirolimus dose requirements or adjusted concentrations, respectively. In the subgroup of patients treated by tacrolimus and sirolimus, adjusted tacrolimus doses were higher in patients carrying at least one CYP3A5 *1 allele (median 0.083 vs. 0.035 mg/kg for CYP3A5*3/*3 patients, P<0.05). Adjusted-prednisolone dose and CYP3A5 polymorphism explained up to 61% of the variability in tacrolimus dose requirements. Unlike tacrolimus, sirolimus adjusted trough concentrations and dose requirements seem not affected by CYP3A5 and MDR1 polymorphisms. Adjusted-prednisone dose has a significant impact on tacrolimus and sirolimus dose requirements.

A Randomized Multicenter Phase III Study of Single Administration of Mecapegfilgrastim (HHPG-19K), a Pegfilgrastim Biosimilar, for Prophylaxis of Chemotherapy-Induced Neutropenia in Patients With Advanced Non-Small-Cell Lung Cancer (NSCLC).

PubMed

Zhou, Caicun; Huang, Yunchao; Wang, Donglin; An, Changshan; Zhou, Fuxiang; Li, Yali; Chen, Gongyan; Wu, Changping; He, Jianxing; Wu, Gang; Song, Xia; Gao, Jianfei; Liu, Wei; Li, Baolan; Shi, Jianhua; Huang, Cheng; Yu, Jingrui; Feng, Jueping; Yue, Hongmei; Shi, Meiqi; Xia, Jielai

2016-03-01

Mecapegfilgrastim (code name HHPG-19K) is a biosimilar to pegylated recombinant human granulocyte-colony stimulating factor (PEG-rhG-CSF). The efficacy and safety of mecapegfilgrastim, using a regimen of once-per-cycle injection of 100-μg/kg or a fixed 6-mg dose, were evaluated for the prophylactic therapy for neutropenia in patients with advanced non-small-cell lung cancer (NSCLC) who were treated with myelosuppressive chemotherapy. Patients were randomized (1:1:1) blindly to 3 treatment arms to receive a single injection of mecapegfilgrastim 100 μg/kg, a 6-mg fixed dose of mecapegfilgrastim, or saline (control) in cycle 1. In cycles 2 to 4 following unblinding at the end of cycle 1, patients in the control arm received daily injections of short-acting rhG-CSF at a dose of 5 μg/kg, whereas patients in the 2 mecapegfilgrastim arms continued the same treatment as in cycle 1. All patients received 4 chemotherapy cycles of docetaxel combined with cisplatin or carboplatin every 21 days. The primary endpoint was the incidence of grade ≥ 3 neutropenia in cycle 1. A single dose of 100 μg/kg or a fixed 6-mg dose of mecapegfilgrastim per cycle effectively reduced chemotherapy-induced neutropenia and was comparable to daily rhG-CSF with regard to all efficacy endpoints, including incidence of grade ≥ 3 neutropenia, incidence of febrile neutropenia, duration of grade ≥ 3 neutropenia, and time to neutrophil recovery. No difference in efficacy parameters was observed between the 2-dose regimens of mecapegfilgrastim across all cycles. Mecapegfilgrastim was well-tolerated and was as safe as daily rhG-CSF. Once-per-cycle injection of mecapegfilgrastim is as effective and safe as daily rhG-CSF for prophylaxis of chemotherapy-induced neutropenia in patients with NSCLC. Mecapegfilgrastim (fixed 6-mg dose) is recommended in clinical practice for its convenient dose management. Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

[Absorbed dose and the effective dose of panoramic temporo mandibular joint radiography].

PubMed

Matsuo, Ayae; Okano, Tsuneichi; Gotoh, Kenichi; Yokoi, Midori; Hirukawa, Akiko; Okumura, Shinji; Koyama, Syuji

2011-01-01

This study measured the radiation doses absorbed by the patient during Panoramic temporo mandibular joint radiography (Panoramic TMJ), Schüllers method and Orbitoramus projection. The dose of the frontal view in Panoramic TMJ was compared to that with Orbitoramus projection and the lateral view in Panoramic TMJ was compared to that with Schüllers method. We measured the doses received by various organs and calculated the effective doses using the guidelines of the International Commission on Radiological Protection in Publication 103. Organ absorbed doses were measured using an anthropomorphic phantom, loaded with thermoluminescent dosimeters (TLD), located at 160 sensitive sites. The dose shows the sum value of irradiation on both the right and left sides. In addition, we set a few different exposure field sizes. The effective dose for a frontal view in Panoramic TMJ was 11 µSv, and that for the lateral view was 14 µSv. The lens of the Orbitoramus projection was 40 times higher than the frontal view in Panoramic TMJ. Although the effective dose of the lateral view in Panoramic TMJ was 3 times higher than that of the small exposure field (10×10 cm on film) in Schüller's method, it was the same as that of a mid-sized exposure field. When the exposure field in the inferior 1/3 was reduced during panoramic TMJ, the effective doses could be decreased. Therefore we recommend that the size of the exposure field in Panoramic TMJ be decreased.

Personalized Feedback on Staff Dose in Fluoroscopy-Guided Interventions: A New Era in Radiation Dose Monitoring.

PubMed

Sailer, Anna M; Vergoossen, Laura; Paulis, Leonie; van Zwam, Willem H; Das, Marco; Wildberger, Joachim E; Jeukens, Cécile R L P N

2017-11-01

Radiation safety and protection are a key component of fluoroscopy-guided interventions. We hypothesize that providing weekly personal dose feedback will increase radiation awareness and ultimately will lead to optimized behavior. Therefore, we designed and implemented a personalized feedback of procedure and personal doses for medical staff involved in fluoroscopy-guided interventions. Medical staff (physicians and technicians, n = 27) involved in fluoroscopy-guided interventions were equipped with electronic personal dose meters (PDMs). Procedure dose data including the dose area product and effective doses from PDMs were prospectively monitored for each consecutive procedure over an 8-month period (n = 1082). A personalized feedback form was designed displaying for each staff individually the personal dose per procedure, as well as relative and cumulative doses. This study consisted of two phases: (1) 1-5th months: Staff did not receive feedback (n = 701) and (2) 6-8th months: Staff received weekly individual dose feedback (n = 381). An anonymous evaluation was performed on the feedback and occupational dose. Personalized feedback was scored valuable by 76% of the staff and increased radiation dose awareness for 71%. 57 and 52% reported an increased feeling of occupational safety and changing their behavior because of personalized feedback, respectively. For technicians, the normalized dose was significantly lower in the feedback phase compared to the prefeedback phase: [median (IQR) normalized dose (phase 1) 0.12 (0.04-0.50) µSv/Gy cm 2 versus (phase 2) 0.08 (0.02-0.24) µSv/Gy cm 2 , p = 0.002]. Personalized dose feedback increases radiation awareness and safety and can be provided to staff involved in fluoroscopy-guided interventions.

Dexmedetomidine in Attenuation of Haemodynamic Response and Dose Sparing Effect on Opioid and Anaesthetic Agents in Patients undergoing Laparoscopic Cholecystectomy- A Randomized Study

PubMed Central

Bhagat, Nandlal; Karim, Habib Md Reazaul; Hajong, Ranendra; Bhattacharyya, Prithwis; Singh, Manorama

2016-01-01

Introduction Perioperative procedures are stressful and lead to haemodynamic instability with potentially devastating consequences. Dexmedetomidine is found to have many of the desired characteristics that are required in perioperative period. Aim To evaluate the ability of pre and intraoperative dexmedetomidine to attenuate stress induced haemodynamic responses, quantifying the anaesthetic agents sparing as well as its cost-effectiveness in patients undergoing laparoscopic cholecystectomy. Materials and Methods The present single blind randomized study was conducted with 120 ASA I and II consented patients who underwent laparoscopic cholecystectomy. Patients were randomly divided into 2 groups (i.e., group D and group N). Prior to induction, group D received 1 μg/kg of Dexmedetomidine and group N received Normal saline infusion over 20 minutes. Group D also received maintenance Dexmedetomidine intraoperatively. Bispectral index and minimum alveolar concentration monitoring was done in both the groups. Haemodynamic parameters were noted till 100 minutes post laryngoscopy. Opioid and anaesthetic agent consumptions were also noted and cost analysis was done. Medcalc–Version 12.5.0.0 software was used for statistics and p <0.05 was considered significant. Results Dexmedetomidine attenuated the stress induced haemodynamics responses and produced stable, relatively non fluctuating haemodynamics throughout. The Minimum Alveolar Concentration (MAC) requirement and the consumptions of Fentanyl and Isoflurane were significantly less in the Dexmedetomidine group (p<0.0001). However, despite anaesthetic dose sparing effect the anaesthetic technique was not cost-effective. Conclusion Dexmedetomidine is effective in attenuating haemodynamic responses in laparoscopic surgery and having dose sparing effect on Fentanyl, Propofol and Isoflurane. However, overall this technique is not cost-effective. PMID:28050479

Structure of the cell wall of mango after application of ionizing radiation

NASA Astrophysics Data System (ADS)

Silva, Josenilda M.; Villar, Heldio P.; Pimentel, Rejane M. M.

2012-11-01

Cells of the mesocarp of mango cultivar Tommy Atkins were analyzed by Transmission Electron Microscope—TEM to evaluate the effects of doses of 0.5 and 1.0 kGy applied immediately after the fruit and after storage for twenty days at a temperature of 12 °C followed by 5 days of simulated marketing at a temperature of 21 °C. No alteration was found in the structure of the cell wall, middle lamella, and plasma membrane of fruits when analyzed immediately after application of doses. The mesocarp cell structure of the cell wall, middle lamella, and the plasma membrane did however undergo changes after storage. Fruits that received a dose of 0.5 kGy displayed slight changes in cell wall structure and slight disintegration of the middle lamella. Fruits that received a dose of 1.0 kGy displayed more severe changes in the structure of the cell wall, greater middle lamella degradation, and displacement of the plasma membrane.

Gabapentin pharmacotherapy for antipsychotic-induced akathisia: single-patient experiment and case report.

PubMed

Sullivan, Maria A; Wilbur, Robert

2014-04-01

This clinical study reports upon the efficacy of gabapentin (Neurontin) for treating severe akathisia (3 on the Barnes Akathisia Rating Scale) in two patients receiving quetiapine (Seroquel), one of whom also received olanzapine (Zyprexa) for a short period. The first patient participated in an open-label experiment in which the bedtime dose of gabapentin was discontinued three times at intervals 1 week apart, resulting in severe akathisia which was quickly terminated by taking his usual 1200 mg gabapentin dose. This patient was also taking high doses of two benzodiazepines and a beta blocker, without therapeutic effect upon his akathisia; only gabapentin was efficacious. The second case is a report of a woman taking a high dose of quetiapine for anxiety who experienced severe akathisia which was relieved by taking 1200 mg of gabapentin. Possible mechanisms of action of gabapentin are discussed. Particular attention is drawn to the difference between neuroleptic-induced akathisia and the neurological condition of restless legs syndrome.

Prophylactic low-dose aspirin is effective antithrombotic therapy for combination treatments of thalidomide or lenalidomide in myeloma.

PubMed

Niesvizky, Ruben; Martínez-Baños, Déborah; Jalbrzikowski, Jessica; Christos, Paul; Furst, Jessica; De Sancho, Maria; Mark, Tomer; Pearse, Roger; Mazumdar, Madhu; Zafar, Faiza; Pekle, Karen; Leonard, John; Jayabalan, David; Coleman, Morton

2007-12-01

Multiple myeloma (MM) patients have a propensity for thromboembolic events (TE), and treatment with thalidomide/dexamethasone or lenalidomide/dexamethasone increases this risk. This report describes the use of low-dose aspirin (81 mg) as primary thromboprophylaxis in three series of MM patients receiving thalidomide or lenalidomide with other drugs. In the first regimen (clarithromycin, thalidomide, dexamethasone), initiation of low-dose aspirin negated the occurrence of any further TE. In a second study, prophylactic aspirin given with thalidomide/dexamethasone resulted in a rate of TE similar to that seen with dexamethasone alone (without aspirin). A third study (n = 72) evaluated thrombosis rates with aspirin and a lenalidomide-containing regimen (clarithromycin, lenalidomide, dexamethasone). Of nine occurrences of thromboembolism, five were associated with aspirin interruption or poor compliance. Low-dose aspirin appears to reduce the incidence of thrombosis with these regimens. Routine use of aspirin as antithrombotic prophylaxis in MM patients receiving immunomodulatory drugs with corticosteroids is warranted.

[Oral loading dose of phenytoin in the treatment of serial seizures, prevention of seizure recurrence and rapid drug substitution].

PubMed

Sokić, D; Janković, S M

1994-01-01

Over a period of nine months twenty-five epileptic patients were treated with the oral loading dose of phenytoin. The dose ranged from 12 to 23 mg/kg body weight during 1 to 12 hours. In 20 patients with serial seizures or intolerance to other antiepileptic drugs this treatment was effective. Seizures also stopped in 2 of 4 patients with serial partial motor seizures. These 2 patients required both higher loading dose and faster rate of administration than the other patients. A patient with epilepsia partialis continua failed to respond to the treatment. Patients that received phenytoin through the naso-gastric tube, in respect to oral administration, required higher doses to obtain therapeutic plasma levels of phenytoin. One patient had mild nausea, 3 mild dizziness, and 1 tinitus on the first day of the treatment. There was no correlation between a given dose and the achieved phenytoin plasma levels. In our opinion the therapy with oral loading dose of phenytoin is highly effective in the treatment of serial generalized seizures and rapid antiepileptic drug substitution, and partially effective in the prevention of partial motor seizures. It produces only mild and transient side-effects.

The Reinforcing and Subjective Effects of Intravenous and Intranasal Buprenorphine in Heroin Users

PubMed Central

Jones, Jermaine D.; Madera, Gabriela; Comer, Sandra D.

2014-01-01

Abuse of buprenorphine (BUP) by the intravenous (IV) route has been documented in several studies, and reports of intranasal (IN) abuse are increasing. However, no studies have directly compared the effects of BUP when it is administered intranasally and intravenously. The present secondary analysis used data from two separate studies to compare the reinforcing and subjective effects of IV and IN buprenorphine. One study evaluated IV buprenorphine (N=13) and the other evaluated IN buprenorphine (N=12). Participants were maintained on 2 mg sublingual (SL) BUP and tested with each intranasal or intravenous buprenorphine test dose (0 mg, 2 mg, 4 mg, 8 mg, and 16 mg). During morning laboratory sessions, participants received money (US $20) and sample doses of IN or IV BUP, and then completed subjective effects questionnaires. Later that day, they completed a self-administration task to receive 10% portions of the drug and/or money they previously sampled. In general, positive subjective ratings for both IV and IN BUP were significantly greater than placebo, with IV BUP having a greater effect than IN BUP. All active BUP doses (IV and IN) maintained significantly higher progressive ratio breakpoint values than placebo, but breakpoint values for IV BUP were greater than for IN BUP. Buprenorphine is an effective maintenance treatment for opioid dependence, valued for its ability to reduce the positive subjective effects of other opioids. Nevertheless, the present data demonstrate that in participants maintained on a low dose of SL BUP, the medication itself has abuse liability when used intravenously or intranasally. PMID:24793093

Metabolic effects of human growth hormone in corticosteroid-treated children

PubMed Central

Morris, Helen G.; Jorgensen, Jacqueline R.; Elrick, Harold; Goldsmith, Richard E.

1968-01-01

The effects of administered human growth hormone (HGH) were evaluated in dwarfed, prepubertal children who were receiving long-term corticosteroid therapy for a chronic disease. During 11 complete metabolic balance studies, the eight corticosteroid-treated children demonstrated impaired response to large doses of HGH with minimal nitrogen and no phosphorus retention. In contrast, two hypopituitary subjects and two asthmatic children not receiving corticosteroid responded to the same preparations of HGH with nitrogen, potassium, and phosphorus retention. Six corticosteroid-treated children were given large doses of HGH (40-120 mg/wk for 4 to 8 months and showed no improvement in their retarded rate of growth, whereas the hypopituitary subjects showed accelerated growth during administration of 10-15 mg of HGH/wk. It is concluded that dwarfism in steroid-treated children results from corticosteroid-induced antagonism of the effects of HGH at the peripheral tissue level. PMID:5637134

Nonaqueous, mini-dose glucagon for treatment of mild hypoglycemia in adults with type 1 diabetes: A dose-seeking study

USDA-ARS?s Scientific Manuscript database

To evaluate mini-dose glucagon in adults with type 1 diabetes using a stable, liquid, ready-to-use preparation, twelve adults with type 1 diabetes receiving treatment with insulin pumps received subcutaneous doses of 75, 150, and 300 ug of nonaqueous glucagon. Plasma glucose, glucagon, and insulin c...

42 CFR 82.5 - Definition of terms used in this part.

Code of Federal Regulations, 2011 CFR

2011-10-01

... Illness Compensation Program Act of 2000, 42 U.S.C. 7384-7385 [1994, supp. 2001]. (i) Equivalent dose is... equivalent dose that is received from radiation sources outside of the body. (k) Internal dose means that portion of the equivalent dose that is received from radioactive materials taken into the body. (l) NIOSH...

Study of Antitumor Activity of Sodium Phenylbutyrate, Histon Deacetylase Inhibitor, on Ehrlich Carcinoma Model.

PubMed

Fadeev, N P; Kharisov, R I; Kovan'ko, E G; Pustovalov, Yu I

2015-09-01

Antitumor activity of sodium phenylbutyrate was studied on 120 outbred female mice with transplanted Ehrlich ascites carcinoma. The animals received the drug in doses of 400, 800, and 1200 mg/kg with drinking water daily for 21 days. The antitumor effect was evaluated by tumor growth inhibition and lifespan prolongation. Phenylbutyrate in the dose of 800 mg/kg was most effective. The drug inhibited the tumor growth by 71%, prolonged the lifespan of animals by 28, and was low-toxic.