Glucose-Dependent Insulinotropic Polypeptide Mitigates 6-OHDA-Induced Behavioral Impairments in Parkinsonian Rats

PubMed Central

Yu, Yu-Wen; Hsueh, Shih-Chang; Lai, Jing-Huei; Chen, Yen-Hua; Kang, Shuo-Jhen; Hsieh, Tsung-Hsun; Hoffer, Barry J.; Li, Yazhou; Greig, Nigel H.; Chiang, Yung-Hsiao

2018-01-01

In the present study, the effectiveness of glucose-dependent insulinotropic polypeptide (GIP) was evaluated by behavioral tests in 6-hydroxydopamine (6-OHDA) hemi-parkinsonian (PD) rats. Pharmacokinetic measurements of GIP were carried out at the same dose studied behaviorally, as well as at a lower dose used previously. GIP was delivered by subcutaneous administration (s.c.) using implanted ALZET micro-osmotic pumps. After two days of pre-treatment, male Sprague Dawley rats received a single unilateral injection of 6-OHDA into the medial forebrain bundle (MFB). The neuroprotective effects of GIP were evaluated by apomorphine-induced contralateral rotations, as well as by locomotor and anxiety-like behaviors in open-field tests. Concentrations of human active and total GIP were measured in plasma during a five-day treatment period by ELISA and were found to be within a clinically translatable range. GIP pretreatment reduced behavioral abnormalities induced by the unilateral nigrostriatal dopamine (DA) lesion produced by 6-OHDA, and thus may be a novel target for PD therapeutic development. PMID:29641447

Prolonged enhancement of REM sleep produced by carbachol microinjection into the amygdala.

PubMed

Calvo, J M; Simón-Arceo, K; Fernández-Mas, R

1996-01-31

The effect on sleep organization of carbachol microinjected into different amygdaloid nuclei was analysed in 12 cats. Single carbachol doses of 8 micrograms in 0.50 microliter saline were delivered unilaterally or bilaterally into the central, basal, lateral or basolateral amygdaloid nucleus. Carbachol administration into the central nucleus induced a prolonged (5 days) enhancement of both REM sleep and its preceeding slow wave sleep episodes with PGO waves (sommeil phasique a ondes lentes, SPHOL), which was more pronounced following bilateral than unilateral carbachol administration. However, neither SPHOL nor REM sleep changes were produced by administration of carbachol into the other amygdaloid nuclei. We conclude that cholinergic activation of the central amygdaloid nucleus produces a long-term facilitation of REM sleep occurrence.

Effect of single dose radiation therapy on weight-bearing lameness in dogs with elbow osteoarthritis.

PubMed

Kapatkin, Amy S; Nordquist, Barbro; Garcia, Tanya C; Griffin, Maureen A; Theon, Alain; Kim, Sun; Hayashi, Kei

2016-07-19

To determine if a single low dose of radiation therapy in dogs with osteoarthritis of the elbow joint was associated with a detectable improvement in their lameness and pain as documented by force platform gait analysis. In this cohort longitudinal observational study, five Labrador Retrievers with lameness due to elbow osteoarthritis that was unresponsive to medical treatment were removed from all non-steroidal anti-inflammatory and analgesic medications. A single treatment of radiation therapy delivering 10 Gray was performed on the affected elbow joint(s). Force platform gait analysis was used to assess the ground reaction forces of a limb affected with elbow osteoarthritis both before and after radiation therapy. Significant differences occurred in the weight-bearing on an affected limb with elbow osteoarthritis after radiation therapy at weeks six and 14. Change due to treatment was particularly apparent in dogs with unilateral elbow osteoarthritis. Administering a single low dose of radiation therapy may have a short-term benefit in dogs with elbow osteoarthritis, which is similar to the evidence supporting the use of radiation therapy in horses with orthopaedic disease.

Unilateral Versus Bilateral Laparoscopic Ovarian Drilling Using Thermal Dose Adjusted According to Ovarian Volume in CC-Resistant PCOS, A Randomized Study.

PubMed

El-Sayed, Mohamed Lotfy Mohamed; Ahmed, Mostafa Abdo; Mansour, Marwa Abdel Azim; Mansour, Shymma Abdel Azim

2017-10-01

This study aimed to evaluate the efficacy of unilateral laparoscopic ovarian drilling versus bilateral laparoscopic ovarian drilling with thermal dose adjusted according to ovarian volume in clomiphene citrate (CC)-resistant PCOS patients in terms of endocrine changes, menstrual cycle resumption, ovulation and pregnancy rates. This study was conducted in the Department of Obstetrics and Gynecology, Zagazig university hospitals. One hundred CC-resistant PCOS patients were divided into two groups. Group (I) (50 patients) underwent unilateral laparoscopic ovarian drilling with thermal dose adjusted according to ovarian volume (60 J/cm 3 of ovarian tissue), and group (II) (50 patients) underwent bilateral laparoscopic ovarian drilling using the same previously mentioned thermal dose. Endocrinal changes and menstrual cycle resumption were assessed within 8 weeks postoperatively, but the ovulation and pregnancy rates were estimated after 6-month follow-up period. There was no statistically significant difference between the two groups as regards demographic data ( p  > 0.05). As regards menstruation cycle resumption (62.5 vs. 81%) ( p  = 0.047), total ovulation rate (54.2 vs. 78.7%) ( p  = 0.011) and cumulative pregnancy rate (33.3 vs. 55.3%) ( p  = 0.031), there was statistically significant difference between both groups. After drilling, there were highly statistically significant decrease in the mean serum levels of luteinizing hormone (LH) and significant decrease in the mean serum levels of testosterone in both groups. Mean serum level of follicle stimulating hormone (FSH) did not change significantly in both groups after drilling. Bilateral laparoscopic ovarian drilling with thermal dose adjusted according to ovarian volume is more effective than the right-sided unilateral technique with thermal dose adjusted according to ovarian volume in terms of menstrual cycle resumption, ovulation and cumulative pregnancy rates in CC-resistant PCOS patients.

A unilateral optic perineuritis in a teenager - A case report.

PubMed

Ameilia, Ahmad; Shatriah, Ismail; Wan-Hitam, Wan Hazabbah; Yunus, Rohaizan

2015-06-01

Optic perineuritis is an uncommon inflammatory disorder that involves optic nerve sheath. Numerous case reports have been published on optic perineuritis in adults, the majority of whom had bilateral presentation. There are limited data on optic perineuritis occurring in pediatric patients. We report a teenager who presented with a unilateral sign that mimicked the presentation of optic neuritis. The orbit and brain magnetic resonance imaging confirmed features of unilateral optic perineuritis. She was treated with a high dose of corticosteroids for 2weeks, and her final visual outcome was satisfactory. No signs of relapse were noted during follow-up visits. Copyright © 2014 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Ocular Lyme borreliosis as a rare presentation of unilateral vision loss.

PubMed

Patterson-Fortin, Jeffrey; Kohli, Anita; Suarez, Maria J; Miller, P Elliott

2016-04-25

Ocular Lyme borreliosis is a rare manifestation of Lyme disease. We describe a case of an 80-year-old woman who presented with a 1-month history of unilateral painless central vision loss. Based on a temporal artery biopsy, she was initially diagnosed with giant cell arteritis and treated with a 3-day course of high-dose intravenous steroids. A more detailed history uncovered multiple previous treatments for Lyme disease and residence in an endemic Lyme area. The patient was subsequently diagnosed with ocular Lyme borreliosis and treated with intravenous antibiotics. After 5 weeks of treatment, unilateral vision loss did not progress and optic disc oedema resolved. 2016 BMJ Publishing Group Ltd.

The Clinical and Service Outcomes of Unilateral and Bilateral ECT Electrode Placements in Australian Aged Psychiatry Services.

PubMed

D'Cunha, Craig; Plakiotis, Christos; Macfarlane, Stephen; Moss, Francine; Reddy, Murali; Singh, Dhiren; Tofler, David; White, Erica; O'Connor, Daniel W

2016-03-01

The aim of the study was to determine whether depressed aged inpatients treated with brief pulse unilateral electroconvulsive therapy (ECT) differed from those treated with bilateral (bitemporal or bifrontal) ECT with respect to numbers of treatments, length of hospital admission, changes in scores on depression and cognitive scales, and serious adverse effects. An audit of routinely collected data regarding 221 acute ECT courses in 7 public aged psychiatry services in Victoria, Australia. Patients given unilateral, bifrontal, and bitemporal treatments were similar with respect to personal, clinical, and treatment characteristics. Most treatments were administered in line with local clinical guidelines and were rated as effective. Psychiatrists preferred unilateral ECT in the first instance with stimulus dosing based on patients' seizure thresholds. Approximately a quarter of unilateral courses were switched later to bitemporal placement, most probably because of insufficient progress. Bilateral treatments were associated with a larger number of treatments, less improvement in scores on mood and cognitive scales, and more refusals to continue treatment than unilateral-only ECT. Brief pulse unilateral ECT proved more effective than bitemporal and bifrontal ECT for most aged patients, especially when coupled with stimulus dosing based on seizure threshold.

In situ TEM study of electron-beam radiation induced boron diffusion and effects on phase and microstructure evolution in nanostructured CoFeB/SiO2 thin film

NASA Astrophysics Data System (ADS)

Liu, B. H.; Teo, H. W.; Mo, Z. H.; Mai, Z. H.; Lam, J.; Xue, J. M.; Zhao, Y. Z.; Tan, P. K.

2017-01-01

Using in situ transmission electron microscopy (TEM), we studied boron diffusion and segregation in CoFeB/SiO2 nanostructured thin film stacks. We also investigated how these phenomena affected the phase and microstructure of CoFeB thin films under electron beam irradiation at 300 kV. A unique phase transformation was observed in CoFeB thin films under high-dose electron irradiation, from a polycrystalline Co3Fe to a unilateral amorphous phase of Co3Fe and nanocrystalline FexCo23-xB6. The unilateral amorphization of the Co3Fe film showed an electron-dose-rate sensitivity with a threshold dose rate. Detailed in situ TEM studies revealed that the unilateral amorphization of the Co3Fe film arose from boron segregation at the bottom of the Co3Fe thin film induced by radiation-enhanced diffusion of boron atoms that were displaced by electron knock-on effects. The radiation-induced nanocrystallization of FexCo23-xB6 was also found to be dose-rate sensitive with a higher electron beam current leading to earlier nucleation and more rapid grain growth. The nanocrystallization of FexCo23-xB6 occurred preferentially at the CoFeB/SiO2 interface. Kinetic studies by in situ TEM revealed the surface crystallization and diffusion-controlled nucleation and grain growth mechanisms. The radiation-enhanced atomic diffusivity and high-concentration of radiation-induced point defects at the Co3Fe/SiO2 interface enhanced the local short-range ordering of Fe, Co, and B atoms, favoring nucleation and grain growth of FexCo23-xB6 at the interface.

Hemodynamic stability ensured by a low dose, low volume, unilateral hypobaric spinal block: modification of a technique.

PubMed

Elzinga, L; Marcus, M; Peek, D; Borg, P; Jansen, J; Koster, J; Enk, D

2009-01-01

We report the case of an 89-year-old female with a history of arterial hypertension, intermittent rapid atrial fibrillation and severe aortic valve stenosis, suffering from femoral neck fracture. Hyperbaric unilateral spinal anesthesia is a known technique to obtain stable hemodynamics combined with the possibility of continuous neurologic evaluation and preservation of cognitive functions. Because a hyperbaric unilateral technique can be very painful in case of traumatic hip fracture, a low dose, low volume, unilateral hypobaric spinal block may be an adequate alternative. In the present case report, a unilateral hypobaric spinal anesthesia was performed using 5 mg of bupivacaine in a 1.5 mL volume and a slow and steady, "air-buffered", directed injection technique, to allow an urgent hip arthroplasty. During surgery the patient was kept in the lateral recumbent position. Hemodynamics remained stable throughout the entire procedure without any need for vasoconstrictors. The impact of aortic valve stenosis combined with atrial fibrillation on anesthetic management and our considerations to opt for a unilateral hypobaric spinal anesthesia are discussed.

Acute effects of unilateral whole body vibration training on single leg vertical jump height and symmetry in healthy men.

PubMed

Shin, Seungho; Lee, Kyeongjin; Song, Changho

2015-12-01

[Purpose] The aim of the present study was to investigate the acute effects of unilateral whole body vibration training on height and symmetry of the single leg vertical jump in healthy men. [Subjects] Thirty males with no history of lower limb dysfunction participated in this study. [Methods] The participants were randomly allocated to one of three groups: the unilateral vibratory stimulation group (n=10), bilateral vibratory stimulation group (n=10), and, no vibratory stimulation group (n=10). The subjects in the unilateral and bilateral stimulation groups participated in one session of whole body vibration training at 26 Hz for 3 min. The no vibratory stimulation group subjects underwent the same training for 3 min without whole body vibration. All participants performed the single leg vertical jump for each lower limb, to account for the strong and weak sides. The single leg vertical jump height and symmetry were measured before and after the intervention. [Results] The single leg vertical jump height of the weak lower limb significantly improved in the unilateral vibratory stimulation group, but not in the other groups. The single leg vertical jump height of the strong lower limb significantly improved in the bilateral vibratory stimulation group, but not in the other groups. The single leg vertical jump symmetry significantly improved in the unilateral vibratory stimulation group, but not in the other groups. [Conclusion] Therefore, the present study found that the effects of whole body vibration training were different depending on the type of application. To improve the single leg vertical jump height in the weak lower limbs as well as limb symmetry, unilateral vibratory stimulation might be more desirable.

Evaluation of an analytic linear Boltzmann transport equation solver for high-density inhomogeneities

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

Lloyd, S. A. M.; Ansbacher, W.; Department of Physics and Astronomy, University of Victoria, Victoria, British Columbia V8W 3P6

2013-01-15

Purpose: Acuros external beam (Acuros XB) is a novel dose calculation algorithm implemented through the ECLIPSE treatment planning system. The algorithm finds a deterministic solution to the linear Boltzmann transport equation, the same equation commonly solved stochastically by Monte Carlo methods. This work is an evaluation of Acuros XB, by comparison with Monte Carlo, for dose calculation applications involving high-density materials. Existing non-Monte Carlo clinical dose calculation algorithms, such as the analytic anisotropic algorithm (AAA), do not accurately model dose perturbations due to increased electron scatter within high-density volumes. Methods: Acuros XB, AAA, and EGSnrc based Monte Carlo are usedmore » to calculate dose distributions from 18 MV and 6 MV photon beams delivered to a cubic water phantom containing a rectangular high density (4.0-8.0 g/cm{sup 3}) volume at its center. The algorithms are also used to recalculate a clinical prostate treatment plan involving a unilateral hip prosthesis, originally evaluated using AAA. These results are compared graphically and numerically using gamma-index analysis. Radio-chromic film measurements are presented to augment Monte Carlo and Acuros XB dose perturbation data. Results: Using a 2% and 1 mm gamma-analysis, between 91.3% and 96.8% of Acuros XB dose voxels containing greater than 50% the normalized dose were in agreement with Monte Carlo data for virtual phantoms involving 18 MV and 6 MV photons, stainless steel and titanium alloy implants and for on-axis and oblique field delivery. A similar gamma-analysis of AAA against Monte Carlo data showed between 80.8% and 87.3% agreement. Comparing Acuros XB and AAA evaluations of a clinical prostate patient plan involving a unilateral hip prosthesis, Acuros XB showed good overall agreement with Monte Carlo while AAA underestimated dose on the upstream medial surface of the prosthesis due to electron scatter from the high-density material. Film measurements support the dose perturbations demonstrated by Monte Carlo and Acuros XB data. Conclusions: Acuros XB is shown to perform as well as Monte Carlo methods and better than existing clinical algorithms for dose calculations involving high-density volumes.« less

MONTE CARLO SIMULATION OF OUT-OF-FIELD ORGAN DOSES AND CANCER RISK IN TANZANIA FOR RADIATION THERAPY OF UNILATERAL RETINOBLASTOMA USING A 60Co UNIT.

PubMed

Suleiman, Suleiman Ameir; Qi, Yaping; Pi, Yifei; George Xu, X

2018-05-01

The use of 60Co teletherapy unit for the treatment of unilateral retinoblastoma (Rb) patients is a very common procedure in many developing countries including Tanzania. The aim of this study was to estimate organ-specific absorbed doses from an external beam radiation therapy 60Co unit for unilateral Rb and to assess the risks of the patients developing a secondary primary cancer. The absorbed dose estimations were based on a Monte Carlo method and a set of age-dependent computational male phantoms. The estimated doses were used to calculate the secondary cancer risks in out-of-field organs using the Biological Effects of Ionising Radiation VII risk models. The survival information and baseline cancer risks were based on relevant statistics for the Tanzanian population. The resulting out-of-field organ doses data showed that organs which are close to the target volume, such as the brain, salivary glands and thyroid glands, received the highest absorbed dose from scattered photons during the treatment of Rb. It was also found that the resulting photons dose to specific organs depends on the patient's age. Younger patients are more sensitive to radiation and also received higher dose contributions from the treatment head due to a larger part of the body exposed to the photon radiation. In all sites considered, the overall risks associated with radiation-induced secondary cancer were relatively lower than the baseline risks. Thus, the results in this article can help to provide good estimations of radiation-induced secondary cancer after radiation treatment of unilateral Rb using 60Co teletherapy unit in Tanzania and other developing countries.

Targeted Delivery of Antiglaucoma Drugs to the Supraciliary Space Using Microneedles

PubMed Central

Kim, Yoo C.; Edelhauser, Henry F.; Prausnitz, Mark R.

2014-01-01

Purpose. In this work, we tested the hypothesis that highly targeted delivery of antiglaucoma drugs to the supraciliary space by using a hollow microneedle allows dramatic dose sparing of the drug compared to topical eye drops. The supraciliary space is the most anterior portion of the suprachoroidal space, located below the sclera and above the choroid and ciliary body. Methods. A single, hollow 33-gauge microneedle, 700 to 800 μm in length, was inserted into the sclera and used to infuse antiglaucoma drugs into the supraciliary space of New Zealand white rabbits (N = 3–6 per group). Sulprostone, a prostaglandin analog, and brimonidine, an α2-adrenergic agonist, were delivered via supraciliary and topical administration at various doses. The drugs were delivered unilaterally, and intraocular pressure (IOP) of both eyes was measured by rebound tonometry for 9 hours after injection to assess the pharmacodynamic responses. To assess safety of the supraciliary injection, IOP change immediately after intravitreal and supraciliary injection were compared. Results. Supraciliary delivery of both sulprostone and brimonidine reduced IOP by as much as 3 mm Hg bilaterally in a dose-related response; comparison with topical administration at the conventional human dose showed approximately 100-fold dose sparing by supraciliary injection for both drugs. A safety study showed that the kinetics of IOP elevation immediately after supraciliary and intravitreal injection of placebo formulations were similar. Conclusions. This study introduced the use of targeted drug delivery to the supraciliary space by using a microneedle and demonstrated dramatic dose sparing of antiglaucoma therapeutic agents compared to topical eye drops. Targeted delivery in this way can increase safety by reducing side effects and could allow a single injection to contain enough drug for long-term sustained delivery. PMID:25212782

Systemic inflammatory response syndrome and prolonged hypoperfusion lesions in an infant with respiratory syncytial virus encephalopathy.

PubMed

Miyamoto, Kenji; Fujisawa, Masahide; Hozumi, Hajime; Tsuboi, Tatsuo; Kuwashima, Shigeko; Hirao, Jun-ichi; Sugita, Kenichi; Arisaka, Osamu

2013-10-01

Respiratory syncytial virus (RSV) is a cause of neurological complications in infants. We report a rare case of RSV encephalopathy in an infant who presented with poor sucking and hypothermia at 17 days of age after suffering from rhinorrhea and a cough for several days. After hospitalization, the patient presented with stupor and hypotonia lasting for at least 24 h, and was intubated, sedated, and ventilated for treatment of pneumonia. These symptoms led to diagnosis of pediatric systemic inflammatory response syndrome (SIRS) caused by RSV infection. High-dose steroid therapy was combined with artificial ventilation because the initial ventilation therapy was ineffective. Interleukin (IL)-6 levels in spinal fluid were markedly increased upon admission, and serum IL-6 and IL-8 levels showed even greater elevation. The patient was diagnosed with RSV encephalopathy. On day 5, high signal intensity in the bilateral hippocampus was observed on diffusion-weighted magnetic resonance imaging (MRI). On day 14, the patient presented with delayed partial seizure and an electroencephalogram showed occasional unilateral spikes in the parietal area, but the hippocampal abnormality had improved to normal on MRI. (99m)Tc-labeled ethylcysteinate dimer single-photon emission computed tomography (SPECT) on day 18 showed hypoperfusion of the bilateral frontal and parietal regions and the unilateral temporal region. SPECT at 3 months after onset still showed hypoperfusion of the bilateral frontal region and unilateral temporal region, but hypoperfusion of the bilateral parietal region had improved. The patient has no neurological deficit at 6 months. These findings suggest that RSV encephalopathy with cytokine storm induces several symptoms and complications, including SIRS and prolonged brain hypoperfusion on SPECT.

The effects of sufentanil added to low-dose hyperbaric bupivacaine in unilateral spinal anaesthesia for outpatients undergoing knee arthroscopy.

PubMed

Sertöz, Nezih; Aysel, İnan; Uyar, Meltem

2014-01-01

The aim of this study is to examine the effects of sufentanil added to low-dose hyperbaric bupivacaine in unilateral spinal anaesthesia for outpatients undergoing knee arthroscopy. Sixty two patients (ASA I-II) aged 20 to 50 who were planning on undergoing a knee arthroscopy were enrolled in this study. Patients were randomly divided into two groups. Unilateral spinal anaesthesia with 1ml 0.5% hyperbaric bupivacaine was administered to Group B (n=33); and unilateral spinal anaesthesia with 0.5ml (2.5µg) sufentanil added to 1ml hyperbaric bupivacaine was administered to Group BS (n=29). There were no statistically significant differences observed between the groups in terms of demographic data, hemodynamic parameters, maximum sensorial, sympathetic and motor block levels, time to motor block resolution, and time of discharge (p>0.05). There were statistically significant differences between the groups in terms of two segments regression time (Group B=52 min., Group BS=59 min.), ambulation time (Group B=147 min., Group BS=157 min.) and urination time (Group B=136 min., Group BS=149 min.) (p<0.05). In this study, no itching was observed in Group B, whereas seven patients in Group BS were observed as having postoperative itching (p<0.05). All patients were successfully given unilateral spinal anaesthesia with sufentanil added to low-dose hyperbaric bupivacaine for an outpatient knee arthroscopy, without affecting the time of discharge. However, for one-day interventions such as arthroscopy, it was concluded that administration of only low-dose hyperbaric bupivacaine was sufficient.

[Peripheral, central and functional vertigo syndromes].

PubMed

Strupp, M; Dieterich, M; Zwergal, A; Brandt, T

2015-12-01

Depending on the temporal course, three forms of vertigo syndrome can be differentiated: 1) vertigo attacks, e.g. benign paroxysmal positional vertigo (BPPV), Menière's disease and vestibular migraine, 2) acute spontaneous vertigo lasting for days, e.g. acute unilateral vestibulopathy, brainstem or cerebellar infarction and 3) symptoms lasting for months or years, e.g. bilateral vestibulopathy and functional vertigo. The specific therapy of the various syndromes is based on three principles: 1) physical treatment with liberatory maneuvers for BPPV and balance training for vestibular deficits, 2) pharmacotherapy, e.g. for acute unilateral vestibulopathy (corticosteroids) and Menière's disease (transtympanic administration of gentamicin or steroids and high-dose betahistine therapy); placebo-controlled pharmacotherapy studies are currently being carried out for acute unilateral vestibulopathy, vestibular paroxysmia, prophylaxis of BPPV, vestibular migraine, episodic ataxia type 2 and cerebellar ataxia; 3) psychotherapy for functional dizziness.

Mumps-containing vaccine effectiveness during outbreaks in two schools in Guangdong, China, 2012.

PubMed

Man, Wang; Jin-Kou, Zhao; Tao, Wang; Li-Xin, Hao; Chao, Ma; Qi-Ru, Su; Hui-Ming, Luo

2012-10-01

Mumps-containing vaccine was licensed in the 1990s in China with a single dose administered routinely to children aged 18-24 months since 2008. However, an increase in reported mumps cases during the period 2009 to 2012 casts doubt on the effectiveness of a single-dose mumps vaccination. In March 2012, large numbers of mumps cases in a day-care centre and primary school in Guangdong Province were investigated to estimate the effectiveness of mumps-containing vaccine. A mumps case was defined as a case with acute onset of unilateral or bilateral swelling of the parotid gland or other salivary glands. Clinical data were collected among students and staff members in the two schools from 6 February to 3 June 2012. Vaccination history was obtained from immunization certificates. Vaccine effectiveness (VE) was calculated among children in classes that had more than two mumps cases. The cohort included 369 children from seven classes, four from the day-care centre and three from the primary school. Vaccination certificates available for 347 children showed immunization coverage of 82% (285/347). The overall attack rate was 14.6% (54/369); the VE for a single dose of mumps vaccine was 65% (95% confidence interval [CI]: 19%-85%) when given within three years and 15% (95% CI: -2%-52%) when given three to six years before the outbreak. For two doses of vaccine the VE was 53% (95% CI: -15-80%). A single dose of mumps-containing vaccine was not effective to prevent these outbreaks among preschool and schoolchildren. A second dose of mumps-containing vaccine to four to five-year-old children should be considered in China.

Seizure threshold increases can be predicted by EEG quality in right unilateral ultrabrief ECT.

PubMed

Gálvez, Verònica; Hadzi-Pavlovic, Dusan; Waite, Susan; Loo, Colleen K

2017-12-01

Increases in seizure threshold (ST) over a course of brief pulse ECT can be predicted by decreases in EEG quality, informing ECT dose adjustment to maintain adequate supra-threshold dosing. ST increases also occur over a course of right unilateral ultrabrief (RUL UB) ECT, but no data exist on the relationship between ST increases and EEG indices. This study (n = 35) investigated if increases in ST over RUL UB ECT treatments could be predicted by a decline in seizure quality. ST titration was performed at ECT session one and seven, with treatment dosing maintained stable (at 6-8 times ST) in intervening sessions. Seizure quality indices (slow-wave onset, mid-ictal amplitude, regularity, stereotypy, and post-ictal suppression) were manually rated at the first supra-threshold treatment, and last supra-threshold treatment before re-titration, using a structured rating scale, by a single trained rater blinded to the ECT session being rated. Twenty-one subjects (60%) had a ST increase. The association between ST changes and EEG quality indices was analysed by logistic regression, yielding a significant model (p < 0.001). Initial ST (p < 0.05) and percentage change in mid-ictal amplitude (p < 0.05) were significant predictors of change in ST. Percentage change in post-ictal suppression reached trend level significance (p = 0.065). Increases in ST over a RUL UB ECT course may be predicted by decreases in seizure quality, specifically decline in mid-ictal amplitude and potentially in post-ictal suppression. Such EEG indices may be able to inform when dose adjustments are necessary to maintain adequate supra-threshold dosing in RUL UB ECT.

Reducing the concentration to 0.4% enantiomeric excess hyperbaric levobupivacaine (s75: r25) provides unilateral spinal anesthesia. Study with different volumes.

PubMed

Imbelloni, Luiz Eduardo; Gouveia, Marildo A; Carneiro, Antonio Fernando; Grigorio, Renata

2012-01-01

Unilateral spinal anesthesia may be obtained with hypobaric or hyperbaric solution. The objective of this study was to compare different doses of enantiomeric excess hyperbaric levobupivacaine to achieve unilateral spinal anesthesia. One hundred and twenty patients were randomized to receive 4 mg, 6 mg or 8 mg of 0.4% enantiomeric excess levobupivacaine. The solutions were administered at the L3-L4, with the patient in a lateral position and kept at this position according to dose administration for 5, 10 or 15 minutes. Sensory block (pinprick) and motor block (scale 0-3) were compared between the operated and contralateral sides. The onset of analgesia was rapid and comparable between groups. Sensory block was significantly higher in the operated than in nonoperated limb at all times of evaluation. Increasing the dose by 1 mL (2mg) corresponded to an increase of two segments in the mode for the operated side. In the operated side, motor block (MB = 3) of patients occurred in 31 (77.5%) with 4 mg, 38 (95%) with 6 mg, and 40 (100%) with 8 mg. There was a positive correlation between increased dose, blockade duration, and hypotension. All patients were satisfied with the technique used. Spinal anesthesia with different volumes of enantiomeric excess hyperbaric bupivacaine (S75: R25) provided a 78% incidence of unilateral spinal block, with the smallest dose used (4 mg) the most efficient. Copyright © 2012 Elsevier Editora Ltda. All rights reserved.

Bilateral implant reconstruction does not affect the quality of postmastectomy radiation therapy

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

Ho, Alice Y., E-mail: hoa1234@mskcc.org; Patel, Nisha; Ohri, Nisha

To determine if the presence of bilateral implants, in addition to other anatomic and treatment-related variables, affects coverage of the target volume and dose to the heart and lung in patients receiving postmastectomy radiation therapy (PMRT). A total of 197 consecutive women with breast cancer underwent mastectomy and immediate tissue expander (TE) placement, with or without exchange for a permanent implant (PI) before radiation therapy at our center. PMRT was delivered with 2 tangential beams + supraclavicular lymph node field (50 Gy). Patients were grouped by implant number: 51% unilateral (100) and 49% bilateral (97). The planning target volume (PTV)more » (defined as implant + chest wall + nodes), heart, and ipsilateral lung were contoured and the following parameters were abstracted from dose-volume histogram (DVH) data: PTV D{sub 95%} > 98%, Lung V{sub 20}Gy > 30%, and Heart V{sub 25}Gy > 5%. Univariate (UVA) and multivariate analyses (MVA) were performed to determine the association of variables with these parameters. The 2 groups were well balanced for implant type and volume, internal mammary node (IMN) treatment, and laterality. In the entire cohort, 90% had PTV D{sub 95%} > 98%, indicating excellent coverage of the chest wall. Of the patients, 27% had high lung doses (V{sub 20}Gy > 30%) and 16% had high heart doses (V{sub 25}Gy > 5%). No significant factors were associated with suboptimal PTV coverage. On MVA, IMN treatment was found to be highly associated with high lung and heart doses (both p < 0.0001), but implant number was not (p = 0.54). In patients with bilateral implants, IMN treatment was the only predictor of dose to the contralateral implant (p = 0.001). In conclusion, bilateral implants do not compromise coverage of the target volume or increase lung and heart dose in patients receiving PMRT. The most important predictor of high lung and heart doses in patients with implant-based reconstruction, whether unilateral or bilateral, is treatment of the IMNs. Refinement of radiation techniques in reconstructed patients who require comprehensive nodal irradiation is warranted.« less

Intraarticular Sacroiliac Joint Injection Under Computed Tomography Fluoroscopic Guidance: A Technical Note to Reduce Procedural Time and Radiation Dose

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

Paik, Nam Chull, E-mail: pncspine@gmail.com

2016-07-15

PurposeA technique for computed tomography fluoroscopy (CTF)-guided intraarticular (IA) sacroiliac joint (SIJ) injection was devised to limit procedural time and radiation dose.MethodsOur Institutional Review Board approved this retrospective analysis and waived the requirement for informed consent. Overall, 36 consecutive diagnostic or therapeutic IA SIJ injections (unilateral, 20; bilateral, 16) performed in 34 patients (female, 18; male, 16) with a mean age of 45.5 years (range 20–76 years) under CTF guidance were analyzed, assessing technical success (i.e., IA contrast spread), procedural time, and radiation dose.ResultsAll injections were successful from a technical perspective and were free of serious complications. Respective median proceduralmore » times and effective doses of SIJ injection were as follows: unilateral, 5.28 min (range 3.58–8.00 min) and 0.11 millisievert (mSv; range 0.07–0.24 mSv); and bilateral, 6.72 min (range 4.17–21.17 min) and 0.11 mSv (range 0.09–0.51 mSv).ConclusionsGiven the high rate of technical success achieved in limited time duration and with little radiation exposure, CTF-guided IA SIJ injection is a practical and low-risk procedure.« less

Clinical efficacy of formula-based bifrontal versus right unilateral electroconvulsive therapy (ECT) in the treatment of major depression among elderly patients: a pragmatic, randomized, assessor-blinded, controlled trial.

PubMed

Bjølseth, Tor Magne; Engedal, Knut; Benth, Jūratė Šaltytė; Dybedal, Gro Strømnes; Gaarden, Torfinn Lødøen; Tanum, Lars

2015-04-01

No prior study has compared the efficacy of bifrontal (BF) vs right unilateral (RUL) electroconvulsive therapy (ECT) by including the subgroup that is most likely to receive it: only elderly patients with major depression (MD). This single-site, randomized, assessor-blinded, controlled trial was conducted from 2009 to 2013. Seventy-three elderly patients with MD, unipolar and bipolar, were treated with a course of formula-based BF ECT or RUL ECT. The 17-item Hamilton Rating Scale for Depression (HRSD17) was used to measure efficacy. Safety was assessed with the Mini Mental State Examination (MMSE). Both electrode placements resulted in highly significant downward trends in symptom severity (all p<0.001), with a non-significant difference between methods (p=0.703). At the end of the ECT course, response rates for the BF and RUL group were 63.9% and 67.6%, respectively. Short-term remission, defined as an HRSD17 score≤7, was achieved in 14 (38.9%) patients in the BF group and 19 (51.4%) patients in the RUL group. Global cognitive function, as measured by the MMSE, did not deteriorate in the two treatment groups. The small number of subjects may have led to reduced power to detect real differences. The MMSE is not sufficient to ascertain the negative effect of ECT on cognition. This study indicates that formula-based BF and RUL ECT are equally efficacious, and that remission rates of formula-based dosing are lower than those previously reported for titrated dosing, in a clinical sample of elderly patients with MD. ClinicalTrials.gov NCT01559324. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

[Low dose isobaric, hyperbaric, or hypobaric bupivacaine for unilateral spinal anesthesia.].

PubMed

Imbelloni, Luiz Eduardo; Beato, Lúcia; Gouveia, Marildo A; Cordeiro, José Antônio

2007-06-01

Unilateral spinal anesthesia has its advantages, especially in patients undergoing outpatient basis surgeries. Low dose, slow speed of administration, and the lateral positioning make easier the unilateral distribution in spinal anesthesia. Isobaric, hyperbaric, and hypobaric solutions of bupivacaine were compared in the unilateral spinal anesthesia in patients undergoing outpatient basis orthopedic surgeries. One hundred and fifty patients were randomly divided in three groups to receive 5 mg of 0.5% isobaric bupivacaine (Iso Group), 5 mg of 0.5% hyperbaric bupivacaine (Hyper Group), or 5 mg of 0.15% hypobaric bupivacaine (Hypo Group). The solutions were administered in the L3-L4 space with the patient in the lateral decubitus and remaining in this position for 20 minutes. Sensitive anesthesia was evaluated by the pin prick test. Motor blockade was determined by the modified Bromage scale. Both blockades were compared with the opposite side and among themselves. There was a significant difference between the side of the surgery and the opposite side in all three groups at 20 minutes, but the frequency of unilateral spinal anesthesia was greater with the hyperbaric and hypobaric solutions. Sensitive and motor blockades were observed in 14 patients in the Iso Group, 38 patients in the Hyper Group, and 40 patients in the Hypo Group. Patients did not develop any hemodynamic changes. Postpuncture headache and transitory neurological symptoms were not observed. Spinal anesthesia with hypobaric and hyperbaric solutions present a higher frequency of unilateral anesthesia. After 20 minutes, isobaric bupivacaine mobilized into cerebrospinal fluid (CSF) resulted in unilateral spinal anesthesia in only 28% of the patients.

A Randomized Controlled Trial of Brief and Ultrabrief Pulse Right Unilateral Electroconvulsive Therapy

PubMed Central

Katalinic, Natalie; Smith, Deirdre J.; Ingram, Anna; Dowling, Nathan; Martin, Donel; Addison, Kerryn; Hadzi-Pavlovic, Dusan; Simpson, Brett; Schweitzer,, Isaac

2015-01-01

Background: Some studies suggest better overall outcomes when right unilateral electroconvulsive therapy (RUL ECT) is given with an ultrabrief, rather than brief, pulse width. Methods: The aim of the study was to test if ultrabrief-pulse RUL ECT results in less cognitive side effects than brief- pulse RUL ECT, when given at doses which achieve comparable efficacy. One hundred and two participants were assigned to receive ultrabrief (at 8 times seizure threshold) or brief (at 5 times seizure threshold) pulse RUL ECT in a double-blind, randomized controlled trial. Blinded raters assessed mood and cognitive functioning over the ECT course. Results: Efficacy outcomes were not found to be significantly different. The ultrabrief group showed less cognitive impairment immediately after a single session of ECT, and over the treatment course (autobiographical memory, orientation). Conclusions: In summary, when ultrabrief RUL ECT was given at a higher dosage than brief RUL ECT (8 versus 5 times seizure threshold), efficacy was comparable while cognitive impairment was less. PMID:25522389

Systematic review of spinal anaesthesia using bupivacaine for ambulatory knee arthroscopy.

PubMed

Nair, G S; Abrishami, A; Lermitte, J; Chung, F

2009-03-01

The use of lidocaine in spinal anaesthesia is associated with transient neurological syndrome (TNS). Bupivacaine has a lower incidence of TNS as an alternative but it may have a prolonged action. This study systematically reviews the literature about the recovery profile of patients undergoing spinal anaesthesia, using bupivacaine for arthroscopic knee surgery. We identified 17 eligible randomized clinical trials (RCTs) (1268 patients). All the articles in this review, except one, used hyperbaric bupivacaine. Five trials compared different doses of bupivacaine (range 3-15 mg). Large doses of bupivacaine (10 and 15 mg) were associated with delayed recovery, and supine positioning was associated with a high incidence of failure. With unilateral positioning, a dose as low as 4-5 mg seems to be sufficient. Five trials comparing bupivacaine or levobupivacaine with ropivacaine showed no significant difference in the time to home discharge. When bupivacaine was combined with fentanyl in two trials, marginal delay in recovery was found [time to discharge (min); weighted mean difference (WMD) 14.1, 95% CI 11.9-40.1] and increased nausea and pruritus but had reduced postoperative pain. Unilateral and bilateral spinal anaesthesia were assessed in two trials, and the latter group was associated with early recovery and discharge [time to discharge (min); WMD -41.6, 95% CI -63.6 to -19.6). The results of our systematic review suggest that 4-5 mg of hyperbaric bupivacaine can effectively produce spinal anaesthesia for knee arthroscopy with unilateral positioning. Ropivacaine or the addition of adjuvants did not improve the recovery time. There is a need for tighter RCTs with more consistent endpoints.

Protective effect of sildenafil citrate on contralateral testis injury after unilateral testicular torsion/detorsion.

PubMed

Yíldíz, Hamit; Durmus, Ali Said; Simşek, Halil; Yaman, Mine

2011-01-01

This study was designed to investigate prevention of contralateral testicular injury with sildenafil citrate after unilateral testicular torsion/detorsion. Thirty-seven adult male rats were divided into four groups: sham operated (group 1, n = 7), torsion/detorsion + saline (group 2, n = 10), torsion/detorsion + 0.7 mg of sildenafil citrate (group 3, n = 10) and torsion/detorsion + 1.4 mg of sildenafil citrate (group 4, n = 10). Unilateral testicular torsion was created by rotating the right testis 720º in a clockwise direction for 2 h in other groups, except for group 1, which was served as sham group. After torsion (2 h) and detorsion (2 h) periods, rats were killed. The level of reduced glutathion (GSH) (p < 0.05) and the activities of catalase (p < 0.01) and glutathione peroxidase (p < 0.05) in the contralateral testis from group 2 were significantly lower and nitric oxide (NO) (p < 0.05) level in the contralateral testis were significantly higher than those of group 1. Administration of low-dose sildenafil citrate (group 3) prevented the increases in malondialdehyde and NO levels and decreases in glutathione peroxidase activities and GSH values induced by testicular torsion. However, administration of high-dose sildenafil citrate (group 4) had no effect on these testicular parameters (p > 0.05). Histopathological changes were detected in groups 2, 3 and 4. These results suggest that biochemically and histologically torsion/detorsion injury occurs in the contralateral testis following 2-h torsion and 2-h detorsion and that administration of low-dose sildenafil citrate before detorsion prevents ischemia/reperfusion cellular damage in testicular tissue.

Dependence of the phototropic response of Arabidopsis thaliana on fluence rate and wavelength

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

Konjevic, R.; Steinitz, B.; Poff, K.L.

1989-12-01

In the phototropic response of Arabidopsis thaliana seedlings, the shape of the fluence-response relation depends on fluence rate and wavelength. At low fluence rates, the response to 450-nm light is characterized by a single maximum at about 0.3 {mu}mol{center dot}m{sup {minus}2}. At higher fluence rates, the response shows two distinct maxima, I and II, at 0.3 and 3.5 {mu}mol{center dot}m{sup {minus}2}, respectively. The response to 500-nm light shows a single maximum at 2 {mu}mol{center dot}m{sup {minus}2}, and the response to 510-nm light shows a single maximum at 4.5 {mu}mol{center dot}m{sup {minus}2}, independent of fluence rate. The response to 490-nm lightmore » shows a maximal at 4.5 {mu}mol{center dot}m{sup {minus}2} and a shoulder at about 0.6 {mu}mol{center dot}m{sup {minus}2}. Preirradiation with high-fluence 510-nm light from above, immediately followed by unilateral 450-nm light, eliminates maximum II but not maximum I. Preirradiation with high-fluence 450-nm light from above eliminates the response to subsequent unilateral irradiation with either 450-nm or 510-nm light. The recovery of the response following high-fluence 450-nm light is considerably slower than the recovery following high-fluence 510-nm light. Unilateral irradiation with low-fluence 510-nm light followed by 450-nm light results in curvature that is approximately the sum of those produced by either irradiation alone. Based on these results, it is proposed that phototropism in A. thaliana seedlings is mediated by at least two blue-light photoreceptor pigments.« less

A low-dose bupivacaine: a comparison of hyperbaric and hypobaric solutions for unilateral spinal anesthesia.

PubMed

Kaya, Menşure; Oğuz, Selma; Aslan, Kemal; Kadioğullari, Nihal

2004-01-01

The injection of small doses of local anesthetic solutions through pencil-point directional needles and maintaining the lateral decubitus position for 15 to 30 minutes after the injection have been suggested to facilitate the unilateral distribution of spinal anesthesia. We evaluated the effects of hypobaric and hyperbaric bupivacaine in attempting to achieve unilateral spinal anesthesia for patients undergoing lower limb orthopedic surgery. Fifty patients were randomly allocated into 2 groups to receive either 1.5 mL hyperbaric bupivacaine 0.5% (7.5 mg; n = 25) or 4.2 mL hypobaric bupivacaine 0.18% (7.5 mg; n = 25). Drugs were administered at the L3-4 interspace with the patient in the lateral position. Patients remained in this position for 15 minutes before turning supine for the operation. Spinal block was assessed by pinprick and modified Bromage scale on both sides. Unilateral spinal block was observed in 20 patients in the hyperbaric group (80%) and in 19 patients in the hypobaric group (76%) while in the lateral position. However, 15 minutes after patients were turned supine, unilateral spinal anesthesia decreased to 68% of cases in the hyperbaric group and 24% of cases in the hypobaric group (P <.05). The motor block was more intense during the first 5 and 10 minutes (P <.05), but at the end of operation there was no difference between the groups. The hemodynamic changes were similar between the groups. As a result, unilateral spinal anesthesia with hyperbaric and hypobaric bupivacaine provided a rapid motor and sensory recovery and good hemodynamic stability, but more unilateral spinal block was achieved in patients in the hyperbaric group when compared with patients in the hypobaric group.

MOG antibody–positive, benign, unilateral, cerebral cortical encephalitis with epilepsy

PubMed Central

Ogawa, Ryo; Takahashi, Toshiyuki; Kaneko, Kimihiko; Akaishi, Tetsuya; Takai, Yoshiki; Sato, Douglas Kazutoshi; Nishiyama, Shuhei; Misu, Tatsuro; Kuroda, Hiroshi; Aoki, Masashi; Fujihara, Kazuo

2017-01-01

Objective: To describe the features of adult patients with benign, unilateral cerebral cortical encephalitis positive for the myelin oligodendrocyte glycoprotein (MOG) antibody. Methods: In this retrospective, cross-sectional study, after we encountered an index case of MOG antibody–positive unilateral cortical encephalitis with epileptic seizure, we tested for MOG antibody using our in-house, cell-based assay in a cohort of 24 consecutive adult patients with steroid-responsive encephalitis of unknown etiology seen at Tohoku University Hospital (2008–2014). We then analyzed the findings in MOG antibody–positive cases. Results: Three more patients, as well as the index case, were MOG antibody–positive, and all were adult men (median age 37 years, range 23–39 years). The main symptom was generalized epileptic seizure with or without abnormal behavior or consciousness disturbance. Two patients also developed unilateral benign optic neuritis (before or after seizure). In all patients, brain MRI demonstrated unilateral cerebral cortical fluid-attenuated inversion recovery hyperintense lesions, which were swollen and corresponded to hyperperfusion on SPECT. CSF studies showed moderate mononuclear pleocytosis with some polymorphonuclear cells and mildly elevated total protein levels, but myelin basic protein was not elevated. A screening of encephalitis-associated autoantibodies, including aquaporin-4, glutamate receptor, and voltage-gated potassium channel antibodies, was negative. All patients received antiepilepsy drugs and fully recovered after high-dose methylprednisolone, and the unilateral cortical MRI lesions subsequently disappeared. No patient experienced relapse. Conclusions: These MOG antibody–positive cases represent unique benign unilateral cortical encephalitis with epileptic seizure. The pathology may be autoimmune, although the findings differ from MOG antibody–associated demyelination and Rasmussen and other known immune-mediated encephalitides. PMID:28105459

Comparison of two doses of hypobaric bupivacaine in unilateral spinal anesthesia for hip fracture surgery: 5 mg versus 7.5 mg

PubMed Central

Kahloul, Mohamed; Nakhli, Mohamed Said; Chouchene, Amine; Chebbi, Nidhal; Mhamdi, Salah; Naija, Walid

2017-01-01

Introduction Hip fracture is a frequent and severe disease. Its prognosis depends on the perioperative hemodynamic stability which can be preserved by the unilateral spinal anesthesia especially with low doses of local anesthetics. This study aims to compare the efficacy and hemodynamic stability of two doses of hypobaric bupivacaine (7.5 mg vs 5 mg) in unilateral spinal anesthesia. Methods In this prospective, randomized, double-blind study, 108 patients scheduled for hip fracture surgery under unilateral spinal anesthesia were enrolled to receive either 5 mg (group 1) or 7.5 mg (group 2) of hypobaric bupivacaine. Spinal anesthesia was performed in lateral position. Patients’ socio-demographic characteristics, hemodynamic profile, sensory and motor blocks parameters were recorded. Results Both groups were comparable regarding to demographic data. Two cases of failure occurred in group 1 and one case in group 2 corresponding to a comparable efficiency rates (96.29% and 98.14% respectively; p = 0.5). A higher mean onset and lower mean regression times of sensory block were significantly noted in group 1 (7.79±3.76 min vs 5.75±2.35 min, p < 0.001 and 91.29±31.55 min vs 112.77±18.77 min, p <0.001 respectively). Incidence of bilateralization (29.62% vs 87.03%, p < 0.001), incidence of hypotensive episodes (59.25% vs 92.59%, p < 0.001) and vascular loading (1481.48±411.65 ml vs 2111.11±596.10 ml, p < 0.001) were significantly higher in group 2. Conclusion The dosage of 5mg of hypobaric bupivacaine in unilateral spinal anesthesia is as effective as the dosage of 7.5 mg with lower bilateralization incidence and better hemodynamic stability. PMID:29515726

Comparison of two doses of hypobaric bupivacaine in unilateral spinal anesthesia for hip fracture surgery: 5 mg versus 7.5 mg.

PubMed

Kahloul, Mohamed; Nakhli, Mohamed Said; Chouchene, Amine; Chebbi, Nidhal; Mhamdi, Salah; Naija, Walid

2017-01-01

Hip fracture is a frequent and severe disease. Its prognosis depends on the perioperative hemodynamic stability which can be preserved by the unilateral spinal anesthesia especially with low doses of local anesthetics. This study aims to compare the efficacy and hemodynamic stability of two doses of hypobaric bupivacaine (7.5 mg vs 5 mg) in unilateral spinal anesthesia. In this prospective, randomized, double-blind study, 108 patients scheduled for hip fracture surgery under unilateral spinal anesthesia were enrolled to receive either 5 mg (group 1) or 7.5 mg (group 2) of hypobaric bupivacaine. Spinal anesthesia was performed in lateral position. Patients' socio-demographic characteristics, hemodynamic profile, sensory and motor blocks parameters were recorded. Both groups were comparable regarding to demographic data. Two cases of failure occurred in group 1 and one case in group 2 corresponding to a comparable efficiency rates (96.29% and 98.14% respectively; p = 0.5). A higher mean onset and lower mean regression times of sensory block were significantly noted in group 1 (7.79±3.76 min vs 5.75±2.35 min, p < 0.001 and 91.29±31.55 min vs 112.77±18.77 min, p <0.001 respectively). Incidence of bilateralization (29.62% vs 87.03%, p < 0.001), incidence of hypotensive episodes (59.25% vs 92.59%, p < 0.001) and vascular loading (1481.48±411.65 ml vs 2111.11±596.10 ml, p < 0.001) were significantly higher in group 2. The dosage of 5mg of hypobaric bupivacaine in unilateral spinal anesthesia is as effective as the dosage of 7.5 mg with lower bilateralization incidence and better hemodynamic stability.

Unilateral donor lung dysfunction does not preclude successful contralateral single lung transplantation.

PubMed

Puskas, J D; Winton, T L; Miller, J D; Scavuzzo, M; Patterson, G A

1992-05-01

Single lung transplantation remains limited by a severe shortage of suitable donor lungs. Potential lung donors are often deemed unsuitable because accepted criteria (both lungs clear on the chest roentgenogram, arterial oxygen tension greater than 300 mm Hg with an inspired oxygen fraction of 1.0, a positive end-expiratory pressure of 5 cm H2O, and no purulent secretions) do not distinguish between unilateral and bilateral pulmonary disease. Many adequate single lung grafts may be discarded as a result of contralateral aspiration or pulmonary trauma. We have recently used intraoperative unilateral ventilation and perfusion to assess single lung function in potential donors with contralateral lung disease. In the 11-month period ending October 1, 1990, we performed 18 single lung transplants. In four of these cases (22%), the donor chest roentgenogram or bronchoscopic examination demonstrated significant unilateral lung injury. Donor arterial oxygen tension, (inspired oxygen fraction 1.0; positive end-expiratory pressure 5 cm H2O) was below the accepted level in each case (246 +/- 47 mm Hg, mean +/- standard deviation). Through the sternotomy used for multiple organ harvest, the pulmonary artery to the injured lung was clamped. A double-lumen endotracheal tube or endobronchial balloon occlusion catheter was used to permit ventilation of the uninjured lung alone. A second measurement of arterial oxygen tension (inspired oxygen fraction 1.0; positive end-expiratory pressure 5 cm H2O) revealed excellent unilateral lung function in all four cases (499.5 +/- 43 mm Hg; p less than 0.0004). These single lung grafts (three right, one left) were transplanted uneventfully into four recipients (three with pulmonary fibrosis and one with primary pulmonary hypertension). Lung function early after transplantation was adequate in all patients. Two patients were extubated within 24 hours. There were two late deaths, one caused by rejection and Aspergillus infection and the other caused by cytomegalovirus 6 months after transplantation. Two patients are alive and doing well. We conclude that assessment of unilateral lung function in potential lung donors is indicated in selected cases, may be quickly and easily performed, and may significantly increase the availability of single lung grafts.

Bilateral versus unilateral interlaminar approach for bilateral decompression in patients with single-level degenerative lumbar spinal stenosis: a multicenter retrospective study of 175 patients on postoperative pain, functional disability, and patient satisfaction.

PubMed

den Boogert, Hugo F; Keers, Joost C; Marinus Oterdoom, D L; Kuijlen, Jos M A

2015-09-01

The bilateral and unilateral interlaminar techniques for bilateral decompression both demonstrate good results for the treatment of degenerative lumbar spinal stenosis (DLSS). Although there is some discussion about which approach is more effective, studies that directly compare these two popular techniques are rare. To address this shortcoming, this study compares postoperative functional disability, pain, and patient satisfaction among patients with single-level DLSS who underwent bilateral decompression using either a bilateral or unilateral approach. This retrospective study included patients who underwent operations between November 1, 2009, and October 1, 2011. These patients underwent single-level bilateral decompressive surgery using either the bilateral or unilateral interlaminar approach at one of 5 participating hospitals. Exclusion criteria included previous lumbar surgery, additional disc surgery, and spondylolisthesis requiring fusion surgery. Primary outcome measures included bodily pain (as reported using the visual analog scale [VAS]), the Roland-Morris Disability Questionnaire (RMDQ), and the Oswestry Disability Index (ODI). In addition, reductions in leg and back symptoms and the patient's general evaluation of the procedure were queried. Finally, patient satisfaction and surgical parameters were evaluated. Questionnaires were sent to each patient's home, and electronic patient files were used to collect the data. One hundred and seventy-five patients returned the questionnaire (74.4% response rate; 68 and 107 patients who underwent the bilateral or unilateral approach, respectively). Mean age at surgery was 68 years (range 34-89 years), and the mean follow-up period was 14.2 months (range 3.3-27.4 years). There were no significant differences in ODI (20.3 vs 22.6 for the bilateral and unilateral approaches, respectively), RMDQ (3.99 vs 4.8, respectively), or pain scores between treatment groups. Back symptoms were reduced in 74.8% (bilateral: 74.6% vs unilateral: 75%; not significant), and leg symptoms in 80.6% of the patients (bilateral: 73.1% vs unilateral: 85.4%; p = 0.048). In total, 72.1% (bilateral) and 80.0% (unilateral) of patients reported good overall treatment results (p = 0.226). Significantly more patients in the unilateral group reported a better overall satisfaction with the procedure (82.1% vs 69.1%; p = 0.047). There were no differences in postoperative functional disability and pain between the surgical techniques. The significant differences in patient satisfaction and reduction in leg symptoms were unrelated to surgical technique. The overall treatment results were satisfactory. Both techniques are safe and effective options for treating patients with single-level DLSS.

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

PubMed Central

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

2014-01-01

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

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

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

Zelefsky, Michael J., E-mail: zelefskm@mskcc.org; Greco, Carlo; Motzer, Robert

2012-04-01

Purpose: To report tumor local progression-free outcomes after treatment with single-dose, image-guided, intensity-modulated radiotherapy and hypofractionated regimens for extracranial metastases from renal cell primary tumors. Patients and Methods: Between 2004 and 2010, 105 lesions from renal cell carcinoma were treated with either single-dose, image-guided, intensity-modulated radiotherapy to a prescription dose of 18-24 Gy (median, 24) or hypofractionation (three or five fractions) with a prescription dose of 20-30 Gy. The median follow-up was 12 months (range, 1-48). Results: The overall 3-year actuarial local progression-free survival for all lesions was 44%. The 3-year local progression-free survival for those who received a highmore » single-dose (24 Gy; n = 45), a low single-dose (<24 Gy; n = 14), or hypofractionation regimens (n = 46) was 88%, 21%, and 17%, respectively (high single dose vs. low single dose, p = .001; high single dose vs. hypofractionation, p < .001). Multivariate analysis revealed the following variables were significant predictors of improved local progression-free survival: 24 Gy dose compared with a lower dose (p = .009) and a single dose vs. hypofractionation (p = .008). Conclusion: High single-dose, image-guided, intensity-modulated radiotherapy is a noninvasive procedure resulting in high probability of local tumor control for metastatic renal cell cancer generally considered radioresistant according to the classic radiobiologic ranking.« less

Analysis of multiple photoreceptor pigments for phototropism in a mutant of Arabidopsis thaliana

NASA Technical Reports Server (NTRS)

Konjevic, R.; Khurana, J. P.; Poff, K. L.

1992-01-01

The shape of the fluence-response relationship for the phototropic response of the JK224 strain of Arabidopsis thaliana depends on the fluence rate and wavelength of the actinic light. At low fluence rate (0.1 micromole m-2 s-1), the response to 450-nm light is characterized by a single maximum at about 9 micromoles m-2. At higher fluence rate (0.4 micromole m-2 s-1), the response shows two maxima, at 4.5 and 9 micromoles m-2. The response to 510-nm light shows a single maximum at 4.5 micromoles m-2. Unilateral preirradiation with high fluence rate (25 micromoles m-2 s-1) 510-nm light eliminates the maximum at 4.5 micromoles m-2 in the fluence response curve to a subsequent unilateral 450-nm irradiation, while the second maximum at 9 micromoles m-2 is unaffected. Based on these results, it is concluded that a single photoreceptor pigment has been altered in the JK224 strain of Arabidopsis thaliana.

Long-term Evaluation of Radiation-Induced Optic Neuropathy After Single-Fraction Stereotactic Radiosurgery

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

Leavitt, Jacqueline A., E-mail: leavitt.jacqueline@mayo.edu; Stafford, Scott L.; Link, Michael J.

2013-11-01

Purpose: To determine the long-term risk of radiation-induced optic neuropathy (RION) in patients having single-fraction stereotactic radiosurgery (SRS) for benign skull base tumors. Methods and Materials: Retrospective review of 222 patients having Gamma Knife radiosurgery for benign tumors adjacent to the anterior visual pathway (AVP) between 1991 and 1999. Excluded were patients with prior or concurrent external beam radiation therapy or SRS. One hundred twenty-nine patients (58%) had undergone previous surgery. Tumor types included confirmed World Health Organization grade 1 or presumed cavernous sinus meningioma (n=143), pituitary adenoma (n=72), and craniopharyngioma (n=7). The maximum dose to the AVP was ≤8.0more » Gy (n=126), 8.1-10.0 Gy (n=39), 10.1-12.0 Gy (n=47), and >12 Gy (n=10). Results: The mean clinical and imaging follow-up periods were 83 and 123 months, respectively. One patient (0.5%) who received a maximum radiation dose of 12.8 Gy to the AVP developed unilateral blindness 18 months after SRS. The chance of RION according to the maximum radiation dose received by the AVP was 0 (95% confidence interval [CI] 0-3.6%), 0 (95% CI 0-10.7%), 0 (95% CI 0-9.0%), and 10% (95% CI 0-43.0%) for patients receiving ≤8 Gy, 8.1-10.0 Gy, 10.1-12.0 Gy, and >12 Gy, respectively. The overall risk of RION in patients receiving >8 Gy to the AVP was 1.0% (95% CI 0-6.2%). Conclusions: The risk of RION after single-fraction SRS in patients with benign skull base tumors who have no prior radiation exposure is very low if the maximum dose to the AVP is ≤12 Gy. Physicians performing single-fraction SRS should remain cautious when treating lesions adjacent to the AVP, especially when the maximum dose exceeds 10 Gy.« less

Postero-Lateral Disc Prosthesis Combined With a Unilateral Facet Replacement Device Maintains Quantity and Quality of Motion at a Single Lumbar Level

PubMed Central

Nayak, Aniruddh N.; Doarn, Michael C.; Gaskins, Roger B.; James, Chris R.; Cabezas, Andres F.; Castellvi, Antonio E.

2014-01-01

Background Mechanically replacing one or more pain generating articulations in the functional spinal unit (FSU) may be a motion preservation alternative to arthrodesis at the affected level. Baseline biomechanical data elucidating the quantity and quality of motion in such arthroplasty constructs is non-existent. Purpose The purpose of the study was to quantify the motion-preserving effect of a posterior total disc replacement (PDR) combined with a unilateral facet replacement (FR) system at a single lumbar level (L4-L5). We hypothesized that reinforcement of the FSU with unilateral FR to replace the resected, native facet joint following PDR implantation would restore quality and quantity of motion and additionally not change biomechanics at the adjacent levels. Study Design In-vitro study using human cadaveric lumbar spines. Methods Six (n = 6) cadaveric lumbar spines (L1-S1) were evaluated using a pure-moment stability testing protocol (±7.5 Nm) in flexion-extension (F/E), lateral bending (LB) and axial rotation (AR). Each specimen was tested in: (1) intact; (2) unilateral FR; and (3) unilateral FR + PDR conditions. Index and adjacent level ROM (using hybrid protocol) were determined opto-electronically. Interpedicular travel (IPT) and instantaneous center of rotation (ICR) at the index level were radiographically determined for each condition. ROM, ICR, and IPT measurements were compared (repeated measures ANOVA) between the three conditions. Results Compared to the intact spine, no significant changes in F/E, LB or AR ROM were identified as a result of unilateral FR or unilateral FR + PDR. No significant changes in adjacent L3-L4 or L5-S1 ROM were identified in any loading mode. No significant differences in IPT were identified between the three test conditions in F/E, LB or AR at the L4-L5 level. The ICRs qualitatively were similar for the intact and unilateral FR conditions and appeared to follow placement (along the anterior-posterior (AP) direction) of the PDR in the disc space Conclusion Biomechanically, quantity and quality of motion are maintained with combined unilateral FR + PDR at a single lumbar spinal level. PMID:25694929

Hippocampal asymmetry in exploratory behavior to vasoactive intestinal polypeptide.

PubMed

Ivanova, Margarita; Ternianov, Alexandar; Belcheva, Stiliana; Tashev, Roman; Negrev, Negrin; Belcheva, Iren

2008-06-01

The effects of vasoactive intestinal polypeptide (VIP) microinjected uni- or bilaterally into the CA1 hippocampal area of male Wistar rats at a dose of 10, 50 and 100 ng on exploratory behavior were examined. VIP microinjected bilaterally at a high dose (100 ng) significantly decreased the horizontal movements, while at low doses (10 and 50 ng) had no effect on the exploratory activity. Microinjections of VIP into the left hippocampal CA1 area at doses 50 and 100 ng suppressed the exploratory activity, while right-side VIP administration at a dose 100 ng significantly increased horizontal movements compared to the respective controls. Vertical activity was stimulated only by VIP administered into the right hippocampal CA1 area at the three doses used. Neither bilateral nor left injections of VIP induced changes in the vertical movements. The main finding was the presence of hippocampal asymmetry in exploratory behavior to unilateral microinjections of VIP depending on the dose and the microinjected hemisphere.

Localized unilateral periorbital edema induced by aspirin.

PubMed

Price, K S; Thomson, D M

1997-11-01

Aspirin intolerance manifested as bronchospasm or urticaria/angioedema has been observed since the beginning of this century. To report a novel case of intolerance to aspirin ingestion. Case report; routine skin testing; pulmonary function testing; aspirin challenge. A 30-year-old man with a history of left ocular trauma at the age of 10 noted a 3-year history of left periorbital angioedema after aspirin but not other nonsteroidal anti-inflammatory drugs. Incremental oral aspirin challenge resulted in this unilateral symptomatology at a dose of 673 mg. To the best of our knowledge, this is the first reported case of unilateral periorbital edema following aspirin ingestion.

Biphasic effects of oxotremorine-M on turning behavior induced by caffeine in 6-OHDA-lesioned rats.

PubMed

Núñez-Taltavull, Juan Francisco; Prat, Gemma; Rubio, Antonia; Robledo, Patricia; Casas, Miguel

2004-12-03

This work studied the interactions between cholinergic and adenosine systems in the denervated striatum. For that purpose, we evaluated the effects of an intrastriatal administration of the muscarincic receptor agonist, oxotremorine-M on turning behavior induced by systemic caffeine in unilaterally 6-hydroxydopamine-lesioned rats. Low doses of oxotremorine-M (0.1 ng/microl) enhanced, whereas high doses (100 ng/microl) attenuated contralateral turning induced by caffeine. These results support a functional link between muscarinic and adenosinergic systems in the denervated striatum and suggest opposite actions of muscarinic M2 and M1 receptors on caffeine-induced turning behavior.

Biomechanics of unilateral and bilateral sacroiliac joint stabilization: laboratory investigation.

PubMed

Lindsey, Derek P; Parrish, Robin; Gundanna, Mukund; Leasure, Jeremi; Yerby, Scott A; Kondrashov, Dimitriy

2018-03-01

OBJECTIVE Bilateral symptoms have been reported in 8%-35% of patients with sacroiliac (SI) joint dysfunction. Stabilization of a single SI joint may significantly alter the stresses on the contralateral SI joint. If the contralateral SI joint stresses are significantly increased, degeneration may occur; alternatively, if the stresses are significantly reduced, bilateral stabilization may be unnecessary for patients with bilateral symptoms. The biomechanical effects of 1) unilateral stabilization on the contralateral SI joint and 2) bilateral stabilization on both SI joints are currently unknown. The objectives of this study were to characterize bilateral SI joint range of motion (ROM) and evaluate and compare the biomechanical effects of unilateral and bilateral implant placement for SI joint fusion. METHODS A lumbopelvic model (L5-pelvis) was used to test the ROM of both SI joints in 8 cadavers. A single-leg stance setup was used to load the lumbar spine and measure the ROM of each SI joint in flexion-extension, lateral bending, and axial rotation. Both joints were tested 1) while intact, 2) after unilateral stabilization, and 3) after bilateral stabilization. Stabilization consisted of lateral transiliac placement of 3 triangular titanium plasma-sprayed (TPS) implants. RESULTS Intact testing showed that during single-leg stance the contralateral SI joint had less ROM in flexion-extension (27%), lateral bending (32%), and axial rotation (69%) than the loaded joint. Unilateral stabilization resulted in significant reduction of flexion-extension ROM (46%) on the treated side; no significant ROM changes were observed for the nontreated side. Bilateral stabilization resulted in significant reduction of flexion-extension ROM of the primary (45%) and secondary (75%) SI joints. CONCLUSIONS This study demonstrated that during single-leg loading the ROMs for the stance (loaded) and swing (unloaded) SI joints are significantly different. Unilateral stabilization for SI joint dysfunction significantly reduces the ROM of the treated side, but does not significantly reduce the ROM of the nontreated contralateral SI joint. Bilateral stabilization is necessary to significantly reduce the ROM for both SI joints.

High-definition transcranial direct current stimulation (HD-tDCS) of left dorsolateral prefrontal cortex affects performance in Balloon Analogue Risk Task (BART).

PubMed

Guo, Heng; Zhang, Zhuoran; Da, Shu; Sheng, Xiaotian; Zhang, Xichao

2018-02-01

Studies on risk preferences have long been of great concern and have examined the neural basis underlying risk-based decision making. However, studies using conventional transcranial direct current stimulation (tDCS) revealed that bilateral stimulation could change risk propensity with limited evidence of precisely focalized unilateral high-definition transcranial direct current stimulation (HD-tDCS). The aim of this experiment was to investigate the effect of HD-tDCS focalizing the left dorsal lateral prefrontal cortex (DLPFC) on risk-taking behavior during the Balloon Analogue Risk Task (BART). This study was designed as a between-subject, single-blind, sham-controlled experiment. University students were randomly assigned to three groups: the anodal group (F3 anode, AF3, F1, F5, FC3 returned), the cathodal group (F3 cathodal, AF3, F1, F5, FC3 returned) and the sham group. Subsequently, 1.5-mA 20-min HD-tDCS was applied during the BART, and the Positive Affect and Negative Affect Scale (PANAS), the Sensation Seeking Scale-5 (SSS-5), and the Behavioral Inhibition System and Behavioral Approach System scale (BIS/BAS) were measured as control variables. The cathodal group earned less total money than the sham group, and no significant difference was observed between the anodal group and the sham group. These results showed that, to some extent, focalized unilateral cathodal HD-tDCS on left DLPFC could change performance during risky tasks and diminish risky decision making. Further studies are needed to investigate the dose effect and electrode distribution of HD-tDCS during risky tasks and examine synchronous brain activity to show the neural basis.

Development and validation of an automated system for detection and assessment of scratching in the rodent

PubMed Central

Marino, Marc; Huang, Polly; Malkmus, Shelle; Robertshaw, Erin; Mac, Elaine A.; Shatterman, Yuri; Yaksh, Tony L.

2012-01-01

Pruritus, the sensation of itch, which evokes reflex scratching behavior, has a diverse etiology. Because of its clinical significance, mechanisms of pruriception are an important topic. In the present work we describe and validate a paw motion detector (PMD) system. The system employs a small removable metal band placed on one hind paw that provides a signal indicative of paw movement through perturbation of an electromagnetic (EM) field. C57Bl/6 mice were fitted with a unilateral hind paw band and adapted to testing cylinders equipped with EM signal emission and detection. The following observations were made: 1) in mice, unilateral SQ injection of 48/80 into the dorsolateral aspect of the neck evoked periodic high frequency bursts of scratching at the injected site with the ipsilateral (banded) but not the contralateral (not banded) hind paw. 2) Cross correlation between PMD and human observer counts after SQ 48/80 using the specified computational algorithm revealed a highly significant correlation. 3) SQ histamine and 48/80 over a 1 hour interval produced dose dependent scratching, which diphenhydramine dose dependently reversed. Chloroquine scratching displayed an inverse u-shaped dose response curve, which was insensitive to diphenhydramine. 4) SQ 48/80 at intervals over 28 days showed no change in the scratching response within the same cohort of mice. 5) Power analysis showed 40% changes in scratching activity could be detected at the p<0.05 level with groups of 4 mice. These observations indicate that the system described can efficiently define the actions and pharmacology of pruritogenic agents. PMID:22971351

Two-stage unilateral versus one-stage bilateral single-port sympathectomy for palmar and axillary hyperhidrosis†

PubMed Central

Ibrahim, Mohsen; Menna, Cecilia; Andreetti, Claudio; Ciccone, Anna Maria; D'Andrilli, Antonio; Maurizi, Giulio; Poggi, Camilla; Vanni, Camilla; Venuta, Federico; Rendina, Erino Angelo

2013-01-01

OBJECTIVES Video-assisted thoracoscopic sympathectomy is currently the best treatment for palmar and axillary hyperhidrosis. It can be performed through either one or two stages of surgery. This study aimed to evaluate the operative and postoperative results of two-stage unilateral vs one-stage bilateral thoracoscopic sympathectomy. METHODS From November 1995 to February 2011, 270 patients with severe palmar and/or axillary hyperhidrosis were recruited for this study. One hundred and thirty patients received one-stage bilateral, single-port video-assisted thoracoscopic sympathectomy (one-stage group) and 140, two-stage unilateral, single-port video-assisted thoracoscopic sympathectomy, with a mean time interval of 4 months between the procedures (two-stage group). RESULTS The mean postoperative follow-up period was 12.5 (range: 1–24 months). After surgery, hands and axillae of all patients were dry and warm. Sixteen (12%) patients of the one-stage group and 15 (11%) of the two-stage group suffered from mild/moderate pain (P = 0.8482). The mean operative time was 38 ± 5 min in the one-stage group and 39 ± 8 min in the two-stage group (P = 0.199). Pneumothorax occurred in 8 (6%) patients of the one-stage group and in 11 (8%) of the two-stage group. Compensatory sweating occurred in 25 (19%) patients of the one-stage group and in 6 (4%) of the two-stage group (P = 0.0001). No patients developed Horner's syndrome. CONCLUSIONS Both two-stage unilateral and one-stage bilateral single-port video-assisted thoracoscopic sympathectomies are effective, safe and minimally invasive procedures. Two-stage unilateral sympathectomy can be performed with a lower occurrence of compensatory sweating, improving permanently the quality of life in patients with palmar and axillary hyperhidrosis. PMID:23442937

Two-stage unilateral versus one-stage bilateral single-port sympathectomy for palmar and axillary hyperhidrosis.

PubMed

Ibrahim, Mohsen; Menna, Cecilia; Andreetti, Claudio; Ciccone, Anna Maria; D'Andrilli, Antonio; Maurizi, Giulio; Poggi, Camilla; Vanni, Camilla; Venuta, Federico; Rendina, Erino Angelo

2013-06-01

Video-assisted thoracoscopic sympathectomy is currently the best treatment for palmar and axillary hyperhidrosis. It can be performed through either one or two stages of surgery. This study aimed to evaluate the operative and postoperative results of two-stage unilateral vs one-stage bilateral thoracoscopic sympathectomy. From November 1995 to February 2011, 270 patients with severe palmar and/or axillary hyperhidrosis were recruited for this study. One hundred and thirty patients received one-stage bilateral, single-port video-assisted thoracoscopic sympathectomy (one-stage group) and 140, two-stage unilateral, single-port video-assisted thoracoscopic sympathectomy, with a mean time interval of 4 months between the procedures (two-stage group). The mean postoperative follow-up period was 12.5 (range: 1-24 months). After surgery, hands and axillae of all patients were dry and warm. Sixteen (12%) patients of the one-stage group and 15 (11%) of the two-stage group suffered from mild/moderate pain (P = 0.8482). The mean operative time was 38 ± 5 min in the one-stage group and 39 ± 8 min in the two-stage group (P = 0.199). Pneumothorax occurred in 8 (6%) patients of the one-stage group and in 11 (8%) of the two-stage group. Compensatory sweating occurred in 25 (19%) patients of the one-stage group and in 6 (4%) of the two-stage group (P = 0.0001). No patients developed Horner's syndrome. Both two-stage unilateral and one-stage bilateral single-port video-assisted thoracoscopic sympathectomies are effective, safe and minimally invasive procedures. Two-stage unilateral sympathectomy can be performed with a lower occurrence of compensatory sweating, improving permanently the quality of life in patients with palmar and axillary hyperhidrosis.

Static lung volumes in healthy subjects assessed by helium dilution during occlusion of one mainstem bronchus.

PubMed

Johansen, B; Bjørtuft, O; Boe, J

1993-04-01

Single lung function is usually assessed by radioisotopes or, more rarely, by bronchospirometry in which a double lumen catheter is used to separate ventilation of the two lungs. The latter is more precise but less comfortable. An alternative bronchoscopic method is described for determining the volume of a single lung. One mainstem bronchus was temporarily occluded with an inflatable balloon during fibreoptic bronchoscopy in 12 healthy volunteers aged 18-29 years. The functional residual capacities (FRC) of the right, left, and both lungs were measured in duplicate by closed circuit helium dilution. Supplementary vital capacity (VC) manoeuvres permitted calculation of single lung capacities (TLC) and residual volumes (RV). The standard deviation of a single determination of capacities of the right, left, and both lungs were: TLC, 80, 96, and 308 ml; VC, 56, 139, 171 ml; FRC, 131, 74, and 287 ml; RV, 112, 185, and 303 ml, respectively. The sum of the right and left unilateral TLC was not different from bilateral TLC (6.12 v 5.95 l) and the sum of the unilateral FRC was not different from the bilateral FRC (2.60 v 2.78 l). The sum of the unilateral VC was lower than bilateral VC (4.52 v 4.80 l), that of the unilateral RV was higher than bilateral RV (1.60 v 1.16 l). For all subdivisions of lung volume, the right lung was larger than the left. The most common complaint was substernal discomfort during complete exhalation. Oxygen saturation rarely fell below 90%. Temporary occlusion of a mainstem bronchus in normal subjects is safe, relatively simple, and allows fairly precise and accurate measurements of unilateral static lung volumes. Occlusion at TLC, however, probably prevents proper emptying of the non-occluded lung.

Dose-dependent protective effect of sildenafil citrate on testicular injury after torsion/detorsion in rats.

PubMed

Yıldız, H; Durmus, A S; Şimşek, H; Yaman, M

2012-05-01

This experiment was designed to investigate the effect of sildenafil citrate on testicular injury after unilateral testicular torsion/detorsion (T/D). Thirty-seven adult male Wistar albino rats were divided into four groups: sham operated group (group 1), T/D+ saline (group 2), T/D+ 0.7 mg sildenafil citrate (group 3) and T/D+ 1.4 mg sildenafil citrate (group 4). Testicular torsion was created by rotating the right testis 720° in a clockwise direction for 2 h in other groups, except for group 1, which was served as sham group. The level of GSH (P < 0.05) in the testis in the group 2 were significantly lower (P < 0.05) and the levels of MDA and NO (P < 0.01 for both) in the testis were significantly higher when compared with those of the group 1. Administration of low dose sildenafil citrate prevented the increases in MDA and NO levels and decreases in GSH values induced by testicular torsion. However, administration of high dose sildenafil citrate did not have any effect on these testicular tissue parameters (P > 0.05). Also, mean values of seminiferous tubules diameters, germinal cell layer thicknesses and mean testicular biopsy score were significantly better in group 3 than groups 2 and 4. These results suggest that T/D injury occurred in testis after unilateral testicular T/D and that administration of low dose sildenafil citrate before detorsion prevents ischemia/reperfusion cellular damage in testicular torsion. Sildenafil citrate probably acts through reduction of reactive oxygen species and support antioxidant enzyme systems. © 2011 Blackwell Verlag GmbH.

A stimulus-centered reading disorder for words and numbers: Is it neglect dyslexia?

PubMed

Arduino, Lisa S; Daini, Roberta; Caterina Silveri, Maria

2005-12-01

A single case, RCG, showing a unilateral reading disorder without unilateral spatial neglect was studied. The disorder was characterized by substitutions of the initial (left) letters of words, nonwords and Arabic numbers, independently of egocentered spatial coordinates. MRI showed a bilateral lesion with the involvement of the splenium. Although, within the framework of the visual word recognition model proposed by Caramazza and Hillis (1990), RCG disorder could be defined as a stimulus-centered neglect dyslexia, we discuss the hypothesis of a dissociation in neural correlates and mechanisms between the syndrome of unilateral spatial neglect and such a unilateral reading disorder.

Does unilateral single-event multilevel surgery improve gait in children with spastic hemiplegia? A retrospective analysis of a long-term follow-up.

PubMed

Schranz, Christian; Kruse, Annika; Kraus, Tanja; Steinwender, Gerhardt; Svehlik, Martin

2017-02-01

Single event multilevel surgery (SEMLS) has become a standard intervention for children with cerebral palsy (CP). SEMLS proved to improve the gait in bilateral spastic cerebral palsy and those improvements can be maintained in the long term. However there is no evidence on the long-term outcome of unilateral SEMLS in children with unilateral spastic cerebral palsy. The gait analyses and clinical data of 14 children (9 male/5 female, mean age 12.1) with unilateral CP (6 children Gross Motor Function Classification System Scale level I and 8 children level II) were retrospectively reviewed at four time-points: preoperatively, 1year, 3-5 years and approximately 10 years after unilateral SEMLS. The Gait Profile Score (GPS) of the affected leg was used as a main and the number of fine tuning procedures as well as complications rate (Clavien-Dindo classification) as secondary outcome measures. The gait improved postoperatively and the GPS of the affected leg significantly declined by 3.73° which is well above the minimal clinical important difference of 1.6°. No deterioration of GPS occurred throughout the follow-up period. Therefore the postoperative improvement was maintained long-term. However, additional fine-tuning procedures had to be performed during the follow-up in 5 children and three complications occurred (one level II and two level III). The results indicate that children with unilateral cerebral palsy benefit from unilateral SEMLS and maintain gait improvements long-term. Copyright © 2016 Elsevier B.V. All rights reserved.

Diffuse chorioretinal atrophy after a single standard low- dose intravitreal melphalan injection in a child with retinoblastoma: a case report.

PubMed

Chao, An- Ning; Kao, Ling-Yuh; Liu, Laura; Wang, Nan-Kai

2016-03-15

Controlling retinoblastoma with seeding is challenging despite advances in treatment modalities. Intravitreal melphalan is an alternative to external beam radiation or enucleation for recurrent or refractory vitreous seeds. Significant ocular side effects following intravitreal melphalan injections are uncommon. Complications have been reported in eyes receiving higher concentrations of melphalan and repetitive injections. We report a case in which diffuse chorioretinal atrophy was developed at the injection site after a single, standard low-dose intravitreal melphalan injection. A 12-month-old female child without a family history of retinoblastoma presented with unilateral group C retinoblastoma in her right eye. A solitary tumour with retinal breaks on the tumour surface, and vitreous seeds overlying the tumour were observed at the 8 o'clock position of the retina. After two cycles of intra-arterial chemotherapy with melphalan, the main tumour displayed significant regression, but the vitreous seeds overlying the main tumour were still active. Because of the persistence of vitreous seeds and the inadequate response to intra-arterial melphalan treatment, intravitreal melphalan (8 μg in 0.05 mL) was injected using a 32-gauge needle 2.5 mm from the 5 o'clock position of the limbus, the meridian opposite to the vitreous seeds. After 1 month, the retina around the injection site demonstrated diffuse retinal pigment epithelium alterations with dense hard exudates. Although the main retinal mass, and vitreous seeds resolved, the hard exudates persisted for more than 2 years after the single low-dose melphalan injection. Intravitreal melphalan injections should be cautiously used for eyes with refractory seeds, particularly when multiple injections are required to control retinoblastoma seeds. Dose- related retinal toxicity could occur in pre-treated eyes even when a relatively low standard dose is used. Such patients should be followed up closely to monitor the treatment response and to assess potential delayed toxicity.

Of blind men and elephants: suggesting SDM-MASS as a compound measure for shared decision making integrating patient, physician and observer views.

PubMed

Geiger, Friedemann; Kasper, Jürgen

2012-01-01

Shared decision making (SDM) between patient and physician is an interpersonal process. Most SDM measures use the view of one party (patient, physician or observer) as a proxy to capture this process although these views typically diverge. This study suggests the compound measure SDM(MASS) (SDM Meeting its concept's ASSumptions) integrating these three perspectives in one single index. SDM(MASS) was derived theoretically and compared empirically to unilateral perspectives of patients, physicians and observers by application to a data set of 10 physicians (40 consultations) receiving an SDM training. The constituting parts of SDM(MASS) were highly reliable (Cronbach's alpha .94; interrater reliability .74-.87). Unilateral appraisal of training effects was divergent. SDM(MASS) revealed no effect. SDM(MASS) combines noteworthy information about SDM processes from different viewpoints and thereby delivers plausible assessments. It could overcome immanent shortcomings of unilateral approaches. However, it is a complex measure needing further validation. Copyright © 2012. Published by Elsevier GmbH.

Bilateral Changes of Spontaneous Activity Within the Central Auditory Pathway Upon Chronic Unilateral Intracochlear Electrical Stimulation.

PubMed

Basta, Dietmar; Götze, Romy; Gröschel, Moritz; Jansen, Sebastian; Janke, Oliver; Tzschentke, Barbara; Boyle, Patrick; Ernst, Arne

2015-12-01

In recent years, cochlear implants have been applied successfully for the treatment of unilateral hearing loss with quite surprising benefit. One reason for this successful treatment, including the relief from tinnitus, could be the normalization of spontaneous activity in the central auditory pathway because of the electrical stimulation. The present study, therefore, investigated at a cellular level, the effect of a unilateral chronic intracochlear stimulation on key structures of the central auditory pathway. Normal-hearing guinea pigs were mechanically single-sided deafened through a standard HiFocus1j electrode array (on a HiRes 90k cochlear implant) being inserted into the first turn of the cochlea. Four to five electrode contacts could be used for the stimulation. Six weeks after surgery, the speech processor (Auria) was fitted, based on tNRI values and mounted on the animal's back. The two experimental groups were stimulated 16 hours per day for 90 days, using a HiRes strategy based on different stimulation rates (low rate (275 pps/ch), high rate (5000 pps/ch)). The results were compared with those of unilateral deafened controls (implanted but not stimulated), as well as between the treatment groups. All animals experienced a standardized free field auditory environment. The low-rate group showed a significantly lower average spontaneous activity bilaterally in the dorsal cochlear nucleus and the medial geniculate body than the controls. However, there was no difference in the inferior colliculus and the primary auditory cortex. Spontaneous activity of the high-rate group was also reduced bilaterally in the dorsal cochlear nucleus and in the primary auditory cortex. No differences could be observed between the high-rate group and the controls in the contra-lateral inferior colliculus and medial geniculate body. The high-rate group showed bilaterally a higher activity in the CN and the MGB compared with the low-rate group, whereas in the IC and in the AC a trend for an opposite effect could be determined. Unilateral intracochlear electrical stimulation seems to facilitate the homeostasis of the network activity, since it decreases the spontaneous activity that is usually elevated upon deafferentiation. The electrical stimulation per se seems to be responsible for the bilateral changes described above, rather than the particular nature of the electrical stimulation (e.g., rate). The normalization effects of electrical stimulation found in the present study are of particular importance in cochlear implant recipients with single-sided deafness.

The effect of methotrexate on the bone healing of mandibular condylar process fracture: an experimental study in rats.

PubMed

Cavalcanti, Samantha Cristine Santos X B; Corrêa, Luciana; Mello, Suzana Beatriz Veríssimo; Luz, João Gualberto C

2014-10-01

Methotrexate (MTX) is an anti-metabolite used in rheumatology and oncology. High doses are indicated for oncological treatment, whereas low doses are indicated for chronic inflammatory diseases. This study evaluated the effect of two MTX treatment schedules on the bone healing of the temporomandibular joint fracture in rats. Seventy-five adult male Wistar rats were used to generate an experimental unilateral medially rotated condylar fracture model that allows an evaluation of bone healing and the articular structures. The animals were subdivided into three groups that each received one of the following treatments intraperitoneally: saline (1 mL/week), low-dose MTX (3 mg/kg/week) and high-dose MTX (30 mg/kg). The histological study comprised fracture site and temporomandibular joint evaluations and bone neoformation was evaluated by histomorphometric analysis. A biochemical parameter of bone formation was also assessed. When compared with saline, high-dose MTX delayed bone fracture repairs. In this latter group, after 90 days, the histological analysis revealed atrophy of the fibrocartilage and the presence of fibrous tissue in the joint space. The histomorphometric analysis revealed diminished bone neoformation. The alkaline phosphatase levels also decreased after MTX treatment. It was concluded that high-dose MTX impaired mandibular condyle repair and induced degenerative articular changes. Copyright © 2014 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

Efficacy of Single-Dose and Triple-Dose Albendazole and Mebendazole against Soil-Transmitted Helminths and Taenia spp.: A Randomized Controlled Trial

PubMed Central

Steinmann, Peter; Utzinger, Jürg; Du, Zun-Wei; Jiang, Jin-Yong; Chen, Jia-Xu; Hattendorf, Jan; Zhou, Hui; Zhou, Xiao-Nong

2011-01-01

Background The control of soil-transmitted helminth (STH) infections currently relies on the large-scale administration of single-dose oral albendazole or mebendazole. However, these treatment regimens have limited efficacy against hookworm and Trichuris trichiura in terms of cure rates (CR), whereas fecal egg reduction rates (ERR) are generally high for all common STH species. We compared the efficacy of single-dose versus triple-dose treatment against hookworm and other STHs in a community-based randomized controlled trial in the People's Republic of China. Methodology/Principal findings The hookworm CR and fecal ERR were assessed in 314 individuals aged ≥5 years who submitted two stool samples before and 3–4 weeks after administration of single-dose oral albendazole (400 mg) or mebendazole (500 mg) or triple-dose albendazole (3×400 mg over 3 consecutive days) or mebendazole (3×500 mg over 3 consecutive days). Efficacy against T. trichiura, Ascaris lumbricoides, and Taenia spp. was also assessed. Albendazole cured significantly more hookworm infections than mebendazole in both treatment regimens (single dose: respective CRs 69% (95% confidence interval [CI]: 55–81%) and 29% (95% CI: 20–45%); triple dose: respective CRs 92% (95% CI: 81–98%) and 54% (95% CI: 46–71%)). ERRs followed the same pattern (single dose: 97% versus 84%; triple dose: 99.7% versus 96%). Triple-dose regimens outperformed single doses against T. trichiura; three doses of mebendazole – the most efficacious treatment tested – cured 71% (95% CI: 57–82%). Both single and triple doses of either drug were highly efficacious against A. lumbricoides (CR: 93–97%; ERR: all >99.9%). Triple dose regimens cured all Taenia spp. infections, whereas single dose applications cured only half of them. Conclusions/Significance Single-dose oral albendazole is more efficacious against hookworm than mebendazole. To achieve high CRs against both hookworm and T. trichiura, triple-dose regimens are warranted. Trial Registration www.controlled-trials.com ISRCTN47375023 PMID:21980373

RS3PE presenting in a unilateral pattern: case report and review of the literature.

PubMed

Keenan, Robert T; Hamalian, Gareen M; Pillinger, Michael H

2009-06-01

To review the clinical features and pathophysiologic implications of remitting seronegative symmetrical synovitis with pitting edema (RS(3)PE) presenting in a unilateral manner. We identified and characterized an index case of RS(3)PE presenting in a unilateral pattern. We subsequently performed a systematic literature search to identify other reports of patients with unilateral RS(3)PE. The index case was a 76-year-old male with a prior history of right hemiparesis owing to a cerebrovascular accident 25 years prior, who developed a classic picture of RS(3)PE involving hand (metacarpophalageal and wrist joint) arthritis and dorsal pitting edema, accompanied by an elevated erythrocyte sedimentation rate, but only in the nonhemiparetic hand. The condition responded rapidly to low-dose prednisone. Our literature search identified 5 other cases of unilateral RS(3)PE, including 2 presented only in the Italian or German literature. Of the 5 cases, 2 were in patients with preexisting neurologic disease, in which the neurologically affected side was spared. One additional case initially presented as unilateral disease but rapidly progressed to bilaterality. Two cases presented in a fully unilateral manner despite no reported neurologic abnormalities on the unaffected sides. While RS(3)PE is almost always a symmetric disease of the upper extremities, it may rarely present in a unilateral fashion. The apparent ability of neuropathic changes to protect against the expression of RS(3)PE in an extremity suggests a role for neural and possibly other local factors in the genesis/modulation of the onset or maintenance of RS(3)PE.

Does unilateral basal ganglia activity functionally influence the contralateral side? What we can learn from STN stimulation in patients with Parkinson's disease.

PubMed

Brun, Yohann; Karachi, Carine; Fernandez-Vidal, Sara; Jodoin, Nicolas; Grabli, David; Bardinet, Eric; Mallet, Luc; Agid, Yves; Yelnik, Jerome; Welter, Marie-Laure

2012-09-01

In humans, the control of voluntary movement, in which the corticobasal ganglia (BG) circuitry participates, is mainly lateralized. However, several studies have suggested that both the contralateral and ipsilateral BG systems are implicated during unilateral movement. Bilateral improvement of motor signs in patients with Parkinson's disease (PD) has been reported with unilateral lesion or high-frequency stimulation (HFS) of the internal part of the globus pallidus or the subthalamic nucleus (STN-HFS). To decipher the mechanisms of production of ipsilateral movements induced by the modulation of unilateral BG circuitry activity, we recorded left STN neuronal activity during right STN-HFS in PD patients operated for bilateral deep brain stimulation. Left STN single cells were recorded in the operating room during right STN-HFS while patients experienced, or did not experience, right stimulation-induced dyskinesias. Most of the left-side STN neurons (64%) associated with the presence of right dyskinesias were inhibited, with a significant decrease in burst and intraburst frequencies. In contrast, left STN neurons not associated with right dyskinesias were mainly activated (48%), with a predominant increase 4-5 ms after the stimulation pulse and a decrease in oscillatory activity. This suggests that unilateral neuronal STN modulation is associated with changes in the activity of the contralateral STN. The fact that one side of the BG system can influence the functioning of the other could explain the occurrence of bilateral dyskinesias and motor improvement observed in PD patients during unilateral STN-HFS, as a result of a bilateral disruption of the pathological activity in the corticosubcortical circuitry.

A giant ovarian cyst in a neonate with classical 21-hydroxylase deficiency with very high testosterone levels demonstrating a high-dose hook effect.

PubMed

Güran, Tülay; Yeşil, Gözde; Güran, Ömer; Cesur, Suna; Bosnalı, Oktav; Celayir, Ayşenur; Topçuoğlu, Sevilay; Bereket, Abdullah

2012-09-01

Congenital adrenal hyperplasia (CAH) is a group of disorders affecting the adrenal steroid synthesis. The most common form, 21-hydroxylase deficiency (21-OHD), leads to decreased production of cortisol and aldosterone with increased androgen secretion. In classic CAH, glucocorticoid treatment can be life-saving and serves to bring the symptoms under control. However, the treatment challenge is to effectively control the excess androgen effect by using the lowest possible glucocorticoid dose. Previous studies suggested a relationship between ovarian cyst formation and adrenal androgen excess, but neonatal large ovarian cysts have been very rarely reported in newborns with CAH. Here, we present the unique case of a neonate with classical 21-OHD who underwent surgery for a giant (10x8x7 cm) unilateral solitary ovarian follicular cyst on the 2nd postnatal day. Hormonal evaluation of the patient revealed high-dose hook effect for serum testosterone levels for the first time by a two-site immunoradiometric assay. Possible mechanisms by which androgen excess may cause ovarian cyst formation are discussed.

Spinal hemianesthesia: Unilateral and posterior

PubMed Central

Imbelloni, Luiz Eduardo

2014-01-01

The injection of a non-isobaric local anesthetic should induce a unilateral spinal anesthesia in patients in a lateral decubitus position. The posterior spinal hemianesthesia only be obtained with hypobaric solutions injected in the jackknife position. The most important factors to be considered when performing a spinal hemianesthesia are: type and gauge of the needle, density of the local anesthetic relative to the CSF, position of the patient, speed of administration of the solution, time of stay in position, and dose/concentration/volume of the anesthetic solution. The distance between the spinal roots on the right-left sides and anterior-posterior is, approximately, 10-15 mm. This distance allows performing unilateral spinal anesthesia or posterior spinal anesthesia. The great advantage of obtaining spinal hemianesthesia is the reduction of cardiovascular changes. Likewise, both the dorsal and unilateral sensory block predominates in relation to the motor block. Because of the numerous advantages of producing spinal hemianesthesia, anesthesiologists should apply this technique more often. This review considers the factors which are relevant, plausible and proven to obtain spinal hemianesthesia. PMID:25886320

Different effects of high- and low-dose phenobarbital on post-stroke seizure suppression and recovery in immature CD1 mice

PubMed Central

Markowitz, Geoffrey J.; Kadam, Shilpa D.; Smith, Dani R.; Johnston, Michael V.; Comi, Anne M.

2011-01-01

Neonatal stroke presents with seizures that are usually treated with phenobarbital. We hypothesized that anticonvulsants would attenuate ischemic injury, but that the dose-dependent effects of standard anticonvulsants would impact important age-dependent and injury-dependent consequences. In this study, ischemia induced by unilateral carotid ligation in postnatal day 12 (P12) CD1 mice was immediately followed by an i.p. dose of vehicle, low-dose or high-dose phenobarbital. Severity of acute behavioral seizures was scored. 5-bromo-2’-deoxyuridine (BrdU) was administered from P18-P20, behavioral testing performed, and mice perfused at P40. Atrophy quantification and counts of BrdU/NeuN-labeled cells in the dentate gyrus were performed. Blood phenobarbital concentrations were measured. 30 mg/kg phenobarbital reduced acute seizures and chronic brain injury, and restored normal weight gain and exploratory behavior. By comparison, 60 mg/kg was a less efficacious anticonvulsant, was not neuroprotective, did not restore normal weight gain, and impaired behavioral and cognitive recovery. Hippocampal neurogenesis was not different between treatment groups. These results suggest a protective effect of lower-dose phenobarbital, but a lack of this effect at higher concentrations after stroke in P12 mice. PMID:21481568

Nicergoline facilitates vestibular compensation in aged male rats with unilateral labyrinthectomy.

PubMed

Rampello, L; Drago, F

1999-05-28

The ergoline derivatives, nicergoline (NIC) or dihydroergocristine (DHE) were administered at various doses (0.1, 0.5 and 1 mg/kg) to aged male rats subjected to labyrinth unilateral lesion (LBX). The nystagmus rate appeared to be lower in animals treated with DHE or NIC 1mg/kg than in saline-injected rats, when observed on day 1 and 2 after operation. The number of falls in the rotorod test of LBX animals was decreased by NIC 0.5 or 1 mg/kg at all observation times. This parameter was affected by DHE only at the higher dose. These results suggest that NIC facilitates vestibular compensation of LBX rats. DHE appeared to be less potent in this respect. Since both drugs act on central dopaminergic neurotransmission, it is possible that this neurotransmission may be involved in their mechanism of action.

Single high-dose irradiation aggravates eosinophil-mediated fibrosis through IL-33 secreted from impaired vessels in the skin compared to fractionated irradiation

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

Lee, Eun-Jung, E-mail: forejs2@yuhs.ac; Kim, Jun Won, E-mail: JUNWON@yuhs.ac; Yoo, Hyun, E-mail: gochunghee@yuhs.ac

We have revealed in a porcine skin injury model that eosinophil recruitment was dose-dependently enhanced by a single high-dose irradiation. In this study, we investigated the underlying mechanism of eosinophil-associated skin fibrosis and the effect of high-dose-per-fraction radiation. The dorsal skin of a mini-pig was divided into two sections containing 4-cm{sup 2} fields that were irradiated with 30 Gy in a single fraction or 5 fractions and biopsied regularly over 14 weeks. Eosinophil-related Th2 cytokines such as interleukin (IL)-4, IL-5, and C–C motif chemokine-11 (CCL11/eotaxin) were evaluated by quantitative real-time PCR. RNA-sequencing using 30 Gy-irradiated mouse skin and functional assays in amore » co-culture system of THP-1 and irradiated-human umbilical vein endothelial cells (HUVECs) were performed to investigate the mechanism of eosinophil-mediated radiation fibrosis. Single high-dose-per-fraction irradiation caused pronounced eosinophil accumulation, increased profibrotic factors collagen and transforming growth factor-β, enhanced production of eosinophil-related cytokines including IL-4, IL-5, CCL11, IL-13, and IL-33, and reduced vessels compared with 5-fraction irradiation. IL-33 notably increased in pig and mouse skin vessels after single high-dose irradiation of 30 Gy, as well as in irradiated HUVECs following 12 Gy. Blocking IL-33 suppressed the migration ability of THP-1 cells and cytokine secretion in a co-culture system of THP-1 cells and irradiated HUVECs. Hence, high-dose-per-fraction irradiation appears to enhance eosinophil-mediated fibrotic responses, and IL-33 may be a key molecule operating in eosinophil-mediated fibrosis in high-dose-per fraction irradiated skin. - Highlights: • Single high-dose irradiation aggravates eosinophil-mediated fibrosis through IL-33. • Vascular endothelial cells damaged by high-dose radiation secrete IL-33. • Blocking IL-33 suppressed migration of inflammatory cells and cytokine secretion. • IL-33 is a key in eosinophil-mediated fibrosis in high-dose-per-fraction radiation.« less

Study design for the fostering eating after stroke with transcranial direct current stimulation trial: a randomized controlled intervention for improving Dysphagia after acute ischemic stroke.

PubMed

Marchina, Sarah; Schlaug, Gottfried; Kumar, Sandeep

2015-03-01

Dysphagia is a major stroke complication but lacks effective therapy that can promote recovery. Noninvasive brain stimulation with and without peripheral sensorimotor activities may be an attractive treatment option for swallowing recovery but has not been systematically investigated in the stroke population. This article describes the study design of the first prospective, single-center, double-blinded trial of anodal versus sham transcranial direct current stimulation (tDCS) used in combination with swallowing exercises in patients with dysphagia from an acute ischemic stroke. The aim of this study is to gather safety data on cumulative sessions of tDCS in acute-subacute phases of stroke, obtain information about effects of this intervention on important physiologic and clinically relevant swallowing parameters, and examine possible dose effects. Ninety-nine consecutive patients with dysphagia from an acute unilateral hemispheric infarction with a Penetration and Aspiration Scale (PAS) score of 4 or more and without other confounding reasons for dysphagia will be enrolled at a single tertiary care center. Subjects will be randomized to either a high or low dose tDCS or a sham group and will undergo 10 sessions over 5 consecutive days concomitantly with effortful swallowing maneuvers. The main efficacy measures are a change in the PAS score before and after treatment; the main safety measures are mortality, seizures, neurologic, motor, and swallowing deterioration. The knowledge gained from this study will help plan a larger confirmatory trial for treating stroke-related dysphagia and advance our understanding of important covariates influencing swallowing recovery and response to the proposed intervention. Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.

A comparison of low dose hyperbaric levobupivacaine and hypobaric levobupivacaine in unilateral spinal anaesthesia.

PubMed

Kaya, M; Oztürk, I; Tuncel, G; Senel, G Ozalp; Eskiçirak, H; Kadioğullari, N

2010-11-01

The aim of this study was to compare the clinical effects and characteristics of hyperbaric and hypobaric levobupivacaine for unilateral spinal anaesthesia. Sixty patients were randomly allocated into two groups to receive either 7.5 mg (1.5 ml) hyperbaric levobupivacaine 0.5% or 7.5 mg (4 ml) hypobaric levobupivacaine 0.1875% for elective arthroscopic surgery of the knee under spinal anaesthesia. The level and duration of sensory block, intensity and duration of motor block were recorded. Unilateral sensory block was observed in 27 patients (90%) in the hyperbaric group and 24 patients (80%) in the hypobaric group in the lateral position. After 15 minutes, patients were turned to supine to redistribute the spinal block toward the non-operative side, but spinal anaesthesia was still unilateral in 18 patients (60%) in the hyperbaric group and 10 patients (33%) in the hypobaric group (P = 0.038). Time to readiness for home discharge and complete recovery of sensory block were similar in both groups. In the hyperbaric group, the motor block scores were higher on the operative side during first 10 minutes than they were in the hypobaric group (P < 0.002). Motor block regression was faster in the hyperbaric group (P = 0.01). Hyperbaric and hypobaric levobupivacaine both provided satisfactory unilateral spinal anaesthesia with good haemodynamic stability for arthroscopic surgery, but with more frequent unilateral spinal anaesthesia in the hyperbaric group.

Dental anomalies associated with unilateral and bilateral cleft lip and palate.

PubMed

Qureshi, Wafa A; Beiraghi, Soraya; Leon-Salazar, Vladimir

2012-01-01

The purpose of this study was to compare the prevalence of dental anomalies in the primary and permanent dentition of patients with unilateral (UCLP) and bilateral (BCLP) cleft lip with or without palate. One hundred two complete clinical records were randomly selected for review from a university-based cleft palate clinic. Only nonsyndromic UCLP and BCLP cases were further selected for analysis of dental anomalies. The prevalence of 9 dental categories, including anomalies in number, crown structure, position, and maxillary-mandibular relationship, was assessed and compared between UCLP and BCLP cases using Fisher's exact test. Of the 102 charts evaluated, there were 67 cases of UCLP and 29 cases of BCLP for a total of 96 cases. There was a high prevalence of dental anomalies in primary and permanent teeth; 93% of UCLP cases and 96% of BCLP cases presented with at least 1 dental anomaly. Significant differences ( P <.05) were only found in the prevalence of anodontia of a single tooth (UCLP=39%, BCLP=14%), multiple anodontia (UCLP=22%, BCLP=54%), and anterior malocclusion (UCLP=15%, BCLP=41%). There is a high prevalence of dental anomalies associated with orofacial clefts regardless of whether they are unilateral or bilateral cleft lip with or without palate.

An unusual case of episodic SUNCT responding to high doses of topiramate.

PubMed

Khalil, Modar; Maniyar, Farooq; Ahmed, Fayyaz

2014-01-01

Trigeminal autonomic cephalalgias (TAC) are rare. Cluster headaches comprise the majority, with short-lasting unilateral neuralgiform headache with conjunctival injection and tearing (SUNCT) being the rarest and shortest in duration. The majority of SUNCT are primary with a few cases occurring secondary to posterior fossa or pituitary lesions. Although activities like exercise or blowing of the nose can trigger SUNCT, onset during orgasm has not been described. Short-lasting aura has been described in TACs including SUNCT, but persistence of focal symptoms and signs without an underlying structural lesion have not been described. Lastly, treatment of SUNCT is difficult, with lamotrigine being the most common effective reported. We report a case of episodic SUNCT with symptoms suggestive of brainstem stroke that completely resolved spontaneously for which no underlying structural cause was found. The onset of first attack occurred during orgasm, and the patient responded to a high dose of topiramate. © 2014 American Headache Society.

CAVITATION SOUNDS DURING CERVICOTHORACIC SPINAL MANIPULATION.

PubMed

Dunning, James; Mourad, Firas; Zingoni, Andrea; Iorio, Raffaele; Perreault, Thomas; Zacharko, Noah; de Las Peñas, César Fernández; Butts, Raymond; Cleland, Joshua A

2017-08-01

No study has previously investigated the side, duration or number of audible cavitation sounds during high-velocity low-amplitude (HVLA) thrust manipulation to the cervicothoracic spine. The primary purpose was to determine which side of the spine cavitates during cervicothoracic junction (CTJ) HVLA thrust manipulation. Secondary aims were to calculate the average number of cavitations, the duration of cervicothoracic thrust manipulation, and the duration of a single cavitation. Quasi-experimental study. Thirty-two patients with upper trapezius myalgia received two cervicothoracic HVLA thrust manipulations targeting the right and left T1-2 articulation, respectively. Two high sampling rate accelerometers were secured bilaterally 25 mm lateral to midline of the T1-2 interspace. For each manipulation, two audio signals were extracted using Short-Time Fourier Transformation (STFT) and singularly processed via spectrogram calculation in order to evaluate the frequency content and number of instantaneous energy bursts of both signals over time for each side of the CTJ. Unilateral cavitation sounds were detected in 53 (91.4%) of 58 cervicothoracic HVLA thrust manipulations and bilateral cavitation sounds were detected in just five (8.6%) of the 58 thrust manipulations; that is, cavitation was significantly (p<0.001) more likely to occur unilaterally than bilaterally. In addition, cavitation was significantly (p<0.0001) more likely to occur on the side contralateral to the clinician's short-lever applicator. The mean number of audible cavitations per manipulation was 4.35 (95% CI 2.88, 5.76). The mean duration of a single manipulation was 60.77 ms (95% CI 28.25, 97.42) and the mean duration of a single audible cavitation was 4.13 ms (95% CI 0.82, 7.46). In addition to single-peak and multi-peak energy bursts, spectrogram analysis also demonstrated high frequency sounds, low frequency sounds, and sounds of multiple frequencies for all 58 manipulations. Cavitation was significantly more likely to occur unilaterally, and on the side contralateral to the short-lever applicator contact, during cervicothoracic HVLA thrust manipulation. Clinicians should expect multiple cavitation sounds when performing HVLA thrust manipulation to the CTJ. Due to the presence of multi-peak energy bursts and sounds of multiple frequencies, the cavitation hypothesis (i.e. intra-articular gas bubble collapse) alone appears unable to explain all of the audible sounds during HVLA thrust manipulation, and the possibility remains that several phenomena may be occurring simultaneously. 2b.

Intratympanic treatment of intractable unilateral Meniere disease: gentamicin or dexamethasone? A randomized controlled trial.

PubMed

Casani, Augusto Pietro; Piaggi, Paolo; Cerchiai, Niccolò; Seccia, Veronica; Franceschini, Stefano Sellari; Dallan, Iacopo

2012-03-01

To determine the efficacy and safety of low-dose intratympanic gentamicin (ITG) compared with intratympanic dexamethasone (ITD) in patients with intractable unilateral Ménière disease (MD). Open prospective randomized controlled study. Tertiary referral center. Sixty patients affected by definite unilateral MD were enrolled between January 1, 2007, and June 30, 2008. Thirty-two patients were treated with a buffered gentamicin solution injected in the middle ear (maximum of 2 injections); 28 patients were treated with ITD (4 mg/mL, 3 injections at intervals of 1 every 3 days). Mean outcome measurements consisted of control of vertigo attacks, pure tone average (PTA), speech discrimination score, functional disability score, and statistical analysis using repeated measures analysis of variance. In the ITG group at 2-year follow-up, complete control of vertigo (class A) was achieved in 26 patients (81%) and substantial control of vertigo (class B) in 4 patients (12.5%). In the ITD group, class A was achieved in 12 (43%), and class B in 5 (18%) patients. In the gentamicin group, 4 patients showed a reduction in PTA of ≥10 dB. In the ITD group, PTA was unchanged or slightly improved in 16 patients (belonging to class A-B) and worse in 12. Low-dose ITG achieved better outcome than ITD in the control of vertigo attacks in patients suffering from unilateral MD, with a very low incidence of hearing deterioration. ITD offers poorer vertigo control rate, and hearing preservation is achieved only in cases with no vertigo recurrences.

Effects of disease severity and medication state on postural control asymmetry during challenging postural tasks in individuals with Parkinson's disease.

PubMed

Barbieri, Fabio A; Polastri, Paula F; Baptista, André M; Lirani-Silva, Ellen; Simieli, Lucas; Orcioli-Silva, Diego; Beretta, Victor S; Gobbi, Lilian T B

2016-04-01

The aim of this study was to investigate the effects of disease severity and medication state on postural control asymmetry during challenging tasks in individuals with Parkinson's disease (PD). Nineteen people with PD and 11 neurologically healthy individuals performed three standing task conditions: bipedal standing, tandem and unipedal adapted standing; the individuals with PD performed the tasks in ON and OFF medication state. The participants with PD were distributed into 2 groups according to disease severity: unilateral group (n=8) and bilateral group (n=11). The two PD groups performed the evaluations both under and without the medication. Two force plates were used to analyze the posture. The symmetric index was calculated for various of center of pressure. ANOVA one-way (groups) and two-way (PD groups×medication), with repeated measures for medication, were calculated. For main effects of group, the bilateral group was more asymmetric than CG. For main effects of medication, only unipedal adapted standing presented effects of PD medication. There was PD groups×medication interaction. Under the effects of medication, the unilateral group presented lower asymmetry of RMS in anterior-posterior direction and area than the bilateral group in unipedal adapted standing. In addition, the unilateral group presented lower asymmetry of mean velocity, RMS in anterior-posterior direction and area in unipedal standing and area in tandem adapted standing after a medication dose. Postural control asymmetry during challenging postural tasks was dependent on disease severity and medication state in people with PD. The bilateral group presented higher postural control asymmetry than the control and unilateral groups in challenging postural tasks. Finally, the medication dose was able to reduce postural control asymmetry in the unilateral group during challenging postural tasks. Copyright © 2015 Elsevier B.V. All rights reserved.

Association of surgical approach with complication rate, progression-free survival time, and disease-specific survival time in cats with mammary adenocarcinoma: 107 cases (1991-2014).

PubMed

Gemignani, Francesco; Mayhew, Philipp D; Giuffrida, Michelle A; Palaigos, Jason; Runge, Jeffrey J; Holt, David E; Robertson, Nicholas A; Seguin, Bernard; Walker, Meaghan; Singh, Ameet; Liptak, Julius M; Romanelli, Giorgio; Martano, Marina; Boston, Sarah E; Lux, Cassie; Busetto, Roberto; Culp, William T N; Skorupski, Katherine A; Burton, Jenna H

2018-06-01

OBJECTIVE To evaluate potential associations between surgical approach and complication rate, progression-free survival time, and disease-specific survival time in cats with mammary adenocarcinoma. DESIGN Retrospective case series. ANIMALS 107 client-owned cats. PROCEDURES Medical records of cats that underwent surgical excision of mammary adenocarcinoma by means of a unilateral or bilateral (staged or single-session) mastectomy at 9 hospitals between 1991 and 2014 were reviewed. Relevant clinicopathologic data and details of surgical and adjuvant treatments were recorded. Outcome data were obtained, including postoperative complications, progression-free survival time, and disease-specific survival time. RESULTS Complications occurred in 12 of 61 (19.7%) cats treated with unilateral mastectomy, 5 of 14 (35.7%) cats treated with staged bilateral mastectomy, and 13 of 32 (40.6%) cats treated with single-session bilateral mastectomy. Complications were significantly more likely to occur in cats undergoing bilateral versus unilateral mastectomy. Median progression-free survival time was longer for cats treated with bilateral mastectomy (542 days) than for cats treated with unilateral mastectomy (289 days). Significant risk factors for disease progression included unilateral mastectomy, tumor ulceration, lymph node metastasis, and tumors arising in the fourth mammary gland. Significant risk factors for disease-specific death included lymph node metastasis and development of regional or distant metastasis. Among cats that did not develop metastasis, unilateral mastectomy was a significant risk factor for disease-specific death. Treatment with chemotherapy was associated with a significantly decreased risk of disease-specific death. CONCLUSIONS AND CLINICAL RELEVANCE Results supported bilateral mastectomy for the treatment of mammary adenocarcinoma in cats to improve progression-free and disease-specific survival time. Performing bilateral mastectomy in a staged fashion may help to decrease the complication rate.

Ultrasonographic findings in dual kidney transplantation.

PubMed

Impedovo, Stefano Vittorio; Martino, Pasquale; Palazzo, Silvano; Ditonno, Pasquale; Tedeschi, Michele; Palumbo, Fabrizio; Tafa, Ardit; Matera, Matteo; Selvaggi, Francesco Paolo; Battaglia, Michele

2012-12-01

Organ shortage has led to using grafts from expanded criteria donors (ECD). Double kidney transplantation is an accepted strategy to increase the donor pool, using organs from an ECD which are not acceptable for single kidney transplantation (SKT). Aim of this retrospective study was to analyse the role of colour Doppler ultrasound (CDUS) in the diagnosis of major surgical complications in DKT, performed with unilateral or bilateral placement. From 2000 to 2011 we performed 54 DKT. Unilateral placement of both kidneys was done in 26 patients and bilateral DKT in 28, through two separate Gibson incisions (18) or one midline incision (10). Each patient underwent at least 3 CDUS before hospital discharge. The main surgical complications, discovered initially thanks to ultrasound (US), were hydronephrosis from ureteral obstruction, lymphocele and deep venous thrombosis (DVT). Mean follow-up was 42.7 months. Good postoperative renalfunction was demonstrated in 25 patients (46.3%), while delayed graft function occurred in 29 (53.7%). US showed ureteral obstruction requiring surgery in 5 unilateral DKT while no patient subjected to bilateral DKT developed severe hydronephrosis. Lymphoocele, surgically drained, was demonstrated in 6 bilateral DKT with a midline incision, 2 bilateral DKT with two separate incisions and 3 unilateral DKT. CDUS also enabled diagnosis of 2 cases of DVT in ipsilateral DKTs. CDUS provides useful information in patients with DKT, allowing the detection of clinically unsuspected unilateral diseases. US study of our patients demonstrated that unilateral DKTs are more susceptible to the development of DVT and ureteral stricture, while the incidence of voluminous lymphocele is more frequent in bilateral DKT through a single midline incision. In this scenario, all patients undergoing DKT should be carefully monitored by US after surgery.

The bilateral movement condition facilitates maximal but not submaximal paretic-limb grip force in people with post-stroke hemiparesis

PubMed Central

DeJong, Stacey L.; Lang, Catherine E.

2012-01-01

Objectives Although healthy individuals have less force production capacity during bilateral muscle contractions compared to unilateral efforts, emerging evidence suggests that certain aspects of paretic upper limb task performance after stroke may be enhanced by moving bilaterally instead of unilaterally. We investigated whether the bilateral movement condition affects grip force differently on the paretic side of people with post-stroke hemiparesis, compared to their non-paretic side and both sides of healthy young adults. Methods Within a single session, we compared: 1) maximal grip force during unilateral vs. bilateral contractions on each side, and 2) force contributed by each side during a 30% submaximal bilateral contraction. Results Healthy controls produced less grip force in the bilateral condition, regardless of side (- 2.4% difference), and similar findings were observed on the non-paretic side of people with hemiparesis (- 4.5% difference). On the paretic side, however, maximal grip force was increased by the bilateral condition in most participants (+11.3% difference, on average). During submaximal bilateral contractions in each group, the two sides each contributed the same percentage of unilateral maximal force. Conclusions The bilateral condition facilitates paretic limb grip force at maximal, but not submaximal levels. Significance In some people with post-stroke hemiparesis, the paretic limb may benefit from bilateral training with high force requirements. PMID:22248812

Changes in regional blood flow induced by unilateral subthalamic nucleus stimulation in patients with Parkinson's disease.

PubMed

Tanei, Takafumi; Kajita, Yasukazu; Nihashi, Takashi; Kaneoke, Yoshiki; Takebayashi, Shigenori; Nakatsubo, Daisuke; Wakabayashi, Toshihiko

2009-11-01

Changes in regional cerebral blood flow (rCBF) induced by unilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN) were investigated in 7 consecutive patients with Parkinson's disease, 4 men and 3 women (mean age 62.3 +/- 8.1 years), who underwent rCBF measurement by N-isopropyl-p-(iodine-123)-iodoamphetamine single photon emission computed tomography at rest before and after unilateral STN DBS preoperatively in the on-drug condition, and postoperatively in the on-drug and on-stimulation condition. Statistical parametric mapping was used to identify significant changes in rCBF from the preoperative to the postoperative conditions. rCBF was increased in the bilateral cingulate cortices and bilateral cerebellar hemispheres. rCBF was decreased in the bilateral medial frontal cortices and left superior temporal cortex. Unilateral STN DBS produced rCBF changes in the bilateral cingulate cortices, cerebellar hemispheres, and medial frontal cortices. These findings indicate that unilateral STN DBS affects rCBF in both hemispheres.

Unilateral retinitis pigmentosa and cone-rod dystrophy

PubMed Central

Farrell, Donald F

2009-01-01

Purpose: The purpose of this paper is to report 14 new cases of unilateral retinitis pigmentosa and three new cases of cone-rod dystrophy and to compare the similarities and dissimilarities to those found in the bilateral forms of these disorders. Methods: A total of 272 cases of retinitis pigmentosa and 167 cases of cone-rod dystrophy were studied by corneal full field electroretinograms and electrooculograms. The student t-test was used to compare categories. Results: The percentage of familial and nonfamilial cases was the same for the bilateral and unilateral forms of the disease. In our series, unilateral retinitis pigmentosa makes up approximately 5% of the total population of retinitis pigmentosa, while unilateral cone-rod dystrophy makes up only about 2% of the total. In the familial forms of unilateral retinitis pigmentosa the most common inheritance pattern was autosomal dominant and all affected relatives had bilateral disease. Conclusion: Unilateral retinitis pigmentosa and cone-rod dystrophy appear to be directly related to the more common bilateral forms of these disorders. The genetic mechanisms which account for asymmetric disorders are not currently understood. It may be a different unidentified mutation at a single loci or it is possible that nonlinked mutations in multiple loci account for this unusual disorder. PMID:19668577

Safety and Efficacy of Single Incision Laparoscopic Surgery for Total Extraperitoneal Inguinal Hernia Repair

PubMed Central

2011-01-01

Almost 20 years after the first laparoscopic inguinal hernia repair was performed, single incision laparoscopic surgery (SILS™) is set to revolutionize minimally invasive surgery. However, the loss of triangulation must be overcome before the technique can be popularized. This study reports the first 100 laparoscopic total extraperitoneal hernia repairs using a single incision. The study cohort comprised 68 patients with a mean age of 44 (range, 18 to 83): 36 unilateral and 32 bilateral hernias. Twelve patients also underwent umbilical hernia repair with the Ventralex patch requiring no additional incisions. A 2.5-cm to 3-cm crescentic incision within the confines of the umbilicus was performed. Standard dissecting instruments and 52-cm/5.5-mm/300 laparoscope were used. Operation times were 50 minutes for unilateral and 80 minutes for bilateral. There was one conversion to conventional 3-port laparoscopic repair and none to open surgery. Outpatient surgery was achieved in all (except one). Analgesic requirements were minimal: 8 Dextropropoxyphene tablets (range, 0 to 20). There were no intraoperative or postoperative complications with a high patient satisfaction score. Single-incision laparoscopic hernia repair is safe and efficient simply by modifying dissection techniques (so-called “inline” and “vertical”). Comparable success can be obtained while negating the risks of bowel and vascular injuries from sharp trocars and achieving improved cosmetic results. PMID:21902942

A Comparative Study to Evaluate the Functional Effect of Unilateral Uvuloplasty after Primary Palatoplasty

PubMed Central

Olivencia-Flores, Claudia; Gavino-Gutierrez, Arquímedes M.; Caceres-Nano, Evelyn; Cotrina-Rabanal, Omar

2015-01-01

Background: The conventional method for uvular repair suturing the 2 hemi-uvulas of the palatal cleft together in the midline does not allow us to obtain a proper anatomical repair. In our hands, the midline straight closure frequently causes retraction of the uvular tissues with the consequent abnormal appearance of the uvula. We described before a method for uvular repair in patients with cleft palate. The technique consists in preserving one of the hemi-uvulas, which is moved to the midline to form the definitive uvula. The purpose of this study was to evaluate the functional effects of the unilateral uvuloplasty for uvular repair in a group of patients with bilateral cleft palate. Methods: This is a retrospective, single-blinded cohort study between 2 groups of 90 patients with bilateral cleft palate who were operated on using the conventional and unilateral uvuloplasty methods of uvular repair from 2000 to 2009. Data collection was accomplished by physical examination to evaluate the presence of postoperative fistulas and hypernasal speech determined at 6 months to 5 years after surgery. In addition, postoperative dimensions of the velopharynx were measured by a single-blind examiner using a computed tomography scan. Results: Our comparative study found statistically significant differences between the 2 groups in favor of the unilateral uvuloplasty group. Conclusions: We observed that the use of unilateral uvuloplasty for uvular reconstruction reduces the velopharyngeal space and the frequency of hypernasality in patients with bilateral cleft palate. PMID:26180716

Right Unilateral Ultrabrief Pulse ECT in Geriatric Depression: Phase 1 of the PRIDE Study.

PubMed

Kellner, Charles H; Husain, Mustafa M; Knapp, Rebecca G; McCall, W Vaughn; Petrides, Georgios; Rudorfer, Matthew V; Young, Robert C; Sampson, Shirlene; McClintock, Shawn M; Mueller, Martina; Prudic, Joan; Greenberg, Robert M; Weiner, Richard D; Bailine, Samuel H; Rosenquist, Peter B; Raza, Ahmad; Kaliora, Styliani; Latoussakis, Vassilios; Tobias, Kristen G; Briggs, Mimi C; Liebman, Lauren S; Geduldig, Emma T; Teklehaimanot, Abeba A; Lisanby, Sarah H

2016-11-01

The Prolonging Remission in Depressed Elderly (PRIDE) study evaluated the efficacy of right unilateral ultrabrief pulse electroconvulsive therapy (ECT) combined with venlafaxine for the treatment of geriatric depression. PRIDE was a two-phase multisite study. Phase 1 was an acute course of right unilateral ultrabrief pulse ECT, combined with open-label venlafaxine at seven academic medical centers. In phase 2 (reported separately), patients who had remitted were randomly assigned to receive pharmacotherapy (venlafaxine plus lithium) or pharmacotherapy plus continuation ECT. In phase 1, depressed patients received high-dose ECT (at six times the seizure threshold) three times per week. Venlafaxine was started during the first week of treatment and continued throughout the study. The primary outcome measure was remission, assessed with the 24-item Hamilton Depression Rating Scale (HAM-D), which was administered three times per week. Secondary outcome measures were post-ECT reorientation and safety. Paired t tests were used to estimate and evaluate the significance of change from baseline in HAM-D scores. Of 240 patients who entered phase 1 of the study, 172 completed it. Overall, 61.7% (148/240) of all patients met remission criteria, 10.0% (24/240) did not remit, and 28.3% (68/240) dropped out; 70% (169/240) met response criteria. Among those who remitted, the mean decrease in HAM-D score was 24.7 points (95% CI=23.4, 25.9), with a mean final score of 6.2 (SD=2.5) and an average change from baseline of 79%. The mean number of ECT treatments to remission was 7.3 (SD=3.1). Right unilateral ultrabrief pulse ECT, combined with venlafaxine, is a rapidly acting and highly effective treatment option for depressed geriatric patients, with excellent safety and tolerability. These data add to the evidence base supporting the efficacy of ECT to treat severe depression in elderly patients.

Biology of high single doses of IORT: RBE, 5 R's, and other biological aspects.

PubMed

Herskind, Carsten; Ma, Lin; Liu, Qi; Zhang, Bo; Schneider, Frank; Veldwijk, Marlon R; Wenz, Frederik

2017-01-19

Intraoperative radiotherapy differs from conventional, fractionated radiotherapy in several aspects that may influence its biological effect. The radiation quality influences the relative biologic effectiveness (RBE), and the role of the five R's of radiotherapy (reassortment, repair, reoxygenation, repopulation, radiosensitivity) is different. Furthermore, putative special biological effects and the small volume receiving a high single dose may be important. The present review focuses on RBE, repair, and repopulation, and gives an overview of the other factors that potentially contribute to the efficacy. The increased RBE should be taken into account for low-energy X-rays while evidence of RBE < 1 for high-energy electrons at higher doses is presented. Various evidence supports a hypothesis that saturation of the primary DNA double-strand break (DSB) repair mechanisms leads to increasing use of an error-prone backup repair system leading to genomic instability that may contribute to inactivate tumour cells at high single doses. Furthermore, the elimination of repopulation of residual tumour cells in the tumour bed implies that some patients are likely to have very few residual tumour cells which may be cured even by low doses to the tumour bed. The highly localised dose distribution of IORT has the potential to inactivate tumour cells while sparing normal tissue by minimising the volume exposed to high doses. Whether special effects of high single doses also contribute to the efficacy will require further experimental and clinical studies.

Effects of Home-Based Constraint-Induced Therapy versus Dose-Matched Control Intervention on Functional Outcomes and Caregiver Well-Being in Children with Cerebral Palsy

ERIC Educational Resources Information Center

Lin, Keh-chung; Wang, Tien-ni; Wu, Ching-yi; Chen, Chia-ling; Chang, Kai-chieh; Lin, Yu-chan; Chen, Yi-ju

2011-01-01

This study compared home-based constraint-induced therapy (CIT) with a dose-matched home-based control intervention for children with cerebral palsy (CP). The differences in unilateral and bilateral motor performance, daily functions, and quality of parental well-being (i.e., the stress level of their parents) were evaluated. The study included 21…

Treatment of traumatic infra orbital nerve paresthesia

PubMed Central

Lone, Parveen Akhter; Singh, R. K.; Pal, U. S.

2012-01-01

This study was done to find out the role of topiramate therapy in infraorbital nerve paresthesia after miniplate fixation in zygomatic complxex fractures. A total 2 cases of unilateral zygomatic complex fracture, 2-3 weeks old with infra orbital nerve paresthesia were slected. Open reduction and plating was done in frontozygomaticregion. Antiepileptic drug tab topiramate was given in therapeutic doses and dose was increased slowly until functional recovery was noticed. PMID:23833503

Management of Unilateral Masseter Hypertrophy and Hypertrophic Scar—A Case Report

PubMed Central

Shetty, Naresh; Malaviya, Rajanikanth K.; Gupta, M. K.

2012-01-01

Masseter muscle hypertrophy is a rare condition of idiopathic cause. It clinically presents as an enlargement of one or both masseter muscles. Most patients complain of facial asymmetry; however, symptoms such as trismus, protrusion, and bruxism may also occur. Several treatment options reported for masseter hypertrophy are present, which range from simple pharmacotherapy to more invasive surgical reduction. Keloid scar with unilateral masseter hypertrophy is a rarely seen in clinical practice. This paper reports a case of unilateral masseter hypertrophy with keloid scar in the angle of the mandible for which surgical treatment was rendered to the patient by using a single approach. PMID:22844620

A comparison of the brainstem auditory evoked response in healthy ears of unilaterally deaf dogs and bilaterally hearing dogs.

PubMed

Plonek, M; Nicpoń, J; Kubiak, K; Wrzosek, M

2017-03-01

Auditory plasticity in response to unilateral deafness has been reported in various animal species. Subcortical changes occurring in unilaterally deaf young dogs using the brainstem auditory evoked response have not been evaluated yet. The aim of this study was to assess the brainstem auditory evoked response findings in dogs with unilateral hearing loss, and compare them with recordings obtained from healthy dogs. Brainstem auditory evoked responses (amplitudes and latencies of waves I, II, III, V, the V/I wave amplitude ratio, wave I-V, I-III and III-V interpeak intervals) were studied retrospectively in forty-six privately owned dogs, which were either unilaterally deaf or had bilateral hearing. The data obtained from the hearing ears in unilaterally deaf dogs were compared to values obtained from their healthy littermates. Statistically significant differences in the amplitude of wave III and the V/I wave amplitude ratio at 75 dB nHL were found between the group of unilaterally deaf puppies and the control group. The recordings of dogs with single-sided deafness were compared, and the results showed no statistically significant differences in the latencies and amplitudes of the waves between left- (AL) and right-sided (AR) deafness. The recordings of the brainstem auditory evoked response in canines with unilateral inborn deafness in this study varied compared to recordings from healthy dogs. Future studies looking into electrophysiological assessment of hearing in conjunction with imaging modalities to determine subcortical auditory plasticity and auditory lateralization in unilaterally deaf dogs are warranted.

Examining the Feasibility, Tolerability, and Preliminary Efficacy of Repetitive Task-Specific Practice for People With Unilateral Spatial Neglect

PubMed Central

Lang, Catherine E.; Birkenmeier, Rebecca; Holm, Margo; Rubinstein, Elaine; Van Swearingen, Jessie; Skidmore, Elizabeth R.

2016-01-01

OBJECTIVE. We examined the feasibility, tolerability, and preliminary efficacy of repetitive task-specific practice for people with unilateral spatial neglect (USN). METHOD. People with USN ≥6 mo poststroke participated in a single-group, repeated-measures study. Attendance, total repetitions, and satisfaction indicated feasibility and pain indicated tolerability. Paired t tests and effect sizes were used to estimate changes in upper-extremity use (Motor Activity Log), function (Action Research Arm Test), and attention (Catherine Bergego Scale). RESULTS. Twenty participants attended 99.4% of sessions and completed a high number of repetitions. Participants reported high satisfaction and low pain, and they demonstrated small, significant improvements in upper-extremity use (before Bonferroni corrections; t = –2.1, p = .04, d = .30), function (t = –3.0, p < .01, d = .20), and attention (t = –3.4, p < .01, d = –.44). CONCLUSION. Repetitive task-specific practice is feasible and tolerable for people with USN. Improvements in upper-extremity use, function, and attention may be attainable. PMID:27294994

Dose Control System in the Optima XE Single Wafer High Energy Ion Implanter

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

Satoh, Shu; Yoon, Jongyoon; David, Jonathan

2011-01-07

Photoresist outgassing can significantly compromise accurate dosimetry of high energy implants. High energy implant even at a modest beam current produces high beam powers which create significantly worse outgassing than low and medium energy implants and the outgassing continues throughout the implant due to the low dose in typical high energy implant recipes. In the previous generation of high energy implanters, dose correction by monitoring of process chamber pressure during photoresist outgassing has been used. However, as applications diversify and requirements change, the need arises for a more versatile photoresist correction system to match the versatility of a single wafermore » high energy ion implanter. We have successfully developed a new dosimetry system for the Optima XE single wafer high energy ion implanter which does not require any form of compensation due to the implant conditions. This paper describes the principles and performance of this new dose system.« less

Effects of listening to pleasant music on chronic unilateral neglect: a single-subject study.

PubMed

Tsai, Pei-Luen; Chen, Mei-Ching; Huang, Yu-Ting; Lin, Keh-Chung

2013-01-01

Recent studies suggest that the positive emotion induced by pleasant music may improve cognitive functions. We used the single-subject design to study whether listening to preferred music may reduce unilateral neglect in two participants with post-stroke neglect. These participants were instructed to listen to their preferred music every day for 5 weeks, followed by 2 weeks of follow-up assessment. Outcome measures involved the Star Cancellation Test, the Line Bisection Test, and the visual exploration task. A combination of visual analysis and the two-standard-deviation band method was used for data analysis. Both participants showed significant intervention-related improvements on all outcome measures except the Line Bisection Test, on which one participant showed no improvement. The therapeutic effects were maintained during the follow-up phase. The findings suggest that positive emotion, evoked by preferred music, may be used to ameliorate unilateral neglect. Further research using controlled trials is warranted to validate the findings.

Unilateral uveitis masquerade syndrome caused by diffuse large B-cell lymphoma diagnosed using multiparametric flow cytometry of the aqueous humor.

PubMed

Monsalvo, Silvia; Serrano, Cristina; Prieto, Elena; Fernández-Sanz, Guillermo; Puente, Maria-Camino; Rodriguez-Pinilla, Maria; Garcia Raso, Aranzazu; Llamas, Pilar; Cordoba, Raul

2017-07-01

The uveitis masquerade syndromes (UMS) are a group of ocular diseases that may mimic chronic intraocular inflammation. Many malignant entities such as non-Hodgkin's lymphomas may masquerade as uveitis. We report a case of an HIV-positive patient with masquerade syndrome presenting unilateral uveitis. 45-year-old Caucasian man with a diagnosis of diffuse large B-cell lymphoma (DLBCL). The patient was diagnosed by a biopsy of an abdominal mass which showed fragments of gastric mucosa with diffuse growth of neoplastic cells. At diagnosis, the patient suffered from unilateral blurring of vision and a sudden decrease of left-eye visual acuity. A slit-lamp examination of the left eye revealed a diagnosis of anterior uveitis. The patient exhibited no signs of posterior uveitis. An anterior-chamber paracentesis was performed and analyzed by multiparameter flow cytometry (MFC), showing cells CD45, CD19, CD20, CD22, and CD38 positives, and moderate expression of CD10 with kappa light chain restriction, showing a monoclonal B-cell population. The patient received CHOP-R with intrathecal methotrexate followed by consolidation high dose methotrexate obtaining a complete response which is ongoing. Differential diagnosis between chronic uveitis and ocular lymphoma may be challenging. We advocate anterior-chamber paracentesis in cases of refractory uveitis in patients with hematologic malignancies. © 2016 International Clinical Cytometry Society. © 2016 International Clinical Cytometry Society.

A Chinese Herbal Decoction, Shaoyao-Gancao Tang, Exerts Analgesic Effect by Down-Regulating the TRPV1 Channel in a Rat Model of Arthritic Pain.

PubMed

Sui, Feng; Zhou, Hai-Yu; Meng, Jing; Du, Xin-Liang; Sui, Yun-Peng; Zhou, Zhi-Kun; Dong, Cheng; Wang, Zhu-Ju; Wang, Wei-Hao; Dai, Li; Ma, Hai; Huo, Hai-Ru; Jiang, Ting-Liang

2016-01-01

Shaoyao-Gancao Tang (SGT) is one of the most frequently used compound formulas in the treatment of pain-related diseases in the medical practice of traditional Chinese medicine (TCM). To investigate the anti-inflammatory and antinociceptive effects, as well as to uncover the molecular mechanism of SGT, the rat pain model of arthritis was experimentally induced by single unilateral injection of rats' left hind paw with Freund's complete adjuvant (FCA). SGT was orally administered to the rats daily at three doses individually for a period of 16 days post-model induction. Swollen degrees and pain thresholds of the rats in different groups were measured for evaluation of the anti-inflammatory and anti-nociceptive effects of SGT. Furthermore, the mRNA and protein expression levels of transient receptor potential ion channel protein vanilloid receptor 1 (TRPV1) channel as well as its calcium-mediating function in the isolated DRG neurons were further detected to provide indexes for exploration of the molecular mechanisms mediating anti-arthritic activities of SGT. As a result, FCA injection induced significant allodynia, inflammation and edema, accompanied by a significant increase in both expression and calcium-mediating function of the TRPV1 channel. Pharmacologically, oral administration of SGT at a high or middle dose demonstrated a significant relief from the above-mentioned pathological conditions in a dose-dependent manner. Simultaneously the mRNA and protein expressional levels of TRPV1 channel, as well as its calcium-mediating function, were down-regulated greatly. These findings suggest that SGT possesses a significant analgesic and anti-inflammatory effect on arthritis rats; its therapeutic activities might be achieved through reversing the elevated expression and function of TRPV1 channel evoked by FCA.

White Phosphorus-Felt Smoke: Effects on Reproduction in the Rat

DTIC Science & Technology

1982-07-01

group exhibited unilateral anophthalmia . Four had prominent renal pelvises, three had underdeveloped testicles, one had narrow atria, and one had an...alive +Significant at p = 0.05. 4. DISCUSSION The major teratogenic effects observed in this study included one case each of unilateral anophthalmia ... anophthalmia and one had narrow atria. With only single incidences of the malformations occurring in each group ., and none in the Fj offspring from the

The impact of salpingectomy and single-dose systemic methotrexate treatments on ovarian reserve in ectopic pregnancy.

PubMed

Sahin, Cagdas; Taylan, Enes; Akdemir, Ali; Ozgurel, Banu; Taskıran, Dilek; Ergenoglu, Ahmet M

2016-10-01

To investigate the effects of salpingectomy and methotrexate treatments on ovarian reserve in ectopic pregnancy. In this prospective study, a total of 131 patients with ectopic pregnancy were divided into 3 groups of methotrexate (MTX) only (Group-1, n: 55), salpingectomy only (Group-2, n: 61), and salpingectomy following MTX (Group-3, n: 15). Pretreatment and post-treatment anti-Müllerian hormone (AMH) levels were evaluated. Significant differences in AMH levels were detected between group 1 and group 2 (2.52±1.28 vs. 1.96±1.66, p=0.043), and group 1 and group 3 (2.52±1.28 vs. 1.77±0.76, p=0.035) at one month postoperative. However, these differences disappeared at the 3rd postoperative month. When AMH levels were compared within the same group, postoperative one month AMH levels were significantly lower than the preoperative AMH levels only in group 3 (p=0.03). However, this difference also disappeared at the 3rd postoperative month. Systemic single-dose methotrexate treatment, unilateral salpingectomy, and salpingectomy following methotrexate administration in ectopic pregnancy were reassuring based on pretreatment and post-treatment AMH levels. Current medical and surgical treatment approaches do not have an obvious negative effect on ovarian reserve. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

The optimal protocol to reduce blood loss and blood transfusion after unilateral total knee replacement: Low-dose IA-TXA plus 30-min drain clamping versus drainage clamping for the first 3 h without IA-TXA.

PubMed

Park, Joo Hyun; Choi, Sung Wook; Shin, Eun Ho; Park, Myung Hoon; Kim, Myung Ku

2017-01-01

Although intraarticular tranexamic acid (IA-TXA) administration or drainage clamping are popular methods used to reduce blood loss after total knee replacement (TKR), the protocol remains controversial. We aimed (1) to establish new protocols through investigating whether two methods, that is, low-dose (500 mg) IA-TXA plus 30-min drain clamping and drainage clamping for the first 3 h without IA-TXA, can reduce blood loss and blood transfusion after unilateral TKR and (2) to make recommendations related to clinical application. This study, conducted from September 2014 to June 2016 related to enrolled 95 patients with primary osteoarthritis who were to have a unilateral cemented TKR, was nonrandomized and retrospective. In group A, the drain was released following tourniquet deflation. In group B, 500-mg TXA was injected into the knee joint via a drain tube after fascia closure and the drain was clamped for the first 30 min to prevent leakage. In group C, the drain was clamped for the first 3-h postoperation. Demographic characteristics and clinical data were collected, including the levels of hematocrit (Hct), the total blood loss (TBL), drained blood volume (BV), the amount of blood transfused, and any complications that developed. We found a significantly lower postoperative TBL, drained BV, decreasing Hct level, and less transfused BV in the IA-TXA injection group (group B) and the 3-h drainage clamping group (group C) compared to the conventional negative drainage group (group A; p < 0.001). There was no significant difference between groups B and C ( p = 0.99). The drainage clamping method can be safer than IA-TXA administration in patients with risk factor of venous thromboembolic complication. Furthermore, the IA-TXA administration can be more optimal than drainage clamping in patients with high bleeding tendency or lateral retinacular release during TKR, who would be concerned about postoperative wound complication.

[Evaluation of central lymph node dissection for papillary thyroid carcinoma in cN0 T1/T2].

PubMed

Zhao, S Y; Ma, Y H; Yin, Z; Zhan, X X; Cheng, R C; Qian, J

2018-02-07

Objective: To evaluate the application of the central lymph node dissection (CLND) for papillary thyroid carcinoma (PTC) in cN0 T1/T2. Methods: Retrospective analysis of 532 cases with PTC in cN0 T1/T2 who underwent CLND between October 2014 and September 2016 in the Department of Thyroid Surgery, the First Affiliated Hospital of the Kunming Medical University. The incidence of central lymph node (CLN) metastasis and risk factors were analyzed. Results: CLN metastasis rates: 41.2% (42/102) in males vs 34.9% (150/430) in females, P =0.252; 33.9% (116/342) in single focal carcinoma vs 40.4% (74/183) in multifocal carcinoma, P =0.157; 44.0% (125/284) in patients with 45 years old or less vs 27.0% (67/248) in patients more than 45 years old, P =0.000; 30.3% (113/373) in microcarcinoma vs 50.9% (81/159) in non-microcarcinoma, P =0.000.In unilateral lesions, ipsilateral CLN metastasis was correlated with the tumor diameter ( P =0.012), but not with the number of lesions ( P =0.653). also contralateral CLN metastasis was correlated with the tumor diameter ( P =0.000), but not with the number of lesions ( P =0.815). For the left or right unilateral single focal lesion, the tumor diameter was not correlated with the metastasis of the posterior to right recurrent laryngeal nerve central lymph nodes (LN-prRLN-CLN) ( P =0.652, P =0.088). But in bilateral multifocal carcinoma the tumor diameter was correlated with metastasis of LN-prRLN-CLN ( P =0.039). Conclusions: Prophylactic CLND is reasonable for PTC in cN0 T1/T2. A bilateral CLND should be conducted for patients with bilateral multi-focus cancer and unilateral or bilateral non-microcarcinoma, especially in patients more than 45 years old. For unilateral single focal microcarcinoma on the right, the content of CLND should be from laryngeal nerve on right center to posterior branche; for unilateral single focal microcarcinoma on the left side, the left CLND should be conducted. An ipsilateral CLND can be considered in patients with unilateral multifocal microcarcinoma, and generally a routine dissection of the LN-prRLN-CLN is not required, however for bilateral non-microcarcinoma and the the non-microcarcinoma on the right side, the LN-prRLN-CLN dissection should be conducted.

Minimum Electric Field Exposure for Seizure Induction with Electroconvulsive Therapy and Magnetic Seizure Therapy.

PubMed

Lee, Won H; Lisanby, Sarah H; Laine, Andrew F; Peterchev, Angel V

2017-05-01

Lowering and individualizing the current amplitude in electroconvulsive therapy (ECT) has been proposed as a means to produce stimulation closer to the neural activation threshold and more focal seizure induction, which could potentially reduce cognitive side effects. However, the effect of current amplitude on the electric field (E-field) in the brain has not been previously linked to the current amplitude threshold for seizure induction. We coupled MRI-based E-field models with amplitude titrations of motor threshold (MT) and seizure threshold (ST) in four nonhuman primates (NHPs) to determine the strength, distribution, and focality of stimulation in the brain for four ECT electrode configurations (bilateral, bifrontal, right-unilateral, and frontomedial) and magnetic seizure therapy (MST) with cap coil on vertex. At the amplitude-titrated ST, the stimulated brain subvolume (23-63%) was significantly less than for conventional ECT with high, fixed current (94-99%). The focality of amplitude-titrated right-unilateral ECT (25%) was comparable to cap coil MST (23%), demonstrating that ECT with a low current amplitude and focal electrode placement can induce seizures with E-field as focal as MST, although these electrode and coil configurations affect differently specific brain regions. Individualizing the current amplitude reduced interindividual variation in the stimulation focality by 40-53% for ECT and 26% for MST, supporting amplitude individualization as a means of dosing especially for ECT. There was an overall significant correlation between the measured amplitude-titrated ST and the prediction of the E-field models, supporting a potential role of these models in dosing of ECT and MST. These findings may guide the development of seizure therapy dosing paradigms with improved risk/benefit ratio.

Unilateral hearing during development: hemispheric specificity in plastic reorganizations

PubMed Central

Kral, Andrej; Heid, Silvia; Hubka, Peter; Tillein, Jochen

2013-01-01

The present study investigates the hemispheric contributions of neuronal reorganization following early single-sided hearing (unilateral deafness). The experiments were performed on ten cats from our colony of deaf white cats. Two were identified in early hearing screening as unilaterally congenitally deaf. The remaining eight were bilaterally congenitally deaf, unilaterally implanted at different ages with a cochlear implant. Implanted animals were chronically stimulated using a single-channel portable signal processor for two to five months. Microelectrode recordings were performed at the primary auditory cortex under stimulation at the hearing and deaf ear with bilateral cochlear implants. Local field potentials (LFPs) were compared at the cortex ipsilateral and contralateral to the hearing ear. The focus of the study was on the morphology and the onset latency of the LFPs. With respect to morphology of LFPs, pronounced hemisphere-specific effects were observed. Morphology of amplitude-normalized LFPs for stimulation of the deaf and the hearing ear was similar for responses recorded at the same hemisphere. However, when comparisons were performed between the hemispheres, the morphology was more dissimilar even though the same ear was stimulated. This demonstrates hemispheric specificity of some cortical adaptations irrespective of the ear stimulated. The results suggest a specific adaptation process at the hemisphere ipsilateral to the hearing ear, involving specific (down-regulated inhibitory) mechanisms not found in the contralateral hemisphere. Finally, onset latencies revealed that the sensitive period for the cortex ipsilateral to the hearing ear is shorter than that for the contralateral cortex. Unilateral hearing experience leads to a functionally-asymmetric brain with different neuronal reorganizations and different sensitive periods involved. PMID:24348345

Unilateral hearing during development: hemispheric specificity in plastic reorganizations.

PubMed

Kral, Andrej; Heid, Silvia; Hubka, Peter; Tillein, Jochen

2013-01-01

The present study investigates the hemispheric contributions of neuronal reorganization following early single-sided hearing (unilateral deafness). The experiments were performed on ten cats from our colony of deaf white cats. Two were identified in early hearing screening as unilaterally congenitally deaf. The remaining eight were bilaterally congenitally deaf, unilaterally implanted at different ages with a cochlear implant. Implanted animals were chronically stimulated using a single-channel portable signal processor for two to five months. Microelectrode recordings were performed at the primary auditory cortex under stimulation at the hearing and deaf ear with bilateral cochlear implants. Local field potentials (LFPs) were compared at the cortex ipsilateral and contralateral to the hearing ear. The focus of the study was on the morphology and the onset latency of the LFPs. With respect to morphology of LFPs, pronounced hemisphere-specific effects were observed. Morphology of amplitude-normalized LFPs for stimulation of the deaf and the hearing ear was similar for responses recorded at the same hemisphere. However, when comparisons were performed between the hemispheres, the morphology was more dissimilar even though the same ear was stimulated. This demonstrates hemispheric specificity of some cortical adaptations irrespective of the ear stimulated. The results suggest a specific adaptation process at the hemisphere ipsilateral to the hearing ear, involving specific (down-regulated inhibitory) mechanisms not found in the contralateral hemisphere. Finally, onset latencies revealed that the sensitive period for the cortex ipsilateral to the hearing ear is shorter than that for the contralateral cortex. Unilateral hearing experience leads to a functionally-asymmetric brain with different neuronal reorganizations and different sensitive periods involved.

Single absorbable polydioxanone pin fixation for distal chevron bunion osteotomies.

PubMed

Deorio, J K; Ware, A W

2001-10-01

The distal chevron osteotomy is a well-established technique for correction of symptomatic mild to moderate metatarsus primus varus with hallux valgus deformity. Fixation of the osteotomy ranges from none to bone pegs, Kirschner wires, screws, or absorbable pins. We evaluated one surgeon's (J.K.D.) results of distal chevron osteotomy fixation with a single, nonpredrilled, 1.3-mm poly-p-dioxanone pin and analyzed any differences in patients with unilateral or bilateral symptomatic metatarsus primus varus with hallux valgus deformities. All osteotomies healed without evidence of infection, osteolysis, nonunion, or necrosis. Equal correction was achieved in unilateral and bilateral procedures. The technique is quick and easy, and adequate fixation is achieved.

CAVITATION SOUNDS DURING CERVICOTHORACIC SPINAL MANIPULATION

PubMed Central

Mourad, Firas; Zingoni, Andrea; Iorio, Raffaele; Perreault, Thomas; Zacharko, Noah; de las Peñas, César Fernández; Butts, Raymond; Cleland, Joshua A.

2017-01-01

Background No study has previously investigated the side, duration or number of audible cavitation sounds during high-velocity low-amplitude (HVLA) thrust manipulation to the cervicothoracic spine. Purpose The primary purpose was to determine which side of the spine cavitates during cervicothoracic junction (CTJ) HVLA thrust manipulation. Secondary aims were to calculate the average number of cavitations, the duration of cervicothoracic thrust manipulation, and the duration of a single cavitation. Study Design Quasi-experimental study Methods Thirty-two patients with upper trapezius myalgia received two cervicothoracic HVLA thrust manipulations targeting the right and left T1-2 articulation, respectively. Two high sampling rate accelerometers were secured bilaterally 25 mm lateral to midline of the T1-2 interspace. For each manipulation, two audio signals were extracted using Short-Time Fourier Transformation (STFT) and singularly processed via spectrogram calculation in order to evaluate the frequency content and number of instantaneous energy bursts of both signals over time for each side of the CTJ. Result Unilateral cavitation sounds were detected in 53 (91.4%) of 58 cervicothoracic HVLA thrust manipulations and bilateral cavitation sounds were detected in just five (8.6%) of the 58 thrust manipulations; that is, cavitation was significantly (p<0.001) more likely to occur unilaterally than bilaterally. In addition, cavitation was significantly (p<0.0001) more likely to occur on the side contralateral to the clinician's short-lever applicator. The mean number of audible cavitations per manipulation was 4.35 (95% CI 2.88, 5.76). The mean duration of a single manipulation was 60.77 ms (95% CI 28.25, 97.42) and the mean duration of a single audible cavitation was 4.13 ms (95% CI 0.82, 7.46). In addition to single-peak and multi-peak energy bursts, spectrogram analysis also demonstrated high frequency sounds, low frequency sounds, and sounds of multiple frequencies for all 58 manipulations. Discussion Cavitation was significantly more likely to occur unilaterally, and on the side contralateral to the short-lever applicator contact, during cervicothoracic HVLA thrust manipulation. Clinicians should expect multiple cavitation sounds when performing HVLA thrust manipulation to the CTJ. Due to the presence of multi-peak energy bursts and sounds of multiple frequencies, the cavitation hypothesis (i.e. intra-articular gas bubble collapse) alone appears unable to explain all of the audible sounds during HVLA thrust manipulation, and the possibility remains that several phenomena may be occurring simultaneously. Level of Evidence 2b PMID:28900571

Bone scintigraphy in the investigation of occult lameness in the dog.

PubMed

Schwarz, T; Johnson, V S; Voute, L; Sullivan, M

2004-05-01

99mTechnetium methylene diphosphonate (99mTc-MDP) scintigraphy was performed in 14 dogs of different breeds after clinical lameness examination, radiography and synovial fluid analysis failed to localise lameness to a specific area of pain. The scintigraphic protocol included an intravenous injection of 17 MBq 99mTc-MDP/kg bodyweight and vascular, soft tissue and bone phase scans in standardised positions with a low-energy all-purpose collimator. Confirmation of diagnosis was achieved in nine dogs by arthroscopy, repeated lesion-orientated radiography, computed tomography and response to treatment. In seven cases, bone phase scans showed single elbow uptakes, in two cases unilateral limb uptake, and in one case each a single shoulder and tibia uptake; in three cases there was no increased uptake. Vascular and soft tissue phase images did not reveal additional information. Diagnosis of humeral condyle fissures, a fragmented medial coronoid process, panosteitis and arthropathy was possible in nine cases. Skeletal pathology was ruled out in three normal scintigrams. In two dogs with unilateral uptake of multiple joints, no diagnostic benefit was gained from scintigraphy. The highly sensitive and relatively specific uptake allowed localisation and characterisation or exclusion of skeletal lesions in most dogs.

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

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

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

2011-03-15

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

Estimating systemic exposure to ethinyl estradiol from an oral contraceptive.

PubMed

Westhoff, Carolyn L; Pike, Malcolm C; Tang, Rosalind; DiNapoli, Marianne N; Sull, Monica; Cremers, Serge

2015-05-01

This study was conducted to compare single-dose pharmacokinetics of ethinyl estradiol in an oral contraceptive with steady-state values and to assess whether any simpler measures could provide an adequate proxy of the "gold standard" 24-hour steady-state area under the curve (AUC) value. Identification of a simple, less expensive measure of systemic ethinyl estradiol exposure would be useful for larger studies that are designed to assess the relationship between an individual's ethinyl estradiol exposure and side-effects. We collected 13 samples over 24 hours for pharmacokinetic analysis on days 1 and 21 of the first cycle of a monophasic oral contraceptive that contained 30 μg ethinyl estradiol and 150 μg levonorgestrel in 17 nonobese healthy white women. We also conducted an abbreviated single-dose 9-sample pharmacokinetic analysis after a month washout. Ethinyl estradiol was measured by liquid chromatography-tandem mass spectrometry. We compared results of a full 13-sample steady-state pharmacokinetic analysis with results that had been calculated with the use of fewer samples (9 or 5) and after the single doses. We calculated Pearson correlation coefficients to evaluate the relationships between these estimates of systemic ethinyl estradiol exposure. The AUC, maximum, and 24-hour values were similar after the 2 single oral contraceptive doses (AUC; r=0.92). The steady-state 13-sample 24-hour AUC value was correlated highly with the average 9-sample AUC value after the 2 single doses (r=0.81; P=.0002). This correlation remained the same if the number of single-dose samples was reduced to 4, taken at time 1, 2.5, 4, and 24 hours. The 24-hour value at steady-state was correlated highly with the 24-hour steady-state AUC value (r=0.92; P<.0001). The average of the 24-hour values after the 2 single doses was also correlated quite highly with the steady-state AUC value (r=0.72; P=.0026). Limited blood sampling, including results from 2 single doses, gave highly correlated estimates of an oral contraceptive user's steady-state ethinyl estradiol exposure. Copyright © 2015 Elsevier Inc. All rights reserved.

Limb symmetry during double-leg squats and single-leg squats on land and in water in adults with long-standing unilateral anterior knee pain; a cross sectional study.

PubMed

Severin, Anna C; Burkett, Brendan J; McKean, Mark R; Wiegand, Aaron N; Sayers, Mark G L

2017-01-01

The presence of pain during movement typically results in changes in technique. However, the physical properties of water, such as flotation, means that water-based exercise may not only reduce compensatory movement patterns but also allow pain sufferers to complete exercises that they are unable to perform on land. The purpose of this study was to assess bilateral kinematics during double-leg squats and single-leg squats on land and in water in individuals with unilateral anterior knee pain. A secondary aim was to quantify bilateral asymmetry in both environments in affected and unaffected individuals using a symmetry index. Twenty individuals with unilateral knee pain and twenty healthy, matched controls performed body weight double- and single-leg squats in both environments while inertial sensors (100 Hz) recorded trunk and lower body kinematics. Repeated-measures statistics tested for environmental effects on movement depths and peak angles within the anterior knee pain group. Differences in their inter-limb symmetry in each environments was compared to the control group using analysis of variance tests. Water immersion allowed for greater movement depths during both exercises (double-leg squat: +7 cm, p  = 0.032, single-leg squat: +9 cm, p  = 0.002) for the knee pain group. The double-leg squat was symmetrical on land but water immersion revealed asymmetries in the lower body frontal plane movements. The single-leg squat revealed decreased hip flexion and frontal plane shank motions on the affected limb in both environments. Water immersion also affected the degree of lower limb asymmetry in both groups, with differences also showing between groups. Individuals with anterior knee pain achieved increased squat depth during both exercises whilst in water. Kinematic differences between the affected and unaffected limbs were often increased in water. Individuals with unilateral anterior knee pain appear to utilise different kinematics in the affected and unaffected limb in both environments.

Integrated beam orientation and scanning-spot optimization in intensity-modulated proton therapy for brain and unilateral head and neck tumors.

PubMed

Gu, Wenbo; O'Connor, Daniel; Nguyen, Dan; Yu, Victoria Y; Ruan, Dan; Dong, Lei; Sheng, Ke

2018-04-01

Intensity-Modulated Proton Therapy (IMPT) is the state-of-the-art method of delivering proton radiotherapy. Previous research has been mainly focused on optimization of scanning spots with manually selected beam angles. Due to the computational complexity, the potential benefit of simultaneously optimizing beam orientations and spot pattern could not be realized. In this study, we developed a novel integrated beam orientation optimization (BOO) and scanning-spot optimization algorithm for intensity-modulated proton therapy (IMPT). A brain chordoma and three unilateral head-and-neck patients with a maximal target size of 112.49 cm 3 were included in this study. A total number of 1162 noncoplanar candidate beams evenly distributed across 4π steradians were included in the optimization. For each candidate beam, the pencil-beam doses of all scanning spots covering the PTV and a margin were calculated. The beam angle selection and spot intensity optimization problem was formulated to include three terms: a dose fidelity term to penalize the deviation of PTV and OAR doses from ideal dose distribution; an L1-norm sparsity term to reduce the number of active spots and improve delivery efficiency; a group sparsity term to control the number of active beams between 2 and 4. For the group sparsity term, convex L2,1-norm and nonconvex L2,1/2-norm were tested. For the dose fidelity term, both quadratic function and linearized equivalent uniform dose (LEUD) cost function were implemented. The optimization problem was solved using the Fast Iterative Shrinkage-Thresholding Algorithm (FISTA). The IMPT BOO method was tested on three head-and-neck patients and one skull base chordoma patient. The results were compared with IMPT plans created using column generation selected beams or manually selected beams. The L2,1-norm plan selected spatially aggregated beams, indicating potential degeneracy using this norm. L2,1/2-norm was able to select spatially separated beams and achieve smaller deviation from the ideal dose. In the L2,1/2-norm plans, the [mean dose, maximum dose] of OAR were reduced by an average of [2.38%, 4.24%] and[2.32%, 3.76%] of the prescription dose for the quadratic and LEUD cost function, respectively, compared with the IMPT plan using manual beam selection while maintaining the same PTV coverage. The L2,1/2 group sparsity plans were dosimetrically superior to the column generation plans as well. Besides beam orientation selection, spot sparsification was observed. Generally, with the quadratic cost function, 30%~60% spots in the selected beams remained active. With the LEUD cost function, the percentages of active spots were in the range of 35%~85%.The BOO-IMPT run time was approximately 20 min. This work shows the first IMPT approach integrating noncoplanar BOO and scanning-spot optimization in a single mathematical framework. This method is computationally efficient, dosimetrically superior and produces delivery-friendly IMPT plans. © 2018 American Association of Physicists in Medicine.

Bilateral LMAN lesions cancel differences in HVC neuronal recruitment induced by unilateral syringeal denervation. Lateral magnocellular nucleus of the anterior neostriatum.

PubMed

Wilbrecht, L; Petersen, T; Nottebohm, F

2002-12-01

Twenty-six-day-old male zebra finches received (1) unilateral section of their tracheosyringeal nerve, (2) bilateral lesions of the lateral magnocellular nucleus of the anterior neostriatum (LMAN), and (3) both operations. All birds were kept with an adult, singing male as a tutor until day 65. Tracheo-syringeal nerve-cut birds were able to imitate this model, but LMAN-lesioned birds were not. Bromodeoxyuridine, a marker of cell division, was injected intramuscularly during post-hatching days 61-65 and all birds were killed at 91 days of age. The number of bromodeoxyuridine+ neurons in the high vocal center of the tracheosyringeal-cut birds was twice as high in the intact as in the nerve cut side. This asymmetry disappeared when nerve section was combined with bilateral LMAN lesions. The latter operation, by itself, had no effect on new neuron counts. We suggest that the single nerve cut produced a hemispheric asymmetry in learning, reflected in new neuron recruitment, which disappeared when LMAN lesions blocked learning.

Improved long-term survival after intra-operative single high-dose ATG-Fresenius induction in renal transplantation: a single centre experience.

PubMed

Kaden, Jürgen; May, Gottfried; Völp, Andreas; Wesslau, Claus

2009-01-01

In organ grafts donor-specific sensitization is initiated immediately after revascularization. Therefore, in 1990 we introduced the intra-operative single high-dose ATG-Fresenius (ATG-F) induction in addition to standard triple drug therapy (TDT) consisting of steroids, azathioprine and cyclosporin. A total of 778 first renal transplantations from deceased donors, performed between 1987 and 1998, were included in this evaluation. This retrospective analysis of clinic records and electronic databases presents data of all recipients of first kidney grafts who received two different ATG-F inductions (1(st) group: 9 mg/kg body weight as single high-dose intra-operatively, n=484; 2(nd) group: 3 mg/kg body weight on 7 or 8 consecutive days as multiple-dose starting also intra-operatively, n=78) and standard TDT alone (3(rd) group: TDT alone, n=216). The 10-year patient survival rates were 72.6+/-2.6% (TDT + ATG-F single high-dose), 79.5+/-5.1% (TDT + ATG-F multiple-dose) and 67.2+/-3.7%% (TDT alone; Kaplan-Meier estimates with standard errors; ATG-F vs TDT alone, p=0.001). The 10-year graft survival rates with censoring of patients that died with a functioning graft were 73.8+/-2.4%, 57.7+/-5.8% and 58.4+/-3.6% (Kaplan-Meier estimates with standard errors; 1(st) vs 2(nd )and 3(rd) group, respectively, p<0.001) and the 10-year graft survival rates with patient death counted as graft failure were 58.3+/-2.7%, 55.7+/-5.8% and 48.2+/-3.5% (Kaplan-Meier estimates with standard errors; ATG-F single high-dose vs TDT, p=0.023). In pre-sensitized recipients there were also significant differences in favour of ATG-F, more notably in the single high-dose ATG-F induction. A total of 69% of the patients in the two cohorts receiving ATG-F did not experience any transplant rejections compared to 56% in patients undergoing TDT alone (p=0.018). The incidence of infectious complications was comparable across all groups. According to evidence obtained from the routine documentation of 778 renal transplantations, ATG-F induction therapy administered as a part of immunosuppressive therapy significantly improves patient survival and reduces the risk of graft failure and transplant rejections.

Estimation and comparison of effective dose (E) in standard chest CT by organ dose measurements and dose-length-product methods and assessment of the influence of CT tube potential (energy dependency) on effective dose in a dual-source CT.

PubMed

Paul, Jijo; Banckwitz, Rosemarie; Krauss, Bernhard; Vogl, Thomas J; Maentele, Werner; Bauer, Ralf W

2012-04-01

To determine effective dose (E) during standard chest CT using an organ dose-based and a dose-length-product-based (DLP) approach for four different scan protocols including high-pitch and dual-energy in a dual-source CT scanner of the second generation. Organ doses were measured with thermo luminescence dosimeters (TLD) in an anthropomorphic male adult phantom. Further, DLP-based dose estimates were performed by using the standard 0.014mSv/mGycm conversion coefficient k. Examinations were performed on a dual-source CT system (Somatom Definition Flash, Siemens). Four scan protocols were investigated: (1) single-source 120kV, (2) single-source 100kV, (3) high-pitch 120kV, and (4) dual-energy with 100/Sn140kV with equivalent CTDIvol and no automated tube current modulation. E was then determined following recommendations of ICRP publication 103 and 60 and specific k values were derived. DLP-based estimates differed by 4.5-16.56% and 5.2-15.8% relatively to ICRP 60 and 103, respectively. The derived k factors calculated from TLD measurements were 0.0148, 0.015, 0.0166, and 0.0148 for protocol 1, 2, 3 and 4, respectively. Effective dose estimations by ICRP 103 and 60 for single-energy and dual-energy protocols show a difference of less than 0.04mSv. Estimates of E based on DLP work equally well for single-energy, high-pitch and dual-energy CT examinations. The tube potential definitely affects effective dose in a substantial way. Effective dose estimations by ICRP 103 and 60 for both single-energy and dual-energy examinations differ not more than 0.04mSv. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

The effect of extracapsular injuries on growth and development of the mandible condyle: an experimental study in growing dogs.

PubMed

Liu, Siying; Tian, Lei; Ding, Mingchao; Liu, Yanpu; Li, Guiyu; Chen, Jinwu; Ding, Yin

2016-11-01

To investigate the effects of condylar extracapsular injuries on the development of the mandibular condyle and try to find a way to treat condylar hyperplasia by electively using such injuries to restrict the overdeveloped mandibular condyle. Sixty 6-month-old beagle puppies were divided randomly into five groups: blank control; unilateral fracture to the condylar neck; unilateral fracture to the condylar neck treated with rigid internal fixation; unilateral periosteum injury; unilateral decortication of the condylar neck. Computed tomography, 99 m Tc single-photon emission computed tomography, and tetracycline-calcein double-labeling were performed after surgery. The puppies were sacrificed 12 and 24 weeks after surgery. Morphologic analyses and examination of growth activity were done. Unilateral fracture of the condylar neck without fixation caused local morphologic changes during the early postoperative period, but compensatory growth of the condyle altered such changes after healing. The other types of injury failed to inhibit the growth of the condyle and the mandible, whereas functional deviation of the chin was found after unilateral fracture of the condylar neck with or without fixation. The four types of extracapsular injury described here failed to inhibit the growth of the mandibular condyle and could not be selected as alternatives to treat condylar hyperplasia. Copyright © 2016 Elsevier Inc. All rights reserved.

Novel test of motor and other dysfunctions in mouse neurological disease models.

PubMed

Barth, Albert M I; Mody, Istvan

2014-01-15

Just like human neurological disorders, corresponding mouse models present multiple deficiencies. Estimating disease progression or potential treatment effectiveness in such models necessitates the use of time consuming and multiple tests usually requiring a large number of scarcely available genetically modified animals. Here we present a novel and simple single camera arrangement and analysis software for detailed motor function evaluation in mice walking on a wire mesh that provides complex 3D information (instantaneous position, speed, distance traveled, foot fault depth, duration, location, relationship to speed of movement, etc.). We investigated 3 groups of mice with various neurological deficits: (1) unilateral motor cortical stroke; (2) effects of moderate ethanol doses; and (3) aging (96-99 weeks old). We show that post stroke recovery can be divided into separate stages based on strikingly different characteristics of motor function deficits, some resembling the human motor neglect syndrome. Mice treated with moderate dose of alcohol and aged mice showed specific motor and exploratory deficits. Other tests rely either partially or entirely on manual video analysis introducing a significant subjective component into the analysis, and analyze a single aspect of motor function. Our novel experimental approach provides qualitatively new, complex information about motor impairments and locomotor/exploratory activity. It should be useful for the detailed characterization of a broad range of human neurological disease models in mice, and for the more accurate assessment of disease progression or treatment effectiveness. Copyright © 2013 Elsevier B.V. All rights reserved.

Hearing Outcomes After Stereotactic Radiosurgery for Unilateral Intracanalicular Vestibular Schwannomas: Implication of Transient Volume Expansion

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

Kim, Young-Hoon; Department of Neurosurgery, Seoul National University College of Medicine, Seoul; Kim, Dong Gyu, E-mail: gknife@plaza.snu.ac.kr

2013-01-01

Purpose: We evaluated the prognostic factors for hearing outcomes after stereotactic radiosurgery (SRS) for unilateral sporadic intracanalicular vestibular schwannomas (IC-VSs) as a clinical homogeneous group of VSs. Methods and Materials: Sixty consecutive patients with unilateral sporadic IC-VSs, defined as tumors in the internal acoustic canal, and serviceable hearing (Gardner-Roberson grade 1 or 2) were treated with SRS as an initial treatment. The mean tumor volume was 0.34 {+-} 0.03 cm{sup 3} (range, 0.03-1.00 cm{sup 3}), and the mean marginal dose was 12.2 {+-} 0.1 Gy (range, 11.5-13.0 Gy). The median follow-up duration was 62 months (range, 36-141 months). Results: Themore » actuarial rates of serviceable hearing preservation were 70%, 63%, and 55% at 1, 2, and 5 years after SRS, respectively. In multivariate analysis, transient volume expansion of {>=}20% from initial tumor size was a statistically significant risk factor for loss of serviceable hearing and hearing deterioration (increase of pure tone average {>=}20 dB) (odds ratio = 7.638; 95% confidence interval, 2.317-25.181; P=.001 and odds ratio = 3.507; 95% confidence interval, 1.228-10.018; P=.019, respectively). The cochlear radiation dose did not reach statistical significance. Conclusions: Transient volume expansion after SRS for VSs seems to be correlated with hearing deterioration when defined properly in a clinically homogeneous group of patients.« less

Churg-Strauss syndrome associated with antiphospholipid antibodies in a patient with retinal vasculitis.

PubMed

Sánchez-Vicente, J L; Gálvez-Carvajal, S; Medina-Tapia, A; Rueda, T; González-García, L; Szewc, M; Muñoz-Morales, A

2016-11-01

We present the case of a 69-year-old woman with unilateral retinal vasculitis. Investigations showed asthma, rhinosinusitis, nasal polyposis, peripheral blood eosinophilia, increased sedimentation rate, proteinuria, and antiphospholipid antibodies. Anti-neutrophil cytoplasmic antibodies (ANCA) were negative. Although her anti-neutrophil cytoplasmatic antibody (ANCA) status was negative, taking into account the other clinical and laboratory features, retinal vasculitis was thought to be an ocular manifestation of Churg-Strauss syndrome. Treatment was started with high-dose corticosteroids and anticoagulant therapy. Copyright © 2016 Sociedad Española de Oftalmología. Publicado por Elsevier España, S.L.U. All rights reserved.

The Role of Unilateral Balloon Kyphoplasty for the Treatment of Patients with OVCFS: A Systematic Review and Meta-Analysis.

PubMed

Xiang, Guang-Heng; Tong, Min-Ji; Lou, Chao; Zhu, Si-Pin; Guo, Wei Jun; Ke, Chen Rong

2018-05-01

An increasing number of studies have been conducted to apply unilateral balloon kyphoplasty in the treatment of ostroporotic vertebral compression fractures (OVCFs). However, the efficacy and safety of unilateral kyphoplasty and whether a unilateral or a bilateral approach is superior is controversial. The purpose of this study was to evaluate the role of unilateral balloon kyphoplasty and use meta-analysis to compare the efficacy and safety of unilateral and bilateral kyphoplasty in patients with OVCFs. A systematic literature search was conducted from 1970 to April 2017 using Medline database and the Cochrane Central Register of Controlled Trials. Articles were limited to those published in English. Randomized controlled trials and nonrandomized comparative studies were also included. The following search terms were used: "osteoporotic vertebral compression fractures," or "OVCF," and "unilateral kyphoplasty," or "unipedicular approach," or "single balloon kyphoplasty," or "one balloon kyphoplasty." A comprehensive search of reference lists of retrieved articles and previous published reviews was also performed to ensure inclusion of all possible studies. All potential articles were independently reviewed by 2 investigators for inclusion into the final analysis. MINORS score was used for nonrandomized studies, and Detsky quality index was applied for prospective randomized controlled trials. Systematic review and meta-analysis was performed for the included studies. After unilateral balloon kyphoplasty the mean postoperative visual analog score (VAS) was from 1.74 to 4.77, mean postoperative kyphotic angle was from 5.9º to 11.22º, and complications involving cement leaks was from 6.8 to 21.9% or adjacent level fractures was from 0 to 5.6%). Unilateral kyphoplasty had significantly lower operative time, and less bone cement volume; however, the postoperative VAS, Oswestry Disability Index (ODI), vertebral height restoration rate, and cement leakage and adjacent vertebral fracture rate, were similar to bilateral kyphoplasty. Only 6 randomized controlled trials and 3 retrospective comparative studies were selected for analysis. Heterogeneity was detected among the studies when we pooled the outcomes. Based on the available evidence, the clinical and radiological results of unilateral balloon kyphoplasty were as good as those of bilateral balloon kyphoplasty for the treatment of OVCFs. And unilateral kyphoplasty had advantages in terms of operation time, radiation exposure, and cost. Unilateral balloon kyphoplasty, bilateral balloon kyphoplasty, osteoporotic vertebral compression fractures, complications of balloon kyphoplasty, meta-analysis.

Monaco and film dosimetry of 3D CRT, IMRT and VMAT cases in a realistic pelvic prosthetic phantom

NASA Astrophysics Data System (ADS)

Ade, Nicholas; du Plessis, F. C. P.

2018-04-01

The dosimetry of patients with metallic hip implants during irradiation of pelvic lesions is challenging due to dose distortions caused by implants. This work presents a dosimetric comparison of various multi-field photon-beam dose distributions in the presence of unilateral hip titanium prosthesis (UHTiP) embedded in a unique pelvic phantom made out of water-equivalent nylon slices. The impact of the UHTiP on the accuracy of dose calculations from a Monaco TPS (treatment planning system) using the X-ray voxel Monte Carlo (XVMC) algorithm was benchmarked against measured dose data using Gafchromic EBT3 film. Multi-field beam arrangements including a 4-field box, 5-field 3DCRT (three-dimensional conformal radiation therapy), 6-field IMRT (intensity modulated radiation therapy) and a single-arc VMAT (volumetric modulated arc therapy) plan were set up for 6 MV and 15 MV beams. These plans were generated for the pelvic phantom that contains the prosthesis with film inserted. Compared to Monaco TPS dose calculations, film measurements showed enhanced dose in the prosthesis which was not predicted by Monaco due to its limitation in relative density assignment. The enhanced prosthesis dose increased with increase in beam energy and decreased with the complexity of the treatment plans, with VMAT giving the least escalated dose. The dose increased between 5% and 19% for 6 MV and between 6% and 21% for 15 MV. A gamma index analysis showed that 70-92% of dose points (excluding the prosthesis) were within 3% discrepancy. Increasing the number of treatment fields increases target dose coverage and improves the agreement between film and Monaco. When the relative electron density (RED) in the prosthesis was varied between 3.72 and 15 the dose discrepancy between film and Monaco increased from 30% to 57% for 6 MV and from 30% to 50% for 15 MV. The study indicates that beam weights for fields that pass through the prosthesis should be minimised and its RED must be correct for accurate dose calculation on Monaco.

Pharmacokinetics and food interaction of a novel prodrug of tenofovir, tenofovir dipivoxil fumarate, in healthy volunteers.

PubMed

Lu, C; Jia, Y; Chen, L; Ding, Y; Yang, J; Chen, M; Song, Y; Sun, X; Wen, A

2013-04-01

Tenofovir dipivoxil fumarate is a novel ester prodrug of tenofovir, a specific anti-hepatitis B virus (HBV) drug candidate. The pharmacokinetic properties and the effects of food intake on tenofovir dipivoxil have not yet been reported in healthy adults. The aim of this study was to evaluate the pharmacokinetic properties and food interaction of tenofovir dipivoxil in healthy Chinese volunteers. Pharmacokinetic studies included an ascending single dose of 150, 300, 600 mg and multiple doses of 300 mg. Food interaction was evaluated following a single oral dose of tenofovir dipivoxil fumarate 300 mg administered with a high-fat and high-energy standard breakfast or after a 12-h fast. Pharmacokinetic parameters of tenofovir given in each treatment period were calculated using non-compartmental analysis. After a single dose of 150, 300 and 600 mg, the main pharmacokinetic parameters for tenofovir were as follows: Cmax 209·6, 456·7, 989·8 ng/mL; AUClast 1744·9, 2663·5, 6010·2 ng h/mL, respectively. After multiple doses of 300 mg, the main pharmacokinetic parameters for tenofovir were Cmax 523·4 ng/mL, AUClast 4152·4 ng h/mL. After a single dose of 300 mg with a high-fat and high-energy standard breakfast, the main pharmacokinetic parameters for tenofovir were Cmax 448·5 ng/mL, AUClast 3286·8 ng h/mL. The plasma Cmax and AUC of tenofovir showed significance difference between a single dose of 300 mg and the accordingly multiple doses (P < 0·05). A standard high-fat meal enhanced mean AUClast values of tenofovir (relative AUClast  = 125·8%; 90% CI 114·5, 136·2); however, food did not show any significant on Cmax (relative Cmax  = 103·4%; 90% CI 94·6, 112·6). Oral tenofovir dipivoxil fumarate produced predictable and dose-proportional plasma tenofovir pharmacokinetics. The accumulation ratio was 1·51, suggesting tenofovir dipivoxil fumarate displayed accumulation after repeated administration. The bioavailability of tenofovir dipivoxil fumarate was increased by approximately 25% as measured by AUClast after a single dose when taken with food, compared with fasting. © 2012 Blackwell Publishing Ltd.

SU-F-J-109: Generate Synthetic CT From Cone Beam CT for CBCT-Based Dose Calculation

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

Wang, H; Barbee, D; Wang, W

Purpose: The use of CBCT for dose calculation is limited by its HU inaccuracy from increased scatter. This study presents a method to generate synthetic CT images from CBCT data by a probabilistic classification that may be robust to CBCT noise. The feasibility of using the synthetic CT for dose calculation is evaluated in IMRT for unilateral H&N cancer. Methods: In the training phase, a fuzzy c-means classification was performed on HU vectors (CBCT, CT) of planning CT and registered day-1 CBCT image pair. Using the resulting centroid CBCT and CT values for five classified “tissue” types, a synthetic CTmore » for a daily CBCT was created by classifying each CBCT voxel to obtain its probability belonging to each tissue class, then assigning a CT HU with a probability-weighted summation of the classes’ CT centroids. Two synthetic CTs from a CBCT were generated: s-CT using the centroids from classification of individual patient CBCT/CT data; s2-CT using the same centroids for all patients to investigate the applicability of group-based centroids. IMRT dose calculations for five patients were performed on the synthetic CTs and compared with CT-planning doses by dose-volume statistics. Results: DVH curves of PTVs and critical organs calculated on s-CT and s2-CT agree with those from planning-CT within 3%, while doses calculated with heterogeneity off or on raw CBCT show DVH differences up to 15%. The differences in PTV D95% and spinal cord max are 0.6±0.6% and 0.6±0.3% for s-CT, and 1.6±1.7% and 1.9±1.7% for s2-CT. Gamma analysis (2%/2mm) shows 97.5±1.6% and 97.6±1.6% pass rates for using s-CTs and s2-CTs compared with CT-based doses, respectively. Conclusion: CBCT-synthesized CTs using individual or group-based centroids resulted in dose calculations that are comparable to CT-planning dose for unilateral H&N cancer. The method may provide a tool for accurate dose calculation based on daily CBCT.« less

Pterional approach versus unilateral frontal approach on tuberculum sellae meningioma: Single centre experiences

PubMed Central

Arifin, Muhammad Zafrullah; Mardjono, Ignatius; Sidabutar, Roland; Wirjomartani, Beny Atmadja; Faried, Ahmad

2012-01-01

Introduction: Tuberculum Sellae Meningioma is one of the most challenging surgeries among neurosurgeons. Many approaches have been established in the effort of removing the tumor and some of them are supported by an advanced neurosurgical technology. In this study, we aim to compare the efficacy of the two most common approaches, the pterional and the unilateral frontal. Materials and Methods: This was a restrospective study that aimed to observe the efficacy of the two most common approaches used in our center, the pterional and the unilateral frontal, in resecting the tuberculum sellae meningioma, which was held in Dr. Hasan Sadikin General Hospital, Bandung, from July 2007-July 2010. Twenty patients were enrolled with half of them operated by the pterional approach and the rest by unilateral frontal approach. We evaluated six parameters: tumor size, degree of tumor removal, surgery duration, post-operative cerebral edema, patients' outcome, and length of stay, which were evaluated to take measure of the efficacy of each procedure. Results: We found that the pterional approach gave more advantages than the unilateral frontal. Total tumor removal, especially in tumor size ≥ 3 cm was achieved in a greater number of subjects in the pterional (P<0.023). Other advantages of the pterional compared to the unilateral frontal were a shorter surgical duration (P=0.024), shorter length of stay (P=0.009) and less frequency of post-operative cerebral edema incidence (P=0.023). Conclusion: According to our facilities and conditions, it seems that the pterional approach have more advantages than the unilateral frontal approach in tuberculum sellae meningioma surgery. PMID:22639687

N-Acetyl-L-Leucine Accelerates Vestibular Compensation after Unilateral Labyrinthectomy by Action in the Cerebellum and Thalamus

PubMed Central

Xiong, Guoming; Potschka, Heidrun; Jahn, Klaus; Bartenstein, Peter; Brandt, Thomas; Dutia, Mayank; Dieterich, Marianne; Strupp, Michael; la Fougère, Christian; Zwergal, Andreas

2015-01-01

An acute unilateral vestibular lesion leads to a vestibular tone imbalance with nystagmus, head roll tilt and postural imbalance. These deficits gradually decrease over days to weeks due to central vestibular compensation (VC). This study investigated the effects of i.v. N-acetyl-DL-leucine, N-acetyl-L-leucine and N-acetyl-D-leucine on VC using behavioural testing and serial [18F]-Fluoro-desoxyglucose ([18F]-FDG)-μPET in a rat model of unilateral chemical labyrinthectomy (UL). Vestibular behavioural testing included measurements of nystagmus, head roll tilt and postural imbalance as well as sequential whole-brain [18F]-FDG-μPET was done before and on days 1,3,7 and 15 after UL. A significant reduction of postural imbalance scores was identified on day 7 in the N-acetyl-DL-leucine (p < 0.03) and the N-acetyl-L-leucine groups (p < 0.01), compared to the sham treatment group, but not in the N-acetyl-D-leucine group (comparison for applied dose of 24 mg i.v. per rat, equivalent to 60 mg/kg body weight, in each group). The course of postural compensation in the DL- and L-group was accelerated by about 6 days relative to controls. The effect of N-acetyl-L-leucine on postural compensation depended on the dose: in contrast to 60 mg/kg, doses of 15 mg/kg and 3.75 mg/kg had no significant effect. N-acetyl-L-leucine did not change the compensation of nystagmus or head roll tilt at any dose. Measurements of the regional cerebral glucose metabolism (rCGM) by means of μPET revealed that only N-acetyl-L-leucine but not N-acetyl-D-leucine caused a significant increase of rCGM in the vestibulocerebellum and a decrease in the posterolateral thalamus and subthalamic region on days 3 and 7. A similar pattern was found when comparing the effect of N-acetyl-L-leucine on rCGM in an UL-group and a sham UL-group without vestibular damage. In conclusion, N-acetyl-L-leucine improves compensation of postural symptoms after UL in a dose-dependent and specific manner, most likely by activating the vestibulocerebellum and deactivating the posterolateral thalamus. PMID:25803613

N-acetyl-L-leucine accelerates vestibular compensation after unilateral labyrinthectomy by action in the cerebellum and thalamus.

PubMed

Günther, Lisa; Beck, Roswitha; Xiong, Guoming; Potschka, Heidrun; Jahn, Klaus; Bartenstein, Peter; Brandt, Thomas; Dutia, Mayank; Dieterich, Marianne; Strupp, Michael; la Fougère, Christian; Zwergal, Andreas

2015-01-01

An acute unilateral vestibular lesion leads to a vestibular tone imbalance with nystagmus, head roll tilt and postural imbalance. These deficits gradually decrease over days to weeks due to central vestibular compensation (VC). This study investigated the effects of i.v. N-acetyl-DL-leucine, N-acetyl-L-leucine and N-acetyl-D-leucine on VC using behavioural testing and serial [18F]-Fluoro-desoxyglucose ([18F]-FDG)-μPET in a rat model of unilateral chemical labyrinthectomy (UL). Vestibular behavioural testing included measurements of nystagmus, head roll tilt and postural imbalance as well as sequential whole-brain [18F]-FDG-μPET was done before and on days 1,3,7 and 15 after UL. A significant reduction of postural imbalance scores was identified on day 7 in the N-acetyl-DL-leucine (p < 0.03) and the N-acetyl-L-leucine groups (p < 0.01), compared to the sham treatment group, but not in the N-acetyl-D-leucine group (comparison for applied dose of 24 mg i.v. per rat, equivalent to 60 mg/kg body weight, in each group). The course of postural compensation in the DL- and L-group was accelerated by about 6 days relative to controls. The effect of N-acetyl-L-leucine on postural compensation depended on the dose: in contrast to 60 mg/kg, doses of 15 mg/kg and 3.75 mg/kg had no significant effect. N-acetyl-L-leucine did not change the compensation of nystagmus or head roll tilt at any dose. Measurements of the regional cerebral glucose metabolism (rCGM) by means of μPET revealed that only N-acetyl-L-leucine but not N-acetyl-D-leucine caused a significant increase of rCGM in the vestibulocerebellum and a decrease in the posterolateral thalamus and subthalamic region on days 3 and 7. A similar pattern was found when comparing the effect of N-acetyl-L-leucine on rCGM in an UL-group and a sham UL-group without vestibular damage. In conclusion, N-acetyl-L-leucine improves compensation of postural symptoms after UL in a dose-dependent and specific manner, most likely by activating the vestibulocerebellum and deactivating the posterolateral thalamus.

Age as a Determinant to Select an Anesthesia Method for Tympanostomy Tube Insertion in a Pediatric Population

PubMed Central

Jung, Kihwan; Kim, Hojong

2015-01-01

Background and Objectives To evaluate the relationship between age and anesthesia method used for tympanostomy tube insertion (TTI) and to provide evidence to guide the selection of an appropriate anesthesia method in children. Subjects and Methods We performed a retrospective review of children under 15 years of age who underwent tympanostomy tube insertion (n=159) or myringotomy alone (n=175) under local or general anesthesia by a single surgeon at a university-based, secondary care referral hospital. Epidermiologic data between local and general anesthesia groups as well as between TTI and myringotomy were analyzed. Medical costs were compared between local and general anesthesia groups. Results Children who received local anesthesia were significantly older than those who received general anesthesia. Unilateral tympanostomy tube insertion was performed more frequently under local anesthesia than bilateral. Logistic regression modeling showed that local anesthesia was more frequently applied in older children (odds ratio=1.041) and for unilateral tympanostomy tube insertion (odds ratio=8.990). The cut-off value of age for local anesthesia was roughly 5 years. Conclusions In a pediatric population at a single medical center, age and whether unilateral or bilateral procedures were required were important factors in selecting an anesthesia method for tympanostomy tube insertion. Our findings suggest that local anesthesia can be preferentially considered for children 5 years of age or older, especially in those with unilateral otitis media with effusion. PMID:26185791

In Vivo Imaging Reveals Significant Tumor Vascular Dysfunction and Increased Tumor Hypoxia-Inducible Factor-1α Expression Induced by High Single-Dose Irradiation in a Pancreatic Tumor Model

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

Maeda, Azusa; Department of Medical Biophysics, University of Toronto, Toronto, Ontario; Chen, Yonghong

Purpose: To investigate the effect of high-dose irradiation on pancreatic tumor vasculature and microenvironment using in vivo imaging techniques. Methods and Materials: A BxPC3 pancreatic tumor xenograft was established in a dorsal skinfold window chamber model and a subcutaneous hind leg model. Tumors were irradiated with a single dose of 4, 12, or 24 Gy. The dorsal skinfold window chamber model was used to assess tumor response, vascular function and permeability, platelet and leukocyte adhesion to the vascular endothelium, and tumor hypoxia for up to 14 days after 24-Gy irradiation. The hind leg model was used to monitor tumor size, hypoxia, and vascularitymore » for up to 65 days after 24-Gy irradiation. Tumors were assessed histologically to validate in vivo observations. Results: In vivo fluorescence imaging revealed temporary vascular dysfunction in tumors irradiated with a single dose of 4 to 24 Gy, but most significantly with a single dose of 24 Gy. Vascular functional recovery was observed by 14 days after irradiation in a dose-dependent manner. Furthermore, irradiation with 24 Gy caused platelet and leukocyte adhesion to the vascular endothelium within hours to days after irradiation. Vascular permeability was significantly higher in irradiated tumors compared with nonirradiated controls 14 days after irradiation. This observation corresponded with increased expression of hypoxia-inducible factor-1α in irradiated tumors. In the hind leg model, irradiation with a single dose of 24 Gy led to tumor growth delay, followed by tumor regrowth. Conclusions: Irradiation of the BxPC3 tumors with a single dose of 24 Gy caused transient vascular dysfunction and increased expression of hypoxia-inducible factor-1α. Such biological changes may impact tumor response to high single-dose and hypofractionated irradiation, and further investigations are needed to better understand the clinical outcomes of stereotactic body radiation therapy.« less

Therapeutic effect of meropenem on an experimental guinea pig model of meningitis with type b β-lactamase-nonproducing ampicillin-resistant Haemophilus influenzae.

PubMed

Fujimoto, Koichi; Kanazawa, Katsunori; Takemoto, Koji; Urasaki, Kokichi; Ueda, Yutaka; Ubukata, Kimiko; Sunakawa, Keisuke

2013-08-01

The purpose of this study was to investigate the relationship between efficacy and percentage of time above the MIC (%T>MIC) in the cerebrospinal fluid (CSF) for different dosing regimens of meropenem against an experimental lethal meningitis model in guinea pigs with type b β-lactamase-nonproducing ampicillin-resistant Haemophilus influenzae (Hib BLNAR). Guinea pigs were intrathecally inoculated with 10(8) CFU/head of Hib BLNAR 8 h before the start of therapy. A single dose of 20, 40, or 80 mg/kg meropenem or multiple doses of 40 mg/kg meropenem were subcutaneously administered. Numbers of bacteria in CSF were counted 8 h after the start of therapy. Meropenem concentration in serum and CSF were determined in infected guinea pigs receiving a single dose of 40 mg/kg. In the single-dose regimen, 40 and 80 mg/kg meropenem significantly reduced the number of bacteria in CSF compared with the control, but 20 mg/kg meropenem did not. The %T>MIC for an 8-h period of 20, 40, and 80 mg/kg meropenem were 41, 52, and 62, respectively. Two and four doses of 40 mg/kg meropenem, for both of which %T>MIC was calculated as 100, had similar efficacy and were significantly superior to a single-dose of 40 mg/kg. In conclusion, meropenem had high efficacy when %T>MIC in the CSF was increased because of the high dose level and shortening of the dosing interval in a guinea pig meningitis model caused by Hib BLNAR, suggesting that high and frequent doses of meropenem are useful for treatment of meningitis with Hib BLNAR.

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

Rana, S; Park, S; Zheng, Y

Purpose: The purpose of this study is to investigate the dosimetric feasibility of hypo-fractionated intensity modulated proton therapy (IMPT) for unilateral metallic prosthesis prostate cancer patients based on proton collaborative group (PCG)-GU002-10 (NCT01230866) protocol criteria. Methods: A total of five unilateral metallic prosthesis prostate cancer cases were included in this retrospective study. For each case, IMPT plans were generated for treatment to be delivered with 7.6 Gy[RBE] per fraction in 5 fractions per week for a total dose of 38 Gy(RBE). Each plan was generated using two anterior-oblique beams and one lateral beam. Treatment plans were optimized with an objectivemore » meeting PCG-GU002-10 (NCT01230866) protocol criteria: (i) planning target volume (PTV): D99.5% > 36.1 Gy[RBE], (ii) rectum: V24 < 35%, V33.6 < 10%, (iii) bladder: V39 < 8 cc, and (iv) femoral head: V23 < 1cc. Results: All five cases satisfied PTV D99.5% (average=36.82 Gy[RBE]; range, 36.36–37.13 Gy[RBE]). PTV D95% ranged from 36.66 Gy[RBE] to 38.65 Gy[RBE] and PTV V100 ranged from 95.47% to 97.95%. For the rectum, V24 was less than 35% (average=14.07 Gy[RBE]; range, 6.22–18.42%, whereas V33.6 Gy[RBE] was less than 10% (average=6.83; range, 3.06 – 9.15%). Rectal mean dose ranged from 4.22 Gy[RBE] to 9.97 Gy[RBE]. For the bladder, V39 was found to be less than 8 cc (average=3.69 cc; range, 0.19–7.68 cc). Bladder mean dose ranged from 4.22 Gy[RBE] to 18.83 Gy[RBE]. For the femoral head, V23 was 0 in all five cases. Conclusion: All five unilateral metallic prosthesis prostate cancer IMPT plans generated with one lateral and two anterior-oblique beams satisfied the dosimetric criteria of PCG-GU002-10 (NCT01230866) protocol.« less

[An outbreak of mumps in a high school: Estimation of vaccine effectiveness. Zaragoza 2011].

PubMed

Compés-Dea, Cecilia; Guimbao-Bescós, Joaquín; Gaspar-Escayola, José Ignacio; Lázaro-Belanche, María Ángeles; Aznar-Brieba, Amaya

2015-01-01

Mumps outbreaks continue to occur, even after the consolidation of vaccination programs. An outbreak of mumps occurred in a high school in Zaragoza during December 2011. To describe the outbreak and estimate vaccine effectiveness. unilateral or bilateral swelling of the parotid or other salivary glands for three or more days without any other apparent cause. People attending the 'Parque Goya' High School or with transmission chain origin in the High School. From two days before the onset of symptoms of the first case to five days after the last case. Samples were collected for virus confirmation (IgM, urine culture and oropharyngeal exudate), and isolates were processed for genotyping. A retrospective cohort study was performed in two high school classrooms to estimate vaccine efficacy. Public health authorities conducted active surveillance, isolation of cases, and vaccination of susceptible contacts. There were 27 cases. Twenty-one (77.8%) were vaccinated with two doses of Measles-Mumps-Rubella vaccine. Twelve (44%) were confirmed microbiologically. G1 genotype was determined in six cases. According to the cohort study, vaccine efficacy for one dose was 34% (95%CI: -44 to 70), and was 67% (95%CI: 28 to 83) for two doses. Vaccine effectiveness was lower than expected. Early detection and isolation of cases have been instrumental in preventing new cases in schools. Copyright © 2014 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

GDF11 induces kidney fibrosis, renal cell epithelial-to-mesenchymal transition, and kidney dysfunction and failure.

PubMed

Pons, Marianne; Koniaris, Leonidas G; Moe, Sharon M; Gutierrez, Juan C; Esquela-Kerscher, Aurora; Zimmers, Teresa A

2018-05-03

GDF11 modulates embryonic patterning and kidney organogenesis. Herein, we sought to define GDF11 function in the adult kidney and in renal diseases. In vitro renal cell lines, genetic, and murine in vivo renal injury models were examined. Among tissues tested, Gdf11 was highest in normal adult mouse kidney. Expression was increased acutely after 5/6 nephrectomy, ischemia-reperfusion injury, kanamycin toxicity, or unilateral ureteric obstruction. Systemic, high-dose GDF11 administration in adult mice led to renal failure, with accompanying kidney atrophy, interstitial fibrosis, epithelial-to-mesenchymal transition of renal tubular cells, and eventually death. These effects were associated with phosphorylation of SMAD2 and could be blocked by follistatin. In contrast, Gdf11 heterozygous mice showed reduced renal Gdf11 expression, renal fibrosis, and expression of fibrosis-associated genes both at baseline and after unilateral ureteric obstruction compared with wild-type littermates. The kidney-specific consequences of GDF11 dose modulation are direct effects on kidney cells. GDF11 induced proliferation and activation of NRK49f renal fibroblasts and also promoted epithelial-to-mesenchymal transition of IMCD-3 tubular epithelial cells in a SMAD3-dependent manner. Taken together, these data suggest that GDF11 and its downstream signals are critical in vivo mediators of renal injury. These effects are through direct actions of GDF11 on renal tubular cells and fibroblasts. Thus, regulation of GDF11 presents a therapeutic target for diseases involving renal fibrosis and impaired tubular function. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

ARE UNILATERAL AND BILATERAL KNEE OSTEOARTHRITIS PATIENTS UNIQUE SUBSETS OF KNEE OSTEOARTHRITIS? A BIOMECHANICAL PERSPECTIVE

PubMed Central

Messier, Stephen P.; Beavers, Daniel P.; Herman, Cassandra; Hunter, David J.; DeVita, Paul

2016-01-01

Objective To compare the gait of adults with unilateral and bilateral symptomatic and radiographic knee osteoarthritis (OA) to determine whether these subgroups can be treated similarly in the clinic and when recruiting for randomized clinical trials, and to use these data to generate future hypotheses regarding gait in these subsets of knee OA patients. Methods Cross-sectional investigation of patients with unilateral and bilateral knee OA on gait mechanics using 136 older adults (age ≥ 55 yrs.; 27 kg.m−2 ≥ BMI ≤ 41 kg.m−2; 82% female) with radiographic knee OA. Comparisons were made between the most affected side of the bilateral group (Bi) and the affected side of the unilateral group (Uni), and between symmetry indices of each group. Results There were no significant differences in any temporal, kinematic, or kinetic measures between the Uni and Bi cohorts. Comparison of symmetry indices between groups also revealed no significant differences. Conclusion The similarity in lower extremity mechanics between unilateral and bilateral knee OA patients is sufficiently robust to consider both subsets as a single cohort. We hypothesize that biomechanical adaptations to knee OA are at least partially systemic in origin and not based solely on the physiological characteristics of an affected knee joint. PMID:26706699

Single-dose radiation therapy for prevention of heterotopic ossification after total hip arthroplasty

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

Healy, W.L.; Lo, T.C.; Covall, D.J.

1990-12-01

Single-dose radiation therapy was prospectively evaluated for its efficacy in prevention of heterotopic ossification in patients at high risk after total hip arthroplasty. Thirty-one patients (34 hips) were treated between 1981 and 1988. Risk factors for inclusion in the protocol included prior evidence of heterotopic ossification, ankylosing spondylitis, and diffuse idiopathic skeletal hyperostosis. Patients with hypertrophic osteoarthritis or traumatic arthritis with osteophytes were not included. Operations on 34 hips included 19 primary total and 11 revision total hip arthroplasties and 4 excisions of heterotopic ossification. All patients received radiotherapy to the hip after operation with a single dose of 700more » centigray. Radiotherapy is recommended on the first postoperative day. After this single-dose radiation treatment, no patient had clinically significant heterotopic ossification. Recurrent disease developed in two hips (6%), as seen on radiography (grades 2 and 3). This series documents a 100% clinical success rate and a 94% radiographic success rate in preventing heterotopic ossification in patients at high risk after total hip arthroplasty. Single-dose radiotherapy is as effective as other radiation protocols in preventing heterotopic ossification after total hip arthroplasty. It is less expensive and easier to administer than multidose radiotherapy.« less

Importance of unilateral examination in olfactometry.

PubMed

Furukawa, M; Kamide, M; Miwa, T; Umeda, R

1988-01-01

Hyposmia, the decreased sense of smell, and anosmia, the loss of sense of smell, may be unilateral or bilateral. If the olfactory acuity examined by means of bilateral test is normal, olfactory disorders are not found; unilateral examination is therefore necessary for definite evaluation of olfactory acuity. As evidence, 7 cases out of 94 patients with chronic rhinosinusitis and 6 cases out of 12 patients who received the surgery of anterior cranial fossa showed definite different olfactory threshold between nasal cavities, and there were no patients who recognized the diminished sense of smell in spite of unilateral high olfactory threshold. Additionally, we have experienced that a patient with brain tumor was diagnosed by the help of unilateral olfactory test. We thus strongly recommend the unilateral olfactometry as a method for simple and reliable test in clinical measurement of the sense of smell.

Glutamate co-transmission from developing medial nucleus of the trapezoid body - Lateral superior olive synapses is cochlear dependent in kanamycin-treated rats

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

Lee, Jae Ho; Pradhan, Jonu; Maskey, Dhiraj

Research highlights: {yields} Glutamate co-transmission is enhanced in kanamycin-treated rats. {yields} VGLUT3 expression is increased in kanamycin-treated rats. {yields} GlyR expression is decreased in kanamycin-treated rats. {yields} GlyR, VGLUT3 expression patterns are asymmetric in unilaterally cochlear ablated rat. -- Abstract: Cochlear dependency of glutamate co-transmission at the medial nucleus of the trapezoid body (MNTB) - the lateral superior olive (LSO) synapses was investigated using developing rats treated with high dose kanamycin. Rats were treated with kanamycin from postnatal day (P) 3 to P8. A scanning electron microscopic study on P9 demonstrated partial cochlear hair cell damage. A whole cell voltagemore » clamp experiment demonstrated the increased glutamatergic portion of postsynaptic currents (PSCs) elicited by MNTB stimulation in P9-P11 kanamycin-treated rats. The enhanced VGLUT3 immunoreactivities (IRs) in kanamycin-treated rats and asymmetric VGLUT3 IRs in the LSO of unilaterally cochlear ablated rats supported the electrophysiologic data. Taken together, it is concluded that glutamate co-transmission is cochlear-dependent and enhanced glutamate co-transmission in kanamycin-treated rats is induced by partial cochlear damage.« less

ESTIMATING SYSTEMIC EXPOSURE TO ETHINYL ESTRADIOL FROM AN ORAL CONTRACEPTIVE

PubMed Central

WESTHOFF, Carolyn L.; PIKE, Malcolm C.; TANG, Rosalind; DINAPOLI, Marianne N.; SULL, Monica; CREMERS, Serge

2015-01-01

Objectives This study was conducted to compare single-dose pharmacokinetics of ethinyl estradiol in an oral contraceptive to steady-state values, and to assess whether any simpler measures could provide an adequate proxy of the ‘gold standard’ 24-hour steady-state area-under-the-curve. Identifying a simple, less expensive, measure of systemic ethinyl estradiol exposure would be useful for larger studies designed to assess the relationship between an individual’s ethinyl estradiol exposure and her side effects. Study Design We conducted a 13 samples over 24 hours pharmacokinetic analysis on day 1 and day 21 of the first cycle of a monophasic oral contraceptive containing 30 mcg ethinyl estradiol and 150 mcg levonorgestrel in 17 non-obese healthy white women. We also conducted an abbreviated single dose 9-sample pharmacokinetic analysis after a month washout. Ethinyl estradiol was measured by liquid chromatography-tandem mass spectrometry. We compared results of full 13-sample steady-state pharmacokinetic analysis with results calculated using fewer samples (9 or 5) and following the single doses. We calculated Pearson correlation coefficients to evaluate the relationships between these estimates of systemic ethinyl estradiol exposure. Results The area-under-the-curve, maximum (Cmax), and 24-hour (C24) values were similar following the two single oral contraceptive doses (area-under-the-curve, r = 0.92). The steady-state 13-sample 24-hour area-under-the-curve was highly correlated with the average 9-sample area-under-the-curve after the two single doses (r = 0.81, p = 0.0002). This correlation remained the same if the number of samples was reduced to 4, taken at time 1, 2.5, 4 and 24 hours. The C24 at steady-state was highly correlated with the 24-hour steady-state area-under-the-curve (r = 0.92, p < 0.0001). The average of the C24 values following the two single doses was also quite highly correlated with the steady-state area-under-the-curve (r = 0.72, p = 0.0026). Conclusions Limited blood sampling, including results from two single doses, gave highly correlated estimates of an oral contraceptive user’s steady-state ethinyl estradiol exposure. PMID:25511238

Behavioural Assessment of the A2a/NR2B Combination in the Unilateral 6-OHDA-Lesioned Rat Model: A New Method to Examine the Therapeutic Potential of Non-Dopaminergic Drugs

PubMed Central

Michel, Anne; Downey, Patrick; Van Damme, Xavier; De Wolf, Catherine; Schwarting, Rainer; Scheller, Dieter

2015-01-01

In Parkinson’s disease (PD), dopaminergic therapies are often associated with the development of motor complications. Attention has therefore been focused on the use of non-dopaminergic drugs. This study developed a new behavioural method capable of demonstrating the added value of combining adenosinergic and glutamatergic receptor antagonists in unilateral 6-OHDA lesioned rats. Rats were dosed orally with Tozadenant, a selective A2A receptor antagonist, and three different doses of Radiprodil, an NR2B-selective NMDA receptor antagonist. The drugs were given alone or in combination and rats were placed in an open-field for behavioural monitoring. Video recordings were automatically analysed. Five different behaviours were scored: distance traveled, ipsi- and contraversive turns, body position, and space occupancy. The results show that A2A or NR2B receptor antagonists given alone or in combination did not produce enhanced turning as observed with an active dose of L-Dopa/benserazide. Instead the treated rats maintained a straight body position, were able to shift from one direction to the other and occupied a significantly larger space in the arena. The highest “Tozadenant/Radiprodil” dose combination significantly increased all five behavioural parameters recorded compared to rats treated with vehicle or the same doses of the drugs alone. Our data suggest that the A2A/NR2B antagonist combination may be able to stimulate motor activity to a similar level as that achieved by L-Dopa but in the absence of the side-effects that are associated with dopaminergic hyperstimulation. If these results translate into the clinic, this combination could represent an alternative symptomatic treatment option for PD. PMID:26322641

Association of HTRA1 polymorphism and bilaterality in advanced age-related macular degeneration.

PubMed

Chen, Haoyu; Yang, Zhenglin; Gibbs, Daniel; Yang, Xian; Hau, Vincent; Zhao, Peiquan; Ma, Xiang; Zeng, Jiexi; Luo, Ling; Pearson, Erik; Constantine, Ryan; Kaminoh, Yuuki; Harmon, Jennifer; Tong, Zongzhong; Stratton, Charity A; Cameron, D Joshua; Tang, Shibo; Zhang, Kang

2008-02-01

Single nucleotide polymorphism (SNP), rs11200638, in the promoter of HTRA1 has recently been shown to increase the risk for AMD. In order to investigate the association of this HTRA1 polymorphism and the bilaterality of AMD, we genotyped rs11200638 in control, unilateral, and bilateral advanced AMD patients. The A allele for SNP rs11200638 in HTRA1, was significantly more prevalent in bilateral wet AMD and GA patients than in unilateral groups (p=.02 and p=.03, respectively). The homozygote odds ratios of bilateral wet AMD and GA are significantly greater than those seen in unilateral groups (twofold and threefold increase, respectively). This finding is consistent with the role of HTRA1 in AMD pathogenesis and will help aid in the clinical management and prognosis of AMD patients.

Human cortical activity related to unilateral movements. A high resolution EEG study.

PubMed

Urbano, A; Babiloni, C; Onorati, P; Babiloni, F

1996-12-20

In the present study a modern high resolution electroencephalography (EEG) technique was used to investigate the dynamic functional topography of human cortical activity related to simple unilateral internally triggered finger movements. The sensorimotor area (M1-S1) contralateral to the movement as well as the supplementary motor area (SMA) and to a lesser extent the ipsilateral M1-S1 were active during the preparation and execution of these movements. These findings suggest that both hemispheres may cooperate in both planning and production of simple unilateral volitional acts.

ASSESSMENT OF VISUAL FUNCTION AND RETINAL STRUCTURE FOLLOWING ACUTE LIGHT EXPOSURE IN THE LIGHT SENSITIVE T4R RHODOPSIN MUTANT DOG

PubMed Central

Iwabe, Simone; Ying, Gui-Shuang; Aguirre, Gustavo D.; Beltran, William A.

2016-01-01

The effect of acute exposure to various intensities of white light on visual behavior and retinal structure was evaluated in the T4R RHO dog, a naturally-occurring model of autosomal dominant retinitis pigmentosa due to a mutation in the Rhodopsin gene. A total of 14 dogs (ages: 4–5.5 months) were used in this study: 3 homozygous mutant RHOT4R/T4R, 8 heterozygous mutant RHOT4R/+, and 3 normal wild-type (WT) dogs. Following overnight dark adaptation, the left eyes were acutely exposed to bright white light with a monocular Ganzfeld dome, while the contralateral right eye was shielded. Each of the 3 homozygous (RHOT4R/T4R) mutant dogs had a single unilateral light exposure (LE) to a different (low, moderate, and high) dose of white light (corneal irradiance/illuminance: 0.1 mW/cm2, 170 lux; 0.5 mW/cm2, 820 lux; or 1 mW/cm2, 1590 lux) for 1min. All 8 heterozygous (RHOT4R/+) mutant dogs were exposed once to the same moderate dose of light. The 3 WT dogs had their left eyes exposed 1, 2, or 3 times to the same highest dose of light. Visual function prior to LE and at 2 weeks and 33 weeks after exposure was objectively assessed in the RHOT4R/T4R and WT dogs by using an obstacle-avoidance course. Transit time through the obstacle course was measured under different scotopic to photopic ambient illuminations. Morphological retinal changes were evaluated by non-invasive in vivo cSLO/sdOCT imaging and histology before and at several time-points (2–36 weeks) after light exposure. The analysis of the transit time through the obstacle course showed that no differences were observed in any of mutant or WT dogs at 2 weeks and 33 weeks post LE. The RHOT4R/T4R retina exposed to the lowest dose of white light showed no obvious changes in ONL thickness at 2 weeks, but mild decrease was noted 36 weeks after LE. The RHOT4R/T4R retina that received a moderate dose (showed an obvious decrease in ONL thickness along the superior and temporal meridians at 2 weeks post LE with more severe damage at 36 weeks post LE in all four meridians. The RHOT4R/T4R retina exposed to the high dose showed at 2 weeks after LE extensive ONL damage in all four meridians. This light intensity did not cause any retinal damage in WT dogs even after repeated (up to 3) LE. Analysis of ONL thickness in heterozygous mutant dogs exposed to the moderate dose of light confirmed the increased sensitivity to light damage of the superior/tapetal retina, and the occurrence of an ongoing cell death process several weeks after the acute LE. In conclusion, a short single exposure to a dose of white light that is not retinotoxic in WT dogs causes in the T4R RHO retina an acute loss of ONL in the central to mid peripheral region that keeps progressing over the course of several weeks. However, this severe retinal damage does not affect visual behavior presumably because of islands of surviving photoreceptors found in the area centralis including the newly discovered canine fovea-like area, and the lack of damage to peripheral photoreceptors. PMID:27085210

Dose rate effect on micronuclei induction in human blood lymphocytes exposed to single pulse and multiple pulses of electrons.

PubMed

Acharya, Santhosh; Bhat, N N; Joseph, Praveen; Sanjeev, Ganesh; Sreedevi, B; Narayana, Y

2011-05-01

The effects of single pulses and multiple pulses of 7 MV electrons on micronuclei (MN) induction in cytokinesis-blocked human peripheral blood lymphocytes (PBLs) were investigated over a wide range of dose rates per pulse (instantaneous dose rate). PBLs were exposed to graded doses of 2, 3, 4, 6, and 8 Gy of single electron pulses of varying pulse widths at different dose rates per pulse, ranging from 1 × 10(6) Gy s(-1) to 3.2 × 10(8) Gy s(-1). Different dose rates per pulse were achieved by changing the dose per electron pulse by adjusting the beam current and pulse width. MN yields per unit absorbed dose after irradiation with single electron pulses were compared with those of multiple pulses of electrons. A significant decrease in the MN yield with increasing dose rates per pulse was observed, when dose was delivered by a single electron pulse. However, no reduction in the MN yield was observed when dose was delivered by multiple pulses of electrons. The decrease in the yield at high dose rates per pulse suggests possible radical recombination, which leads to decreased biological damage. Cellular response to the presence of very large numbers of chromosomal breaks may also alter the damage.

A systematic review of effectiveness and safety of different regimens of levonorgestrel oral tablets for emergency contraception.

PubMed

Shohel, Mohammad; Rahman, Mohammad Mahfuzur; Zaman, Asif; Uddin, Mir Muhammad Nasir; Al-Amin, Md Mamun; Reza, Hasan Mahmud

2014-04-04

Unintended pregnancy is a complex phenomenon which raise to take an emergency decision. Low contraceptive prevalence and high user failure rates are the leading causes of this unexpected situation. High user failure rates suggest the vital role of emergency contraception to prevent unplanned pregnancy. Levonorgestrel - a commonly used progestin for emergency contraception. However, little is known about its pharmacokinetics and optimal dose for use. Hence, there is a need to conduct a systematic review of the available evidences. Randomized, double-blind trials were sought, evaluating healthy women with regular menstrual cycles, who requested emergency contraception within 72 h of unprotected coitus, to one of three regimens: 1.5 mg single dose levonorgestrel, two doses of 0.75 mg levonorgestrel given 12 h apart or two doses of 0.75 mg levonorgestrel given 24 h apart. The primary outcome was unintended pregnancy; other outcomes were side-effects and timing of next menstruation. Every trial under consideration successfully established the contraceptive effectiveness of levonorgestrel for preventing unintended pregnancy. Moreover, a single dose of levonorgestrel 1.5 mg for emergency contraception supports its safety and efficacy profile. If two doses of levonorgestrel 0.75 mg are intended for administration, the second dose can positively be taken 12-24 h after the first dose without compromising its contraceptive efficacy. The main side effect was frequent menstrual irregularities. No serious adverse events were reported. The review shows that, emergency contraceptive regimen of single-dose levonorgestrel is not inferior in efficacy to the two-dose regimen. All the regimens studied were very efficacious for emergency contraception and prevented a high proportion of pregnancies if taken within 72 h of unprotected coitus. Single levonorgestrel dose (1.5 mg) can substitute two 0.75 mg doses 12 or 24 h apart. With either regimen, the earlier the treatment is given, the more effective it seems to be.

A systematic review of effectiveness and safety of different regimens of levonorgestrel oral tablets for emergency contraception

PubMed Central

2014-01-01

Background Unintended pregnancy is a complex phenomenon which raise to take an emergency decision. Low contraceptive prevalence and high user failure rates are the leading causes of this unexpected situation. High user failure rates suggest the vital role of emergency contraception to prevent unplanned pregnancy. Levonorgestrel - a commonly used progestin for emergency contraception. However, little is known about its pharmacokinetics and optimal dose for use. Hence, there is a need to conduct a systematic review of the available evidences. Methods Randomized, double-blind trials were sought, evaluating healthy women with regular menstrual cycles, who requested emergency contraception within 72 h of unprotected coitus, to one of three regimens: 1.5 mg single dose levonorgestrel, two doses of 0.75 mg levonorgestrel given 12 h apart or two doses of 0.75 mg levonorgestrel given 24 h apart. The primary outcome was unintended pregnancy; other outcomes were side-effects and timing of next menstruation. Results Every trial under consideration successfully established the contraceptive effectiveness of levonorgestrel for preventing unintended pregnancy. Moreover, a single dose of levonorgestrel 1.5 mg for emergency contraception supports its safety and efficacy profile. If two doses of levonorgestrel 0.75 mg are intended for administration, the second dose can positively be taken 12–24 h after the first dose without compromising its contraceptive efficacy. The main side effect was frequent menstrual irregularities. No serious adverse events were reported. Conclusions The review shows that, emergency contraceptive regimen of single-dose levonorgestrel is not inferior in efficacy to the two-dose regimen. All the regimens studied were very efficacious for emergency contraception and prevented a high proportion of pregnancies if taken within 72 h of unprotected coitus. Single levonorgestrel dose (1.5 mg) can substitute two 0.75 mg doses 12 or 24 h apart. With either regimen, the earlier the treatment is given, the more effective it seems to be. PMID:24708837

Comparison between Unilateral and Bilateral Plyometric Training on Single and Double Leg Jumping Performance and Strength.

PubMed

Bogdanis, Gregory C; Tsoukos, Athanasios; Kaloheri, Olga; Terzis, Gerasimos; Veligekas, Panagiotis; Brown, Lee E

2017-04-18

This study compared the effects of unilateral and bilateral plyometric training on single and double-leg jumping performance, maximal strength and rate of force development (RFD). Fifteen moderately trained subjects were randomly assigned to either a unilateral (U, n=7) or bilateral group (B, n=8). Both groups performed maximal effort plyometric leg exercises two times per week for 6 weeks. The B group performed all exercises with both legs, while the U group performed half the repetitions with each leg, so that total exercise volume was the same. Jumping performance was assessed by countermovement jumps (CMJ) and drop jumps (DJ), while maximal isometric leg press strength and RFD were measured before and after training for each leg separately and both legs together. CMJ improvement with both legs was not significantly different between U (12.1±7.2%) and B (11.0±5.5%) groups. However, the sum of right and left leg CMJ only improved in the U group (19.0±7.1%, p<0.001) and was unchanged in the B group (3.4±8.4%, p=0.80). Maximal isometric leg press force with both legs was increased similarly between groups (B: 20.1±6.5%, U: 19.9±6.2%). However, the sum of right and left leg maximal force increased more in U compared to B group (23.8±9.1% vs. 11.9±6.2%, p=0.009, respectively). Similarly, the sum of right and left leg RFD0-50 and RFD0-100 were improved only in the U group (34-36%, p<0.01). Unilateral plyometric training was more effective at increasing both single and double-leg jumping performance, isometric leg press maximal force and RFD when compared to bilateral training.

Position Sense in Chronic Pain: Separating Peripheral and Central Mechanisms in Proprioception in Unilateral Limb Pain.

PubMed

Tsay, Anthony J; Giummarra, Melita J

2016-07-01

Awareness of limb position is derived primarily from muscle spindles and higher-order body representations. Although chronic pain appears to be associated with motor and proprioceptive disturbances, it is not clear if this is due to disturbances in position sense, muscle spindle function, or central representations of the body. This study examined position sense errors, as an indicator of spindle function, in participants with unilateral chronic limb pain. The sample included 15 individuals with upper limb pain, 15 with lower limb pain, and 15 sex- and age-matched pain-free control participants. A 2-limb forearm matching task in blindfolded participants, and a single-limb pointer task, with the reference limb hidden from view, was used to assess forearm position sense. Position sense was determined after muscle contraction or stretch, intended to induce a high or low spindle activity in the painful and nonpainful limbs, respectively. Unilateral upper and lower limb chronic pain groups produced position errors comparable with healthy control participants for position matching and pointer tasks. The results indicate that the painful and nonpainful limb are involved in limb-matching. Lateralized pain, whether in the arm or leg, does not influence forearm position sense. Painful and nonpainful limbs are involved in bilateral limb-matching. Muscle spindle function appears to be preserved in the presence of chronic pain. Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

Relationship between selected measures of strength and hip and knee excursion during unilateral and bilateral landings in women.

PubMed

McCurdy, Kevin; Walker, John; Armstrong, Rusty; Langford, George

2014-09-01

The purpose of this study was to compare the relationship between several measures of single-joint, isometric, eccentric, and squat strength and unilateral and bilateral landing mechanics at the hip and knee in women. Twenty six healthy female subjects with previous athletic experience (height, 165.1 ± 7.01 cm; mass, 60.91 ± 7.14 kg; age, 20.9 ± 1.62 years) participated in this study. Hip and knee mechanics were measured using the MotionMonitor capture system (Innovative Sports Training, Inc.) with 3-dimensional electromagnetic sensors during bilateral (60 cm) and unilateral drop jumps (30 cm). On a separate day, isometric hip extension, external rotation, and abduction strength (lbs) were measured using a handheld dynamometer (Hoggan Health Industries, Inc.). Eccentric and isometric knee strength were measured on the Biodex IV Isokinetic Dynamometer (Biodex Medical Systems, Inc.). Free weight was used to measure the bilateral squat and a modified single-leg squat. The strongest correlations were found between squat strength and knee valgus (-0.77 ≤ r ≤ -0.83) and hip adduction (-0.5 ≤ r ≤ -0.65). After controlling for squat strength, hip external rotation strength and unilateral knee valgus (-0.41), hip abduction strength and bilateral knee valgus (-0.43), and knee flexion strength and bilateral hip adduction (-0.57) remained significant. Eccentric knee flexion strength and unilateral knee internal rotation was the only significant correlation for eccentric strength (-0.40). Squat strength seems to be the best predictor of knee valgus and was consistently related to hip adduction. Isometric and eccentric measures demonstrated few significant correlations with hip and knee excursion while demonstrating a low-to-moderate relationship. Hip and knee flexion and rotation do not seem to be related to strength. Squat strength should receive consideration during risk assessment for noncontact knee injury.

Integration of an Axcelis Optima HD Single Wafer High Current Implanter for p- and n-S/D Implants in an Existing Batch Implanter Production Line

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

Schmeide, Matthias; Kontratenko, Serguei; Krimbacher, Bernhard

2008-11-03

This paper is focused on the integration and qualification of an Axcelis Optima HD single wafer high current spot beam implanter in an existing 200 mm production line with different types of Axcelis batch implanters for high current applications. Both the design of the beamline and the beam shape are comparable between single wafer and batch high current spot beam implanters. In contrast to the single wafer high current ribbon beam implanter, energy contamination is not a concern for the considered spot beam tool because the drift mode can be used down to energies in the 2 keV region. Themore » most important difference between single wafer and batch high current implanters is the significantly higher dose rate and, therefore, the higher damage rate for the single wafer tool due to the different scanning architecture. The results of the integration of high dose implantations, mainly for p- and n-S/D formation, for DRAM 110 nm without pre-amorphization implantation (PAI), CMOS Logic from around 250 nm down to 90 nm without and with PAI, are presented and discussed. Dopant concentration profile analysis using SIMS was performed for different technologies and implantation conditions. The impurity activation was measured using sheet resistance and in some cases spreading resistance technique was applied. The amorphous layer thickness was measured using TEM. Finally, device data are presented in combination with dose, energy and beam current variations. The results have shown that the integration of implantation processes into crystalline structure without PAI is more complex and time consuming than implantations into amorphous layer where the damage difference due to the different dose rates is negligible.« less

Comparison of the Pharmacokinetics of Droxidopa After Dosing in the Fed Versus Fasted State and with 3-Times-Daily Dosing in Healthy Elderly Subjects.

PubMed

Chen, Jack J; Hewitt, L Arthur

2018-03-01

Droxidopa is an oral prodrug of norepinephrine approved for the treatment of symptomatic neurogenic orthostatic hypotension. This two-part, randomized, crossover study evaluated the 24-h pharmacokinetic profile of droxidopa in 24 healthy elderly subjects. Noncompartmental analysis was used to calculate the area under the plasma concentration-time curve (AUC), maximum plasma concentration (C max ), time of C max (t max ), and elimination half-life (t ½e ) of droxidopa and metabolites. Droxidopa was administered in the fed (high-fat/high-calorie meal) or fasted state either as a single 300-mg dose (three 100-mg capsules) or 3 times/day (TID) (three 100-mg capsules) at 4-h intervals. Administration of a single droxidopa dose in the fed versus fasted state decreased mean C max (2057 vs 3160 ng/mL) and mean AUC (10,927 vs 13,857 h × ng/mL) and increased median t max twofold (4.00 vs 2.00 h). Differences between the fed and fasted state for mean t ½e (2.58 vs 2.68 h) were not observed. Fed versus fasted geometric mean ratios for C max and AUC were 66% [90% confidence interval (CI) 60.7-71.7] and 80% (90% CI 72.6-88.1), respectively. With TID dosing, similar values for C max were observed after each dose (range 2789-3389 ng/mL) with no return to baseline between doses. Norepinephrine C max was 895 pg/mL following dose 1, with no further increases upon subsequent doses; norepinephrine levels remained above baseline for 12-16 h after dose 1. Absorption of a single dose of droxidopa is slowed after a high-fat/high-calorie meal; for consistent effect, administer droxidopa in the same manner (with or without food). Pharmacokinetic parameters of droxidopa are similar after single and TID dosing. ClinicalTrials.gov Identifier: NCT01149629.

Lengthening Temporalis Myoplasty for Single-Stage Smile Reconstruction in Children with Facial Paralysis.

PubMed

Panossian, Andre

2016-04-01

Free muscle transfer for dynamic smile reanimation in facial paralysis is not always predictable with regard to cosmesis. Hospital stays range from 5 to 7 days. Prolonged operative times, longer hospital stays, and excessive cheek bulk are associated with free flap options. Lengthening temporalis myoplasty offers single-stage smile reanimation with theoretical advantages over free tissue transfer. From 2012 to 2014, 18 lengthening temporalis myoplasties were performed in 14 children for smile reconstruction. A retrospective chart review was completed for demographics, operative times, length of hospital stay, and perioperative complications. Fourteen consecutive patients with complete facial paralysis were included. Four patients underwent single-stage bilateral reconstruction, and 10 underwent unilateral procedures. Diagnoses included Möbius syndrome (n = 5), posterior cranial fossa tumors (n = 4), posttraumatic (n = 2), hemifacial microsomia (n = 1), and idiopathic (n = 2). Average patient age was 10.1 years. Average operative time was 410 minutes (499 minutes for bilateral lengthening temporalis myoplasty and 373 for unilateral lengthening temporalis myoplasty). Average length of stay was 3.3 days (4.75 days for bilateral lengthening temporalis myoplasty and 2.8 for unilateral lengthening temporalis myoplasty). Nine patients required minor revisions. Lengthening temporalis myoplasty is a safe alternative to free tissue transfer for dynamic smile reconstruction in children with facial paralysis. Limited donor-site morbidity, shorter operative times, and shorter hospital stays are some benefits over free flap options. However, revisions are required frequently secondary to tendon avulsions and adhesions. Therapeutic, IV.

Single Dose Versus 3 Doses of Intramuscular Benzathine Penicillin for Early Syphilis in HIV: A Randomized Clinical Trial.

PubMed

Andrade, Roberto; Rodriguez-Barradas, Maria C; Yasukawa, Kosuke; Villarreal, Erick; Ross, Michael; Serpa, Jose A

2017-03-15

Patients coinfected with syphilis and human immunodeficiency virus (HIV) may have a slower decrease in rapid plasma reagin (RPR) titers. Currently a single dose of 2.4 million units of intramuscular benzathine penicillin G (BPG) is recommended for the treatment of early syphilis. Some observational studies have suggested that this regimen may lead to high failure rates in coinfected patients. We conducted an open-label randomized clinical trial to compare the efficacy of single-dose and 3-dose regimens of BPG for the treatment of early syphilis in HIV-infected individuals. RPR titers were monitored every 3 months. Treatment success was defined as a decrease in RPR titers of ≥2 dilutions (4-fold) during a 12-month follow-up period. Sixty-four patients were included. In the intention-to-treat analysis, treatment success rates were 80% (28 of 35 subjects) and 93% (27 of 29 subjects) in the single-dose and 3-dose regimens, respectively (absolute difference, 13% [95% confidence interval {CI}, -5% to 30%; P = .17). In the per-protocol analysis, success rates were 93% (27 of 29) and 100% in the single-dose and 3-dose regimens, respectively (absolute difference, 7% [95% CI, -7% to 22%]; P = .49). CD4 T-cell count, RPR titer and syphilis stage did not affect treatment results. When compared with a single dose of BPG, a 3-dose regimen did not improve syphilis serological outcomes. Our results support the Centers for Disease Control and Prevention recommendation of a single dose of BPG in HIV-infected patients with early syphilis. NCT02611765. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Relationships of Muscle Function and Subjective Knee Function in Patients After ACL Reconstruction.

PubMed

Bodkin, Stephan; Goetschius, John; Hertel, Jay; Hart, Joe

2017-07-01

After anterior cruciate ligament reconstruction (ACLR), relationships between objective measures of muscle function and patient-reported outcomes may change over time. Examining these measures at different time frames after surgery may help develop individualized approaches to improve post-ALCR analysis. To examine the associations between subjective knee function and lower-extremity muscle function in individual patients at various time points after ACLR. Descriptive laboratory study. Fifty-one participants who underwent primary, unilateral ACLR (15 males, 36 females; mean age, 22.9 ± 4.5 years; mean height, 172.4 ± 10.1 cm; mean weight, 68.7 ± 13.1 kg) were separated into 3 groups depending on time since surgery (early, <2 years; middle, 2-5 years; late, >5 years). Subjective knee function was quantified using the International Knee Documentation Committee (IKDC) subjective knee form and the Knee injury and Osteoarthritis Outcome Score (KOOS). Isometric knee extension and flexion strength were collected at 90 deg/s. Single-leg hop performance was measured using the single hop, triple hop, cross-over hop, and 6-m timed hop. Coefficient correlations were calculated between subjective knee function and objective measures of muscle function for each group. The early group demonstrated moderate correlations between the KOOS and unilateral measures of flexion peak torque ( r = 0.514, P = .035) and flexion power ( r = 0.54, P = .027). The middle group demonstrated the strongest correlations between the KOOS and symmetry measures of the single hop ( r = 0.69, P = .002) and extension work ( r = 0.71, P = .002) as well as unilateral measures of the triple hop ( r = 0.52, P = .034) and extension work ( r = 0.66, P = .004). The late group demonstrated strong correlations between the 6-m timed hop symmetry and the IKDC ( r = 0.716, P = .001) and KOOS ( r = 0.71, P = .001). Patients with a post-ACLR status of less than 2 years exhibited stronger relationships with unilateral strength measures to subjective function; graft type was found to change these relationships. Patients at 2 to 5 years postsurgery demonstrated relationships with both unilateral and symmetry measures of muscle function to subjective function. Patients who were more than 5 years after ACLR exhibited strong associations between hopping symmetry and subjective function. Future clinical guidelines for patients after ACLR may need to consider time since surgery as a potential factor.

Surgical treatment of unilateral condylar hyperplasia with piezosurgery.

PubMed

Chiarini, Luigi; Albanese, Massimo; Anesi, Alexandre; Galzignato, Pier-Francesco; Mortellaro, Carmen; Nocini, Pierfrancesco; Bertossi, Dario

2014-05-01

Unilateral condylar hyperplasia (UCH) is a disorder of unknown etiology mainly seen in growing patients, which results in facial asymmetry. High condylectomy alone or in association with orthognathic surgery can improve the occlusion and the facial aesthetics. Between 2005 and 2012, a total of 5 patients underwent high condylectomy for UCH using a piezoelectric cutting device. All patients were treated postoperatively with functional rehabilitation. The long-term follow-up showed that all patients had a satisfactory temporomandibular joint articular function associated with stable occlusion without any recurrence of further condylar growth. High condylectomy in the surgical treatment of unilateral UCH seems to be the procedure of choice in growing patients. The use of a piezoelectric cutting device allows a safe and less invasive high condylectomy.

Pharmacokinetics of sulfamethoxazole and trimethoprim in Pacific white shrimp, Litopenaeus vannamei, after oral administration of single-dose and multiple-dose.

PubMed

Ma, Rongrong; Wang, Yuan; Zou, Xiong; Hu, Kun; Sun, Beibei; Fang, Wenhong; Fu, Guihong; Yang, Xianle

2017-06-01

The tissue distribution and depletion of sulfamethoxazole (SMZ) and trimethoprim (TMP) were studied in Pacific white shrimp, Litopenaeus vannamei, after single-dose and multiple-dose oral administration of SMZ-TMP (5:1) via medicated feed. In single-dose oral administration, shrimps were fed once at a dose of 100 mg/kg (drug weight/body weight). In multiple-dose oral administration, shrimps were fed three times a day for three consecutive days at a dose of 100mg/kg. The results showed the kinetic characteristic of SMZ was different from TMP in Pacific white shrimp. In the single-dose administration, the SMZ was widely distributed in the tissues, while TMP was highly concentrated in the hepatopancreas. The t 1/2z values of SMZ were larger and persist longer than TMP in Pacific white shrimp. In the multiple-dose administration, SMZ accumulated well in the tissues, and reached steady state level after successive administrations, while TMP did not. TMP concentration even appeared the downward trend with the increase of drug times. Compared with the single dose, the t 1/2z values of SMZ in hepatopancreas (8.22-11.33h) and muscle (6.53-10.92h) of Pacific white shrimps rose, but the haemolymph dropped (13.76-11.03) in the multiple-dose oral administration. Meanwhile, the corresponding values of TMP also rose in hepatopancreas (4.53-9.65h) and muscle (2.12-2.71h), and declined in haemolymph (7.38-5.25h) following single-dose and multiple-dose oral administration in Pacific white shrimps. In addition, it is worth mentioning that the ratios of SMZ and TMP were unusually larger than the general aim ratio. Copyright © 2017 Elsevier B.V. All rights reserved.

Single-dose replication-defective VSV-based Nipah virus vaccines provide protection from lethal challenge in Syrian hamsters.

PubMed

Lo, Michael K; Bird, Brian H; Chattopadhyay, Anasuya; Drew, Clifton P; Martin, Brock E; Coleman, Joann D; Rose, John K; Nichol, Stuart T; Spiropoulou, Christina F

2014-01-01

Nipah virus (NiV) continues to cause outbreaks of fatal human encephalitis due to spillover from its bat reservoir. We determined that a single dose of replication-defective vesicular stomatitis virus (VSV)-based vaccine vectors expressing either the NiV fusion (F) or attachment (G) glycoproteins protected hamsters from over 1000 times LD50 NiV challenge. This highly effective single-dose protection coupled with an enhanced safety profile makes these candidates ideal for potential use in livestock and humans. Published by Elsevier B.V.

Pharmacokinetics and Bioavailability of Plant Lignan 7-Hydroxymatairesinol and Effects on Serum Enterolactone and Clinical Symptoms in Postmenopausal Women: A Single-Blinded, Parallel, Dose-Comparison Study

PubMed Central

Udani, Jay K.; Brown, Donald J.; Tan, Maria Olivia C.; Hardy, Mary

2013-01-01

Objective 7-Hydroxymaitairesinol (7-HMR) is a naturally occurring plant lignan found in whole grains and the Norway spruce (Piciea abies). The purpose of this study was to evaluate the bioavailability of a proprietary 7-HMR product (HMRlignan, Linnea SA, Locarno, Switzerland) through measurement of lignan metabolites and metabolic precursors. Methods A single-blind, parallel, pharmacokinetic and dose-comparison study was conducted on 22 post-menopausal females not receiving hormone replacement therapy. Subjects were enrolled in either a 36 mg/d (low-dose) or 72 mg/d dose (high-dose) regimen for 8 weeks. Primary measured outcomes included plasma levels of 7-HMR and enterolactone (ENL), and single-dose pharmacokinetic analysis was performed on a subset of subjects in the low-dose group. Safety data and adverse event reports were collected as well as data on hot flash frequency and severity. Results Pharmacokinetic studies demonstrated 7-HMR Cmax = 757.08 ng/ml at 1 hour and ENL Cmax = 4.8 ng/ml at 24 hours. From baseline to week 8, plasma 7-HMR levels increased by 191% in the low-dose group (p < 0.01) and by 1238% in the high-dose group (p < 0.05). Plasma ENL levels consistently increased as much as 157% from baseline in the low-dose group and 137% in the high-dose group. Additionally, the mean number of weekly hot flashes decreased by 50%, from 28.0/week to 14.3/week (p < 0.05) in the high-dose group. No significant safety issues were identified in this study. Conclusion The results demonstrate that HMRlignan is quickly absorbed into the plasma and is metabolized to ENL in healthy postmenopausal women. Clinically, the data demonstrate a statistically significant improvement in hot flash frequency. Doses up to 72 mg/d HMRlignan for 8 weeks were safe and well tolerated in this population. PMID:24606716

Pharmacokinetics and bioavailability of plant lignan 7-hydroxymatairesinol and effects on serum enterolactone and clinical symptoms in postmenopausal women: a single-blinded, parallel, dose-comparison study.

PubMed

Udani, Jay K; Brown, Donald J; Tan, Maria Olivia C; Hardy, Mary

2013-01-01

7-Hydroxymaitairesinol (7-HMR) is a naturally occurring plant lignan found in whole grains and the Norway spruce (Piciea abies). The purpose of this study was to evaluate the bioavailability of a proprietary 7-HMR product (HMRlignan, Linnea SA, Locarno, Switzerland) through measurement of lignan metabolites and metabolic precursors. A single-blind, parallel, pharmacokinetic and dose-comparison study was conducted on 22 postmenopausal females not receiving hormone replacement therapy. Subjects were enrolled in either a 36 mg/d (low-dose) or 72 mg/d dose (high-dose) regimen for 8 weeks. Primary measured outcomes included plasma levels of 7-HMR and enterolactone (ENL), and single-dose pharmacokinetic analysis was performed on a subset of subjects in the low-dose group. Safety data and adverse event reports were collected as well as data on hot flash frequency and severity. Pharmacokinetic studies demonstrated 7-HMR C max = 757.08 ng/ml at 1 hour and ENL C max = 4.8 ng/ml at 24 hours. From baseline to week 8, plasma 7-HMR levels increased by 191% in the low-dose group (p < 0.01) and by 1238% in the high-dose group (p < 0.05). Plasma ENL levels consistently increased as much as 157% from baseline in the low-dose group and 137% in the high-dose group. Additionally, the mean number of weekly hot flashes decreased by 50%, from 28.0/week to 14.3/week (p < 0.05) in the high-dose group. No significant safety issues were identified in this study. The results demonstrate that HMRlignan is quickly absorbed into the plasma and is metabolized to ENL in healthy postmenopausal women. Clinically, the data demonstrate a statistically significant improvement in hot flash frequency. Doses up to 72 mg/d HMRlignan for 8 weeks were safe and well tolerated in this population.

Induction of cleft palate in newborn pigs by maternal ingestion of poison hemlock (Conium maculatum).

PubMed

Panter, K E; Keeler, R F; Buck, W B

1985-06-01

Cleft palates were induced in newborn pigs of gilts fed Conium maculatum seed or plant during gestation days 30 through 45. Twelve of 23 newborn pigs born to 3 gilts given Utah-grown C maculatum seed and 9 of 12 newborn pigs born to a single gilt given the fresh Utah spring-growth C maculatum plant had cleft palates. The cleft palates ranged from a unilateral cleft, involving only 1 side of the palate, to a full bilateral cleft. Brachygnathia was also observed in some of these newborn pigs with cleft palate. Other malformations were not observed. Chemical analysis of seed and plant samples indicated that gamma-coniceine was the responsible teratogenic alkaloid. A daily dose of plant or seed that provided greater than or equal to 1.07 mg of gamma-coniceine/kg of body weight fed to gilts during the 30th through the 45th day of pregnancy resulted in teratogenic effects.

Bilateral and multiple cavitation sounds during upper cervical thrust manipulation

PubMed Central

2013-01-01

Background The popping produced during high-velocity, low-amplitude (HVLA) thrust manipulation is a common sound; however to our knowledge, no study has previously investigated the location of cavitation sounds during manipulation of the upper cervical spine. The primary purpose was to determine which side of the spine cavitates during C1-2 rotatory HVLA thrust manipulation. Secondary aims were to calculate the average number of pops, the duration of upper cervical thrust manipulation, and the duration of a single cavitation. Methods Nineteen asymptomatic participants received two upper cervical thrust manipulations targeting the right and left C1-2 articulation, respectively. Skin mounted microphones were secured bilaterally over the transverse process of C1, and sound wave signals were recorded. Identification of the side, duration, and number of popping sounds were determined by simultaneous analysis of spectrograms with audio feedback using custom software developed in Matlab. Results Bilateral popping sounds were detected in 34 (91.9%) of 37 manipulations while unilateral popping sounds were detected in just 3 (8.1%) manipulations; that is, cavitation was significantly (P < 0.001) more likely to occur bilaterally than unilaterally. Of the 132 total cavitations, 72 occurred ipsilateral and 60 occurred contralateral to the targeted C1-2 articulation. In other words, cavitation was no more likely to occur on the ipsilateral than the contralateral side (P = 0.294). The mean number of pops per C1-2 rotatory HVLA thrust manipulation was 3.57 (95% CI: 3.19, 3.94) and the mean number of pops per subject following both right and left C1-2 thrust manipulations was 6.95 (95% CI: 6.11, 7.79). The mean duration of a single audible pop was 5.66 ms (95% CI: 5.36, 5.96) and the mean duration of a single manipulation was 96.95 ms (95% CI: 57.20, 136.71). Conclusions Cavitation was significantly more likely to occur bilaterally than unilaterally during upper cervical HVLA thrust manipulation. Most subjects produced 3–4 pops during a single rotatory HVLA thrust manipulation targeting the right or left C1-2 articulation; therefore, practitioners of spinal manipulative therapy should expect multiple popping sounds when performing upper cervical thrust manipulation to the atlanto-axial joint. Furthermore, the traditional manual therapy approach of targeting a single ipsilateral or contralateral facet joint in the upper cervical spine may not be realistic. PMID:23320608

Corpus luteum function following single and double ovulation during estrous cycle in Sanjabi ewes.

PubMed

Shabankareh, H Karami; Habibizad, J; Torki, M

2009-09-01

This study compared the effect of double and single ovulation on serum progesterone concentrations and luteal characteristics in Sanjabi ewes at different days of the estrous cycle. The estrous cycles of 197 Sanjabi ewes were synchronized by a 12-day treatment with intravaginal sponges (Chronogest). Estrus was detected in 144 ewes 27-39 h after sponge removal. Daily blood samples were taken every morning and analyzed for serum progesterone (P4). Ewes were then transported to a local abattoir, where nine ewes were slaughtered on each experimental day (days 1-16 after estrus) for ovary collection. The ovarian follicles were measured and categorized by size (very small <2mm; small 2-3.5mm; medium 3.5-5mm; large >5mm). On each slaughter day, the number of corpora lutea per ewe was classified as single and double ovulation. The results show that the effect of dominant follicles was less during the mid-luteal phase. Ovulation rate of right, left and both ovaries were (54.9%), (23.6%) and (21.5%), respectively. The incidence of double ovulations was 40.2%. In the case of ewes exhibiting double ovulation, 46.6% occurred unilateral (ewes exhibited both ovulations on the right ovary); whereas 53.4% occurred bilateral (ewes exhibited ovulations on the right and left ovaries). Unilateral double ovulation was not observed in the left ovary. The right ovary appeared to play a significantly greater role in ewes showing single and double ovulations than the left ovary (P<0.05). Serum progesterone concentration showed minimum and maximum levels of 0.29+/-0.15 and 5.51+/-0.75 ng/ml on days 16 and 11 post-estrous, respectively (P<0.001). The mean volume of individual corpus lutea in ewes with single ovulations was significantly higher than in ewes with double ovulations (P<0.01). However, the total volume of corpus lutea in ewes with single ovulation was significantly lower than in ewes with double ovulations in some days of estrous cycle (P<0.01). The serum progesterone concentration was significantly higher in double than single ovulating animals on days 1-16 of the estrous cycle (P<0.001). These results indicated a relatively high incidence of double ovulation in ewes associated with increasing total luteal volume and high circulating concentrations of progesterone.

Efficacy and Safety of Single and Double Doses of Ivermectin versus 7-Day High Dose Albendazole for Chronic Strongyloidiasis

PubMed Central

Suputtamongkol, Yupin; Premasathian, Nalinee; Bhumimuang, Kid; Waywa, Duangdao; Nilganuwong, Surasak; Karuphong, Ekkapun; Anekthananon, Thanomsak; Wanachiwanawin, Darawan; Silpasakorn, Saowaluk

2011-01-01

Background Strongyloidiasis, caused by an intestinal helminth Strongyloides stercoralis, is common throughout the tropics. It remains an important health problem due to autoinfection, which may result in hyperinfection and disseminated infection in immunosuppressed patients, especially patients receiving chemotherapy or corticosteroid treatment. Ivermectin and albendazole are effective against strongyloidiasis. However, the efficacy and the most effective dosing regimen are to be determined. Methods A prospective, randomized, open study was conducted in which a 7-day course of oral albendazole 800 mg daily was compared with a single dose (200 microgram/kilogram body weight), or double doses, given 2 weeks apart, of ivermectin in Thai patients with chronic strongyloidiasis. Patients were followed-up with 2 weeks after initiation of treatment, then 1 month, 3 months, 6 months, 9 months, and 1 year after treatment. Combination of direct microscopic examination of fecal smear, formol-ether concentration method, and modified Koga agar plate culture were used to detect strongyloides larvae in two consecutive fecal samples in each follow-up visit. The primary endpoint was clearance of strongyloides larvae from feces after treatment and at one year follow-up. Results Ninety patients were included in the analysis (30, 31 and 29 patients in albendazole, single dose, and double doses ivermectin group, respectively). All except one patient in this study had at least one concomitant disease. Diabetes mellitus, systemic lupus erythrematosus, nephrotic syndrome, hematologic malignancy, solid tumor and human immunodeficiency virus infection were common concomitant diseases in these patients. The median (range) duration of follow-up were 19 (2–76) weeks in albendazole group, 39 (2–74) weeks in single dose ivermectin group, and 26 (2–74) weeks in double doses ivermectin group. Parasitological cure rate were 63.3%, 96.8% and 93.1% in albendazole, single dose oral ivermectin, and double doses of oral ivermectin respectively (P = 0.006) in modified intention to treat analysis. No serious adverse event associated with treatment was found in any of the groups. Conclusion/Significance This study confirms that both a single, and a double dose of oral ivermectin taken two weeks apart, is more effective than a 7-day course of high dose albendazole for patients with chronic infection due to S. stercoralis. Double dose of ivermectin, taken two weeks apart, might be more effective than a single dose in patients with concomitant illness. Trial Registration ClinicalTrials.gov NCT00765024 PMID:21572981

Xerostomia and its predictors following parotid-sparing irradiation of head-and-neck cancer.

PubMed

Eisbruch, A; Kim, H M; Terrell, J E; Marsh, L H; Dawson, L A; Ship, J A

2001-07-01

To assess long-term xerostomia in patients receiving parotid-sparing radiation therapy (RT) for head-and-neck cancer, and to find the patient and therapy-related factors that affect its severity. From March 1994 through January 2000, 84 patients received comprehensive bilateral neck RT using conformal and multisegmental intensity-modulated RT (IMRT) aiming to spare the major salivary glands. Before RT and periodically through 2 years after the completion of RT, salivary flow rates from each of the major salivary glands were selectively measured. At the same time intervals, each patient completed an 8-item self-reported xerostomia-specific questionnaire (XQ). To gain a relative measure of the effect of RT on the minor salivary glands, whose output could not be measured, the surfaces of the oral cavity (extending to include the surface of the base of tongue) were outlined in the planning CT scans. The mean doses to the new organ ("oral cavity") were recorded. Forty-eight patients receiving unilateral neck RT were similarly studied and served as a benchmark for comparison. Factors predicting the XQ scores were analyzed using a random-effects model. The XQ was found to be reliable and valid in measuring patient-reported xerostomia. The spared salivary glands which had received moderate doses in the bilateral RT group recovered to their baseline salivary flow rates during the second year after RT, and the spared glands in the unilateral RT group, which had received very low doses, demonstrated increased salivary production beyond their pre-RT levels. The increase in the salivary flow rates during the second year after RT paralleled an improvement in xerostomia in both patient groups. The improvement in xerostomia was faster in the unilateral compared with the bilateral RT group, but the difference narrowed at 2 years. The major salivary gland flow rates had only a weak correlation with the xerostomia scores. Factors found to be independently associated with the xerostomia scores were the pre-RT baseline scores, the time since RT, and the mean doses to the major salivary glands (notably to the submandibular glands) and to the oral cavity. An improvement over time in xerostomia, occurring in tandem with rising salivary production from the spared major salivary glands, suggests a long-term clinical benefit from their sparing. The oral cavity mean dose, representing RT effect on the minor salivary glands, was found to be a significant, independent predictor of xerostomia. Thus, in addition to the major salivary glands, sparing the uninvolved oral cavity should be considered as a planning objective to further reduce xerostomia.

High-dose total-body irradiation and autologous marrow reconstitution in dogs: dose-rate-related acute toxicity and fractionation-dependent long-term survival

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

Deeg, H.J.; Storb, R.; Weiden, P.L.

1981-11-01

Beagle dogs treated by total-body irradiation (TBI) were given autologous marrow grafts in order to avoid death from marrow toxicity. Acute and delayed non-marrow toxicities of high single-dose (27 dogs) and fractionated TBI (20 dogs) delivered at 0.05 or 0.1 Gy/min were compared. Fractionated TBI was given in increments of 2 Gy every 6 hr for three increments per day. Acute toxicity and early mortality (<1 month) at identical total irradiation doses were comparable for dogs given fractionated or single-dose TBI. With single-dose TBI, 14, 16, and 18 Gy, respectively, given at 0.05 Gy/min, 0/5, 5/5, and 2/2 dogs diedmore » from acute toxicity; with 10, 12, and 14 Gy, respectively, given at 0.1 Gy/min, 1/5, 4/5, and 5/5 dogs died acutely. With fractionated TBI, 14 and 16 Gy, respectively, given at 0.1 Gy/min, 1/5, 4/5, and 2/2 dogs died auctely. Early deaths were due to radiation enteritis with or without associated septicemia (29 dogs; less than or equal to Day 10). Three dogs given 10 Gy of TBI at 0.1 Gy/min died from bacterial pneumonia; one (Day 18) had been given fractionated and two (Days 14, 22) single-dose TBI. Fifteen dogs survived beyond 1 month; eight of these had single-dose TBI (10-14 Gy) and all died within 7 months of irradiation from a syndrome consisting of hepatic damage, pancreatic fibrosis, malnutrition, wasting, and anemia. Seven of the 15 had fractionated TBI, and only one (14 Gy) died on Day 33 from hepatic failure, whereas 6 (10-14 Gy) are alive and well 250 to 500 days after irradiation. In conclusion, fractionated TBI did not offer advantages over single-dose TBI with regard to acute toxicity and early mortality; rather, these were dependent upon the total dose of TBI. The total acutely tolerated dose was dependent upon the exposure rate; however, only dogs given fractionated TBI became healthy long-term survivors.« less

The effects of a high-fat meal on single-dose vemurafenib pharmacokinetics.

PubMed

Ribas, Antoni; Zhang, Weijiang; Chang, Ilsung; Shirai, Keisuke; Ernstoff, Marc S; Daud, Adil; Cowey, C Lance; Daniels, Gregory; Seja, Elizabeth; O'Laco, Elizabeth; Glaspy, John A; Chmielowski, Bartosz; Hill, Todd; Joe, Andrew K; Grippo, Joseph F

2014-04-01

Vemurafenib is an orally bioavailable BRAF inhibitor approved for the treatment of BRAF(V600) -mutant metastatic melanoma. It is important to understand the effects of a high-fat meal on the pharmacokinetics (PK) of vemurafenib in humans because it is a Biopharmaceutics Classification System Class IV drug and its PK can be altered by food. An open-label, multicenter, randomized, 2-period crossover study was performed to evaluate the effect of food (high-fat meal) on the PK of a single oral dose of vemurafenib. Secondary objectives were safety and tolerability, efficacy with best overall response rate, and overall survival during the treatment period. The concomitant intake of food (high-fat meal) increased mean Cmax 3.5 to 7.5 µg/mL and mean AUC0-∞ 119 to 360 µg·h/mL after a single 960 mg dose of vemurafenib (N = 13-15 patients). An effect of food on single-dose exposure is suggested by point estimates and 90% CI of geometric mean ratios for vemurafenib plasma AUC0-∞ (4.7) and Cmax (2.5). Toxicity and response rate of vemurafenib in this study were consistent with prior experience in patients with BRAF(V600) -mutant metastatic melanoma. A high-fat meal increased the exposure to vemurafenib without altering the mean terminal half-life. © 2014, The American College of Clinical Pharmacology.

Knee Joint Loading during Single-Leg Forward Hopping.

PubMed

Krupenevich, Rebecca L; Pruziner, Alison L; Miller, Ross H

2017-02-01

Increased or abnormal loading on the intact limb is thought to contribute to the relatively high risk of knee osteoarthritis in this limb for individuals with unilateral lower limb loss. This theory has been assessed previously by studying walking, but knee joint loading during walking is often similar between individuals with and without limb loss, prompting assessment of other movements that may place unusual loads on the knee. One such movement, hopping, is a form of locomotion that individuals with unilateral lower limb loss may situationally use instead of walking, but the mechanical effects of hopping on the intact limb are unknown. Compare knee joint kinetics of healthy adults during single-leg forward hopping compared to walking, a more traditional form of locomotion. Twenty-four healthy adults walked and hopped at self-selected speeds of 1.5 and 2.3 m·s, respectively. Joint moments were calculated using inverse dynamics. A paired Student's t-test was utilized to compare peak, impulse, and loading rate (LR) of knee adduction moment (KAM), and peak knee flexion moment (KFM) between walking and hopping. Peak KFM and KAM LR were greater during hopping compared to walking (peak KFM: 20.73% vs 5.51% body weight (BW) × height (Ht), P < 0.001; KAM LR: 0.47 vs. 0.33 BW·Ht·s, P = 0.01). Kinetic measures affecting knee joint loading are greater in hopping compared to walking. It may be advisable to limit single-leg forward hopping in the limb loss population until it is known if these loads increase knee osteoarthritis risk.

An Ai Chi-based aquatic group improves balance and reduces falls in community-dwelling adults: A pilot observational cohort study.

PubMed

Skinner, Elizabeth H; Dinh, Tammy; Hewitt, Melissa; Piper, Ross; Thwaites, Claire

2016-11-01

Falls are associated with morbidity, loss of independence, and mortality. While land-based group exercise and Tai Chi programs reduce the risk of falls, aquatic therapy may allow patients to complete balance exercises with less pain and fear of falling; however, limited data exist. The objective of the study was to pilot the implementation of an aquatic group based on Ai Chi principles (Aquabalance) and to evaluate the safety, intervention acceptability, and intervention effect sizes. Pilot observational cohort study. Forty-two outpatients underwent a single 45-minute weekly group aquatic Ai Chi-based session for eight weeks (Aquabalance). Safety was monitored using organizational reporting systems. Patient attendance, satisfaction, and self-reported falls were also recorded. Balance measures included the Timed Up and Go (TUG) test, the Four Square Step Test (FSST), and the unilateral Step Tests. Forty-two patients completed the program. It was feasible to deliver Aquabalance, as evidenced by the median (IQR) attendance rate of 8.0 (7.8, 8.0) out of 8. No adverse events occurred and participants reported high satisfaction levels. Improvements were noted on the TUG, 10-meter walk test, the Functional Reach Test, the FSST, and the unilateral step tests (p < 0.05). The proportion of patients defined as high falls risk reduced from 38% to 21%. The study was limited by its small sample size, single-center nature, and the absence of a control group. Aquabalance was safe, well-attended, and acceptable to participants. A randomized controlled assessor-blinded trial is required.

Comparative Study of Constant Dose Intrathecal Hypobaric Levobupivacaine with Varying Baricities in Lower Limb Surgeries

PubMed Central

Biji, K. P.; Sunil, M.; Ramadas, K. T.

2017-01-01

Background: Hypobaric spinal anesthesia is advantageous for unilateral lower extremity fractures as it obviates pain of lying on fractured limb for performing subarachnoid block. Aims: This study compares block characteristics and complications of three different baricities of constant dose intrathecal hypobaric levobupivacaine to determine an optimum baricity. Settings and Design: One-twenty American Society of Anesthesiologists Physical Status 1 and 2 patients aged 18–65 years undergoing unilateral lower limb surgeries were divided into three equal groups for this prospective cohort study. Materials and Methods: To 2 mL intrathecal 0.5% isobaric levobupivacaine (10 mg), 0.4 mL, 0.6 mL, and 0.8 mL of distilled water were added in Groups A, B, and C, respectively. Baricities of Groups A, B, and C are 0.999294, 0.998945, and 0.998806, respectively. Development of sensory and motor block was assessed by the pinprick method and Bromage scale, respectively. The total duration of analgesia and complications were noted. Statistical Analysis Used: Mean, standard error, one-way ANOVA, and Bonferroni were used to analyze quantitative variables; proportions and Chi-square tests for qualitative variables. Results: Demographic parameters, motor block of operated limb, and complications were comparable. Group C had the fastest onset of sensory block (10.10 min) and maximum duration of analgesia (478.97 min; P < 0.001); but high sensory levels in 48.7%. Group B had T10 sensory level in 92.5%; onset comparable to Group C (P = 0.248), and reasonable duration of analgesia (332.50 min). Group A had inadequate sensory levels, slow onset, and early regression. Conclusions: Group B (baricity - 0.998945) has better block characteristics among three groups compared. PMID:28928563

Comparative Study of Constant Dose Intrathecal Hypobaric Levobupivacaine with Varying Baricities in Lower Limb Surgeries.

PubMed

Biji, K P; Sunil, M; Ramadas, K T

2017-01-01

Hypobaric spinal anesthesia is advantageous for unilateral lower extremity fractures as it obviates pain of lying on fractured limb for performing subarachnoid block. This study compares block characteristics and complications of three different baricities of constant dose intrathecal hypobaric levobupivacaine to determine an optimum baricity. One-twenty American Society of Anesthesiologists Physical Status 1 and 2 patients aged 18-65 years undergoing unilateral lower limb surgeries were divided into three equal groups for this prospective cohort study. To 2 mL intrathecal 0.5% isobaric levobupivacaine (10 mg), 0.4 mL, 0.6 mL, and 0.8 mL of distilled water were added in Groups A, B, and C, respectively. Baricities of Groups A, B, and C are 0.999294, 0.998945, and 0.998806, respectively. Development of sensory and motor block was assessed by the pinprick method and Bromage scale, respectively. The total duration of analgesia and complications were noted. Mean, standard error, one-way ANOVA, and Bonferroni were used to analyze quantitative variables; proportions and Chi-square tests for qualitative variables. Demographic parameters, motor block of operated limb, and complications were comparable. Group C had the fastest onset of sensory block (10.10 min) and maximum duration of analgesia (478.97 min; P < 0.001); but high sensory levels in 48.7%. Group B had T 10 sensory level in 92.5%; onset comparable to Group C ( P = 0.248), and reasonable duration of analgesia (332.50 min). Group A had inadequate sensory levels, slow onset, and early regression. Group B (baricity - 0.998945) has better block characteristics among three groups compared.

Effects of omitting elective neck irradiation to nodal Level IB in nasopharyngeal carcinoma patients with negative Level IB lymph nodes treated by intensity-modulated radiotherapy: a Phase 2 study.

PubMed

Li, Mei; Huang, Xiao-Guang; Yang, Zhi-Ning; Lu, Jia-Yang; Zhan, Yi-Zhou; Xie, Wen-Jia; Zhou, Dong-Jie; Wang, Li; Zhu, Di-Xia; Lin, Zhi-Xiong

2016-09-01

To investigate the need for elective neck irradiation (ENI) to nodal Level IB in patients with nasopharyngeal carcinoma (NPC) with negative Level IB lymph nodes (IB-negative) treated by intensity-modulated radiotherapy (IMRT). We conducted a Phase 2 prospective study in 123 newly diagnosed IB-negative patients with NPC treated by IMRT, who met at least 1 of the following criteria: (1) unilateral or bilateral Level II involvement with 1 of the following: Level IIA involvement or any Level II node ≥2 cm/with extracapsular spread; (2) ≥2 unilateral node-positive regions. Bilateral Level IB nodes were not contoured as part of the treatment target and treated electively. Level IB regional recurrence rate; pattern of treatment failure; 3-year overall survival (3y-OS), 3-year local control (3y-LC) and 3-year regional control (3y-RC) rates; toxicities; and dosimetric data for planning target volumes, organs at risk, Level IB and submandibular glands (SMGs) were evaluated. Two patients developed failures at Level IB (1.6%). The 3y-LC, 3y-RC and 3y-OS rates were 93.5%, 93.5% and 78.0%, respectively. Bilateral Level IB received unplanned high-dose irradiation with a mean dose (Dmean) ≥50 Gy in 60% of patients. The average Dmean of bilateral SMGs was approximately 53 Gy. ENI to Level IB may be unnecessary in IB-negative patients with NPC treated by IMRT. A further Phase 3 study is warranted. Based on the results of this first Phase 2 study, we suggest omitting ENI to Level IB in Ib-negative patients with NPC with extensive nodal disease treated by IMRT.

Genetical and ultrastructural aspects of self and cross incompatibility in interspecific hybrids between self-compatible Lycopersicum esculentum and self-incompatible L. peruvianum.

PubMed

De Nettancourt, D; Devreux, M; Laneri, U; Cresti, M; Pacini, E; Sarfatti, G

1974-01-01

Cytological and genetical analyses were made of the breeding system of embryo-cultured interspecific tomato hybrids between L. esculentum and L. peruvianum. It was found that fluorescence techniques and electron microscopy allowed a distinction to be made between pollen tubes inhibited by a unilateral incompatibility reaction and pollen tubes inhibited by a self-incompatibility reaction, after self-pollination of the hybrids or after reciprocal crossing between the hybrid and the parental species. The observed differences, if real and reliable, demonstrate that unilateral incompatibility in esculentum pollen tubes is governed by a single gametophytic factor which is either linked or allelic to the S-locus. This finding is discussed with reference to recent reports that unilateral incompatibility is controlled, in peruvianum styles, by a number of different dominant genes and it is concluded that these dominant genes, the S-locus of self-incompatibility and the gametophytic factor regulating the unilateral reaction in esculentum pollen belong to the same linkage group. The strong sterility barriers which prevent practically all backcrosses between the hybrid and the parental species were shown to be independent of the factors regulating stylar incompatibility. L. peruvianum is heterozygous for the sterility genes which prevent fertilization or embryo formation when the interspecific hybrid is crossed, as pistillate parent, to different accessions of L. peruvianum. One peruvianum stock was found which, as a pollinator, was highly cross-fertile with the hybrids.The presence of a concentric endoplasmic reticulum in inhibited pollen tubes was observed to be a constant feature of both the self- and the unilateral incompatibility reactions and was interpreted as an indication that incompatibility might lead to a general cessation of protein synthesis. Although incompatible tubes very much resemble, in this respect, the pollen tubes cultured in vitro, it seems probable, on theoretical grounds, that the inhibition of pollen tubes in incompatible styles does not result from an absence of growth promoting substances but from the presence of a metabolic inhibitor.

Topical administration of regorafenib eye drops: phase I dose‐escalation study in healthy volunteers

PubMed Central

Höchel, Joachim; Becka, Michael; Boettger, Michael K.; Rohde, Beate; Schug, Barbara; Kunert, Kathleen S.; Donath, Frank

2018-01-01

Aim Regorafenib is a multikinase inhibitor under investigation for use in neovascular age‐related macular degeneration. In this phase I study, regorafenib eye drops were administered to healthy volunteers to provide information on safety, tolerability and systemic exposure. Methods This was a single‐centre, randomized, double‐masked, parallel‐group, dose‐escalation, placebo‐controlled study. Subjects received regorafenib eye drops (30 mg ml−1, 25 μl) as a 0.75 mg single dose (Cohort 1), 0.75 mg twice daily (bid) or thrice daily (tid) over 14 days (Cohorts 2 and 3, respectively), 1.5 mg tid unilaterally for 3 days, then bilaterally for up to 14 days (Cohort 4), or placebo. Plasma samples were taken to estimate systemic exposure. Safety and functional assessments were performed throughout the study. Results Thirty‐six subjects received regorafenib and 12 received placebo. Regorafenib was safe and well tolerated over the dose range. No pathological changes occurred in the anterior, vitreous or posterior eye compartments. Mild eyelid redness, oedema and conjunctival hyperaemia were observed across all regorafenib cohorts; these were comparable with the effects seen with placebo. Predominant symptoms were blurred vision in the active and placebo groups. Systemic safety evaluations showed no clinically relevant findings. Absolute systemic exposure after multiple administrations of regorafenib eye drops at a dose of 0.75 mg was 600–700‐fold lower than after multiple oral administration of 160 mg day−1, the dose approved in cancer indications. Conclusion These results indicate a favourable safety and tolerability profile of regorafenib eye drops up to 30 mg ml−1 tid for use in clinical studies. PMID:29315699

MRI Assessment of Uterine Artery Patency and Fibroid Infarction Rates 6 Months after Uterine Artery Embolization with Nonspherical Polyvinyl Alcohol

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

Das, Raj, E-mail: rajdas@nhs.net; Gonsalves, Michael; Vlahos, Ioannis

Purpose: We have observed significant rates of uterine artery patency after uterine artery embolization (UAE) with nonspherical polyvinyl alcohol (nsPVA) on 6 month follow-up MR scanning. The study aim was to quantitatively assess uterine artery patency after UAE with nsPVA and to assess the effect of continued uterine artery patency on outcomes. Methods: A single centre, retrospective study of 50 patients undergoing bilateral UAE for uterine leiomyomata was undertaken. Pelvic MRI was performed before and 6 months after UAE. All embolizations were performed with nsPVA. Outcome measures included uterine artery patency, uterine and dominant fibroid volume, dominant fibroid percentage infarction,more » presence of ovarian arterial collaterals, and symptom scores assessed by the Uterine Fibroid Symptom and Quality of Life questionnaire (UFS-QOL). Results: Magnetic resonance angiographic evidence of uterine artery recanalization was demonstrated in 90 % of the patients (64 % bilateral, 26 % unilateral) at 6 months. Eighty percent of all dominant fibroids demonstrated >90 % infarction. The mean percentage reduction in dominant fibroid volume was 35 %. No significant difference was identified between nonpatent, unilateral, and bilateral recanalization of the uterine arteries with regard to percentage dominant fibroid infarction or dominant fibroid volume reduction. The presence of bilaterally or unilaterally patent uterine arteries was not associated with inferior clinical outcomes (symptom score or UFS-QOL scores) at 6 months. Conclusion: The high rates of uterine artery patency challenge the current paradigm that nsPVA is a permanent embolic agent and that permanent uterine artery occlusion is necessary to optimally treat uterine fibroids. Despite high rates of uterine artery recanalization in this cohort, satisfactory fibroid infarction rates and UFS-QOL scores were achieved.« less

Protective effect of green tea polyphenol EGCG against neuronal damage and brain edema after unilateral cerebral ischemia in gerbils.

PubMed

Lee, Hyung; Bae, Jae Hoon; Lee, Seong-Ryong

2004-09-15

Previous studies have demonstrated that a green tea polyphenol, (-)-epigallocatechine gallate (EGCG), has a potent free radical scavenging and antioxidant effect. Glutamate leads to excitotoxicity and oxidative stress, which are important pathophysiologic responses to cerebral ischemia resulting in brain edema and neuronal damage. We investigated the effect of EGCG on excitotoxic neuronal damage in a culture system and the effect on brain edema formation and lesion after unilateral cerebral ischemia in gerbils. In vitro, excitotoxicity was induced by 24-hr incubation with N-methyl-D-aspartate (NMDA; 10 microM), AMPA (10 microM), or kainate (20 microM). EGCG (5 microM) was added to the culture media alone or with excitotoxins. We examined malondialdehyde (MDA) level and neuronal viability to evaluate the effect of EGCG. In vivo, unilateral cerebral ischemia was induced by occlusion of the right common carotid artery for 30, 60, or 90 min and followed by reperfusion of 24 hr. Brain edema, MDA, and infarction were examined to evaluate the protective effect of EGCG. EGCG (25 or 50 mg/kg, intraperitoneally) was administered twice, at 30 min before and immediately after ischemia. EGCG reduced excitotoxin-induced MDA production and neuronal damage in the culture system. In the in vivo study, treatment of gerbils with the lower EGCG dose failed to show neuroprotective effects; however, the higher EGCG dose attenuated the increase in MDA level caused by cerebral ischemia. EGCG also reduced the formation of postischemic brain edema and infarct volume. These results demonstrate EGCG may have future possibilities as a neuroprotective agent against excitotoxicity-related neurologic disorders such as brain ischemia.

Intractable bone marrow edema syndrome of the hip.

PubMed

Gao, Fuqiang; Sun, Wei; Li, Zirong; Guo, Wanshou; Kush, Nepali; Ozaki, Koji

2015-04-01

There is a need for an effective and noninvasive treatment for intractable bone marrow edema syndrome of the hip. Forty-six patients with intractable bone marrow edema syndrome of the hip were retrospectively studied to compare the short-term clinical effects of treatment with high-energy extracorporeal shock wave therapy vs femoral head core decompression. The postoperative visual analog scale score decreased significantly more in the extracorporeal shock wave therapy group compared with the femoral head core decompression group (P<.05). For unilateral lesions, postoperative Harris Hip Scores for all hips in the extracorporeal shock wave therapy group were more significantly improved than Harris Hip Scores for all hips in the femoral head core decompression group (P<.05). Patients who underwent extracorporeal shock wave therapy also resumed daily activities significantly earlier. Average overall operative time was similar in both groups. Symptoms disappeared significantly sooner in the extracorporeal shock wave therapy group in patients with both unilateral (P<.01) and bilateral lesions (P<.05). Hospital costs were significantly lower with extracorporeal shock wave therapy compared with femoral head core decompression. The intraoperative fluoroscopy radiation dose was lower in extracorporeal shock wave therapy than in femoral head core decompression for both unilateral (P<.05) and bilateral lesions (P<.01). On magnetic resonance imaging (MRI), bone marrow edema improved in all patients during the follow-up period. After extracorporeal shock wave therapy, all patients remained pain-free and had normal findings on posttreatment radiographs and MRI scans. Extracorporeal shock wave therapy appears to be a valid, reliable, and noninvasive tool for rapidly resolving intractable bone marrow edema syndrome of the hip, and it has a low complication rate and relatively low cost compared with other conservative and surgical treatment approaches. Copyright 2015, SLACK Incorporated.

Ultraviolet radiation exposure triggers neurokinin-1 receptor upregulation in ocular tissues in vivo.

PubMed

Gross, Janine; Wegener, Alfred R; Kronschlaeger, Martin; Holz, Frank G; Schönfeld, Carl-Ludwig; Meyer, Linda M

2018-04-26

The purpose of this study was to investigate the neurokinin receptor-1 (NKR-1) protein expression in ocular tissues before and after supra-cataract threshold ultraviolet radiation (UVR-B peak at 312 nm) exposure in vivo in a mouse model. Six-week-old C57Bl/6 mice were unilaterally exposed to a single (2.9 kJ/m 2 ) and an above 3-fold UVR-B cataract threshold dose (9.4 kJ/m 2 ) of UVR. UVR-exposure (λpeak = 312 nm) was performed in mydriasis using a Bio-Spectra exposure system. After latency periods of 3 and 7 days, eyes were fixed in 4% paraformaldehyde, embedded in paraffin, sectioned and stained with fluorescence coupled antibody for NKR-1 and DAPI for cell nuclei staining. Control animals received only anesthesia but no UVR-exposure. Cataract development was documented with a Leica dark-field microscope and quantified as integrated optical density (IOD). NKR-1 is ubiquitously present in ocular tissues. An above 3-fold cataract threshold dose of UV-radiation induced NKR-1 upregulation after days 3 and 7 in the epithelium and endothelium of the cornea, the endothelial cells of the iris vessels, the pigmented epithelium/stroma of the ciliary body, the lens epithelium, pronounced in the nuclear bow region and the inner plexiform layer of the retina. A significant upregulation of NKR-1 could not be provoked with a single cataract threshold dose (2.9 kJ/m 2 UVR-B) ultraviolet irradiation. All exposed eyes developed anterior subcapsular cataracts. Neurokinin-1 receptor is present ubiquitously in ocular tissues including the lens epithelium and the nuclear bow region of the lens. UV-radiation exposure to an above 3-fold UVR-B cataract threshold dose triggers NKR-1 upregulation in the eye in vivo. The involvement of inflammation in ultraviolet radiation induced cataract and the role of neuroinflammatory peptides such as substance P and its receptor, NKR-1, might have been underestimated to date. Copyright © 2018. Published by Elsevier Ltd.

Prospective study of inner ear radiation dose and hearing loss in head-and-neck cancer patients

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

Pan, Charlie C.; Eisbruch, Avraham; Lee, Julia S.

Purpose: To determine the relationship between the radiation dose to the inner ear and long-term hearing loss. Methods and Materials: Eligible patients included those receiving curative radiotherapy (RT) for head-and-neck cancer. After enrollment, patients underwent three-dimensional conformal RT planning and delivery (180-200 cGy/fraction) appropriate for their disease site and stage. The inner ear was contoured on axial CT planning images. Dose-volume histograms, as well as the mean and maximal dose for each structure, were calculated. Patients underwent pure tone audiometry at baseline (before treatment) and 1, 6, 12, 24, and 36 months after RT. The threshold level (the greater themore » value, the more hearing loss) in decibels was recorded for 250, 500, 1000, 2000, 4000, and 8000 Hz. For patients receiving predominantly unilateral RT, the contralateral ear served as the de facto control. The differences in threshold level between the ipsilateral and contralateral ears were calculated, and the temporal pattern and dose-response relation of hearing loss were analyzed using statistical methods that take into account the correlation between two ears in the same subject and repeated, sequential measurements of each subject. Results: Of the 40 patients enrolled in this study, 35 qualified for analysis. Four patients who received concurrent chemotherapy and RT were analyzed separately. The 31 unilaterally treated patients received a median dose of 47.4 Gy (range, 14.1-68.8 Gy) to the ipsilateral inner ear and 4.2 Gy (range, 0.5-31.3 Gy) to the contralateral inner ear. Hearing loss was associated with the radiation dose received by the inner ear (loss of 210dB was observed in ears receiving {>=}45 Gy) and was most appreciable in the higher frequencies ({>=}2000 Hz). For a 60-year-old patient with no previous hearing loss in either ear, after receiving 45 Gy, the ipsilateral ear, according to our clinical model, would have a 19.3-dB (95% confidence interval [CI], 15.5-23.0) and 5.4-dB (95% CI, 3.5-7.5) hearing decrement compared with the contralateral ear for 8000 Hz and 1000 Hz, respectively. Age and an initial hearing difference within an ear pair also affected hearing loss. The baseline hearing threshold was inversely related to radiation-induced hearing loss. The degree of hearing loss was dependent on the frequency tested, age, baseline hearing, and baseline difference in hearing between a patient's two ears. Conclusion: High-frequency ({>=}2000 Hz) hearing acuity worsens significantly after RT in a dose-dependent fashion. A larger number of patients needs to be studied to validate these results. This knowledge can be applied to create guidelines regarding future dose limits to the auditory apparatus for patients undergoing head-and-neck RT.« less

Single-hit mechanism of tumour cell killing by radiation.

PubMed

Chapman, J D

2003-02-01

To review the relative importance of the single-hit mechanism of radiation killing for tumour response to 1.8-2.0 Gy day(-1) fractions and to low dose-rate brachytherapy. Tumour cell killing by ionizing radiation is well described by the linear-quadratic equation that contains two independent components distinguished by dose kinetics. Analyses of tumour cell survival curves that contain six or more dose points usually provide good estimates of the alpha- and beta-inactivation coefficients. Superior estimates of tumour cell intrinsic radiosensitivity are obtained when synchronized populations are employed. The characteristics of single-hit inactivation of tumour cells are reviewed and compared with the characteristics of beta-inactivation. Potential molecular targets associated with single-hit inactivation are discussed along with strategies for potentiating cell killing by this mechanism. The single-hit mechanism of tumour cell killing shows no dependence on dose-rate and, consequently, no evidence of sublethal damage repair. It is uniquely potentiated by high linear-energy-transfer radiation, exhibits a smaller oxygen enhancement ratio and exhibits a larger indirect effect by hydroxyl radicals than the beta-mechanism. alpha-inactivation coefficients vary slightly throughout interphase but mitotic cells exhibit extremely high alpha-coefficients in the range of those observed for lymphocytes and some repair-deficient cells. Evidence is accumulating to suggest that chromatin in compacted form could be a radiation-hypersensitive target associated with single-hit radiation killing. Analyses of tumour cell survival curves demonstrate that it is the single-hit mechanism (alpha) that determines the majority of cell killing after doses of 2Gy and that this mechanism is highly variable between tumour cell lines. The characteristics of single-hit inactivation are qualitatively and quantitatively distinct from those of beta-inactivation. Compacted chromatin in tumour cells should be further investigated as a radiation-hypersensitive target that could be modulated for therapeutic advantage.

Different types of working memory binding in epilepsy patients with unilateral anterior temporal lobectomy.

PubMed

van Geldorp, Bonnie; Bouman, Zita; Hendriks, Marc P H; Kessels, Roy P C

2014-03-01

The medial temporal lobe is an important structure for long-term memory formation, but its role in working memory is less clear. Recent studies have shown hippocampal involvement during working memory tasks requiring binding of information. It is yet unclear whether this is limited to tasks containing spatial features. The present study contrasted three binding conditions and one single-item condition in patients with unilateral anterior temporal lobectomy. A group of 43 patients with temporal lobectomy (23 left; 20 right) and 20 matched controls were examined with a working memory task assessing spatial relational binding (object-location), non-spatial relational binding (object-object), conjunctive binding (object-colour) and working memory for single items. We varied the delay period (3 or 6s), as there is evidence showing that delay length may modulate working memory performance. The results indicate that performance was worse for patients than for controls in both relational binding conditions, whereas patients were unimpaired in conjunctive binding. Single-item memory was found to be marginally impaired, due to a deficit on long-delay trials only. In conclusion, working memory binding deficits are found in patients with unilateral anterior temporal lobectomy. The role of the medial temporal lobe in working memory is not limited to tasks containing spatial features. Rather, it seems to be involved in relational binding, but not in conjunctive binding. The medial temporal lobe gets involved when working memory capacity does not suffice, for example when relations have to be maintained or when the delay period is long. Copyright © 2014 Elsevier Inc. All rights reserved.

Intradermal capsaicin as a neuropathic pain model in patients with unilateral sciatica

PubMed Central

Aykanat, Verna; Gentgall, Melanie; Briggs, Nancy; Williams, Desmond; Yap, Sharon; Rolan, Paul

2012-01-01

AIM This study compared the responses between patients with unilateral sciatica and pain-free volunteers following administration of intradermal capsaicin. METHODS Fourteen patients with unilateral sciatica and 12 pain-free volunteers received one injection per hour over 4 h of 1 µg and 10 µg capsaicin, into each calf. For each dose, spontaneous pain (10 cm VAS), area of flare (cm2) and the sum of allodynia and hyperalgesia radii across eight axes (cm) were recorded pre-injection and at 5, 15, 30, 45 and 60 min post injection. RESULTS Sciatica subjects experienced higher spontaneous pain and hyperalgesia responses in both legs compared with pain-free volunteers. The largest mean difference in spontaneous pain was 2.8 cm (95% CI 1.6, 3.9) at 5 min in the unaffected leg following 10 µg. The largest mean difference in hyperalgesia was 19.7 cm (95% CI 12.4, 27.0) at 60 min in the unaffected leg following 10 µg. Allodynia was greater in patients than in controls with the largest mean difference of 2.9 cm (95% CI 1, 4.8) at 5 min following 10 µg in the affected leg. Allodynia was also higher in the affected leg compared with the unaffected leg in sciatica patients with the highest mean difference of 3.0 cm (95% CI 1.2, 4.7) at 5 min following 10 µg. CONCLUSIONS The responses to intradermal capsaicin are quantitatively and qualitatively different in unilateral sciatica patients compared with pain-free controls. PMID:21740458

Type IIIb Endoleak and Relining: A Mathematical Model of Distraction Forces.

PubMed

Swaelens, Charles; Poole, Robert J; Torella, Francesco; McWilliams, Richard G; England, Andrew; Fisher, Robert K

2016-04-01

To examine the changes in distraction force following relining of a conventional abdominal aortic stent-graft with a type IIIb endoleak using the Nellix endovascular sealing device compared to a unilateral stent-graft. Relining is often used to repair type IIIb endoleaks, but the consequences to graft stability are unknown. A mathematical model was constructed based on pressure and volume flow through the stent-grafts, incorporating recognized distraction force equations. Steady flow was presumed at peak systolic pressures to calculate the maximum distraction force, with gravity ignored. Distraction forces for 28- to 36-mm-diameter stent-graft bodies with 16-mm limbs were calculated and compared to forces following relining with single and double Nellix devices or the Renu unilateral device. Distraction forces for the 28-, 32-, and 36-mm stent-grafts prior to relining were 5.99, 10.21, and 14.99 N, respectively. Similar forces were reported after relining with bilateral Nellix devices (5.86, 10.08, and 14.86 N, respectively). However, use of a unilateral Nellix increased the distraction forces to 9.92, 14.14, and 18.92 N, respectively. These were comparable to the increase observed after relining with a Renu unilateral stent-graft (9.87, 14.09, and 18.86 N, respectively). The proportional increase in distraction force for a unilateral relining ranged from 26% to 66%, with the greatest increase noted in the smaller diameter main bodies. Relining a stent-graft with a type IIIb endoleak using bilateral Nellix devices does not increase the distraction force. However, a unilateral Nellix device or the Renu system could theoretically increase the distraction force by up to 66%, potentially risking migration and type Ia endoleak. In clinical practice, these results suggest that a relining with bilateral Nellix may have benefits over the Renu unilateral stent-graft. © The Author(s) 2016.

QMRA for Drinking Water: 2. The Effect of Pathogen Clustering in Single-Hit Dose-Response Models.

PubMed

Nilsen, Vegard; Wyller, John

2016-01-01

Spatial and/or temporal clustering of pathogens will invalidate the commonly used assumption of Poisson-distributed pathogen counts (doses) in quantitative microbial risk assessment. In this work, the theoretically predicted effect of spatial clustering in conventional "single-hit" dose-response models is investigated by employing the stuttering Poisson distribution, a very general family of count distributions that naturally models pathogen clustering and contains the Poisson and negative binomial distributions as special cases. The analysis is facilitated by formulating the dose-response models in terms of probability generating functions. It is shown formally that the theoretical single-hit risk obtained with a stuttering Poisson distribution is lower than that obtained with a Poisson distribution, assuming identical mean doses. A similar result holds for mixed Poisson distributions. Numerical examples indicate that the theoretical single-hit risk is fairly insensitive to moderate clustering, though the effect tends to be more pronounced for low mean doses. Furthermore, using Jensen's inequality, an upper bound on risk is derived that tends to better approximate the exact theoretical single-hit risk for highly overdispersed dose distributions. The bound holds with any dose distribution (characterized by its mean and zero inflation index) and any conditional dose-response model that is concave in the dose variable. Its application is exemplified with published data from Norovirus feeding trials, for which some of the administered doses were prepared from an inoculum of aggregated viruses. The potential implications of clustering for dose-response assessment as well as practical risk characterization are discussed. © 2016 Society for Risk Analysis.

Effects of prefrontal tDCS on executive function: Methodological considerations revealed by meta-analysis.

PubMed

Imburgio, Michael J; Orr, Joseph M

2018-05-01

A meta-analysis of studies using single-session transcranial direct current stimulation (tDCS) to target the dorsolateral prefrontal cortex (DLPFC) was undertaken to examine the effect of stimulation on executive function (EF) in healthy samples. 27 studies were included in analyses, yielding 71 effect sizes. The most relevant measure for each task was determined a priori and used to calculate Hedge's g. Methodological characteristics of each study were examined individually as potential moderators of effect size. Stimulation effects on three domains of EF (inhibition of prepotent responses, mental set shifting, and information updating and monitoring) were analyzed separately. In line with previous work, the current study found no significant effect of anodal unilateral tDCS, cathodal unilateral tDCS, or bilateral tDCS on EF. Further moderator and subgroup analyses were only carried out for anodal unilateral montages due to the small number of studies using other montages. Subgroup analyses revealed a significant effect of anodal unilateral tDCS on updating tasks, but not on inhibition or set-shifting tasks. Cathode location significantly moderated the effect of anodal unilateral tDCS. Extracranial cathodes yielded a significant effect on EF while cranial cathodes yielded no effect. Anode size also significantly moderated effect of anodal unilateral tDCS, with smaller anodes being more effective than larger anodes. In summary, anodal DLPFC stimulation is more effective at improving updating ability than inhibition and set-shifting ability, but anodal stimulation can significantly improve general executive function when extracranial cathodes or small anodes are used. Future meta-analyses may examine how stimulation's effects on specific behavioral tasks, rather than broader domains, might be affected by methodological moderators. Copyright © 2018 Elsevier Ltd. All rights reserved.

Postoperative alar base symmetry in complete unilateral cleft lip and palate:A prospective study.

PubMed

Vyloppilli, Suresh; Krishnakumar, K S; Sayd, Shermil; Latheef, Sameer; Narayanan, Saju V; Pati, Ajit

2017-11-01

In the evolution of cleft lip repair, there have been continuous attempts to minimize local trauma and to improve lip and nasal appearances. In order to obtain an aesthetically balanced development of midface, the primary surgical correction of the nasolabial area is of paramount importance. In this study, the importance of a back-cut extending cephalically above the inferior turbinate at the mucocutaneous junction which elevates the nostril floor on the cleft side for the purpose of achieving symmetry of the alar bases are analyzed by pre and postoperative photographic anthropometry. This study comprised of fifty cases of the unilateral complete cleft lip. At the time of surgery, the patient age ranged from 3-9 months. The surgeries, performed by a single surgeon, employed the standard Millard technique, incorporating Mohler modifications of lip repair. Anthropometric analysis revealed that the preoperative mean difference between the normal side and the cleft side was 0.2056 with a standard deviation of 0.133. In the postoperative analysis, the mean difference was reduced to 0.0174 with a standard deviation of 0.141. The paired t-test showed that the p-value is <0.001, indicating high statistical significance. To conclude, in complete unilateral cleft lip and palate, the geometrically placed nasal back-cut incision has a definite role in the correction of the alar base symmetry during primary surgery. Copyright © 2017 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

Transient osteoporosis of the hip in pregnancy associated with generalized low bone mineral density--a case report.

PubMed

Anai, Takanobu; Urata, Kenichirou; Mori, Atsue; Miyazaki, Fumiko; Okamoto, Sumiaki

2013-01-01

Transient osteoporosis of the hip (TOH) in pregnancy is characterized by severe pain in unilateral or bilateral hips and has been diagnosed as localized osteopenia. However, we evaluated a case of unilateral TOH with generalized profound osteoporosis involving both the hips and the lumbar vertebrae by dual-energy X-ray absorptiometry. The diagnosis was based on the clinical course and confirmed by magnetic resonance imaging. Three-dimensional helical computed tomography (3D-CT), which has not been used in patients with TOH, revealed a markedly thin bilateral proximal femoral cortex, particularly in the symptomatic femoral head. Despite the difference in the severity of bone destruction between the two femora, they both showed the same pattern of damage on 3D-CT. Furthermore, despite continuing treatment with the same dose of alendronate and calcitriol, a high rate of bone mineral density gain, involving both the femora and lumbar vertebrae, was limited to the early postpartum months. A majority of reported female patients with TOH are pregnant. Thus, the association between TOH and pregnancy was not considered to be fortuitous, and chemical or hormonal factors related to pregnancy may play an etiologic role in this disease. The possible etiologies of TOH in pregnancy are also discussed. © 2013 S. Karger AG, Basel.

Topical Application of Apricot Kernel Extract Improves Dry Eye Symptoms in a Unilateral Exorbital Lacrimal Gland Excision Mouse

PubMed Central

Kim, Chan-Sik; Jo, Kyuhyung; Lee, Ik-Soo; Kim, Junghyun

2016-01-01

The purpose of this study was to investigate the therapeutic effects of topical application of apricot kernel extract (AKE) in a unilateral exorbital lacrimal gland excision mouse model of experimental dry eye. Dry eye was induced by surgical removal of the lacrimal gland. Eye drops containing 0.5 or 1 mg/mL AKE were administered twice a day from day 3 to day 7 after surgery. Tear fluid volume and corneal irregularity scores were determined. In addition, we examined the immunohistochemical expression level of Muc4. The topical administration of AKE dose-dependently improved all clinical dry eye symptoms by promoting the secretion of tear fluid and mucin. Thus, the results of this study indicate that AKE may be an efficacious topical agent for treating dry eye disease. PMID:27886047

Topical Application of Apricot Kernel Extract Improves Dry Eye Symptoms in a Unilateral Exorbital Lacrimal Gland Excision Mouse.

PubMed

Kim, Chan-Sik; Jo, Kyuhyung; Lee, Ik-Soo; Kim, Junghyun

2016-11-23

The purpose of this study was to investigate the therapeutic effects of topical application of apricot kernel extract (AKE) in a unilateral exorbital lacrimal gland excision mouse model of experimental dry eye. Dry eye was induced by surgical removal of the lacrimal gland. Eye drops containing 0.5 or 1 mg/mL AKE were administered twice a day from day 3 to day 7 after surgery. Tear fluid volume and corneal irregularity scores were determined. In addition, we examined the immunohistochemical expression level of Muc4. The topical administration of AKE dose-dependently improved all clinical dry eye symptoms by promoting the secretion of tear fluid and mucin. Thus, the results of this study indicate that AKE may be an efficacious topical agent for treating dry eye disease.

Mesenchymal Stem Cells Increase T-Regulatory Cells and Improve Healing Following Trauma and Hemorrhagic Shock (MSCs Increase Tregs and Improve Healing After T/HS)

PubMed Central

Gore, Amy V.; Bible, Letitia E.; Song, Kimberly; Livingston, David H.; Mohr, Alicia M.; Sifri, Ziad C.

2015-01-01

Background Rodent lungs undergo full histologic recovery within one week following unilateral lung contusion (LC). However, when LC is followed by hemorrhagic shock (HS), healing is impaired. We hypothesize that the intravenous administration of mesenchymal stem cells (MSC) to animals undergoing combined LC followed by HS (LCHS) will improve wound healing. Methods Male Sprague-Dawley rats (n=5-6/group) were subjected to LCHS with or without the injection of a single iv dose of 5 × 106 MSCs following return of shed blood after HS. Rats were sacrificed seven days following injury. Flow cytometry was used to determine the T regulatory (Treg) cell population in peripheral blood (PB). Lung histology was graded using a well-established lung injury score (LIS). Components of the LIS include average inflammatory cells/high power field (hpf) over 30 fields, interstitial edema, pulmonary edema, and alveolar integrity with total scores ranging from 0-11. Data analyzed by ANOVA followed by Tukey's multiple comparison test, expressed as mean ± SD. p<0.05 considered significant. Results Seven days following isolated LC animals demonstrate lung healing with a LIS unchanged from naive. The addition of HS results in a persistently elevated LIS score, whereas addition of MSC to LCHS decreased the LIS score back to naïve levels. The change in LIS was driven by a significant decrease in edema scores. In rats undergoing LC alone, 10.5 ± 3.3% of CD4+ cells were Tregs. The addition of HS caused no significant change in Treg population (9.3±0.7%), whereas LCHS+MSC significantly increased the population to 18.2±6.8% in PB (p<0.05 vs LCHS). Conclusion Impaired wound healing following trauma and hemorrhagic shock is improved by a single dose of MSCs given immediately after injury. This enhanced healing is associated with an increase in the T regulatory cell population and a significant decrease in lung edema score as compared to animals undergoing LCHS. Further study into the role of Tregs in MSC-mediated wound healing is warranted. PMID:26091313

Dioctophyma renale (Goeze, 1782) Infection in a Domestic Dog from Hamedan, Western Iran

PubMed Central

ZOLHAVARIEH, Seyed Masoud; NORIAN, Alireza; YAVARI, Morteza

2016-01-01

Dioctophyma renale infection is found in a wide range of mammalian species, typically in temperate areas of the world. Here, we report for the first time, the parasitism of a domestic dog by D. renale in Hamedan, Iran, a mountainous cold region, lacking significant amounts of rainfall, high humidity and temperature. A 2.5 yr old male mixed breed dog was presented with a two months history of progressive hematuria and muscle weakness. Complete blood count and serum biochemistry were performed with results indicating impaired renal function. Urinalysis, showed hematuria as well as parasitic eggs, suggestive of D. renale infection. Urinary system ultrasonography revealed a hypoecogenic tubular structure in the right kidney. The animal was treated with fenbendazole (45 mg/kg, PO, QD - five days) and ivermectin (0.02 mg/kg, SC, single dose). One week later, repeated laboratory examination confirmed presence of at least one alive worm in the affected kidney. A unilateral nephrectomy was performed; one female (60 × 5 cm) and one male (30 × 3.8 cm) live worm were taken out of the extremely thin walled right kidney. One month later, due to failure of the remained kidney and poor condition, the patient deceased. We conclude that dioctophymosis can be found in cold and or relatively dry area. Moreover, the results showed that the worm was not affected with common anthelmintic drugs. PMID:27095981

Dioctophyma renale (Goeze, 1782) Infection in a Domestic Dog from Hamedan, Western Iran.

PubMed

Zolhavarieh, Seyed Masoud; Norian, Alireza; Yavari, Morteza

2016-01-01

Dioctophyma renale infection is found in a wide range of mammalian species, typically in temperate areas of the world. Here, we report for the first time, the parasitism of a domestic dog by D. renale in Hamedan, Iran, a mountainous cold region, lacking significant amounts of rainfall, high humidity and temperature. A 2.5 yr old male mixed breed dog was presented with a two months history of progressive hematuria and muscle weakness. Complete blood count and serum biochemistry were performed with results indicating impaired renal function. Urinalysis, showed hematuria as well as parasitic eggs, suggestive of D. renale infection. Urinary system ultrasonography revealed a hypoecogenic tubular structure in the right kidney. The animal was treated with fenbendazole (45 mg/kg, PO, QD - five days) and ivermectin (0.02 mg/kg, SC, single dose). One week later, repeated laboratory examination confirmed presence of at least one alive worm in the affected kidney. A unilateral nephrectomy was performed; one female (60 × 5 cm) and one male (30 × 3.8 cm) live worm were taken out of the extremely thin walled right kidney. One month later, due to failure of the remained kidney and poor condition, the patient deceased. We conclude that dioctophymosis can be found in cold and or relatively dry area. Moreover, the results showed that the worm was not affected with common anthelmintic drugs.

Transcatheter Arterial Embolization Therapy for a Hypoplastic Pelvic Kidney with a Single Vaginal Ectopic Ureter to Control Incontinence: The Usefulness of Three-Dimensional CT Angiography Using Multidetector-Row Helical CT

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

Kudoh, Kouichi, E-mail: cdk70770@par.odn.ne.jp; Kadota, Masataka; Nakayama, Yoshiharu

2003-09-15

A girl with continuous urinary incontinence was successfully treated by angiographic embolization of a hypoplastic pelvic kidney with a single unilateral vaginal ectopic opening of the ureter. For this intervention, CT angiography was useful for detecting the corresponding renal artery of the hypoplastic kidney.

A Multi-Compartment, Single and Multiple Dose Pharmacokinetic Study of the Vaginal Candidate Microbicide 1% Tenofovir Gel

PubMed Central

Schwartz, Jill L.; Rountree, Wes; Kashuba, Angela D. M.; Brache, Vivian; Creinin, Mitchell D.; Poindexter, Alfred; Kearney, Brian P.

2011-01-01

Background Tenofovir (TFV) gel is being evaluated as a microbicide with pericoital and daily regimens. To inhibit viral replication locally, an adequate concentration in the genital tract is critical. Methods and Findings Forty-nine participants entered a two-phase study: single-dose (SD) and multi-dose (MD), were randomized to collection of genital tract samples (endocervical cells [ECC], cervicovaginal aspirate and vaginal biopsies) at one of seven time points [0.5, 1, 2, 4, 6, 8, or 24 hr(s)] post-dose following SD exposure of 4 mL 1% TFV gel and received a single dose. Forty-seven were randomized to once (QD) or twice daily (BID) dosing for 2 weeks and to collection of genital tract samples at 4, 8 or 24 hrs after the final dose, but two discontinued prior to gel application. Blood was collected during both phases at the seven times post-dose. TFV exposure was low in blood plasma for SD and MD; median Cmax was 4.0 and 3.4 ng/mL, respectively (C≤29 ng/mL). TFV concentrations were high in aspirates and tissue after SD and MD, ranging from 1.2×104 to 9.9×106 ng/mL and 2.1×102 to 1.4×106 ng/mL, respectively, and did not noticeably differ between proximal and distal tissue. TFV diphosphate (TFV-DP), the intracellular active metabolite, was high in ECC, ranging from 7.1×103 to 8.8×106 ng/mL. TFV-DP was detectable in approximately 40% of the tissue samples, ranging from 1.8×102 to 3.5×104 ng/mL. AUC for tissue TFV-DP was two logs higher after MD compared to SD, with no noticeable differences when comparing QD and BID. Conclusions Single-dose and multiple-dose TFV gel exposure resulted in high genital tract concentrations for at least 24 hours post-dose with minimal systemic absorption. These results support further study of TFV gel for HIV prevention. Trial registration ClinicalTrials.gov NCT00561496 PMID:22039430

SLI381 (Adderall XR), a two-component, extended-release formulation of mixed amphetamine salts: bioavailability of three test formulations and comparison of fasted, fed, and sprinkled administration.

PubMed

Tulloch, Simon J; Zhang, Yuxin; McLean, Angus; Wolf, Kathleen N

2002-11-01

To assess the bioavailability of three test formulations of a single dose of extended-release Adderall 20-mg capsules compared with two doses of immediate-release Adderall 10-mg tablets, and to assess the bioequivalence of a single 30-mg dose of the chosen extended-release Adderall formulation (designated as SLI381) administered in applesauce (sprinkled) and the same dose administered as an intact capsule with or without food. Randomized, open-label, crossover study. Clinical research unit. Forty-one healthy adults. Study A had four treatment sequences: three test formulations (A, B, and C) of a single dose of extended-release Adderall 20 mg, and two 10-mg doses of Adderall given 4 hours apart. Study B had three treatment sequences: a single dose of SLI381 30 mg as an intact capsule after overnight fast, an intact capsule after a high-fat breakfast, and the contents of a capsule sprinkled in 1 tablespoon of applesauce. The 20-mg test formulation A had comparable pharmacokinetic profiles and bioequivalence in rate and extent of drug absorption to Adderall 10 mg twice/day for both d- and l-amphetamine. Formulations B and C had statistically significant differences from the reference drug in some pharmacokinetic parameters. A 30-mg dose of SLI381 showed no significant differences in rate and extent of absorption of d- and l-amphetamine for fasted or sprinkled conditions compared with the high-fat meal condition. SLI381 20 mg/day is bioequivalent to Adderall 10 mg twice/day. SLI381 30 mg administered in applesauce is bioequivalent in terms of both rate and extent of absorption to the same dose administered as an intact capsule in both fasted and fed states.

A phase I study to assess the single and multiple dose pharmacokinetics of THC/CBD oromucosal spray.

PubMed

Stott, C G; White, L; Wright, S; Wilbraham, D; Guy, G W

2013-05-01

A Phase I study to assess the single and multipledose pharmacokinetics (PKs) and safety and tolerability of oromucosally administered Δ(9)-tetrahydrocannabinol (THC)/cannabidiol (CBD) spray, an endocannabinoid system modulator, in healthy male subjects. Subjects received either single doses of THC/CBD spray as multiple sprays [2 (5.4 mg THC and 5.0 mg CBD), 4 (10.8 mg THC and 10.0 mg CBD) or 8 (21.6 mg THC and 20.0 mg CBD) daily sprays] or multiple doses of THC/CBD spray (2, 4 or 8 sprays once daily) for nine consecutive days, following fasting for a minimum of 10 h overnight prior to each dosing. Plasma samples were analyzed by gas chromatography-mass spectrometry for CBD, THC, and its primary metabolite 11-hydroxy-THC, and various PK parameters were investigated. Δ(9)-Tetrahydrocannabinol and CBD were rapidly absorbed following single-dose administration. With increasing single and multiple doses of THC/CBD spray, the mean peak plasma concentration (Cmax) increased for all analytes. There was evidence of dose-proportionality in the single but not the multiple dosing data sets. The bioavailability of THC was greater than CBD at single and multiple doses, and there was no evidence of accumulation for any analyte with multiple dosing. Inter-subject variability ranged from moderate to high for all PK parameters in this study. The time to peak plasma concentration (Tmax) was longest for all analytes in the eight spray group, but was similar in the two and four spray groups. THC/CBD spray was well-tolerated in this study and no serious adverse events were reported. The mean Cmax values (<12 ng/mL) recorded in this study were well below those reported in patients who smoked/inhaled cannabis, which is reassuring since elevated Cmax values are linked to significant psychoactivity. There was also no evidence of accumulation on repeated dosing.

Tumor Heterogeneity of FIGO Stage III Carcinoma of the Uterine Cervix

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

Kim, Yong Bae; Lee, Ik Jae; Kim, Song Yih

2009-12-01

Purpose: The purpose of this study was to analyze tumor heterogeneity based on tumor extent and suggest reappraisal of the system of the International Federation of Gynecology and Obstetrics (FIGO) for Stage III carcinoma of the uterine cervix from a radiotherapeutic viewpoint. Methods and Materials: Between 1986 and 2004, 407 patients with FIGO Stage III (FIGO Stage IIIa in 19 and IIIb in 388) were treated with external beam radiotherapy (RT) and high-dose rate brachytherapy. All patients were reviewed with respect to tumor extent. Patterns of failure and survival parameters were analyzed by use of the chi{sup 2} test andmore » Kaplan-Meier method. Results: The complete response rate was 79.6%, and the 5-year overall survival rates for Stage IIIa and Stage IIIb carcinoma of the cervix were 82.1% and 54.8%, respectively. To determine which parameters of tumor extent had an influence on prognosis for Stage IIIb patients, pelvic wall (PW) extension and hydronephrosis (HD) retained significance on multivariate analysis. Stage IIIb patients were divided into three subgroups according to PW extension and HD: low risk (unilateral PW extension without HD), intermediate risk (HD without PW extension or bilateral PW extension without HD), and high risk (unilateral or bilateral PW extension with HD). The high-risk group had a remarkably low complete response rate, high locoregional failure rate, and low 5-year survival rate compared with the intermediate- and low-risk groups. Conclusions: FIGO Stage III carcinoma of the cervix covers considerably heterogeneous subgroups according to tumor extent. Before initiation of treatment, we suggest that physicians determine a tailored treatment policy based on tumor heterogeneity for each Stage III patient.« less

Process Performance of Optima XEx Single Wafer High Energy Implanter

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

Kim, J. H.; Yoon, Jongyoon; Kondratenko, S.

2011-01-07

To meet the process requirements for well formation in future CMOS memory production, high energy implanters require more robust angle, dose, and energy control while maintaining high productivity. The Optima XEx high energy implanter meets these requirements by integrating a traditional LINAC beamline with a robust single wafer handling system. To achieve beam angle control, Optima XEx can control both the horizontal and vertical beam angles to within 0.1 degrees using advanced beam angle measurement and correction. Accurate energy calibration and energy trim functions accelerate process matching by eliminating energy calibration errors. The large volume process chamber and UDC (upstreammore » dose control) using faraday cups outside of the process chamber precisely control implant dose regardless of any chamber pressure increase due to PR (photoresist) outgassing. An optimized RF LINAC accelerator improves reliability and enables singly charged phosphorus and boron energies up to 1200 keV and 1500 keV respectively with higher beam currents. A new single wafer endstation combined with increased beam performance leads to overall increased productivity. We report on the advanced performance of Optima XEx observed during tool installation and volume production at an advanced memory fab.« less

Diverse spectrum of tumors in male Sprague-Dawley rats following single high doses of N-ethyl-N-nitrosourea (ENU).

PubMed Central

Stoica, G.; Koestner, A.

1984-01-01

In this study, 30-day-old male Sprague-Dawley rats, were inoculated intraperitoneally with a single dose of 45, 90, and 180 mg/kg of N-ethyl-N-Nitrosourea (ENU). A wide spectrum of neoplasms occurred. The most common tumors were those of the mammary gland and of the nervous system. Although the incidence of mammary tumors was highest in the two high-dose groups (90 and 180 mg/kg ENU), the incidence of neurogenic tumors was highest in the 45 mg/kg dose group. Mammary tumor development led to early death and precluded development of tumors of the nervous system, which require a longer latency period. A variety of neoplasms of other organs have been associated particularly with high doses of ENU, including ameloblastic tumors, carcinomas of the thyroid, prostate, kidney, pancreas, intestine, and lung, hemilymphatic tumors, and sarcomas. It is concluded that large doses of ENU are capable of expanding the tumor spectrum in young male rats beyond the target organs generally affected with lower doses, as described in earlier reports. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 PMID:6465287

Reliability of the Melbourne assessment of unilateral upper limb function.

PubMed

Randall, M; Carlin, J B; Chondros, P; Reddihough, D

2001-11-01

This study examines the reliability of the Melbourne Assessment of Unilateral Upper Limb Function: a quantitative test of quality of movement in children with neurological impairment. The assessment was administered to 20 children aged from 5 to 16 years (mean age 9 years 10 months, SD 2 years 10 months) who had various types and degrees of cerebral palsy (CP). The performances of the 20 children during assessment were videotaped for subsequent scoring by 15 occupational therapists. Scores were analyzed for internal consistency of test items, inter- and intrarater reliability of scorings of the same videotapes, and test-retest reliability using repeat videotaping. Results revealed very high internal consistency of test items (alpha=0.96), moderate to high agreement both within and between raters for all test items (intraclass correlations of at least 0.7) apart from item 16 (hand to mouth and down), and high interrater reliability (0.95) and intrarater reliability (0.97) for total test scores. Test-retest results revealed moderate to high intrarater reliability for item totals (mean of 0.83 and 0.79) for each rater and high reliability for test totals (0.98 and 0.97). These findings indicate that the Melbourne Assessment of Unilateral Upper Limb Function is a reliable tool for measuring the quality of unilateral upper-limb movement in children with CP.

Combination of High-Dose Methylprednisolone and Defibrotide for Veno-Occlusive Disease in Pediatric Hematopoietic Stem Cell Transplant Recipients.

PubMed

Gloude, Nicholas J; Jodele, Sonata; Teusink-Cross, Ashley; Grimley, Michael; Davies, Stella M; Lane, Adam; Myers, Kasiani C

2018-01-01

Veno-occlusive disease (VOD) is a serious complication of hematopoietic stem cell transplant (HSCT), with high mortality in severe cases and until recently very limited therapeutic options consisting largely of supportive care. Defibrotide was recently approved in the United States for the treatment of severe VOD in patients with renal or pulmonary dysfunction after HSCT. Our group previously published on the use of high-dose methylprednisolone (500 mg/m 2 per dose every 12 hours for 6 doses) in patients with VOD, showing good success. A small subset of these individuals were also treated with defibrotide, but additional studies using the combination of high-dose methylprednisolone and defibrotide for the treatment of VOD are lacking. We present a single-institution retrospective chart review of 15 HSCT patients with VOD treated with the combination of high-dose methylprednisolone and defibrotide. VOD developed at a median of 17 days post-HSCT, and combination therapy was initiated within 1 day of VOD diagnosis. Twelve of 15 patients (80%) had multiorgan failure. Our single-center experience using both high-dose methylprednisolone and defibrotide showed a day +100 survival rate of 73% and an overall VOD complete resolution rate of 66.7%, higher than the rates reported in the recent literature using defibrotide alone (40% to 50% day +100 overall survival). These data suggest that the combination of high-dose steroids and defibrotide may be superior to defibrotide alone and warrant further investigation. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Bilateral juvenile nasopharyngeal angiofibroma: report of a case.

PubMed

Wu, Edward C; Chark, Davin W; Bhandarkar, Naveen D

2014-07-01

Juvenile nasopharyngeal angiofibroma (JNA) is the most common benign neoplasm of the nasopharynx. Almost always unilateral on diagnosis, JNAs are locally invasive and may extend across the midline, giving a false bilateral appearance; as such, true bilateral JNA is exceedingly rare. We present a recent case of true bilateral JNA. Single case report of a patient with bilateral JNA, including clinical presentation, diagnosis, and management. The patient presented with unilateral nasal obstruction and recurrent epistaxis. Computed tomography and magnetic resonance imaging demonstrated bilateral, noncontiguous masses. Angiography revealed independent vascular supplies from each respective side with no bilateral supply noted. The patient underwent preoperative embolization followed by endoscopic surgical removal of the larger mass; no complications were noted. Follow-up at 2 years demonstrated no recurrence or growth. The vast majority of JNAs are unilateral, though invasive growth to the contralateral side may appear "bilateral" in presentation. Proper identification of true bilateral JNA is helpful in guiding management, wherein excision of both tumors may not be necessary. © 2014 ARS-AAOA, LLC.

Isolated unilateral cytomegalovirus retinitis: a rare long-term complication after pediatric liver transplantation.

PubMed

Squires, James E; Sisk, Robert A; Balistreri, William F; Kohli, Rohit

2013-02-01

To highlight the rare yet devastating complication of CMV retinitis in a minimally immunosuppressed patient eight yr after liver transplantation for biliary atresia. A 22-yr-old female status-post deceased donor liver transplant at age 13 secondary to biliary atresia receiving single agent immunosuppression presented with acute, unilateral, profound decrease in visual acuity. The patient was diagnosed to have acute onset unilateral CMV retinitis. Retinal examination uncovered classical appearance of retinal whitening and retinal hemorrhages with extensive macular involvement. CMV retinitis can occur as a late complication following liver transplantation. Additionally, CMV retinal disease can occur in the absence of laboratory evidence of CMV infection and independent of additional clinical features suggesting CMV disease. Currently, there is no standard of care regarding screening for CMV retinitis, and thus, further research is needed to define the need for potential changes in current clinical practices and post-transplant screening protocols. © 2012 John Wiley & Sons A/S.

Evaluation of the dosimetric properties of a synthetic single crystal diamond detector in high energy clinical proton beams.

PubMed

Mandapaka, A K; Ghebremedhin, A; Patyal, B; Marinelli, Marco; Prestopino, G; Verona, C; Verona-Rinati, G

2013-12-01

To investigate the dosimetric properties of a synthetic single crystal diamond Schottky diode for accurate relative dose measurements in large and small field high-energy clinical proton beams. The dosimetric properties of a synthetic single crystal diamond detector were assessed by comparison with a reference Markus parallel plate ionization chamber, an Exradin A16 microionization chamber, and Exradin T1a ion chamber. The diamond detector was operated at zero bias voltage at all times. Comparative dose distribution measurements were performed by means of Fractional depth dose curves and lateral beam profiles in clinical proton beams of energies 155 and 250 MeV for a 14 cm square cerrobend aperture and 126 MeV for 3, 2, and 1 cm diameter circular brass collimators. ICRU Report No. 78 recommended beam parameters were used to compare fractional depth dose curves and beam profiles obtained using the diamond detector and the reference ionization chamber. Warm-up∕stability of the detector response and linearity with dose were evaluated in a 250 MeV proton beam and dose rate dependence was evaluated in a 126 MeV proton beam. Stem effect and the azimuthal angle dependence of the diode response were also evaluated. A maximum deviation in diamond detector signal from the average reading of less than 0.5% was found during the warm-up irradiation procedure. The detector response showed a good linear behavior as a function of dose with observed deviations below 0.5% over a dose range from 50 to 500 cGy. The detector response was dose rate independent, with deviations below 0.5% in the investigated dose rates ranging from 85 to 300 cGy∕min. Stem effect and azimuthal angle dependence of the diode signal were within 0.5%. Fractional depth dose curves and lateral beam profiles obtained with the diamond detector were in good agreement with those measured using reference dosimeters. The observed dosimetric properties of the synthetic single crystal diamond detector indicate that its behavior is proton energy independent and dose rate independent in the investigated energy and dose rate range and it is suitable for accurate relative dosimetric measurements in large as well as in small field high energy clinical proton beams.

Clinical Phenotype Predicts Early Staged Bilateral Deep Brain Stimulation in Parkinson’s Disease

PubMed Central

Sung, Victor W.; Watts, Ray L.; Schrandt, Christian J.; Guthrie, Stephanie; Wang, Deli; Amara, Amy W.; Guthrie, Barton L.; Walker, Harrison C.

2014-01-01

Object While many centers place bilateral DBS systems simultaneously, unilateral STN DBS followed by a staged contralateral procedure has emerged as a treatment option for many patients. However little is known about whether the preoperative phenotype predicts when staged placement of a DBS electrode in the opposite subthalamic nucleus will be required. We aimed to determine whether preoperative clinical phenotype predicts early staged placement of a second subthalamic deep brain stimulation (DBS) electrode in patients who undergo unilateral subthalamic DBS for Parkinson's disease (PD). Methods Eighty-two consecutive patients with advanced PD underwent unilateral subthalamic DBS contralateral to the most affected hemibody and had at least 2 years of follow-up. Multivariate logistic regression determined preoperative characteristics that predicted staged placement of a second electrode in the opposite subthalamic nucleus. Preoperative measurements included aspects of the Unified Parkinson Disease Rating Scale (UPDRS), motor asymmetry index, and body weight. Results At 2 years follow-up, 28 of the 82 patients (34%) had undergone staged placement of a contralateral electrode while the remainder chose to continue with unilateral stimulation. Statistically significant improvements in UPDRS total and part 3 scores were retained at the end of the 2 year follow-up period in both subsets of patients. Multivariate logistic regression showed that the most important predictors for early staged placement of a second subthalamic stimulator were low asymmetry index (odds ratio 13.4; 95% confidence interval 2.8, 64.9), high tremor subscore (OR 7.2; CI 1.5, 35.0), and low body weight (OR 5.5; CI 1.4, 22.3). Conclusions This single center study provides evidence that elements of the preoperative PD phenotype predict whether patients will require early staged bilateral subthalamic DBS. These data may aid in the management of patients with advanced PD who undergo subthalamic DBS. PMID:24074493

The Efficacy of Single-Dose versus Double-Dose Praziquantel Treatments on Schistosoma mansoni Infections: Its Implication on Undernutrition and Anaemia among Primary Schoolchildren in Two On-Shore Communities, Northwestern Tanzania

PubMed Central

Buza, Joram; Mpolya, Emmanuel A.; Angelo, Teckla; Kinung'hi, Safari M.

2017-01-01

Administering more than one treatment may increase Praziquantel cure and egg reduction rates, thereby hastening achievement of schistosomiasis transmission control. A total of 431 S. mansoni-infected schoolchildren were randomized to receive either a single or repeated 40 mg/kg Praziquantel dose. Heights, weights, and haemoglobin levels were determined using a stadiometer, weighing scale, and HemoCue, respectively. At 8 weeks, cure rate was higher on repeated dose (93.10%) compared to single dose (68.68%) (p < 0.001). The egg reduction rate was higher on repeated dose (97.54%) compared to single dose (87.27%) (p = 0.0062). Geometric mean egg intensity was lower among those on repeated dose (1.30 epg) compared to single dose (3.18 epg) (p = 0.036) but not at 5 (p > 0.05) and 8 (p > 0.05) months with no difference in reinfection rate. No difference in the prevalence of stunting was observed between the two treatment regimens (p > 0.05) at 8 months, but there was an increase in the prevalence of wasting among those on repeated dose (p < 0.001). There was an increase in the mean haemoglobin levels at 8 months with no difference between the two arms (p > 0.05). To achieve reduction of transmission intensity and disease control in highly endemic areas, repeated treatments alone may not be sufficient. This trial was registered with PACTR201601001416338. PMID:29094048

DOSE-DEPENDENT TRANSITIONS IN MECHANISMS OF TOXICITY: CASE STUDIES

EPA Science Inventory

Experience with dose response and mechanisms of toxicity has shown that multiple mechanisms may exist for a single agent along the continuum of the full dose-response curve. It is highly likely that critical, limiting steps in any given mechanistic pathway may become overwhelmed ...

[Case of anti VGKC-complex antibody associated disorder presenting with severe pain and fasciculations predominant in unilateral upper extremity].

PubMed

Hara, Kenju; Watanabe, Osamu; Shibano, Ken; Ishiguro, Hideaki

2012-01-01

A 21-year-old man complained of severe pain and muscle twitching localized in his right arm. Neurological examination showed muscle fasciculations in his right forearm but no myokymia or myotonia. Needle electromyography revealed fibrillation potentials in his biceps brachii muscle and extensor carpi radialis muscle at rest but no myokymic discharges. His serum anti-voltage-gated potassium channel (VGKC)-complex antibody level was significantly high (194.2pM; controls <100pM). Although anticonvulsant therapy relieved his pain, he was readmitted to our hospital because of severe pain in his left arm and both thighs three months later. A high-dose intravenous immunoglobulin (IVIG) therapy followed by steroid pulse therapy relieved his pain. This case with neither muscle cramp nor myokymia expands the phenotype of anti VGKC-complex antibody associated disorder.

A second dose of kisspeptin-54 improves oocyte maturation in women at high risk of ovarian hyperstimulation syndrome: a Phase 2 randomized controlled trial.

PubMed

Abbara, Ali; Clarke, Sophie; Islam, Rumana; Prague, Julia K; Comninos, Alexander N; Narayanaswamy, Shakunthala; Papadopoulou, Deborah; Roberts, Rachel; Izzi-Engbeaya, Chioma; Ratnasabapathy, Risheka; Nesbitt, Alexander; Vimalesvaran, Sunitha; Salim, Rehan; Lavery, Stuart A; Bloom, Stephen R; Huson, Les; Trew, Geoffrey H; Dhillo, Waljit S

2017-09-01

Can increasing the duration of LH-exposure with a second dose of kisspeptin-54 improve oocyte maturation in women at high risk of ovarian hyperstimulation syndrome (OHSS)? A second dose of kisspeptin-54 at 10 h following the first improves oocyte yield in women at high risk of OHSS. Kisspeptin acts at the hypothalamus to stimulate the release of an endogenous pool of GnRH from the hypothalamus. We have previously reported that a single dose of kisspeptin-54 results in an LH-surge of ~12-14 h duration, which safely triggers oocyte maturation in women at high risk of OHSS. Phase-2 randomized placebo-controlled trial of 62 women at high risk of OHSS recruited between August 2015 and May 2016. Following controlled ovarian stimulation, all patients (n = 62) received a subcutaneous injection of kisspeptin-54 (9.6 nmol/kg) 36 h prior to oocyte retrieval. Patients were randomized 1:1 to receive either a second dose of kisspeptin-54 (D; Double, n = 31), or saline (S; Single, n = 31) 10 h thereafter. Patients, embryologists, and IVF clinicians remained blinded to the dosing allocation. Study participants: Sixty-two women aged 18-34 years at high risk of OHSS (antral follicle count ≥23 or anti-Mullerian hormone level ≥40 pmol/L). Setting: Single centre study carried out at Hammersmith Hospital IVF unit, London, UK. Primary outcome: Proportion of patients achieving an oocyte yield (percentage of mature oocytes retrieved from follicles ≥14 mm on morning of first kisspeptin-54 trigger administration) of at least 60%. Secondary outcomes: Reproductive hormone levels, implantation rate and OHSS occurrence. A second dose of kisspeptin-54 at 10 h following the first induced further LH-secretion at 4 h after administration. A higher proportion of patients achieved an oocyte yield ≥60% following a second dose of kisspeptin-54 (Single: 14/31, 45%, Double: 21/31, 71%; absolute difference +26%, CI 2-50%, P = 0.042). Patients receiving two doses of kisspeptin-54 had a variable LH-response following the second kisspeptin dose, which appeared to be dependent on the LH-response following the first kisspeptin injection. Patients who had a lower LH-rise following the first dose of kisspeptin had a more substantial 'rescue' LH-response following the second dose of kisspeptin. The variable LH-response following the second dose of kisspeptin resulted in a greater proportion of patients achieving an oocyte yield ≥60%, but without also increasing the frequency of ovarian over-response and moderate OHSS (Single: 1/31, 3.2%, Double: 0/31, 0%). Further studies are warranted to directly compare kisspeptin-54 to more established triggers of oocyte maturation. Triggering final oocyte maturation with kisspeptin is a novel therapeutic option to enable the use of fresh embryo transfer even in the woman at high risk of OHSS. The study was designed, conducted, analysed and reported entirely by the authors. The Medical Research Council (MRC), Wellcome Trust & National Institute of Health Research (NIHR) provided research funding to carry out the studies. There are no competing interests to declare. Clinicaltrial.gov identifier NCT01667406. 8 August 2012. 10 August 2015. © The Author 2017. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology.

Percutaneous Pediculoplasty for Vertebral Hemangioma Involving the Neural Arch: A Case Report

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

Fuwa, Sokun, E-mail: sofuwa@luke.or.jp; Numaguchi, Yuji; Kobayashi, Nobuo

2008-01-15

Vertebral hemangiomas occasionally involve the neural arch and they can be symptomatic. We report a case of symptomatic vertebral hemangioma mainly involving the unilateral neural arch which was successfully treated with percutaneous pediculoplasty using a single-needle technique.

Pharmacodynamic and pharmacokinetic profile of S 17092, a new orally active prolyl endopeptidase inhibitor, in elderly healthy volunteers. A phase I study.

PubMed

Morain, P; Robin, J L; De Nanteuil, G; Jochemsen, R; Heidet, V; Guez, D

2000-10-01

The aim of this study was to characterize the pharmacodynamics and the pharmacokinetics of S 17092, a new orally active prolyl endopeptidase inhibitor following single and repeated administration in elderly healthy volunteers. This was a double-blind, randomized, placebo-controlled, single and multiple dose study in elderly healthy male and female volunteers (n = 36). Four doses were investigated in sequential order: 100, 400, 800 and 1200 mg. Each dose was administered orally once a day in single administration and then, after a 1 week washout period, during 7 days. Pharmacodynamics were assessed by measurement of plasmatic prolyl endopeptidase (PEP) activity, quantitative electroencephalogram (EEG) and psychometric tests. S 17092 concentrations in plasma were quantified by high performance liquid chromatography with tandem mass spectrometric detection. PEP activity in plasma was dose-dependently inhibited both after administration of a single dose and after repeated doses of S 17092. The mean maximal inhibition was obtained within 0.5-2 h after dosing, while inhibition lasted at least 12 h after dose administration. S 17092 appeared to be a centrally active substance as it induced statistically significant modifications in EEG compared with placebo. S 17092 at 100 mg exerted an acute increase in alpha band following single administration at 4 h and 8 h postdosing. When administered repeatedly over 7 days S 17092 did not appear to induce significant lasting central nervous system (CNS) effects. In psychometric tests, response times in the numeric working memory were significantly reduced compared with placebo, following the 800 mg dose. There were some beneficial residual effects of the 1200 mg dose on day 13: delayed word recall and word recognition sensitivity improved compared with the declines noted under placebo. Maximum measured concentration (Cmax) and area under the curve (AUC) parameters increased in proportion to the dose. The terminal half-life (t(1/2)) values ranged between 9 and 31 h on day 1 and between 7 and 18 h on day 14. A high interindividual variability was observed at all dose levels. S 17092 was well tolerated with no clinically significant changes in laboratory or physical parameters observed at any dose. S 17092 had a potent, dose-dependent inhibitory effect on plasmatic PEP, increased alpha band EEG at the 100 mg dose and improved performance in two verbal memory tests at the 1200 mg dose while there were disruption to the vigilance task. The results obtained in elderly healthy subjects indicated that S 17092 is suitable for once-daily dosing without any serious adverse events.

Postoperative analgesic efficacy of single high dose and low dose rectal acetaminophen in pediatric ophthalmic surgery

PubMed Central

Gandhi, Ranju; Sunder, Rani

2012-01-01

Background: Analgesic efficacy of rectal acetaminophen is variable in different surgical procedures. Little data is available on its efficacy in ophthalmic surgeries. We conducted this prospective, randomized, double blind study to evaluate and compare the efficacy of single high dose and low dose rectal acetaminophen in pediatric ophthalmic surgery over a 24 hour period. Materials and Methods: 135 children scheduled for elective ophthalmic surgery were randomly allocated to one of the three groups, high, low, or control (H, L, or N) and received rectal acetaminophen 40 mg/kg, 20 mg/kg or no rectal drug respectively after induction of general anesthesia. Postoperative observations included recovery score, hourly observational pain score (OPS) up to 8 hours, time to first analgesic demand, and requirement of rescue analgesics and antiemetics over a 24 hour period. Results: Nineteen of 30 (63%) of children in group N required postoperative rescue analgesic versus 5/48 (10%) of group H (P <0.0001) and 10/47 (23%) of group L (P =0.0005) during 24 hour period. Mean time to requirement of first analgesic was 206±185 min in group H, 189±203min in group L, and 196 ±170 min in group N (P=0.985). OPS was significantly lower in group H and L compared to group N during first 8 hours. Requirement of rescue antiemetic was 18.7% in group H as compared to 23% each in group L and group N (P >0.5). Conclusions: Single dose rectal acetaminophen can provide effective postoperative analgesia for pediatric ophthalmic surgery at both high dose (40 mg/kg) and low dose (20 mg/kg) both in early postoperative and over a 24 hour period. PMID:23225924

Introducing iron isomaltoside 1000 (Monofer®)-development rationale and clinical experience.

PubMed

Kalra, Philip A

2011-06-01

Patients with chronic kidney disease (CKD) often suffer from iron deficiency anaemia necessitating treatment with intravenous (IV) iron. Several studies demonstrate that oral iron is insufficient in these patients and that IV supplementation is a more effective treatment. Until now, use of available parenteral iron preparations has been limited by dosing schedules and the need, in some cases, for a test dose, and despite the availability of a range of different IV iron compounds, there is still a need for improved compounds. The new IV iron, iron isomaltoside 1000 Monofer®, is composed of iron and chemically modified isomalto-oligosaccharides which have a mean molecular weight of 1000 Da and consist predominantly of 3-5 glucose units. In contrast to dextrans, the carbohydrate isomaltoside 1000 is a linear and unbranched structure with theoretically a low immunological potential. Hence, a test dose is not necessary. Iron isomaltoside 1000 contains strongly bound iron within the iron-isomaltoside formulation, which enables a controlled slow release of bioavailable iron to the iron-binding proteins, with potentially a reduced risk of free iron toxicity. This allows flexible dosing including high and rapid dosing securing convenient iron therapy for a wide range of patients. The development of Monofer® has been enthusiastically acknowledged by clinicians, and in 2009, there has been fast approval by European authorities via a decentralized registration procedure. This new IV iron is currently being marketed in several European countries. This article describes the development rationale and summarizes the clinical data assessing the use of iron isomaltoside 1000 administered without a test dose by either repeated bolus injections or fast high single iron infusions [defined as total dose infusion (TDI)] to patients suffering from CKD. Since CKD is associated with a high prevalence of cardiovascular disease, data from a small trial applying high single doses of iron isomatoside 1000 in patients with chronic heart failure (CHF) are also reviewed. Collectively, the available data demonstrate adequate efficacy and a good safety profile of iron isomaltoside 1000 in CKD and CHF patients even when administered without a test dose and as single rapid high-dose infusions.

A quality improvement project to reduce the intraoperative use of single-dose fentanyl vials across multiple patients in a pediatric institution.

PubMed

Buck, David; Subramanyam, Rajeev; Varughese, Anna

2016-01-01

The use of a single-dose vial across multiple patients presents a risk to sterility and is against CDC guidelines. We initiated a quality improvement (QI) project to reduce the intraoperative use of single-dose vials of fentanyl across multiple patients at Cincinnati Children's Hospital Medical Center (CCHMC). The initial step of the improvement project was the development of a Key Driver Diagram. The diagram has the SMART aim of the project, key drivers inherent to the process we are trying to improve, and specific interventions targeting the key drivers. The number of patients each week receiving an IV dose of fentanyl, from a vial previously accessed for another patient was tracked in a high turnover operating room (OR). The improvement model used was based on the concept of building Plan-Do-Study-Act (PDSA) cycles. Tests of change included provider education, provision of an increased number of fentanyl vials, alternate wasting processes, and provision of single-use fentanyl syringes by the pharmacy. Prior to initiation of this project, it was common for a single fentanyl vial to be accessed for multiple patients. Our data showed an average percentage of failures of just over 50%. During the end of the project, after 7 months, the mean percentage failures had dropped to 5%. Preparation of 20 mcg single-use fentanyl syringes by pharmacy, combined with education of providers on appropriate use, was successful in reducing failures to below our goal of 25%. Appropriately sized fentanyl syringes prepared by pharmacy, education on correct use of single-dose vials, and reminders in the OR, reduced the percentage of patients receiving a dose of fentanyl from a vial previously accessed for another patient in a high-volume otolaryngology room. © 2015 John Wiley & Sons Ltd.

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

PubMed

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

2012-01-01

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

Patients With Chondrolabral Pathology Have Bilateral Functional Impairments 12 to 24 Months After Unilateral Hip Arthroscopy: A Cross-sectional Study.

PubMed

Kemp, Joanne L; Risberg, May Arna; Schache, Anthony G; Makdissi, Michael; Pritchard, Michael G; Crossley, Kay M

2016-11-01

Study Design Cross-sectional study. Background Functional task performance in patients with chondrolabral pathology following hip arthroscopy is unknown. Objectives To investigate in people with chondrolabral pathology following hip arthroscopy (1) the bilateral differences in functional task performance compared to controls, (2) the association of hip muscle strength with functional task performance, and (3) the association of functional task performance scores with good outcome, as measured by International Hip Outcome Tool score. Methods Seventy-one patients who had unilateral hip arthroscopy for hip pain and 60 controls were recruited. Patient-reported outcomes included the 4 subscales of the International Hip Outcome Tool. Hip muscle strength measures included abduction, adduction, extension, flexion, external rotation, and internal rotation. Functional tasks assessed included the single hop test, the side bridge test, and the single-leg rise test. For aim 1, analyses of covariance tests were used. For aim 2, stepwise multiple linear regression analyses were used. For aim 3, receiver operating characteristic curve analyses were used. Results Compared to controls, the chondrolabral pathology group had significantly worse performance on both legs for each of the functional tasks (P<.001). Greater hip abduction strength was moderately associated with better performance on functional tasks in the chondrolabral pathology group (adjusted R 2 range, 0.197-0.407; P<.001). Cutoff values associated with good outcome were 0.37 (hop distance/height) for the single hop, 16 repetitions for the single-leg rise, and 34 seconds for the side bridge test. Conclusion Patients with hip chondrolabral pathology had reduced functional task performance bilaterally 12 to 24 months after unilateral hip arthroscopy when compared to controls. Level of Evidence Therapy/symptom prevalence, level 3b. J Orthop Sports Phys Ther 2016;46(11):947-956. doi:10.2519/jospt.2016.6577.

Tissue responses to low protracted doses of high LET radiations or photons: Early and late damage relevant to radio-protective countermeasures

NASA Astrophysics Data System (ADS)

Ainsworth, E. J.; Afzal, S. M. J.; Crouse, D. A.; Hanson, W. R.; Fry, R. J. M.

Early and late murine tissue responses to single or fractionated low doses of heavy charged particles, fission-spectrum neutrons or gamma rays are considered. Damage to the hematopoietic system is emphasized, but results on acute lethality, host response to challenge with transplanted leukemia cells and life-shortening are presented. Low dose rates per fraction were used in some neutron experiments. Split-dose lethality studies (LD 50/30) with fission neutrons indicated greater accumulation of injury during a 9 fraction course (over 17 days) than was the case for γ-radiation. When total doses of 96 or 247 cGy of neutrons or γ rays were given as a single dose or in 9 fractions, a significant sparing effect on femur CFU-S depression was observed for both radiation qualities during the first 11 days, but there was not an earlier return to normal with dose fractionation. During the 9 fraction sequence, a significant sparing effect of low dose rate on CFU-S depression was observed in both neutron and γ-irradiated mice. CFU-S content at the end of the fractionation sequence did not correlate with measured LD 50/30. Sustained depression of femur and spleen CFU-S and a significant thrombocytopenia were observed when a total neutron dose of 240 cGy was given in 72 fractions over 24 weeks at low dose rates. The temporal aspects of CFU-S repopulation were different after a single versus fractionated neutron doses. The sustained reduction in the size of the CFU-S population was accompanied by an increase in the fraction in DNA synthesis. The proliferation characteristics and effects of age were different for radial CFU-S population closely associated with bone, compared with the axial population that can be readily aspirated from the femur. In aged irradiated animals, the CFU-S proliferation/redistribution response to typhoid vaccine showed both an age and radiation effect. After high single doses of neutrons or γ rays, a significant age- and radiation-related deficiency in host defense mechanisms was detected by a shorter mean survival time following challenge with transplantable leukemia cells. Comparison of dose-response curves for life shortening after irradiation with fission-spectrum neutrons or high energy silicon particles indicated high initial slopes for both radiation qualities at low doses, but for higher doses of silicon, the effect per Gy decreased to a value similar to that for γ rays. The two component life-shortening curve for silicon particles has implications for the potential efficacy of radioprotectants. Recent studies on protection against early and late effects by aminothiols, prostaglandins, and other compounds are discussed.

The use and reliability of SymNose for quantitative measurement of the nose and lip in unilateral cleft lip and palate patients.

PubMed

Mosmuller, David; Tan, Robin; Mulder, Frans; Bachour, Yara; de Vet, Henrica; Don Griot, Peter

2016-10-01

It is essential to have a reliable assessment method in order to compare the results of cleft lip and palate surgery. In this study the computer-based program SymNose, a method for quantitative assessment of the nose and lip, will be assessed on usability and reliability. The symmetry of the nose and lip was measured twice in 50 six-year-old complete and incomplete unilateral cleft lip and palate patients by four observers. For the frontal view the asymmetry level of the nose and upper lip were evaluated and for the basal view the asymmetry level of the nose and nostrils were evaluated. A mean inter-observer reliability when tracing each image once or twice was 0.70 and 0.75, respectively. Tracing the photographs with 2 observers and 4 observers gave a mean inter-observer score of 0.86 and 0.92, respectively. The mean intra-observer reliability varied between 0.80 and 0.84. SymNose is a practical and reliable tool for the retrospective assessment of large caseloads of 2D photographs of cleft patients for research purposes. Moderate to high single inter-observer reliability was found. For future research with SymNose reliable outcomes can be achieved by using the average outcomes of single tracings of two observers. Copyright © 2016 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

Meta-analysis on the Safety and Efficacy of the Reperfusion Use of a Single High Dose of Anti-T-Lymphocyte Globulin Fresenius in Kidney Transplantation.

PubMed

Du, X; Wang, W; Sun, Z-J; Su, L L; Zhang, X-D

2016-01-01

The aim of this study was to evaluate the effects of a single high dose of the anti-T-lymphocyte globulin Fresenius (ATG-F), given before kidney transplantation, on the prevention of acute rejection response and infections and on the survival rate of the renal graft and patient. Databases including PubMed, Embase, and the Cochrane Library were searched to identify randomized controlled trials relevant to studying the presurgical use of a single high dose of ATG-F. Five RCTs that included 346 patients were selected. The meta-analysis suggested that the application of ATG-F reduced the postsurgical acute rejection reaction incidence compared to that of the control group (relative risk = 0.50, 95% confidence interval = 0.35-0.71, P = .0001). However, the application of ATG-F exhibited no significant effect on the incidence of urinary tract infection, cytomegalovirus infection, and delayed graft function. Furthermore, the one-year patient survival rate and kidney graft survival rate were not affected. The meta-analysis suggested that the reperfusion use of a single high dose (9 mg/kg) of ATG-F could effectively reduce the incidence of postsurgical acute rejection response without affecting the occurrence of infections, the survival rates of kidney grafts and patients, or the incidence of delayed graft function. Copyright © 2016 The Authors. Published by Elsevier Inc. 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.

Spanish Transcultural Adaptation and Validity of the Behavioral Inattention Test

PubMed Central

Sánchez-Cabeza, Ángel; Huertas-Hoyas, Elisabet; Máximo-Bocanegra, Nuria; Rosa María Martínez-Piédrola; Pérez-de-Heredia-Torres, Marta

2017-01-01

Objective To adapt, validate, and translate the Behavioral Inattention Test as an assessment tool for Spanish individuals with unilateral spatial neglect. Design A cross-sectional descriptive study. Setting University laboratories. Participants A sample of 75 Spanish stroke patients and 18 healthy control subjects. Interventions Not applicable. Main Outcome Measures The Behavioral Inattention Test. Results The Spanish version of the Behavioral Inattention Test shows a high degree of reliability both in the complete test (α = .90) and in the conventional (α = .93) and behavioral subtests (α = .75). The concurrent validity between the total conventional and behavioral scores was high (r = −.80; p < 0.001). Significant differences were found between patients with and without unilateral spatial neglect (p < 0.001). In the comparison between right and left damaged sides, differences were found in all items, except for article reading (p = 0.156) and card sorting (p = 0.117). Conclusions This measure is a useful tool for evaluating unilateral spatial neglect as it provides information on everyday problems. The BIT discriminates between stroke patients with and without unilateral spatial neglect. This measure constitutes a reliable tool for the diagnosis, planning, performance, and design of specific treatment programs intended to improve the functionality and quality of life of people with unilateral spatial neglect. PMID:29097959

Children with optic nerve hypoplasia face a high risk of neurodevelopmental disorders.

PubMed

Dahl, Sara; Wickström, Ronny; Ek, Ulla; Teär Fahnehjelm, Kristina

2018-03-01

Optic nerve hypoplasia (ONH) is a congenital ocular malformation that has been associated with neurodevelopmental disorders, but the prevalence in unilateral disease and less severe visual impairment is unknown. We studied intellectual disability and autism spectrum disorders (ASDs) in patients with ONH. This was a population-based cross-sectional cohort study of 65 patients (33 female) with ONH below 20 years of age, living in Stockholm in December 2009, with data analysed in January 2016. Of these 35 were bilateral and 30 were unilateral. Neurodevelopmental disorders were diagnosed or confirmed by neurological assessments, the Five to Fifteen parent questionnaire and reviewing previous neuropsychological investigations or conducting neuropsychological tests. Bilateral ONH patients had lower mean full scale intelligence quotient scores than unilateral patients (84.4 and 99.4, respectively, p = 0.049). We assessed intellectual disability in 55 eligible patients, and it was more common in patients with bilateral ONH (18 of 32, 56%) than unilateral ONH (two of 23, 9%, p < 0.001). ASDs were diagnosed in seven of 42 (17%) patients. Children with bilateral ONH had a high risk of neurodevelopmental disorders, especially intellectual disability. The risk was lower in unilateral ONH, but the levels of neurodevelopmental disorders warrant screening of both groups. ©2017 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

Behavioral effects of ketamine and toxic interactions with psychostimulants

PubMed Central

Hayase, Tamaki; Yamamoto, Yoshiko; Yamamoto, Keiichi

2006-01-01

Background The anesthetic drug ketamine (KT) has been reported to be an abused drug and fatal cases have been observed in polydrug users. In the present study, considering the possibility of KT-enhanced toxic effects of other drugs, and KT-induced promotion of an overdose without making the subject aware of the danger due to the attenuation of several painful subjective symptoms, the intraperitoneal (i.p.) KT-induced alterations in behaviors and toxic interactions with popular co-abused drugs, the psychostimulants cocaine (COC) and methamphetamine (MA), were examined in ICR mice. Results A single dose of KT caused hyperlocomotion in a low (30 mg/kg, i.p.) dose group, and hypolocomotion followed by hyperlocomotion in a high (100 mg/kg, i.p.) dose group. However, no behavioral alterations derived from enhanced stress-related depression or anxiety were observed in the forced swimming or the elevated plus-maze test. A single non-fatal dose of COC (30 mg/kg, i.p.) or MA (4 mg/kg, i.p.) caused hyperlocomotion, stress-related depression in swimming behaviors in the forced swimming test, and anxiety-related behavioral changes (preference for closed arms) in the elevated plus-maze test. For the COC (30 mg/kg) or MA (4 mg/kg) groups of mice simultaneously co-treated with KT, the psychostimulant-induced hyperlocomotion was suppressed by the high dose KT, and the psychostimulant-induced behavioral alterations in the above tests were reversed by both low and high doses of KT. For the toxic dose COC (70 mg/kg, i.p.)- or MA (15 mg/kg, i.p.)-only group, mortality and severe seizures were observed in some animals. In the toxic dose psychostimulant-KT groups, KT attenuated the severity of seizures dose-dependently. Nevertheless, the mortality rate was significantly increased by co-treatment with the high dose KT. Conclusion Our results demonstrated that, in spite of the absence of stress-related depressive and anxiety-related behavioral alterations following a single dose of KT treatment, and in spite of the KT-induced anticonvulsant effects and attenuation of stress- and anxiety-related behaviors caused by COC or MA, the lethal effects of these psychostimulants were increased by KT. PMID:16542420

Does unilateral laparoscopic diathermy adjusted to ovarian volume increase the chances of ovulation in women with polycystic ovary syndrome?

PubMed

Sunj, M; Canic, T; Baldani, D P; Tandara, M; Jeroncic, A; Palada, I

2013-09-01

Does unilateral volume-adjusted laparoscopic diathermy increase the chances of ovulation in women with polycystic ovary syndrome (PCOS)? Although unilateral laparoscopic ovarian drilling (ULOD) using adjusted thermal doses was more efficient than bilateral laparoscopic ovarian drilling (BLOD) using fixed doses, the chances of ovulation were improved in patients irrespective of the technique used. The adjustment of the thermal dose to ovarian volume in BLOD increases ovulation and pregnancy rates compared with fixed-dose treatment, but BLOD causes the formation of adhesions, particularly on the left ovary, and increases the risk of damage to ovarian tissue. In contrast, ULOD with a fixed thermal dose minimizes the risk of ovarian tissue damage, and can increase the activity in both right and left ovaries, although this varies in humans and in other species. This prospective, longitudinal, study, between September 2009 and January 2013, included 96 infertile women with PCOS who were unresponsive to clomiphene citrate treatment and had underwent either ULOD or BLOD. After surgery, the groups were followed up for 6 months to assess ovulatory response. Patients were assigned to two groups; one group underwent laparoscopic ovarian drilling of the right ovary alone, while both ovaries were treated in the second group. The ULOD group (n = 49) received thermal doses adjusted to the volume of the right ovary (60 J/cm³). The BLOD group (n = 47) received fixed doses of 600 J per ovary, regardless of its volume. The two treatment groups were matched by the number of participants, age and baseline parameters. The ovulation rate during the first menstrual cycle after LOD was significantly higher in the ULOD group than in the BLOD group [73 versus 49%; absolute risk reduction (ARR), -0.25; 95% confidence interval (CI), -0.44 to -0.03; P = 0.014]. Treatment with ULOD on the right ovary significantly increased the chances of ovulation in patients with a larger right ovary compared with those who had a smaller right ovary (100 versus 36%; ARR, -0.64; 95% CI, -0.84 to -0.37; P = 0.004). Interestingly, the chances of ovulation were also significantly higher in patients in the BLOD group who had a larger right ovary compared with those who had a smaller right ovary (88 versus 33%; ARR, -0.55; 95% CI, -0.73 to -0.28; P = 0.002). The pregnancy rate was also significantly higher in patients with a larger right ovary compared with those with a smaller right ovary, regardless of the treatment group. The 6-month follow-up was too short to demonstrate any long-term differences in the ovulation rates. Future research should therefore extend the follow-up beyond 6 months. Another limitation is that ULOD was used to treat only the right ovary. Future studies should investigate whether ULOD treatment of the larger ovary, whether left or right, would significantly increase the ovulation rate. This study represents an advance in the determination of the optimal laparoscopic treatment for women with PCOS, as it was shown that improved results can be achieved using less thermal energy in volume-adjusted ULOD.

Pharmacokinetics of voriconazole after oral administration of single and multiple doses in Hispaniolan Amazon parrots (Amazona ventralis).

PubMed

Sanchez-Migallon Guzman, David; Flammer, Keven; Papich, Mark G; Grooters, Amy M; Shaw, Shannon; Applegate, Jeff; Tully, Thomas N

2010-04-01

To determine the pharmacokinetics and safety of voriconazole administered orally in single and multiple doses in Hispaniolan Amazon parrots (Amazona ventralis). 15 clinically normal adult Hispaniolan Amazon parrots. Single doses of voriconazole (12 or 24 mg/kg) were administered orally to 15 and 12 birds, respectively; plasma voriconazole concentrations were determined at intervals via high-pressure liquid chromatography. In a multiple-dose trial, voriconazole (18 mg/kg) or water was administered orally to 6 and 4 birds, respectively, every 8 hours for 11 days (beginning day 0); trough plasma voriconazole concentrations were evaluated on 3 days. Birds were monitored daily, and clinicopathologic variables were evaluated before and after the trial. Voriconazole elimination half-life was short (0.70 to 1.25 hours). In the single-dose experiments, higher drug doses yielded proportional increases in the maximum plasma voriconazole concentration (C(max)) and area under the curve (AUC). In the multiple-dose trial, C(max), AUC, and plasma concentrations at 2 and 4 hours were decreased on day 10, compared with day 0 values; however, there was relatively little change in terminal half-life. With the exception of 1 voriconazole-treated parrot that developed polyuria, adverse effects were not evident. In Hispaniolan Amazon parrots, oral administration of voriconazole was associated with proportional kinetics following administration of single doses and a decrease in plasma concentration following administration of multiple doses. Oral administration of 18 mg of voriconazole/kg every 8 hours would require adjustment to maintain therapeutic concentrations during long-term treatment. Safety and efficacy of voriconazole treatment in this species require further investigation.

Pharmacokinetics of Mirabegron, a β3-Adrenoceptor Agonist for Treatment of Overactive Bladder, in Healthy East Asian Subjects.

PubMed

Iitsuka, Hiromi; van Gelderen, Marcel; Katashima, Masataka; Takusagawa, Shin; Sawamoto, Taiji

2015-05-01

The objective of these studies was to evaluate the pharmacokinetic profile, safety, and tolerability of mirabegron, a β3-adrenoceptor agonist for the treatment of overactive bladder, including food effects (low- or high-fat meals) and sex, in healthy East Asian subjects. In total, 5 pharmacokinetic studies of mirabegron were conducted in healthy East Asian subjects. Food effects were assessed in 3 randomized, single-dose studies in young Japanese male subjects (study 1), male and female subjects (study 2), and young Taiwanese male and female subjects (study 3). In the other 2 single- and multiple-dose studies in young Chinese male and female subjects (study 4 and study 5), mirabegron was administered as a single dose under fasted conditions. After the washout period, mirabegron was administered once daily under fed conditions for 8 days. Pharmacokinetic parameters were determined using noncompartmental methods. Safety and tolerability assessments included physical examinations, vital signs, 12-lead ECG, clinical laboratory tests (biochemistry, hematology, and urinalysis), and adverse event monitoring. After administration of single oral doses of mirabegron, exposure under fed conditions was lower than under fasted conditions in Japanese and Taiwanese subjects. In Japanese subjects, a greater reduction in mirabegron Cmax and AUC0-∞ was observed after a low-fat meal compared with a high-fat meal. In Chinese subjects, Cmax was reached at approximately 4.0 hours after single oral doses. Mirabegron accumulated 2- to 3-fold on once-daily dosing of multiple-dose relative to single-dose data. Steady state was reached within 7 days. After administration of mirabegron, mean values for Cmax and AUC in female subjects were higher than those in male subjects. Mirabegron was well tolerated in Japanese, Taiwanese, and Chinese subjects. Our studies confirm the higher exposure levels of mirabegron in female compared with male East Asian subjects as found earlier in Western subjects. Furthermore, the effects of food on the pharmacokinetic profiles appeared to be similar among the 3 populations tested in our studies. The findings suggest that there are no significant pharmacokinetic differences among the Japanese, Taiwanese, and Chinese populations. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

[Analysis of the speech discrimination scores of patients with congenital unilateral microtia and external auditory canal atresia in noise].

PubMed

Zhang, Y; Li, D D; Chen, X W

2017-06-20

Objective: Case-control study analysis of the speech discrimination of unilateral microtia and external auditory canal atresia patients with normal hearing subjects in quiet and noisy environment. To understand the speech recognition results of patients with unilateral external auditory canal atresia and provide scientific basis for clinical early intervention. Method: Twenty patients with unilateral congenital microtia malformation combined external auditory canal atresia, 20 age matched normal subjects as control group. All subjects used Mandarin speech audiometry material, to test the speech discrimination scores (SDS) in quiet and noisy environment in sound field. Result: There's no significant difference of speech discrimination scores under the condition of quiet between two groups. There's a statistically significant difference when the speech signal in the affected side and noise in the nomalside (single syllable, double syllable, statements; S/N=0 and S/N=-10) ( P <0.05). There's no significant difference of speech discrimination scores when the speech signal in the nomalside and noise in the affected side. There's a statistically significant difference in condition of the signal and noise in the same side when used one-syllable word recognition (S/N=0 and S/N=-5) ( P <0.05), while double syllable word and statement has no statistically significant difference ( P >0.05). Conclusion: The speech discrimination scores of unilateral congenital microtia malformation patients with external auditory canal atresia under the condition of noise is lower than the normal subjects. Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.

A rehabilitation program based on music practice for patients with unilateral spatial neglect: a single-case study.

PubMed

Guilbert, Alma; Clément, Sylvain; Moroni, Christine

2017-02-01

Two major limitations of unilateral spatial neglect (USN) rehabilitation methods are actually reported: a lack of long-term efficiency and a lack of generalization to daily life. The aim of our case study was to underline how a multisensory method-music practice-could avoid these limitations. Mrs BV suffered from a chronic severe USN. She had rehabilitation sessions of music practice over 8 weeks. An improvement of her USN was found on paper-pencil tests but also in daily activities. Benefits subsisted 4 months after rehabilitation. Music practice seemed to avoid the major limitations of USN rehabilitations and could represent a promising tool.

MODELING THE INTERACTION THRESHOLD: THE BREAK-POINT BETWEEN ADDITIVITY AND NON-ADDITIVITY

EPA Science Inventory

Dose-dependent changes in toxicity mechanisms of single chemicals may take place along the full dose-response spectrum. At high doses, the possibility exists for some steps in the principle mechanism of toxicity to shift to other mechanisms. The possibility of mechanism shifts fo...

Effectiveness of conventional versus virtual reality based vestibular rehabilitation in the treatment of dizziness, gait and balance impairment in adults with unilateral peripheral vestibular loss: a randomised controlled trial.

PubMed

Meldrum, Dara; Herdman, Susan; Moloney, Roisin; Murray, Deirdre; Duffy, Douglas; Malone, Kareena; French, Helen; Hone, Stephen; Conroy, Ronan; McConn-Walsh, Rory

2012-03-26

Unilateral peripheral vestibular loss results in gait and balance impairment, dizziness and oscillopsia. Vestibular rehabilitation benefits patients but optimal treatment remains unknown. Virtual reality is an emerging tool in rehabilitation and provides opportunities to improve both outcomes and patient satisfaction with treatment. The Nintendo Wii Fit Plus® (NWFP) is a low cost virtual reality system that challenges balance and provides visual and auditory feedback. It may augment the motor learning that is required to improve balance and gait, but no trials to date have investigated efficacy. In a single (assessor) blind, two centre randomised controlled superiority trial, 80 patients with unilateral peripheral vestibular loss will be randomised to either conventional or virtual reality based (NWFP) vestibular rehabilitation for 6 weeks. The primary outcome measure is gait speed (measured with three dimensional gait analysis). Secondary outcomes include computerised posturography, dynamic visual acuity, and validated questionnaires on dizziness, confidence and anxiety/depression. Outcome will be assessed post treatment (8 weeks) and at 6 months. Advances in the gaming industry have allowed mass production of highly sophisticated low cost virtual reality systems that incorporate technology previously not accessible to most therapists and patients. Importantly, they are not confined to rehabilitation departments, can be used at home and provide an accurate record of adherence to exercise. The benefits of providing augmented feedback, increasing intensity of exercise and accurately measuring adherence may improve conventional vestibular rehabilitation but efficacy must first be demonstrated. Clinical trials.gov identifier: NCT01442623.

A case report of bicornis bicollis uterus with unilateral cervical atresia: an unusual aetiology of chronic debilitating pelvic pain in a Cameroonian teenager.

PubMed

Dohbit, Julius Sama; Meka, Esther; Tochie, Joel Noutakdie; Kamla, Igor; Mwadjie, Darolles; Foumane, Pascal

2017-06-02

Congenital uterine anomalies like bicornis or bicornuate uterus are relatively rare in sub-Saharan Africa. They are associated with an increased rate of spontaneous abortion, preterm delivery, and infertility. The occurrence of bicornis bicollis uterus with unilateral cervical atresia is exceptional and its management is controversial. We hereby report a rare cause of chronic pelvic pain in a Cameroonian teenager due to unilateral obstructive hematometra and hematosalpinx in the non-communicating horn of a bicornis bicollis uterus. A 13-year-old premenarchal non-virgin female presented with chronic and severe cyclical crampy pelvic pain. On clinical examination, she had a perforated hymen, a single vagina, and one uterine cervix. A two-dimensional pelvic ultrasonography revealed hematometra but missed out the underlying anomaly. Failure to drain the hematometra by serial cervical dilatations prompted an exploratory laparotomy which revealed: bicornis bicollis uterus with a right rudimentary uterine horn communicating with the vagina and a left non-communicating uterine horn distended by hematometra due to a homolateral cervical atresia. She underwent utero-vaginal canalization and a left hemi-hysterotomy with drainage of the hematometra. The postoperative period was uneventful. Regular cyclic menses occurred thereafter beginning at the first postoperative month. She had complete resolution of symptoms without recurrence after six months. Due to the risk of compromised fertility from bicornis uterus and the diagnostic challenges akin to resource-limited settings, we highlight the need for a high index of suspicion by healthcare providers when faced with chronic pelvic pain in premenarchal adolescents.

Hybrid cochlear implantation: quality of life, quality of hearing, and working performance compared to patients with conventional unilateral or bilateral cochlear implantation.

PubMed

Härkönen, Kati; Kivekäs, Ilkka; Kotti, Voitto; Sivonen, Ville; Vasama, Juha-Pekka

2017-10-01

The objective of the present study is to evaluate the effect of hybrid cochlear implantation (hCI) on quality of life (QoL), quality of hearing (QoH), and working performance in adult patients, and to compare the long-term results of patients with hCI to those of patients with conventional unilateral cochlear implantation (CI), bilateral CI, and single-sided deafness (SSD) with CI. Sound localization accuracy and speech-in-noise test were also compared between these groups. Eight patients with high-frequency sensorineural hearing loss of unknown etiology were selected in the study. Patients with hCI had better long-term speech perception in noise than uni- or bilateral CI patients, but the difference was not statistically significant. The sound localization accuracy was equal in the hCI, bilateral CI, and SSD patients. QoH was statistically significantly better in bilateral CI patients than in the others. In hCI patients, residual hearing was preserved in all patients after the surgery. During the 3.6-year follow-up, the mean hearing threshold at 125-500 Hz decreased on average by 15 dB HL in the implanted ear. QoL and working performance improved significantly in all CI patients. Hearing outcomes with hCI are comparable to the results of bilateral CI or CI with SSD, but hearing in noise and sound localization are statistically significantly better than with unilateral CI. Interestingly, the impact of CI on QoL, QoH, and working performance was similar in all groups.

Pharmacokinetics and Safety of MP-376 (Levofloxacin Inhalation Solution) in Cystic Fibrosis Subjects▿

PubMed Central

Geller, David E.; Flume, Patrick A.; Griffith, David C.; Morgan, Elizabeth; White, Dan; Loutit, Jeffery S.; Dudley, Michael N.

2011-01-01

The pharmacokinetics and tolerability of nebulized MP-376 (levofloxacin inhalation solution [Aeroquin]) were determined in cystic fibrosis (CF) subjects. Ten CF subjects received single 180-mg doses of two formulations of MP-376, followed by a multiple-dose phase of 240 mg once daily for 7 days. Serum and expectorated-sputum samples were assayed for levofloxacin content. Safety was evaluated following the single- and multiple-dose study phases. Nebulized MP-376 produced high concentrations of levofloxacin in sputum. The mean maximum plasma concentration (Cmax) ranged between 2,563 and 2,932 mg/liter for 180-mg doses of the 50- and 100-mg/ml formulations, respectively. After 7 days of dosing, the mean Cmax for the 240-mg dose was 4,691 mg/liter. The mean serum levofloxacin Cmax ranged between 0.95 and 1.28 for the 180-mg doses and was 1.71 for the 240-mg dose. MP-376 was well tolerated. Nebulized MP-376 produces high sputum and low serum levofloxacin concentrations. The pharmacokinetics, safety, and tolerability were similar for the two formulations. MP-376 240 mg (100 mg/ml) is being advanced into late-stage clinical development. PMID:21444699

Neighborhood-targeted and case-triggered use of a single dose of oral cholera vaccine in an urban setting: Feasibility and vaccine coverage.

PubMed

Parker, Lucy A; Rumunu, John; Jamet, Christine; Kenyi, Yona; Lino, Richard Laku; Wamala, Joseph F; Mpairwe, Allan M; Muller, Vincent; Llosa, Augusto E; Uzzeni, Florent; Luquero, Francisco J; Ciglenecki, Iza; Azman, Andrew S

2017-06-01

In June 2015, a cholera outbreak was declared in Juba, South Sudan. In addition to standard outbreak control measures, oral cholera vaccine (OCV) was proposed. As sufficient doses to cover the at-risk population were unavailable, a campaign using half the standard dosing regimen (one-dose) targeted high-risk neighborhoods and groups including neighbors of suspected cases. Here we report the operational details of this first public health use of a single-dose regimen of OCV and illustrate the feasibility of conducting highly targeted vaccination campaigns in an urban area. Neighborhoods of the city were prioritized for vaccination based on cumulative attack rates, active transmission and local knowledge of known cholera risk factors. OCV was offered to all persons older than 12 months at 20 fixed sites and to select groups, including neighbors of cholera cases after the main campaign ('case-triggered' interventions), through mobile teams. Vaccination coverage was estimated by multi-stage surveys using spatial sampling techniques. 162,377 individuals received a single-dose of OCV in the targeted neighborhoods. In these neighborhoods vaccine coverage was 68.8% (95% Confidence Interval (CI), 64.0-73.7) and was highest among children ages 5-14 years (90.0%, 95% CI 85.7-94.3), with adult men being less likely to be vaccinated than adult women (Relative Risk 0.81, 95% CI: 0.68-0.96). In the case-triggered interventions, each lasting 1-2 days, coverage varied (range: 30-87%) with an average of 51.0% (95% CI 41.7-60.3). Vaccine supply constraints and the complex realities where cholera outbreaks occur may warrant the use of flexible alternative vaccination strategies, including highly-targeted vaccination campaigns and single-dose regimens. We showed that such campaigns are feasible. Additional work is needed to understand how and when to use different strategies to best protect populations against epidemic cholera.

Double-blind evaluation of the safety and pharmacokinetics of multiple oral once-daily 750-milligram and 1-gram doses of levofloxacin in healthy volunteers.

PubMed

Chien, S C; Wong, F A; Fowler, C L; Callery-D'Amico, S V; Williams, R R; Nayak, R; Chow, A T

1998-04-01

The safety and pharmacokinetics of once-daily oral levofloxacin in 16 healthy male volunteers were investigated in a randomized, double-blind, placebo-controlled study. Subjects were randomly assigned to the treatment (n = 10) or placebo group (n = 6). In study period 1, 750 mg of levofloxacin or a placebo was administered orally as a single dose on day 1, followed by a washout period on days 2 and 3; dosing resumed for days 4 to 10. Following a 3-day washout period, 1 g of levofloxacin or a placebo was administered in a similar fashion in period 2. Plasma and urine levofloxacin concentrations were measured by high-pressure liquid chromatography. Pharmacokinetic parameters were estimated by model-independent methods. Levofloxacin was rapidly absorbed after single and multiple once-daily 750-mg and 1-g doses with an apparently large volume of distribution. Peak plasma levofloxacin concentration (Cmax) values were generally attained within 2 h postdose. The mean values of Cmax and area under the concentration-time curve from 0 to 24 h (AUC0-24) following a single 750-mg dose were 7.1 microg/ml and 71.3 microg x h/ml, respectively, compared to 8.6 microg/ml and 90.7 microg x h/ml, respectively, at steady state. Following the single 1-g dose, mean Cmax and AUC0-24 values were 8.9 microg/ml and 95.4 microg x h/ml, respectively; corresponding values at steady state were 11.8 microg/ml and 118 microg x h/ml. These Cmax and AUC0-24 values indicate modest and similar degrees of accumulation upon multiple dosing at the two dose levels. Values of apparent total body clearance (CL/F), apparent volume of distribution (Vss/F), half-life (t1/2), and renal clearance (CL[R]) were similar for the two dose levels and did not vary from single to multiple dosing. Mean steady-state values for CL/F, Vss/F, t1/2, and CL(R) following 750 mg of levofloxacin were 143 ml/min, 100 liters, 8.8 h, and 116 ml/min, respectively; corresponding values for the 1-g dose were 146 ml/min, 105 liters, 8.9 h, and 105 ml/min. In general, the pharmacokinetics of levofloxacin in healthy subjects following 750-mg and 1-g single and multiple once-daily oral doses appear to be consistent with those found in previous studies of healthy volunteers given 500-mg doses. Levofloxacin was well tolerated at either high dose level. The most frequently reported drug-related adverse events were nausea and headache.

Double-Blind Evaluation of the Safety and Pharmacokinetics of Multiple Oral Once-Daily 750-Milligram and 1-Gram Doses of Levofloxacin in Healthy Volunteers

PubMed Central

Chien, Shu-Chean; Wong, Frank A.; Fowler, Cynthia L.; Callery-D’Amico, Susan V.; Williams, R. Rex; Nayak, Ramchandra; Chow, Andrew T.

1998-01-01

The safety and pharmacokinetics of once-daily oral levofloxacin in 16 healthy male volunteers were investigated in a randomized, double-blind, placebo-controlled study. Subjects were randomly assigned to the treatment (n = 10) or placebo group (n = 6). In study period 1, 750 mg of levofloxacin or a placebo was administered orally as a single dose on day 1, followed by a washout period on days 2 and 3; dosing resumed for days 4 to 10. Following a 3-day washout period, 1 g of levofloxacin or a placebo was administered in a similar fashion in period 2. Plasma and urine levofloxacin concentrations were measured by high-pressure liquid chromatography. Pharmacokinetic parameters were estimated by model-independent methods. Levofloxacin was rapidly absorbed after single and multiple once-daily 750-mg and 1-g doses with an apparently large volume of distribution. Peak plasma levofloxacin concentration (Cmax) values were generally attained within 2 h postdose. The mean values of Cmax and area under the concentration-time curve from 0 to 24 h (AUC0–24) following a single 750-mg dose were 7.1 μg/ml and 71.3 μg · h/ml, respectively, compared to 8.6 μg/ml and 90.7 μg · h/ml, respectively, at steady state. Following the single 1-g dose, mean Cmax and AUC0–24 values were 8.9 μg/ml and 95.4 μg · h/ml, respectively; corresponding values at steady state were 11.8 μg/ml and 118 μg · h/ml. These Cmax and AUC0–24 values indicate modest and similar degrees of accumulation upon multiple dosing at the two dose levels. Values of apparent total body clearance (CL/F), apparent volume of distribution (Vss/F), half-life (t1/2), and renal clearance (CLR) were similar for the two dose levels and did not vary from single to multiple dosing. Mean steady-state values for CL/F, Vss/F, t1/2, and CLR following 750 mg of levofloxacin were 143 ml/min, 100 liters, 8.8 h, and 116 ml/min, respectively; corresponding values for the 1-g dose were 146 ml/min, 105 liters, 8.9 h, and 105 ml/min. In general, the pharmacokinetics of levofloxacin in healthy subjects following 750-mg and 1-g single and multiple once-daily oral doses appear to be consistent with those found in previous studies of healthy volunteers given 500-mg doses. Levofloxacin was well tolerated at either high dose level. The most frequently reported drug-related adverse events were nausea and headache. PMID:9559801

Alternative methods for CYP2D6 phenotyping: comparison of dextromethorphan metabolic ratios from AUC, single point plasma, and urine.

PubMed

Chen, Rui; Wang, Haotian; Shi, Jun; Hu, Pei

2016-05-01

CYP2D6 is a high polymorphic enzyme. Determining its phenotype before CYP2D6 substrate treatment can avoid dose-dependent adverse events or therapeutic failures. Alternative phenotyping methods of CYP2D6 were compared to aluate the appropriate and precise time points for phenotyping after single-dose and ultiple-dose of 30-mg controlled-release (CR) dextromethorphan (DM) and to explore the antimodes for potential sampling methods. This was an open-label, single and multiple-dose study. 21 subjects were assigned to receive a single dose of CR DM 30 mg orally, followed by a 3-day washout period prior to oral administration of CR DM 30 mg every 12 hours for 6 days. Metabolic ratios (MRs) from AUC∞ after single dosing and from AUC0-12h at steady state were taken as the gold standard. The correlations of metabolic ratios of DM to dextrorphan (MRDM/DX) values based on different phenotyping methods were assessed. Linear regression formulas were derived to calculate the antimodes for potential sample methods. In the single-dose part of the study statistically significant correlations were found between MRDM/DX from AUC∞ and from serial plasma points from 1 to 30 hours or from urine (all p-values < 0.001). In the multiple-dose part, statistically significant correlations were found between MRDM/DX from AUC0-12h on day 6 and MRDM/DX from serial plasma points from 0 to 36 hours after the last dosing (all p-values < 0.001). Based on reported urinary antimode and linear regression analysis, the antimodes of AUC and plasma points were derived to profile the trend of antimodes as the drug concentrations changed. MRDM/DX from plasma points had good correlations with MRDM/DX from AUC. Plasma points from 1 to 30 hours after single dose of 30-mg CR DM and any plasma point at steady state after multiple doses of CR DM could potentially be used for phenotyping of CYP2D6.

Changes in the Flow-Volume Curve According to the Degree of Stenosis in Patients With Unilateral Main Bronchial Stenosis

PubMed Central

Yoo, Jung-Geun; Yi, Chin A; Lee, Kyung Soo; Jeon, Kyeongman; Um, Sang-Won; Koh, Won-Jung; Suh, Gee Young; Chung, Man Pyo; Kwon, O Jung

2015-01-01

Objectives The shape of the flow-volume (F-V) curve is known to change to showing a prominent plateau as stenosis progresses in patients with tracheal stenosis. However, no study has evaluated changes in the F-V curve according to the degree of bronchial stenosis in patients with unilateral main bronchial stenosis. Methods We performed an analysis of F-V curves in 29 patients with unilateral bronchial stenosis with the aid of a graphic digitizer between January 2005 and December 2011. Results The primary diseases causing unilateral main bronchial stenosis were endobronchial tuberculosis (86%), followed by benign bronchial tumor (10%), and carcinoid (3%). All unilateral main bronchial stenoses were classified into one of five grades (I, ≤25%; II, 26%-50%; III, 51%-75%; IV, 76%-90%; V, >90% to near-complete obstruction without ipsilateral lung collapse). A monophasic F-V curve was observed in patients with grade I stenosis and biphasic curves were observed for grade II-IV stenosis. Both monophasic (81%) and biphasic shapes (18%) were observed in grade V stenosis. After standardization of the biphasic shape of the F-V curve, the breakpoints of the biphasic curve moved in the direction of high volume (x-axis) and low flow (y-axis) according to the progression of stenosis. Conclusion In unilateral bronchial stenosis, a biphasic F-V curve appeared when bronchial stenosis was >25% and disappeared when obstruction was near complete. In addition, the breakpoint moved in the direction of high volume and low flow with the progression of stenosis. PMID:26045916

Aerosol Delivery with Two Nebulizers Through High-Flow Nasal Cannula: A Randomized Cross-Over Single-Photon Emission Computed Tomography-Computed Tomography Study.

PubMed

Dugernier, Jonathan; Hesse, Michel; Jumetz, Thibaud; Bialais, Emilie; Roeseler, Jean; Depoortere, Virginie; Michotte, Jean-Bernard; Wittebole, Xavier; Ehrmann, Stephan; Laterre, Pierre-François; Jamar, François; Reychler, Gregory

2017-10-01

High-flow nasal cannula use is developing in ICUs. The aim of this study was to compare aerosol efficiency by using two nebulizers through a high-flow nasal cannula: the most commonly used jet nebulizer (JN) and a more efficient vibrating-mesh nebulizer (VN). Aerosol delivery of diethylenetriaminepentaacetic acid labeled with technetium-99m (4 mCi/4 mL) to the lungs by using a VN (Aerogen Solo ® ; Aerogen Ltd., Galway, Ireland) and a constant-output JN (Opti-Mist Plus Nebulizer ® ; ConvaTec, Bridgewater, NJ) through a high-flow nasal cannula (Optiflow ® ; Fisher & Paykel, New Zealand) was compared in six healthy subjects. Flow rate was set at 30 L/min through the heated humidified circuit. Pulmonary and extrapulmonary deposition was measured by single-photon emission computed tomography combined with a low-dose computed tomographic scan and by planar scintigraphy. Lung deposition was only 3.6 (2.1-4.4) and 1 (0.7-2)% of the nominal dose with the VN and the JN, respectively (p < 0.05). The JN showed higher retained doses than the VN. However, both nebulizers were associated with substantial deposition in the single limb circuit, the humidification chamber, and the nasal cannula [58.2 (51.6-61.6)% of the nominal dose with the VN versus 19.2 (15.8-22.9)% of the nominal dose with the JN, p < 0.05] and in the upper respiratory tract [17.6 (13.4-27.9)% of the nominal dose with the VN and 8.6 (6.0-11.0)% of the nominal dose with the JN, p < 0.05], especially in the nasal cavity. In the specific conditions of the study, pulmonary drug delivery through the high-flow nasal cannula is about 1%-4% of the initial amount of drugs placed in the nebulizer, despite the higher efficiency of the VN as compared with the JN.

Processing speed can monitor stimulant-medication effects in adults with attention deficit disorder with hyperactivity.

PubMed

Nielsen, Niels Peter; Wiig, Elisabeth H; Bäck, Svante; Gustafsson, Jan

2017-05-01

Treatment responses to methylphenidate by adults with ADHD are generally monitored against DSM-IV/DSM-V symptomatology, rating scales or interviews during reviews. To evaluate the use of single- and dual-dimension processing-speed and efficiency measures to monitor the effects of pharmacological treatment with methylphenidate after a short period off medication. A Quick Test of Cognitive Speed (AQT) monitored the effects of immediate-release methylphenidate in 40 previously diagnosed and medicated adults with ADHD. Processing speed was evaluated with prior prescription medication, without medication after a 2-day period off ADHD medication, and with low-dose (10/20 mg) and high-dose (20/40 mg) methylphenidate hydrochloride (Medikinet IR). Thirty-three participants responded to the experimental treatments. One-way ANOVA with post-hoc analysis (Scheffe) indicated significant main effects for single dimension colour and form and dual-dimension colour-form naming. Post-hoc analysis indicated statistical differences between the no- and high-dose medication conditions for colour and form, measures of perceptual speed. For colour-form naming, a measure of cognitive speed, there was a significant difference between no- and low-dose medication and between no- and high-dose medications, but not between low- and high-dose medications. Results indicated that the AQT tests effectively monitored incremental effects of the methylphenidate dose on processing speed after a 2-day period off medication. Thus, perceptual (colour and form) and cognitive speed (two-dimensional colour-form naming) and processing efficiency (lowered shift costs) increased measurably with high-dose medication. These preliminary findings warrant validation with added measures of associated behavioural and cognitive changes.

Occipital neuralgia associates with high cervical spinal cord lesions in idiopathic inflammatory demyelinating disease.

PubMed

Kissoon, Narayan R; Watson, James C; Boes, Christopher J; Kantarci, Orhun H

2018-01-01

Background The association of trigeminal neuralgia with pontine lesions has been well documented in multiple sclerosis, and we tested the hypothesis that occipital neuralgia in multiple sclerosis is associated with high cervical spinal cord lesions. Methods We retrospectively reviewed the records of 29 patients diagnosed with both occipital neuralgia and demyelinating disease by a neurologist from January 2001 to December 2014. We collected data on demographics, clinical findings, presence of C2-3 demyelinating lesions, and treatment responses. Results The patients with both occipital neuralgia and multiple sclerosis were typically female (76%) and had a later onset (age > 40) of occipital neuralgia (72%). Eighteen patients (64%) had the presence of C2-3 lesions and the majority had unilateral symptoms (83%) or episodic pain (78%). All patients with documented sensory loss (3/3) had C2-3 lesions. Most patients with progressive multiple sclerosis (6/8) had C2-3 lesions. Of the eight patients with C2-3 lesions and imaging at onset of occipital neuralgia, five (62.5%) had evidence of active demyelination. None of the patients with progressive multiple sclerosis (3/3) responded to occipital nerve blocks or high dose intravenous steroids, whereas all of the other phenotypes with long term follow-up (eight patients) had good responses. Conclusions A cervical spine MRI should be considered in all patients presenting with occipital neuralgia. In patients with multiple sclerosis, clinical features in occipital neuralgia that were predictive of the presence of a C2-3 lesion were unilateral episodic symptoms, sensory loss, later onset of occipital neuralgia, and progressive multiple sclerosis phenotype. Clinical phenotype predicted response to treatment.

Sustained neuroprotection from a single intravitreal injection of PGJ₂ in a nonhuman primate model of nonarteritic anterior ischemic optic neuropathy.

PubMed

Miller, Neil R; Johnson, Mary A; Nolan, Theresa; Guo, Yan; Bernstein, Alexander M; Bernstein, Steven L

2014-10-08

Prostaglandin J₂ (PGJ₂) is neuroprotective in a murine model of nonarteritic anterior ischemic optic neuropathy (NAION). After assessing for potential toxicity, we evaluated the efficacy of a single intravitreal (IVT) injection of PGJ₂ in a nonhuman primate model of NAION (pNAION). We assessed PGJ₂ toxicity by administering it as a single high-dose intravenous (IV) injection, consecutive daily high-dose IV injections, or a single IVT injection in one eye of five adult rhesus monkeys. To assess efficacy, we induced pNAION in one eye of five adult male rhesus monkeys using a laser-activated rose bengal induction method. We then injected the eye with either PGJ₂ or phosphate-buffered saline (PBS) intravitreally immediately or 5 hours post induction. We performed a clinical assessment, optical coherence tomography, electrophysiological testing, fundus photography, and fluorescein angiography in all animals prior to induction and at 1 day, 1 week, 2 weeks, and 4 weeks after induction. Following analysis of the first eye, we induced pNAION in the contralateral eye and then injected either PGJ₂ or PBS. We euthanized all animals 5 weeks after final assessment of the fellow eye and performed both immunohistochemical and light and electron microscopic analyses of the retina and optic nerves. PGJ₂ caused no permanent systemic toxicity regardless of the amount injected or route of delivery, and there was no evidence of any ocular toxicity with the dose of PGJ₂ used in efficacy studies. Transient reduction in the amplitudes of the visual evoked potentials and the N95 component of the pattern electroretinogram (PERG) occurred after both IV and IVT administration of high doses of PGJ₂; however, the amplitudes returned to normal in all animals within 1 week. In all eyes, a single IVT dose of PGJ₂ administered immediately or shortly after induction of pNAION resulted in a significant reduction of clinical, electrophysiological, and histological damage compared with vehicle-injected eyes (P = 0.03 for both VEP and PERG; P = 0.05 for axon counts). In nonhuman primates, PGJ₂ administered either intravenously or intravitreally produces no permanent toxicity at even four times the dose given for neuroprotection. Additionally, a single IVT dose of PGJ₂ is neuroprotective when administered up to 5 hours after induction of pNAION. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

Efficacy of a Single-Dose, Inactivated Oral Cholera Vaccine in Bangladesh.

PubMed

Qadri, Firdausi; Wierzba, Thomas F; Ali, Mohammad; Chowdhury, Fahima; Khan, Ashraful I; Saha, Amit; Khan, Iqbal A; Asaduzzaman, Muhammad; Akter, Afroza; Khan, Arifuzzaman; Begum, Yasmin A; Bhuiyan, Taufiqur R; Khanam, Farhana; Chowdhury, Mohiul I; Islam, Taufiqul; Chowdhury, Atique I; Rahman, Anisur; Siddique, Shah A; You, Young A; Kim, Deok R; Siddik, Ashraf U; Saha, Nirod C; Kabir, Alamgir; Cravioto, Alejandro; Desai, Sachin N; Singh, Ajit P; Clemens, John D

2016-05-05

A single-dose regimen of the current killed oral cholera vaccines that have been prequalified by the World Health Organization would make them more attractive for use against endemic and epidemic cholera. We conducted an efficacy trial of a single dose of the killed oral cholera vaccine Shanchol, which is currently given in a two-dose schedule, in an urban area in which cholera is highly endemic. Nonpregnant residents of Dhaka, Bangladesh, who were 1 year of age or older were randomly assigned to receive a single dose of oral cholera vaccine or oral placebo. The primary outcome was vaccine protective efficacy against culture-confirmed cholera occurring 7 to 180 days after dosing. Prespecified secondary outcomes included protective efficacy against severely dehydrating culture-confirmed cholera during the same interval, against cholera and severe cholera occurring 7 to 90 versus 91 to 180 days after dosing, and against cholera and severe cholera according to age at baseline. A total of 101 episodes of cholera, 37 associated with severe dehydration, were detected among the 204,700 persons who received one dose of vaccine or placebo. The vaccine protective efficacy was 40% (95% confidence interval [CI], 11 to 60%; 0.37 cases per 1000 vaccine recipients vs. 0.62 cases per 1000 placebo recipients) against all cholera episodes, 63% (95% CI, 24 to 82%; 0.10 vs. 0.26 cases per 1000 recipients) against severely dehydrating cholera episodes, and 63% (95% CI, -39 to 90%), 56% (95% CI, 16 to 77%), and 16% (95% CI, -49% to 53%) against all cholera episodes among persons vaccinated at the age of 5 to 14 years, 15 or more years, and 1 to 4 years, respectively, although the differences according to age were not significant (P=0.25). Adverse events occurred at similar frequencies in the two groups. A single dose of the oral cholera vaccine was efficacious in older children (≥5 years of age) and in adults in a setting with a high level of cholera endemicity. (Funded by the Bill and Melinda Gates Foundation and others; ClinicalTrials.gov number, NCT02027207.).

Safety, tolerability and pharmacokinetics of the histamine H3 receptor antagonist, ABT-288, in healthy young adults and elderly volunteers

PubMed Central

Othman, Ahmed A; Haig, George; Florian, Hana; Locke, Charles; Zhang, Jun; Dutta, Sandeep

2013-01-01

Aim The objective of this work was to characterize the safety, tolerability and pharmacokinetics of ABT-288, a highly selective histamine H3 receptor antagonist, in healthy young adults and elderly subjects following single and multiple dosing in a phase 1 setting. Methods Single doses (0.1, 0.3, 1, 3, 10, 20 and 40 mg ABT-288) and multiple doses (0.5, 1.5, 3 and 6 mg ABT-288 once-daily for 14 days) were evaluated in young adults and multiple doses (0.5, 1.5, 3 and 5 mg ABT-288 once-daily for 12 days) were evaluated in elderly subjects using randomized, double-blind, placebo-controlled, dose-escalating study designs. The effect of food on ABT-288 pharmacokinetics (5 mg single dose) was evaluated using an open label, randomized, crossover design. Results ABT-288 safety, tolerability and pharmacokinetics were comparable in young and elderly subjects. Single doses up to 40 mg and multiple doses up to 3 mg once-daily were generally safe and well tolerated. The most frequently reported adverse events were hot flush, headache, abnormal dreams, insomnia, nausea and dizziness. ABT-288 exposure (AUC) was dose-proportional over the evaluated dose ranges. The mean elimination half-life ranged from 40 to 61 h across dose groups. Steady state was achieved by day 10 of once-daily dosing with 3.4- to 4.2-fold accumulation. Food did not have a clinically meaningful effect on ABT-288 exposure. Conclusions Based on the above results, 1 and 3 mg once-daily doses of ABT-288 were advanced to phase 2 evaluation in Alzheimer's patients. PMID:23016924

Safety, tolerability and pharmacokinetics of the histamine H3 receptor antagonist, ABT-288, in healthy young adults and elderly volunteers.

PubMed

Othman, Ahmed A; Haig, George; Florian, Hana; Locke, Charles; Zhang, Jun; Dutta, Sandeep

2013-05-01

The objective of this work was to characterize the safety, tolerability and pharmacokinetics of ABT-288, a highly selective histamine H3 receptor antagonist, in healthy young adults and elderly subjects following single and multiple dosing in a phase 1 setting. Single doses (0.1, 0.3, 1, 3, 10, 20 and 40 mg ABT-288) and multiple doses (0.5, 1.5, 3 and 6 mg ABT-288 once-daily for 14 days) were evaluated in young adults and multiple doses (0.5, 1.5, 3 and 5 mg ABT-288 once-daily for 12 days) were evaluated in elderly subjects using randomized, double-blind, placebo-controlled, dose-escalating study designs. The effect of food on ABT-288 pharmacokinetics (5 mg single dose) was evaluated using an open label, randomized, crossover design. ABT-288 safety, tolerability and pharmacokinetics were comparable in young and elderly subjects. Single doses up to 40 mg and multiple doses up to 3 mg once-daily were generally safe and well tolerated. The most frequently reported adverse events were hot flush, headache, abnormal dreams, insomnia, nausea and dizziness. ABT-288 exposure (AUC) was dose-proportional over the evaluated dose ranges. The mean elimination half-life ranged from 40 to 61 h across dose groups. Steady state was achieved by day 10 of once-daily dosing with 3.4- to 4.2-fold accumulation. Food did not have a clinically meaningful effect on ABT-288 exposure. Based on the above results, 1 and 3 mg once-daily doses of ABT-288 were advanced to phase 2 evaluation in Alzheimer's patients. © 2012 Abbott Laboratories. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society.

The Effect of Compartmental Asymmetry on the Monitoring of Pulmonary Mechanics and Lung Volumes.

PubMed

Keenan, Joseph C; Cortes-Puentes, Gustavo A; Adams, Alexander B; Dries, David J; Marini, John J

2016-11-01

Esophageal pressure measurement for computation of transpulmonary pressure (P tp ) has begun to be incorporated into clinical use for evaluating forces across the lungs. Gaps exist in our understanding of how esophageal pressure (and therefore P tp ), a value measured at a single site, responds when respiratory system compartments are asymmetrically affected by whole-lung atelectasis or unilateral injury as well as changes in chest wall compliance. We reasoned that P tp would track with aerated volume changes as estimated by functional residual capacity (FRC) and tidal volume. We examined this hypothesis in the setting of asymmetric lungs and changes in intra-abdominal pressure. This study was conducted in the animal laboratory of a university-affiliated hospital. Models of unilateral atelectasis and unilateral and bilateral lung injury exposed to intra-abdominal hypertension (IAH) in 10 deeply sedated mechanically ventilated swine. Atelectasis was created by balloon occlusion of the left main bronchus. Unilateral lung injury was induced by saline lavage of isolated right lung. Diffuse lung injury was induced by saline lavage of both lungs. The peritoneum was insufflated with air to create a model of pressure-regulated IAH. We measured esophageal pressures, airway pressures, FRC by gas dilution, and oxygenation. FRC was reduced by IAH in normal lungs (P < .001) and both asymmetric lung pathologies (P < .001). P tp at end-expiration was decreased by IAH in bilateral (P = .001) and unilateral lung injury (P = .003) as well as unilateral atelectasis (P = .019). In the setting of both lung injury models, end-expiratory P tp showed a moderate correlation in tracking with FRC. P tp tracks with aerated lung volume in the setting of thoracic asymmetry and changes in intra-abdominal pressure. However, used alone, it cannot distinguish the relative contributions of air-space distention and recruitment of lung units. Copyright © 2016 by Daedalus Enterprises.

Fosfomycin trometamol: a review of its use as a single-dose oral treatment for patients with acute lower urinary tract infections and pregnant women with asymptomatic bacteriuria.

PubMed

Keating, Gillian M

2013-11-01

Fosfomycin trometamol (fosfomycin tromethamine) [Monuril(®), Monurol(®), Monural(®)] is approved in numerous countries worldwide, mainly for the treatment of uncomplicated urinary tract infections (UTIs). Fosfomycin has good in vitro activity against common uropathogens, such as Escherichia coli (including extended-spectrum β-lactamase-producing E. coli), Proteus mirabilis, Klebsiella pneumoniae and Staphylococcus saprophyticus, and the susceptibility of uropathogens to fosfomycin has remained relatively stable over time. A single oral dose of fosfomycin trometamol 3 g (the approved dosage) achieves high concentrations in urine. Results of recent randomized trials indicate that single-dose fosfomycin trometamol had similar clinical and/or bacteriological efficacy to 3- to 7-day regimens of ciprofloxacin, norfloxacin, cotrimoxazole or nitrofurantoin in women with uncomplicated lower UTIs. In addition, single-dose fosfomycin trometamol had similar bacteriological efficacy to a 5-day course of cefuroxime axetil or a 7-day course of amoxicillin/clavulanic acid in pregnant women with asymptomatic bacteriuria, and similar clinical and/or bacteriological efficacy to a 5-day course of cefuroxime axetil or amoxicillin/clavulanic acid or a 3-day course of ceftibuten in pregnant women with a lower UTI. Single-dose fosfomycin trometamol was generally well tolerated, with gastrointestinal adverse events (e.g. diarrhoea, nausea) reported most commonly. In conclusion, single-dose fosfomycin trometamol is an important option for the first-line empirical treatment of uncomplicated lower UTIs.

DSL prescriptive targets for bone conduction devices: adaptation and comparison to clinical fittings.

PubMed

Hodgetts, William E; Scollie, Susan D

2017-07-01

To develop an algorithm that prescribes targets for bone conduction frequency response shape, compression, and output limiting, along with a clinical method that ensures accurate transforms between assessment and verification stages of the clinical workflow. Technical report of target generation and validation. We recruited 39 adult users of unilateral percutaneous bone conduction hearing aids with a range of unilateral, bilateral, mixed and conductive hearing losses across the sample. The initial algorithm over-prescribed output compared to the user's own settings in the low frequencies, but provided a good match to user settings in the high frequencies. Corrections to the targets were derived and implemented as a low-frequency cut aimed at improving acceptance of the wearer's own voice during device use. The DSL-BCD prescriptive algorithm is compatible with verification of devices and fine-tuning to target for percutaneous bone conduction hearing devices that can be coupled to a skull simulator. Further study is needed to investigate the appropriateness of this prescriptive algorithm for other input levels, and for other clinical populations including those with single-sided deafness, bilateral devices, children and users of transcutaneous bone conduction hearing aids.

The impact of histology and delivered dose on local control of spinal metastases treated with stereotactic radiosurgery.

PubMed

Yamada, Yoshiya; Katsoulakis, Evangelia; Laufer, Ilya; Lovelock, Michael; Barzilai, Ori; McLaughlin, Lily A; Zhang, Zhigang; Schmitt, Adam M; Higginson, Daniel S; Lis, Eric; Zelefsky, Michael J; Mechalakos, James; Bilsky, Mark H

2017-01-01

OBJECTIVE An analysis of factors contributing to durable radiographic control of spinal metastases was undertaken, drawing from a large single-institution database in an attempt to elucidate indications and dose requirements for successful treatment. METHODS All patients treated at a single institution with stereotactic radiosurgery (SRS) of the spine as first-line therapy were assessed for local progression of the treated site, defined as radiographic enlargement of the treated tumor and/or biopsy-proven evidence of active tumor cells. All patients were followed with CT, PET, or MR imaging every 3-6 months until death. Treatment decisions were made by a multidisciplinary team of radiation oncologists, neurosurgeons, and neuroradiologists. Target volumes were defined according to the international consensus guidelines and were reviewed in a multidisciplinary conference. Image-guided techniques and intensity modulation were used for every case. The tumor's histological type, gross tumor volume (GTV), dose that covers 95% of the GTV (GTV D95), percentage of GTV covered by 95% of the prescribed dose (GTV V95), planning target volume (PTV), dose that covers 95% of the PTV (PTV D95), and percentage of PTV covered by 95% of the prescribed dose (PTV V95) were analyzed for significance in relation to local control, based on time to local progression. RESULTS A total of 811 lesions were treated in 657 patients between 2003 and 2015 at a single institution. The mean follow-up and overall survival for the entire cohort was 26.9 months (range 2-141 months). A total of 28 lesions progressed and the mean time to failure was 26 months (range 9.7-57 months). The median prescribed dose was 2400 cGy (range 1600-2600 cGy). Both GTV D95 and PTV D95 were highly significantly associated with local failure in univariate analysis, but GTV and PTV and histological type did not reach statistical significance. The median GTV D95 for the cohort equal to or above the GTV D95 1830 cGy cut point (high dose) was 2356 cGy, and it was 1709 cGy for the cohort of patients who received less than 1830 cGy (low dose). In terms of PTV D95, the median dose for those equal to or above the cut point of 1740 cGy (high dose) was 2233 cGy, versus 1644 cGy for those lesions below the PTV D95 cut point of 1740 cGy (low dose). CONCLUSIONS High-dose single-session SRS provides durable long-term control, regardless of the histological findings or tumor size. In this analysis, the only significant factors predictive of local control were related to the actual dose of radiation given. Although the target volumes were well treated with the intended dose, those lesions irradiated to higher doses (median GTV D95 2356 cGy, minimum 1830 cGy) had a significantly higher probability of durable local control than those treated with lower doses (median PTV D95 2232 cGy, minimum of 1740 cGy) (p < 0.001). Patients in the high-dose cohort had a 2% cumulative rate of local failure. Histological findings were not associated with local failure, suggesting that radioresistant histological types benefit in particular from radiosurgery. For patients with a favorable prognosis, a higher dose of SRS is important for long-term outcomes.

The impact of histology and delivered dose on local control of spinal metastases treated with stereotactic radiosurgery

PubMed Central

Yamada, Yoshiya; Katsoulakis, Evangelia; Laufer, Ilya; Lovelock, Michael; Barzilai, Ori; McLaughlin, Lily A.; Zhang, Zhigang; Schmitt, Adam M.; Higginson, Daniel S.; Lis, Eric; Zelefsky, Michael J.; Mechalakos, James; Bilsky, Mark H.

2017-01-01

Objective An analysis of factors contributing to durable radiographic control of spinal metastases was undertaken, drawing from a large single-institution database in an attempt to elucidate indications and dose requirements for successful treatment. Methods All patients treated at a single institution with stereotactic radiosurgery (SRS) of the spine as first-line therapy were assessed for local progression of the treated site, defined as radiographic enlargement of the treated tumor and/or biopsy-proven evidence of active tumor cells. All patients were followed with CT, PET, or MR imaging every 3–6 months until death. Treatment decisions were made by a multidisciplinary team of radiation oncologists, neurosurgeons, and neuroradiologists. Target volumes were defined according to the international consensus guidelines and were reviewed in a multidisciplinary conference. Image-guided techniques and intensity modulation were used for every case. The tumor’s histological type, gross tumor volume (GTV), dose that covers 95% of the GTV (GTV D95), percentage of GTV covered by 95% of the prescribed dose (GTV V95), planning target volume (PTV), dose that covers 95% of the PTV (PTV D95), and percentage of PTV covered by 95% of the prescribed dose (PTV V95) were analyzed for significance in relation to local control, based on time to local progression. Results A total of 811 lesions were treated in 657 patients between 2003 and 2015 at a single institution. The mean follow-up and overall survival for the entire cohort was 26.9 months (range 2–141 months). A total of 28 lesions progressed and the mean time to failure was 26 months (range 9.7–57 months). The median prescribed dose was 2400 cGy (range 1600–2600 cGy). Both GTV D95 and PTV D95 were highly significantly associated with local failure in univariate analysis, but GTV and PTV and histological type did not reach statistical significance. The median GTV D95 for the cohort equal to or above the GTV D95 1830 cGy cut point (high dose) was 2356 cGy, and it was 1709 cGy for the cohort of patients who received less than 1830 cGy (low dose). In terms of PTV D95, the median dose for those equal to or above the cut point of 1740 cGy (high dose) was 2233 cGy, versus 1644 cGy for those lesions below the PTV D95 cut point of 1740 cGy (low dose). Conclusions High-dose single-session SRS provides durable long-term control, regardless of the histological findings or tumor size. In this analysis, the only significant factors predictive of local control were related to the actual dose of radiation given. Although the target volumes were well treated with the intended dose, those lesions irradiated to higher doses (median GTV D95 2356 cGy, minimum 1830 cGy) had a significantly higher probability of durable local control than those treated with lower doses (median PTV D95 2232 cGy, minimum of 1740 cGy) (p < 0.001). Patients in the high-dose cohort had a 2% cumulative rate of local failure. Histological findings were not associated with local failure, suggesting that radioresistant histological types benefit in particular from radiosurgery. For patients with a favorable prognosis, a higher dose of SRS is important for long-term outcomes. PMID:28041329

Pharmacodynamic and pharmacokinetic profile of S 17092, a new orally active prolyl endopeptidase inhibitor, in elderly healthy volunteers. A phase I study

PubMed Central

Morain, P; Robin, J L; De Nanteuil, G; Jochemsen, R; Heidet, V; Guez, D

2000-01-01

Aims The aim of this study was to characterize the pharmacodynamics and the pharmacokinetics of S 17092, a new orally active prolyl endopeptidase inhibitor following single and repeated administration in elderly healthy volunteers. Methods This was a double-blind, randomized, placebo-controlled, single and multiple dose study in elderly healthy male and female volunteers (n = 36). Four doses were investigated in sequential order: 100, 400, 800 and 1200 mg. Each dose was administered orally once a day in single administration and then, after a 1 week washout period, during 7 days. Pharmacodynamics were assessed by measurement of plasmatic prolyl endopeptidase (PEP) activity, quantitative electroencephalogram (EEG) and psychometric tests. S 17092 concentrations in plasma were quantified by high performance liquid chromatography with tandem mass spectrometric detection. Results PEP activity in plasma was dose-dependently inhibited both after administration of a single dose and after repeated doses of S 17092. The mean maximal inhibition was obtained within 0.5–2 h after dosing, while inhibition lasted at least 12 h after dose administration. S 17092 appeared to be a centrally active substance as it induced statistically significant modifications in EEG compared with placebo. S 17092 at 100 mg exerted an acute increase in alpha band following single administration at 4 h and 8 h postdosing. When administered repeatedly over 7 days S 17092 did not appear to induce significant lasting central nervous system (CNS) effects. In psychometric tests, response times in the numeric working memory were significantly reduced compared with placebo, following the 800 mg dose. There were some beneficial residual effects of the 1200 mg dose on day 13: delayed word recall and word recognition sensitivity improved compared with the declines noted under placebo. Maximum measured concentration (Cmax) and area under the curve (AUC) parameters increased in proportion to the dose. The terminal half-life (t½) values ranged between 9 and 31 h on day 1 and between 7 and 18 h on day 14. A high interindividual variability was observed at all dose levels. S 17092 was well tolerated with no clinically significant changes in laboratory or physical parameters observed at any dose. Conclusions S 17092 had a potent, dose-dependent inhibitory effect on plasmatic PEP, increased alpha band EEG at the 100 mg dose and improved performance in two verbal memory tests at the 1200 mg dose while there were disruption to the vigilance task. The results obtained in elderly healthy subjects indicated that S 17092 is suitable for once-daily dosing without any serious adverse events. PMID:11012558

The Combination of Micro Diaphragm Pumps and Flow Sensors for Single Stroke Based Liquid Flow Control

PubMed Central

Jenke, Christoph; Pallejà Rubio, Jaume; Kibler, Sebastian; Häfner, Johannes; Richter, Martin; Kutter, Christoph

2017-01-01

With the combination of micropumps and flow sensors, highly accurate and secure closed-loop controlled micro dosing systems for liquids are possible. Implementing a single stroke based control mode with piezoelectrically driven micro diaphragm pumps can provide a solution for dosing of volumes down to nanoliters or variable average flow rates in the range of nL/min to μL/min. However, sensor technologies feature a yet undetermined accuracy for measuring highly pulsatile micropump flow. Two miniaturizable in-line sensor types providing electrical readout—differential pressure based flow sensors and thermal calorimetric flow sensors—are evaluated for their suitability of combining them with mircopumps. Single stroke based calibration of the sensors was carried out with a new method, comparing displacement volumes and sensor flow volumes. Limitations of accuracy and performance for single stroke based flow control are described. Results showed that besides particle robustness of sensors, controlling resistive and capacitive damping are key aspects for setting up reproducible and reliable liquid dosing systems. Depending on the required average flow or defined volume, dosing systems with an accuracy of better than 5% for the differential pressure based sensor and better than 6.5% for the thermal calorimeter were achieved. PMID:28368344

The Burnia: Laparoscopic Sutureless Inguinal Hernia Repair in Girls.

PubMed

Novotny, Nathan M; Puentes, Maria C; Leopold, Rodrigo; Ortega, Mabel; Godoy-Lenz, Jorge

2017-04-01

Laparoscopic inguinal hernia repair in children is in evolution. Multiple methods of passing the suture around the peritoneum at the level of the internal inguinal ring exist. Cauterization of the peritoneum at the internal ring is thought to increase scarring and decrease recurrence. We have employed a sutureless, cautery only, laparoscopic single port repair of inguinal hernias and patent processus vaginalis (PPV) in girls. After institutional ethical review was obtained, a retrospective review of sutureless laparoscopic inguinal hernia repairs in girls by 4 surgeons at separate institutions was performed. Patient demographics, intraoperative findings, and postoperative outcomes were recorded and analyzed. The technique involves an umbilical 30° camera and either a separate 3 mm stab incision in the midclavicular line or a 3 mm Maryland grasper placed next to the camera, and the distal most portion of the hernia sac is grasped and pulled into the abdomen and cauterized obliterating the sac. Eighty inguinal hernias were repaired using this technique in 67 girls between July 2009 and September 2015. The ages and weights ranged from 1 month to 16 years and from 2 to 69 kg, respectively. There was one conversion to open approach because an incarcerated ovary was too close to the ring. A single umbilical incision was utilized in 85%. Fifty-seven percent patients had hernias on the right whereas 42% had hernias on the left. Of the patients with presumed unilateral hernias, 22 patients were found to have PPV and were treated through the same incisions, 17/22 were found during a contralateral hernia surgery and 5/22 were found incidentally during appendectomy. Average operative time for unilateral and bilateral hernias was 22 minutes (5-38 minutes) and 31 minutes (11-65 minutes), respectively. No patient required a hospital stay because of the hernia repair. At an average of 25 months follow-up (1.6-75 months), there were no recurrences. The only complication was a single lateral port site hernia on a 2 kg, former 24 week postmenstrual age girl before adapting the technique to single-site surgery for all. Laparoscopic sutureless inguinal hernia repair is safe and effective in girls of all ages. The single-site modification allows for superior cosmetic result and lower complication profile. The Burnia allows for adequate treatment of unilateral and bilateral inguinal hernias with a single incision in the umbilicus.

Bone architecture adaptations after spinal cord injury: impact of long-term vibration of a constrained lower limb.

PubMed

Dudley-Javoroski, S; Petrie, M A; McHenry, C L; Amelon, R E; Saha, P K; Shields, R K

2016-03-01

This study examined the effect of a controlled dose of vibration upon bone density and architecture in people with spinal cord injury (who eventually develop severe osteoporosis). Very sensitive computed tomography (CT) imaging revealed no effect of vibration after 12 months, but other doses of vibration may still be useful to test. The purposes of this report were to determine the effect of a controlled dose of vibratory mechanical input upon individual trabecular bone regions in people with chronic spinal cord injury (SCI) and to examine the longitudinal bone architecture changes in both the acute and chronic state of SCI. Participants with SCI received unilateral vibration of the constrained lower limb segment while sitting in a wheelchair (0.6g, 30 Hz, 20 min, three times weekly). The opposite limb served as a control. Bone mineral density (BMD) and trabecular micro-architecture were measured with high-resolution multi-detector CT. For comparison, one participant was studied from the acute (0.14 year) to the chronic state (2.7 years). Twelve months of vibration training did not yield adaptations of BMD or trabecular micro-architecture for the distal tibia or the distal femur. BMD and trabecular network length continued to decline at several distal femur sub-regions, contrary to previous reports suggesting a "steady state" of bone in chronic SCI. In the participant followed from acute to chronic SCI, BMD and architecture decline varied systematically across different anatomical segments of the tibia and femur. This study supports that vibration training, using this study's dose parameters, is not an effective anti-osteoporosis intervention for people with chronic SCI. Using a high-spatial-resolution CT methodology and segmental analysis, we illustrate novel longitudinal changes in bone that occur after spinal cord injury.

Quadrupedal rodent gait compensations in a low dose monoiodoacetate model of osteoarthritis.

PubMed

Lakes, Emily H; Allen, Kyle D

2018-06-01

Rodent gait analysis provides robust, quantitative results for preclinical musculoskeletal and neurological models. In prior work, surgical models of osteoarthritis have been found to result in a hind limb shuffle-stepping gait compensation, while a high dose monoiodoacetate (MIA, 3 mg) model resulted in a hind limb antalgic gait. However, it is unknown whether the antalgic gait caused by MIA is associated with severity of degeneration from the high dosage or the whole-joint degeneration associated with glycolysis inhibition. This study evaluates rodent gait changes resulting from a low dose, 1 mg unilateral intra-articular injection of MIA compared to saline injected and naïve rats. Spatiotemporal and dynamic gait parameters were collected from a total of 42 male Lewis rats spread across 3 time points: 1, 2, and 4 weeks post-injection. To provide a detailed analysis of this low dose MIA model, gait analysis was used to uniquely quantify both fore and hind limb gait parameters. Our data indicate that 1 mg of MIA caused relatively minor degeneration and a shuffle-step gait compensation, similar to the compensation observed in prior surgical models. These data from a 1 mg MIA model show a different gait compensation compared to a previously studied 3 mg model. This 1 mg MIA model resulted in gait compensations more similar to a previously studied surgical model of osteoarthritis. Additionally, this study provides detailed 4 limb analysis of rodent gait that includes spatiotemporal and dynamic data from the same gait trial. These data highlight the importance of measuring dynamic data in combination with spatiotemporal data, since compensatory gait patterns may not be captured by spatial, temporal, or dynamic characterizations alone. Copyright © 2018 Elsevier B.V. All rights reserved.

Pharmacokinetics of sarizotan after oral administration of single and repeat doses in healthy subjects.

PubMed

Krösser, S; Tillner, J; Fluck, M; Ungethüm, W; Wolna, P; Kovar, A

2007-05-01

Sarizotan is a 5-HTIA receptor agonist with high affinity for D3 and D4 receptors. Here we report the pharmacokinetic and tolerability results from four Phase 1 studies. Two single-dose (5 -25 mg, n = 25, 0.5 - 5 mg, n = 16) and two multiple-dose (10 and 20 mg b.i.d., n = 30, 5 mg b.i.d., n = 12) studies with orally administered sarizotan HCl were carried out in healthy subjects. Plasma sarizotan HCl concentrations were measured using a validated HPLC method and fluorescence or MS/MS detection. Pharmacokinetic parameters were obtained using standard non-compartmental methods. Sarizotan was rapidly absorbed, group-median times to reach maximum concentration (tmax) ranged from 0.5 -2.25 h after single doses and during steady state. Maximum plasma concentration (Cmax) and tmax were slightly dependent on formulation and food intake, whereas area under the curve (AUC) was unaffected by these factors. AUC and Cmax increased dose-proportionally over the tested dose range. Independently of dose and time, sarizotan HCl plasma concentrations declined polyexponentially with a terminal elimination half-life (t1/2) of 5 - 7 h. Accumulation factors corresponded to t1/2 values, and steady state was reached within 24 h. Plasma metabolite concentrations were considerably lower than those of the parent drug. The ratio metabolite AUC : parent drug AUC was time- and dose-independent for all three metabolites suggesting that the metabolism of sarizotan is non-saturable in the tested dose range. The pharmacokinetics of sarizotan were dose-proportional and time-independent for the dose range 0.5 -25 mg). The drug was well-tolerated by healthy subjects up to a single dose of 20 mg.

Quality and efficiency of statin prescribing across countries with a special focus on South Africa: findings and future implications.

PubMed

Godman, Brian; Bishop, Iain; Campbell, Stephen M; Malmström, Rickard E; Truter, Ilse

2015-04-01

Statins are recommended first-line treatment for hyperlipidemia, with published studies suggesting limited differences between them. However, there are reports of under-dosing. South Africa has introduced measures to enhance generic utilization. Part one documents prescribed doses of statins in 2011. Part two determines the extent of generics versus originator and single-sourced statins in 2011 and their costs. Underdosing of simvastatin in 2011 with average prescribed dose of 23.7 mg; however, not for atorvastatin (20.91 mg) or rosuvastatin (15.02 mg). High utilization of generics versus originators at 93-99% for atorvastatin and simvastatin, with limited utilization of single-sourced statins (22% of total statins - defined daily dose basis), mirroring Netherlands, Sweden and UK. Generics priced 33-51% below originator prices. Opportunity to increase simvastatin dosing through education, prescribing targets and incentives. Opportunity to lower generic prices with generic simvastatin 96-98% below single-sourced prices in some European countries.

EEG-based classification of imaginary left and right foot movements using beta rebound.

PubMed

Hashimoto, Yasunari; Ushiba, Junichi

2013-11-01

The purpose of this study was to investigate cortical lateralization of event-related (de)synchronization during left and right foot motor imagery tasks and to determine classification accuracy of the two imaginary movements in a brain-computer interface (BCI) paradigm. We recorded 31-channel scalp electroencephalograms (EEGs) from nine healthy subjects during brisk imagery tasks of left and right foot movements. EEG was analyzed with time-frequency maps and topographies, and the accuracy rate of classification between left and right foot movements was calculated. Beta rebound at the end of imagination (increase of EEG beta rhythm amplitude) was identified from the two EEGs derived from the right-shift and left-shift bipolar pairs at the vertex. This process enabled discrimination between right or left foot imagery at a high accuracy rate (maximum 81.6% in single trial analysis). These data suggest that foot motor imagery has potential to elicit left-right differences in EEG, while BCI using the unilateral foot imagery can achieve high classification accuracy, similar to ordinary BCI, based on hand motor imagery. By combining conventional discrimination techniques, the left-right discrimination of unilateral foot motor imagery provides a novel BCI system that could control a foot neuroprosthesis or a robotic foot. Copyright © 2013 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Acute encephalopathy with unilateral cortical-subcortical lesions in two unrelated kindreds treated with glucocorticoids prenatally for congenital adrenal hyperplasia due to 21-hydroxylase deficiency: established facts and novel insight.

PubMed

Grunt, Sebastian; Steinlin, Maja; Weisstanner, Christian; Schöning, Martin; Mullis, Primus E; Flück, Christa E

2013-01-01

Prenatal glucocorticoid (GC) treatment of the female fetus with 21-hydroxylase deficiency (21-OHD) may prevent genital virilization and androgen effects on the brain, but prenatal GC therapy is controversial because of possible adverse effects on fetal programming, the cardiovascular system and the brain. We report 2 patients with congenital adrenal hyperplasia (CAH) due to 21-OHD who were treated prenatally with dexamethasone, suffered from an acute encephalopathy and showed focal and multifocal cortical and subcortical diffusion restrictions in early MRI and signs of permanent alterations in the follow-up neuroimaging studies. Both patients recovered from the acute episode. Whereas the first patient recovered without neurological sequelae the second patient showed hemianopsia and spastic hemiplegia in the neurological follow-up examination. These are 2 children with CAH, both treated prenatally with high doses of dexamethasone to prevent virilization. The question arises whether prenatal high-dose GC treatment in patients with CAH might represent a risk factor for brain lesions in later life. Adverse effects/events should be reported systematically in patients undergoing prenatal GC treatment and long-term follow-up studies involving risk factors for cerebrovascular disease should be performed. Copyright © 2013 S. Karger AG, Basel.

Direction discrimination learning in normal and visually deprived cats and the effects of lateral suprasylvian lesions.

PubMed

Burnat, K; Zernicki, B

1997-01-01

We used 5 binocularly deprived cats (BD cats), 4 control cats reared also in the laboratory (C cats) and 4 cats reared in a normal environment (N cats). The cats were trained to discriminate an upward or downward-moving light spot versus a stationary spot (detection task) and then an upward versus a downward spot (direction task). The N and C cats learned slowly. The learning was slower than in previously studied discriminations of stationary stimuli. However, all N and C cats mastered the detection task and except one C cat the direction task. In contrast, 4 BD cats failed in the detection task and all in the direction task. This result is consistent with single-cell recording data showing impairment of direction analysis in the visual system in BD cats. After completing the training the upper part of the middle suprasylvian sulcus was removed unilaterally in 7 cats and bilaterally in 6 cats. Surprisingly, the unilateral lesions were more effective: the clear-cut retention deficits were found in 5 cats lesioned unilaterally, whereas only in one cat lesioned bilaterally.

Bioavailability of a Sustained Release Formulation of Curcumin

PubMed Central

Madhavi, Doddabele; Kagan, Daniel

2014-01-01

Context Curcumin has a number of beneficial effects, such as functioning as a potent antioxidant,1 anti-inflammatory, 2 and anticancer agent. Because of its poor oral bioavailability, very high oral doses and repeated dosing have been used to obtain effective plasma levels, with mixed results. High doses of curcumin may cause gastric disturbance, often resulting in poor patient compliance. Objective The objective of this study was to compare the relative bioavailability of MicroActive Curcumin—an advanced, micronized formulation of curcumin that is 25% curcuminoids in a sustained release matrix—with that of an unformulated, 95% pure curcumin powder. Design A dissolution study compared the solubility of the formulated and the unformulated curcumin. The research team also performed a single-dose, 12-h, crossover uptake study with 10 participants and a high-dose tolerability and accumulation study with 3 participants, comparing the 2 forms of curcumin. Setting The study was done in MAZE Laboratories (Purchase, NY, USA). Participants Ten healthy male and female volunteers, aged 21–66 y, took part in the single-dose study. Three participants, 2 female and 1 male aged 40–55 y, took part in the tolerability and accumulation study. The participants were people from the community. Intervention For the dissolution study, the research team filled hard gelatin capsules with unformulated 95% curcumin powder and the MicroActive Curcumin powder to the equivalent of 25 mg curcuminoids. For the single-dose study, participants received 500 mg of curcumin in 2 forms. MicroActive Curcumin capsules were administered after breakfast, and blood samples were drawn at 1, 2, 4, 8, and 12 h postdose. After a 7-d washout period, the protocol was repeated for unformulated, 95% curcumin powder capsules. For the tolerability study, the unformulated, 95% curcumin powder was given at a dose that provided 2 g of curcumin for 7 d followed by 5 g of curcumin for an additional 7 d. After a washout period of 14 d, the protocol was repeated with MicroActive Curcumin. Participants then continued to take the MicroActive Curcumin for >3 mo. Outcome Measures For the dissolution study, the curcumin was quantified at room temperature using reverse-phase, high-performance liquid chromatography (HPLC) with a Phenomenex Luna column (150 × 4.6 mm, 5 μm) (Phenomenex Inc, Torrance, CA, USA). For the single-dose and the tolerability studies, hydrolysis of conjugates and extraction of curcuminoids from the plasma were performed. The curcuminoids were quantified using reverse-phase HPLC with an ultraviolet-visible detector as described above. Results The dissolution study indicated that the sustained-release curcumin had greater dissolution for 12 h at all points tested, compared with the unformulated curcumin. Very little of the unformulated curcumin powder had been released at the end of the 12 h. The results of the single-dose uptake study indicated that the sustained-release formula was 9.7 × more bioavailable than the unformulated powder (P < .001, paired t test). Additionally, all participants showed uptake from the sustained-release formulation. That formulation also resulted in significant increases in the plasma demethoxylated curcuminoids, but the research team did not observe the same increases for the unformulated curcumin powder. The sustained-release formulation was well tolerated, without adverse effects in the high-dose tolerability study. Conclusions Formulation of micronized curcumin in a combination of surfactants, oils, and polymers improves the absorption of curcumin. In addition, the unique plasma demethylated curcuminoid profile may enhance the therapeutic effects of MicroActive Curcumin not observed with unformulated curcumin at moderate and well-tolerated doses. MicroActive Curcumin was well tolerated, without any adverse effects in a high-dose tolerability study. These properties have the potential to make high-dose curcumin supplementation more accessible through simplified incorporation into food and beverage preparations. PMID:26770097

Intranasal Mesenchymal Stem Cell Treatment for Neonatal Brain Damage: Long-Term Cognitive and Sensorimotor Improvement

PubMed Central

Donega, Vanessa; van Bel, Frank; Kas, Martien J. H.; Kavelaars, Annemieke; Heijnen, Cobi J.

2013-01-01

Mesenchymal stem cell (MSC) administration via the intranasal route could become an effective therapy to treat neonatal hypoxic-ischemic (HI) brain damage. We analyzed long-term effects of intranasal MSC treatment on lesion size, sensorimotor and cognitive behavior, and determined the therapeutic window and dose response relationships. Furthermore, the appearance of MSCs at the lesion site in relation to the therapeutic window was examined. Nine-day-old mice were subjected to unilateral carotid artery occlusion and hypoxia. MSCs were administered intranasally at 3, 10 or 17 days after hypoxia-ischemia (HI). Motor, cognitive and histological outcome was investigated. PKH-26 labeled cells were used to localize MSCs in the brain. We identified 0.5×106 MSCs as the minimal effective dose with a therapeutic window of at least 10 days but less than 17 days post-HI. A single dose was sufficient for a marked beneficial effect. MSCs reach the lesion site within 24 h when given 3 or 10 days after injury. However, no MSCs were detected in the lesion when administered 17 days following HI. We also show for the first time that intranasal MSC treatment after HI improves cognitive function. Improvement of sensorimotor function and histological outcome was maintained until at least 9 weeks post-HI. The capacity of MSCs to reach the lesion site within 24 h after intranasal administration at 10 days but not at 17 days post-HI indicates a therapeutic window of at least 10 days. Our data strongly indicate that intranasal MSC treatment may become a promising non-invasive therapeutic tool to effectively reduce neonatal encephalopathy. PMID:23300948

The atypical excretion profile of meldonium: Comparison of urinary detection windows after single- and multiple-dose application in healthy volunteers.

PubMed

Görgens, Christian; Guddat, Sven; Bosse, Christina; Geyer, Hans; Pop, Valentin; Schänzer, Wilhelm; Thevis, Mario

2017-05-10

Following a one-year monitoring program providing unequivocal analytical evidence for a high prevalence in international elite sports, meldonium has been included in the World Anti-Doping Agency's (WADA) list of prohibited substances that came into effect on 1 January 2016. Despite of the polar and hydrophilic nature of the molecule, an unusual long detection window was observed in pilot elimination studies. Consequently, in the present study, urinary excretion profiles after single-dose (5 volunteers, 1×500mg) and multiple-dose oral application (5 volunteers; 2×500mg/day for 6days) were determined in order to facilitate the result management concerning meldonium findings in doping controls. Particularly the option to differentiate between recent use and tapering concentrations was studied. Urinary meldonium concentrations were determined using an analytical approach based on hydrophilic interaction liquid chromatography and high resolution tandem mass spectrometry. The study corroborates the hypothesis of a non-linear, dose-depended and biphasic excretion profile after oral application of meldonium and demonstrates that urinary detection windows are of considerable extent with up to 65 and 117days (concentrations>LOQ of 10ng/mL) following single- and multiple-dose applications, respectively. Copyright © 2017 Elsevier B.V. All rights reserved.

Conservative management of staghorn calculi: a single-centre experience.

PubMed

Deutsch, Peter G; Subramonian, Kesavapilla

2016-09-01

To evaluate the outcomes of conservatively managed staghorn calculi, specifically looking at morbidity and mortality, incidence of infections and progressive changes in renal function. A total of 22 patients with unilateral or bilateral staghorn calculi, who were treated conservatively, were included in the study. Patients were reviewed yearly with symptom assessment, urine culture and measurement of estimated glomerular filtration rate. The presentations to the urology department of staghorn calculi were incidental (41%), haematuria (36%), abdominal discomfort (5%) and recurrent urinary tract infections (UTIs; 18%). The reasons for conservative management in the cohort were comorbidities (59%), patient choice (36%) or poor access/anatomy (5%). In the whole cohort the rate of recurrent UTIs was 50%, the progressive renal failure rate was 14%, the disease-specific mortality rate was 9%, the dialysis dependence rate was 9% and the rate of hospital attendances attributable to stone-related morbidity was 27%. Comparison of outcome measures between the unilateral and bilateral staghorn stones showed statistically significant differences in disease-specific mortality (0 vs 40%) and morbidity (12 vs 80%) in favour of the unilateral group. Although there was a lower incidence of UTIs (41 vs 80%), renal deterioration (6 vs 40%) and dialysis requirement (6 vs 20%) in the unilateral group, these findings were not statistically significant. From the results, we conclude that conservative management of staghorn calculi is not as unsafe as previously thought. Careful patient selection to include unilateral asymptomatic stones with minimal infection, and thorough counselling with regard to the risks, could make conservative management a suitable option for specific patient groups. © 2015 The Authors BJU International © 2015 BJU International Published by John Wiley & Sons Ltd.

Individual MRI and radiographic features of knee OA in subjects with unilateral knee pain: Health ABC study

PubMed Central

Javaid, MK; Kiran, A; Guermazi, A; Kwoh, K; Zaim, S; Carbone, L; Harris, T.; McCulloch, C.E.; Arden, NK; Lane, NE; Felson, D; Nevitt, M

2012-01-01

Strong associations between radiographic features of knee OA and pain have been demonstrated in persons with unilateral knee symptoms. Our objectives were to compare radiographic with MRI features of knee OA and assess the discrimination between painful and non-painful knees in persons with unilateral symptoms. 283 individuals with unilateral knee pain aged 71 to 80 years from Health ABC, a study of weight-related diseases and mobility, had bilateral knee radiographs, read for KL grade and individual radiographic features, and 1.5T MRIs, read using WORMS. The association of structural features with pain was assessed using a within-person case/control design and conditional logistic regression. Receiver operator characteristics (ROC) were then used to test the discriminatory performance of structural features. In conditional logistic analyses, knee pain was significantly associated with both radiographic (any JSN grade >=1: OR 3.20 (1.79 – 5.71) and MRI (any cartilage defect:>=2: OR 3.67 (1.49 – 9.04)) features. However, most subjects had MR detected osteophytes, cartilage and bone marrow lesions in both knees and no individual structural feature discriminated well between painful and non-painful knees using ROC. The best performing MRI feature (synovitis/effusion) was not significantly more informative than KL grade >=2 (p=0.42). In persons with unilateral knee pain, MR and radiographic features were associated with knee pain confirming an important role in the etiology of pain. However, no single MRI or radiographic finding performed well in discriminating painful from non-painful knees. Further work is needed to examine how structural and non-structural factors influence knee pain. PMID:22736267

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

Bilhim, Tiago, E-mail: tiagobilhim@hotmail.com; Pisco, Joao; Rio Tinto, Hugo

This study was designed to compare baseline data and clinical outcome between patients with prostate enlargement/benign prostatic hyperplasia (PE/BPH) who underwent unilateral and bilateral prostatic arterial embolization (PAE) for the relief of lower urinary tract symptoms (LUTS). This single-center, ambispective cohort study compared 122 consecutive patients (mean age 66.7 years) with unilateral versus bilateral PAE from March 2009 to December 2011. Selective PAE was performed with 100- and 200-{mu}m nonspherical polyvinyl alcohol (PVA) particles by a unilateral femoral approach. Bilateral PAE was performed in 103 (84.4 %) patients (group A). The remaining 19 (15.6 %) patients underwent unilateral PAE (groupmore » B). Mean follow-up time was 6.7 months in group A and 7.3 months in group B. Mean prostate volume, PSA, International prostate symptom score/quality of life (IPSS/QoL) and post-void residual volume (PVR) reduction, and peak flow rate (Qmax) improvement were 19.4 mL, 1.68 ng/mL, 11.8/2.0 points, 32.9 mL, and 3.9 mL/s in group A and 11.5 mL, 1.98 ng/mL, 8.9/1.4 points, 53.8 mL, and 4.58 mL/s in group B. Poor clinical outcome was observed in 24.3 % of patients from group A and 47.4 % from group B (p = 0.04). PAE is a safe and effective technique that can induce 48 % improvement in the IPSS score and a prostate volume reduction of 19 %, with good clinical outcome in up to 75 % of treated patients. Bilateral PAE seems to lead to better clinical results; however, up to 50 % of patients after unilateral PAE may have a good clinical outcome.« less

Effects of repetitive transcranial magnetic stimulation combined with sensory cueing on unilateral neglect in subacute patients with right hemispheric stroke: a randomized controlled study.

PubMed

Yang, Nicole Yh; Fong, Kenneth Nk; Li-Tsang, Cecilia Wp; Zhou, D

2017-09-01

To compare the effects of rTMS combined with sensory cueing, rTMS alone, and conventional rehabilitation on unilateral neglect, hemiplegic arm functions and performance of activities of daily living. A single-blinded randomized controlled trial. A convalescent hospital. Sixty inpatients with left unilateral neglect after stroke. Patients were randomly assigned to three groups: rTMS combined with sensory cueing, rTMS, and conventional rehabilitation alone. rTMS at 1 Hz was applied over P5 of the contralesional hemisphere while vibration cueing was emitted using a wristwatch device on the hemiplegic arm, five days per week for two weeks. The first two groups received the same dosage of conventional rehabilitation on top of their experimental interventions. Blinded assessments were administered at baseline, 2 weeks postintervention, and 6 weeks follow-up. Neglect and arm motor performance. Both rTMS combined with sensory cueing (99.6±33.0) and rTMS alone (88.2±28.7) significantly reduced unilateral neglect than conventional rehabilitation (72.7±33.1) when measured using the conventional subtests of the Behavioural Inattention Test, but the combination was better than rTMS alone. Hemiplegic arm functions and activities of daily living improved in all patients across the three groups but no significant differences were found between the groups. The combination of inhibitory P5-rTMS with sensory cueing was better than either rTMS or conventional rehabilitation alone in producing a stronger and long-lasting improvement in unilateral neglect, but the improvement was not associated with improved arm function or independence in activities of daily living.

Single-dose Universal Hepatitis A Immunization in One-year-old Children in Argentina: High Prevalence of Protective Antibodies up to 9 Years After Vaccination.

PubMed

Urueña, Analía; González, Jorge E; Rearte, Analía; Pérez Carrega, María E; Calli, Rogelio; Pagani, María F; Uboldi, Andrea; Vicentín, Rosalía; Caglio, Patricia; Cañero-Velasco, María C; Gentile, Angela; Ramonet, Margarita; Vizzotti, Carla

2016-12-01

Single-dose hepatitis A virus (HAV) vaccination was implemented in all Argentinean children 12 months of age in 2005. Previous studies demonstrated high prevalence of protective antibody response 4 years after single-dose vaccination. This study assessed long-term seroprotection against HAV after vaccination. Children who received 1 dose of HAV vaccine at 1 year of age at least 6 years before enrollment were included at 5 centers in Argentina between 2013 and 2014. Demographic and socioeconomic characteristics were collected through a questionnaire. Blood samples were tested for anti-HAV antibodies. Antibody values ≥10 mIU/mL were considered seroprotective. Logistic regression analysis was performed to evaluate the association between demographic and socioeconomic variables and seroprotection. A total of 1088 children were included, with a median postvaccination interval of 7.7 years (range 6.3-9.2 years). Of these children, 97.4% (95% confidence interval: 96.3%-98.3%) had protective antibodies against HAV. No association between demographic or socioeconomic variables and seroprotection was found. Geometric mean concentration of antibody levels against HAV was 170.5 mUI/mL (95% confidence interval: 163.2-178.2 mUI/mL). Single-dose universal hepatitis A immunization in 1-year-old children resulted in sustained immunologic protection for up to 9 years in Argentina. These findings, along with the low current disease burden, confirm the success of the intervention.

Herpes zoster: A clinicocytopathological insight.

PubMed

Shah, Snehal; Singaraju, Sasidhar; Einstein, A; Sharma, Ashish

2016-01-01

Herpes zoster or shingles is reactivation of the varicella zoster virus that had entered the cutaneous nerve endings during an earlier episode of chicken pox traveled to the dorsal root ganglia and remained in a latent form. This condition is characterized by occurrence of multiple, painful, unilateral vesicles and ulceration which shows a typical single dermatome involvement. In this case report, we present a patient with herpes zoster involving the mandibular division of the trigeminal nerve, with unilateral vesicles over the right side of lower third of face along the trigeminal nerve tract, with intraoral involvement of buccal mucosa, labial mucosa and the tongue of the same side. Cytopathology revealed classic features of herpes infection including inclusion bodies, perinuclear halo and multinucleated cells.

An unusual co-presentation of rhinolithiasis and squamous cell carcinoma in the nasal cavity.

PubMed

Özdemir, Süleyman; Görgülü, Orhan; Akbaş, Yücel; Selçuk, Tahsin; Sayar, Hamide; Tarkan, Özgür

2012-07-01

Rhinoliths are nasal stones that result from mineralisation of salts around an endogenous or exogenous nidus within the nasal cavity. They are uncommon nasal masses and usually unilateral and single, situated in the floor of the nose. The patient typically presents with nasal obstruction, facial pain and foul-smelling nasal secretion. To the best of our knowledge, the occurrence of squamous cell carcinoma with rhinolithiasis has not been previously reported in the English-language literature. In this article, we present a 63-year-old man, who had unilateral rhinolithiasis with squamous cell carcinoma within the nasal cavity. Copyright © 2011 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

Linac-based extracranial radiosurgery with Elekta volumetric modulated arc therapy and an anatomy-based treatment planning system: Feasibility and initial experience

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

Cilla, Savino, E-mail: savinocilla@gmail.com; Deodato, Francesco; Macchia, Gabriella

We reported our initial experience in using Elekta volumetric modulated arc therapy (VMAT) and an anatomy-based treatment planning system (TPS) for single high-dose radiosurgery (SRS-VMAT) of liver metastases. This study included a cohort of 12 patients treated with a 26-Gy single fraction. Single-arc VMAT plans were generated with Ergo++ TPS. The prescription isodose surface (IDS) was selected to fulfill the 2 following criteria: 95% of planning target volume (PTV) reached 100% of the prescription dose and 99% of PTV reached a minimum of 90% of prescription dose. A 1-mm multileaf collimator (MLC) block margin was added around the PTV. Formore » a comparison of dose distributions with literature data, several conformity indexes (conformity index [CI], conformation number [CN], and gradient index [GI]) were calculated. Treatment efficiency and pretreatment dosimetric verification were assessed. Early clinical data were also reported. Our results reported that target and organ-at-risk objectives were met for all patients. Mean and maximum doses to PTVs were on average 112.9% and 121.5% of prescribed dose, respectively. A very high degree of dose conformity was obtained, with CI, CN, and GI average values equal to 1.29, 0.80, and 3.63, respectively. The beam-on-time was on average 9.3 minutes, i.e., 0.36 min/Gy. The mean number of monitor units was 3162, i.e., 121.6 MU/Gy. Pretreatment verification (3%-3 mm) showed an optimal agreement with calculated values; mean γ value was 0.27 and 98.2% of measured points resulted with γ < 1. With a median follow-up of 16 months complete response was observed in 12/14 (86%) lesions; partial response was observed in 2/14 (14%) lesions. No radiation-induced liver disease (RILD) was observed in any patients as well no duodenal ulceration or esophagitis or gastric hemorrhage. In conclusion, this analysis demonstrated the feasibility and the appropriateness of high-dose single-fraction SRS-VMAT in liver metastases performed with Elekta VMAT and Ergo++ TPS. Preliminary clinical outcomes showed a high rate of local control and minimum incidence of acute toxicity.« less

Role of (-)-epigallocatechin gallate in the pharmacokinetic interaction between nadolol and green tea in healthy volunteers.

PubMed

Abe, Osamu; Ono, Tomoyuki; Sato, Hideyuki; Müller, Fabian; Ogata, Hiroshi; Miura, Itaru; Shikama, Yayoi; Yabe, Hirooki; Onoue, Satomi; Fromm, Martin F; Kimura, Junko; Misaka, Shingen

2018-06-01

The aim of the present study is to investigate a possible role of a single dose of (-)-epigallocatechin gallate (EGCG), the major catechin in green tea, for the pharmacokinetic interaction between green tea and nadolol in humans. In a randomized three-phase crossover study, 13 healthy volunteers received single doses of 30 mg nadolol orally with water (control), or an aqueous solution of EGCG-concentrated green tea extract (GTE) at low or high dose. Plasma concentrations and urinary excretion of nadolol were determined up to 48 h. In addition, blood pressure and pulse rate were monitored. In vitro transport kinetic experiments were performed using human embryonic kidney 293 cells stably expressing organic anion transporting polypeptide (OATP)1A2 to evaluate the inhibitory effect of EGCG on OATP1A2-mediated substrate transport. Single coadministration of low and high dose GTE significantly reduced the plasma concentrations of nadolol. The geometric mean ratios with 90% CI for area under the plasma concentration-time curves from 0 to infinity of nadolol were 0.72 (0.56-0.87) for the low and 0.60 (0.51-0.69) for the high dose. There were no significant differences in T max , elimination half-life, and renal clearance between GTE and water phases. No significant changes were observed for blood pressure and pulse rate between phases. EGCG competitively inhibited OATP1A2-mediated uptake of sulphobromophthalein and nadolol with K i values of 21.6 and 19.4 μM, respectively. EGCG is suggested to be a key contributor to the interaction of green tea with nadolol. Moreover, even a single coadministration of green tea may significantly affect nadolol pharmacokinetics.

Chronic consumption of a low calorie, high polyphenol cranberry beverage attenuates inflammation and improves glucoregulation and HDL cholesterol in healthy overweight humans: a randomized controlled trial.

PubMed

Chew, Boon; Mathison, Bridget; Kimble, Lindsey; McKay, Diane; Kaspar, Kerrie; Khoo, Christina; Chen, C-Y Oliver; Blumberg, Jeffrey

2018-02-23

We studied the health benefits of low calorie cranberry beverage consumption on glucoregulation, oxidative damage, inflammation, and lipid metabolism in overweight but otherwise healthy humans. 78 overweight or obese men and women (30-70 years; BMI 27-35 kg/m 2 ) with abdominal adiposity (waist: hip > 0.8 for women and > 0.9 for men; waist: height ≥ 0.5) consumed 450 mL placebo or low calorie, high polyphenol cranberry extract beverage (CEB) daily for 8 week in a randomized, double-blind, placebo-controlled, parallel design trial. Blood and urine samples were collected after overnight fast at baseline and after 8 weeks of daily beverage consumption. Blood and urine samples were also collected during 3 oral glucose tolerance test (OGTT) challenges: (1) pre-intervention without the test beverages, (2) following a single dose of placebo or CEB at baseline (week 0), and (3) following a single dose of placebo or CEB at 8 week. Compared to placebo, a single CEB dose at baseline lowered endothelin-1 and elevated nitric oxide and the reduced:oxidized glutathione ratio (P < 0.05). Interferon-γ was elevated (P < 0.05) after a single CEB dose at baseline; however, after 8 week of CEB intervention, fasting C-reactive protein was lower (P < 0.05). CEB consumption for 8 week also reduced serum insulin and increased HDL cholesterol compared to placebo (P < 0.05). An acute dose of low calorie, high polyphenol cranberry beverage improved antioxidant status, while 8 week daily consumption reduced cardiovascular disease risk factors by improving glucoregulation, downregulating inflammatory biomarkers, and increasing HDL cholesterol.

Current practice of antibiotic prophylaxis for surgical fixation of closed long bone fractures: a survey of 297 members of the Orthopaedic Trauma Association.

PubMed

Gans, Itai; Jain, Amit; Sirisreetreerux, Norachart; Haut, Elliott R; Hasenboehler, Erik A

2017-01-01

The risk of postoperative surgical site infection after long bone fracture fixation can be decreased with appropriate antibiotic use. However, there is no agreement on the superiority of a single- or multiple-dose perioperative regimen of antibiotic prophylaxis. The purpose of this study is to determine the following: 1) What are the current practice patterns of orthopaedic trauma surgeons in using perioperative antibiotics for closed long bone fractures? 2) What is the current knowledge of published antibiotic prophylaxis guidelines among orthopaedic trauma surgeons? 3) Are orthopaedic surgeons willing to change their current practices? A questionnaire was distributed via email between September and December 2015 to 955 Orthopaedic Trauma Association members, of whom 297 (31%) responded. Most surgeons (96%) use cefazolin as first-line infection prophylaxis. Fifty-nine percent used a multiple-dose antibiotic regimen, 39% used a single-dose regimen, and 2% varied this decision according to patient factors. Thirty-six percent said they were unfamiliar with Centers for Disease Control and Prevention (CDC) antibiotic prophylaxis guidelines; only 30% were able to select the correct CDC recommendation from a multiple-choice list. However, 44% of surgeons said they followed CDC recommendations. Fifty-six percent answered that a single-dose antibiotic prophylaxis regimen was not inferior to a multiple-dose regimen. If a level-I study comparing a single preoperative dose versus multiple perioperative antibiotic dosing regimen for treatment of closed long bone fractures were published, most respondents (64%) said they would fully follow these guidelines, and 22% said they would partially change their practice to follow these guidelines. There is heterogeneity in the use of single- versus multiple-dose antibiotic prophylaxis for surgical repair of closed long bone fractures. Many surgeons were unsure of current evidence-based recommendations regarding perioperative antibiotic use. Most respondents indicated they would be receptive to high-level evidence regarding the single- versus multiple-dose perioperative prophylactic antibiotics for the treatment of closed long bone fractures.

Impact of Cricothyroid Muscle Contraction on Vocal Fold Vibration: Experimental Study with High-Speed Videoendoscopy.

PubMed

Ishikawa, Camila Cristina; Pinheiro, Thais Gonçalves; Hachiya, Adriana; Montagnoli, Arlindo Neto; Tsuji, Domingos Hiroshi

2017-05-01

The aim of this study was to evaluate the effects of cricothyroid muscle contraction on vocal fold vibration, as evaluated with high-speed videoendoscopy, and to identify one or more aspects of vocal fold vibration that could be used as an irrefutable indicator of unilateral cricothyroid muscle paralysis. This was an experimental study employing excised human larynges. Twenty freshly excised human larynges were evaluated during artificially produced vibration. Each larynx was assessed in three situations: bilateral cricothyroid muscle contraction, unilateral cricothyroid muscle contraction, and no contraction of either cricothyroid muscle. The following parameters were evaluated by high-speed videoendoscopy: fundamental frequency, periodicity, amplitude of vocal fold vibration, and phase symmetry between the vocal folds. Although neither unilateral nor bilateral cricothyroid muscle contraction altered the periodicity of vibration or the occurrence of phase asymmetry, there was a significant decrease in fundamental frequency in parallel with decreasing longitudinal tension. We also found an increase in vibration amplitude of right and left vocal folds, which were similar in terms of their behavior for this parameter in the various situations studied. Our results suggest that differences in vibration amplitude and phase symmetry between vocal folds are not reliable indicators of unilateral cricothyroid muscle paralysis. Copyright © 2017 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

Pharmacokinetic Variability of Drugs Used for Prophylactic Treatment of Migraine.

PubMed

Tfelt-Hansen, Peer; Ågesen, Frederik Nybye; Pavbro, Agniezka; Tfelt-Hansen, Jacob

2017-05-01

In this review, we evaluate the variability in the pharmacokinetics of 11 drugs with established prophylactic effects in migraine to facilitate 'personalized medicine' with these drugs. PubMed was searched for 'single-dose' and 'steady-state' pharmacokinetic studies of these 11 drugs. The maximum plasma concentration was reported in 248 single-dose and 115 steady-state pharmacokinetic studies, and the area under the plasma concentration-time curve was reported in 299 single-dose studies and 112 steady-state pharmacokinetic studies. For each study, the coefficient of variation was calculated for maximum plasma concentration and area under the plasma concentration-time curve, and we divided the drug variability into two categories; high variability, coefficient of variation >40%, or low or moderate variability, coefficient of variation <40%. Based on the area under the plasma concentration-time curve in steady-state studies, the following drugs have high pharmacokinetic variability: propranolol in 92% (33/36), metoprolol in 85% (33/39), and amitriptyline in 60% (3/5) of studies. The following drugs have low or moderate variability: atenolol in 100% (2/2), valproate in 100% (15/15), topiramate in 88% (7/8), and naproxen and candesartan in 100% (2/2) of studies. For drugs with low or moderate pharmacokinetic variability, treatment can start without initial titration of doses, whereas titration is used to possibly enhance tolerability of topiramate and amitriptyline. The very high pharmacokinetic variability of metoprolol and propranolol can result in very high plasma concentrations in a small minority of patients, and those drugs should therefore be titrated up from a low initial dose, depending mainly on the occurrence of adverse events.

In vivo assessment of the gastric mucosal tolerance dose after single fraction, small volume irradiation of liver malignancies by computed tomography-guided, high-dose-rate brachytherapy

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

Streitparth, Florian; Pech, Maciej; Boehmig, Michael

2006-08-01

Purpose: The aim of this study was to assess the tolerance dose of gastric mucosa for single-fraction computed tomography (CT)-guided, high-dose-rate (HDR) brachytherapy of liver malignancies. Methods and Materials: A total of 33 patients treated by CT-guided HDR brachytherapy of liver malignancies in segments II and/or III were included. Dose planning was performed upon a three-dimensional CT data set acquired after percutaneous applicator positioning. All patients received gastric protection post-treatment. For further analysis, the contours of the gastric wall were defined in every CT slice using Brachyvision Software. Dose-volume histograms were calculated for each treatment and correlated with clinical datamore » derived from questionnaires assessing Common Toxicity Criteria (CTC). All patients presenting symptoms of upper GI toxicity were examined endoscopically. Results: Summarizing all patients the minimum dose applied to 1 ml of the gastric wall (D{sub 1ml}) ranged from 6.3 to 34.2 Gy; median, 14.3 Gy. Toxicity was present in 18 patients (55%). We found nausea in 16 (69%), emesis in 9 (27%), cramping in 13 (39%), weight loss in 12 (36%), gastritis in 4 (12%), and ulceration in 5 patients (15%). We found a threshold dose D{sub 1ml} of 11 Gy for general gastric toxicity and 15.5 Gy for gastric ulceration verified by an univariate analysis (p = 0.01). Conclusions: For a single fraction, small volume irradiation we found in the upper abdomen a threshold dose D{sub 1ml} of 15.5 Gy for the clinical endpoint ulceration of the gastric mucosa. This in vivo assessment is in accordance with previously published tolerance data.« less

Application of strict criteria in adrenal venous sampling increases the proportion of missed patients with unilateral disease who benefit from surgery for primary aldosteronism.

PubMed

Kline, Gregory; Leung, Alexander; So, Benny; Chin, Alex; Harvey, Adrian; Pasieka, Janice L

2018-06-01

Adrenal vein sampling (AVS) is intended to confirm unilateral forms of primary aldosteronism, which are amenable to surgical cure. Excessively strict AVS criteria to define lateralization may result in many patients incorrectly categorized as bilateral primary aldosteronism and opportunity for surgical cure missed. Retrospective review of an AVS-primary aldosteronism database in which surgical cases are verified by standardized outcomes. Having used 'less strict' AVS criteria for lateralization, we examined the distribution of AVS lateralization indices in our confirmed unilateral primary aldosteronism cases both with and without cosyntropin stimulation. The proportion of proven unilateral cases that would have been missed with stricter AVS interpretation criteria was calculated. Particular focus was given to the proportion of missed cases according to use of international guidelines. False-positive lateralization with 'less strict' interpretation was also calculated. Of 80 surgical primary aldosteronism cases, 10-23% would have been missed with AVS lateralization indices of 3 : 1 to 5 : 1, with or without cosyntropin. If strict selectivity indices (for confirmation of catheterization) were combined with strict lateralization indices, up to 70% of unilateral primary aldosteronism cases could have been missed. Use of Endocrine Society AVS guidelines would have missed 21-43% of proven unilateral cases. 'Less strict' AVS interpretation yielded one case (1.2%) of false lateralization. Excessively strict AVS interpretation criteria will result in a high rate of missed unilateral primary aldosteronism with subsequent loss of opportunity for intervention. Use of more lenient lateralization criteria will improve the detection rate of unilateral primary aldosteronism with very low false-positive rate.

Assessing Muscle-Strength Asymmetry via a Unilateral-Stance Isometric Midthigh Pull.

PubMed

Dos'Santos, Thomas; Thomas, Christopher; Jones, Paul A; Comfort, Paul

2017-04-01

To investigate the within-session reliability of bilateral- and unilateral-stance isometric midthigh-pull (IMTP) force-time characteristics including peak force (PF), relative PF, and impulse at time bands (0-100, 0-200, 0-250, and 0-300 milliseconds) and to compare isometric force-time characteristics between right and left and dominant (D) and nondominant (ND) limbs. Professional male rugby league and multisport male college athletes (N = 54; age, 23.4 ± 4.2 y; height, 1.80 ± 0.05 m; mass, 88.9 ± 12.9 kg) performed 3 bilateral IMTP trials and 6 unilateral-stance IMTP trials (3 per leg) on a force plate sampling at 600 Hz. Intraclass correlation coefficients (ICCs) and coefficients of variation (CVs) demonstrated high within-session reliability for bilateral and unilateral IMTP PF (ICC = .94, CV = 4.7-5.5%). Lower reliability measures and greater variability were observed for bilateral and unilateral IMTP impulse at time bands (ICC = .81-.88, CV = 7.7-11.8%). Paired-sample t tests and Cohen d effect sizes revealed no significant differences for all isometric force-time characteristics between right and left limbs in male college athletes (P >.05, d ≤ 0.32) and professional rugby league players (P > .05, d ≤ 0.11); however, significant differences were found between D and ND limbs in male college athletes (P < .001, d = 0.43-0.91) and professional rugby league players (P < .001, d = 0.27-0.46). This study demonstrated high within-session reliability for unilateral-stance IMTP PF, revealing significant differences in isometric force-time characteristics between D and ND limbs in male athletes.

Development of the Mini-Assisting Hand Assessment: evidence for content and internal scale validity.

PubMed

Greaves, Susan; Imms, Christine; Dodd, Karen; Krumlinde-Sundholm, Lena

2013-11-01

To describe the development of the Mini-Assisting Hand Assessment (Mini-AHA) for children with signs of unilateral cerebral palsy (CP) aged 8 to 18 months, and evaluate aspects of content and internal scale validity. The ability of the video-recorded Mini-AHA play session to provoke bimanual performance in children with unilateral CP and typical development was evaluated. Original AHA test items were examined for their suitability for younger children and possible new items were generated. Data from 108 assessments of children with unilateral CP (86 children, 53 males, 33 females; mean age 13 mo, SD 3 mo, range 8-18 mo) were entered into a Rasch measurement model analysis to evaluate internal scale validity. A Spearman's correlation analysis explored the relationship between age and ability measures for children with unilateral CP. The frequency of maximum scores in 40 children with typical development (22 males, 18 females; mean age 12 mo, SD 3 mo) was examined. The Mini-AHA play session provoked bimanual responses in typically developing children 99% of the time. Person and item fit criteria established 20 items for the scale. The resultant unidimensional scale also demonstrated excellent discriminative features through high separation reliability. The item calibration values covered the range of person ability measures well. Age was not related to the ability measures for children with unilateral CP (rs =0.178). All children with typical development achieved maximum scores. Accumulated evidence shows that the Mini-AHA validly measures use of the affected hand during bimanual performance for children with unilateral CP aged 8 to 18 months. The Mini-AHA has the potential to be a useful assessment to evaluate functional hand use and the effects of intervention in an age group when potential for change is high. © 2013 Mac Keith Press.

Consensus or controversy? The classification and treatment decision-making by 491 maxillofacial surgeons from around the world in three cases of a unilateral mandibular condyle fracture.

PubMed

Kommers, Sofie C; Boffano, Paolo; Forouzanfar, Tymour

2015-12-01

Many studies are available in the literature on both classification and treatment of unilateral mandibular condyle fractures. To date however, controversy regarding the best treatment for unilateral mandibular condyle fractures remains. In this study, an attempt was made to quantify the level of agreement between a sample of maxillofacial surgeons worldwide, on the classification and treatment decisions in three different unilateral mandibular condyle fracture cases. In total, 491 of 3044 participants responded. In all three mandibular condyle fracture cases, a fairly high level of disagreement was found. Only in the case of a subcondylar fracture, assuming dysocclusion was present, more than 81% of surgeons agreed that the best treatment would be open reduction and internal fixation. Based on the study results, there is considerable variation among surgeons worldwide with regard to treatment of unilateral mandibular condyle fracture. 3D imaging in higher fractures tends to lead to more invasive treatment decisions. Copyright © 2015 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

Excretion of sodium and methylglucamine diatrizoate after longtime unilateral ureteric stasis in the rabbit.

PubMed

Owman, T

1979-01-01

The excretion of sodium and meglumine diatrizoate was examined following one or two weeks of unilateral ureteric occlusion. No difference between the two diatrizoate salts was found. A slow compensatory increase of the function of the intact kidney occurred, but after two weeks it was still insufficient at high blood concentration levels.

The incidence of the different sources of noise on the uncertainty in radiochromic film dosimetry using single channel and multichannel methods

NASA Astrophysics Data System (ADS)

González-López, Antonio; Vera-Sánchez, Juan Antonio; Ruiz-Morales, Carmen

2017-11-01

The influence of the various sources of noise on the uncertainty in radiochromic film (RCF) dosimetry using single channel and multichannel methods is investigated in this work. These sources of noise are extracted from pixel value (PV) readings and dose maps. Pieces of an RCF were each irradiated to different uniform doses, ranging from 0 to 1092 cGy. Then, the pieces were read at two resolutions (72 and 150 ppp) with two flatbed scanners: Epson 10000XL and Epson V800, representing two states of technology. Noise was extracted as described in ISO 15739 (2013), separating its distinct constituents: random noise and fixed pattern (FP) noise. Regarding the PV maps, FP noise is the main source of noise for both models of digitizer. Also, the standard deviation of the random noise in the 10000XL model is almost twice that of the V800 model. In the dose maps, the FP noise is smaller in the multichannel method than in the single channel ones. However, random noise is higher in this method, throughout the dose range. In the multichannel method, FP noise is reduced, as a consequence of this method’s ability to eliminate channel independent perturbations. However, the random noise increases, because the dose is calculated as a linear combination of the doses obtained by the single channel methods. The values of the coefficients of this linear combination are obtained in the present study, and the root of the sum of their squares is shown to range between 0.9 and 1.9 over the dose range studied. These results indicate the random noise to play a fundamental role in the uncertainty of RCF dosimetry: low levels of random noise are required in the digitizer to fully exploit the advantages of the multichannel dosimetry method. This is particularly important for measuring high doses at high spatial resolutions.

High-dose tranexamic acid reduces intraoperative and postoperative blood loss in posterior lumbar interbody fusion.

PubMed

Kushioka, Junichi; Yamashita, Tomoya; Okuda, Shinya; Maeno, Takafumi; Matsumoto, Tomiya; Yamasaki, Ryoji; Iwasaki, Motoki

2017-03-01

OBJECTIVE Tranexamic acid (TXA), a synthetic antifibrinolytic drug, has been reported to reduce blood loss in orthopedic surgery, but there have been few reports of its use in spine surgery. Previous studies included limitations in terms of different TXA dose regimens, different levels and numbers of fused segments, and different surgical techniques. Therefore, the authors decided to strictly limit TXA dose regimens, surgical techniques, and fused segments in this study. There have been no reports of using TXA for prevention of intraoperative and postoperative blood loss in posterior lumbar interbody fusion (PLIF). The purpose of the study was to evaluate the efficacy of high-dose TXA in reducing blood loss and its safety during single-level PLIF. METHODS The study was a nonrandomized, case-controlled trial. Sixty consecutive patients underwent single-level PLIF at a single institution. The first 30 patients did not receive TXA. The next 30 patients received 2000 mg of intravenous TXA 15 minutes before the skin incision was performed and received the same dose again 16 hours after the surgery. Intra- and postoperative blood loss was compared between the groups. RESULTS There were no statistically significant differences in preoperative parameters of age, sex, body mass index, preoperative diagnosis, or operating time. The TXA group experienced significantly less intraoperative blood loss (mean 253 ml) compared with the control group (mean 415 ml; p < 0.01). The TXA group also had significantly less postoperative blood loss over 40 hours (mean 321 ml) compared with the control group (mean 668 ml; p < 0.01). Total blood loss in the TXA group (mean 574 ml) was significantly lower than in the control group (mean 1080 ml; p < 0.01). From 2 hours to 40 hours, postoperative blood loss in the TXA group was consistently significantly lower. There were no perioperative complications, including thromboembolic events. CONCLUSIONS High-dose TXA significantly reduced both intra- and postoperative blood loss without causing any complications during or after single-level PLIF.

Nevirapine Resistance by Timing of HIV Type 1 Infection in Infants Treated with Single-Dose Nevirapine

PubMed Central

Micek, Mark A.; Blanco, Ana Judith; Beck, Ingrid A.; Dross, Sandra; Matunha, Laurinda; Montoya, Pablo; Seidel, Kristy; Gantt, Soren; Matediane, Eduardo; Jamisse, Lilia; Gloyd, Stephen; Frenkel, Lisa M.

2011-01-01

Background In women, single-dose nevirapine for prophylaxis against mother-to-child transmission of human immunodeficiency virus type 1 (HIV-1) selects for nevirapine-resistant HIV-1, which subsequently decays rapidly. We hypothesized that the selection, acquisition, and decay of nevirapine-resistant HIV-1 differs in infants, varying by the timing of HIV-1 infection. Methods We conducted a prospective, observational study of 740 Mozambican infants receiving single-dose nevirapine prophylaxis and determined the timing of infection and concentrations of nevirapine-resistant HIV-1 over time. Results Infants with established in utero infection had a high rate (87.0%) of selection of nevirapine-resistant HIV-1 mutants, which rapidly decayed to undetectable levels. The few without nevirapine resistance received zidovudine with single-dose nevirapine and/or their mothers took alternative antiretroviral drugs. Infants with acute in utero infection had a lower rate of nevirapine-resistant HIV-1 (33.3%; P =.006, compared with established in utero infection), but mutants persisted over time. Infants with peripartum infection also had a lower rate of nevirapine-resistant HIV-1 (38.1%; P =.001, compared with established in utero infection) but often acquired 100% mutant virus that persisted over time (P =.017, compared with established in utero infection). Conclusions The detection and persistence of nevirapine-resistant HIV-1 in infants after single-dose nevirapine therapy vary by the timing of infection and the antiretroviral regimen. In infants with persistent high-level nevirapine-resistant HIV-1, nevirapine-based antiretroviral therapy is unlikely to ever be efficacious because of concentrations in long-lived viral reservoirs. However, the absence or decay of nevirapine-resistant HIV-1 in many infants suggests that nevirapine antiretroviral therapy may be effective if testing can identify these individuals. PMID:20384494

Health economic assessment of universal immunization of toddlers against Hepatitis A Virus (HAV) in Mexico

PubMed Central

Carlos, Fernando; Gómez, Jorge Alberto; Anaya, Pablo; Romano-Mazzotti, Luis

2016-01-01

Hepatitis A virus (HAV) has shifted from high to intermediate endemicity in Mexico, which may increase the risk of clinically significant HAV infections in older children, adolescents and adults. The objective of this study was to evaluate the cost-utility of single-dose or 2-dose universal infant HAV vaccination strategy in Mexico, compared with no vaccination. A previously published dynamic model estimated the expected number of HAV cases with each strategy, and a decision model was used to estimate the costs and quality-adjusted life-years (QALYs) expected with each strategy. The time horizon was 25 years (2012–2036) and the base case analysis was conducted from the perspective of the Mexican public health system. Costs and QALYs after the first year were discounted at 5% annually. Input data were taken from national databases and published sources where available. The single-dose HAV vaccination strategy had an incremental cost-utility ratio (ICUR) of Mexican peso (MXN) 2,270 per QALY gained, compared with no vaccination. The two-dose strategy had an ICUR of MXN 14,961/QALY compared with no vaccination, and an ICUR of MXN 78,280/QALY compared with the single-dose strategy. The estimated ICURs were below the threshold of 1 x Mexican gross domestic product per capita. When indirect costs were included (societal perspective), the single-dose HAV vaccination strategy would be expected to improve health outcomes and to be cost-saving. This analysis indicates that routine vaccination of toddlers against HAV would be cost-effective in Mexico using either a single-dose or a 2-dose vaccination strategy. GSK study identifier: HO-12-12877. PMID:26503702

Health economic assessment of universal immunization of toddlers against Hepatitis A Virus (HAV) in Mexico.

PubMed

Carlos, Fernando; Gómez, Jorge Alberto; Anaya, Pablo; Romano-Mazzotti, Luis

2016-01-01

Hepatitis A virus (HAV) has shifted from high to intermediate endemicity in Mexico, which may increase the risk of clinically significant HAV infections in older children, adolescents and adults. The objective of this study was to evaluate the cost-utility of single-dose or 2-dose universal infant HAV vaccination strategy in Mexico, compared with no vaccination. A previously published dynamic model estimated the expected number of HAV cases with each strategy, and a decision model was used to estimate the costs and quality-adjusted life-years (QALYs) expected with each strategy. The time horizon was 25 years (2012-2036) and the base case analysis was conducted from the perspective of the Mexican public health system. Costs and QALYs after the first year were discounted at 5% annually. Input data were taken from national databases and published sources where available. The single-dose HAV vaccination strategy had an incremental cost-utility ratio (ICUR) of Mexican peso (MXN) 2,270 per QALY gained, compared with no vaccination. The two-dose strategy had an ICUR of MXN 14,961/QALY compared with no vaccination, and an ICUR of MXN 78,280/QALY compared with the single-dose strategy. The estimated ICURs were below the threshold of 1 x Mexican gross domestic product per capita. When indirect costs were included (societal perspective), the single-dose HAV vaccination strategy would be expected to improve health outcomes and to be cost-saving. This analysis indicates that routine vaccination of toddlers against HAV would be cost-effective in Mexico using either a single-dose or a 2-dose vaccination strategy. GSK study identifier: HO-12-12877.

Adaptive intensity modulated radiotherapy for advanced prostate cancer

NASA Astrophysics Data System (ADS)

Ludlum, Erica Marie

The purpose of this research is to develop and evaluate improvements in intensity modulated radiotherapy (IMRT) for concurrent treatment of prostate and pelvic lymph nodes. The first objective is to decrease delivery time while maintaining treatment quality, and evaluate the effectiveness and efficiency of novel one-step optimization compared to conventional two-step optimization. Both planning methods are examined at multiple levels of complexity by comparing the number of beam apertures, or segments, the amount of radiation delivered as measured by monitor units (MUs), and delivery time. One-step optimization is demonstrated to simplify IMRT planning and reduce segments (from 160 to 40), MUs (from 911 to 746), and delivery time (from 22 to 7 min) with comparable plan quality. The second objective is to examine the capability of three commercial dose calculation engines employing different levels of accuracy and efficiency to handle high--Z materials, such as metallic hip prostheses, included in the treatment field. Pencil beam, convolution superposition, and Monte Carlo dose calculation engines are compared by examining the dose differences for patient plans with unilateral and bilateral hip prostheses, and for phantom plans with a metal insert for comparison with film measurements. Convolution superposition and Monte Carlo methods calculate doses that are 1.3% and 34.5% less than the pencil beam method, respectively. Film results demonstrate that Monte Carlo most closely represents actual radiation delivery, but none of the three engines accurately predict the dose distribution when high-Z heterogeneities exist in the treatment fields. The final objective is to improve the accuracy of IMRT delivery by accounting for independent organ motion during concurrent treatment of the prostate and pelvic lymph nodes. A leaf-shifting algorithm is developed to track daily prostate position without requiring online dose calculation. Compared to conventional methods of adjusting patient position, adjusting the multileaf collimator (MLC) leaves associated with the prostate in each segment significantly improves lymph node dose coverage (maintains 45 Gy compared to 42.7, 38.3, and 34.0 Gy for iso-shifts of 0.5, 1 and 1.5 cm). Altering the MLC portal shape is demonstrated as a new and effective solution to independent prostate movement during concurrent treatment.

Effects of food on the pharmacokinetics of ponatinib in healthy subjects.

PubMed

Narasimhan, N I; Dorer, D J; Niland, K; Haluska, F; Sonnichsen, Daryl

2013-12-01

Ponatinib is a potent oral tyrosine kinase inhibitor with activity against BCR-ABL, the primary driver of chronic myeloid leukaemia and Philadelphia chromosome-positive acute lymphoblastic leukaemia. This single-centre, single-dose, randomized, open-label, three-period crossover study evaluated the pharmacokinetics and bioavailability of a single oral dose of ponatinib (45-mg tablet) under fasting conditions and following consumption of high- and low-fat meals by healthy subjects. Subjects were randomly assigned to one of the six possible treatment sequences, each evaluating three ponatinib 45-mg treatments: administered under fasting conditions; administered after a high-fat meal; or administered after a standardized low-fat meal. The high-fat meal derived approximately 50% of its total caloric content from fat, with approximately 150, 250 and 500-600 calories derived from protein, carbohydrates and fat, respectively (total of approximately 900-1000 calories). The standardized low-fat meal derived no more than 20% of total caloric content from fat, with approximately 56, 428 and 63 calories derived from protein, carbohydrates and fat, respectively (total of approximately 547 calories). During each of the three treatment periods, blood samples were collected predose and at 13 time points over the 96-h post-dose interval. Plasma concentrations of ponatinib were measured by liquid chromatography/tandem mass spectrometry. Mixed-model analyses of variance (anova) were performed on natural log-transformed PK parameters Cmax and AUC0-∞. Geometric mean maximum plasma concentration (Cmax) values for the fasted, low-fat and high-fat regimens were 54·7, 51·6 and 51·5 ng/mL, respectively. Geometric mean area under the concentration-time curve from time zero to infinity (AUC0-∞) values for the fasted, low-fat and high-fat regimens were 1273, 1244 and 1392 h × ng/mL, respectively. All limits of the 90% CIs of the estimated geometric mean ratios for Cmax and all AUC comparisons fell within the 80%-125% margins. These results indicate that consumption of a high- or low-fat meal within 30 min prior to administration of ponatinib had no effect on the single-dose pharmacokinetics of ponatinib. Food does not affect the single-dose pharmacokinetics of ponatinib. These data demonstrate that ponatinib may be administered with or without food. © 2013 The Authors. Journal of Clinical Pharmacy and Therapeutics published by John Wiley & Sons Ltd.

Clock-drawing test and unilateral spatial neglect.

PubMed

Ishiai, S; Sugishita, M; Ichikawa, T; Gono, S; Watabiki, S

1993-01-01

We investigated the ability of 25 patients with left unilateral spatial neglect to make a clock face by putting numbers inside a printed circle. Impairment seen in this clock-drawing test did not parallel neglect severity as judged by results of the line-cancellation and line-bisection tests, as well as the copying of a daisy. The score for clock drawing correlated highly with the verbal WAIS score. Most neglect patients with a verbal IQ of 87 or more could draw a clock face fairly well and used planning in placing the numbers 12, 3, 6, and 9 before the others. In clock drawing, verbal intelligence may compensate for left unilateral spatial neglect. We therefore recommend use of the line-cancellation and line-bisection tests, as well as the copying test, but do not recommend use of the clock-drawing test in the diagnosis of left unilateral spatial neglect.

Five-Year Outcomes of High-Dose Single-Fraction Spinal Stereotactic Radiosurgery

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

Moussazadeh, Nelson; Department of Neurological Surgery, Weill Cornell Medical College, New York Presbyterian Hospital, New York, New York; Lis, Eric

Purpose: To characterize local tumor control and toxicity risk in very long-term survivors (>5 years) after high-dose spinal image guided, intensity modulated radiation therapy delivered as single-dose stereotactic radiosurgery (SRS). Previously published spinal SRS outcome analyses have included a heterogeneous population of cancer patients, mostly with short survival. This is the first study reporting the long-term tumor control and toxicity profiles after high-dose single-fraction spinal SRS. Methods and Materials: The study population included all patients treated from June 2004 to July 2009 with single-fraction spinal SRS (dose 24 Gy) who had survived at least 5 years after treatment. The endpoints examined included diseasemore » progression, surgical or radiation retreatment, in-field fracture development, and radiation-associated toxicity, scored using the Radiation Therapy Oncology Group radiation morbidity scoring criteria and the Common Terminology Criteria for Adverse Events, version 4.0. Local control and fracture development were assessed using Kaplan-Meier analysis. Results: Of 278 patients, 31 (11.1%), with 36 segments treated for spinal tumors, survived at least 5 years after treatment and were followed up radiographically and clinically for a median of 6.1 years (maximum 102 months). The histopathologic findings for the 5-year survivors included radiation-resistant metastases in 58%, radiation-sensitive metastases in 22%, and primary bone tumors in 19%. In this selected cohort, 3 treatment failures occurred at a median of 48.6 months, including 2 recurrences in the radiation field and 1 patient with demonstrated progression at the treatment margins. Ten lesions (27.8%) were associated with acute grade 1 cutaneous or gastrointestinal toxicity. Delayed toxicity ≥3 months after treatment included 8 cases (22.2%) of mild neuropathy, 2 (5.6%) of gastrointestinal discomfort, 8 (22.2%) of dermatitides, and 3 (8.3%) of myalgias/myositis. Thirteen treated levels (36.1%) in 12 patients demonstrated progressive vertebral body collapse or endplate fractures at a median of 25.7 months (range 11.6-76.0), of which 5 (14%) became symptomatic and subsequently required percutaneous cement augmentation or surgery. Conclusions: In the longest-term series to date, high-dose single-fraction spinal SRS retained an excellent safety profile among long-term survivors (>5 years)« less

Laparoscopic inguinal hernia repair in children with transperitoneal division of the hernia sac and proximal purse string closure of peritoneum: our modified new approach.

PubMed

Wheeler, A A; Matz, S T; Schmidt, S; Pimpalwar, A

2011-12-01

To describe our results of laparoscopic transperitoneal division of the hernia sac with purse string closure of the proximal peritoneum for inguinal hernia repair in children. A retrospective case review of all patients undergoing laparoscopic herniorrhaphy with herniotomy by a single surgeon between January and August 2007 was performed evaluating perioperative and postoperative outcomes. A complete intracorporeal laparoscopic technique was utilized to inspect bilateral inguinal canals followed by circumferential division of the peritoneum at the deep ring (patent processus vaginalis) followed by purse string closure of the proximal peritoneum. 31 inguinal hernias were repaired laparoscopically in 26 patients (23 boys, 3 girls). Median age was 36 months (range 1-168 months). 22 children had unilateral inguinal hernia repairs including 2 recurrent hernias; 4 children underwent repair of bilateral inguinal hernias. Mean operating time for unilateral and bilateral inguinal hernia repairs were 48.5 ± 14 min and 61 ± 13.8 min, respectively. 2 patients with a preoperative unilateral inguinal hernia were found to have bilateral inguinal hernias upon laparoscopic examination which were repaired. Postoperative pain was minimal in 20 (77%) patients at discharge. Mean telephone follow-up at 8 ± 9.6 months demonstrated no recurrences to date. Laparoscopic inguinal hernia repair with transperitoneal division of the hernia sac and purse string closure of the proximal peritoneum allows for a minimally invasive option for pediatric inguinal hernia repair that mimics open inguinal hernia repair. At medium term follow-up there have been no recurrences to date, high parent satisfaction, minimal scarring and good cosmetic results. © Georg Thieme Verlag KG Stuttgart · New York.

The modification of high-dose therapy shortens the duration of neutropaenia by delay of leucocyte nadir.

PubMed

Kiefer, T; Krüger, W H; Schüler, F; Lotze, C; Hirt, C; Dölken, G

2006-06-01

Infections during neutropaenia contribute still significantly to mortality and morbidity after high-dose therapy and autologous stem cell transplantation. Further acceleration of haemopoietic recovery seems impossible for biological reasons. Another approach to shorten neutropaenia could be to remove drugs from high-dose therapy protocols with strong contribution to immunosuppression and neutropaenia and unproven antineoplastic activity. In this retrospective matched-pair analysis, conventional busulphan/cyclophosphamide (Bu/Cy) high-dose therapy was compared to single-agent busulphan conditioning before autologous stem cell transplantation. This modification led to a significant shorter neutropaenic interval by protraction of cell decrease and to a significant mitigation of neutropaenia. After single-agent busulphan conditioning, leucocytes dropped below 1/nl at median 1.5 days later when compared to the patients from the busulphanBu/Cy control group (P=0.001). In a significant percentage of patients (n=6, 60%) leucocytes did not fall below 0.5 cells/nl at any time. In contrast, all patients from the Bu/Cy control group experienced deep neutropaenia (P=0.004). Thrombocytopaenia and requirement for transfusions of platelets or red cells were not influenced. Antineoplastic activity seemed to be preserved as determined by survival analysis. In conclusion, modification of high-dose regimen with the intention to shorten neutropaenia with preserved antitumour activity could be an approach to reduce infection-related morbidity and mortality and to consider economic necessities.

Economic Analyses in Anterior Cruciate Ligament Reconstruction: A Qualitative and Systematic Review.

PubMed

Saltzman, Bryan M; Cvetanovich, Gregory L; Nwachukwu, Benedict U; Mall, Nathan A; Bush-Joseph, Charles A; Bach, Bernard R

2016-05-01

As the health care system in the United States (US) transitions toward value-based care, there is an increased emphasis on understanding the cost drivers and high-value procedures within orthopaedics. To date, there has been no systematic review of the economic literature on anterior cruciate ligament reconstruction (ACLR). To evaluate the overall evidence base for economic studies published on ACLR in the orthopaedic literature. Data available on the economics of ACLR are summarized and cost drivers associated with the procedure are identified. Systematic review. All economic studies (including US-based and non-US-based) published between inception of the MEDLINE database and October 3, 2014, were identified. Given the heterogeneity of the existing evidence base, a qualitative, descriptive approach was used to assess the collective results from the economic studies on ACLR. When applicable, comparisons were made for the following cost-related variables associated with the procedure for economic implications: outpatient versus inpatient surgery (or outpatient vs overnight hospital stay vs >1-night stay); bone-patellar tendon-bone (BPTB) graft versus hamstring (HS) graft source; autograft versus allograft source; staged unilateral ACLR versus bilateral ACLR in a single setting; single- versus double-bundle technique; ACLR versus nonoperative treatment; and other unique comparisons reported in single studies, including computer-assisted navigation surgery (CANS) versus traditional surgery, early versus delayed ACLR, single- versus double-incision technique, and finally the costs of ACLR without comparison of variables. A total of 24 studies were identified and included; of these, 17 included studies were cost identification studies. The remaining 7 studies were cost utility analyses that used economic models to investigate the effect of variables such as the cost of allograft tissue, fixation devices, and physical therapy, the percentage and timing of revision surgery, and the cost of revision surgery. Of the 24 studies, there were 3 studies with level 1 evidence, 8 with level 2 evidence, 6 with level 3 evidence, and 7 with level 4 evidence. The following economic comparisons were demonstrated: (1) ACLR is more cost-effective than nonoperative treatment with rehabilitation only (per 3 cost utility analyses); (2) autograft use had lower total costs than allograft use, with operating room supply costs and allograft costs most significant (per 5 cost identification studies and 1 cost utility analysis); (3) results on hamstring versus BPTB graft source are conflicting (per 2 cost identification studies); (4) there is significant cost reduction with an outpatient versus inpatient setting (per 5 studies using cost identification analyses); (5) bilateral ACLR is more cost efficient than 2 unilateral ACLRs in separate settings (per 2 cost identification studies); (6) there are lower costs with similarly successful outcomes between single- and double-bundle technique (per 3 cost identification studies and 2 cost utility analyses). Results from this review suggest that early single-bundle, single (endoscopic)-incision outpatient ACLR using either BPTB or HS autograft provides the most value. In the setting of bilateral ACL rupture, single-setting bilateral ACLR is more cost-effective than staged unilateral ACLR. Procedures using CANS technology do not yet yield results that are superior to the results of a standard surgical procedure, and CANS has substantially greater costs. © 2015 The Author(s).

Converging levels of analysis in the cognitive neuroscience of visual attention.

PubMed Central

Duncan, J

1998-01-01

Experiments using behavioural, lesion, functional imaging and single neuron methods are considered in the context of a neuropsychological model of visual attention. According to this model, inputs compete for representation in multiple visually responsive brain systems, sensory and motor, cortical and subcortical. Competition is biased by advance priming of neurons responsive to current behavioural targets. Across systems competition is integrated such that the same, selected object tends to become dominant throughout. The behavioural studies reviewed concern divided attention within and between modalities. They implicate within-modality competition as one main restriction on concurrent stimulus identification. In contrast to the conventional association of lateral attentional focus with parietal lobe function, the lesion studies show attentional bias to be a widespread consequence of unilateral cortical damage. Although the clinical syndrome of unilateral neglect may indeed be associated with parietal lesions, this probably reflects an assortment of further deficits accompanying a simple attentional imbalance. The functional imaging studies show joint involvement of lateral prefrontal and occipital cortex in lateral attentional focus and competition. The single unit studies suggest how competition in several regions of extrastriate cortex is biased by advance priming of neurons responsive to current behavioural targets. Together, the concepts of competition, priming and integration allow a unified theoretical approach to findings from behavioural to single neuron levels. PMID:9770224

Clinical Outcomes of Intravitreal Preservative-Free Triamcinolone Preparation (Triesence®) for Cystoid Macular Oedema and Inflammation in Patients with Uveitis.

PubMed

Steeples, Laura R; Anand, Nitin; Moraji, Jiten; Jones, Nicholas P

2017-03-20

To assess the outcomes of intravitreal benzyl alcohol-free triamcinolone acetonide suspension in uveitis-related macular oedema. Single-center retrospective cohort study of 66 injections to 44 eyes of 40 patients. Uveitis diagnosis, systemic and local therapy, intraocular pressure (IOP), central retinal thickness (CRT), number of injections, time to re-injection and side-effects were noted during 6-months minimum follow-up. Sixty eight percent of eyes received a single injection. 18% required 2 injections, and 13% received ≥3 injections with mean time to second and third injections of 25.5 and 52.7 weeks, respectively. 90% of injections were unilateral. Mean CRT reduced, and by 12-weeks visual acuity improvement >0.3logMar was achieved in 46%. Cataract progression (47%) and IOP>21 mmHg (45%) were the commonest adverse events. Preservative-free triamcinolone is an additional option for uveitis-related macular oedema, particularly in unilateral cases, with favorable CRT and visual outcomes. Repeat injections may be necessary, and the period of efficacy varies between eyes.

A Single Session of Mirror-based Tactile and Motor Training Improves Tactile Dysfunction in Children with Unilateral Cerebral Palsy: A Replicated Randomized Controlled Case Series.

PubMed

Auld, Megan L; Johnston, Leanne M; Russo, Remo N; Moseley, G Lorimer

2017-10-01

This replicated randomized controlled crossover case series investigated the effect of mirror-based tactile and motor training on tactile registration and perception in children with unilateral cerebral palsy (UCP). Six children with UCP (6-18 years; median 10 years, five male, three-left hemiplegia, four-manual ability classification system (MACS) I, one MACS II and one MACS III) participated. They attended two 90-minute sessions - one of mirror-based training and one of standard practice, bimanual therapy - in alternated order. Tactile registration (Semmes Weinstein Monofilaments) and perception (double simultaneous or single-point localization) were assessed before and after each session. Change was estimated using reliable change index (RCI). Tactile perception improved in four participants (RCI > 1.75), with mirror-based training, but was unchanged with bimanual therapy (RCI < 1.0 for all participants). Neither intervention affected tactile registration. Mirror-based training demonstrates potential to improve tactile perception in children with UCP. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Single dose of an adenovirus vectored mouse interferon-α protects mice from lethal EV71 challenge.

PubMed

Sun, Jialei; Ennis, Jane; Turner, Jeffrey D; Chu, Justin Jang Hann

2016-10-01

Enterovirus 71 (EV71) causes hand-foot-and-mouth diseases as well as neurological complications in young children. Interferon (IFN) can inhibit the replication of many viruses with low cytotoxic effects. Previously, an adenovirus vectored mouse interferon-α (DEF201), subtype 5, was generated by Wu et al, 2007. In this study, the antiviral effects of DEF201 against EV71 were evaluated in a murine model. 6-day-old BALB/c mice were administered a single dose of DEF201 before or after infection with lethal dose of EV71. The survival rate, clinical symptoms, tissue viral loads and histology pathogenesis were evaluated. IFN gene expression following a single dose of DEF201 maintained high concentrations of 100-9000 pg/mL for more than 7 days in mice serum. Pre-infection administration of a single dose of 10 6  PFU of DEF201 offered full protection of the mice against EV71 infection compared with the empty Ad5 vector control. In addition, virus load in DEF201-treated mice muscle tissue was significantly decreased as compared with empty vector control. Histopathology analysis revealed that DEF201 significantly prevented the development of severe tissue damage with reduction of viral antigen in the murine muscle tissue. Post-infection treatment at 6 h offered full protection and partial protection at 12 h, indicating that DEF201 could be used as an anti-EV71 therapeutic agent in early stage of EV71 infection. In addition, our study showed that DEF201 enhanced the neutralization ability of serum in EV71-vaccinated mice, implying that DEF201 could promote the production of specific anti-EV71 antibodies. In conclusion, single dose of DEF201 is highly efficacious as a prophylactic agent against EV71 infection in vivo. Copyright © 2016 Elsevier B.V. All rights reserved.

Sustained Neuroprotection From a Single Intravitreal Injection of PGJ2 in a Nonhuman Primate Model of Nonarteritic Anterior Ischemic Optic Neuropathy

PubMed Central

Miller, Neil R.; Johnson, Mary A.; Nolan, Theresa; Guo, Yan; Bernstein, Alexander M.; Bernstein, Steven L.

2014-01-01

Purpose. Prostaglandin J2 (PGJ2) is neuroprotective in a murine model of nonarteritic anterior ischemic optic neuropathy (NAION). After assessing for potential toxicity, we evaluated the efficacy of a single intravitreal (IVT) injection of PGJ2 in a nonhuman primate model of NAION (pNAION). Methods. We assessed PGJ2 toxicity by administering it as a single high-dose intravenous (IV) injection, consecutive daily high-dose IV injections, or a single IVT injection in one eye of five adult rhesus monkeys. To assess efficacy, we induced pNAION in one eye of five adult male rhesus monkeys using a laser-activated rose bengal induction method. We then injected the eye with either PGJ2 or phosphate-buffered saline (PBS) intravitreally immediately or 5 hours post induction. We performed a clinical assessment, optical coherence tomography, electrophysiological testing, fundus photography, and fluorescein angiography in all animals prior to induction and at 1 day, 1 week, 2 weeks, and 4 weeks after induction. Following analysis of the first eye, we induced pNAION in the contralateral eye and then injected either PGJ2 or PBS. We euthanized all animals 5 weeks after final assessment of the fellow eye and performed both immunohistochemical and light and electron microscopic analyses of the retina and optic nerves. Results. Toxicity: PGJ2 caused no permanent systemic toxicity regardless of the amount injected or route of delivery, and there was no evidence of any ocular toxicity with the dose of PGJ2 used in efficacy studies. Transient reduction in the amplitudes of the visual evoked potentials and the N95 component of the pattern electroretinogram (PERG) occurred after both IV and IVT administration of high doses of PGJ2; however, the amplitudes returned to normal in all animals within 1 week. Efficacy: In all eyes, a single IVT dose of PGJ2 administered immediately or shortly after induction of pNAION resulted in a significant reduction of clinical, electrophysiological, and histological damage compared with vehicle-injected eyes (P = 0.03 for both VEP and PERG; P = 0.05 for axon counts). Conclusions. In nonhuman primates, PGJ2 administered either intravenously or intravitreally produces no permanent toxicity at even four times the dose given for neuroprotection. Additionally, a single IVT dose of PGJ2 is neuroprotective when administered up to 5 hours after induction of pNAION. PMID:25298416

Exercise intervention for unilateral amputees with low back pain: study protocol for a randomised, controlled trial.

PubMed

Wasser, Joseph G; Herman, Daniel C; Horodyski, MaryBeth; Zaremski, Jason L; Tripp, Brady; Page, Phillip; Vincent, Kevin R; Vincent, Heather K

2017-12-29

Atraumatic lower limb amputation is a life-changing event for approximately 185,000 persons in the United States each year. A unilateral amputation is associated with rapid changes to the musculoskeletal system including leg and back muscle atrophy, strength loss, gait asymmetries, differential mechanical joint loading and leg length discrepancies. Even with high-quality medical care and prostheses, amputees still develop secondary musculoskeletal conditions such as chronic low back pain (LBP). Resistance training interventions that focus on core stabilization, lumbar strength and dynamic stability during loading have strong potential to reduce LBP and address amputation-related changes to the musculoskeletal system. Home-based resistance exercise programs may be attractive to patients to minimize travel and financial burdens. This study will be a single-assessor-blinded, pre-post-test randomised controlled trial involving 40 men and women aged 18-60 years with traumatic, unilateral transtibial amputation. Participants will be randomised to a home-based, resistance exercise group (HBRX) or a wait-list control group (CON). The HBRX will consist of 12 weeks of elastic resistance band and bodyweight training to improve core and lumbopelvic strength. Participants will be monitored via Skype or Facetime on a weekly basis. The primary outcome will be pain severity (11-point Numerical Pain Rating Scale; NRS pain ). Secondary outcomes will include pain impact on quality of life (Medical Outcomes Short Form 36, Oswestry Disability Index and Roland Morris Disability Questionnaire), kinematics and kinetics of walking gait on an instrumented treadmill, muscle morphology (muscle thickness of multifidus, transversus abdominis, internal oblique), maximal muscle strength of key lumbar and core muscles, and daily step count. The study findings will determine whether a HBRX program can decrease pain severity and positively impact several physiological and mechanical factors that contribute to back pain in unilateral transtibial amputees with chronic LBP. We will determine the relative contribution of the exercise-induced changes in these factors on pain responsiveness in this population. ClinicalTrials.gov, ID: NCT03300375 . Registered on 2 October 2017.

Factors impacting short and long-term kidney graft survival: modification by single intra-operative -high-dose induction with ATG-Fresenius.

PubMed

Kaden, Jürgen; May, Gottfried; Völp, Andreas; Wesslau, Claus

2011-01-01

A majority of recipients benefited from the intra-operative single high-dose induction (HDI) with ATG-Fresenius (ATG-F) still leaving a group of recipients who did not profit from this kind of induction. Therefore the aim of this retrospective analysis was 1st to identify the risk factors impacting short and long-term graft survival, and 2nd to assess the efficacy of this type of induction in kidney graft recipients with or without these risk factors. A total of 606 recipients receiving two different immunosuppressive treatment regimens (1st: Triple drug therapy [TDT, n=196] consisting mainly of steroids, azathioprine and cyclosporine; 2nd: TDT + 9 mg/kg ATG-F intra-operatively [HDI, n=410]) were included in this analysis and grouped according to their kidney graft survival time (short GST: ≤1 yr, n=100 and long GST: >5 yrs, n=506). The main risk factors associated with a shortened graft survival were pre-transplant sensitization, re-transplantation, rejections (in particular vascular or mixed ones) and the necessity of a long-term anti-rejection therapy. Adding ATG-F single high dose induction to TDT was more efficient in prolonging kidney graft survival than TDT alone not only in recipients without any risk factors (p<0.005) but also in recipients with at least one risk factor (p<0.021). Only in 4.6% of recipients having two or more risk factors this effect could not be demonstrated. The intra-operative single high-dose induction with ATG-F significantly improves the kidney graft survival in recipients with or without risk factors and can therefore be recommended.

Symmetrical and overloaded effect of diffusion in information filtering

NASA Astrophysics Data System (ADS)

Zhu, Xuzhen; Tian, Hui; Chen, Guilin; Cai, Shimin

2017-10-01

In physical dynamics, mass diffusion theory has been applied to design effective information filtering models on bipartite network. In previous works, researchers unilaterally believe objects' similarities are determined by single directional mass diffusion from the collected object to the uncollected, meanwhile, inadvertently ignore adverse influence of diffusion overload. It in some extent veils the essence of diffusion in physical dynamics and hurts the recommendation accuracy and diversity. After delicate investigation, we argue that symmetrical diffusion effectively discloses essence of mass diffusion, and high diffusion overload should be published. Accordingly, in this paper, we propose an symmetrical and overload penalized diffusion based model (SOPD), which shows excellent performances in extensive experiments on benchmark datasets Movielens and Netflix.

Excellent Result With the Use of Single-Dose OK-432 in Cervical Macrocystic Lymphangioma.

PubMed

Efe, Nihal; Altas, Enver; Mazlumoglu, Muhammet Recai; Aktan, Bulent; Ucuncu, Harun; Eren, Suat; Oner, Fatih

2016-10-01

Though the lymphangioma is a benign neoplasm, it may make an invasion to vital structures by progressively growing. For lymphangioma, which progressed in such a way, surgical treatment has high morbidity and recurrence risk. On these cases, OK-432 is a frequently used sclerotherapy agent. The authors report the result they obtained by the use of single-dose OK-432 on an inoperable pediatric cervical macrocystic lymphangioma case and also their experiences.

The cochlear implant as a tinnitus treatment.

PubMed

Vallés-Varela, Héctor; Royo-López, Juan; Carmen-Sampériz, Luis; Sebastián-Cortés, José M; Alfonso-Collado, Ignacio

2013-01-01

Tinnitus is a symptom of high prevalence in patients with cochlear pathology. We studied the evolution of tinnitus in patients undergoing unilateral cochlear implantation for treatment of profound hearing loss. This was a longitudinal, retrospective study of patients that underwent unilateral cochlear implantation and who had bilateral tinnitus. Tinnitus was assessed quantitatively and qualitatively before surgery and at 6 and 12 months after surgery. We evaluated 20 patients that underwent unilateral cochlear implantation with a Nucleus(®) CI24RE Contour Advance™ electrode device. During the periods in which the device was in operation, improvement or disappearance of tinnitus was evidenced in the ipsilateral ear in 65% of patients, and in the contralateral ear, in 50%. In periods in which the device was disconnected, improvement or disappearance of tinnitus was found in the ipsilateral ear in 50% of patients, and in the ear contralateral to the implant in 45% of the patients. In 10% of the patients, a new tinnitus appeared in the ipsilateral ear. The patients with profound hearing loss and bilateral tinnitus treated with unilateral cochlear implantation improved in a high percentage of cases, in the ipsilateral ear and in the contralateral ear. Copyright © 2012 Elsevier España, S.L. All rights reserved.

A calibration method for patient specific IMRT QA using a single therapy verification film

PubMed Central

Shukla, Arvind Kumar; Oinam, Arun S.; Kumar, Sanjeev; Sandhu, I.S.; Sharma, S.C.

2013-01-01

Aim The aim of the present study is to develop and verify the single film calibration procedure used in intensity-modulated radiation therapy (IMRT) quality assurance. Background Radiographic films have been regularly used in routine commissioning of treatment modalities and verification of treatment planning system (TPS). The radiation dosimetery based on radiographic films has ability to give absolute two-dimension dose distribution and prefer for the IMRT quality assurance. However, the single therapy verification film gives a quick and significant reliable method for IMRT verification. Materials and methods A single extended dose rate (EDR 2) film was used to generate the sensitometric curve of film optical density and radiation dose. EDR 2 film was exposed with nine 6 cm × 6 cm fields of 6 MV photon beam obtained from a medical linear accelerator at 5-cm depth in solid water phantom. The nine regions of single film were exposed with radiation doses raging from 10 to 362 cGy. The actual dose measurements inside the field regions were performed using 0.6 cm3 ionization chamber. The exposed film was processed after irradiation using a VIDAR film scanner and the value of optical density was noted for each region. Ten IMRT plans of head and neck carcinoma were used for verification using a dynamic IMRT technique, and evaluated using the gamma index method with TPS calculated dose distribution. Results Sensitometric curve has been generated using a single film exposed at nine field region to check quantitative dose verifications of IMRT treatments. The radiation scattered factor was observed to decrease exponentially with the increase in the distance from the centre of each field region. The IMRT plans based on calibration curve were verified using the gamma index method and found to be within acceptable criteria. Conclusion The single film method proved to be superior to the traditional calibration method and produce fast daily film calibration for highly accurate IMRT verification. PMID:24416558

Correlation of local failure with measures of dose insufficiency in the high-dose single-fraction treatment of bony metastases.

PubMed

Lovelock, D Michael; Zhang, Zhigang; Jackson, Andrew; Keam, Jennifer; Bekelman, Justin; Bilsky, Mark; Lis, Eric; Yamada, Yoshiya

2010-07-15

In the setting of high-dose single-fraction image-guided radiotherapy of spine metastases, the delivered dose is hypothesized to be a significant factor in local control. We investigated the dependence of local control on measures of dose insufficiency. The minimum doses received by the hottest 100%, 98%, and 95% (D(min), D(98), and D(95)) of the gross target volume (GTV) were computed for 91 consecutively treated lesions observed in 79 patients. Prescribed doses of 18-24 Gy were delivered in a single fraction. The spinal cord and cauda equina were constrained to a maximum dose of 12-14 Gy and 16 Gy, respectively. A rank-sum test was used to assess the differences between radiographic local failure and local control. With a median follow-up of 18 months, seven local failures have occurred. The distributions of GTV D(min), D(98), and D(95) for treatments resulting in local failure were found to be statistically different from the corresponding distributions of the patient group as a whole. Taking no account of histology, p values calculated for D(min), D(98), and D(95) were 0.004, 0.012, and 0.031, respectively. No correlations between local failure and target volume or between local failure and anatomic location were found. The results indicate that D(min), D(98), and D(95) may be important risk factors for local failure. No local failures in any histology were observed when D(min) was >15 Gy, suggesting that this metric may be an important predictor of local control. Copyright 2010 Elsevier Inc. All rights reserved.

CORRELATION OF LOCAL FAILURE WITH MEASURES OF DOSE INSUFFICIENCY IN THE HIGH-DOSE SINGLE-FRACTION TREATMENT OF BONY METASTASES

PubMed Central

Lovelock, D. Michael; Zhang, Zhigang; Jackson, Andrew; Keam, Jennifer; Bekelman, Justin; Bilsky, Mark; Lis, Eric; Yamada, Yoshiya

2011-01-01

Purpose In the setting of high-dose single-fraction image-guided radiotherapy of spine metastases, the delivered dose is hypothesized to be a significant factor in local control. We investigated the dependence of local control on measures of dose insufficiency. Methods and Materials The minimum doses received by the hottest 100%, 98%, and 95% (Dmin, D98, and D95) of the gross target volume (GTV) were computed for 91 consecutively treated lesions observed in 79 patients. Prescribed doses of 18–24 Gy were delivered in a single fraction. The spinal cord and cauda equina were constrained to a maximum dose of 12–14 Gy and 16 Gy, respectively. A rank-sum test was used to assess the differences between radiographic local failure and local control. Results With a median follow-up of 18 months, seven local failures have occurred. The distributions of GTV Dmin, D98, and D95 for treatments resulting in local failure were found to be statistically different from the corresponding distributions of the patient group as a whole. Taking no account of histology, p values calculated for Dmin, D98, and D95 were 0.004, 0.012, and 0.031, respectively. No correlations between local failure and target volume or between local failure and anatomic location were found. Conclusions The results indicate that Dmin, D98, and D95 may be important risk factors for local failure. No local failures in any histology were observed when Dmin was >15 Gy, suggesting that this metric may be an important predictor of local control. PMID:20350795

The effects of Kinesio Taping on body functions and activity in unilateral spastic cerebral palsy: a single-blind randomized controlled trial.

PubMed

Kaya Kara, Ozgun; Atasavun Uysal, Songul; Turker, Duygu; Karayazgan, Sedef; Gunel, Mintaze Kerem; Baltaci, Gul

2015-01-01

The aim of this study was to investigate the effects of Kinesio Taping (KT) on the body functions and activity of children with unilateral spastic cerebral palsy (CP). This study was designed as a single-blind, randomized, controlled trial. Thirty children with unilateral spastic CP were randomized and split equally between the KT group (eight males, seven females; mean age 9y [SD 2y 3mo] range 7-12y) and the control group (seven males, eight females; mean age 9y 7mo [SD 3y 4mo] range 7-14y) receiving usual care. All participants were evaluated with the Functional Independence Measure for Children (WeeFIM), the Bruininks-Oseretsky Test of Motor Proficiency (BOTMP), the Gross Motor Function Measure (GMFM), short-term muscle power, agility and functional muscle strength tests. Wilcoxon signed-rank and Mann-Whitney U tests were used to evaluate within and between-group differences respectively. The level of significance was accepted as p<0.05. There were significant differences in muscle power sprint (p=0.003), lateral step-up test right (p=0.016), sit to stand (p=0.018), attain stand through half knee right (p=0.003), BOTMP Gross scores (p=0.019), and WeeFIM total (p=0.003) and self-care scores (p=0.022) between the groups (p<0.05). Kinesio Taping is a promising additional approach to increase proprioceptive feedback and improve physical fitness, gross motor function, and activities of daily living in children with CP. © 2014 Mac Keith Press.

SU-E-T-224: Considerations for the Proper Treatment of Multiple Cranial Metastases with Single Isocenter Volumetric Modulated Arc Therapy

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

Audet, C; Poffenbarger, B; Hwang, A

2015-06-15

Purpose: To investigate some limitations of single isocenter VMAT for cranial multiple met cases. Methods: A single isocenter VMAT plan (Varian, Eclipse AAA10 commissioned down to 1 cm) was designed for two 7mm diameter spherical targets in a rectangular Solid Water (Gammex) phantom. The targets were separated by a distance of 6cm and the isocenter was centered in one of the targets. The plan was delivered (Varian, Truebeam STx) three separate times with different artificial couch angle errors of 0, 0.5 and 1 degree. The coronal dose distributions were measured with calibrated EBT3 film placed at mid-phantom. EBT3 film dosimetrymore » was also performed on the delivery of separate multiple arc vmat plans to targets below 6mm in diameter. Results: Measurements of the sup/inf dose profiles through the high dose distributions show no movement of the central axis high dose region and shifts of the high dose region intended for the off-axis target. For the 1 degree rotation error, the high dose region was shifted 1.04mm from the target. This corresponds to the shift expected from triangulation (60mmxTan(1deg)=1.047mm). Furthermore, a streak of 10% interleaf leakage dose was observed and is likely a Result of the off axis target traveling a wide path such that a long length of MLC is exposed for the whole arc. The calculated dose was about 10% to 15% low compared to that measured on film for a 5mm diameter target. Conclusion: Judicious use of additional margin for off axis targets or limits on the span of multiple mets treated with one isocenter is recommended. The magnitude of the margin should be based on the rotational errors evaluated for the positioning system and the distance of the target from the isocenter. A lower limit of lesion size that can be accurately treated with VMAT should be determined.« less

Differences in GFR and Tissue Oxygenation, and Interactions between Stenotic and Contralateral Kidneys in Unilateral Atherosclerotic Renovascular Disease.

PubMed

Herrmann, Sandra M S; Saad, Ahmed; Eirin, Alfonso; Woollard, John; Tang, Hui; McKusick, Michael A; Misra, Sanjay; Glockner, James F; Lerman, Lilach O; Textor, Stephen C

2016-03-07

Atherosclerotic renal artery stenosis (ARAS) can reduce renal blood flow, tissue oxygenation, and GFR. In this study, we sought to examine associations between renal hemodynamics and tissue oxygenation with single-kidney function, pressor hormones, and inflammatory biomarkers in patients with unilateral ARAS undergoing medical therapy alone or stent revascularization. Nonrandomized inpatient studies were performed in patients with unilateral ARAS (>60% occlusion) before and 3 months after revascularization (n=10) or medical therapy (n=20) or patients with essential hypertension (n=32) under identical conditions. The primary study outcome was change in single-kidney GFR. Individual kidney hemodynamics and volume were measured using multidetector computed tomography. Tissue oxygenation (using R(2)* as a measure of deoxyhemoglobin) was determined by blood oxygen level-dependent magnetic resonance imaging at 3 T. Renal vein neutrophil gelatinase-associated lipocalin (NGAL), monocyte chemoattractant protein-1 (MCP-1), and plasma renin activity were measured. Total GFR did not change over 3 months in either group, but the stenotic kidney (STK) GFR rose over time in the stent compared with the medical group (+2.2[-1.8 to 10.5] versus -5.3[-7.3 to -0.3] ml/min; P=0.03). Contralateral kidney (CLK) GFR declined in the stent group (43.6±19.7 to 36.6±19.5 ml/min; P=0.03). Fractional tissue hypoxia fell in the STK (fraction R(2)* >30/s: 22.1%±20% versus 14.9%±18.3%; P<0.01) after stenting. Renal vein biomarkers correlated with the degree of hypoxia in the STK: NGAL(r=0.3; P=0.01) and MCP-1(r=0.3; P=0.02; more so after stenting). Renal vein NGAL was inversely related to renal blood flow in the STK (r=-0.65; P<0.001). Biomarkers were highly correlated between STK and CLK, NGAL (r=0.94; P<0.001), and MCP-1 (r=0.96; P<0.001). These results showed changes over time in single-kidney GFR that were not evident in parameters of total GFR. Furthermore, they delineate the relationship of measurable tissue hypoxia within the STK and markers of inflammation in human ARAS. Renal vein NGAL and MCP-1 indicated persistent interactions between the ischemic kidney and both CLK and systemic levels of inflammatory cytokines. Copyright © 2016 by the American Society of Nephrology.

Inter-rater reliability of three standardized functional tests in patients with low back pain

PubMed Central

Tidstrand, Johan; Horneij, Eva

2009-01-01

Background Of all patients with low back pain, 85% are diagnosed as "non-specific lumbar pain". Lumbar instability has been described as one specific diagnosis which several authors have described as delayed muscular responses, impaired postural control as well as impaired muscular coordination among these patients. This has mostly been measured and evaluated in a laboratory setting. There are few standardized and evaluated functional tests, examining functional muscular coordination which are also applicable in the non-laboratory setting. In ordinary clinical work, tests of functional muscular coordination should be easy to apply. The aim of this present study was to therefore standardize and examine the inter-rater reliability of three functional tests of muscular functional coordination of the lumbar spine in patients with low back pain. Methods Nineteen consecutive individuals, ten men and nine women were included. (Mean age 42 years, SD ± 12 yrs). Two independent examiners assessed three tests: "single limb stance", "sitting on a Bobath ball with one leg lifted" and "unilateral pelvic lift" on the same occasion. The standardization procedure took altered positions of the spine or pelvis and compensatory movements of the free extremities into account. The inter-rater reliability was analyzed by Cohen's kappa coefficient (κ) and by percentage agreement. Results The inter-rater reliability for the right and the left leg respectively was: for the single limb stance very good (κ: 0.88–1.0), for sitting on a Bobath ball good (κ: 0.79) and very good (κ: 0.88) and for the unilateral pelvic lift: good (κ: 0.61) and moderate (κ: 0.47). Conclusion The present study showed good to very good inter-rater reliability for two standardized tests, that is, the single-limb stance and sitting on a Bobath-ball with one leg lifted. Inter-rater reliability for the unilateral pelvic lift test was moderate to good. Validation of the tests in their ability to evaluate lumbar stability is required. PMID:19490644

Irradiation effects in UO2 and CeO2

NASA Astrophysics Data System (ADS)

Ye, Bei; Oaks, Aaron; Kirk, Mark; Yun, Di; Chen, Wei-Ying; Holtzman, Benjamin; Stubbins, James F.

2013-10-01

Single crystal CeO2, as a surrogate material to UO2, was irradiated with 500 keV xenon ions at 800 °C while being observed using in situ transmission electron microscopy (TEM). Experimental results show the formation and growth of defect clusters including dislocation loops and cavities as a function of increasing atomic displacement dose. At high dose, the dislocation loop structure evolves into an extended dislocation line structure, which appears to remain stable to the high dose levels examined in this study. A high concentration of cavities was also present in the microstructure. Despite high atomic displacement doses, the specimen remained crystalline to a cumulated dose of 5 × 1015 ions/cm2, which is consistent with the known stability of the fluorite structure under high dose irradiation. Kinetic Monte Carlo calculations show that oxygen mobility is substantially higher in hypo-stoichiometric UO2/CeO2 than hyper-stoichiometric systems. This result is consistent with the ability of irradiation damage to recover even at intermediate irradiation temperatures.

Bilateral rectal sheath hematomas after low-molecular weight heparin treatment in uremia.

PubMed

Xu, Lu; Liu, Lei; Li, Xinjian

2017-11-01

Rectus sheath hematomas (RSHs) are uncommon. They are usually unilateral and rarely bilateral. In this paper, we report the first case of spontaneous bilateral RSHs in a uremic patient after the administration of the first dose of low-molecular weight heparin during hemodialysis. The most interesting aspect of this case is that the main symptom of RSH in our patient was urinary bladder irritation. We highlight the importance of the prompt diagnosis and management of this medical emergency.

Combined effects of sensory cueing and limb activation on unilateral neglect in subacute left hemiplegic stroke patients: a randomized controlled pilot study.

PubMed

Fong, Kenneth N K; Yang, Nicole Y H; Chan, Marko K L; Chan, Dora Y L; Lau, Andy F C; Chan, Dick Y W; Cheung, Joyce T Y; Cheung, Hobby K Y; Chung, Raymond C K; Chan, Chetwyn C H

2013-07-01

To compare the effects of contralesional sensory cueing and limb activation with that of sham control in the treatment of unilateral neglect after stroke. A randomized, single-blinded, sham-controlled pilot study. Two rehabilitation hospitals. Forty subacute left hemiplegic stroke inpatients with unilateral neglect. Participants were assigned randomly to 1 of 2 groups. The experimental group wore a wristwatch cueing device over the hemiplegic arm for three hours a day, five days per week, for three weeks, and also underwent conventional rehabilitation. Patients were encouraged to move their hemiplegic arm five consecutive times after each prompt. The sham group underwent the same rehabilitation process, except they wore a sham device. Neglect, arm motor performance, and overall functioning were assessed pre- and posttraining, and at follow-up. There were no significant differences between groups in outcome measures except the neglect drawing tasks (p = 0.034) (the mean gain score from baseline to follow-up assessment was 5.2 (3.7) in the experimental group and 1.9 (3.5) in the sham group), across three time intervals. The experimental group showed greater improvement in arm motor performance than did the sham group. The results did not confirm that sensory cueing and limb activation treatment is effective when compared with those receiving placebo to reduce unilateral neglect, but it might be useful for promoting hemiplegic arm performance in stroke patients.

Implementation of dual-energy technique for virtual monochromatic and linearly mixed CBCTs

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

Li Hao; Giles, William; Ren Lei

Purpose: To implement dual-energy imaging technique for virtual monochromatic (VM) and linearly mixed (LM) cone beam CTs (CBCTs) and to demonstrate their potential applications in metal artifact reduction and contrast enhancement in image-guided radiation therapy (IGRT). Methods: A bench-top CBCT system was used to acquire 80 kVp and 150 kVp projections, with an additional 0.8 mm tin filtration. To implement the VM technique, these projections were first decomposed into acrylic and aluminum basis material projections to synthesize VM projections, which were then used to reconstruct VM CBCTs. The effect of VM CBCT on the metal artifact reduction was evaluated withmore » an in-house titanium-BB phantom. The optimal VM energy to maximize contrast-to-noise ratio (CNR) for iodine contrast and minimize beam hardening in VM CBCT was determined using a water phantom containing two iodine concentrations. The LM technique was implemented by linearly combining the low-energy (80 kVp) and high-energy (150 kVp) CBCTs. The dose partitioning between low-energy and high-energy CBCTs was varied (20%, 40%, 60%, and 80% for low-energy) while keeping total dose approximately equal to single-energy CBCTs, measured using an ion chamber. Noise levels and CNRs for four tissue types were investigated for dual-energy LM CBCTs in comparison with single-energy CBCTs at 80, 100, 125, and 150 kVp. Results: The VM technique showed substantial reduction of metal artifacts at 100 keV with a 40% reduction in the background standard deviation compared to a 125 kVp single-energy scan of equal dose. The VM energy to maximize CNR for both iodine concentrations and minimize beam hardening in the metal-free object was 50 keV and 60 keV, respectively. The difference of average noise levels measured in the phantom background was 1.2% between dual-energy LM CBCTs and equivalent-dose single-energy CBCTs. CNR values in the LM CBCTs of any dose partitioning are better than those of 150 kVp single-energy CBCTs. The average CNR for four tissue types with 80% dose fraction at low-energy showed 9.0% and 4.1% improvement relative to 100 kVp and 125 kVp single-energy CBCTs, respectively. CNRs for low-contrast objects improved as dose partitioning was more heavily weighted toward low-energy (80 kVp) for LM CBCTs. Conclusions: Dual-energy CBCT imaging techniques were implemented to synthesize VM CBCT and LM CBCTs. VM CBCT was effective at achieving metal artifact reduction. Depending on the dose-partitioning scheme, LM CBCT demonstrated the potential to improve CNR for low contrast objects compared to single-energy CBCT acquired with equivalent dose.« less

SU-F-T-02: Estimation of Radiobiological Doses (BED and EQD2) of Single Fraction Electronic Brachytherapy That Equivalent to I-125 Eye Plaque: By Using Linear-Quadratic and Universal Survival Curve Models

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

Kim, Y; Waldron, T; Pennington, E

Purpose: To test the radiobiological impact of hypofractionated choroidal melanoma brachytherapy, we calculated single fraction equivalent doses (SFED) of the tumor that equivalent to 85 Gy of I125-BT for 20 patients. Corresponding organs-at-risks (OARs) doses were estimated. Methods: Twenty patients treated with I125-BT were retrospectively examined. The tumor SFED values were calculated from tumor BED using a conventional linear-quadratic (L-Q) model and an universal survival curve (USC). The opposite retina (α/β = 2.58), macula (2.58), optic disc (1.75), and lens (1.2) were examined. The % doses of OARs over tumor doses were assumed to be the same as for amore » single fraction delivery. The OAR SFED values were converted into BED and equivalent dose in 2 Gy fraction (EQD2) by using both L-Q and USC models, then compared to I125-BT. Results: The USC-based BED and EQD2 doses of the macula, optic disc, and the lens were on average 118 ± 46% (p < 0.0527), 126 ± 43% (p < 0.0354), and 112 ± 32% (p < 0.0265) higher than those of I125-BT, respectively. The BED and EQD2 doses of the opposite retina were 52 ± 9% lower than I125-BT. The tumor SFED values were 25.2 ± 3.3 Gy and 29.1 ± 2.5 Gy when using USC and LQ models which can be delivered within 1 hour. All BED and EQD2 values using L-Q model were significantly larger when compared to the USC model (p < 0.0274) due to its large single fraction size (> 14 Gy). Conclusion: The estimated single fraction doses were feasible to be delivered within 1 hour using a high dose rate source such as electronic brachytherapy (eBT). However, the estimated OAR doses using eBT were 112 ∼ 118% higher than when using the I125-BT technique. Continued exploration of alternative dose rate or fractionation schedules should be followed.« less

Transcriptomic Dose-Response Analysis for Mode of Action and Risk Assessment

EPA Science Inventory

Microarray and RNA-seq technologies can play an important role in assessing the health risks associated with environmental exposures. The utility of gene expression data to predict hazard has been well documented. Early toxicogenomics studies used relatively high, single doses w...

Inactivated yellow fever 17D vaccine: development and nonclinical safety, immunogenicity and protective activity.

PubMed

Monath, Thomas P; Lee, Cynthia K; Julander, Justin G; Brown, Alicja; Beasley, David W; Watts, Douglas M; Hayman, Edward; Guertin, Patrick; Makowiecki, Joseph; Crowell, Joseph; Levesque, Philip; Bowick, Gavin C; Morin, Merribeth; Fowler, Elizabeth; Trent, Dennis W

2010-05-14

In the last 10 years new concerns have arisen about safety of the live, attenuated yellow fever (YF) 17D vaccine, in particular viscerotropic adverse events, which have a case-fatality rate of 64%. A non-replicating cell culture-based vaccine would not cause these adverse events, and potentially could be used in persons with precautions or contraindications to use of the live vaccine, including age <9 months and >60 years, egg allergy, immune suppression, and pregnancy. We developed a whole virion vaccine from the 17D strain inactivated with beta-propiolactone, and adsorbed to aluminum hydroxide. The inactivated vaccine was highly immunogenic in mice, hamsters, and cynomolgus macaques. After a single dose in hamsters and macaques, neutralizing antibody titers were similar to those elicited by the live 17D vaccine (YF-VAX, Sanofi Pasteur). After two doses of inactivated vaccine, neutralizing antibody titers in hamsters were significantly higher than after a single dose of YF-VAX [geometric mean titer (GMT) 20,480 vs. 1940, respectively (P<0.001, ANOVA)]. Hamsters given a single dose or two doses of inactivated vaccine or a single dose of YF-VAX were fully protected against hepatitis, viremia, weight loss and death after challenge with YF virus (Jimenez strain). A clinical trial of the inactivated vaccine (XRX-001) has been initiated. Copyright 2010 Elsevier Ltd. All rights reserved.

Biomechanical study of four kinds of percutaneous screw fixation in two types of unilateral sacroiliac joint dislocation: a finite element analysis.

PubMed

Zhang, Lihai; Peng, Ye; Du, Chengfei; Tang, Peifu

2014-12-01

To compare the biomechanical stability of four different kinds of percutaneous screw fixation in two types of unilateral sacroiliac joint dislocation. Finite element models of unstable Tile type B and type C pelvic ring injuries were created in this study. Modelling was based on fixation with a single S1 screw (S1-1), single S2 screw (S2-1), two S1 screws (S1-2) and a combination of a single S1 and a single S2 screw (S1–S2). The biomechanical test of two types of pelvic instability (rotational or vertical) with four types of percutaneous fixation were compared. Displacement, flexion and lateral bend (in bilateral stance) were recorded and analyzed. Maximal inferior translation (displacement) was found in the S2-1 group in type B and C dislocations which were 1.58 mm and 1.90 mm, respectively. Maximal flexion was found in the S2-1 group in type B and C dislocations which were 1.55° and 1.95°, respectively. The results show that the flexion from most significant angulation to least is S2-1, S1-1, S1-2, and S1–S2 in type B and C dislocations. All the fixations have minimal lateral bend. Our findings suggest single screw S1 fixation should be adequate fixation for a type B dislocation. For type C dislocations, one might consider a two screw construct (S1–S2) to give added biomechanical stability if clinically indicated.

The Hematopoietic Syndrome of the Acute Radiation Syndrome in Rhesus Macaques: A Systematic Review of the Lethal Dose Response Relationship.

PubMed

MacVittie, Thomas J; Farese, Ann M; Jackson, William

2015-11-01

Well characterized animal models that mimic the human response to potentially lethal doses of radiation are required to assess the efficacy of medical countermeasures under the criteria of the U.S. Food and Drug Administration "animal rule." Development of a model requires the determination of the radiation dose response relationship and time course of mortality and morbidity across the hematopoietic acute radiation syndrome. The nonhuman primate, rhesus macaque, is a relevant animal model that may be used to determine the efficacy of medical countermeasures to mitigate major signs of morbidity and mortality at selected lethal doses of total body irradiation. A systematic review of relevant studies that determined the dose response relationship for the hematopoietic acute radiation syndrome in the rhesus macaque relative to radiation quality, dose rate, and exposure uniformity has never been performed. The selection of data cohorts was made from the following sources: Ovid Medline (1957-present), PubMed (1954-present), AGRICOLA (1976-present), Web of Science (1954-present), and U.S. HHS REPORT (2002 to present). The following terms were used: Rhesus, total body-irradiation, total body x irradiation, TBI, irradiation, gamma radiation, hematopoiesis, LD50/60, Macaca mulatta, whole-body irradiation, nonhuman primate, NHP, monkey, primates, hematopoietic radiation syndrome, mortality, and nuclear radiation. The reference lists of all studies, published and unpublished, were reviewed for additional studies. The total number of hits across all search sites was 3,001. There were a number of referenced, unpublished, non-peer reviewed government reports that were unavailable for review. Fifteen studies, 11 primary (n = 863) and four secondary (n = 153) studies [n = 1,016 total nonhuman primates (NHP), rhesus Macaca mulatta] were evaluated to provide an informative and consistent review. The dose response relationships (DRRs) were determined for uniform or non-uniform total body irradiation (TBI) with 250 kVp or 2 MeV x radiation, Co gamma radiation and reactor- and nuclear weapon-derived mixed gamma: neutron-radiation, delivered at various dose rates from a total body, bilateral, rotational, or unilateral exposure aspect. The DRRs established by a probit analysis vs. linear dose relationship were characterized by two main parameters or dependent variables: a slope and LD50/30. Respective LD50/30 values for studies that used 250 kVp x radiation (five primary studies combined, n = 338), 2 MeV x radiation, Co gamma radiation, and steady-state reactor-derived mixed gamma:neutron radiation for total body uniform exposures were 521 rad [498, 542], 671 rad [632, 715], 644 rad [613, 678], and 385 rad [357, 413]. The respective slopes were steep and ranged from 0.738 to 1.316. The DRR, LD50/30 values and slopes were also determined for total body, non-uniform, unilateral, pulse-rate exposures of mixed gamma:neutron radiation derived at reactor and nuclear weapon detonations. The LD50/30 values were, respectively, 395 rad [337, 432] and 412 rad [359, 460]. Secondary data sets of limited studies that did not describe a DRR were used to support the mid-to-high lethal dose range for the H-ARS and the threshold dose range for the concurrent acute GI ARS. The available evidence provided a reliable and extensive database that characterized the DRR for the H-ARS in young rhesus macaques exposed to 250 kVp uniform total body x radiation without the benefit of medical management. A less substantial but consistent database demonstrated the DRR for total body exposure of differing radiation quality, dose rate and non-uniform exposure. The DRR for the H-ARS is characterized by steep slopes and relative LD50/30 values that reflect the radiation quality, exposure aspect, and dose rate over a range in time from 1954-2012.

Mutagenic effects of a single and an exact number of alpha particles in mammalian cells

NASA Technical Reports Server (NTRS)

Hei, T. K.; Wu, L. J.; Liu, S. X.; Vannais, D.; Waldren, C. A.; Randers-Pehrson, G.

1997-01-01

One of the main uncertainties in risk estimation for environmental radon exposure using lung cancer data from underground miners is the extrapolation from high- to low-dose exposure where multiple traversal is extremely rare. The biological effects of a single alpha particle are currently unknown. Using the recently available microbeam source at the Radiological Research Accelerator Facility at Columbia University, we examined the frequencies and molecular spectrum of S1- mutants induced in human-hamster hybrid (A(L)) cells by either a single or an exact number of alpha particles. Exponentially growing cells were stained briefly with a nontoxic concentration of Hoechst dye for image analysis, and the location of individual cells was computer-monitored. The nucleus of each cell was irradiated with either 1,2,4, or 8 alpha particles at a linear energy transfer of 90 keV/microm consistent with the energy spectrum of domestic radon exposure. Although single-particle traversal was only slightly cytotoxic to A(L) cells (survival fraction approximately 0.82), it was highly mutagenic, and the induced mutant fraction averaged 110 mutants per 10(5) survivors. In addition, both toxicity and mutant induction were dose-dependent. Multiplex PCR analysis of mutant DNA showed that the proportion of mutants with multilocus deletions increased with the number of particle traversals. These data provide direct evidence that a single a particle traversing a nucleus will have a high probability of resulting in a mutation and highlight the need for radiation protection at low doses.

Mutagenic effects of a single and an exact number of alpha particles in mammalian cells.

PubMed

Hei, T K; Wu, L J; Liu, S X; Vannais, D; Waldren, C A; Randers-Pehrson, G

1997-04-15

One of the main uncertainties in risk estimation for environmental radon exposure using lung cancer data from underground miners is the extrapolation from high- to low-dose exposure where multiple traversal is extremely rare. The biological effects of a single alpha particle are currently unknown. Using the recently available microbeam source at the Radiological Research Accelerator Facility at Columbia University, we examined the frequencies and molecular spectrum of S1- mutants induced in human-hamster hybrid (A(L)) cells by either a single or an exact number of alpha particles. Exponentially growing cells were stained briefly with a nontoxic concentration of Hoechst dye for image analysis, and the location of individual cells was computer-monitored. The nucleus of each cell was irradiated with either 1,2,4, or 8 alpha particles at a linear energy transfer of 90 keV/microm consistent with the energy spectrum of domestic radon exposure. Although single-particle traversal was only slightly cytotoxic to A(L) cells (survival fraction approximately 0.82), it was highly mutagenic, and the induced mutant fraction averaged 110 mutants per 10(5) survivors. In addition, both toxicity and mutant induction were dose-dependent. Multiplex PCR analysis of mutant DNA showed that the proportion of mutants with multilocus deletions increased with the number of particle traversals. These data provide direct evidence that a single a particle traversing a nucleus will have a high probability of resulting in a mutation and highlight the need for radiation protection at low doses.

Imaging of VMAT2 binding sites in the brain by (18)F-AV-133: the effect of a pseudo-carrier.

PubMed

Zhu, Lin; Qiao, Hongwen; Lieberman, Brian P; Wu, Jingxiao; Liu, Yajing; Pan, Zhongyun; Ploessl, Karl; Choi, Seok Rye; Chan, Piu; Kung, Hank F

2012-10-01

Recently, 9-[(18)F]fluoropropyl-(+)-dihydrotetrabenazine ((18)F-AV-133) was reported as a new vesicular monoamine transporter (VMAT2) imaging agent for diagnosis of Parkinson's disease (PD). To shorten the preparation of (18)F-AV-133 and to make it more widely available, we evaluated a simple, rapid purification with a solid-phase extraction method (SPE) using an Oasis HLB cartridge instead of high pressure liquid chromatography (HPLC). The SPE method produced doses containing a pseudo-carrier, 9-hydroxypropyl-(+)-dihydrotetrabenazine (AV-149). To test the possible side effects of this pseudo-carrier, comparative dynamic PET scans of the brains of normal monkeys (2 each) and uni-laterally 6-OH-dopamine-lesioned PD monkeys (2 each) were performed using (18)F-AV-133 doses prepared by either SPE (containing pseudo-carrier) or HPLC (containing no pseudo-carrier). Autoradiographs of post mortem monkey brain sections were evaluated to confirm the relative (18)F-AV-133 uptake in the PD monkey brains and the effects of the pseudo-carrier on VMAT2 binding. The radiochemical purity of the (18)F-AV-133, whether prepared by SPE or by HPLC, was excellent (>99%). PET scans of normal and PD monkey brains showed an expected reduction of VMAT2 in the lesioned areas of the striatum. It was not affected by the presence of the pseudo-carrier, AV-149 (maximally 250 μg/dose). The reduced uptake in the striatum of the lesioned monkey brains was confirmed by autoradiography. Ex vivo inhibition studies of (18)F-AV-133 binding in rat brains, conducted with increasing amounts of AV-149, suggested that at the highest concentration (3.5mg/kg) the VMAT2 binding in the striatum was only moderately blocked (20% reduction). The pseudo-carrier, AV-149, did not affect the (18)F-AV-133/PET imaging of VMAT2 binding sites in normal or uni-laterally lesioned monkey brains. The new streamlined SPE purification method will enable (18)F-AV-133 to be widely available for routine clinical application in determining changes in monoamine neurons for patient with movement disorders or other psychiatric illnesses. Copyright © 2012 Elsevier Inc. All rights reserved.

Regenerate Healing Outcomes in Unilateral Mandibular Distraction Osteogenesis Using Quantitative Histomorphometry

PubMed Central

Schwarz, Daniel A.; Arman, Krikor G.; Kakwan, Mehreen S.; Jamali, Ameen M.; Elmeligy, Ayman A.; Buchman, Steven R.

2015-01-01

Background The authors’ goal was to ascertain regenerate bone-healing metrics using quantitative histomorphometry at a single consolidation period. Methods Rats underwent either mandibular distraction osteogenesis (n=7) or partially reduced fractures (n=7); their contralateral mandibles were used as controls (n=11). External fixators were secured and unilateral osteotomies performed, followed by either mandibular distraction osteogenesis (4 days’ latency, then 0.3 mm every 12 hours for 8 days; 5.1 mm) or partially reduced fractures (fixed immediately postoperatively; 2.1 mm); both groups underwent 4 weeks of consolidation. After tissue processing, bone volume/tissue volume ratio, osteoid volume/tissue volume ratio, and osteocyte count per high-power field were analyzed by means of quantitative histomorphometry. Results Contralateral mandibles had statistically greater bone volume/tissue volume ratio and osteocyte count per high-power field compared with both mandibular distraction osteogenesis and partially reduced fractures by almost 50 percent, whereas osteoid volume/tissue volume ratio was statistically greater in both mandibular distraction osteogenesis specimens and partially reduced fractures compared with contralateral mandibles. No statistical difference in bone volume/tissue volume ratio, osteoid volume/tissue volume ratio, or osteocyte count per high-power field was found between mandibular distraction osteogenesis specimens and partially reduced fractures. Conclusions The authors’ findings demonstrate significantly decreased bone quantity and maturity in mandibular distraction osteogenesis specimens and partially reduced fractures compared with contralateral mandibles using the clinically analogous protocols. If these results are extrapolated clinically, treatment strategies may require modification to ensure reliable, predictable, and improved outcomes. PMID:20463629

Microdose Induced Drain Leakage Effects in Power Trench MOSFETs: Experiment and Modeling

NASA Astrophysics Data System (ADS)

Zebrev, Gennady I.; Vatuev, Alexander S.; Useinov, Rustem G.; Emeliyanov, Vladimir V.; Anashin, Vasily S.; Gorbunov, Maxim S.; Turin, Valentin O.; Yesenkov, Kirill A.

2014-08-01

We study experimentally and theoretically the micro-dose induced drain-source leakage current in the trench power MOSFETs under irradiation with high-LET heavy ions. We found experimentally that cumulative increase of leakage current occurs by means of stochastic spikes corresponding to a strike of single heavy ion into the MOSFET gate oxide. We simulate this effect with the proposed analytic model allowing to describe (including Monte Carlo methods) both the deterministic (cumulative dose) and stochastic (single event) aspects of the problem. Based on this model the survival probability assessment in space heavy ion environment with high LETs was proposed.

Risk factors for amblyopia in the vision in preschoolers study.

PubMed

Pascual, Maisie; Huang, Jiayan; Maguire, Maureen G; Kulp, Marjean Taylor; Quinn, Graham E; Ciner, Elise; Cyert, Lynn A; Orel-Bixler, Deborah; Moore, Bruce; Ying, Gui-Shuang

2014-03-01

To evaluate risk factors for unilateral amblyopia and for bilateral amblyopia in the Vision in Preschoolers (VIP) study. Multicenter, cross-sectional study. Three- to 5-year-old Head Start preschoolers from 5 clinical centers, overrepresenting children with vision disorders. All children underwent comprehensive eye examinations, including threshold visual acuity (VA), cover testing, and cycloplegic retinoscopy, performed by VIP-certified optometrists and ophthalmologists who were experienced in providing care to children. Monocular threshold VA was tested using a single-surround HOTV letter protocol without correction, and retested with full cycloplegic correction when retest criteria were met. Unilateral amblyopia was defined as an interocular difference in best-corrected VA of 2 lines or more. Bilateral amblyopia was defined as best-corrected VA in each eye worse than 20/50 for 3-year-olds and worse than 20/40 for 4- to 5-year-olds. Risk of amblyopia was summarized by the odds ratios and their 95% confidence intervals estimated from logistic regression models. In this enriched sample of Head Start children (n = 3869), 296 children (7.7%) had unilateral amblyopia, and 144 children (3.7%) had bilateral amblyopia. Presence of strabismus (P<0.0001) and greater magnitude of significant refractive errors (myopia, hyperopia, astigmatism, and anisometropia; P<0.00001 for each) were associated independently with an increased risk of unilateral amblyopia. Presence of strabismus, hyperopia of 2.0 diopters (D) or more, astigmatism of 1.0 D or more, or anisometropia of 0.5 D or more were present in 91% of children with unilateral amblyopia. Greater magnitude of astigmatism (P<0.0001) and bilateral hyperopia (P<0.0001) were associated independently with increased risk of bilateral amblyopia. Bilateral hyperopia of 3.0 D or more or astigmatism of 1.0 D or more were present in 76% of children with bilateral amblyopia. Strabismus and significant refractive errors were risk factors for unilateral amblyopia. Bilateral astigmatism and bilateral hyperopia were risk factors for bilateral amblyopia. Despite differences in selection of the study population, these results validated the findings from the Multi-Ethnic Pediatric Eye Disease Study and Baltimore Pediatric Eye Disease Study. Copyright © 2014 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Risk Factors for Amblyopia in the Vision In Preschoolers Study

PubMed Central

Pascual, Maisie; Huang, Jiayan; Maguire, Maureen G; Kulp, Marjean Taylor; Quinn, Graham E; Ciner, Elise; Cyert, Lynn A; Orel-Bixler, Deborah; Moore, Bruce; Ying, Gui-shuang

2013-01-01

Objective To evaluate risk factors for unilateral amblyopia and for bilateral amblyopia in the Vision In Preschoolers (VIP) Study. Design Multicenter, cross-sectional Study. Participants Three- to 5-year old Head Start preschoolers from 5 clinical centers, over-representing children with vision disorders. Methods All children underwent comprehensive eye exams including threshold visual acuity (VA), cover testing, and cycloplegic retinoscopy, performed by VIP-certified optometrists and ophthalmologists who were experienced in providing care to children. Monocular threshold VA was tested using single-surround HOTV letter protocol without correction, and retested with full cycloplegic correction when retest criteria were met. Unilateral amblyopia was defined as an inter-ocular difference in best-corrected VA ≥2 lines. Bilateral amblyopia was defined as best-corrected VA in each eye worse than 20/50 for 3-year-olds and worse than 20/40 for 4- to 5-year-olds. Main Outcome Measures Risk of amblyopia was summarized by The odds ratios (ORs) and their 95% confidence intervals (95% CIs) estimated from logistic regression models. Results In this enriched sample of Head Start children (N=3869), 296 (7.7%) children had unilateral amblyopia, and 144 (3.7%) children had bilateral amblyopia. Presence of strabismus (p<0.0001), greater magnitude of significant refractive errors (myopia, hyperopia, astigmatism, and anisometropia, each p<0.00001) were independently associated with increased risk of unilateral amblyopia. Presence of strabismus, hyperopia ≥2.0 D, astigmatism ≥1.0 D, or anisometropia ≥0.5 D were present in 91% of children with unilateral amblyopia. Greater magnitude of astigmatism (p<0.0001) and of bilateral hyperopia (p<0.0001) were independently associated with increased risk of bilateral amblyopia. Bilateral hyperopia ≥3.0 diopters (D) or astigmatism ≥1.0 D were present in 76% of children with bilateral amblyopia. Conclusion Strabismus and significant refractive errors were risk factors for unilateral amblyopia. Bilateral astigmatism and bilateral hyperopia were risk factors for bilateral amblyopia. Despite differences in selection of study population, these results validated the findings from the Multi-ethnic Pediatric Eye Disease Study and Baltimore Pediatric Eye Disease Study. PMID:24140117

Changes in Morphological and Elastic Properties of Patellar Tendon in Athletes with Unilateral Patellar Tendinopathy and Their Relationships with Pain and Functional Disability

PubMed Central

Zhang, Zhi Jie; Ng, Gabriel Yin-fat; Lee, Wai Chun; Fu, Siu Ngor

2014-01-01

Background Patellar tendinopathy (PT) is one of the most common knee disorders among athletes. Changes in morphology and elasticity of the painful tendon and how these relate to the self-perceived pain and dysfunction remain unclear. Objectives To compare the morphology and elastic properties of patellar tendons between athlete with and without unilateral PT and to examine its association with self-perceived pain and dysfunction. Methods In this cross-sectional study, 33 male athletes (20 healthy and 13 with unilateral PT) were enrolled. The morphology and elastic properties of the patellar tendon were assessed by the grey and elastography mode of supersonic shear imaging (SSI) technique while the intensity of pressure pain, self-perceived pain and dysfunction were quantified with a 10-lb force to the most painful site and the Victorian Institute of Sport Assessment-patella (VISA-P) questionnaire, respectively. Results In athletes with unilateral PT, the painful tendons had higher shear elastic modulus (SEM) and larger tendon than the non-painful side (p<0.05) or the dominant side of the healthy athletes (p<0.05). Significant correlations were found between tendon SEM ratio (SEM of painful over non-painful tendon) and the intensity of pressure pain (rho  = 0.62; p = 0.024), VISA-P scores (rho  = −0.61; p = 0.026), and the sub-scores of the VISA-P scores on going down stairs, lunge, single leg hopping and squatting (rho ranged from −0.63 to −0.67; p<0.05). Conclusions Athletes with unilateral PT had stiffer and larger tendon on the painful side than the non-painful side and the dominant side of healthy athletes. No significant differences on the patellar tendon morphology and elastic properties were detected between the dominant and non-dominant knees of the healthy control. The ratio of the SEM of painful to non-painful sides was associated with pain and dysfunction among athletes with unilateral PT. PMID:25303466

Identifying risk factors for L'Hermitte's sign after IMRT for head and neck cancer.

PubMed

Laidley, Hannah M; Noble, David J; Barnett, Gill C; Forman, Julia R; Bates, Amy M; Benson, Richard J; Jefferies, Sarah J; Jena, Rajesh; Burnet, Neil G

2018-05-04

L'Hermitte's sign (LS) after chemoradiotherapy for head and neck cancer appears related to higher spinal cord doses. IMRT plans limit spinal cord dose, but the incidence of LS remains high. One hundred seventeen patients treated with TomoTherapy™ between 2008 and 2015 prospectively completed a side-effect questionnaire (VoxTox Trial Registration: UK CRN ID 13716). Baseline patient and treatment data were collected. Radiotherapy plans were analysed; mean and maximum spinal cord dose and volumes receiving 10, 20, 30 and 40 Gy were recorded. Dose variation across the cord was examined. These data were included in a logistic regression model. Forty two patients (35.9%) reported LS symptoms. Concurrent weekly cisplatin did not increase LS risk (p = 0.70, OR = 1.23 {95% CI 0.51-2.34}). Of 13 diabetic participants (9 taking metformin), only 1 developed LS (p = 0.025, OR = 0.13 {95% CI 0.051-3.27}). A refined binary logistic regression model showed that patients receiving unilateral radiation (p = 0.019, OR = 2.06 {95% CI 0.15-0.84}) were more likely to develop LS. Higher V 40Gy (p = 0.047, OR = 1.06 {95% CI 1.00-1.12}), and younger age (mean age 56.6 vs 59.7, p = 0.060, OR = 0.96 {95% CI 0.92-1.00}) were associated with elevated risk of LS, with borderline significance. In this cohort, concomitant cisplatin did not increase risk, and LS incidence was lower in diabetic patients. Patient age and dose gradients across the spinal cord may be important factors.

Micronucleus induction in Vicia faba roots. Part 1. Absence of dose-rate, fractionation, and oxygen effect at low doses of low LET radiations.

PubMed

Marshall, I; Bianchi, M

1983-08-01

Micronucleus indication in Vicia faba roots has been evaluated after irradiation with 60Co gamma-rays. The dependence of the damage on dose, dose rate, fractionation, and oxygen has been studied. The best fit to the experimental data in the dose region between 7 and 190 cGy is represented, for single-dose exposures, by a linear + quadratic relationship. In the low-dose region, between 7 and 20 cGy, where the linear dose dependence is dominant, no dose-rate, fractionation, or oxygen effect could be observed. These effects were, however, present in the high-dose region, where the quadratic dependence is dominant.

Clinical trial: single- and multiple-dose pharmacokinetics of polyethylene glycol (PEG-3350) in healthy young and elderly subjects.

PubMed

Pelham, R W; Nix, L C; Chavira, R E; Cleveland, M Vb; Stetson, P

2008-07-01

The pharmacokinetics of polyethylene glycol 3350 (PEG-3350) have not been fully described because of lack of a sufficiently sensitive analytical method. To describe the pharmacokinetics of PEG-3350 in humans. A highly sensitive, high performance liquid chromatography with mass spectrometry (HPLC/MS/MS) method was developed for PEG-3350 in urine, plasma and faeces with quantification limits of 30 ng/mL, 100 ng/mL and 500 microg/g respectively. Noncompartmental pharmacokinetics methods were used and the effects of gender, age, renal status and dosing frequency were examined after the oral administration of 17 g to healthy volunteers. Peak PEG-3350 plasma concentrations occurred at 2-4 h and declined to nonquantifiable levels usually within 18 h after single and multiple doses, with a half-life of about 4-6 h. Steady state was reached within 5 days of dosing. Mean urinary excretion of the administered dose ranged from 0.19% to 0.25%. Age, gender or mild kidney impairment did not alter the pharmacokinetics of PEG-3350. Mean faecal excretion of the administered dose was 93% in young subjects. For the first time, a highly sensitive assay allowed comprehensive pharmacokinetics studies of PEG-3350 in humans. These studies confirmed that orally administered PEG-3350 is minimally absorbed, rapidly excreted and primarily eliminated via faeces.

Serum tocopherol levels in very preterm infants after a single dose of vitamin E at birth.

PubMed

Bell, Edward F; Hansen, Nellie I; Brion, Luc P; Ehrenkranz, Richard A; Kennedy, Kathleen A; Walsh, Michele C; Shankaran, Seetha; Acarregui, Michael J; Johnson, Karen J; Hale, Ellen C; Messina, Lynn A; Crawford, Margaret M; Laptook, Abbot R; Goldberg, Ronald N; Van Meurs, Krisa P; Carlo, Waldemar A; Poindexter, Brenda B; Faix, Roger G; Carlton, David P; Watterberg, Kristi L; Ellsbury, Dan L; Das, Abhik; Higgins, Rosemary D

2013-12-01

Our aim was to examine the impact of a single enteral dose of vitamin E on serum tocopherol levels. The study was undertaken to see whether a single dose of vitamin E soon after birth can rapidly increase the low α-tocopherol levels seen in very preterm infants. If so, this intervention could be tested as a means of reducing the risk of intracranial hemorrhage. Ninety-three infants <27 weeks' gestation and <1000 g were randomly assigned to receive a single dose of vitamin E or placebo by gastric tube within 4 hours of birth. The vitamin E group received 50 IU/kg of vitamin E as dl-α-tocopheryl acetate (Aquasol E). The placebo group received sterile water. Blood samples were taken for measurement of serum tocopherol levels by high-performance liquid chromatography before dosing and 24 hours and 7 days after dosing. Eighty-eight infants received the study drug and were included in the analyses. The α-tocopherol levels were similar between the groups at baseline but higher in the vitamin E group at 24 hours (median 0.63 mg/dL vs. 0.42 mg/dL, P = .003) and 7 days (2.21 mg/dL vs 1.86 mg/dL, P = .04). There were no differences between groups in γ-tocopherol levels. At 24 hours, 30% of vitamin E infants and 62% of placebo infants had α-tocopherol levels <0.5 mg/dL. A 50-IU/kg dose of vitamin E raised serum α-tocopherol levels, but to consistently achieve α-tocopherol levels >0.5 mg/dL, a higher dose or several doses of vitamin E may be needed.

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.

Cysteine proteinases from papaya (Carica papaya) in the treatment of experimental Trichuris suis infection in pigs: two randomized controlled trials.

PubMed

Levecke, Bruno; Buttle, David J; Behnke, Jerzy M; Duce, Ian R; Vercruysse, Jozef

2014-05-30

Cysteine proteinases (CPs) from papaya (Carica papaya) possess anthelmintic properties against human soil-transmitted helminths (STH, Ascaris lumbricoides, Trichuris trichiura and hookworm), but there is a lack of supportive and up-to-date efficacy data. We therefore conducted two randomized controlled trials in pigs to assess the efficacy of papaya CPs against experimental infections with T. suis. First, we assessed efficacy by means of egg (ERR) and adult worm reduction rate (WRR) of a single-oral dose of 450 μmol active CPs (CP450) against low (inoculum of 300 eggs) and high (inoculum of 3,000 eggs) intensity T. suis infections and compared the efficacy with those obtained after a single-oral dose of 400 mg albendazole (ALB). In the second trial, we determined and compared the efficacy of a series of CP doses (45 [CP45], 115 [CP115], 225 [CP225], and 450 [CP450] μmol) against high intensity infections. CP450 was highly efficacious against both levels of infection intensity, resulting in ERR and WRR of more than 97%. For both levels of infection intensity, CP450 was significantly more efficacious compared to ALB by means of WRR (low infection intensity: 99.0% vs. 39.0%; high infection intensity; 97.4% vs. 23.2%). When the efficacy was assessed by ERR, a significant difference was only observed for high intensity infections, CP450 being more efficacious than ALB (98.9% vs. 59.0%). For low infection intensities, there was no significant difference in ERR between CP450 (98.3%) and ALB (64.4%). The efficacy of CPs increased as a function of increasing dose. When determined by ERR, the efficacy ranged from 2.1% for CP45 to 99.2% for CP450. For WRR the results varied from -14.0% to 99.0%, respectively. Pairwise comparison revealed a significant difference in ERR and WRR only between CP45 and CP450, the latter being more efficacious. A single dose of 450 μmol CPs provided greater efficacy against T. suis infections in pigs than a single-oral dose of 400 mg ALB. Although these results highlight the possibility of papaya CPs for controlling human STH, further development is needed in order to obtain and validate an oral formulation for human application.

Pharmacokinetics and safety of the selective progesterone receptor modulator vilaprisan in healthy postmenopausal women
.

PubMed

Schultze-Mosgau, Marcus-Hillert; Schuett, Barbara; Hafner, Frank-Thorsten; Zollmann, Frank; Kaiser, Andreas; Hoechel, Joachim; Rohde, Beate

2017-01-01

Vilaprisan is a novel, potent, and highly selective progesterone receptor modulator, which might offer a promising option for the treatment of uterine fibroids. In this randomized, placebo-controlled, parallel-group phase 1 study, the pharmacokinetics and safety of vilaprisan were investigated in healthy postmenopausal women. Subjects received a single oral dose of vilaprisan (1, 5, 15, or 30 mg) or placebo and - after a wash-out period - daily doses of the same strength over 28 days. Safety assessments included vital signs, ECGs, clinical laboratory tests, and adverse events. Blood samples for pharmacokinetic (PK) profiles were collected over 14 days after single dose (sd) and multiple dose (md; day 28). Vilaprisan was well tolerated. Mild to moderate adverse events occurred with similar frequency at all dose levels. Following single dose, maximum vilaprisan concentrations were observed 1 - 2 hours post-dose. Terminal half-lives ranged from 31 to 38 hours. Maximum concentrations of vilaprisan (Cmax) and exposure to vilaprisan (AUC) increased roughly dose-proportionally from 3.74 µg/L (1 mg) to 68.6 µg/L (30 mg) and 58.5 µg×h/L to 1,590 µg×h/L, respectively. With daily dosing, accumulation consistent with the long terminal half-life was observed (AUC(0-24)md/AUC(0-24)sd ratios: 1.9 to 3.2). The ratio AUC(0-24)md/AUCsd increased with dose from ~ 1 (1 mg) to 1.5 (30 mg). Exposure to vilaprisan increased roughly dose-proportionally in the dose range studied and accumulated after multiple dosing as expected based on t1/2, indicating linear pharmacokinetics of vilaprisan in the expected therapeutic dose range.
.

Framework Surgery for Treatment of Unilateral Vocal Fold Paralysis

PubMed Central

Daniero, James J.; Garrett, C. Gaelyn; Francis, David O.

2014-01-01

Laryngeal framework surgery is the current gold standard treatment for unilateral vocal fold paralysis. It provides a permanent solution to glottic insufficiency caused by injury to the recurrent laryngeal nerve. Various modifications to the original Isshiki type I laryngoplasty procedure have been described to improve voice and swallowing outcomes. The success of this procedure is highly dependent on the experience of the surgeon as it epitomizes the intersection of art and science in the field. The following article reviews the evidence, controversies, and complications related to laryngoplasty for unilateral vocal fold paralysis. It also provides a detailed analysis of how and when arytenoid-positioning procedures should be considered, and summarizes the literature on postoperative outcomes. PMID:24883239

Structural-metabolic organization of field 4 of the cat brain in normal conditions and after unilateral enucleation of the eye.

PubMed

Zykin, P A

2005-01-01

Comparative data on the structural-metabolic organization of field 4 of the cat brain in normal conditions and after unilateral enucleation of the eye are presented. Cytochrome oxidase was detected histochemically. Data were processed by a computerized method using an original video capture system. Data were obtained demonstrating the uneven distribution of enzyme along sublayer IlIb of field 4 in animals with unilateral enucleation. A hypothesis based on published data is suggested whereby the alternation of high- and low-reactive areas is evidence for the ordering of the retinal representations of the right and left eyes in the sensorimotor cortex.

Dose fractionation theorem in 3-D reconstruction (tomography)

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

Glaeser, R.M.

It is commonly assumed that the large number of projections for single-axis tomography precludes its application to most beam-labile specimens. However, Hegerl and Hoppe have pointed out that the total dose required to achieve statistical significance for each voxel of a computed 3-D reconstruction is the same as that required to obtain a single 2-D image of that isolated voxel, at the same level of statistical significance. Thus a statistically significant 3-D image can be computed from statistically insignificant projections, as along as the total dosage that is distributed among these projections is high enough that it would have resultedmore » in a statistically significant projection, if applied to only one image. We have tested this critical theorem by simulating the tomographic reconstruction of a realistic 3-D model created from an electron micrograph. The simulations verify the basic conclusions of high absorption, signal-dependent noise, varying specimen contrast and missing angular range. Furthermore, the simulations demonstrate that individual projections in the series of fractionated-dose images can be aligned by cross-correlation because they contain significant information derived from the summation of features from different depths in the structure. This latter information is generally not useful for structural interpretation prior to 3-D reconstruction, owing to the complexity of most specimens investigated by single-axis tomography. These results, in combination with dose estimates for imaging single voxels and measurements of radiation damage in the electron microscope, demonstrate that it is feasible to use single-axis tomography with soft X-ray microscopy of frozen-hydrated specimens.« less

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

PubMed Central

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

2011-01-01

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

Experience of micromultileaf collimator linear accelerator based single fraction stereotactic radiosurgery: Tumor dose inhomogeneity, conformity, and dose fall off

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

Hong, Linda X.; Garg, Madhur; Lasala, Patrick

2011-03-15

Purpose: Sharp dose fall off outside a tumor is essential for high dose single fraction stereotactic radiosurgery (SRS) plans. This study explores the relationship among tumor dose inhomogeneity, conformity, and dose fall off in normal tissues for micromultileaf collimator (mMLC) linear accelerator (LINAC) based cranial SRS plans. Methods: Between January 2007 and July 2009, 65 patients with single cranial lesions were treated with LINAC-based SRS. Among them, tumors had maximum diameters {<=}20 mm: 31; between 20 and 30 mm: 21; and >30 mm: 13. All patients were treated with 6 MV photons on a Trilogy linear accelerator (Varian Medical Systems,more » Palo Alto, CA) with a tertiary m3 high-resolution mMLC (Brainlab, Feldkirchen, Germany), using either noncoplanar conformal fixed fields or dynamic conformal arcs. The authors also created retrospective study plans with identical beam arrangement as the treated plan but with different tumor dose inhomogeneity by varying the beam margins around the planning target volume (PTV). All retrospective study plans were normalized so that the minimum PTV dose was the prescription dose (PD). Isocenter dose, mean PTV dose, RTOG conformity index (CI), RTOG homogeneity index (HI), dose gradient index R{sub 50}-R{sub 100} (defined as the difference between equivalent sphere radius of 50% isodose volume and prescription isodose volume), and normal tissue volume (as a ratio to PTV volume) receiving 50% prescription dose (NTV{sub 50}) were calculated. Results: HI was inversely related to the beam margins around the PTV. CI had a ''V'' shaped relationship with HI, reaching a minimum when HI was approximately 1.3. Isocenter dose and mean PTV dose (as percentage of PD) increased linearly with HI. R{sub 50}-R{sub 100} and NTV{sub 50} initially declined with HI and then reached a plateau when HI was approximately 1.3. These trends also held when tumors were grouped according to their maximum diameters. The smallest tumor group (maximum diameters {<=}20 mm) had the most HI dependence for dose fall off. For treated plans, CI averaged 2.55{+-}0.79 with HI 1.23{+-}0.06; the average R{sub 50}-R{sub 100} was 0.41{+-}0.08, 0.55{+-}0.10, and 0.65{+-}0.09 cm, respectively, for tumors {<=}20 mm, between 20 and 30 mm, and >30 mm. Conclusions: Tumor dose inhomogeneity can be used as an important and convenient parameter to evaluate mMLC LINAC-based SRS plans. Sharp dose fall off in the normal tissue is achieved with sufficiently high tumor dose inhomogeneity. By adjusting beam margins, a homogeneity index of approximately 1.3 would provide best conformity for the authors' SRS system.« less

EEG-fMRI evaluation of patients with mesial temporal lobe sclerosis.

PubMed

Avesani, Mirko; Giacopuzzi, Silvia; Bongiovanni, Luigi Giuseppe; Borelli, Paolo; Cerini, Roberto; Pozzi Mucelli, Roberto; Fiaschi, Antonio

2014-02-01

This preliminary study sought more information on blood oxygen level dependent (BOLD) activation, especially contralateral temporal/extratemporal spread, during continuous EEG-fMRI recordings in four patients with mesial temporal sclerosis (MTS). In two patients, EEG showed unilateral focal activity during the EEG-fMRI session concordant with the interictal focus previously identified with standard and video-poly EEG. In the other two patients EEG demonstrated a contralateral diffusion of the irritative focus. In the third patient (with the most drug-resistant form and also extratemporal clinical signs), there was an extratemporal diffusion over frontal regions, ipsilateral to the irritative focus. fMRI analysis confirmed a single activation in the mesial temporal region in two patients whose EEG showed unilateral focal activity, while it demonstrated a bilateral activation in the mesial temporal regions in the other two patients. In the third patient, fMRI demonstrated an activation in the supplementary motxor area. This study confirms the most significant activation with a high firing rate of the irritative focus, but also suggests the importance of using new techniques (such as EEG-fMRI to examine cerebral blood flow) to identify the controlateral limbic activation, and any other extratemporal activations, possible causes of drug resistance in MTS that may require a more precise pre-surgical evaluation with invasive techniques.

EEG-fMRI Evaluation of Patients with Mesial Temporal Lobe Sclerosis

PubMed Central

Avesani, Mirko; Giacopuzzi, Silvia; Bongiovanni, Luigi Giuseppe; Borelli, Paolo; Cerini, Roberto; Pozzi Mucelli, Roberto; Fiaschi, Antonio

2014-01-01

Summary This preliminary study sought more information on blood oxygen level dependent (BOLD) activation, especially contralateral temporal/extratemporal spread, during continuous EEG-fMRI recordings in four patients with mesial temporal sclerosis (MTS). In two patients, EEG showed unilateral focal activity during the EEG-fMRI session concordant with the interictal focus previously identified with standard and video-poly EEG. In the other two patients EEG demonstrated a contralateral diffusion of the irritative focus. In the third patient (with the most drug-resistant form and also extratemporal clinical signs), there was an extratemporal diffusion over frontal regions, ipsilateral to the irritative focus. fMRI analysis confirmed a single activation in the mesial temporal region in two patients whose EEG showed unilateral focal activity, while it demonstrated a bilateral activation in the mesial temporal regions in the other two patients. In the third patient, fMRI demonstrated an activation in the supplementary motxor area. This study confirms the most significant activation with a high firing rate of the irritative focus, but also suggests the importance of using new techniques (such as EEG-fMRI to examine cerebral blood flow) to identify the controlateral limbic activation, and any other extratemporal activations, possible causes of drug resistance in MTS that may require a more precise pre-surgical evaluation with invasive techniques. PMID:24571833

Dedicated Linac for Radioneurosurgery at the National Institute of Neurology and Neurosurgery of Mexico

NASA Astrophysics Data System (ADS)

Celis-López, Miguel A.; Lárraga-Gutiérrez, José M.

2003-09-01

The objective is to present a description and the main clinical applications of this dedicated Linac for benign and malignant tumors in the central nervous system. The Novalis (BrainLab, Germany) is a 6 MV dedicated linac for a single high dose Radiosurgery (RS) and for fractionated doses in Stereotactic Radiotherapy with a high level of precision at the isocenter.

Single Low Dose Primaquine (0.25 mg/kg) Does Not Cause Clinically Significant Haemolysis in G6PD Deficient Subjects.

PubMed

Bancone, Germana; Chowwiwat, Nongnud; Somsakchaicharoen, Raweewan; Poodpanya, Lalita; Moo, Paw Khu; Gornsawun, Gornpan; Kajeechiwa, Ladda; Thwin, May Myo; Rakthinthong, Santisuk; Nosten, Suphak; Thinraow, Suradet; Nyo, Slight Naw; Ling, Clare L; Wiladphaingern, Jacher; Kiricharoen, Naw Lily; Moore, Kerryn A; White, Nicholas J; Nosten, Francois

2016-01-01

Primaquine is the only drug consistently effective against mature gametocytes of Plasmodium falciparum. The transmission blocking dose of primaquine previously recommended was 0.75 mg/kg (adult dose 45 mg) but its deployment was limited because of concerns over haemolytic effects in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency. G6PD deficiency is an inherited X-linked enzymatic defect that affects an estimated 400 million people around the world with high frequencies (15-20%) in populations living in malarious areas. To reduce transmission in low transmission settings and facilitate elimination of P. falciparum, the World Health Organization now recommends adding a single dose of 0.25 mg/kg (adult dose 15 mg) to Artemisinin-based Combination Therapies (ACTs) without G6PD testing. Direct evidence of the safety of this low dose is lacking. Adverse events and haemoglobin variations after this treatment were assessed in both G6PD normal and deficient subjects in the context of targeted malaria elimination in a malaria endemic area on the North-Western Myanmar-Thailand border where prevalence of G6PD deficiency (Mahidol variant) approximates 15%. The tolerability and safety of primaquine (single dose 0.25 mg base/kg) combined with dihydroartemisinin-piperaquine (DHA-PPQ) given three times at monthly intervals was assessed in 819 subjects. Haemoglobin concentrations were estimated over the six months preceding the ACT + primaquine rounds of mass drug administration. G6PD deficiency was assessed with a phenotypic test and genotyping was performed in male subjects with deficient phenotypes and in all females. Fractional haemoglobin changes in relation to G6PD phenotype and genotype and primaquine round were assessed using linear mixed-effects models. No adverse events related to primaquine were reported during the trial. Mean fractional haemoglobin changes after each primaquine treatment in G6PD deficient subjects (-5.0%, -4.2% and -4.7%) were greater than in G6PD normal subjects (0.3%, -0.8 and -1.7%) but were clinically insignificant. Fractional drops in haemoglobin concentration larger than 25% following single dose primaquine were observed in 1.8% of the population but were asymptomatic. The single low dose (0.25mg/kg) of primaquine is clinically well tolerated and can be used safely without prior G6PD testing in populations with high prevalence of G6PD deficiency. The present evidence supports a broader use of low dose primaquine without G6PD testing for the treatment and elimination of falciparum malaria. ClinicalTrials.gov NCT01872702.

76 FR 57089 - Self-Regulatory Organizations; Chicago Stock Exchange, Incorporated; Order Approving a Proposed...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-15

... execution of the stock leg of a stock-option order could be cancelled only if market conditions in the... Consolidated Tape in order that the parties and other market participants are aware that the transaction may be... cancellation will help prevent the possible abuse by a single party acting unilaterally. The Exchange...

Feasibility of a Single Contrast Bolus High-Pitch Pulmonary CT Angiography Protocol Followed by Low-Dose Retrospectively ECG-Gated Cardiac CT in Patients with Suspected Pulmonary Embolism.

PubMed

Schäfer, Julia Carmen; Haubenreisser, Holger; Meyer, Mathias; Grüttner, Joachim; Walter, Thomas; Borggrefe, Martin; Schoepf, Joseph U; Nance, John W; Schönberg, Stefan O; Henzler, Thomas

2018-06-01

 To prospectively evaluate the feasibility of single contrast bolus high-pitch CT pulmonary angiography (CTPA) subsequently followed by low-dose retrospectively ECG-gated cardiac CT (4D-cCT) in patients with suspected pulmonary embolism (PE) to accurately evaluate right ventricular (RV) function.  62 patients (33 female, age 65.1 ± 17.5 years) underwent high-pitch CTPA examination with 80cc of iodinated contrast material. 5 s after the end of the high-pitch CTPA study, a low-dose retrospectively ECG-gated cardiac CT examination was automatically started. The volume CT dose index (CTDI vol) and dose length product (DLP) were recorded in all patients and the effective dose was calculated. For the assessment of image quality, attenuation was measured as Hounsfield units (HUs) within various regions of interest (ROIs). These ROIs were used to calculate the signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR). Subjective image quality was assessed using a five-point Likert scale. On 4D-cCT, the ejection fraction of both ventricles (RVEF, LVEF) as well as the ratio of RVEF and LVEF (RVEF/LVEF) was assessed. The statistical difference of all parameters between the PE and non-PE group was calculated.  The mean effective radiation dose was 4.22 ± 2.05 mSv. Attenuation measurements on CTPA showed the highest attenuation values in the main pulmonary artery (442.01 ± 187.64). On 4D-cCT attenuation values were highest in the descending aorta (560.59 ± 208.81). The CNR and SNR values on CTPA were highest within the main pulmonary artery (CNR = 12.43 ± 4.57; SNR = 15.14 ± 4.90). On 4D-cCT images, the highest SNR and CNR could be measured in the descending aorta (CNR = 10.26 ± 5.57; SNR = 10.86 ± 5.17). The mean LVEF was 60.73 %± 14.65 %, and the mean RVEF was 44.90 %± 9.54 %. The mean RVEF/LVEF was 0.79 ± 0.29. There was no significant difference between the PE and non-PE group for either of the parameters.  The investigated combined CTPA and 4D-cCT protocol is feasible using a single contrast bolus and allows the evaluation of RV function in patients with suspected PE. Further studies have to evaluate the additional value of this protocol regarding risk stratification in patients with PE.   · High-pitch CTPA is fast enough to leave sufficient contrast material within the heart that can be used for an additional low-dose functional cardiac CT examination.. · The tube current of the evaluated 4D-cCT is reduced over the entire cardiac cycle without any full dose peak.. · Low-dose cardiac CT subsequently performed after high-pitch CTPA allows for detailed analysis of RV function.. · Schäfer JC, Haubenreisser H, Meyer M et al. Feasibility of a Single Contrast Bolus High-Pitch Pulmonary CT Angiography Protocol Followed by Low-Dose Retrospectively ECG-Gated Cardiac CT in Patients with Suspected Pulmonary Embolism. Fortschr Röntgenstr 2018; 190: 542 - 550. © Georg Thieme Verlag KG Stuttgart · New York.

Fructose-Glucose Composite Carbohydrates and Endurance Performance: Critical Review and Future Perspectives.

PubMed

Rowlands, David S; Houltham, S; Musa-Veloso, K; Brown, F; Paulionis, L; Bailey, D

2015-11-01

Sports beverages formulated with fructose and glucose composites enhance exogenous carbohydrate oxidation, gut comfort, and endurance performance, relative to single-saccharide formulations. However, a critical review of performance data is absent. We conducted a comprehensive literature review of the effect of fructose:glucose/maltodextrin (glucose or maltodextrin) composites versus glucose/maltodextrin on endurance performance. Mechanistic associations were drawn from effects on carbohydrate metabolism, gut, and other sensory responses. Overall, 14 studies contained estimates of 2.5-3.0-h endurance performance in men, mostly in cycling. Relative to isocaloric glucose/maltodextrin, the ingestion of 0.5-1.0:1-ratio fructose:glucose/maltodextrin beverages at 1.3-2.4 g carbohydrate·min(-1) produced small to moderate enhancements (1-9 %; 95 % confidence interval 0-19) in mean power. When 0.5:1-ratio composites were ingested at ≥1.7 g·min(-1), improvements were larger (4-9 %; 2-19) than at 1.4-1.6 g·min(-1) (1-3 %; 0-6). The effect sizes at higher ingestion rates were associated with increased exogenous carbohydrate oxidation rate, unilateral fluid absorption, and lower gastrointestinal distress, relative to control. Solutions containing a 0.7-1.0:1 fructose:glucose ratio were absorbed fastest; when ingested at 1.5-1.8 g·min(-1), a 0.8:1 fructose:glucose ratio conveyed the highest exogenous carbohydrate energy and endurance power compared with lower or higher fructose:glucose ratios. To conclude, ingesting 0.5-1.0:1-ratio fructose:glucose/maltodextrin beverages at 1.3-2.4 g·min(-1) likely benefits 2.5-3.0 h endurance power versus isocaloric single saccharide. Further ratio and dose-response research should determine if meaningful performance benefits of composites accrue with ingestion <1.3 g·min(-1), relative to higher doses. Effects should be established in competition, females, other food formats, and in heat-stress and ultra-endurance exercise where carbohydrate demands may differ from the current analysis.

Safety, tolerability and pharmacokinetics of doravirine, a novel HIV non-nucleoside reverse transcriptase inhibitor, after single and multiple doses in healthy subjects.

PubMed

Anderson, Matt S; Gilmartin, Jocelyn; Cilissen, Caroline; De Lepeleire, Inge; Van Bortel, Luc; Dockendorf, Marissa F; Tetteh, Ernestina; Ancona, June K; Liu, Rachael; Guo, Ying; Wagner, John A; Butterton, Joan R

2015-01-01

Doravirine is a novel non-nucleoside inhibitor of HIV-1 reverse transcriptase with potent activity against wild-type virus (95% inhibitory concentration 19 nM, 50% human serum). Doravirine has low potential to cause drug-drug interactions since it is primarily eliminated by oxidative metabolism and does not inhibit or significantly induce drug-metabolizing enzymes. The pharmacokinetics and safety of doravirine were investigated in two double-blind, dose-escalation studies in healthy males. Thirty-two subjects received single doses of doravirine (6-1,200 mg) or matching placebo tablets; 40 subjects received doravirine (30-750 mg) or matching placebo tablets once daily for 10 days. In addition, the effect of doravirine (120 mg for 14 days) on single-dose pharmacokinetics of the CYP3A substrate midazolam was evaluated (10 subjects). The maximum plasma concentration (Cmax) of doravirine was achieved within 1-5 h with an apparent terminal half-life of 12-21 h. Consistent with single-dose pharmacokinetics, steady state was achieved after approximately 7 days of once daily administration, with accumulation ratios (day 10/day 1) of 1.1-1.5 in the area under the plasma concentration-time curve during the dosing interval (AUC0-24 h), Cmax and trough plasma concentration (C24 h). All dose levels produced C24 h>19 nM. Administration of 50 mg doravirine with a high-fat meal was associated with slight elevations in AUC time zero to infinity (AUC0-∞) and C24 h with no change in Cmax. Midazolam AUC0-∞ was slightly reduced by coadministration of doravirine (geometric mean ratio 0.82, 90% CI 0.70, 0.97). There was no apparent relationship between adverse event frequency or intensity and doravirine dose. No rash or significant central nervous system events other than headache were reported. Doravirine is generally well tolerated in single doses up to 1,200 mg and multiple doses up to 750 mg once daily for up to 10 days, with a pharmacokinetic profile supportive of once-daily dosing. Doravirine at steady state slightly reduced the exposure of coadministered midazolam, to a clinically unimportant extent.

High dose hydrocortisone immediately after trauma may alter the trajectory of PTSD: interplay between clinical and animal studies.

PubMed

Zohar, Joseph; Yahalom, Hila; Kozlovsky, Nitsan; Cwikel-Hamzany, Shlomit; Matar, Michael A; Kaplan, Zeev; Yehuda, Rachel; Cohen, Hagit

2011-11-01

High-dose corticosteroids have been reported to reduce symptoms of acute stress and post-traumatic stress in polytrauma patients and in animal studies. The underlying mechanism of action remains largely unclear. These issues were addressed in parallel in the clinical and preclinical studies below. In this preliminary study, 25 patients with acute stress symptoms were administered a single intravenous bolus of high-dose hydrocortisone (100-140 mg) or placebo within 6 h of a traumatic event in a prospective, randomized, double-blind, placebo-controlled pilot study. Early single high-dose hydrocortisone intervention attenuated the core symptoms of both the acute stress and of subsequent PTSD in patients. High-dose hydrocortisone treatment given in the first few hours after a traumatic experience was associated with significant favorable changes in the trajectory of exposure to trauma, as expressed by the reduced risk of the development of PTSD post-trauma. In parallel, a comparative study of morphological arborization in dentate gyrus and its modulating molecules was performed in stress-exposed animals treated with high-dose hydrocortisone. Steroid-treated stressed animals displayed significantly increased dendritic growth and spine density, with increased levels of brain-derived neurotrophic factor (BDNF) and obtunded postsynaptic density-95 (PSD-95) levels. The animal study provided insights into the potential mechanism of this intervention, as it identified relevant morphological and biochemical associations to the clinical observations. Thus, evidence from clinical and animal studies suggests that there is a "window of opportunity" in the early aftermath of trauma to help those who are vulnerable to the development of chronic PTSD. Copyright © 2011 Elsevier B.V. and ECNP. All rights reserved.

Mechanics in the Production of Mandibular Fractures: A Clinical, Retrospective Case-Control Study

PubMed Central

Yang, Rongtao; Li, Zhi; Li, Zubing

2016-01-01

As the mandible is susceptible to fracture, the aim of this study was to use multivariate logistic regression analysis to identify and distinguish various internal factors that may influence the location of mandibular fractures. The study included 1131 patients with maxillofacial fractures during the period from January 2000 to December 2009 to evaluate the association of mandibular fracture location (unilateral symphysis, body, angle, condylar, or bilateral condylar fractures) with various internal factors. Among the 1131 patients, 869 had mandibular fractures. Data on age, sex, soft tissue injuries, dental trauma, and maxillofacial fracture type were collected and analyzed using multivariate logistic regression. In total, 387, 210, 139, 319, and 172 patients were diagnosed with unilateral symphysis, body, angle, unilateral, or bilateral condylar fractures, respectively. The dental trauma in patients with bilateral condylar fractures differed from that in patients with unilateral condylar fractures. Patients with mandibular fracture (unilateral symphysis, body, unilateral or bilateral condylar) possessed an approximately equal risk of soft tissue injuries in the mandible. Patients with either unilateral or bilateral condylar fractures were associated with a low risk of mandibular angle fracture (OR < 1). Similarly, patients with mandibular angle fracture were associated with a low risk of unilateral or bilateral condylar fractures (OR < 1). Moreover, patients with symphysis fracture were associated with a low risk of bilateral condylar fractures (90 of 387 [23.3%], OR 0.899). By contrast, patients with bilateral condylar fractures were associated with a high risk of symphysis fracture (90 of 172 [52.3%], OR 17.38). Patients with condylar fractures, particularly those with bilateral condylar fractures, were infrequently associated with secondary mandibular fractures. Mandibular fractures tended to have less of an association with midfacial fractures. The occurrence of mandibular fractures is strongly correlated with age, sex, soft tissue injuries, dental trauma, and the pattern and position of the maxillofacial fractures in patients. PMID:26900699

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.

Unrestricted Hepatocyte Transduction with Adeno-Associated Virus Serotype 8 Vectors in Mice

PubMed Central

Nakai, Hiroyuki; Fuess, Sally; Storm, Theresa A.; Muramatsu, Shin-ichi; Nara, Yuko; Kay, Mark A.

2005-01-01

Recombinant adeno-associated virus (rAAV) vectors can mediate long-term stable transduction in various target tissues. However, with rAAV serotype 2 (rAAV2) vectors, liver transduction is confined to only a small portion of hepatocytes even after administration of extremely high vector doses. In order to investigate whether rAAV vectors of other serotypes exhibit similar restricted liver transduction, we performed a dose-response study by injecting mice with β-galactosidase-expressing rAAV1 and rAAV8 vectors via the portal vein. The rAAV1 vector showed a blunted dose-response similar to that of rAAV2 at high doses, while the rAAV8 vector dose-response remained unchanged at any dose and ultimately could transduce all the hepatocytes at a dose of 7.2 × 1012 vector genomes/mouse without toxicity. This indicates that all hepatocytes have the ability to process incoming single-stranded vector genomes into duplex DNA. A single tail vein injection of the rAAV8 vector was as efficient as portal vein injection at any dose. In addition, intravascular administration of the rAAV8 vector at a high dose transduced all the skeletal muscles throughout the body, including the diaphragm, the entire cardiac muscle, and substantial numbers of cells in the pancreas, smooth muscles, and brain. Thus, rAAV8 is a robust vector for gene transfer to the liver and provides a promising research tool for delivering genes to various target organs. In addition, the rAAV8 vector may offer a potential therapeutic agent for various diseases affecting nonhepatic tissues, but great caution is required for vector spillover and tight control of tissue-specific gene expression. PMID:15596817

Quantitative comparison of cortical and deep grey matter in pathological subtypes of unilateral cerebral palsy.

PubMed

Scheck, Simon M; Pannek, Kerstin; Fiori, Simona; Boyd, Roslyn N; Rose, Stephen E

2014-10-01

The aim of this study was to quantify grey matter changes in children with unilateral cerebral palsy (UCP), differentiating between cortical or deep grey matter (CDGM) lesions, periventricular white matter (PWM) lesions, and unilateral and bilateral lesions. In a cross-sectional study we obtained high resolution structural magnetic resonance images from 72 children (41 males, 31 females, mean age 10y 9mo [SD 3y 1mo], range 5y 1mo-17y 1mo) with UCP (33 left, 39 right hemiplegia; Manual Ability Classification System level I n=29, II n=43; Gross Motor Function Classification System level I n=46, II n=26), and 19 children with typical development (CTD; eight males, 11 females, mean age 11y 2mo [SD 2y 7mo], range 7y 8mo-16y 4mo). Images were classified by lesion type and analyzed using voxel-based morphometry (VBM) and subcortical volumetric analysis. Deep grey matter volumes were not significantly different between children with CDGM and PWM lesions, with the thalamus, putamen, and globus pallidus being reduced unilaterally in both groups compared with CTD (p≤0.001). Children with CDGM lesions additionally showed widespread cortical changes involving all lobes using VBM (p<0.01). Children with bilateral lesions had reduced thalamus and putamen volumes bilaterally (p<0.001). The thalamic volume was reduced bilaterally in children with unilateral lesions (p=0.004). Lesions to the PWM cause secondary changes to the deep grey matter structures similar to primary changes seen in CDGM lesions. Despite having a unilateral phenotype, grey matter changes are observed bilaterally, even in children with unilateral lesions. © 2014 Mac Keith Press.

Alteration in behavioral sensitivity to amphetamine after treatment with oxotremorine. Effect of dose and test environment.

PubMed

Gralewicz, Sławomir; Lutz, Piotr; Wiaderna, Dorota; Tomas, Tadeusz

2003-12-17

Our earlier experiment revealed that rats pretreated once with an anticholinesterase develop hyposensitivity to amphetamine (AMPH). One of the likely causes of this effect might be a transient hyperexcitation of the central muscarinic receptors. It has appeared, however, that rats pretreated with oxotremorine (OX), a muscarinic agonist, show an augmented behavioral response to AMPH weeks later. The present experiments were performed in order to obtain more information on the relationship between the OX-induced sensitization to AMPH and the OX dose and dosing regime (single or repeated), and to find out whether the environment associated with the acute effects of OX could affect the response to AMPH. In experiment 1, adult male rats were given a single i.p. injection of OX in home cages at a moderate (0.5 mg/kg) or high (1.0 mg/kg) dose. In experiment 2, the rats received eight 1.0 mg/kg doses of OX in the course of three days. After each injection, some animals returned to their home cages, and some were placed in the test cages for 30 min. In both experiments, the response to AMPH was assessed on day 21 after the treatment. The obtained results indicate that: (i) a single i.p. exposure to OX results in an increase of the rat's behavioral sensitivity to AMPH but the moderate dose is more effective in inducing this effect; (ii) repeated exposure to OX at high doses, in a regime enabling development of tolerance to the acute OX effects, does not alter the rat sensitivity to AMPH, and (iii) expression of the AMPH response is suppressed in environment which has been associated with acute effects of OX.

Sarizotan, a serotonin 5-HT1A receptor agonist and dopamine receptor ligand. 1. Neurochemical profile.

PubMed

Bartoszyk, G D; Van Amsterdam, C; Greiner, H E; Rautenberg, W; Russ, H; Seyfried, C A

2004-02-01

Sarizotan exhibited high affinities only to serotonin 5-HT1A receptors and dopamine DA D4>D3>D2 receptors with the profile of a 5-HT1A agonist and DA antagonist demonstrated by the inhibition of cAMP-stimulation and guinea pig ileum contraction, decreased accumulation of the 5-HT precursor 5-hydroxytryptophan and increased levels of 5-HT metabolites, increased accumulation of DA precursor dihydroxyphenylalanine (DOPA) and the reduced levels of DA metabolites in intact rats. However, sarizotan at higher doses decreased DA precursor accumulation in reserpinized rats and induced contralateral rotational behavior in unilaterally substantia nigra lesioned rats, indicating some intrinsic dopaminergic activity; at D2 receptors sarizotan may act as a partial agonist, depending on the dopaminergic impulse flow. Sarizotan represents a new approach for the treatment of extrapyramidal motor complications such as l-DOPA-induced dyskinesia in Parkinson's disease.

High-dose, single-bolus eptifibatide: a safe and cost-effective alternative to conventional glycoprotein IIb/IIIa inhibitor use for elective coronary interventions.

PubMed

Fischell, Tim A; Attia, Tamer; Rane, Santosh; Salman, Waddah

2006-10-01

Adjunctive pharmacotherapy with eptifibatide, a glycoprotein (GP) IIb/IIIa inhibitor, as an intravenous bolus followed by infusion has been shown to improve outcomes in elective coronary interventions (PCI). However, bleeding complications and costs have limited the routine adoption of this regimen. The goal of this study was to examine the safety, efficacy and cost-effectiveness of high-dose, single-bolus eptifibatide, without post-intervention infusion, in "real-world" patients undergoing elective PCI. We studied 401 patients with stable and unstable angina who were treated with a high-dose (20 mg), single bolus of eptifibatide plus heparin prior to the start of elective PCI. Exclusion criteria included recent MI, stenting of bypass graft(s), rotational atherectomy and/or brachytherapy. The primary study endpoints were major adverse clinical events (MACE), defined as the in-hospital and 30-day incidence of death from any cause, Q-wave or non-Q-wave MI, repeat target vessel revascularization and/or major bleeding complications. Relevant demographic and procedural characteristics included mean age: 66.4 +/- 11.2; male gender: 242/401 (61%); number of vessels treated per patient: 1.46 +/- 0.42; and number of stents deployed per patient: 1.82 +/- 0.65. In-hospital non-Q-wave MI (CPK and/or CPK-MB > 3 times the upper limit of normal) occurred in 7/401 patients (1.75%) and MACE was 2.25%. Major bleeding complications were seen in 2/401 patients (0.49%). There were 4 additional MACE events at 30-day follow up (total MACE and bleeding = 3.25%). The average anticoagulation cost was 66 dollars/patient. Intravenous eptifibatide, administered as a high-dose (20 mg) single-vial bolus, is a safe, effective and highly cost-effective alternative to the conventional regimens of bolus plus prolonged intravenous GP IIb/IIIa inhibitor infusion for patients undergoing elective PCI.

Bacteremia due to viridans streptococcus in neutropenic patients with cancer: clinical spectrum and risk factors.

PubMed

Bochud, P Y; Eggiman, P; Calandra, T; Van Melle, G; Saghafi, L; Francioli, P

1994-01-01

Between 1988 and 1991, 26 episodes of bacteremia due to viridans streptococci occurred in 25 neutropenic patients undergoing intensive chemotherapy for hematologic malignancies. Complications related to the bacteremia were observed in 10 episodes: unilateral pulmonary infiltrates (4), acute respiratory distress syndrome (ARDS) (4), hypotension (3), and endocarditis (2). All patients with ARDS had received high doses of cytosine arabinoside and had bacteremia due to Streptococcus mitis. Death occurred in three patients (12%) but was possibly related to bacteremia in only one case. Case patients who had received prophylaxis with quinolones were compared with matched control patients who received similar prophylaxis but who did not have bacteremia due to viridans streptococci. Multivariate analysis of predisposing factors showed that high doses of cytosine arabinoside (P = .01), the presence of mucositis (P = .02), and the absence of previous therapy with parenteral antibiotics (P = .01) were independent risk factors for the development of viridans streptococcal bacteremia. Of 259 patients who had received quinolone prophylaxis during the study period, 22 (8.5%) developed an episode of viridans streptococcal bacteremia as compared with three episodes (3.7%) in 82 patients who had received a quinolone and penicillin (P = .07). However, the latter three episodes were caused by strains with decreased susceptibility to penicillin, thus suggesting that resistance to penicillin might limit the use of this antibiotic as a prophylactic agent in the future.

The dose-response effect of medical exercise therapy on impairment in patients with unilateral longstanding subacromial pain.

PubMed

Osterås, Håvard; Torstensen, Tom Arild

2010-01-05

The primary aim of this study was to investigate the effect of medical exercise therapy in shoulder impingement patients, along with possible correlations between impairment variables. A prospective unblended randomized clinical trial. Over four months, 61 participants were randomly assigned into a high-graded exercise therapy group (HD) (n=31) and into a low-graded exercise therapy group (LD) (n=30). Prognostic variables were similar between the groups at baseline. Five (8%) patients dropped out during the treatment period, and another four (6%) dropped out before followup. Pain was a composite score of a visual analogue scale (VAS). Isometric strength was measured during four resisted break tests on the shoulder. Function was measured by means of a functional assessment questionnaire (Shoulder Rating Questionnaire, SRQ). Both groups trained three times per week for twelve weeks, with tests pre- and posttraining and six months follow-up. The HD group achieved significantly (p < 0.05) better outcome effects than the LD group for pain, range of motion, isometric functional strength and function, but both groups increased function from pretest to posttest. In patients with uncomplicated subacromial pain syndrome, medical exercise therapy is an efficient treatment alternative, where high-grade doses should be emphasized. A major limitation is that the measurements were not undertaken by another person than the treating physiotherapists.

Evaluation of a 3D diamond detector for medical radiation dosimetry

NASA Astrophysics Data System (ADS)

Kanxheri, K.; Servoli, L.; Oh, A.; Munoz Sanchez, F.; Forcolin, G. T.; Murphy, S. A.; Aitkenhead, A.; Moore, C. J.; Morozzi, A.; Passeri, D.; Bellini, M.; Corsi, C.; Lagomarsino, S.; Sciortino, S.

2017-01-01

Synthetic diamond has several properties that are particularly suited to applications in medical radiation dosimetry. It is tissue equivalent, not toxic and shows a high resistance to radiation damage, low leakage current and stability of response. It is an electrical insulator, robust and realizable in small size; due to these features there are several examples of diamond devices, mainly planar single-crystalline chemical vapor depositation (sCVD) diamond, used for relative dose measurement in photon beams. Thanks to a new emerging technology, diamond devices with 3-dimensional structures are produced by using laser pulses to create graphitic paths in the diamond bulk. The necessary bias voltage to operate such detector decreases considerably while the signal response and radiation resistance increase. In order to evaluate the suitability of this new technology for measuring the dose delivered by radiotherapy beams in oncology a 3D polycrystalline (pCVD) diamond detector designed for single charged particle detection has been tested and the photon beam profile has been studied. The good linearity and high sensitivity to the dose observed in the 3D diamond, opens the way to the possibility of realizing a finely segmented device with the potential for dose distribution measurement in a single exposure for small field dosimetry that nowadays is still extremely challenging.

Vitamin D in newborns. A randomised controlled trial comparing daily and single oral bolus vitamin D in infants.

PubMed

Huynh, Julie; Lu, Thao; Liew, Danny; Doery, James Cg; Tudball, Ronald; Jona, Madeleine; Bhamjee, Roisin; Rodda, Christine P

2017-02-01

There are no published data to demonstrate the efficacy of bolus dose vitamin D in newborn infants. The study sought to evaluate this alternative approach of supplementation. This single centre, open randomised controlled trial was conducted from August 2013 to May 2014. It compared the efficacy and safety of daily (400 IU) versus a bolus dose (50 000 IU) of cholecalciferol in newborn infants of vitamin D deficient mothers. The primary outcome measure was the rate of 25 hydroxyvitamin D (25OHD) repletion-defined as 25OHD greater than 50 nmol/L. The secondary objective was determining safety using adjusted total serum calcium. Of 70 eligible infants, 36 received a daily dose and 34 received a single high-dose cholecalciferol. Mean 25OHD in the bolus group (154 nmol/L, 95% confidence interval (CI) 131-177) was higher than the daily group (48 nmol/L, 95% CI 42-54) at 1-2 weeks of age. This was reversed at 3-4 months, (65 nmol/L, 95% CI 59-71) compared with the daily group (81 nmol/L, 95% CI 77-85). More infants in the single bolus group achieved vitamin D repletion (100 vs. 31%) at 1-2 weeks. By 3-4 months, both groups achieved similar vitamin D repletion rates (91 vs. 89%). Mean adjusted total serum calcium in the bolus group were normal at 1-2 weeks (2.73 mmol/L) and 3-4 months (2.55 mmol/L). Single bolus dosing of 50 000 IU cholecalciferol achieves higher 25OHD repletion rates at 1-2 weeks of age compared with daily dosing, but repletion rates were similar by 3-4 months. There was no hypercalcaemia documented with single bolus dosing in this study. © 2016 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).

A novel self-micro-emulsifying delivery system (SMEDS) formulation significantly improves the fasting absorption of EPA and DHA from a single dose of an omega-3 ethyl ester concentrate.

PubMed

Qin, Yan; Nyheim, Hilde; Haram, Else Marie; Moritz, Joseph M; Hustvedt, Svein Olaf

2017-10-16

Absorption of EPA and DHA from Omega-3-acid ethyl ester (EE) concentrate supplements occurs most efficiently when taken in context of a fatty meal; adequate fat intake is required to release bile salts that emulsify and pancreatic enzymes that digest omega-3-containing lipids in the intestine. Current guidelines recommend reduction in fat intake and therefore there is a need to optimize the absorption of Omega-3 in those consuming low-fat or no-fat meals. To this end, BASF has developed an Absorption Acceleration Technology, a novel self-micro-emulsifying delivery system (SMEDS) formulation of highly concentrated Omega-3-acid EE which enables rapid emulsification and microdroplet formation upon entering the aqueous environment of the gut therefore enhances the absorption. Two separate single dose, crossover studies were conducted to determine the relative bioavailability of omega-3-acid EE concentrate, either as a novel SMEDS formulation (PRF-021) or as control, in healthy fasted male and female adults at two dose levels (Study 1 "low dose": 630 mg EPA + DHA in PRF-021 vs. 840 mg EPA + DHA in control; Study 2 "high dose": 1680 mg EPA + DHA in PRF-021 vs. 3360 mg EPA + DHA in control). Blood samples were collected immediately before supplementation and at defined time intervals for 48 h. Plasma concentration of total EPA and DHA were determined for pharmacokinetic analysis, area under the curve (AUC) and maximum observed concentration (C max ) was determined. Total EPA plus DHA absorption from SMEDS formulation PRF-021 were 6.4 and 11.5 times higher compared to control in low- and high-dose studies respectively, determined as the ratio of baseline corrected, dose normalized AUC 0-24h of PRF-021 over that of control. EPA and DHA individually showed differing levels of enhancement: the AUC 0-24h ratio for EPA was 23.8 and 25.7 in low and high dose studies, respectively, and the AUC 0-24h ratio for DHA was 3.6 and 5.6 in low and high dose studies, respectively. C max was also increased for both EPA and DHA 2.7- to 9.2-fold. PRF-021 is a novel SMEDS formulation of Omega-3-acid EE demonstrating a marked improvement in absorption of a single dose of EPA and DHA EE under fasted conditions. This allows adequate absorption of Omega-3 from the supplement without the requirement of a high-fat meal.

Interference experiment with asymmetric double slit by using 1.2-MV field emission transmission electron microscope.

PubMed

Harada, Ken; Akashi, Tetsuya; Niitsu, Kodai; Shimada, Keiko; Ono, Yoshimasa A; Shindo, Daisuke; Shinada, Hiroyuki; Mori, Shigeo

2018-01-17

Advanced electron microscopy technologies have made it possible to perform precise double-slit interference experiments. We used a 1.2-MV field emission electron microscope providing coherent electron waves and a direct detection camera system enabling single-electron detections at a sub-second exposure time. We developed a method to perform the interference experiment by using an asymmetric double-slit fabricated by a focused ion beam instrument and by operating the microscope under a "pre-Fraunhofer" condition, different from the Fraunhofer condition of conventional double-slit experiments. Here, pre-Fraunhofer condition means that each single-slit observation was performed under the Fraunhofer condition, while the double-slit observations were performed under the Fresnel condition. The interference experiments with each single slit and with the asymmetric double slit were carried out under two different electron dose conditions: high-dose for calculation of electron probability distribution and low-dose for each single electron distribution. Finally, we exemplified the distribution of single electrons by color-coding according to the above three types of experiments as a composite image.

Prevalence of dental anomalies in children with cleft lip and unilateral and bilateral cleft lip and palate.

PubMed

Rullo, R; Festa, V M; Rullo, R; Addabbo, F; Chiodini, P; Vitale, M; Perillo, L

2015-09-01

To examine the prevalence of different types of dental anomalies in children with nonsyndromic cleft lip, unilateral cleft lip-palate, and bilateral cleft lip-palate. A sample of 90 patients (aged 4-20 years) affected by isolated cleft lip, unilateral and bilateral cleft lip and palate was examined. Cleft patients were classified into one of three groups according to cleft type: (1) Unilateral Cleft Lip-Palate, (2) Bilateral Cleft Lip-Palate, and (3) Cleft Lip. Intraoral exams, panoramic radiographs and dental casts, were used to analyse the prevalence of the various dental anomalies included in this study. There were no statistically significant differences between patients with cleft lip, unilateral cleft lip and palate and bilateral cleft lip and palate. The congenital absence of the cleft-side lateral incisor was observed in 40% of the sample, and a total of 30% patients showed supernumerary teeth at the incisors region. Second premolar agenesis was found in 4.4% of patients, whereas in 18.9% of the sample there was an ectopic dental eruption. Lateral or central incisors rotation was noted in 31.1% of the sample, while shape anomaly, lateral incisor microdontia, and enamel hypoplasia were detected respectively in 25.6%, 5.6% and 18.9% of cleft patients. High prevalence of different dental anomalies in children with cleft lip and unilateral and bilateral cleft lip and palate has been confirmed. This study, in particular, shows the presence of ectopic and rotated teeth in the cleft area.

ELQ-300 prodrugs for enhanced delivery and single-dose cure of malaria.

PubMed

Miley, Galen P; Pou, Sovitj; Winter, Rolf; Nilsen, Aaron; Li, Yuexin; Kelly, Jane X; Stickles, Allison M; Mather, Michael W; Forquer, Isaac P; Pershing, April M; White, Karen; Shackleford, David; Saunders, Jessica; Chen, Gong; Ting, Li-Min; Kim, Kami; Zakharov, Lev N; Donini, Cristina; Burrows, Jeremy N; Vaidya, Akhil B; Charman, Susan A; Riscoe, Michael K

2015-09-01

ELQ-300 is a preclinical candidate that targets the liver and blood stages of Plasmodium falciparum, as well as the forms that are crucial to transmission of disease: gametocytes, zygotes, and ookinetes. A significant obstacle to the clinical development of ELQ-300 is related to its physicochemical properties. Its relatively poor aqueous solubility and high crystallinity limit absorption to the degree that only low blood concentrations can be achieved following oral dosing. While these low blood concentrations are sufficient for therapy, the levels are too low to establish an acceptable safety margin required by regulatory agencies for clinical development. One way to address the challenging physicochemical properties of ELQ-300 is through the development of prodrugs. Here, we profile ELQ-337, a bioreversible O-linked carbonate ester prodrug of the parent molecule. At the molar equivalent dose of 3 mg/kg of body weight, the delivery of ELQ-300 from ELQ-337 is enhanced by 3- to 4-fold, reaching a maximum concentration of drug in serum (C max) of 5.9 μM by 6 h after oral administration, and unlike ELQ-300 at any dose, ELQ-337 provides single-dose cures of patent malaria infections in mice at low-single-digit milligram per kilogram doses. Our findings show that the prodrug strategy represents a viable approach to overcome the physicochemical limitations of ELQ-300 to deliver the active drug to the bloodstream at concentrations sufficient for safety and toxicology studies, as well as achieving single-dose cures. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Variations in the technique for autologous limbal transplantation.

PubMed

Mataix, B; Alcántara, A; Caro, M; Montero, J; Ponte, B; Rodríguez de la Rúa, E

2016-10-01

To present the results on the use of a single block limbal autograft, combined with amniotic membrane transplantation and sectoral sequential postoperative epitheliectomy of the conjunctiva in 2 patients with unilateral total limbal stem cell deficiency. A single block limbal autograft combined with amniotic membrane transplantation may be sufficient to restore a stable corneal surface, but sometimes sequential sectoral conjunctival epitheliectomy may be required to treat anomalous epithelial remnants. Copyright © 2016 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.

Comparison of CREME (cosmic-ray effects on microelectronics) model LET (linear energy transfer) spaceflight dosimetry data

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

Letaw, J.R.; Adams, J.H.

The galactic cosmic radiation (GCR) component of space radiation is the dominant cause of single-event phenomena in microelectronic circuits when Earth's magnetic shielding is low. Spaceflights outside the magnetosphere and in high inclination orbits are examples of such circumstances. In high-inclination orbits, low-energy (high LET) particles are transmitted through the field only at extreme latitudes, but can dominate the orbit-averaged dose. GCR is an important part of the radiation dose to astronauts under the same conditions. As a test of the CREME environmental model and particle transport codes used to estimate single event upsets, we have compiled existing measurements ofmore » HZE doses were compiled where GCR is expected to be important: Apollo 16 and 17, Skylab, Apollo Soyuz Test Project, and Kosmos 782. The LET spectra, due to direct ionization from GCR, for each of these missions has been estimated. The resulting comparisons with data validate the CREME model predictions of high-LET galactic cosmic-ray fluxes to within a factor of two. Some systematic differences between the model and data are identified.« less

Unilateral flank ovariohysterectomy in guinea pigs (Cavia porcellus).

PubMed

Rozanska, D; Rozanski, P; Orzelski, M; Chlebicka, N; Putowska, K

2016-11-01

To describe a simple, minimally invasive method of ovariohysterectomy via a unilateral flank approach in guinea pigs, for use in routine desexing of healthy female guinea pigs or treatment of ovarian cysts. The subjects of this retrospective study were 41 client-owned guinea pigs submitted for routine desexing or treatment of ovarian cysts. They included 16 healthy female guinea pigs aged 8-12 months (Group 1), and 15 females aged from 9 months to 3 years (Group 2), and 10 females aged from 3 to 7 years (Group 3) with different-sized ovarian cysts. Prior to surgery, the animals received clinical examination, blood testing (complete blood count and serum biochemistry profile) and examination of the abdomen using ultrasonography, to assess the condition of the reproductive tract and ensure the guinea pigs were fit for surgery. Ovariohysterectomy was performed via a unilateral flank incision made close to the erector spinae muscle starting approximately 1 cm caudal to the last rib. Both ovaries, uterine horns, and the uterine cervix were localised, ligated, and dissected through this unilateral retroperitoneal incision. Ovariohysterectomy was successfully completed via a single flank incision in 38/41 (93%) guinea pigs. Three guinea pigs with ovarian cysts from Group 3, which were >6 years old died during surgery due to circulatory and respiratory failure under anaesthesia. In the remaining 38 cases, surgery proceeded without complications. A further two guinea pigs from Group 3 were reluctant to move or eat for the first 3 days after surgery but recovered after provision of supportive care. All 38 animals fully recovered and wound healing was normal. This is the first report of ovariohysterectomy via a unilateral flank incision in guinea pigs. This approach is a simple, minimally invasive and safe alternative to the midline or bilateral flank approaches currently used for surgery of the reproductive tract in guinea pigs.

Blood flow changes after unilateral carotid artery ligation monitored by optical coherence tomography

NASA Astrophysics Data System (ADS)

Ma, Yushu; Liang, Chengbo; Suo, Yanyan; Zhao, Yuqian; Wang, Yi; Xu, Tao; Wang, Ruikang; Ma, Zhenhe

2016-03-01

Unilateral carotid artery ligation which could induce adaptive improvement is a classic model that has been widely used to study pathology of ischemic disease. In those studies, blood flow is an important parameter to characterize the ischemia. Optical coherence tomography (OCT) is a powerful imaging modality which can provide depth resolved images in biological tissue with high spatial and temporal resolution. SPF rats was anesthetized with isoflurane and divided into two groups. In first group, bilateral carotid artery was surgically exposed, and then left carotid artery was ligated. Blood flow changes of the contralateral carotid artery was monitored using high speed spectral domain optical coherence tomography, including the absolute flow velocity and the flow volume. In the other group, skull window was opened at the ipsilateral cerebral cortex of ligation and blood supply of small artery was measured before and after the ligation. The measured results demonstrate the blood supply compensation process after unilateral carotid artery ligation. With the superiority of high resolution, OCT is an effective technology in monitoring results of carotid artery after ligation.

The comparative performance of the single intradermal test and the single intradermal comparative tuberculin test in Irish cattle, using tuberculin PPD combinations of differing potencies.

PubMed

Good, M; Clegg, T A; Costello, E; More, S J

2011-11-01

In national bovine tuberculosis (BTB) control programmes, testing is generally conducted using a single source of bovine purified protein derivative (PPD) tuberculin. Alternative tuberculin sources should be identified as part of a broad risk management strategy as problems of supply or quality cannot be discounted. This study was conducted to compare the impact of different potencies of a single bovine PPD tuberculin on the field performance of the single intradermal comparative tuberculin test (SICTT) and single intradermal test (SIT). Three trial potencies of bovine PPD tuberculin, as assayed in naturally infected bovines, namely, low (1192IU/dose), normal (6184IU/dose) and high (12,554IU/dose) were used. Three SICTTs (using) were conducted on 2102 animals. Test results were compared based on reactor-status and changes in skin-thickness at the bovine tuberculin injection site. There was a significant difference in the number of reactors detected using the high and low potency tuberculins. In the SICTT, high and low potency tuberculin detected 40% more and 50% fewer reactors, respectively, than normal potency tuberculin. Furthermore, use of the low potency tuberculin in the SICTT failed to detect 20% of 35 animals with visible lesions, and in the SIT 11% of the visible lesion animals would have been classified as negative. Tuberculin potency is critical to the performance of both the SICTT and SIT. Tuberculin of different potencies will affect reactor disclosure rates, confounding between-year or between-country comparisons. Independent checks of tuberculin potency are an important aspect of quality control in national BTB control programmes. Copyright © 2011 Elsevier Ltd. All rights reserved.

The protective effects of ascorbic acid, cimetidine, and nifedipine on diethyldithiocarbamate-induced hepatic toxicity in albino rats.

PubMed

Gaafa, Khadiga Mohammed; Badawy, Mohammed M; Hamza, Alaaeldin A

2011-10-01

The aim of the present work was to clarify the involvement of free radicals, cytochrome P450 toxic metabolites, and deregulation of calcium homeostasis in the mechanism of diethyldithiocarbamate (DDC) hepatotoxicity. This was elucidated through the preadministration of ascorbic acid (a free radical scavenger), cimetidine (an inhibitor of cytochrome P450 enzymes), or nifedipine (a calcium-blocking agent) before DDC treatment to male albino rats. DDC was administered either as a single dose [800 mg/kg body weight (b.w.), subcutaneously, s.c.] or daily repeated doses for 30 days (400 mg/kg b.w., s.c.). Oxidative stress indicators [e.g., malondialdehyde (MDA), reduced glutathione (GSH), and superoxide dismutase enzyme (SOD)] showed that single or repeated DDC doses induce an increase in MDA level and a decrease in SOD activity in the liver, whereas it causes depletion in hepatic GSH after a single dose and an elevation in its value after repeated doses. Severe histopathological changes were also observed in the livers of rats treated with single or repeated DDC doses. Ascorbic acid, cimetidine, and nifedipine pretreatments were found to induce highly protective effects against the evinced DDC hepatotoxicity, manifesting that free radical, cytochrome P450, and calcium-dependent processes contribute to DDC liver toxicity. Finally, although multiple mechanisms may be involved in the hepatotoxic changes induced by DDC, calcium disarrangement and free radical formation play a more critical role than cytochrome P450 in metabolic events leading to toxic effects of DDC.

Comparison of image quality, myocardial perfusion, and LV function between standard imaging and single-injection ultra-low-dose imaging using a high-efficiency SPECT camera: the MILLISIEVERT study

PubMed Central

Einstein, Andrew J.; Blankstein, Ron; Andrews, Howard; Fish, Mathews; Padgett, Richard; Hayes, Sean W.; Friedman, John D.; Qureshi, Mehreen; Rakotoarivelo, Harivony; Slomka, Piotr; Nakazato, Ryo; Bokhari, Sabahat; Di Carli, Marcello; Berman, Daniel S.

2015-01-01

SPECT myocardial perfusion imaging (MPI) plays a central role in coronary artery disease diagnosis; but concerns exist regarding its radiation burden. Compared to standard Anger-SPECT (A-SPECT) cameras, new high-efficiency (HE) cameras with specialized collimators and solid-state cadmium-zinc-telluride detectors offer potential to maintain image quality (IQ), while reducing administered activity and thus radiation dose to patients. No previous study has compared IQ, interpretation, total perfusion deficit (TPD), or ejection fraction (EF) in patients receiving both ultra-low-dose (ULD) imaging on a HE-SPECT camera and standard low-dose (SLD) A-SPECT imaging. Methods We compared ULD-HE-SPECT to SLD-A-SPECT imaging by dividing the rest dose in 101 patients at 3 sites scheduled to undergo clinical A-SPECT MPI using a same day rest/stress Tc-99m protocol. Patients received HE-SPECT imaging following an initial ~130 MBq (3.5mCi) dose, and SLD-A-SPECT imaging following the remainder of the planned dose. Images were scored visually by 2 blinded readers for IQ and summed rest score (SRS). TPD and EF were assessed quantitatively. Results Mean activity was 134 MBq (3.62 mCi) for ULD-HE-SPECT (effective dose 1.15 mSv) and 278 MBq (7.50 mCi, 2.39 mSv) for SLD-A-SPECT. Overall IQ was superior for ULD-HE-SPECT (p<0.0001), with twice as many studies graded excellent quality. Extracardiac activity and overall perfusion assessment were similar. Between-method correlations were high for SRS (r=0.87), TPD (r=0.91), and EF (r=0.88). Conclusion ULD-HE-SPECT rest imaging correlates highly with SLD-A-SPECT. It has improved image quality, comparable extracardiac activity, and achieves radiation dose reduction to 1 mSv for a single injection. PMID:24982439

Sound Source Localization and Speech Understanding in Complex Listening Environments by Single-sided Deaf Listeners After Cochlear Implantation.

PubMed

Zeitler, Daniel M; Dorman, Michael F; Natale, Sarah J; Loiselle, Louise; Yost, William A; Gifford, Rene H

2015-09-01

To assess improvements in sound source localization and speech understanding in complex listening environments after unilateral cochlear implantation for single-sided deafness (SSD). Nonrandomized, open, prospective case series. Tertiary referral center. Nine subjects with a unilateral cochlear implant (CI) for SSD (SSD-CI) were tested. Reference groups for the task of sound source localization included young (n = 45) and older (n = 12) normal-hearing (NH) subjects and 27 bilateral CI (BCI) subjects. Unilateral cochlear implantation. Sound source localization was tested with 13 loudspeakers in a 180 arc in front of the subject. Speech understanding was tested with the subject seated in an 8-loudspeaker sound system arrayed in a 360-degree pattern. Directionally appropriate noise, originally recorded in a restaurant, was played from each loudspeaker. Speech understanding in noise was tested using the Azbio sentence test and sound source localization quantified using root mean square error. All CI subjects showed poorer-than-normal sound source localization. SSD-CI subjects showed a bimodal distribution of scores: six subjects had scores near the mean of those obtained by BCI subjects, whereas three had scores just outside the 95th percentile of NH listeners. Speech understanding improved significantly in the restaurant environment when the signal was presented to the side of the CI. Cochlear implantation for SSD can offer improved speech understanding in complex listening environments and improved sound source localization in both children and adults. On tasks of sound source localization, SSD-CI patients typically perform as well as BCI patients and, in some cases, achieve scores at the upper boundary of normal performance.

Intravenous Single-Dose Toxicity of Redaporfin-Based Photodynamic Therapy in Rodents

PubMed Central

Rocha, Luis B.; Schaberle, Fábio; Dąbrowski, Janusz M.; Simões, Sérgio; Arnaut, Luis G.

2015-01-01

We assessed the tolerability and safety in rodents of a single intravenous (i.v.) dose of redaporfin, a novel photosensitizer for Photodynamic Therapy (PDT) of cancer. Two approaches were used to evaluate acute toxicity: (i) a dose escalation study in BALB/c mice to evaluate the maximum tolerated dose of redaporfin; and (ii) a safety toxicology study in Wistar rats, of a single dose of redaporfin, with or without illumination, to evaluate possible signs of systemic toxicity. Redaporfin formulation was well tolerated by mice, with no signs of adverse reactions up to 75 mg/kg. In rats, there were no relevant changes, except for a significant, but transient, increase in the blood serum markers for hepatic function and muscle integrity, and also on neutrophil counts, observed after the application of light. The overall results showed that redaporfin-PDT is very well tolerated. No abnormalities were observed, including reactions at the injection site or skin phototoxicity, although the animals were maintained in normal indoor lighting. Redaporfin also showed a high efficacy in the treatment of male BALB/c mice with subcutaneously implanted colon (CT26) tumours. Vascular-PDT with 1.5 mg/kg redaporfin and a light dose of 74 J/cm2 led to the complete tumour regression in 83% of the mice. PMID:26670231

Modeling Rabbit Responses to Single and Multiple Aerosol ...

EPA Pesticide Factsheets

Journal Article Survival models are developed here to predict response and time-to-response for mortality in rabbits following exposures to single or multiple aerosol doses of Bacillus anthracis spores. Hazard function models were developed for a multiple dose dataset to predict the probability of death through specifying dose-response functions and the time between exposure and the time-to-death (TTD). Among the models developed, the best-fitting survival model (baseline model) has an exponential dose-response model with a Weibull TTD distribution. Alternative models assessed employ different underlying dose-response functions and use the assumption that, in a multiple dose scenario, earlier doses affect the hazard functions of each subsequent dose. In addition, published mechanistic models are analyzed and compared with models developed in this paper. None of the alternative models that were assessed provided a statistically significant improvement in fit over the baseline model. The general approach utilizes simple empirical data analysis to develop parsimonious models with limited reliance on mechanistic assumptions. The baseline model predicts TTDs consistent with reported results from three independent high-dose rabbit datasets. More accurate survival models depend upon future development of dose-response datasets specifically designed to assess potential multiple dose effects on response and time-to-response. The process used in this paper to dev

Dosimetric response for crystalline and nanostructured aluminium oxide to a high-current pulse electron beam.

PubMed

Nikiforov, S V; Kortov, V S

2014-11-01

The main thermoluminescent (TL) and dosimetric properties of the detectors based on anion-defective crystalline and nanostructured aluminium oxide after exposure to a high-current pulse electron beam are studied. TL peaks associated with deep-trapping centres are registered. It is shown that the use of deep-trap TL at 200-600°С allows registering absorbed doses up to 750 kGy for single-crystalline detectors and those up to 6 kGy for nanostructured ones. A wide range of the doses registered, high reproducibility of the TL signal and low fading contribute to a possibility of using single-crystalline and nanostructured aluminium oxide for the dosimetry of high-current pulse electron beams. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Unilateral Eye Blinking Arising From the Ictal Ipsilateral Occipital Area.

PubMed

Falsaperla, Raffaele; Perciavalle, Valentina; Pavone, Piero; Praticò, Andrea Domenico; Elia, Maurizio; Ruggieri, Martino; Caraballo, Roberto; Striano, Pasquale

2016-07-01

We report on an 18-month-old boy with unilateral left eye blinking as a single ictal manifestation without facial twitching. The clinical onset of this phenomenon was first recorded (as an occasional event) at age 3 months, and it was overlooked. By age 6 months, the child's blinking increased to almost daily occurrence in clusters: during blinking the infant showed intact awareness and occasional jerks in the upper limbs and right leg. A video-electroencephalography (video-EEG) documented clinical correlation with a focal pattern arising from the left occipital region, and brain magnetic resonance imaging (MRI) revealed severe brain damage, consisting in poroencephalic hollows and increased spaces in the convexities involving a large area of the left cerebral hemisphere. The boy was prescribed sodium valproate (30 mg/kg/d), resulting in drastic reduction of his clinical seizures. Follow-up to his current age documented good general status, with persistent partial right hemilateral seizures. The blinking progressively disappeared, and is no longer recorded. The pathogenic hypotheses of the unilateral ictal blinking include involvement of the ipsilateral cerebral hemisphere and/or the cerebellar pathways. Review of previous reports of unilateral eye blinking, arising from the ictal ipsilateral brain, revealed that different damaged regions may give rise to blinking ictal phenomena, likely via the trigeminal fibres innervating the subdural intracranial structures and the pial vessels in the ipsilateral affected brain. The eye blinking in the present child represents a further example of an ictal phenomenon, which is predictive of the damaged brain region. © EEG and Clinical Neuroscience Society (ECNS) 2014.

Clinical presentation of retinoblastoma in Alexandria: A step toward earlier diagnosis.

PubMed

Soliman, Sameh E; Eldomiaty, Wesam; Goweida, Mohamed B; Dowidar, Amgad

2017-01-01

To evaluate the clinical presentation of retinoblastoma in Alexandria, Egypt, correlate the timing of accurate diagnosis with the presence of advanced disease and identify causes of delayed presentation. Retrospective noncomparative single institution study reviews demographic and clinical data of all new children with retinoblastoma presenting to Alexandria Main University ocular oncology clinic (OOC) from January 2012 to June 2014. Diagnosis time was from initial parental complaint to retinoblastoma diagnosis and referral time was from retinoblastoma diagnosis to presentation to the Alexandria OCC. Delayed Diagnosis and referral were counted if >2 weeks. Advanced presentation is defined as clinical TNMH (8th edition) staging of cT2 or cT3 (international intraocular retinoblastoma classification group D or E) in at least one eye or the presence of extra-ocular disease (cT4). Seventy eyes of 47 children were eligible: 52% unilateral, 7% with family history and 96% presented with leukocorea. Sixty-four percent of children had advanced intraocular disease and none had extra-ocular disease. Delayed presentation occurred in 58% of children and was significantly associated with advanced disease in both unilaterally and bilaterally affected children (p = 0.003, 0.002 respectively). The delay in diagnosis was more in unilateral cases while the delay in referral was more in bilateral cases. The main cause of delayed presentation in unilateral retinoblastoma was misdiagnosis (30%) while parental shopping for second medical opinion (30%) was the main cause in bilateral children. Delayed diagnosis is a problem affecting retinoblastoma management. Better medical education and training, health education and earlier screening are recommended to achieve earlier diagnosis.

Diagnostic performance of multidetector computed tomography in distinguishing unilateral from bilateral abnormalities in primary hyperaldosteronism: comparison of multidetector computed tomography with adrenal vein sampling.

PubMed

Raman, Siva P; Lessne, Mark; Kawamoto, Satomi; Chen, Yifei; Salvatori, Roberto; Prescott, Jason D; Fishman, Elliot K

2015-01-01

The management of patients with primary hyperaldosteronism (PH) varies depending on whether the unregulated aldosterone secretion localizes to a single unilateral adrenal gland, traditionally determined using adrenal vein sampling (AVS). This study seeks to determine if the performance of multidetector computed tomography (MDCT) examinations performed using the latest scanner technology can reasonably match the results of AVS, and potentially avoid AVS in some patients. Computed tomographic scans in 56 patients with PH were independently reviewed by 2 radiologists for the presence of adrenal nodules and qualitative adrenal thickening. Results were correlated with AVS results. Of 35 patients with MDCT evidence of unilateral nodules, the imaging findings correctly predicted AVS localization in only 23 (65.7%) cases. When stratified by size, MDCT was accurate in only 71.4% of cases for nodules measuring 10 mm or less, and only 55.0% of cases for nodules measuring 11 to 20 mm. Of the 12 cases where MDCT did not correctly localize, AVS localized to the contralateral adrenal gland in 4 cases, whereas AVS suggested no lateralization in 8 cases. In patients with normal bilateral adrenal glands on MDCT, 2/7 (28.6%) of cases demonstrated unilateral localization on AVS, and in patients with bilateral adrenal nodules, only 3/14 (21.4%) did not demonstrate lateralization on AVS. Multidetector computed tomography, even when performed with the latest generation of MDCT scanners, does not offer sufficient diagnostic accuracy to replace AVS in patients with PH.

Individualized Low-Amplitude Seizure Therapy: Minimizing Current for Electroconvulsive Therapy and Magnetic Seizure Therapy.

PubMed

Peterchev, Angel V; Krystal, Andrew D; Rosa, Moacyr A; Lisanby, Sarah H

2015-08-01

Electroconvulsive therapy (ECT) at conventional current amplitudes (800-900 mA) is highly effective but carries the risk of cognitive side effects. Lowering and individualizing the current amplitude may reduce side effects by virtue of a less intense and more focal electric field exposure in the brain, but this aspect of ECT dosing is largely unexplored. Magnetic seizure therapy (MST) induces a weaker and more focal electric field than ECT; however, the pulse amplitude is not individualized and the minimum amplitude required to induce a seizure is unknown. We titrated the amplitude of long stimulus trains (500 pulses) as a means of determining the minimum current amplitude required to induce a seizure with ECT (bilateral, right unilateral, bifrontal, and frontomedial electrode placements) and MST (round coil on vertex) in nonhuman primates. Furthermore, we investigated a novel method of predicting this amplitude-titrated seizure threshold (ST) by a non-convulsive measurement of motor threshold (MT) using single pulses delivered through the ECT electrodes or MST coil. Average STs were substantially lower than conventional pulse amplitudes (112-174 mA for ECT and 37.4% of maximum device amplitude for MST). ST was more variable in ECT than in MST. MT explained 63% of the ST variance and is hence the strongest known predictor of ST. These results indicate that seizures can be induced with less intense electric fields than conventional ECT that may be safer; efficacy and side effects should be evaluated in clinical studies. MT measurement could be a faster and safer alternative to empirical ST titration for ECT and MST.

Singlet oxygen and ROS in a new light: low-dose subcellular photodynamic treatment enhances proliferation at the single cell level.

PubMed

Blázquez-Castro, Alfonso; Breitenbach, Thomas; Ogilby, Peter R

2014-09-01

Two-photon excitation of a sensitizer with a focused laser beam was used to create a spatially-localized subcellular population of reactive oxygen species, ROS, in single HeLa cells. The sensitizer used was protoporphyrin IX, PpIX, endogenously derived from 5-aminolevulinic acid delivered to the cells. Although we infer that singlet oxygen, O2(a(1)Δg), is one ROS produced upon irradiation of PpIX under these conditions, it is possible that the superoxide ion, O2(-˙), may also play a role in this system. With a "high" dose of PpIX-sensitized ROS, the expected death of the cell was observed. However, under "low dose" conditions, clear signs of cell proliferation were observed. The present results facilitate studies of ROS-mediated signalling in imaging-based single cell experiments.

[Safety Evaluation of Rare Sugar Syrup: Single-dose Oral Toxicity in Rats, Reverse Mutation Assay, Chromosome Aberration Assay, and Acute Non-Effect Level for Diarrhea of a Single Dose in Humans].

PubMed

Yamada, Takako; Iida, Tetsuo; Takamine, Satoshi; Hayashi, Noriko; Okuma, Kazuhiro

2015-01-01

The safety of rare sugar syrup obtained from high-fructose corn syrup under slightly alkaline conditions was studied. Mutagenicity of rare sugar syrup was assessed by a reverse mutation assay using Salmonella typhimurium and Escherichia coli, and an in vitro chromosomal aberration assay using Chinese hamster lung cell line (CHL/IU). No mutagenicity of rare sugar syrup was detected under these experimental conditions. Oral administration of single dose (15,000 mg/kg) of rare sugar syrup to rats caused no abnormalities, suggesting no adverse effect of rare sugar syrup. In humans, the acute non-effect level of rare sugar syrup for causing diarrhea was estimated as 0.9 g/kg body weight as dry solid base in both males and females.

Single dose treatment of malaria - current status and perspectives.

PubMed

Mischlinger, Johannes; Agnandji, Selidji T; Ramharter, Michael

2016-07-01

Despite increased international efforts for control and ultimate elimination, malaria remains a major health problem. Currently, artemisinin-based combination therapies are the treatment of choice for uncomplicated malaria exhibiting high efficacy in clinical trial settings in sub-Saharan Africa. However, their administration over a three-day period is associated with important problems of treatment adherence resulting in markedly reduced effectiveness of currently recommended antimalarials under real world settings. Antimalarial drug candidates and antimalarial drug combinations currently under advanced clinical development for the indication as single dose antimalarial therapy. Expert commentary: Several new drug candidates and combinations are currently undergoing pivotal proof-of-concept studies or clinical development programmes. The development of a single dose combination therapy would constitute a breakthrough in the control of malaria. Such an innovative treatment approach would simultaneously close the effectiveness gap of current three-day therapies and revolutionize population based interventions in the context of malaria elimination campaigns.

Aluminum surface modification by a non-mass-analyzed nitrogen ion beam

NASA Astrophysics Data System (ADS)

Ohira, Shigeo; Iwaki, Masaya

Non-mass-analyzed nitrogen ion implantation into polycrystal and single crystal aluminum sheets has been carried out at an accelerating voltage of 90 kV and a dose of 1 × 10 18 N ions/cm 2 using a Zymet implanter model Z-100. The pressure during implantation rose to 10 -3 Pa due to the influence of N gas feeding into the ion source. The characteristics of the surface layers were investigated by means of Auger electron spectroscopy (AES), X-ray diffraction (XRD), transmission electron diffraction (TED), and microscopy (TEM). The AES depth profiling shows a rectangular-like distribution of N atoms and little migration of O atoms near the surface. The high dose N-implantation forms c-axis oriented aluminum nitride (AIN) crystallines, and especially irradiation of Al single crystals with N ions leads to the formation of a hcp AlN single crystal. It is concluded that the high dose N-implantation in Al can result in the formation of AlN at room temperature without any thermal annealing. Furthermore, non-mass-analyzed N-implantation at a pressure of 10 -3 Pa of the nitrogen atmosphere causes the formation of pure AlN single crystals in the Al surface layer and consequently it can be practically used for AlN production.

Multiple anatomy optimization of accumulated dose

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

Watkins, W. Tyler, E-mail: watkinswt@virginia.edu; Siebers, Jeffrey V.; Moore, Joseph A.

Purpose: To investigate the potential advantages of multiple anatomy optimization (MAO) for lung cancer radiation therapy compared to the internal target volume (ITV) approach. Methods: MAO aims to optimize a single fluence to be delivered under free-breathing conditions such that the accumulated dose meets the plan objectives, where accumulated dose is defined as the sum of deformably mapped doses computed on each phase of a single four dimensional computed tomography (4DCT) dataset. Phantom and patient simulation studies were carried out to investigate potential advantages of MAO compared to ITV planning. Through simulated delivery of the ITV- and MAO-plans, target dosemore » variations were also investigated. Results: By optimizing the accumulated dose, MAO shows the potential to ensure dose to the moving target meets plan objectives while simultaneously reducing dose to organs at risk (OARs) compared with ITV planning. While consistently superior to the ITV approach, MAO resulted in equivalent OAR dosimetry at planning objective dose levels to within 2% volume in 14/30 plans and to within 3% volume in 19/30 plans for each lung V20, esophagus V25, and heart V30. Despite large variations in per-fraction respiratory phase weights in simulated deliveries at high dose rates (e.g., treating 4/10 phases during single fraction beams) the cumulative clinical target volume (CTV) dose after 30 fractions and per-fraction dose were constant independent of planning technique. In one case considered, however, per-phase CTV dose varied from 74% to 117% of prescription implying the level of ITV-dose heterogeneity may not be appropriate with conventional, free-breathing delivery. Conclusions: MAO incorporates 4DCT information in an optimized dose distribution and can achieve a superior plan in terms of accumulated dose to the moving target and OAR sparing compared to ITV-plans. An appropriate level of dose heterogeneity in MAO plans must be further investigated.« less

Error Types and Error Positions in Neglect Dyslexia: Comparative Analyses in Neglect Patients and Healthy Controls

ERIC Educational Resources Information Center

Weinzierl, Christiane; Kerkhoff, Georg; van Eimeren, Lucia; Keller, Ingo; Stenneken, Prisca

2012-01-01

Unilateral spatial neglect frequently involves a lateralised reading disorder, neglect dyslexia (ND). Reading of single words in ND is characterised by left-sided omissions and substitutions of letters. However, it is unclear whether the distribution of error types and positions within a word shows a unique pattern of ND when directly compared to…

Primary carcinoma of the distal male urethra: a case treated with lymphadenectomy and interstitial radiation therapy

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

Ticho, B.H.; Perez-Tamayo, C.; Konnak, J.W.

1988-06-01

We report a case of primary squamous cell carcinoma of the distal male urethra with a single inguinal node metastasis. Treatment consisted of unilateral pelvic and inguinal lymphadenectomy, and a combined course of external beam and interstitial radiation therapy to the distal urethra and penis by the Henschke modification of the Paris technique.

Bionic Running for Unilateral Transtibial Military Amputees

DTIC Science & Technology

2010-01-01

Bellman, R., 2010, “An Active Ankle-Foot Prosthesis With Biomechanical Energy Regeneration”, Transactions of the ASME Journal...Lefeber, D., 2008, “A Biomechanical Transtibial Prosthesis Powered by Pleated Pneumatic Artificial Muscles,” Model Identification and Control, 4, 394- 405. ...Inc., have designed, built, and demonstrated a first of its kind motor powered, single board computer controlled, running prosthesis for military

Quantifying metal artefact reduction using virtual monochromatic dual-layer detector spectral CT imaging in unilateral and bilateral total hip prostheses.

PubMed

Wellenberg, R H H; Boomsma, M F; van Osch, J A C; Vlassenbroek, A; Milles, J; Edens, M A; Streekstra, G J; Slump, C H; Maas, M

2017-03-01

To quantify the impact of prosthesis material and design on the reduction of metal artefacts in total hip arthroplasties using virtual monochromatic dual-layer detector Spectral CT imaging. The water-filled total hip arthroplasty phantom was scanned on a novel 128-slice Philips IQon dual-layer detector Spectral CT scanner at 120-kVp and 140-kVp at a standard computed tomography dose index of 20.0mGy. Several unilateral and bilateral hip prostheses consisting of different metal alloys were inserted and combined which were surrounded by 18 hydroxyapatite calcium carbonate pellets representing bone. Images were reconstructed with iterative reconstruction and analysed at monochromatic energies ranging from 40 to 200keV. CT numbers in Hounsfield Units (HU), noise measured as the standard deviation in HU, signal-to-noise-ratios (SNRs) and contrast-to-noise-ratios (CNRs) were analysed within fixed regions-of-interests placed in and around the pellets. In 70 and 74keV virtual monochromatic images the CT numbers of the pellets were similar to 120-kVp and 140-kVp polychromatic results, therefore serving as reference. A separation into three categories of metal artefacts was made (no, mild/moderate and severe) where pellets were categorized based on HU deviations. At high keV values overall image contrast was reduced. For mild/moderate artefacts, the highest average CNRs were attained with virtual monochromatic 130keV images, acquired at 140-kVp. Severe metal artefacts were not reduced. In 130keV images, only mild/moderate metal artefacts were significantly reduced compared to 70 and 74keV images. Deviations in CT numbers, noise, SNRs and CNRs due to metal artefacts were decreased with respectively 64%, 57%, 62% and 63% (p<0.001) compared to unaffected pellets. Optimal keVs, based on CNRs, for different unilateral and bilateral metal hip prostheses consisting of different metal alloys varied from 74 to 150keV. The Titanium alloy resulted in less severe artefacts and were reduced more effectively compared to the Cobalt alloy. Virtual monochromatic dual-layer Spectral CT imaging results in a significant reduction of streak artefacts produced by beam-hardening in mild and moderate artefacts by improving CT number accuracy, SNRs and CNRs, while decreasing noise values in a total hip arthroplasty phantom. An optimal monochromatic energy of 130keV was found ranging from 74keV to 150keV for different unilateral and bilateral hip prostheses consisting of different metal alloys. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Effects of tramadol alone, in combination with meloxicam or dipyrone, on postoperative pain and the analgesic requirement in dogs undergoing unilateral mastectomy with or without ovariohysterectomy.

PubMed

Teixeira, Renata Cr; Monteiro, Eduardo R; Campagnol, Daniela; Coelho, Karina; Bressan, Thais F; Monteiro, Betânia S

2013-11-01

To compare the effects of tramadol alone, or in combination with dipyrone or meloxicam, on postoperative pain and analgesia requirement after unilateral mastectomy with or without ovariohysterectomy in dogs. Prospective, randomized, clinical study. Twenty seven bitches undergoing unilateral mastectomy with or without ovariohysterectomy. Anesthesia was induced with propofol and maintained with isoflurane and a constant rate infusion of morphine. Before the end of surgery, dogs were randomly assigned to receive intravenous tramadol alone (3 mg kg(-1), group T), combined with dipyrone (30 mg kg(-1), group TD) or meloxicam (0.2 mg kg(-1), group TM). Dogs received additional doses of tramadol (groups T and TM) or tramadol with dipyrone (group TD) at 8 and 16 hours after extubation. Postoperative pain was assessed by a blinded observer before anesthesia (baseline) and at 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours after extubation using a visual analog scale (VAS) and a modified Glasgow scale. Rescue analgesia (morphine, 0.5 mg kg(-1)) was administered if the Glasgow pain score was >3.5. There were no significant differences among groups in pain scores evaluated by the VAS or the Glasgow scale. In groups T, TD and TM, pain scores were significantly higher than at baseline for 6, 8 and 2 hours, respectively. Rescue analgesia was administered to 3/9, 2/9 and 1/9 dogs in groups T, TD and TM, respectively (p > 0.05) [Correction added on 15 August 2013, after first online publication: 'T, TM and TD' was changed to 'T, TD and TM'.]. Under the conditions of this study, tramadol alone or in combination with dypyrone or meloxicam provided effective analgesia for 24 hours in most dogs after unilateral mastectomy with or without ovariohysterectomy. Further evaluation of combination therapies is needed in larger groups of dogs. © 2013 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.

The Effects of Pregabalin and the Glial Attenuator Minocycline on the Response to Intradermal Capsaicin in Patients with Unilateral Sciatica

PubMed Central

Sumracki, Nicole M.; Hutchinson, Mark R.; Gentgall, Melanie; Briggs, Nancy; Williams, Desmond B.; Rolan, Paul

2012-01-01

Background Patients with unilateral sciatica have heightened responses to intradermal capsaicin compared to pain-free volunteers. No studies have investigated whether this pain model can screen for novel anti-neuropathic agents in patients with pre-existing neuropathic pain syndromes. Aim This study compared the effects of pregabalin (300 mg) and the tetracycline antibiotic and glial attenuator minocycline (400 mg) on capsaicin-induced spontaneous pain, flare, allodynia and hyperalgesia in patients with unilateral sciatica on both their affected and unaffected leg. Methods/Results Eighteen patients with unilateral sciatica completed this randomised, double-blind, placebo-controlled, three-way cross-over study. Participants received a 10 µg dose of capsaicin into the middle section of their calf on both their affected and unaffected leg, separated by an interval of 75 min. Capsaicin-induced spontaneous pain, flare, allodynia and hyperalgesia were recorded pre-injection and at 5, 20, 40, 60 and 90 min post-injection. Minocycline tended to reduce pre-capsaicin injection values of hyperalgesia in the affected leg by 28% (95% CI 0% to 56%). The area under the effect time curves for capsaicin-induced spontaneous pain, flare, allodynia and hyperalgesia were not affected by either treatment compared to placebo. Significant limb differences were observed for flare (AUC) (−38% in affected leg, 95% CI for difference −19% to −52%). Both hand dominance and sex were significant covariates of response to capsaicin. Conclusions It cannot be concluded that minocycline is unsuitable for further evaluation as an anti-neuropathic pain drug as pregabalin, our positive control, failed to reduce capsaicin-induced neuropathic pain. However, the anti-hyperalgesic effect of minocycline observed pre-capsaicin injection is promising pilot information to support ongoing research into glial-mediated treatments for neuropathic pain. The differences in flare response between limbs may represent a useful biomarker to further investigate neuropathic pain. Inclusion of a positive control is imperative for the assessment of novel therapies for neuropathic pain. PMID:22685578

Effects of CDP-choline on striatal dopamine level and behavior in rats.

PubMed

Shibuya, M; Kageyama, N; Taniguchi, T; Hidaka, H; Fujiwara, M

1981-02-01

To further assess the effects of CDP (cytidine diphosphate)-choline on Parkinsonian symptoms, striatal dopamine (DA) was measured fluorometrically in rats after injection of CDP-choline. CDP-choline (300 mg/kg, i.p.) increased the DA content in the striatum (p less than 0.05) one hour after injection. The behavioral effect of CDP-choline was then tested in rats in which the unilateral nigro-striatal DA neurons had degenerated following an intranigral injection of 6-hydroxydopamine (6-OHDA). CDP-choline alone did not produce behavioral changes in these rats. However, pretreatment with a single dose of CDP-choline (900 mg/kg, i.p.) suppressed both the apomorphine-induced contralateral and the d-amphetamine-induced ipsilateral circling. The same dose of CDP-choline suppressed the number of treadmill revolutions in mice. On the other hand, a 7-day consecutive treatment with 300 mg/kg of CDP-choline enhanced the apomorphine-induced contralateral circling (by 42%, p less than 0.05). The same treatment with CDP-choline raised the striatal DA content by 29% (p less than 0.05) on the intact side, but not on the 6-OHDA injected side. These results indicate that CDP-choline has either a direct nor an indirect DA agonistic effect. The increase in DA content, decrease in locomotion and enhancement of the effect of apomorphine can be explained on the hypothesis that CDP-choline may act as an antagonist on the DA neurons and receptors. The validity of this apparently paradoxical use of CDP-choline with antagonistic effect on DA neurons in the treatment of Parkinson's disease is discussed.

Effect of vaccination with recombinant canine distemper virus vaccine immediately before exposure under shelter-like conditions.

PubMed

Larson, L J; Schultz, R D

2006-01-01

Vaccination with modified-live virus (MLV) canine distemper virus (CDV) vaccine has historically been recommended for animals in high-risk environments because of the rapid onset of immunity following vaccination. Recombinant CDV (rCDV) vaccine was deemed a suitable alternative to MLV-CDV vaccination in pet dogs, but insufficient data precluded its use where CDV was a serious threat to puppies, such as in shelters, kennels, and pet stores. In this study, dogs experimentally challenged hours after a single dose of rCDV or MLV vaccine became sick but recovered, whereas unvaccinated dogs became sick and died. Dogs vaccinated with a single dose of rCDV or MLV vaccine 1 week before being experimentally challenged remained healthy and showed no clinical signs. Dogs given one dose of rCDV vaccine hours before being placed in a CDV-contaminated environment did not become sick. These findings support the hypothesis that rCDV vaccine has a similar time-to-immunity as MLV-CDV vaccines and can likewise protect dogs in high-risk environments after one dose.

“Gunslinger’s gait”: a new cause of unilaterally reduced arm swing

PubMed Central

Araújo, Rui; Ferreira, Joaquim J; Antonini, Angelo

2015-01-01

Objective To postulate a new possible cause of a unilaterally reduced arm swing in addition to the known medical conditions such as shoulder pathology, Erb’s palsy, stroke, and Parkinson’s disease. Methods Analysis of YouTube videos depicting the gait of highly ranked Russian officials. Results We found a similar walking pattern in President Vladimir Putin, Prime Minister Dmitry Medvedev and three other highly ranked Russian officials, all presenting with a consistently reduced right arm swing in the absence of other overt neurological abnormalities. Conclusions We propose that this new gait pattern, which we term “gunslinger’s gait,” may result from a behavioural adaptation, possibly triggered by KGB or other forms of weapons training where trainees are taught to keep their right hand close to the chest while walking, allowing them to quickly draw a gun when faced with a foe. This should be included in the differential diagnosis of a unilaterally reduced arm swing. PMID:26666758

Dynamic contrast-enhanced breast MRI at 7 Tesla utilizing a single-loop coil: a feasibility trial.

PubMed

Umutlu, Lale; Maderwald, Stefan; Kraff, Oliver; Theysohn, Jens M; Kuemmel, Sherko; Hauth, Elke A; Forsting, Michael; Antoch, Gerald; Ladd, Mark E; Quick, Harald H; Lauenstein, Thomas C

2010-08-01

The aim of this study was to assess the feasibility of dynamic contrast-enhanced ultra-high-field breast imaging at 7 Tesla. A total of 15 subjects, including 5 patients with histologically proven breast cancer, were examined on a 7 Tesla whole-body magnetic resonance imaging system using a unilateral linearly polarized single-loop coil. Subjects were placed in prone position on a biopsy support system, with the coil placed directly below the region of interest. The examination protocol included the following sequences: 1) T2-weighted turbo spin echo sequence; 2) six dynamic T1-weighted spoiled gradient-echo sequences; and 3) subtraction imaging. Contrast-enhanced T1-weighted imaging at 7 Tesla could be obtained at high spatial resolution with short acquisition times, providing good image accuracy and a conclusively good delineation of small anatomical and pathological structures. T2-weighted imaging could be obtained with high spatial resolution at adequate acquisition times. Because of coil limitations, four high-field magnetic resonance examinations showed decreased diagnostic value. This first scientific approach of dynamic contrast-enhanced breast magnetic resonance imaging at 7 Tesla demonstrates the complexity of ultra-high-field breast magnetic resonance imaging and countenances the implementation of further advanced bilateral coil concepts to circumvent current limitations from the coil and ultra-high-field magnetic strength. 2010 AUR. Published by Elsevier Inc. All rights reserved.

Mumps Outbreak among Highly Vaccinated Teenagers and Children in the Central Region of Portugal, 2012-2013.

PubMed

Cordeiro, Eugénio; Ferreira, Muriel; Rodrigues, Fernanda; Palminha, Paula; Vinagre, Elsa; Pimentel, João Pedro

2015-01-01

Mumps vaccine was introduced in the National Immunization Program in Portugal in 1987, rapidly reaching a national coverage > 92%, with important reduction in the annual incidence of the disease. We report a mumps outbreak in the Central Region of Portugal, occurred in the winter 2012-13. Cases of salivary-gland swelling and other symptoms compatible with mumps were investigated. Geodemographics, clinical, laboratory and vaccination data were analyzed. Over six months, 148 outbreak-related cases were reported: 87.8% occurred in three of the 16 affected counties and 78.4% had a known epidemiological link. Median age was 14.5 years (2-62) and 70.3% were 11-20 years old; 61.5% were male. The mean duration of disease was seven days (2-20). The disease was generally mild; 80.4% had fever and in 55.4% there was unilateral involvement of the parotid gland. Seven cases had orchitis, one oophoritis and one had nephritis. Two cases were hospitalized. School transmission predominated and class attack rates were < 30%. Most of the cases occurred in vaccinated individuals (92%) of whom 86.8% had received 2 doses; 17.7% had received one dose of the vaccine containing the Rubini strain. Mumps virus genotype G was identified in 4 cases. This mumps outbreak among a highly vaccinated population, occurring mostly in teenagers at school, could be due to the partial effectiveness of the vaccine against the disease (particularly in the group vaccinated with Rubini strain), waning immunity overtime and genotype mismatch. This outbreak report shows the importance of discussion about the need of more booster dose of the actual vaccine or new vaccine including more genotypes to improve immunogenicity.

Effectiveness and Safety of Spot Scanning Proton Radiation Therapy for Chordomas and Chondrosarcomas of the Skull Base: First Long-Term Report

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

Ares, Carmen, E-mail: carmen.ares@psi.c; Hug, Eugen B.; Lomax, Antony J.

2009-11-15

Purpose: To evaluate effectiveness and safety of spot-scanning-based proton radiotherapy (PT) in skull-base chordomas and chondrosarcomas. Methods and Materials: Between October 1998 and November 2005, 64 patients with skull-base chordomas (n = 42) and chondrosarcomas (n = 22) were treated at Paul Scherrer Institute with PT using spot-scanning technique. Median total dose for chordomas was 73.5 Gy(RBE) and 68.4 Gy(RBE) for chondrosarcomas at 1.8-2.0 Gy(RBE) dose per fraction. Local control (LC), disease specific survival (DSS), and overall survival (OS) rates were calculated. Toxicity was assessed according to CTCAE, v. 3.0. Results: Mean follow-up period was 38 months (range, 14-92 months).more » Five patients with chordoma and one patient with chondrosarcoma experienced local recurrence. Actuarial 5-year LC rates were 81% for chordomas and 94% for chondrosarcomas. Brainstem compression at the time of PT (p = 0.007) and gross tumor volume >25 mL (p = 0.03) were associated with lower LC rates. Five years rates of DSS and OS were 81% and 62% for chordomas and 100% and 91% for chondrosarcomas, respectively. High-grade late toxicity consisted of one patient with Grade 3 and one patient with Grade 4 unilateral optic neuropathy, and two patients with Grade 3 central nervous system necrosis. No patient experienced brainstem toxicity. Actuarial 5-year freedom from high-grade toxicity was 94%. Conclusions: Our data indicate safety and efficacy of spot-scanning based PT for skull-base chordomas and chondrosarcomas. With target definition, dose prescription and normal organ tolerance levels similar to passive-scattering based PT series, complication-free, tumor control and survival rates are at present comparable.« less

The Incidence of Atypical Femoral Fractures in Patients with Rheumatic Disease: Yamagata Prefectural Committee of Atypical Femoral Fractures (YamaCAFe) Study.

PubMed

Takakubo, Yuya; Ohta, Daichi; Ishi, Masaji; Ito, Juji; Oki, Hiroharu; Naganuma, Yasushi; Uno, Tomohiro; Sasaki, Akiko; Akabane, Takeru; Dairaku, Katsuyuki; Goto, Shinichi; Goto, Yasuo; Kanauchi, Yumiko; Kobayashi, Shinji; Nakajima, Taku; Masuda, Keiji; Matsuda, Michiharu; Mura, Nariyuki; Takenouchi, Kenji; Tsuchida, Hiroyuki; Onuma, Yasushi; Shibuya, Junichirou; Seino, Mitsuyoshi; Yamaguchi, Osamu; Hiragami, Ken; Urayama, Yasuhiro; Furukawa, Takashi; Okuda, Shouta; Ogura, Ken; Nakamura, Takeshi; Sasaki, Kan; Konta, Tsuneo; Takagi, Michiaki

2017-08-01

Atypical femoral fractures (AFFs) have been reported to occur with minimal or spontaneous subtrochanteric and femoral shaft fractures with a characteristic transverse pattern, compared with typical femoral fractures in young patients with high-energy trauma. AFFs are related to long-term use of bisphosphonates (BPs), glucocorticoids and rheumatic diseases. We have estimated a blind analysis of AFFs in rheumatic patients receiving BPs and glucocorticoids ordinary over a long time in all Yamagata prefectural area through radiographic examination. The 123 AFFs including suspected cases over six years were collected and reviewed by two independent orthopedic surgeons. We found 86 patients with a total of 99 AFFs between 2009 and 2014 (1.43 cases/100,000 person/year). Of these 99 AFFs, 11 were in 8 rheumatic patients including three patients with bilateral AFFs. The incidence of AFFs in rheumatic patients had trend to increase from 2012. The mean age of all 8 patients was 54.9 years. All 8 patients received BPs and 7/8 received prednisolone (PSL). The mean dose of PSL was 14 mg/day. Compared to patients with unilateral AFFs, those with bilateral AFFs in rheumatic patients were on a higher dose of PSL (20 mg/day vs. 7 mg/day) and had less femoral neck-shaft angle (129° vs. 136°, p < 0.05). In conclusion, the incidence of AFFs in rheumatic patients showed a trend to increase from 2012 to 2014 in Yamagata prefecture. Careful management of AFFs is of particular importance in rheumatic patients who have taken high doses of PSL and have small femoral neck-shaft angle.

Efficient production of therapeutic doses of [131I]-metaiodobenzylguanidine for clinical use.

PubMed

Prabhakar, G; Mathur, Anupam; Shunmugam, G; Teje, Y D; Sachdev, S S; Sivaprasad, N

2011-01-01

[(131)I]-metaiodobenzylguanidine (mIBG) is a known radiopharmaceutical used for the treatment of neuroendocrine tumors. The development of therapeutic [(131)I]-mIBG doses at production level is highly challenging due to rapid product degradation and high radiation exposures to the production plant personnel. In the present work, a working module for the production of 10 doses (100 mCi each) in a single operation was developed following copper (I) assisted isotope exchange. The labeled product complies with the pharmaceutical specifications suitable for in-vivo patient use. Copyright © 2010 Elsevier Ltd. All rights reserved.

Safety and Pharmacokinetics of Multiple 750-Milligram Doses of Intravenous Levofloxacin in Healthy Volunteers

PubMed Central

Chow, Andrew T.; Fowler, Cynthia; Williams, R. Rex; Morgan, Nancy; Kaminski, Susan; Natarajan, Jaya

2001-01-01

The safety and pharmacokinetics of a once-daily high intravenous dose of levofloxacin (750 mg) in 18 healthy volunteers were studied in a double-blind, randomized, placebo-controlled, single-center parallel group study. Levofloxacin was well tolerated, and higher maximum concentration of drug in serum and area under the concentration-time curve values were achieved. For difficult-to-treat infections, high daily doses of levofloxacin may be beneficial, and intravenous administration may be preferred in certain clinical settings, such as when treating patients in intensive care units, warranting further evaluation. PMID:11408234

Safety and pharmacokinetics of multiple 750-milligram doses of intravenous levofloxacin in healthy volunteers.

PubMed

Chow, A T; Fowler, C; Williams, R R; Morgan, N; Kaminski, S; Natarajan, J

2001-07-01

The safety and pharmacokinetics of a once-daily high intravenous dose of levofloxacin (750 mg) in 18 healthy volunteers were studied in a double-blind, randomized, placebo-controlled, single-center parallel group study. Levofloxacin was well tolerated, and higher maximum concentration of drug in serum and area under the concentration-time curve values were achieved. For difficult-to-treat infections, high daily doses of levofloxacin may be beneficial, and intravenous administration may be preferred in certain clinical settings, such as when treating patients in intensive care units, warranting further evaluation.

Influence of nonylphenol and octylphenol exposure on 5-HT, 5-HT transporter, and 5-HT2A receptor.

PubMed

Liu, Chunhong; Lai, Yuting; Ouyang, Junyan; Yang, Tongwang; Guo, Youting; Yang, Jie; Huang, Shaowen

2017-03-01

Nonylphenol (NP) and octylphenol (OP) are priority environmental contaminants that have a potential role as endocrine disruptors. They can be biomagnified in the food chain and pose an estrogenic health risk to human health. A 28-day oral toxicity study was performed to observe the impact of single and combined exposure to NP and OP on 5-HT transporter (SERT) as well as 5-HT 2A receptor. Results showed that the 5-HT levels in rat plasma increased with exposure to middle-dose and high-dose NP, to high-dose OP, and to low, middle, and high doses of combined NP and OP (P < 0.05), while the 5-HT levels in rat platelets increased when exposed to NP/OP or combined NP and OP of middle or high dose (P < 0.05). The expression levels of SERT in rat platelets decreased when exposed to high-dose NP/OP or high dose of combined NP and OP (P < 0.05). Meanwhile, the expression levels of 5-HT 2A in rat platelets decreased when exposed to high-dose NP/OP as well as combined NP and OP (P < 0.05). These findings suggested that exposure to NP and OP could influence the metabolic network of 5-hydroxytryptamine via transportation and receptor binding pathways.

Pharmacokinetics of voriconazole after oral administration of single and multiple doses in African grey parrots (Psittacus erithacus timneh).

PubMed

Flammer, Keven; Nettifee Osborne, Julie A; Webb, Donna J; Foster, Laura E; Dillard, Stacy L; Davis, Jennifer L

2008-01-01

To determine the pharmacokinetics and safety of orally administered voriconazole in African grey parrots. 20 clinically normal Timneh African grey parrots (Psittacus erithacus timneh). In single-dose trials, 12 parrots were each administered 6, 12, and 18 mg of voriconazole/kg orally and plasma concentrations of voriconazole were determined via high-pressure liquid chromatography. In a multiple-dose trial, voriconazole (18 mg/kg) was administered orally to 6 birds every 12 hours for 9 days; a control group (2 birds) received tap water. Treatment effects were assessed via observation, clinicopathologic analyses (3 assessments), and measurement of trough plasma voriconazole concentrations (2 assessments). Voriconazole's elimination half-life was short (1.1 to 1.6 hours). Higher doses resulted in disproportional increases in the maximum plasma voriconazole concentration and area under the curve. Trough plasma voriconazole concentrations achieved in the multiple-dose trial were lower than those achieved after administration of single doses. Polyuria (the only adverse treatment effect) developed in treated and control birds but was more severe in the treatment group. In African grey parrots, voriconazole has dose-dependent pharmacokinetics and may induce its own metabolism. Oral administration of 12 to 18 mg of voriconazole/kg twice daily is a rational starting dose for treatment of African grey parrots infected with Aspergillus or other fungal organisms that have a minimal inhibitory concentration for voriconazole < or = 0.4 microg/mL. Higher doses may be needed to maintain plasma voriconazole concentrations during long-term treatment. Safety and efficacy of various voriconazole treatment regimens in this species require investigation.

Staged bilateral single-port thoracoscopic lung volume reduction surgery: A report of 11 cases

PubMed Central

Zhang, Miao; Wang, Heng; Pan, Xue-Feng; Wu, Wen-Bin; Zhang, Hui

2016-01-01

The aim of the present study was to investigate the feasibility and efficacy of staged bilateral single-port thoracoscopic lung volume reduction surgery (LVRS) for patients with chronic obstructive pulmonary emphysema (COPE). Eleven male patients with a mean age of 60.27±12.11 years with bilateral COPE and bullae were admitted to the Department of Thoracic Surgery, Xuzhou Central Hospital from January 2013 to June 2014. The patients underwent staged bilateral single-port thoracoscopic LVRS. The hyperinflated bullae were resected using endoscopic staplers (Endo-GIA), followed by continuous suture and biological glue for reinforcement of the margin. In addition, pulmonary function, blood gas assay, 6-min walk distance (6MWD) and life quality evaluated by a short form 36-item health survey questionnaire (SF-36) were recorded before and after LVRS, respectively. All the patients survived after surgery. The chest tube drainage time was 9.09±1.31 days and postoperative hospital stay was 15.73±2.75 days, with 5 cases of persistent air leakage and 7 cases of pulmonary infection which were finally cured. The patients were followed up for 3 to 12 months, and the pulmonary function, partial pressure of oxygen (pO2), 6MWD and life quality after unilateral or bilateral LVRS were improved compared to these parameters before surgery. However, there was no significant difference between unilateral and bilateral LVRS in terms of life quality. In conclusion, staged bilateral single-port thoracoscopic LVRS may improve the short-term life quality of patients with COPE. PMID:27882084

Defining unnecessary disinfection procedures for single-dose and multiple-dose vials.

PubMed

Buckley, T; Dudley, S M; Donowitz, L G

1994-11-01

Recommendations in the literature conflict on the necessity of disinfecting single-use vials prior to aspiration of fluid. Interventions to disinfect the stopper surface on multiple-dose vials vary considerably. To determine the necessity of alcohol disinfection of the stopper on single-dose vials and to compare povidone-iodine and alcohol versus alcohol-only disinfection of the stopper prior to each needle penetration on multiple-dose vials. The rubber stopper surfaces of 100 single-dose vials were cultured for the presence of bacteria. To determine the efficacy of two procedures for disinfection of multiple-dose vials, 87 stopper surfaces routinely disinfected with both povidone-iodine and alcohol were cultured for bacteria. After a change in practice, 100 multiple-dose vials routinely disinfected with alcohol only were cultured for the presence of bacteria. Of the cultures done on single-dose vial stoppers, 99% were sterile. A comparison of the two disinfection techniques for multiple-dose vials revealed that 83 (95%) of the 87 vials prepped with both povidone-iodine and alcohol were sterile, compared with all stoppers disinfected with alcohol only. This study shows the lack of necessity of any disinfection procedure on the rubber stopper of single-dose vials and the efficacy of alcohol only for disinfecting the stopper of multiple-dose vials.

Bone architecture adaptations after spinal cord injury: impact of long-term vibration of a constrained lower limb

PubMed Central

Dudley-Javoroski, S.; Petrie, M. A.; McHenry, C. L.; Amelon, R. E.; Saha, P. K.

2015-01-01

Summary This study examined the effect of a controlled dose of vibration upon bone density and architecture in people with spinal cord injury (who eventually develop severe osteoporosis). Very sensitive computed tomography (CT) imaging revealed no effect of vibration after 12 months, but other doses of vibration may still be useful to test. Introduction The purposes of this report were to determine the effect of a controlled dose of vibratory mechanical input upon individual trabecular bone regions in people with chronic spinal cord injury (SCI) and to examine the longitudinal bone architecture changes in both the acute and chronic state of SCI. Methods Participants with SCI received unilateral vibration of the constrained lower limb segment while sitting in a wheelchair (0.6g, 30 Hz, 20 min, three times weekly). The opposite limb served as a control. Bone mineral density (BMD) and trabecular micro-architecture were measured with high-resolution multi-detector CT. For comparison, one participant was studied from the acute (0.14 year) to the chronic state (2.7 years). Results Twelve months of vibration training did not yield adaptations of BMD or trabecular micro-architecture for the distal tibia or the distal femur. BMD and trabecular network length continued to decline at several distal femur sub-regions, contrary to previous reports suggesting a “steady state” of bone in chronic SCI. In the participant followed from acute to chronic SCI, BMD and architecture decline varied systematically across different anatomical segments of the tibia and femur. Conclusions This study supports that vibration training, using this study’s dose parameters, is not an effective antiosteoporosis intervention for people with chronic SCI. Using a high-spatial-resolution CT methodology and segmental analysis, we illustrate novel longitudinal changes in bone that occur after spinal cord injury. PMID:26395887

Testing the effects of long-acting steroids in edema and ecchymosis after closed rhinoplasty

PubMed Central

Gutierrez, Santiago; Wuesthoff, Carolina

2014-01-01

BACKGROUND: Steroids have proven to be of some benefit in rhinoplasty edema and ecchymosis when administered at a high and repeated dose. OBJECTIVE: To evaluate the effects of single-dose, long-acting intramuscular steroids on postoperative edema and ecchymosis after closed rhinoplasty with osteotomies compared with placebo. METHODS: A randomized, double-blinded, placebo-controlled trial was performed. Fifty-four patients were randomly assigned to two groups: 28 received a single dose of long-acting dexamethasone (mean [± SD] dose 16±4 mg) immediately before anesthetic induction; the remaining 26 received an intramuscular injection of saline solution. The same surgeon performed all surgeries, with patients under general anesthesia. Acetaminophen was the only analgesic used to control postoperative pain. High-resolution digital photographs were taken on postoperative days 1, 3, 7 and 14. Scoring was performed separately for eyelid swelling and ecchymosis by an independent observer using a graded scale (0 to 5) for edema and a scoring system (0 to 13) for ecchymosis. RESULTS: No statistically significant differences in terms of age, sex or amount of bleeding during surgery were found between the two groups. No statistically significant difference was observed in the decrease of both ecchymosis and edema between placebo and high-dose, long-acting dexamethasone. A statistically significant difference in operation time was found, favouring the steroid group. No severe complications were observed due to steroid use. DISCUSSION: Osteotomies are basically a form of (controlled) trauma, with considerable disruption of the abundant blood vessels in this facial region and, therefore, are associated with with undesirable effects. A recent meta-analysis failed to show benefits of the use of steroids after postoperative day 3. Only a trend toward reduction in edema and ecchymosis with the use of long-acting steroids compared with placebo was demonstrated in the present study. CONCLUSION: There was no benefit in administering single-dose, long-acting steroids in patients undergoing closed rhinoplasty with osteotomies. PMID:25114618

Fulminant bilateral papilloedema during low-dose steroid taper in a child with systemic idiopathic arthritis treated with tocilizumab.

PubMed

Burstzyn, Lulu; Levin, Simon; Rotenberg, Brian; Van Hooren, Tamara; Leung, Andrew; Berard, Roberta; Ardelean, Daniela S

2017-01-01

Systemic juvenile idiopathic arthritis (SJIA) is one of the most severe forms of arthritis that affects children younger than 16 years of age at onset. SJIA often requires corticosteroids to control the inflammation. However, long-term corticosteroid use may have adverse effects, including intracranial hypertension (IH). Biologic therapies have been used as corticosteroid sparing agents. We report the first case of a child with steroid-dependent SJIA treated with tocilizumab, an IL-6 receptor monoclonal antibody, who developed fulminant IH, bilateral papilloedema and vision loss when oral prednisone was weaned from 2 to 1 mg per day. Despite repeated lumbar punctures and high dose acetazolamide, he required urgent unilateral optic nerve sheath fenestration (ONSF). This endoscopic surgical intervention released the pressure exerted by the cerebrospinal fluid on the optic nerve and stopped the progression of vision loss. Nine weeks after the diagnosis of bilateral papilloedema, his vision was completely restored in one eye and partially recovered in the contralateral one. Long-term treatment with corticosteroids even at very low dose and tocilizumab may predispose to severe IH, papilloedema and vision loss. The role that tocilizumab might have played in this case in unclear. Early recognition and prompt treatment of papilloedema is crucial in avoiding permanent vision loss. Fulminant papilloedema in an immunocompromised child carries additional significant challenges. Early ONSF is a safe and effective intervention in refractory papilloedema. Children with severe papilledema secondary to IH should be managed by a multidisciplinary team in tertiary centres.

Single Low Dose Primaquine (0.25mg/kg) Does Not Cause Clinically Significant Haemolysis in G6PD Deficient Subjects

PubMed Central

Bancone, Germana; Chowwiwat, Nongnud; Somsakchaicharoen, Raweewan; Poodpanya, Lalita; Moo, Paw Khu; Gornsawun, Gornpan; Kajeechiwa, Ladda; Thwin, May Myo; Rakthinthong, Santisuk; Nosten, Suphak; Thinraow, Suradet; Nyo, Slight Naw; Ling, Clare L.; Wiladphaingern, Jacher; Kiricharoen, Naw Lily; Moore, Kerryn A.; White, Nicholas J.; Nosten, Francois

2016-01-01

Background Primaquine is the only drug consistently effective against mature gametocytes of Plasmodium falciparum. The transmission blocking dose of primaquine previously recommended was 0.75mg/kg (adult dose 45mg) but its deployment was limited because of concerns over haemolytic effects in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency. G6PD deficiency is an inherited X-linked enzymatic defect that affects an estimated 400 million people around the world with high frequencies (15–20%) in populations living in malarious areas. To reduce transmission in low transmission settings and facilitate elimination of P. falciparum, the World Health Organization now recommends adding a single dose of 0.25mg/kg (adult dose 15mg) to Artemisinin-based Combination Therapies (ACTs) without G6PD testing. Direct evidence of the safety of this low dose is lacking. Adverse events and haemoglobin variations after this treatment were assessed in both G6PD normal and deficient subjects in the context of targeted malaria elimination in a malaria endemic area on the North-Western Myanmar-Thailand border where prevalence of G6PD deficiency (Mahidol variant) approximates 15%. Methods and Findings The tolerability and safety of primaquine (single dose 0.25 mg base/kg) combined with dihydroartemisinin-piperaquine (DHA-PPQ) given three times at monthly intervals was assessed in 819 subjects. Haemoglobin concentrations were estimated over the six months preceding the ACT + primaquine rounds of mass drug administration. G6PD deficiency was assessed with a phenotypic test and genotyping was performed in male subjects with deficient phenotypes and in all females. Fractional haemoglobin changes in relation to G6PD phenotype and genotype and primaquine round were assessed using linear mixed-effects models. No adverse events related to primaquine were reported during the trial. Mean fractional haemoglobin changes after each primaquine treatment in G6PD deficient subjects (-5.0%, -4.2% and -4.7%) were greater than in G6PD normal subjects (0.3%, -0.8 and -1.7%) but were clinically insignificant. Fractional drops in haemoglobin concentration larger than 25% following single dose primaquine were observed in 1.8% of the population but were asymptomatic. Conclusions The single low dose (0.25mg/kg) of primaquine is clinically well tolerated and can be used safely without prior G6PD testing in populations with high prevalence of G6PD deficiency. The present evidence supports a broader use of low dose primaquine without G6PD testing for the treatment and elimination of falciparum malaria. Trial Registration ClinicalTrials.gov NCT01872702 PMID:27010542

A Long-Acting Human Growth Hormone With Delayed Clearance (VRS-317): Results of a Double-Blind, Placebo-Controlled, Single Ascending Dose Study in Growth Hormone–Deficient Adults

PubMed Central

Yuen, Kevin C. J.; Conway, Gerard S.; Popovic, Vera; Merriam, George R.; Bailey, Timothy; Hamrahian, Amir H.; Biller, Beverly M. K.; Kipnes, Mark; Moore, Jerome A.; Humphriss, Eric; Cleland, Jeffrey L.

2013-01-01

Background: Administration of daily recombinant human GH (rhGH) poses a considerable challenge to patient compliance. Reduced dosing frequency may improve treatment adherence and potentially overall treatment outcomes. Objectives: This study assessed the safety and tolerability and the potential for achieving IGF-I levels within the target range in adults with GH deficiency after a single dose of the long-acting rhGH analog, VRS-317. Design: This was a randomized, double-blind, placebo-controlled, single ascending dose study. Patients: Fifty adults with growth hormone deficiency (mean age, 45 years) were studied in 5 treatment groups of 10 subjects each (8 active drug and 2 placebo). Setting: The study was conducted in 17 adult endocrinology centers in North America and Europe. Main Outcome Measures: Adverse events, laboratory safety assessments, and VRS-317 pharmacokinetics and pharmacodynamics (IGF-I and IGF binding protein-3) were analyzed. Results: At 0.80 mg/kg, VRS-317 had a mean terminal elimination half-life of 131 hours. Single VRS-317 doses of 0.05, 0.10, 0.20, 0.40, and 0.80 mg/kg (approximately equivalent to daily rhGH doses of 0.3–5.0 μg/kg over 30 d) safely increased the amplitude and duration of IGF-I responses in a dose-dependent manner. After a single 0.80 mg/kg dose, serum IGF-I was maintained in the normal range between −1.5 and 1.5 SD values for a mean of 3 weeks. No unexpected or serious adverse events were observed. Conclusions: The elimination half-life for VRS-317 is 30- to 60-fold longer and stimulates more durable IGF-I responses than previously studied rhGH products. Prolonged IGF-I responses do not come at the expense of overexposure to high IGF-I levels. The pharmacokinetics and pharmacodynamics combined with the observed safety profile indicate the potential for safe and effective monthly dosing. PMID:23585663

Corticosteroid injection for the treatment of carpal tunnel syndrome

PubMed Central

O'Gradaigh, D; Merry, P

2000-01-01

OBJECTIVE—To compare low and high dose, and short and long acting corticosteroids in the treatment of carpal tunnel syndrome.
METHODS—A randomised, controlled, single blind trial with electromyographic and subjective outcome measures.
RESULTS—25 mg hydrocortisone is as effective as higher doses or long acting triamcinolone at a six week and six month follow up.
CONCLUSION—As low dose steroid is as effective, and potentially less toxic, this should be the recommended dose for injection of carpal tunnel syndrome.

 PMID:11053073

Absolute bioavailability and pharmacokinetics of avosentan in man.

PubMed

Dieterle, W; Hengelage, T

2009-09-01

Avosentan is a potent, selective endothelin A receptor blocker. The pharmacokinetics of avosentan were investigated in healthy male and female volunteers, following oral and i.v. administration of single doses of avosentan and its absolute bioavailability was determined. In a randomized, balanced open-label, three-period oral crossover study, 26 healthy subjects (19 males and 7 females) received Treatments A, B and C. Treatment A consisted of a single dose of a 25 mg film-coated tablet of avosentan, Treatment B of a single dose of a 50 mg film-coated tablet of avosentan and Treatment C of 10 mg avosentan in 20 ml solution for infusion for 20 minutes (10 mg avosentan in 20 ml phosphate buffer pH 9.0 containing 1% polysorbate 20). Plasma concentrations of avosentan and its hydroxymethyl metabolite Ro 68-5925 were measured by liquid chromatography-tandem mass spectrometry. The absolute bioavailability values (compared with i.v. infusion) for the 25 and 50 mg film-coated tablets were 81% and 72%, respectively. The extent of absorption, as measured by partial and total AUC, increased almost proportionally with the dose. The estimated proportionality coefficient for AUC0- yen was 1.12 (90% CI 1.06, 1.18). For the rate of absorption (Cmax) strict dose-proportionality was not demonstrated (proportionality coefficient 1.13 (90% CI 1.0, 1.28)). No relevant gender differences in the pharmacokinetic characteristics were evident after a single i.v. dose and at an oral dose of 25 mg, whereas after oral administration of 50 mg of avosentan differences were seen in Cmax and t1/2. The absolute bioavailability of avosentan film-coated tablets is high, i.e. 70 - 80%.

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.

Dopamine D2 receptor-mediated G-protein activation in rat striatum: functional autoradiography and influence of unilateral 6-hydroxydopamine lesions of the substantia nigra.

PubMed

Newman-Tancredi, A; Cussac, D; Brocco, M; Rivet, J M; Chaput, C; Touzard, M; Pasteau, V; Millan, M J

2001-11-30

Unilateral 6-hydroxydopamine (6-OHDA) lesions of substantia nigra pars compacta (SNPC) neurons in rats induce behavioural hypersensitivity to dopaminergic agonists. However, the role of specific dopamine receptors is unclear, and potential alterations in their transduction mechanisms remain to be evaluated. The present study addressed these issues employing the dopaminergic agonist, quinelorane, which efficaciously stimulated G-protein activation (as assessed by [35S]GTPgammaS binding) at cloned hD2 (and hD3) receptors. At rat striatal membranes, dopamine stimulated [35S]GTPgammaS binding by 1.9-fold over basal, but its actions were only partially reversed by the selective D2/D3 receptor antagonist, raclopride, indicating the involvement of other receptor subtypes. In contrast, quinelorane-induced stimulation (48% of the effect of dopamine) was abolished by raclopride, and by the D2 receptor antagonist, L741,626. Further, novel antagonists selective for D3 and D4 receptors, S33084 and S18126, respectively, blocked the actions of quinelorane at concentrations corresponding to their affinities for D2 receptors. Quinelorane potently induced contralateral rotation in unilaterally 6-OHDA-lesioned rats, an effect abolished by raclopride and L741,626, but not by D3 and D4 receptor-selective doses of S33084 and S18126, respectively. In functional ([35S]GTPgammaS) autoradiography experiments, quinelorane stimulated G-protein activation in caudate putamen and, to a lesser extent, in nucleus accumbens and cingulate cortex of naive rats. In unilaterally SNPC-lesioned rats, quinelorane-induced G-protein activation in the caudate putamen on the non-lesioned side was similar to that seen in naive animals (approximately 50% stimulation), but significantly greater on the lesioned side (approximately 80%). This increase was both pharmacologically and regionally specific since it was reversed by raclopride, and was not observed in nucleus accumbens or cingulate cortex. In conclusion, the present data indicate that, in rat striatum, the actions of quinelorane are mediated primarily by D2 receptors, and suggest that behavioural hypersensitivity to this agonist, induced by unilateral SNPC lesions, is associated with an increase in D2, but not D3 or D4, receptor-mediated G-protein activation.

Time-course study of different innate immune mediators produced by UV-irradiated skin: comparative effects of short and daily versus a single harmful UV exposure.

PubMed

Cela, Eliana M; Friedrich, Adrian; Paz, Mariela L; Vanzulli, Silvia I; Leoni, Juliana; González Maglio, Daniel H

2015-05-01

The modulatory effects of solar UV radiation on the immune system have been widely studied. As the skin is the main target of UV radiation, our purpose was to compare the impact on skin innate immunity of two contrasting ways to be exposed to sunlight. Hairless mice were UV irradiated with a single high UV dose simulating a harmful exposure, or with repetitive low UV doses simulating short occasional daily exposures. Skin samples were taken at different times after UV irradiation to evaluate skin histology, inflammatory cell recruitment, epidermal T-cell population and the mitochondrial function of epidermal cells. The transcriptional profiles of pro-inflammatory cytokines, chemokines, antimicrobial peptides and Toll-like receptors were evaluated by RT-PCR and ELISA in tissue homogenates. Finally, a lymphangiography was performed to assess modification in the lymphatic vessel system. A single high UV dose produces a deep inflammatory state characterized by the production of pro-inflammatory cytokines and chemokines that, in turn, induces the recruitment of neutrophils and macrophages into the irradiated area. On the other hand, repetitive low UV doses drive the skin to a photo-induced alert state in which there is no sign of inflammation, but the epithelium undergoes changes in thickness, the lymphatic circulation increases, and the transcription of antimicrobial peptides is induced. © 2014 John Wiley & Sons Ltd.

Determinants of antibody persistence across doses and continents after single-dose rVSV-ZEBOV vaccination for Ebola virus disease: an observational cohort study.

PubMed

Huttner, Angela; Agnandji, Selidji Todagbe; Combescure, Christophe; Fernandes, José F; Bache, Emmanuel Bache; Kabwende, Lumeka; Ndungu, Francis Maina; Brosnahan, Jessica; Monath, Thomas P; Lemaître, Barbara; Grillet, Stéphane; Botto, Miriam; Engler, Olivier; Portmann, Jasmine; Siegrist, Denise; Bejon, Philip; Silvera, Peter; Kremsner, Peter; Siegrist, Claire-Anne

2018-04-04

The recombinant vesicular stomatitis virus (rVSV) vaccine expressing the Zaire Ebola virus (ZEBOV) glycoprotein is efficacious in the weeks following single-dose injection, but duration of immunity is unknown. We aimed to assess antibody persistence at 1 and 2 years in volunteers who received single-dose rVSV-ZEBOV in three previous trials. In this observational cohort study, we prospectively followed-up participants from the African and European phase 1 rVSV-ZEBOV trials, who were vaccinated once in 2014-15 with 300 000 (low dose) or 10-50 million (high dose) plaque-forming units (pfu) of rVSV-ZEBOV vaccine to assess ZEBOV glycoprotein (IgG) antibody persistence. The primary outcome was ZEBOV glycoprotein-specific IgG geometric mean concentrations (GMCs) measured yearly by ELISA compared with 1 month (ie, 28 days) after immunisation. We report GMCs up to 2 years (Geneva, Switzerland, including neutralising antibodies up to 6 months) and 1 year (Lambaréné, Gabon; Kilifi, Kenya) after vaccination and factors associated with higher antibody persistence beyond 6 months, according to multivariable analyses. Trials and the observational study were registered at ClinicalTrials.gov (Geneva: NCT02287480 and NCT02933931; Kilifi: NCT02296983) and the Pan-African Clinical Trials Registry (Lambaréné PACTR201411000919191). Of 217 vaccinees from the original studies (102 from the Geneva study, 75 from the Lambaréné study, and 40 from the Kilifi study), 197 returned and provided samples at 1 year (95 from the Geneva study, 63 from the Lambaréné, and 39 from the Kilifi study) and 90 at 2 years (all from the Geneva study). In the Geneva group, 44 (100%) of 44 participants who had been given a high dose (ie, 10-50 million pfu) of vaccine and who were seropositive at day 28 remained seropositive at 2 years, whereas 33 (89%) of 37 who had been given the low dose (ie, 300 000 pfu) remained seropositive for 2 years (p=0·042). In participants who had received a high dose, ZEBOV glycoprotein IgG GMCs decreased significantly between their peak (at 1-3 months) and month 6 after vaccination in Geneva (p<0·0001) and Lambaréné (p=0·0298) but not in Kilifi (p=0·5833) and subsequently remained stable at all sites apart from Geneva, where GMC in those given a high dose of vaccine increased significantly between 6 months and 1 year (p=0·0264). Antibody persistence was similar at 1 year and at 6 months in those who had received a low dose of vaccine, with lower titres among participants from the Geneva study at 2 years than at 1 year after vaccination (GMC ratio 0·61, 95% CI 0·49-0·77; p<0·0001). In multivariable analyses, predictors of increased IgG GMCs beyond 6 months included high-dose versus low-dose vaccination (Geneva p=0·0133; Lambaréné p=0·008) and vaccine-related arthritis (p=0·0176), but not sex, age, or baseline seropositivity (all p>0·05). Neutralising antibodies seem to be less durable, with seropositivity dropping from 64-71% at 28 days to 27-31% at 6 months in participants from the Geneva study. Antibody responses to single-dose rVSV-ZEBOV vaccination are sustained across dose ranges and settings, a key criterion in countries where booster vaccinations would be impractical. The Wellcome Trust and Innovative Medicines Initiative 2 Joint Undertaking. Copyright © 2018 Elsevier Ltd. All rights reserved.

Accelerated heavy particles and the lens. VII: The cataractogenic potential of 450 MeV/amu iron ions

NASA Technical Reports Server (NTRS)

Worgul, B. V.; Brenner, D. J.; Medvedovsky, C.; Merriam, G. R. Jr; Huang, Y.

1993-01-01

PURPOSE. To determine the cataractogenic potential dose of high velocity iron ions as a fixation of dose administered singly or fractionated. The dose is critical to risk assessment and to theories of radiation action and cataractogenesis. METHODS. Twenty-eight-day-old rats were examined by slit-lamp biomicroscopy on a weekly-bi-weekly basis for more than 2 yr after radiation exposure. For the acute exposure study doses of 1, 2, 5, 25, and 50 cGy were evaluated. The fractionated regimens involved total doses of 2, 25, and 50 cGy. The reference radiation consisted of 50, 100, 200, or 700 cGy of 250 kilovolt (peak) x-rays. RESULTS. In accordance with previous findings in the rat using 570 MeV/amu 40Ar ions, the relative biologic effectiveness increased rapidly with decreasing dose, reaching values as high as 100. Unlike 40Ar ions, fractionation of the 56Fe doses did not produce a consistent enhancement at any of the doses examined. CONCLUSIONS. The data support the previous findings of a high cataractogenic potential for high linear energy transfer (LET) radiation. The effectiveness for the production of cataracts increases with decreasing dose relative to x-rays and is independent of dose protraction. Although the present study did not reveal a consistent enhancement of effect when the ions were applied in fractions, the results are consistent with at least one theory of the inverse dose-rate effect observed for high-LET radiation.

Asymmetrical Interhemispheric Connections Develop in Cat Visual Cortex after Early Unilateral Convergent Strabismus: Anatomy, Physiology, and Mechanisms

PubMed Central

Bui Quoc, Emmanuel; Ribot, Jérôme; Quenech’Du, Nicole; Doutremer, Suzette; Lebas, Nicolas; Grantyn, Alexej; Aushana, Yonane; Milleret, Chantal

2011-01-01

In the mammalian primary visual cortex, the corpus callosum contributes to the unification of the visual hemifields that project to the two hemispheres. Its development depends on visual experience. When this is abnormal, callosal connections must undergo dramatic anatomical and physiological changes. However, data concerning these changes are sparse and incomplete. Thus, little is known about the impact of abnormal postnatal visual experience on the development of callosal connections and their role in unifying representation of the two hemifields. Here, the effects of early unilateral convergent strabismus (a model of abnormal visual experience) were fully characterized with respect to the development of the callosal connections in cat visual cortex, an experimental model for humans. Electrophysiological responses and 3D reconstruction of single callosal axons show that abnormally asymmetrical callosal connections develop after unilateral convergent strabismus, resulting from an extension of axonal branches of specific orders in the hemisphere ipsilateral to the deviated eye and a decreased number of nodes and terminals in the other (ipsilateral to the non-deviated eye). Furthermore this asymmetrical organization prevents the establishment of a unifying representation of the two visual hemifields. As a general rule, we suggest that crossed and uncrossed retino-geniculo-cortical pathways contribute successively to the development of the callosal maps in visual cortex. PMID:22275883

Dorsolateral onlay urethroplasty for anterior urethral strictures by a unilateral urethral mobilization approach.

PubMed

Singh, Bhupendra P; Pathak, Hemant R; Andankar, Mukund G

2009-04-01

For management of long segment anterior urethral stricture, dorsal onlay urethroplasty is currently the most favored single-stage procedure. Conventional dorsal onlay urethroplasty requires circumferential mobilization of the urethra, which might cause ischemia of the urethra in addition to chordee. To determine the feasibility and short-term outcomes of applying a dorsolateral free graft to treat anterior urethral stricture by unilateral urethral mobilization through a perineal approach. A prospective study from September 2005 to March 2008 in a tertiary care teaching hospital. Seventeen patients with long or multiple strictures of the anterior urethra were treated by a dorsolateral free buccal mucosa graft. The pendulous urethra was accessed by penile eversion through the perineal wound. The urethra was not separated from the corporal bodies on one side and was only mobilized from the midline on the ventral aspect to beyond the midline on the dorsal aspect. The urethra was opened in the dorsal midline over the stricture. The buccal mucosa graft was secured on the ventral tunica of the corporal bodies. Mean and median. After a follow-up of 12-30 months, one recurrence developed and 1 patient needed an internal urethrotomy. A unilateral urethral mobilization approach for dorsolateral free graft urethroplasty is feasible for panurethral strictures of any length with good short-term success.

Miniopen Transforaminal Lumbar Interbody Fusion with Unilateral Fixation: A Comparison between Ipsilateral and Contralateral Reherniation

PubMed Central

Liu, Fubing; Jiang, Chun

2016-01-01

The aim of this study was to evaluate the risk factors between ipsilateral and contralateral reherniation and to compare the effectiveness of miniopen transforaminal lumbar interbody fusion (TLIF) with unilateral fixation for each group. From November 2007 to December 2014, clinical and radiographic data of each group (ipsilateral or contralateral reherniation) were collected and compared. Functional assessment (Visual Analog Scale (VAS) score and Japanese Orthopaedic Association (JOA)) and radiographic evaluation (fusion status, disc height, lumbar lordosis (LL), and functional spine unit (FSU) angle) were applied to compare surgical effect for each group preoperatively and at final followup. MacNab questionnaire was applied to further evaluate the satisfactory rate after the discectomy and fusion. No difference except pain-free interval was found between ipsilateral and contralateral groups. There was a significant difference in operative time between two groups. No differences were found in clinical and radiographic data for assessment of surgical effect between two groups. The satisfactory rate was decreasing in both groups with time passing after discectomy. Difference in pain-free interval may be a distinction for ipsilateral and contralateral reherniation. Miniopen TLIF with unilateral pedicle screw fixation can be a recommendable way for single level reherniation regardless of ipsilateral or contralateral reherniation. PMID:27885358

Monaural Congenital Deafness Affects Aural Dominance and Degrades Binaural Processing

PubMed Central

Tillein, Jochen; Hubka, Peter; Kral, Andrej

2016-01-01

Cortical development extensively depends on sensory experience. Effects of congenital monaural and binaural deafness on cortical aural dominance and representation of binaural cues were investigated in the present study. We used an animal model that precisely mimics the clinical scenario of unilateral cochlear implantation in an individual with single-sided congenital deafness. Multiunit responses in cortical field A1 to cochlear implant stimulation were studied in normal-hearing cats, bilaterally congenitally deaf cats (CDCs), and unilaterally deaf cats (uCDCs). Binaural deafness reduced cortical responsiveness and decreased response thresholds and dynamic range. In contrast to CDCs, in uCDCs, cortical responsiveness was not reduced, but hemispheric-specific reorganization of aural dominance and binaural interactions were observed. Deafness led to a substantial drop in binaural facilitation in CDCs and uCDCs, demonstrating the inevitable role of experience for a binaural benefit. Sensitivity to interaural time differences was more reduced in uCDCs than in CDCs, particularly at the hemisphere ipsilateral to the hearing ear. Compared with binaural deafness, unilateral hearing prevented nonspecific reduction in cortical responsiveness, but extensively reorganized aural dominance and binaural responses. The deaf ear remained coupled with the cortex in uCDCs, demonstrating a significant difference to deprivation amblyopia in the visual system. PMID:26803166

Monaural Congenital Deafness Affects Aural Dominance and Degrades Binaural Processing.

PubMed

Tillein, Jochen; Hubka, Peter; Kral, Andrej

2016-04-01

Cortical development extensively depends on sensory experience. Effects of congenital monaural and binaural deafness on cortical aural dominance and representation of binaural cues were investigated in the present study. We used an animal model that precisely mimics the clinical scenario of unilateral cochlear implantation in an individual with single-sided congenital deafness. Multiunit responses in cortical field A1 to cochlear implant stimulation were studied in normal-hearing cats, bilaterally congenitally deaf cats (CDCs), and unilaterally deaf cats (uCDCs). Binaural deafness reduced cortical responsiveness and decreased response thresholds and dynamic range. In contrast to CDCs, in uCDCs, cortical responsiveness was not reduced, but hemispheric-specific reorganization of aural dominance and binaural interactions were observed. Deafness led to a substantial drop in binaural facilitation in CDCs and uCDCs, demonstrating the inevitable role of experience for a binaural benefit. Sensitivity to interaural time differences was more reduced in uCDCs than in CDCs, particularly at the hemisphere ipsilateral to the hearing ear. Compared with binaural deafness, unilateral hearing prevented nonspecific reduction in cortical responsiveness, but extensively reorganized aural dominance and binaural responses. The deaf ear remained coupled with the cortex in uCDCs, demonstrating a significant difference to deprivation amblyopia in the visual system. © The Author 2016. Published by Oxford University Press.

Evaluation of volumetric modulated arc therapy for cranial radiosurgery using multiple noncoplanar arcs

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

Audet, Chantal; Poffenbarger, Brett A.; Chang, Pauling

2011-11-15

Purpose: To evaluate a commercial volumetric modulated arc therapy (VMAT), using multiple noncoplanar arcs, for linac-based cranial radiosurgery, as well as evaluate the combined accuracy of the VMAT dose calculations and delivery. Methods: Twelve patients with cranial lesions of variable size (0.1-29 cc) and two multiple metastases patients were planned (Eclipse RapidArc AAA algorithm, v8.6.15) using VMAT (1-6 noncoplanar arcs), dynamic conformal arc (DCA, {approx}4 arcs), and IMRT (nine static fields). All plans were evaluated according to a conformity index (CI), healthy brain tissue doses and volumes, and the dose to organs at risk. A 2D dose distribution was measuredmore » (Varian Novalis Tx, HD120 MLC, 1000 MU/min, 6 MV beam) for the {approx}4 arc VMAT treatment plans using calibrated film dosimetry. Results: The CI (0-1 best) average for all plans was best for {approx}4 noncoplanar arc VMAT at 0.86 compared with {approx}0.78 for IMRT and a single arc VMAT and 0.68 for DCA. The volumes of healthy brain receiving 50% of the prescribed target coverage dose or more (V{sub 50%}) were lowest for the four arc VMAT [RA(4)] and DCA plans. The average ratio of the V{sub 50%} for the other plans to the RA(4) V{sub 50%} were 1.9 for a single noncoplanar arc VMAT [RA(1nc)], 1.4 for single full coplanar arc VMAT [RA(1f)] and 1.3 for IMRT. The V{sub 50%} improved significantly for single isocenter multiple metastases plan when two noncoplanar VMAT arcs were added to a full single coplanar one. The maximum dose to 5 cc of the outer 1 cm rim of healthy brain which one may want to keep below nonconsequential doses of 300-400 cGy, was 2-3 times greater for IMRT, RA(1nc) and RA(1f) plans compared with the multiple noncoplanar arc DCA and RA(4) techniques. Organs at risk near (0-4 mm) to targets were best spared by (i) single noncoplanar arcs when the targets are lateral to the organ at risk and (ii) by skewed nonvertical planes of IMRT fields when the targets are not lateral to the organ at risk. The highest dose gradient observed between an organ at risk and a target at the edge of a VMAT arc plane or plane of IMRT fields was 17%/mm. The average absolute percent difference between the measured and calculated central axis dose for all the VMAT plans was 3.6 {+-} 2.2%. The measured perpendicular profile widths and shifts were on average within 0.5 mm of planned values. The average total MUs for VMAT plans was double the DCA average and similar to the IMRT average. Conclusions: For the aforementioned planning and delivery system and cranial lesions greater than 7 mm in diameter, multiple noncoplanar arc VMAT consistently provides accurate and high quality cranial radiosurgery dose distributions with low doses to healthy brain tissue and high dose conformity to the target. These qualities may make multiple noncoplanar arc VMAT suitable for a greater range of prescription doses or larger and more irregular lesions. For smaller and/or rounder lesions there are other clinically acceptable treatment techniques that may involve fewer couch angles or arcs and reduce treatment times.« less

Primary unilateral cleft lip repair.

PubMed

Adenwalla, H S; Narayanan, P V

2009-10-01

The unilateral cleft lip is a complex deformity. Surgical correction has evolved from a straight repair through triangular and quadrilateral repairs to the Rotation Advancement Technique of Millard. The latter is the technique followed at our centre for all unilateral cleft lip patients. We operate on these at five to six months of age, do not use pre-surgical orthodontics, and follow a protocol to produce a notch-free vermillion. This is easy to follow even for trainees. We also perform closed alar dissection and extensive primary septoplasty in all these patients. This has improved the overall result and has no long-term deleterious effect on the growth of the nose or of the maxilla. Other refinements have been used for prevention of a high-riding nostril, and correction of the vestibular web.

Primary unilateral cleft lip repair

PubMed Central

Adenwalla, H. S.; Narayanan, P. V.

2009-01-01

The unilateral cleft lip is a complex deformity. Surgical correction has evolved from a straight repair through triangular and quadrilateral repairs to the Rotation Advancement Technique of Millard. The latter is the technique followed at our centre for all unilateral cleft lip patients. We operate on these at five to six months of age, do not use pre-surgical orthodontics, and follow a protocol to produce a notch-free vermillion. This is easy to follow even for trainees. We also perform closed alar dissection and extensive primary septoplasty in all these patients. This has improved the overall result and has no long-term deleterious effect on the growth of the nose or of the maxilla. Other refinements have been used for prevention of a high-riding nostril, and correction of the vestibular web. PMID:19884683

Case Report: Bilateral reexpansion pulmonary edema following treatment of a unilateral hemothorax

PubMed Central

de Wolf, Steven P; Deunk, Jaap; Cornet, Alexander D; Elbers, Paul WG

2014-01-01

Bilateral re-expansion pulmonary edema (RPE) is an extremely rare entity. We report the unique case of bilateral RPE following a traumatic, unilateral hemopneumothorax in a young healthy male. Bilateral RPE occurred only one hour after drainage of a unilateral hemopneumothorax. The patient was treated with diuretics and supplemental oxygen. Diagnosis was confirmed by excluding other causes, using laboratory findings, chest radiography, pulmonary and cardiac ultrasound and high resolution computed tomography. His recovery was uneventful. The pathophysiology of bilateral RPE is not well known. Treatment is mainly supportive and consists of diuretics, mechanical ventilation, inotropes and steroids. In case of a pulmonary deterioration after the drainage of a traumatic pneumothorax, bilateral RPE should be considered after exclusion of more common causes of dyspnea. PMID:25713699

Human Gait and Postural Control after Unilateral Total Knee Arthroplasty

PubMed Central

STAN, Gabriel; ORBAN, Horia

2014-01-01

Introduction: This study assesses the changes in human gait in the early postoperative phase of unilateral TKA, by evaluating the variability of free moment. Materials and method: The study group consisted of 10 patients from the Orthopedic Department of the 'Elias' University Hospital in Bucharest who undergone unilateral knee arthroplasty with the same type of posterior cruciate ligament substituting prosthesis. For the evaluation of free moment an AMTI AccuGait force platform was used. Results: Regarding the free moment peaks, for the operated and non-operated limb, increased significantly (p <0.05) in the postoperative period. The stance time was higher post-surgery for both limbs. Discussion: In the early postoperative phase of unilateral TKA, free moment is higher on both the operated and the non-operated limbs, which means that the knees are subjected to higher torques. Shortly after TKA, patients tend to walk with lower speed, with small steps and reduced cadence. Stance time differences between the operated and the non-operated limbs can lead to overuse of the latter, worsening its condition. Conclusions: It is highly important to adopt a well-managed rehabilitation program in order to increase walking stability. The cost effectiveness of this procedure could be highly dependent on the rehab program. The parameters studied in this article are useful in assessing the rehabilitation protocol. PMID:25705305

Dosimetric evaluation of two treatment planning systems for high dose rate brachytherapy applications

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

Shwetha, Bondel; Ravikumar, Manickam, E-mail: drravikumarm@gmail.com; Supe, Sanjay S.

2012-04-01

Various treatment planning systems are used to design plans for the treatment of cervical cancer using high-dose-rate brachytherapy. The purpose of this study was to make a dosimetric comparison of the 2 treatment planning systems from Varian medical systems, namely ABACUS and BrachyVision. The dose distribution of Ir-192 source generated with a single dwell position was compared using ABACUS (version 3.1) and BrachyVision (version 6.5) planning systems. Ten patients with intracavitary applications were planned on both systems using orthogonal radiographs. Doses were calculated at the prescription points (point A, right and left) and reference points RU, LU, RM, LM, bladder,more » and rectum. For single dwell position, little difference was observed in the doses to points along the perpendicular bisector. The mean difference between ABACUS and BrachyVision for these points was 1.88%. The mean difference in the dose calculated toward the distal end of the cable by ABACUS and BrachyVision was 3.78%, whereas along the proximal end the difference was 19.82%. For the patient case there was approximately 2% difference between ABACUS and BrachyVision planning for dose to the prescription points. The dose difference for the reference points ranged from 0.4-1.5%. For bladder and rectum, the differences were 5.2% and 13.5%, respectively. The dose difference between the rectum points was statistically significant. There is considerable difference between the dose calculations performed by the 2 treatment planning systems. It is seen that these discrepancies are caused by the differences in the calculation methodology adopted by the 2 systems.« less

Intraoperative irradiation: precision medicine for quality cancer control promotion.

PubMed

Calvo, Felipe A

2017-02-02

Intraoperative irradiation was implemented 4 decades ago, pioneering the efforts to improve precision in local cancer therapy by combining real-time surgical exploration/resection with high single dose radiotherapy (Gunderson et al., Intraoperative irradiation: techniques and results, 2011). Clinical and technical developments have led to very precise radiation dose deposit. The ability to deliver a very precise dose of radiation is an essential element of contemporary multidisciplinary individualized oncology.This issue of Radiation Oncology contains a collection of expert review articles and updates with relevant data regarding intraoperative radiotherapy. Technology, physics, biology of single dose and clinical results in a variety of cancer sites and histologies are described and analyzed. The state of the art for advanced cancer care through medical innovation opens a significant opportunity for individualize cancer management across a broad spectrum of clinical practice. The advantage for tailoring diagnostic and treatment decisions in an individualized fashion will translate into precise medical treatment.

Nicotinamide riboside is uniquely and orally bioavailable in mice and humans.

PubMed

Trammell, Samuel A J; Schmidt, Mark S; Weidemann, Benjamin J; Redpath, Philip; Jaksch, Frank; Dellinger, Ryan W; Li, Zhonggang; Abel, E Dale; Migaud, Marie E; Brenner, Charles

2016-10-10

Nicotinamide riboside (NR) is in wide use as an NAD + precursor vitamin. Here we determine the time and dose-dependent effects of NR on blood NAD + metabolism in humans. We report that human blood NAD + can rise as much as 2.7-fold with a single oral dose of NR in a pilot study of one individual, and that oral NR elevates mouse hepatic NAD + with distinct and superior pharmacokinetics to those of nicotinic acid and nicotinamide. We further show that single doses of 100, 300 and 1,000 mg of NR produce dose-dependent increases in the blood NAD + metabolome in the first clinical trial of NR pharmacokinetics in humans. We also report that nicotinic acid adenine dinucleotide (NAAD), which was not thought to be en route for the conversion of NR to NAD + , is formed from NR and discover that the rise in NAAD is a highly sensitive biomarker of effective NAD + repletion.

Tumor Induction in Mice After Localized Single- or Fractionated-Dose Irradiation: Differences in Tumor Histotype and Genetic Susceptibility Based on Dose Scheduling

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

Edmondson, Elijah F., E-mail: elijah.edmondson@colostate.edu; Hunter, Nancy R.; Weil, Michael M.

2015-07-15

Purpose: To investigate differences in tumor histotype, incidence, latency, and strain susceptibility in mice exposed to single-dose or clinically relevant, fractioned-dose γ-ray radiation. Methods and Materials: C3Hf/Kam and C57BL/6J mice were locally irradiated to the right hindlimb with either single large doses between 10 and 70 Gy or fractionated doses totaling 40 to 80 Gy delivered at 2-Gy/d fractions, 5 d/wk, for 4 to 8 weeks. The mice were closely evaluated for tumor development in the irradiated field for 800 days after irradiation, and all tumors were characterized histologically. Results: A total of 210 tumors were induced within the radiation field in 788 mice. Anmore » overall decrease in tumor incidence was observed after fractionated irradiation (16.4%) in comparison with single-dose irradiation (36.1%). Sarcomas were the predominant postirradiation tumor observed (n=201), with carcinomas occurring less frequently (n=9). The proportion of mice developing tumors increased significantly with total dose for both single-dose and fractionated schedules, and latencies were significantly decreased in mice exposed to larger total doses. C3Hf/Kam mice were more susceptible to tumor induction than C57BL/6J mice after single-dose irradiation; however, significant differences in tumor susceptibilities after fractionated radiation were not observed. For both strains of mice, osteosarcomas and hemangiosarcomas were significantly more common after fractionated irradiation, whereas fibrosarcomas and malignant fibrous histiocytomas were significantly more common after single-dose irradiation. Conclusions: This study investigated the tumorigenic effect of acute large doses in comparison with fractionated radiation in which both the dose and delivery schedule were similar to those used in clinical radiation therapy. Differences in tumor histotype after single-dose or fractionated radiation exposures provide novel in vivo evidence for differences in tumor susceptibility among stromal cell populations.« less

Symptoms, disability and handicap in unilateral peripheral vestibular disorders. Effects of early presentation and initiation of balance exercises.

PubMed

Bamiou, D E; Davies, R A; McKee, M; Luxon, L M

2000-01-01

The aim of this study was to obtain a profile of disability and handicap in patients with unilateral peripheral vestibular disorders presenting to a specialist tertiary care unit. Two validated questionnaires were sent to patients who had a unilateral peripheral vestibular disorder as defined by strict criteria. Some patients still suffered moderate handicap and disability 5 years after the initial symptoms related to a unilateral vestibular disorder, although the duration of symptoms (onset to questionnaire completion) did not correlate with severity of disability and handicap, as judged by questionnaire scores. However, patients presenting to the unit within 6 months of onset of vertigo commenced balance exercises significantly earlier and had significantly lower disability scores than patients presenting later. A high proportion of non-compliance with, and delay in initiation of, vestibular rehabilitation exercises was noted in the total patient sample, while compliance with, and early initiation of, Cooksey Cawthorne exercises were significantly correlated with low disability and questionnaire scores. These findings suggest that early referral to a specialist balance unit for patients with persistent dizziness is associated with better outcome.

Pharmacokinetics of pregabalin controlled-release in healthy volunteers: effect of food in five single-dose, randomized, clinical pharmacology studies.

PubMed

Chew, Marci L; Plotka, Anna; Alvey, Christine W; Pitman, Verne W; Alebic-Kolbah, Tanja; Scavone, Joseph M; Bockbrader, Howard N

2014-09-01

The pharmacokinetic properties of the immediate-release (IR) and the recently developed controlled-release (CR) formulation of pregabalin are dose proportional. Pregabalin IR can be taken with or without food. This analysis characterizes the effect of food on pregabalin CR. The objectives of this analysis were: (1) to evaluate the effect of administration time and fat or caloric content of an accompanying meal on the pharmacokinetic properties of a single dose of pregabalin CR (330 mg) relative to a single dose of pregabalin IR (300 mg); (2) to evaluate the pharmacokinetic properties of a single dose of pregabalin CR administered fasted relative to a single dose of pregabalin CR administered immediately after food; and (3) to determine the safety and tolerability of single-dose administration of pregabalin CR and IR with and without food. The effect of food on the pharmacokinetic properties of pregabalin CR was determined in five phase I, open-label, single-dose, crossover studies (24-28 participants/study). Caloric and fat content of meals were varied and treatments were administered in the morning, at midday, or in the evening. Blood samples were collected up to 48 h post-dose. Pharmacokinetic parameters were estimated from plasma concentration-time data using standard noncompartmental methods. Adverse events were monitored throughout all studies. One hundred and twenty-eight healthy participants (19-54 years of age) received pregabalin. Peak plasma concentrations (C max) were lower for CR than the respective pregabalin IR doses, and time to C max occurred later. When pregabalin CR was administered with food at midday or in the evening, total exposures [area under the plasma concentration-time curve from time zero extrapolated to infinite time (AUC∞)] were equivalent for pregabalin CR and IR formulations regardless of fat or caloric content. When pregabalin CR was administered with an 800-1,000 calorie medium-fat breakfast, AUC∞ was equivalent for pregabalin CR and IR. Bioequivalence criteria for comparison of pregabalin CR after a low- or medium-calorie breakfast relative to pregabalin IR were not met; however, bioavailability of the pregabalin CR vs. IR formulation was relatively high (75-86 %). When pregabalin CR was administered fasted, the AUC∞ was 70-78 % of the AUC∞ of pregabalin CR administered with food and bioequivalence criteria were not met. Additionally, the AUC∞ of the pregabalin CR formulation administered fasted was 62-69 % of that of pregabalin IR administered fasted and bioequivalence criteria were not met. Single-dose pregabalin CR and IR were well tolerated in all studies, with no serious or severe adverse events reported. Time of day of administration and the fat and caloric content of the accompanying meal had minimal overall effect on the pharmacokinetic properties and bioavailability of the pregabalin CR formulation.

THE SIGNIFICANCE OF SCOLIOSIS IN POST-IRRADIATED WILMS'S TUMOR AND NEUROBLASTOMA

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

Rubin, P.; Duthie, R.B.; Young, L.W.

1962-10-01

Radiographic changes in the vertebrae are described that were observed following orthovoltage therapeutic irradiation in the treatment of Wilms's tumor, neuroblastoma, and medulloblastoma. Historical data and treatment faetors are tabulated for 17 cases. Observations on the incidence and severity of scoliosis and accompanying bony changes in l3 cases are presented. A review of the findings showed that the degree of scoliosis that developed was not related to the the fields of irradiation, whether they were unilateral or bilateral, and that the osseous changes in the vertebrae, pelvis, or ribs. The use of irradiation with surgery in the treatment of Wilms'smore » tumor is discussed. Radiological techniques are described to deliver maximum doses to the tumor and minimum doses to the surrounding normal structures in the treatment of these tumors. (C.H.)« less

Charged-Iron-Particles Found in Galactic Cosmic Rays are Potent Inducers of Epithelial Ovarian Tumors.

PubMed

Mishra, Birendra; Lawson, Gregory W; Ripperdan, Ryan; Ortiz, Laura; Luderer, Ulrike

2018-05-21

Astronauts traveling in deep space are exposed to high-charge and energy (HZE) particles from galactic cosmic rays. We have previously determined that irradiation of adult female mice with iron HZE particles induces DNA double-strand breaks, oxidative damage and apoptosis in ovarian follicles, causing premature ovarian failure. These effects occur at lower doses than with conventional photon irradiation. Ovarian failure with resultant loss of negative feedback and elevated levels of gonadotropin hormones is thought to play a role in the pathophysiology of ovarian cancer. Therefore, we hypothesized that charged-iron-particle irradiation induces ovarian tumorigenesis in mice. In this study, three-month-old female mice were exposed to 0 cGy (sham) or 50 cGy iron ions and aged to 18 months. The 50 cGy irradiated mice had increased weight gain with age and lack of estrous cycling, consistent with ovarian failure. A total of 47% and 7% of mice irradiated with 50 cGy had unilateral and bilateral ovarian tumors, respectively, whereas 14% of mice in the 0 cGy group had unilateral tumors. The tumors contained multiple tubular structures, which were lined with cells positive for the epithelial marker cytokeratin, and had few proliferating cells. In some tumors, packets of cells between the tubular structures were immunopositive for the granulosa cell marker FOXL2. Based on these findings, tumors were diagnosed as tubular adenomas or mixed tubular adenoma/granulosa cell tumors. In conclusion, charged-iron-particle-radiation induces ovarian tumors in mice, raising concerns about ovarian tumors as late sequelae of deep space travel in female astronauts.

Unilateral laparoscopic ovariectomy in a red fox (Vulpes vulpes) with an ovarian cyst.

PubMed

Lee, Seung Y; Jung, Dong H; Park, Se J; Seek, Seong H; Yang, Jeong J; Lee, Jae W; Lee, Bae K; Lee, Hee C; Yeon, Seong C

2014-09-01

Unilateral laparoscopic ovariectomy was attempted in a red fox (Vulpes vulpes) with an ovarian cyst through single portal access. The ovarian cyst was resistant to conservative therapy using gonadotropin-releasing hormone. A 10-mm laparoscope with an operating channel was introduced into the abdomen via a 12-mm umbilical portal. The left ovary and cyst (34.1 x 30.8 mm) were fixed to the left abdominal wall by a transabdominal suspension suture. The ovarian pedicles and ligaments were progressively cauterized and transected with a multifunction bipolar electrocoagulation forceps. The resected cystic ovary was exteriorized through the umbilical portal site. The surgical time was 42 min, and no intra- and postoperative complications were encountered. Two months after the surgery mating was observed, and the fox gave birth to three healthy cubs 56 days after the mating. This is the first report of using laparoscopy in the red fox with an ovarian cyst.

Disposition and pharmacokinetics in rats of McN-5707, a potential antidepressant drug

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

Ng, K.T.; Holland, M.L.; Hills, J.F.

1986-03-01

A single 80 mg/kg oral solution dose of McN-5707-/sup 14/C x HBr (trans-6-(2-chlorophenyl)-1,2,3,5,6,10b-hexahydropyrrolo(2,1-a)isoquinoline hydrobromide (1:1)) was administered orally to 40 Wistar rats. Total /sup 14/C concentrations in plasma were high (> 4.5 ..mu..g x equiv/mL) for at least 24 hours after dosing. Unchanged McN-5707 represented < 10% of the total /sup 14/C concs in plasma at 45 min and < 1% at 24 hours after dosing. In the 8 days following dose administration, 23% of the dose was excreted in urine and 70% of the dose was excreted in feces. Analysis (HPLC and TLC) of glusulase treated urine, plasma andmore » fecal samples revealed the presence of multiple metabolites of McN-5707. Unchanged McN-5707 was found only in fecal extracts (2-7% of dose). Single solution doses of McN-5707 x HBr were administered p.o. (20 mg/kg) and i.v. (4 mg/kg) to 39 Wistar rats. Plasma samples were analyzed for McN-5707 using a capillary GC assay. These studies indicated that McN-5707 was well absorbed and extensively metabolized in rats following oral doses.« less

Meal frequency of pre-exercise carbohydrate feedings.

PubMed

Chryssanthopoulos, C; Petridou, A; Maridaki, M; Mougios, V

2008-04-01

This study compared the effect of single and multiple carbohydrate feedings before exercise on biochemical and physiological responses during exercise. Eight males performed 3 runs for 1 h at 70 % VO(2max) after consuming a meal containing 2.5 g carbohydrate per kg body mass in a single dose 3 h before exercise (SF), the same meal in 5 equal doses at 3, 2.5, 2, 1.5, and 1 h before exercise (MF), or a liquid placebo 3 h before exercise (P). RER and carbohydrate oxidation rates were higher in SF and MF compared to P trials, but there was no difference between SF and MF trials. Pre-exercise insulin was 2.0- and 3.4- fold higher in SF and MF, respectively, compared to P, and 1.7-fold higher in MF compared to SF. Glycerol and NEFA were higher in P compared to SF and MF trials before and at the end of exercise. In conclusion, a carbohydrate meal containing 2.5 g . kg(-1) ingested in doses over 3 h before running produced higher hyperinsulinemia pre-exercise than that produced when the meal was consumed in a single dose. Nevertheless, estimated carbohydrate utilization and adipose tissue lipolysis during exercise after multiple feedings seemed to be as high as after a single feeding.

The effect of unilateral thalamic deep brain stimulation on the vocal dysfunction in a patient with spasmodic dysphonia: interrogating cerebellar and pallidal neural circuits.

PubMed

Poologaindran, Anujan; Ivanishvili, Zurab; Morrison, Murray D; Rammage, Linda A; Sandhu, Mini K; Polyhronopoulos, Nancy E; Honey, Christopher R

2018-02-01

Spasmodic dysphonia (SD) is a neurological disorder of the voice where a patient's ability to speak is compromised due to involuntary contractions of the intrinsic laryngeal muscles. Since the 1980s, SD has been treated with botulinum toxin A (BTX) injections into the throat. This therapy is limited by the delayed-onset of benefits, wearing-off effects, and repeated injections required every 3 months. In a patient with essential tremor (ET) and coincident SD, the authors set out to quantify the effects of thalamic deep brain stimulation (DBS) on vocal function while investigating the underlying motor thalamic circuitry. A 79-year-old right-handed woman with ET and coincident adductor SD was referred to our neurosurgical team. While primarily treating her limb tremor, the authors studied the effects of unilateral, thalamic DBS on vocal function using the Unified Spasmodic Dysphonia Rating Scale (USDRS) and voice-related quality of life (VRQOL). Since dystonia is increasingly being considered a multinodal network disorder, an anterior trajectory into the left thalamus was deliberately chosen such that the proximal contacts of the electrode were in the ventral oralis anterior (Voa) nucleus (pallidal outflow) and the distal contacts were in the ventral intermediate (Vim) nucleus (cerebellar outflow). In addition to assessing on/off unilateral thalamic Vim stimulation on voice, the authors experimentally assessed low-voltage unilateral Vim, Voa, or multitarget stimulation in a prospective, randomized, doubled-blinded manner. The evaluators were experienced at rating SD and were familiar with the vocal tremor of ET. A Wilcoxon signed-rank test was used to study the pre- and posttreatment effect of DBS on voice. Unilateral left thalamic Vim stimulation (DBS on) significantly improved SD vocal dysfunction compared with no stimulation (DBS off), as measured by the USDRS (p < 0.01) and VRQOL (p < 0.01). In the experimental interrogation, both low-voltage Vim (p < 0.01) and multitarget Vim + Voa (p < 0.01) stimulation were significantly superior to low-voltage Voa stimulation. For the first time, the effects of high-frequency stimulation of different neural circuits in SD have been quantified. Unexpectedly, focused Voa (pallidal outflow) stimulation was inferior to Vim (cerebellar outflow) stimulation despite the classification of SD as a dystonia. While only a single case, scattered reports exist on the positive effects of thalamic DBS on dysphonia. A Phase 1 pilot trial (DEBUSSY; clinical trial no. NCT02558634, clinicaltrials.gov) is underway at the authors' center to evaluate the safety and preliminary efficacy of DBS in SD. The authors hope that this current report stimulates neurosurgeons to investigate this new indication for DBS.

Do We Need a Single Standard of Value for Institutional Assessment? An Essay Response to Asao Inoue's "Community-Based Assessment Pedagogy"

ERIC Educational Resources Information Center

Elbow, Peter

2006-01-01

Inoue [Inoue, A. B. (2005). "Community-based assessment pedagogy." "Assessing Writing: An International Journal, 3", 208-238] sets up a radically experimental writing class as a kind of laboratory of assessment. He seeks to avoid the standard situation where a teacher unilaterally assesses and grades student writing, using only his or her own…

The biological fate of decabromodiphenyl ethane following ...

EPA Pesticide Factsheets

1. The disposition of decabromodiphenyl ethane (DBDPE) was investigated based on concerns over its structural similarities to decaBDE, high potential for environmental persistence & bioaccumulation, and high production volume. 2. In the present study, female Sprague Dawley rats were administered a single dose of [14C]-DBDPE by oral, topical, or IV routes. Another set of rats were administered 10 daily oral doses of 14C]-DBDPE. Male B6C3F1/Tac mice were administered a single oral dose.3. DBDPE was poorly absorbed following oral dosing, with 95% of administered [14C]-radioactivity recovered in the feces, 1% recovered in the urine and less than 3% in the tissues at 72 h. DBDPE excretion was similar in male mice and female rats. Accumulation of [14C]-DBDPE was observed in liver and the adrenal gland after 10 daily oral doses.4. The dermis acted as a depot for dermally applied DBDPE; conservative estimates predict approx. 14 ± 8% of DBDPE may be absorbed into human skin in vivo; approx. 7 ± 4% of the parent chemical is expected to reach systemic circulation following continuous exposure (24 h). 5. Following intravenous administration, 6% of the dose was recovered in urine and 28% in the feces, while ~70% of the dose remained in tissues after 72 hours, with the highest concentrations found in the liver (42%) and lung (17%). Decabromodiphenyl ethane (DBDPE) is an additive brominated flame retardant used in a variety commercial products. It has been detected in indo

Inclisiran in Patients at High Cardiovascular Risk with Elevated LDL Cholesterol.

PubMed

Ray, Kausik K; Landmesser, Ulf; Leiter, Lawrence A; Kallend, David; Dufour, Robert; Karakas, Mahir; Hall, Tim; Troquay, Roland P T; Turner, Traci; Visseren, Frank L J; Wijngaard, Peter; Wright, R Scott; Kastelein, John J P

2017-04-13

In a previous study, a single injection of inclisiran, a chemically synthesized small interfering RNA designed to target PCSK9 messenger RNA, was found to produce sustained reductions in low-density lipoprotein (LDL) cholesterol levels over the course of 84 days in healthy volunteers. We conducted a phase 2, multicenter, double-blind, placebo-controlled, multiple-ascending-dose trial of inclisiran administered as a subcutaneous injection in patients at high risk for cardiovascular disease who had elevated LDL cholesterol levels. Patients were randomly assigned to receive a single dose of placebo or 200, 300, or 500 mg of inclisiran or two doses (at days 1 and 90) of placebo or 100, 200, or 300 mg of inclisiran. The primary end point was the change from baseline in LDL cholesterol level at 180 days. Safety data were available through day 210, and data on LDL cholesterol and proprotein convertase subtilisin-kexin type 9 (PCSK9) levels were available through day 240. A total of 501 patients underwent randomization. Patients who received inclisiran had dose-dependent reductions in PCSK9 and LDL cholesterol levels. At day 180, the least-squares mean reductions in LDL cholesterol levels were 27.9 to 41.9% after a single dose of inclisiran and 35.5 to 52.6% after two doses (P<0.001 for all comparisons vs. placebo). The two-dose 300-mg inclisiran regimen produced the greatest reduction in LDL cholesterol levels: 48% of the patients who received the regimen had an LDL cholesterol level below 50 mg per deciliter (1.3 mmol per liter) at day 180. At day 240, PCSK9 and LDL cholesterol levels remained significantly lower than at baseline in association with all inclisiran regimens. Serious adverse events occurred in 11% of the patients who received inclisiran and in 8% of the patients who received placebo. Injection-site reactions occurred in 5% of the patients who received injections of inclisiran. In our trial, inclisiran was found to lower PCSK9 and LDL cholesterol levels among patients at high cardiovascular risk who had elevated LDL cholesterol levels. (Funded by the Medicines Company; ORION-1 ClinicalTrials.gov number, NCT02597127 .).

Azithromycin in the treatment of uncomplicated genital chlamydial infections.

PubMed

Stamm, W E

1991-09-12

Chlamydia trachomatis is among the most prevalent of sexually transmitted diseases and causes serious sequelae, especially in women. A major difficulty facing the clinician has been the effective treatment of patients with chlamydial infections, since existing drugs require 7 or more days of multidose therapy, and hence considerable commitment from the patient. Many patients, especially those who are minimally symptomatic or asymptomatic, are likely to be noncompliant when given such multiple day regimens and thus may fail therapy. Azithromycin is an azalide antibiotic that has a minimum inhibitory concentration against C. trachomatis of between 0.03 and 0.25 mg/L, as well as good in vitro activity against other sexually transmitted pathogens that are often present concurrently. Azithromycin also achieves high intracellular concentrations, which may be beneficial in eradicating Chlamydia, an obligate intracellular pathogen. More importantly, azithromycin has high tissue bioavailability and a tissue half-life of between 2 and 4 days. These pharmacokinetic properties imply that the dosing period for azithromycin can be greatly reduced while still achieving high antimicrobial activity at sites of infection. Clinical experience to date shows that a single 1 g oral dose of azithromycin is as effective as a standard 7-day twice daily regimen of doxycycline and more effective than 7 days of ciprofloxacin in eradicating uncomplicated chlamydial genital infections. As such, azithromycin is the first single-dose therapy for the treatment of urethritis and cervicitis due to C. trachomatis. Single-dose therapy for chlamydial infection, which could be administered under supervision in the clinic, would be a significant advance in the management and public health control of chlamydial infections.

High lenticular tolerance to ultraviolet radiation-B by pigmented guinea-pig; application of a safety limit strategy for UVR-induced cataract.

PubMed

Mody, Vino C; Kakar, Manoj; Söderberg, Per G; Löfgren, Stefan

2012-05-01

The purpose of this study was to determine a threshold measure, maximum tolerable dose (MTD), for avoidance of UVR-B-induced cataract in the pigmented guinea-pig. Thirty pupil-dilated anesthetized young female guinea-pigs, divided into five equal groups, received between 0 and 84.9 kJ/m(2) unilateral UVR-B. Lens extraction and in vitro lens photography occurred 24 hr after exposure. Measurement of intensity of lens light scattering served as quantifying tool for the degree of cataract. Data analysis included regression, using a second order polynomial model. The applied MTD concept was based on the UVR-B dose-response curve obtained for the pigmented guinea-pig. A smaller number of pigmented guinea-pigs, pigmented rats and albino rats underwent morphometric analysis of the anterior segment geometry. All eyes exposed to UVR-B developed cataract in the anterior subcapsular region. MTD for avoidance of UVR-B-induced cataract was 69.0 kJ/m(2) in the pigmented guinea-pig. Iris was considerably thicker in the guinea-pig than in the rats. Lens blockage by the dilated iris was lowest in the guinea-pig. Maximum tolerable dose for avoidance of UVR-B-induced cataract in the pigmented guinea-pig was 69.0 kJ/m(2), over 10-fold higher than the threshold 5 kJ/m(2) obtained by Pitts et al. in the pigmented rabbit. Maximum tolerable dose is an appropriate method for estimation of toxicity for UVR-B-induced cataract in the guinea-pig. The pigmented guinea-pig is significantly less sensitive to UVR-B exposure than the pigmented rabbit and pigmented rat. © 2010 The Authors. Journal compilation © 2010 Acta Ophthalmol.

Dose and Chemical Modification Considerations for Continuous Cyclic AMP Analog Delivery to the Injured CNS

PubMed Central

Fouad, Karim; Ghosh, Mousumi; Vavrek, Romana; Tse, Arthur D.

2009-01-01

Abstract In this investigation, two cell-permeable synthetic analogs of cAMP, dibutyryl-cAMP (db-cAMP) and 8-bromo-cAMP, which are widely used to elevate intracellular cAMP levels under experimental conditions, were investigated for their ability to dose-dependently improve histological and functional outcomes following continuous delivery in two models of incomplete spinal cord injury (SCI). The cAMP analogs were delivered via osmotic minipumps at 1–250 mM through an indwelling cortical cannula or by intrathecal infusion for up to 4 weeks after either a T8 unilateral over-hemisection or a C2-3 dorsolateral quadrant lesion, respectively. In both SCI models, continuous db-cAMP delivery was associated with histopathological changes that included sporadic micro-hemorrhage formation and cavitation, enhanced macrophage infiltration and tissue damage at regions beyond the immediate application site; no deleterious or beneficial effect of agent delivery was observed at the spinal injury site. Furthermore, these changes were accompanied by pronounced behavioral deficits that included an absence of progressive locomotor recovery, increased extensor tone, paralysis, and sensory abnormalities. These deleterious effects were not observed in saline-treated animals, in animals in which the db-cAMP dose did not exceed 1 mM, or in those animals that received a high dose (250 mM) of the alternative cAMP analog, 8-bromo-cAMP. These results demonstrate that, for continuous intraparenchymal or intrathecal administration of cAMP analogs for the study of biological or therapeutic effects within the central nervous system (CNS), consideration of the effective concentration applied as well as the potential toxicity of chemical moieties on the parent molecule and/or their activity needs to be taken into account. PMID:19397425

SU-F-19A-03: Dosimetric Advantages in Critical Structure Dose Sparing by Using a Multichannel Cylinder in High Dose Rate Brachytherapy to Treat Vaginal Cuff Cancer

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

Syh, J; Syh, J; Patel, B

2014-06-15

Purpose: The multichannel cylindrical vaginal applicator is a variation of traditional single channel cylindrical vaginal applicator. The multichannel applicator has additional peripheral channels that provide more flexibility in the planning process. The dosimetric advantage is to reduce dose to adjacent organ at risk (OAR) such as bladder and rectum while maintaining target coverage with the dose optimization from additional channels. Methods: Vaginal HDR brachytherapy plans are all CT based. CT images were acquired in 2 mm thickness to keep integrity of cylinder contouring. The CTV of 5mm Rind with prescribed treatment length was reconstructed from 5mm expansion of inserted cylinder.more » The goal was 95% of CTV covered by 95% of prescribed dose in both single channel planning (SCP)and multichannel planning (MCP) before proceeding any further optimization for dose reduction to critical structures with emphasis on D2cc and V2Gy . Results: This study demonstrated noticeable dose reduction to OAR was apparent in multichannel plans. The D2cc of the rectum and bladder were showing the reduced dose for multichannel versus single channel. The V2Gy of the rectum was 93.72% and 83.79% (p=0.007) for single channel and multichannel respectively (Figure 1 and Table 1). To assure adequate coverage to target while reducing the dose to the OAR without any compromise is the main goal in using multichannel vaginal applicator in HDR brachytherapy. Conclusion: Multichannel plans were optimized using anatomical based inverse optimization algorithm of inverse planning simulation annealing. The optimization solution of the algorithm was to improve the clinical target volume dose coverage while reducing the dose to critical organs such as bladder, rectum and bowels. The comparison between SCP and MCP demonstrated MCP is superior to SCP where the dwell positions were based on geometric array only. It concluded that MCP is preferable and is able to provide certain features superior to SCP.« less

Detecting structural variances of Co 3O 4 catalysts by controlling beam-induced sample alterations in the vacuum of a transmission electron microscope

DOE PAGES

Kisielowski, C.; Frei, H.; Specht, P.; ...

2016-11-02

This article summarizes core aspects of beam-sample interactions in research that aims at exploiting the ability to detect single atoms at atomic resolution by mid-voltage transmission electron microscopy. Investigating the atomic structure of catalytic Co 3O 4 nanocrystals underscores how indispensable it is to rigorously control electron dose rates and total doses to understand native material properties on this scale. We apply in-line holography with variable dose rates to achieve this goal. Genuine object structures can be maintained if dose rates below ~100 e/Å 2s are used and the contrast required for detection of single atoms is generated by capturing largemore » image series. Threshold doses for the detection of single atoms are estimated. An increase of electron dose rates and total doses to common values for high resolution imaging of solids stimulates object excitations that restructure surfaces, interfaces, and defects and cause grain reorientation or growth. We observe a variety of previously unknown atom configurations in surface proximity of the Co 3O 4 spinel structure. These are hidden behind broadened diffraction patterns in reciprocal space but become visible in real space by solving the phase problem. Finallly, an exposure of the Co 3O 4 spinel structure to water vapor or other gases induces drastic structure alterations that can be captured in this manner.« less

Increased apoptotic potential and dose-enhancing effect of gold nanoparticles in combination with single-dose clinical electron beams on tumor-bearing mice.

PubMed

Chang, Meng-Ya; Shiau, Ai-Li; Chen, Yu-Hung; Chang, Chih-Jui; Chen, Helen H-W; Wu, Chao-Liang

2008-07-01

High atomic number material, such as gold, may be used in conjunction with radiation to provide dose enhancement in tumors. In the current study, we investigated the dose-enhancing effect and apoptotic potential of gold nanoparticles in combination with single-dose clinical electron beams on B16F10 melanoma tumor-bearing mice. We revealed that the accumulation of gold nanoparticles was detected inside B16F10 culture cells after 18 h of incubation, and moreover, the gold nanoparticles were shown to be colocalized with endoplasmic reticulum and Golgi apparatus in cells. Furthermore, gold nanoparticles radiosensitized melanoma cells in the colony formation assay (P = 0.02). Using a B16F10 tumor-bearing mouse model, we further demonstrated that gold nanoparticles in conjunction with ionizing radiation significantly retarded tumor growth and prolonged survival compared to the radiation alone controls (P < 0.05). Importantly, an increase of apoptotic signals was detected inside tumors in the combined treatment group (P < 0.05). Knowing that radiation-induced apoptosis has been considered a determinant of tumor responses to radiation therapy, and the length of tumor regrowth delay correlated with the extent of apoptosis after single-dose radiotherapy, these results may suggest the clinical potential of gold nanoparticles in improving the outcome of melanoma radiotherapy.

A double-blind, randomized, placebo-controlled, single-dose study of the cyclooxygenase-2 inhibitor, GW406381, as a treatment for acute migraine.

PubMed

Wentz, A L; Jimenez, T B; Dixon, R M; Aurora, S K; Gold, M

2008-04-01

The objective of the present study was to explore the clinical efficacy and tolerability of GW406381, a cyclooxygenase-2 (COX-2) inhibitor with relatively high CNS penetration, in acute migraine. This was a double-blind, single-dose study of GW406381 compared with placebo and naproxen sodium compared with placebo (protocol number CXA20008). Three hundred and thirty-seven subjects were randomized 1:1:1 to GW406381 (70 mg), naproxen sodium (825 mg), or placebo for the treatment of one migraine headache of moderate or severe intensity in a potential 8-week period. The primary end-point was the proportion of subjects with headache relief [reduction in headache severity score from pre-dose 2 (moderate) or 3 (severe) to 0 (no pain) or 1 (mild)] at 2 h post-dose for GW406381 compared with placebo. Significantly higher proportions of subjects treated with GW406381 (50%, P = 0.032) or naproxen sodium (56%, P = 0.005) than with placebo (35%) reported headache relief at 2 h post-dose. Additional significant benefits were observed on many secondary outcomes, including proportions of subjects pain-free, for both GW406381 and naproxen sodium treatment compared with placebo. Both active treatments were well tolerated. Single-dose GW406381 (70 mg) and naproxen sodium (825 mg) were effective and well tolerated in the treatment of acute migraine.

PaxVax CVD 103-HgR single-dose live oral cholera vaccine.

PubMed

Levine, Myron M; Chen, Wilbur H; Kaper, James B; Lock, Michael; Danzig, Lisa; Gurwith, Marc

2017-03-01

Cholera remains a problem in developing countries and a risk for travelers. Hypochlorhydria, blood group O, cardiac and renal disease increase the risk of developing cholera gravis. Oral vaccines containing inactivated Vibrio cholerae and requiring two doses are available in some countries. No cholera vaccine had been available for U.S. travelers for decades until 2016 when CVD 103-HgR (VAXCHORA™), an oral live attenuated vaccine, was licensed by the U.S. FDA. Areas covered: Enduring protection following wild-type cholera provided the rationale to develop a single-dose live oral vaccine. CVD 103-HgR is well-tolerated and protects against cholera caused by V. cholerae O1 of either serotype (Inaba, Ogawa) and biotype (El Tor, Classical). Since 90% vaccine efficacy is evident 10 days post-ingestion of a single dose, CVD 103-HgR can rapidly protect travelers. Vibriocidal antibody seroconversion correlates with protection; >90% of U.S. adult (including elderly) vaccinees seroconvert. The U.S. Public Health Service's Advisory Committee on Immunization Practices recommends CVD 103-HgR for U.S. travelers to areas of ongoing cholera transmission. Expert commentary: Next steps include evaluations in children, post-licensure safety and effectiveness monitoring, diminishing cold chain constraints, optimizing a 'high-dose' formulation for developing countries, and diminishing/eliminating the need for water to administer a dose.

Rectal artemisinins for malaria: a review of efficacy and safety from individual patient data in clinical studies

PubMed Central

Gomes, Melba; Ribeiro, Isabela; Warsame, Marian; Karunajeewa, Harin; Petzold, Max

2008-01-01

Background Rectal administration of artemisinin derivatives has potential for early treatment for severe malaria in remote settings where injectable antimalarial therapy may not be feasible. Preparations available include artesunate, artemisinin, artemether and dihydroartemisinin. However each may have different pharmacokinetic properties and more information is needed to determine optimal dose and comparative efficacy with each another and with conventional parenteral treatments for severe malaria. Methods Individual patient data from 1167 patients in 15 clinical trials of rectal artemisinin derivative therapy (artesunate, artemisinin and artemether) were pooled in order to compare the rapidity of clearance of Plasmodium falciparum parasitaemia and the incidence of reported adverse events with each treatment. Data from patients who received comparator treatment (parenteral artemisinin derivative or quinine) were also included. Primary endpoints included percentage reductions in parasitaemia at 12 and 24 hours. A parasite reduction of >90% at 24 hours was defined as parasitological success. Results Artemisinin and artesunate treatment cleared parasites more rapidly than parenteral quinine during the first 24 hours of treatment. A single higher dose of rectal artesunate treatment was five times more likely to achieve >90% parasite reductions at 24 hours than were multiple lower doses of rectal artesunate, or a single lower dose administration of rectal artemether. Conclusion Artemisinin and artesunate suppositories rapidly eliminate parasites and appear to be safe. There are less data on artemether and dihydroartemisinin suppositories. The more rapid parasite clearance of single high-dose regimens suggests that achieving immediate high drug concentrations may be the optimal strategy. PMID:18373841

Urinary bactericidal activity of single doses (250, 500, 750 and 1000 mg) of levofloxacin against fluoroquinolone-resistant strains of Escherichia coli.

PubMed

Stein, Gary E; Schooley, Sharon L; Nicolau, David P

2008-10-01

Increasing resistance to fluoroquinolones in uropathogens has become a clinical concern. The purpose of this study was to analyse the urinary bactericidal activity (UBA) of levofloxacin against fluoroquinolone-resistant strains of Escherichia coli. Ten healthy adult subjects (aged 23-60 years) received single doses of levofloxacin (250, 500, 750 and 1000 mg) and then blood and urine samples were collected in intervals (0-1.5, 1.5-4, 4-8, 8-12 and 12-24h) over 24h. Both serum and urine concentrations were measured by a validated high-performance liquid chromatography assay. Bactericidal titres in urine were determined against E. coli isolates with minimum inhibitory concentrations of 0.125, 4, 8, 16, 32 and 64microg/mL for levofloxacin. The mean serum pharmacokinetic parameters for these doses of levofloxacin were similar to previously published values. The mean peak urinary concentrations (0-1.5h) were 210, 347, 620 and 536microg/mL for the 250, 500, 750 and 1000 mg dose, respectively. Each dose of levofloxacin exhibited early (0-1.5h time period) bactericidal activity in urine in virtually all subjects against E. coli strains with MICs

Chromosomal instability induced by heavy ion irradiation

NASA Technical Reports Server (NTRS)

Limoli, C. L.; Ponnaiya, B.; Corcoran, J. J.; Giedzinski, E.; Morgan, W. F.

2000-01-01

PURPOSE: To establish the dose-response relationship for the induction of chromosomal instability in GM10115 cells exposed to high-energy iron ions (1 GeV/nucleon, mean LET 146 keV/microm) and gold ions (11 GeV/nucleon, mean LET 1450 keV/microm). Past work has established that sparsely ionizing X-rays can induce a long-lived destabilization of chromosomes in a dose-dependent manner at an incidence of approximately 3% per gray. The present investigation assesses the capacity of High-Z and High-energy (HZE) particles to elicit this same endpoint. MATERIALS AND METHODS: Clonal populations derived from single progenitor cells surviving heavy-ion irradiation were analyzed cytogenetically to identify those clones showing a persistent destablization of chromosomes. RESULTS: Dose-response data, with a particular emphasis at low dose (< 1.0 Gy), indicate a frequency of approximately 4% per gray for the induction of chromosomal instability in clones derived from single progenitor cells surviving exposure to iron ions. The induction of chromosomal instability by gold ions was, however, less responsive to applied dose, as the observed incidence of this phenotype varied from 0 to 10% over 1-8 Gy. Both iron and gold ions gave dose-dependent increases in the yield of chromosomal aberrations (both chromosome- and chromatid-type) measured at the first mitosis following irradiation, as well as shoulderless survival curves having D0=0.87 and 1.1 Gy respectively. CONCLUSIONS: Based on the present dose-response data, the relative biological effectiveness of iron ions is 1.3 for the induction of chromosomal instability, and this indicates that heavy ions are only slightly more efficient than X-rays at eliciting this delayed phenotype.

Blood flow-independent accumulation of cisplatin in the guinea pig cochlea.

PubMed

Miettinen, S; Laurell, G; Andersson, A; Johansson, R; Laurikainen, E

1997-01-01

Considerable interindividual variability in the ototoxic effect of cisplatin has become the unpredictable dose-limiting factor in its use as curative as well as palliative therapy. The drug accumulates in highly vascular areas in the cochlea, causing dose-related hair cell loss. The purpose of this study was to assess blood flow-dependent aspects of cisplatin absorption in the cochlea in order to better understand factors that may influence cisplatin-induced ototoxicity. The effect of reduced cochlear blood flow on the ototoxic action of cisplatin was studied in guinea pigs. Before cisplatin administration the cochlear vasculature in each animal was unilaterally pre-constricted, by the application of 2% epinephrine to the round window. A 20-30% reduction in cochlear blood flow, assessed by laser Doppler flowmetry, was maintained before and after intravenous infusion of 0.1% cisplatin. Cisplatin infusion affected cochlear blood flow but not vessel conductivity. The cochlear blood flow decrease, maintained by local epinephrine application to the round window during cisplatin infusion, did not alter the cisplatin-induced hearing loss. In addition, the concentration of free cisplatin in scala tympani perilymph did not differ between epinephrine-treated and non-treated ears. Our results indicate that cisplatin transport into the cochlea is not an energy-dependent process in the lateral wall vasculature.

Friendship Quality, Peer Group Affiliation, and Peer Antisocial Behavior as Moderators of the Link Between Negative Parenting and Adolescent Externalizing Behavior

PubMed Central

Lansford, Jennifer E.; Criss, Michael M.; Pettit, Gregory S.; Dodge, Kenneth A.; Bates, John E.

2009-01-01

Quality of peer relationships and perceived peer antisocial behavior were examined as moderators of the link between negative parenting and externalizing behavior problems in school from middle childhood to early adolescence. Data on negative parenting (i.e., unilateral parental decision making, low supervision and awareness, and harsh discipline) were collected from 362 parents in the summer preceding the adolescents’ entry into Grade 6. Adolescent reports of positive peer relationships and peer antisocial behavior were assessed in the winter of Grade 7. The outcome measure was teacher report of adolescent externalizing behavior in the spring of Grade 7, controlling for externalizing behavior in Grade 5. High levels of friendship quality and peer group affiliation attenuated the association between unilateral parental decision making and adolescent externalizing behavior in school; this was particularly true when adolescents associated with peers perceived to be low in antisocial behavior. In addition, having low-quality peer relationships and having peers perceived to be highly antisocial further amplified the association between unilateral parental decision making and adolescent externalizing behavior problems. Finally, high levels of friend and peer group antisocial behavior exacerbated the predictiveness of harsh discipline for adolescents’ externalizing behavior. PMID:20209019

Effects of TD-5108 on Gastrointestinal Transit and Bowel Function in Health and Pharmacokinetics in Health and Constipation

PubMed Central

Manini, Mhd Louai; Camilleri, Michael; Goldberg, Michael; Sweetser, Seth; McKinzie, Sanna; Burton, Duane; Wong, Shekman; Kitt, Michael M.; Li, Yu-Ping; Zinsmeister, Alan R.

2010-01-01

Background TD-5108 is a potent, selective high intrinsic activity serotonin 5-HT4 receptor agonist. Aim To assess effects of TD-5108 on gastrointestinal transit and compare its pharmacokinetics (PK) in healthy volunteers (HV) and chronic constipation (CC) patients. Methods 60 HV were randomly assigned, double-blind to placebo, 5, 15, 30 or 50 mg TD-5108 (single and 6-day dosing). Primary endpoints were colonic transit (geometric center at 24 hours, GC24) and ascending colon emptying (ACE) T1/2 after first dose. Secondary endpoints included gastric emptying (GE) T1/2 and colonic filling at 6 h (CF6). Results Single dose TD-5108 significantly accelerated GC24, ACE T1/2, and CF6; 30 and 50°mg TD-5108 accelerated all 3 endpoints. With multiple doses, TD-5108 30 mg accelerated GC24, and overall accelerated GE T1/2 at 15–50 mg. PK studies showed dose proportionality in health, and no significant differences between health and chronic constipation with a 15 mg oral dose of TD-5108. Stimulation of bowel function after15 mg TD-5108 were similar in CC and controls. There were no serious adverse events; notable adverse were the predictable GI effects such as diarrhea or altered bowel movements. Conclusions TD-5108 significantly accelerated intestinal and colonic transit after single dosing and accelerated gastric emptying after multiple dosing. Further studies of its potential as a gastrointestinal and colonic prokinetic are warranted. PMID:19691492

Correlation between the single, high dose of ingested baclofen and clinical symptoms.

PubMed

Anand, Jacek Sein; Zając, Maciej; Waldman, Wojciech; Wojtyła, Andrzej; Biliński, Przemysław; Jaworska-Łuczak, Barbara

2017-12-23

Baclofen is a drug used mainly to treat muscle spasticity. Its overdose can lead to life-threatening clinical symptoms, including acute respiratory failure requiring mechanical ventilation. The aim of this study was to assess the prevalence of selected clinical symptoms associated with baclofen poisoning comparing to an ingested dose. 60 cases of oral baclofen poisoning were analyzed. Gender, age distribution, and correlation between the dose of ingested baclofen were studied, as well as and following clinical parameters: degree of altered consciousness, heart rate, blood pressure, presence of acute respiratory failure, duration of mechanical ventilation, and presence of psychotic symptoms. The study found statistically significant correlations between dosage of ingested baclofen and presence of acute respiratory failure, as well as duration of mechanical ventilation. No statistically significant correlations were found between the dose of ingested baclofen and presence of hypertension, bradycardia, acute psychotic symptoms, or level of consciousness disturbance. However, it was found that patients who suffered from hypertension, bradycardia, and altered mental status ingested a larger dose of baclofen. There is a statistically significant correlation between the dose of ingested baclofen and the presence of acute respiratory failure, and duration of mechanical ventilation. Patients who have taken a single dose of baclofen of 200 mg, or higher, should be managed in centres able to provide continuous monitoring of life functions. Those with a higher level of a single dose of baclofen ingestion (>500 mg), should be hospitalized in a Toxicology Unit or Intensive Care Unit able to provide airway support and mechanical ventilation.

Combination of blood flow asymmetry in the cerebral and cerebellar hemispheres on brain perfusion SPECT predicts 5-year outcome in patients with symptomatic unilateral major cerebral artery occlusion.

PubMed

Nomura, Jun-ichi; Ogasawara, Kuniaki; Saito, Hideo; Terasaki, Kazunori; Matsumoto, Yoshiyasu; Takahashi, Yoshihiro; Ogasawara, Yasushi; Saura, Hiroaki; Yoshida, Koji; Sato, Yuiko; Kubo, Yoshitaka; Ogawa, Akira

2014-03-01

Misery perfusion increases the risk of stroke recurrence in patients with symptomatic major cerebral artery occlusion. The ratio of brain perfusion contralateral-to-affected asymmetry in the cerebellar hemisphere to brain perfusion affected-to-contralateral asymmetry in the cerebral hemisphere (CblPR/CbrPR) indicates affected-to-contralateral asymmetry of oxygen extraction fraction (OEF) in the cerebral hemisphere. The purpose of the present study was to determine whether the CblPR/CbrPR on brain perfusion single-photon emission computed tomography (SPECT) predicts 5-year outcomes in patients with symptomatic unilateral occlusion of the middle cerebral artery (MCA) or internal carotid artery (ICA). Brain perfusion was assessed using N-isopropyl-p-[123I]-iodoamphetamine (123I-IMP) SPECT in 70 patients. A region of interest (ROI) was manually placed in the bilateral MCA territories and in the bilateral cerebellar hemispheres, and the CblPR/CbrPR was calculated. All patients were prospectively followed for 5 years. The primary end points were stroke recurrence or death. A total of 17 patients exhibited the primary end points, 11 of whom experienced subsequent ipsilateral strokes. Multivariate analysis revealed that only high CblPR/CbrPR was significantly associated with the development of the primary end point or subsequent ipsilateral strokes (95% confidential limits [CIs], 1.130-3.145; P  =  0.0114 or 95% CIs, 2.558-5.140; P  =  0.0045, respectively). The CblPR/CbrPR provided 65% (11/17) or 91% (10/11) sensitivity and 88% (47/53) or 88% (52/59) specificity in predicting the primary end point or subsequent ipsilateral strokes, respectively. The CblPR/CbrPR on brain perfusion SPECT predicts 5-year outcomes in patients with symptomatic unilateral occlusion of the MCA or ICA.

Modulation of inflammation by low and high doses of ionizing radiation: Implications for benign and malign diseases.

PubMed

Frey, Benjamin; Hehlgans, Stephanie; Rödel, Franz; Gaipl, Udo S

2015-11-28

Inflammation is a homeostatic mechanism aiming to maintain tissue integrity. The underlying immunological mechanisms and the interrelationship between ionizing radiation and inflammation are complex and multifactorial on cellular and chemical levels. On the one hand, radiation with single doses exceeding 1 Gy might initiate inflammatory reactions and thereby impact on tumor development. On the other hand, radiation is capable of attenuating an established inflammatory process, which is clinically used for the treatment of inflammatory and degenerative diseases with low-dose radiotherapy (single dose <1 Gy). At higher doses, ionizing radiation, especially in combination with additional immune stimulation, fosters the induction of immunogenic forms of tumor cell death and shifts the tumor microenvironment as well as the infiltration of immune cells from an anti- to a pro-inflammatory state. Distinct tumor infiltrating immune cells predict the response to radiochemotherapy in a multitude of tumor entities. While a high tumor infiltration of these adaptive immune cells mostly predicts a favorable disease outcome, a high infiltration of tumor-associated macrophages predicts an unfavorable response. Pro-inflammatory events should dominate over anti-inflammatory ones in this scenario. This review focuses on how ionizing radiation modulates inflammatory events in benign inflammatory and in malign diseases. A special focus is set on the role of tumor infiltrating lymphocytes and macrophages as biomarkers to predict treatment response and anti-tumor immunity and on mechanisms implicated in the anti-inflammatory effects of low-dose radiation therapy. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Muscle activity of the core during bilateral, unilateral, seated and standing resistance exercise.

PubMed

Saeterbakken, Atle Hole; Fimland, Marius Steiro

2012-05-01

Little is known about the effect of performing common resistance exercises standing compared to seated and unilaterally compared to bilaterally on muscle activation of the core. Thus, the purpose of this study was to compare the electromyographic activity (EMG) of the superficial core muscles (i.e. rectus abdominis, external oblique and erector spinae) between seated, standing, bilateral and unilateral dumbbell shoulder presses. 15 healthy males performed five repetitions at 80% of one-repetition maximum of the exercises in randomized order. Results were analyzed with a two-way analysis of variance and a Bonferroni post hoc test. The position × exercise interaction was significantly different for rectus abdominis (P = 0.016), but not for external oblique (P = 0.100) and erector spinae (P = 0.151). The following EMG results were observed: For rectus abdominis: ~49% lower in seated bilateral versus unilateral (P < 0.001), similar in standing bilateral versus unilateral (P = 0.408), ~81% lower in bilateral seated versus standing (P < 0.001), ~59% lower in unilateral seated versus standing (P < 0.001); For external oblique: ~81% lower in seated bilateral versus unilateral (P < 0.001), ~68% lower in standing bilateral than unilateral (P < 0.001), ~58% lower in bilateral seated versus standing (P < 0.001), ~28% lower in unilateral seated versus standing (P = 0.002); For erector spinae: similar in seated bilateral versus unilateral (P = 0.737), ~18% lower in standing bilateral versus unilateral (P = 0.001), similar in seated versus standing bilateral (P = 0.480) and unilateral (P = 0.690). In conclusion, to enhance neuromuscular activation of the superficial core muscles, standing exercises should be used instead of seated exercises, and unilateral exercises should be used instead of bilateral exercises.

Durable antibody responses following one dose of the bivalent human papillomavirus L1 virus-like particle vaccine in the Costa Rica Vaccine Trial.

PubMed

Safaeian, Mahboobeh; Porras, Carolina; Pan, Yuanji; Kreimer, Aimee; Schiller, John T; Gonzalez, Paula; Lowy, Douglas R; Wacholder, Sholom; Schiffman, Mark; Rodriguez, Ana C; Herrero, Rolando; Kemp, Troy; Shelton, Gloriana; Quint, Wim; van Doorn, Leen-Jan; Hildesheim, Allan; Pinto, Ligia A

2013-11-01

The Costa Rica HPV16/18 Vaccine Trial (CVT) showed that four-year vaccine efficacy against 12-month HPV16/18 persistent infection was similarly high among women who received one, two, or the recommended three doses of the bivalent HPV16/18 L1 virus-like particle (VLP) vaccine. Live-attenuated viral vaccines, but not simple-subunit vaccines, usually induce durable lifelong antibody responses after a single dose. It is unclear whether noninfectious VLP vaccines behave more like live-virus or simple-subunit vaccines in this regard. To explore the likelihood that efficacy will persist longer term, we investigated the magnitude and durability of antibodies to this vaccine by measuring HPV16- and HPV18-specific antibodies by VLP-ELISA using serum from enrollment, vaccination, and annual visits through four years in four vaccinated groups; one-dose (n = 78), two-doses separated by one month (n = 140), two doses separated by six months (n = 52), and three scheduled doses (n = 120, randomly selected). We also tested enrollment sera from n = 113 HPV16- or HPV18 L1-seropositive women prevaccination, presumably from natural infection. At four years, 100% of women in all groups remained HPV16/18 seropositive; both HPV16/18 geometric mean titers (GMT) among the extended two-dose group were non-inferior to the three-dose group, and ELISA titers were highly correlated with neutralization titers in all groups. Compared with the natural infection group, HPV16/18 GMTs were, respectively, at least 24 and 14 times higher among the two-dose and 9 and 5 times higher among one-dose vaccinees. Antibody levels following one-dose remained stable from month 6 through month 48. Results raise the possibility that even a single dose of HPV VLPs will induce long-term protection. ©2013 AACR.

High-Riding Congenital Hip Dislocation: THA With Unilateral vs Bilateral Transverse Femoral Shortening Osteotomy.

PubMed

Can, Ata; Sarikaya, Ilker A; Yontar, Necip S; Erdogan, Ayse O; Gorgun, Baris; Erdogan, Fahri

2018-05-01

We argue that 1-stage bilaterally total hip arthroplasty (THA) could be acceptable in bilateral coxarthrosis because of high-riding developmental dysplasia of the hip (DDH). Sixty-nine cases (51 patients) of high-riding DDH in patients who underwent THA from 2010 to 2013 were reviewed. Patients were divided into 2 groups: unilateral (group 1) and 1-stage bilateral surgery (group 2). The clinical measurements were the visual analog scale and Harris Hip Score. The average follow-up was 37.3 months for group 1 and 38.8 months for group 2. The hospital stay time was 5.2 days in group 1 and 6.2 days in group 2 (P = .334). The mean Harris Hip Score and visual analog scale score were improved significantly after surgery for both groups, and there was no statistically significant difference (P = .988). There was no difference between groups 1 and 2 in terms of complications (P = .137). Our data confirm that 1-stage bilateral transverse osteotomy with THA is an effective method as unilateral and it does not increase the length of patients' hospital stays and features a low risk of postoperative complications in the treatment of patients with high-riding DDH. Copyright © 2017 Elsevier Inc. All rights reserved.

Cost-Effectiveness of Pediatric Cochlear Implantation in Rural China.

PubMed

Qiu, Jianxin; Yu, Chongxian; Ariyaratne, Thathya V; Foteff, Chris; Ke, Zhangmin; Sun, Yi; Zhang, Li; Qin, Feifei; Sanderson, Georgina

2017-07-01

To evaluate the cost utility of cochlear implantation (CI) for severe to profound sensorineural hearing loss (SNHL) among children from rural settings in P.R. China (China). A cost-utility analysis (CUA) was undertaken using data generated from a single-center substudy of the Cochlear Pediatric Implanted Recipient Observational Study (Cochlear P-IROS). The data were projected over a 20-year time horizon using a decision tree model. The Chinese healthcare payer and patient perspectives were adopted. Unilateral CI of children with a severe-to-profound SNHL compared with their preimplantation state of no treatment or amplification with hearing aids ("no CI" status). Incremental costs per quality adjusted life year (QALY) gained. The mean total discounted cost of unilateral CI was CNY 252,506 (37,876 USD), compared with CNY 29,005 (4,351 USD) for the no CI status from the healthcare payer plus patient perspective. A total discounted benefit of 8.9 QALYs was estimated for CI recipients compared with 6.7 QALYs for the no CI status. From the healthcare payer plus patient perspective, incremental cost-effectiveness ratio (ICER) for unilateral CI compared with no CI was CNY 100,561 (15,084 USD) per QALY. The healthcare payer perspective yielded an ICER of CNY 40,929 (6,139 USD) per QALY. Both ICERs fell within one to three times China's gross domestic product per capita (GDP, 2011-2015), considered "cost-effective" by World Health Organization (WHO) standards. Treatment with unilateral CI is a cost-effective hearing solution for children with severe to profound SNHL in rural China. Increased access to mainstream education and greater opportunities for employment, are potential downstream benefits of CI that may yield further societal and economic benefits. CI may be considered favorably for broader inclusion in medical insurance schemes across China.

Pharmacokinetics of terbinafine after oral administration of a single dose to Hispaniolan Amazon parrots (Amazona ventralis).

PubMed

Evans, Erika E; Emery, Lee C; Cox, Sherry K; Souza, Marcy J

2013-06-01

To determine pharmacokinetics after oral administration of a single dose of terbinafine hydrochloride to Hispaniolan Amazon parrots (Amazona ventralis). 6 healthy adult Hispaniolan Amazon parrots. A single dose of terbinafine hydrochloride (60 mg/kg) was administered orally to each bird, which was followed immediately by administration of a commercially available gavage feeding formula. Blood samples were collected at the time of drug administration (time 0) and 0.25, 0.5, 1, 2, 4, 8, 12, and 24 hours after drug administration. Plasma concentrations of terbinafine were determined via high-performance liquid chromatography. Data from 1 bird were discarded because of a possible error in the dose of drug administered. After oral administration of terbinafine, the maximum concentration for the remaining 5 fed birds ranged from 109 to 671 ng/mL, half-life ranged from 6 to 13.5 hours, and time to the maximum concentration ranged from 2 to 8 hours. No adverse effects were observed. Analysis of the results indicated that oral administration of terbinafine at a dose of 60 mg/kg to Amazon parrots did not result in adverse effects and may be potentially of use in the treatment of aspergillosis. Additional studies are needed to determine treatment efficacy and safety.

Faecal egg counts and expulsion dynamics of the whipworm, Trichuris trichiura following self-infection.

PubMed

Hansen, E P; Tejedor, A M; Thamsborg, S M; Alstrup Hansen, T V; Dahlerup, J F; Nejsum, P

2016-05-01

More than 400 million humans are estimated to be infected with the intestinal helminth parasite, Trichuris trichiura. The infection is chronic in nature and high-intensity infection can lead to colitis, anaemia, Trichuris Dysentery Syndrome and reduced cognitive performance. Single doses of 400 mg albendazole or 500 mg mebendazole (MBZ) are used in mass drug administration programmes, but this has been shown to be insufficient. In this study, worm expulsion dynamics are described after MBZ treatment, given as a multi-dose and single-dose treatment in two separate T. trichiura self-infection studies. Worm expulsion dynamics post-treatment showed a similar pattern regardless of the dose regime, with the first worms observed on day 2 and the last worms expelled on days 9 and 13 post-treatment. Establishment of a chronic infection was observed following the inefficient single-dose treatment. The prepatent period was 13-16 weeks in both studies and worms were found to have a lifespan of at least 1 year and 10 months. These self-infection studies provide key information on the chronicity of T. trichiura infections, expulsion dynamics after anthelmintic treatment and the prepatent period, as well as the fecundity of female worms, which was around 18,000 eggs/female per day.

Three-dimensional visualization of endolymphatic hydrops after intravenous administration of single-dose gadodiamide.

PubMed

Naganawa, Shinji; Yamazaki, Masahiro; Kawai, Hisashi; Bokura, Kiminori; Sone, Michihiko; Nakashima, Tsutomu

2013-01-01

Endolymphatic hydrops can be visualized with high contrast-to-noise ratio even after intravenous injection of single-dose gadolinium-based contrast material (IV-SD-GBCM) using HYDROPS-Mi2 images. We applied 3-dimensional rendering software to process HYDROPS-Mi2 images of 15 ears with and without suspected Ménière's disease and separately visualized the volumes of endo- and perilymph in patients with Ménière's disease even after IV-SD-GBCM. Such dimensional visualization will aid understanding of the pathophysiology of Ménière's disease.

Palonosetron as an anti-emetic and anti-nausea agent in oncology.

PubMed

Aapro, Matti S

2007-12-01

Palonosetron (Aloxi(®), Onicit(®), Paloxi(®)) is a second-generation 5-HT(3) receptor antagonist (RA) with an extended half-life of ~40 hours and high binding affinity for the 5-HT₃ receptor that is markedly different from other 5-HT(3) RAs. Phase III trials demonstrate that a single dose of palonosetron compared with traditional 5-HT₃ RAs is more effective in preventing chemotherapy-induced nausea and vomiting (CINV) during the first 24 hours following chemotherapy (acute CINV), and also exhibits prolonged efficacy to provide significantly better protection from CINV in the delayed and overall phases. This superior and extended protection from CINV conferred by palonosetron following a single intravenous dose before chemotherapy simplifies dosing schedules. Recent research has focused on optimization of palonosetron-based antiemetic regimens, particularly in combination with steroids and neurokinin-1 RAs. The available clinical data indicate high control rates for palonosetron, suggesting a synergistic potential for protection in patients scheduled to receive emetogenic drug regimens.

Salvage low-dose-rate 125I partial prostate brachytherapy after dose-escalated external beam radiotherapy

PubMed Central

Chang, Lynn

2014-01-01

Purpose To report outcomes on 5 patients treated with salvage partial low-dose-rate (LDR) 125-iodine (125I) permanent prostate seed brachytherapy (BT) for biopsy-proven locally persistent prostate cancer, following failure of dose-escalated external beam radiotherapy (EBRT). Material and methods A retrospective review of the Fox Chase Cancer Center prostate cancer database identified five patients treated with salvage partial LDR 125I seed implant for locally persistent disease following dose-escalated EBRT to 76-84 Gy in 2 Gy per fraction equivalent. All patients had post-EBRT biopsies confirming unilateral locally persistent prostate cancer. Pre-treatment, EBRT and BT details, as well as post-treatment characteristics were documented and assessed. Results The median follow-up post-implant was 41 months. All five patients exhibited low acute genitourinary and gastrointestinal toxicities. Increased erectile dysfunction was noted in three patients. There were no biochemical failures following salvage LDR 125I seed BT to date, with a median post-salvage PSA of 0.4 ng/mL. Conclusions In carefully selected patients with local persistence of disease, partial LDR 125I permanent prostate seed implant appears to be a feasible option for salvage local therapy with an acceptable toxicity profile. Further study is needed to determine long-term results of this approach. PMID:25337135

Long-term Pulmonary Responses to Quadweekly Intermittent Intratracheal Spray Instillations of Magnetite (Fe3O4) Nanoparticles for 52 Weeks in Fischer 344 Rats.

PubMed

Tada, Yukie; Yano, Norio; Takahashi, Hiroshi; Yuzawa, Katsuhiro; Ando, Hiroshi; Kubo, Yoshikazu; Nagasawa, Akemichi; Inomata, Akiko; Ogata, Akio; Nakae, Dai

2013-12-01

Information about potential risks of iron nanomaterials is still limited, while a wide variety of applications are expected. We recently reported acute phase responses of male and female Fischer 344 rats after a single intratracheal spray instillation of Fe3O4 nanoparticles (magnetite), clearly showing dose-dependent pulmonary inflammatory changes (Tada et al., J Toxicol Pathol 25, 233-239, 2012). The present study assessed long-term responses of male and female Fischer 344 rats to multiple administrations of magnetite. Ten-week-old male and female Fischer 344 rats (n=20/group) were exposed to a total of 13 quadweekly intermittent intratracheal spray instillations of magnetite during the experimental period of 52 weeks, at doses of 0, 0.2 (low), 1.0 (medium) and 5.0 (high-dose) mg/kg body weight per administration. Absolute and relative lung weights of the high-dose group were significantly higher than those of the control group. Macroscopically, slight enlargement and scattered black patches were recognized in the lungs and the lung-associated lymph nodes of the high-dose group. Histopathologically, infiltration of macrophages phagocytosing magnetite (all dose groups) and of chronic inflammatory cells (medium- and high-dose males and high-dose females), alveolar bronchiolization and granuloma (high-dose group) were observed. In addition, alveolar hyperplasias were observed in some rats of the high-dose group, and cytoplasmic overexpression of β-catenin protein was immunohistochemically found in such lesions. The present results clearly show that instilled magnetite causes chronic inflammatory responses in the lung. These responses occur in a dose-dependent manner without apparent differences among sexes.

Long-term mesalamine maintenance in ulcerative colitis: which is more important? Adherence or daily dose.

PubMed

Khan, Nabeel; Abbas, Ali M; Koleva, Yordanka N; Bazzano, Lydia A

2013-05-01

There are limited data about the long-term follow-up of patients with ulcerative colitis (UC) maintained on high versus low doses of mesalamine. We evaluated the best long-term average daily dose that would keep the disease in remission. Nationwide ulcerative colitis data were obtained from the Veterans Affairs health care system for the period 2001 to 2011. Those who started mesalamine maintenance during this period were included. Average daily dose and the level of adherence were assessed for the period between the first mesalamine dispense and the date of first flare defined as the first filling of 40 mg/day or more of oral prednisone or any dose of intravenous steroids. Patients with ulcerative colitis maintained on an average daily dose 2.4 to 2.8 g/day (low dose) were compared with 4.4 to 4.8 g/day (high dose). Adherence was assessed using continuous single interval medication availability indicator. We included 4452 patients with a median follow-up of 6 years. There was no significant reduction in the risk of flares when comparing high versus low average mesalamine dose among patients with high [hazard ratio = 0.96, P = 0.8)] and medium (hazard ratio = 0.74, P = 0.17) adherence. However, there was a significant reduction in the risk of flares with high dose of mesalamine among patients with low adherence (hazard ratio = 0.28, P = 0.003). Our data show that when starting a patient on mesalamine, there is no difference in the long-term flare risk between low versus high average daily dose as long as the patients have a high to moderate level of adherence.

Pharmacokinetic profiles of repaglinide in elderly subjects with type 2 diabetes.

PubMed

Hatorp, V; Huang, W C; Strange, P

1999-04-01

Pharmacokinetic profiles of single- and multiple-dose regimens of repaglinide were evaluated in 12 elderly subjects with type 2 diabetes. On day 1, following a 10-hour fast, subjects received a single 2-mg dose of repaglinide. Starting on day 2 and continuing for 7 days, each subject received a 2-mg dose of repaglinide 15 minutes before each of the three main meals. On day 9, subjects received a single 2-mg dose of repaglinide. Pharmacokinetic profiles, including area under the curve (AUC), log(AUC), maximal concentration (Cmax), log(Cmax), time to maximal concentration (Tmax), and half-life (T(1/2)), were determined at completion of the single- and multiple-dose regimens (days 1 and 9, respectively). Trough repaglinide values were collected on days 2 through 7. The mean log(AUC) values after multiple dosing were significantly higher than the values obtained after a single dose. The mean values for log(Cmax), and Tmax were comparable after each dosing regimen. The T(1/2) of repaglinide after multiple dosing was 1.7 hours. The trough values for repaglinide were low. No hypoglycemic events were reported. The pharmacokinetic profiles of repaglinide after single- and multiple-dose regimens were similar, and repaglinide was well tolerated by elderly subjects with type 2 diabetes.

A Chinese patient with pusher syndrome and unilateral spatial neglect syndrome.

PubMed

Chen, Xiao-Wei; Lin, Cheng-He; Zheng, Hua; Lin, Zhen-Lan

2014-07-01

To observe clinical manifestations, behavioral characteristics, and effects of rehabilitation on a patient with pusher syndrome and unilateral spatial neglect caused by right thalamic hemorrhage. Assessment of pusher syndrome was made by the Scale for Contraversive pushing (SCP), and unilateral spatial neglect syndrome was diagnosed using line cancellation, letter and star cancellation, line bisection tests and copy and continuation of graphic sequence test. Behavioral therapy, occupational therapy, reading training and traditional Chinese medicine methods were adopted for treatment of pusher syndrome and unilateral spatial neglect. The patient showed typical pusher syndrome and unilateral spatial neglect symptoms. The pusher syndrome and unilateral spatial neglect symptoms were significantly improved following rehabilitation treatments. Pusher syndrome and unilateral spatial neglect syndrome occurred simultaneously after right thalamic hemorrhage. Early rehabilitation therapy can reduce the symptoms of pusher syndrome and unilateral spatial neglect syndrome and improve motor function.

The effects of peritoneal dialysis on the single dose and steady state pharmacokinetics of valproic acid in a uremic epileptic child.

PubMed

Orr, J M; Farrell, K; Abbott, F S; Ferguson, S; Godolphin, W J

1983-01-01

The pharmacokinetics of valproic acid (VPA) have been studied during peritoneal dialysis in a uremic male epileptic child following a single 500 mg dose and after multiple doses over 5 months (700 mg daily) of valproic acid as the syrup. Serum level decline was biphasic in both instances with a terminal half-life of 27.2 after the single dose and 10.2 h at steady-state. Total serum clearance was 0.0236 l/h/kg after the single dose and increased to 0.0408 l/h/kg after 5 months. Free (intrinsic) serum clearances were 0.1489 and 0.1518 l/h/kg and serum free fractions were 0.224 and 0.272 respectively for the single dose and steady-state studies. Peritoneal dialysis for periods of 12 or 24 h removed an average of 4.5% of the VPA dose.

Poster - 08: Preliminary Investigation into Collapsed-Cone based Dose Calculations for COMS Eye Plaques

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

Morrison, Hali; Menon, Geetha; Sloboda, Ron

Purpose: To investigate the accuracy of model-based dose calculations using a collapsed-cone algorithm for COMS eye plaques loaded with I-125 seeds. Methods: The Nucletron SelectSeed 130.002 I-125 seed and the 12 mm COMS eye plaque were incorporated into a research version of the Oncentra® Brachy v4.5 treatment planning system which uses the Advanced Collapsed-cone Engine (ACE) algorithm. Comparisons of TG-43 and high-accuracy ACE doses were performed for a single seed in a 30×30×30 cm{sup 3} water box, as well as with one seed in the central slot of the 12 mm COMS eye plaque. The doses along the plaque centralmore » axis (CAX) were used to calculate the carrier correction factor, T(r), and were compared to tabulated and MCNP6 simulated doses for both the SelectSeed and IsoAid IAI-125A seeds. Results: The ACE calculated dose for the single seed in water was on average within 0.62 ± 2.2% of the TG-43 dose, with the largest differences occurring near the end-welds. The ratio of ACE to TG-43 calculated doses along the CAX (T(r)) of the 12 mm COMS plaque for the SelectSeed was on average within 3.0% of previously tabulated data, and within 2.9% of the MCNP6 simulated values. The IsoAid and SelectSeed T(r) values agreed within 0.3%. Conclusions: Initial comparisons show good agreement between ACE and MC doses for a single seed in a 12 mm COMS eye plaque; more complicated scenarios are being investigated to determine the accuracy of this calculation method.« less

Primaquine or other 8-aminoquinoline for reducing Plasmodium falciparum transmission

PubMed Central

Graves, Patricia M; Gelband, Hellen; Garner, Paul

2015-01-01

Background Mosquitoes become infected with Plasmodium when they ingest gametocyte-stage parasites from an infected person's blood. Plasmodium falciparum gametocytes are sensitive to the drug primaquine (PQ) and other 8-aminoquinolines (8AQ); these drugs could prevent parasite transmission from infected people to mosquitoes, and consequently reduce the incidence of malaria. However, PQ will not directly benefit the individual, and could be harmful to those with glucose-6-phosphate dehydrogenase (G6PD) deficiency. In 2010, The World Health Organization (WHO) recommended a single dose of PQ at 0.75 mg/kg, alongside treatment for P. falciparum malaria to reduce transmission in areas approaching malaria elimination. In 2013 the WHO revised this to 0.25 mg/kg due to concerns about safety. Objectives To assess whether giving PQ or an alternative 8AQ alongside treatment for P. falciparum malaria reduces malaria transmission, and to estimate the frequency of severe or haematological adverse events when PQ is given for this purpose. Search methods We searched the following databases up to 10 Feb 2014 for trials: the Cochrane Infectious Diseases Group Specialized Register; the Cochrane Central Register of Controlled Trials (CENTRAL), published in The Cochrane Library; MEDLINE; EMBASE; LILACS; metaRegister of Controlled Trials (mRCT); and the WHO trials search portal using 'malaria*', 'falciparum', and 'primaquine' as search terms. In addition, we searched conference proceedings and reference lists of included studies, and contacted researchers and organizations. Selection criteria Randomized controlled trials (RCTs) or quasi-RCTs comparing PQ (or alternative 8AQ) given as a single dose or short course alongside treatment for P. falciparum malaria with malaria treatment given without PQ/8AQ in adults or children. Data collection and analysis Two authors independently screened all abstracts, applied inclusion criteria, and extracted data. We sought evidence of an impact on transmission (community incidence), infectiousness (mosquitoes infected from humans) and potential infectiousness (gametocyte measures). We calculated the area under the curve (AUC) for gametocyte density over time for comparisons for which data were available. We sought data on haematological and other adverse effects, as well as secondary outcomes of asexual clearance time and recrudescence. We stratified by whether the malaria treatment regimen included an artemisinin derivative or not; by PQ dose category (low < 0.4 mg/kg; medium ≥ 0.4 to < 0.6 mg/kg; high ≥ 0.6 mg/kg); and by PQ schedules. We used the GRADE approach to assess evidence quality. Main results We included 17 RCTs and one quasi-RCT. Eight studies tested for G6PD status: six then excluded participants with G6PD deficiency, one included only those with G6PD deficiency, and one included all irrespective of status. The remaining ten trials either did not report on whether they tested (8), or reported that they did not test (2). Nine trials included study arms with artemisinin-based malaria treatment regimens, and eleven included study arms with non-artemisinin-based treatments. Only two trials evaluated PQ given at low doses (0.25 mg/kg in one and 0.1 mg/kg in the other). PQ with artemisinin-based treatments: No trials evaluated effects on malaria transmission directly (incidence, prevalence, or entomological inoculation rate), and none evaluated infectiousness to mosquitoes. For potential infectiousness, the proportion of people with detectable gametocytaemia on day eight was reduced by around two thirds with high dose PQ category (RR 0.29, 95% CI 0.22 to 0.37, seven trials, 1380 participants, high quality evidence), and with medium dose PQ category (RR 0.34, 95% CI 0.19 to 0.59, two trials, 269 participants, high quality evidence), but the trial evaluating low dose PQ category (0.1 mg/kg) did not demonstrate an effect (RR 0.67, 95% CI 0.44 to 1.02, one trial, 223 participants, low quality evidence). Reductions in log(10)AUC estimates for gametocytaemia on days 1 to 43 with medium and high doses ranged from 24.3% to 87.5%. For haemolysis, one trial reported percent change in mean haemoglobin against baseline, and did not detect a difference between the two arms (very low quality evidence). PQ with non-artemisinin treatments: No trials assessed effects on malaria transmission directly. Two small trials from the same laboratory evaluated infectiousness to mosquitoes, and report that infectivity was eliminated on day 8 in 15/15 patients receiving high dose PQ compared to 1/15 in the control group (low quality evidence). For potential infectiousness, the proportion of people with detectable gametocytaemia on day 8 was reduced by around half with high dose PQ category (RR 0.44, 95% CI 0.27 to 0.70, three trials, 206 participants, high quality evidence), and by around a third with medium dose category (RR 0.62, 0.50 to 0.76, two trials, 283 participants, high quality evidence), but the single trial using low dose PQ category did not demonstrate a difference between groups (one trial, 59 participants, very low quality evidence). Reduction in log(10)AUC for gametocytaemia days 1 to 43 were 24.3% and 27.1% for two arms in one trial giving medium dose PQ. No trials systematically sought evidence of haemolysis. Two trials evaluated the 8AQ bulaquine, and suggest the effects may be greater than PQ, but the small number of participants (n = 112) preclude a definite conclusion. Authors' conclusions In individual patients, PQ added to malaria treatments reduces gametocyte prevalence when given in doses greater than 0.4 mg/kg. Whether this translates into preventing people transmitting malaria to mosquitoes has rarely been tested in controlled trials, but there appeared to be a strong reduction in infectiousness in the two small studies that evaluated this. No included trials evaluated whether this policy has an impact on community malaria transmission either in low-endemic settings approaching elimination, or in highly-endemic settings where many people are infected but have no symptoms and are unlikely to be treated. For the currently recommended low dose regimen, there is little direct evidence to be confident that the effect of reduction in gametocyte prevalence is preserved. Most trials excluded people with G6PD deficiency, and thus there is little reliable evidence from controlled trials of the safety of PQ in single dose or short course. PLAIN LANGUAGE SUMMARY A single dose of primaquine added to malaria treatment to prevent malaria transmission We conducted a review of the effects of adding a single dose (or short course) of primaquine to malaria treatment with the aim of reducing the transmission of malaria. We included 17 randomized controlled trials and one quasi-randomized controlled trial. What is primaquine and how might it reduce transmission Primaquine is an antimalarial drug which does not cure malaria illness, but is known to kill the gametocyte stage of the malaria parasite which infects mosquitoes when they bite humans. Primaquine is also known to have potentially serious side effects in people with an enzyme deficiency common in many malaria endemic settings (glucose-6-phosphate dehydrogenase (G6PD) deficiency). In these people, high doses of primaquine given over several days sometimes destroys red blood cells, causing anaemia and, in some cases, possibly life-threatening effects. The World Health Organization (WHO) recommends adding a single dose of primaquine to malaria treatment with the intention of reducing malaria transmission and to contribute to malaria elimination. This recommendation was made in 2010, but in 2013 the WHO amended its recommendation from a dose of 0.75 mg/kg to 0.25 mg/kg due to concerns about safety, and indirect evidence suggesting this was as effective as the higher dose.This review examines the evidence of benefits and harms of using primaquine in this way, and looks for evidence that primaquine will reduce malaria transmission in communities. What the research says We did not find any studies that tested whether primaquine added to malaria treatment reduces the community transmission of malaria. When added to current treatments for malaria (artemisinin-based combination therapy), we found no studies evaluating the effects of primaquine on the number of mosquitoes infected. However, primaquine does reduce the duration of infectiousness (the period that gametocytes are detected circulating in the blood) when given at doses of 0.4 mg/kg or above (high quality evidence). We only found one study using 0.1 mg/kg but this study did not conclusively show that primaquine was still effective at this dose (low quality evidence). When added to older treatments for malaria, two studies showed that primaquine at doses of 0.75 mg/kg reduced the number of mosquitoes infected after biting humans (low quality evidence). Doses above 0.4 mg/kg reduced the duration of detectable gametocytes (high quality evidence), but in a single study of the currently recommended 0.25 mg/kg no effect was demonstrated (very low quality evidence). Some studies excluded patients with G6PD deficiency, some included them, and some did not comment. Overall the safety of PQ given as a single dose was poorly evaluated across all studies, so these data do not demonstrate whether the drug is safe or potentially harmful at this dosing level. PMID:25693791

Primaquine or other 8-aminoquinoline for reducing P. falciparum transmission

PubMed Central

Graves, Patricia M; Gelband, Hellen; Garner, Paul

2014-01-01

Background Mosquitoes become infected with Plasmodium when they ingest gametocyte-stage parasites from an infected person's blood. Plasmodium falciparum gametocytes are sensitive to the drug primaquine (PQ) and other 8-aminoquinolines (8AQ); these drugs could prevent parasite transmission from infected people to mosquitoes, and consequently reduce the incidence of malaria. However, PQ will not directly benefit the individual, and could be harmful to those with glucose-6-phosphate dehydrogenase (G6PD) deficiency. In 2010, The World Health Organization (WHO) recommended a single dose of PQ at 0.75 mg/kg, alongside treatment for P. falciparum malaria to reduce transmission in areas approaching malaria elimination. In 2013 the WHO revised this to 0.25 mg/kg due to concerns about safety. Objectives To assess whether giving PQ or an alternative 8AQ alongside treatment for P. falciparum malaria reduces malaria transmission, and to estimate the frequency of severe or haematological adverse events when PQ is given for this purpose. Search methods We searched the following databases up to 10 Feb 2014 for trials: the Cochrane Infectious Diseases Group Specialized Register; the Cochrane Central Register of Controlled Trials (CENTRAL), published in The Cochrane Library; MEDLINE; EMBASE; LILACS; metaRegister of Controlled Trials (mRCT); and the WHO trials search portal using 'malaria*', 'falciparum', and 'primaquine' as search terms. In addition, we searched conference proceedings and reference lists of included studies, and contacted researchers and organizations. Selection criteria Randomized controlled trials (RCTs) or quasi-RCTs comparing PQ (or alternative 8AQ) given as a single dose or short course alongside treatment for P. falciparum malaria with malaria treatment given without PQ/8AQ in adults or children. Data collection and analysis Two authors independently screened all abstracts, applied inclusion criteria, and extracted data. We sought evidence of an impact on transmission (community incidence), infectiousness (mosquitoes infected from humans) and potential infectiousness (gametocyte measures). We calculated the area under the curve (AUC) for gametocyte density over time for comparisons for which data were available. We sought data on haematological and other adverse effects, as well as secondary outcomes of asexual clearance time and recrudescence. We stratified by whether the malaria treatment regimen included an artemisinin derivative or not; by PQ dose category (low < 0.4 mg/kg; medium ≥ 0.4 to < 0.6 mg/kg; high ≥ 0.6 mg/kg); and by PQ schedules. We used the GRADE approach to assess evidence quality. Main results We included 17 RCTs and one quasi-RCT. Eight studies tested for G6PD status: six then excluded participants with G6PD deficiency, one included only those with G6PD deficiency, and one included all irrespective of status. The remaining ten trials either did not report on whether they tested (8), or reported that they did not test (2). Nine trials included study arms with artemisinin-based malaria treatment regimens, and eleven included study arms with non-artemisinin-based treatments. Only two trials evaluated PQ given at low doses (0.25 mg/kg in one and 0.1 mg/kg in the other). PQ with artemisinin-based treatments: No trials evaluated effects on malaria transmission directly (incidence, prevalence, or entomological inoculation rate), and none evaluated infectiousness to mosquitoes. For potential infectiousness, the proportion of people with detectable gametocytaemia on day eight was reduced by around two thirds with high dose PQ category (RR 0.29, 95% CI 0.22 to 0.37, seven trials, 1380 participants, high quality evidence), and with medium dose PQ category (RR 0.34, 95% CI 0.19 to 0.59, two trials, 269 participants, high quality evidence), but the trial evaluating low dose PQ category (0.1 mg/kg) did not demonstrate an effect (RR 0.67, 95% CI 0.44 to 1.02, one trial, 223 participants, low quality evidence). Reductions in log(10)AUC estimates for gametocytaemia on days 1 to 43 with medium and high doses ranged from 24.3% to 87.5%. For haemolysis, one trial reported percent change in mean haemoglobin against baseline, and did not detect a difference between the two arms (very low quality evidence). PQ with non-artemisinin treatments: No trials assessed effects on malaria transmission directly. Two small trials from the same laboratory evaluated infectiousness to mosquitoes, and report that infectivity was eliminated on day 8 in 15/15 patients receiving high dose PQ compared to 1/15 in the control group (low quality evidence). For potential infectiousness, the proportion of people with detectable gametocytaemia on day 8 was reduced by around half with high dose PQ category (RR 0.44, 95% CI 0.27 to 0.70, three trials, 206 participants, high quality evidence), and by around a third with medium dose category (RR 0.62, 0.50 to 0.76, two trials, 283 participants, high quality evidence), but the single trial using low dose PQ category did not demonstrate a difference between groups (one trial, 59 participants, very low quality evidence). Reduction in log(10)AUC for gametocytaemia days 1 to 43 were 24.3% and 27.1% for two arms in one trial giving medium dose PQ. No trials systematically sought evidence of haemolysis. Two trials evaluated the 8AQ bulaquine, and suggest the effects may be greater than PQ, but the small number of participants (n = 112) preclude a definite conclusion. Authors' conclusions In individual patients, PQ added to malaria treatments reduces gametocyte prevalence when given in doses greater than 0.4 mg/kg. Whether this translates into preventing people transmitting malaria to mosquitoes has rarely been tested in controlled trials, but there appeared to be a strong reduction in infectiousness in the two small studies that evaluated this. No included trials evaluated whether this policy has an impact on community malaria transmission either in low-endemic settings approaching elimination, or in highly-endemic settings where many people are infected but have no symptoms and are unlikely to be treated. For the currently recommended low dose regimen, there is little direct evidence to be confident that the effect of reduction in gametocyte prevalence is preserved. Most trials excluded people with G6PD deficiency, and thus there is little reliable evidence from controlled trials of the safety of PQ in single dose or short course. PLAIN LANGUAGE SUMMARY A single dose of primaquine added to malaria treatment to prevent malaria transmission We conducted a review of the effects of adding a single dose (or short course) of primaquine to malaria treatment with the aim of reducing the transmission of malaria. We included 17 randomized controlled trials and one quasi-randomized controlled trial. What is primaquine and how might it reduce transmission Primaquine is an antimalarial drug which does not cure malaria illness, but is known to kill the gametocyte stage of the malaria parasite which infects mosquitoes when they bite humans. Primaquine is also known to have potentially serious side effects in people with an enzyme deficiency common in many malaria endemic settings (glucose-6-phosphate dehydrogenase (G6PD) deficiency). In these people, high doses of primaquine given over several days sometimes destroys red blood cells, causing anaemia and, in some cases, possibly life-threatening effects. The World Health Organization (WHO) recommends adding a single dose of primaquine to malaria treatment with the intention of reducing malaria transmission and to contribute to malaria elimination. This recommendation was made in 2010, but in 2013 the WHO amended its recommendation from a dose of 0.75 mg/kg to 0.25 mg/kg due to concerns about safety, and indirect evidence suggesting this was as effective as the higher dose.This review examines the evidence of benefits and harms of using primaquine in this way, and looks for evidence that primaquine will reduce malaria transmission in communities. What the research says We did not find any studies that tested whether primaquine added to malaria treatment reduces the community transmission of malaria. When added to current treatments for malaria (artemisinin-based combination therapy), we found no studies evaluating the effects of primaquine on the number of mosquitoes infected. However, primaquine does reduce the duration of infectiousness (the period that gametocytes are detected circulating in the blood) when given at doses of 0.4 mg/kg or above (high quality evidence). We only found one study using 0.1 mg/kg but this study did not conclusively show that primaquine was still effective at this dose (low quality evidence). When added to older treatments for malaria, two studies showed that primaquine at doses of 0.75 mg/kg reduced the number of mosquitoes infected after biting humans (low quality evidence). Doses above 0.4 mg/kg reduced the duration of detectable gametocytes (high quality evidence), but in a single study of the currently recommended 0.25 mg/kg no effect was demonstrated (very low quality evidence). Some studies excluded patients with G6PD deficiency, some included them, and some did not comment. Overall the safety of PQ given as a single dose was poorly evaluated across all studies, so these data do not demonstrate whether the drug is safe or potentially harmful at this dosing level. PMID:24979199

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

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

Song, Changhoon; Hong, Beom-Ju; Bok, Seoyeon

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

Long-term evaluation of mucosal and systemic immunity and protection conferred by different polio booster vaccines.

PubMed

Xiao, Yuhong; Daniell, Henry

2017-09-25

Oral polio vaccine (OPV) and Inactivated Polio Vaccine (IPV) have distinct advantages and limitations. IPV does not provide mucosal immunity and introduction of IPV to mitigate consequences of circulating vaccine-derived polio virus from OPV has very limited effect on transmission and OPV campaigns are essential for interrupting wild polio virus transmission, even in developed countries with a high coverage of IPV and protected sewer systems. The problem is magnified in many countries with limited resources. Requirement of refrigeration for storage and transportation for both IPV and OPV is also a major challenge in developing countries. Therefore, we present here long-term studies on comparison of a plant-based booster vaccine, which is free of virus and cold chain with IPV boosters and provide data on mucosal and systemic immunity and protection conferred by neutralizing antibodies. Mice were primed subcutaneously with IPV and boosted orally with lyophilized plant cells containing 1μg or 25μg polio viral protein 1 (VP1), once a month for three months or a single booster one year after the first prime. Our results show that VP1-IgG1 titers in single or double dose IPV dropped to background levels after one year of immunization. This decrease correlated with >50% reduction in seropositivity in double dose and <10% seropositivity in single dose IPV against serotype 1. Single dose IPV offered no or minimal protection against serotype 1 and 2 but conferred protection against serotype 3. VP1-IgA titers were negligible in IPV single or double dose vaccinated mice. VP1 antigen with two plant-derived adjuvants induced significantly high level and long lasting VP1-IgG1, IgA and neutralizing antibody titers (average 4.3-6.8 log2 titers). Plant boosters with VP1 and plant derived adjuvants maintained the same level titers from 29 to 400days and conferred the same level of protection against all three serotypes throughout the duration of this study. Even during period, when no plant booster was given (∼260days), VP1-IgG1 titers were maintained at high levels. Lyophilized plant cells expressing VP1 can be stored without losing efficacy, eliminating cold chain. Virus-free, cold-chain free vaccine is ready for further clinical development. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Condylectomy and "surgery first" approach: An expedited treatment for condylar hyperplasia in a patient with facial asymmetry.

PubMed

López, Diego Fernando; Aristizábal, Juan Fernando; Martínez-Smit, Rosana

2017-01-01

Condylar Hyperplasia (CH) is a self-limiting pathology condition that produces severe facial deformity at the expense of mandibular asymmetry. In this case report a 15-year-old female patient was diagnosed with Unilateral Condylar Hiperplasia (UCH) by mean of single-photon emission computed tomography (SPECT) and histological study. A high condylectomy in the right condyle was performed to stop the active status of the hyperplasia. A month after condylectomy, orthognathic jaw impaction and asymmetric mandibular setback surgery was performed with the Surgery First Approach (SFA). After 10 days, orthodontic appointments were made every two weeks during 4 months. The active phase of treatment lasted 14 months. Excellent facial and occlusal outcomes were obtained and after 24 months in retention the results remained stable.

Influence of Al³⁺ addition on the flocculation and sedimentation of activated sludge: comparison of single and multiple dosing patterns.

PubMed

Wen, Yue; Zheng, Wanlin; Yang, Yundi; Cao, Asheng; Zhou, Qi

2015-05-15

In this study, the flocculation and sedimentation performance of activated sludge (AS) with single and multiple dosing of trivalent aluminum (Al(3+)) were studied. The AS samples were cultivated in sequencing batch reactors at 22 °C. The dosages of Al(3+) were 0.00, 0.125, 0.5, 1.0, and 1.5 meq/L for single dosing, and 0.1 meq/L for multiple dosing. Under single dosing conditions, as Al(3+) dosage increased, the zeta potential, total interaction energy, and effluent turbidity decreased, whereas the sludge volume index (SVI) increased, indicating that single Al(3+) dosing could enhance sludge flocculation, but deteriorate sedimentation. By comparison, adding an equal amount of Al(3+) through multiple dosing achieved a similar reduction in turbidity, but the zeta potential was higher, while the loosely bound extracellular polymeric substances (LB-EPS) content and SVI remarkably declined. Although the difference in the flocculation performances between the two dosing patterns was not significant, the underlying mechanisms were quite distinct: the interaction energy played a more important role under single dosing conditions, whereas multiple dosing was more effective in reducing the EPS content. Multiple dosing, which allows sufficient time for sludge restructuring and floc aggregation, could simultaneously optimize sludge flocculation and sedimentation. Copyright © 2015 Elsevier Ltd. All rights reserved.

Children with unilateral hearing loss may have lower intelligence quotient scores: A meta-analysis.

PubMed

Purcell, Patricia L; Shinn, Justin R; Davis, Greg E; Sie, Kathleen C Y

2016-03-01

In this meta-analysis, we reviewed observational studies investigating differences in intelligence quotient (IQ) scores of children with unilateral hearing loss compared to children with normal hearing. PubMed Medline, Cumulative Index to Nursing and Allied Health Literature, Embase, PsycINFO. A query identified all English-language studies related to pediatric unilateral hearing loss published between January 1980 and December 2014. Titles, abstracts, and articles were reviewed to identify observational studies reporting IQ scores. There were 261 unique titles, with 29 articles undergoing full review. Four articles were identified, which included 173 children with unilateral hearing loss and 202 children with normal hearing. Ages ranged from 6 to 18 years. Three studies were conducted in the United States and one in Mexico. All were of high quality. All studies reported full-scale IQ results; three reported verbal IQ results; and two reported performance IQ results. Children with unilateral hearing loss scored 6.3 points lower on full-scale IQ, 95% confidence interval (CI) [-9.1, -3.5], P value < 0.001; and 3.8 points lower on performance IQ, 95% CI [-7.3, -0.2], P value 0.04. When investigating verbal IQ, we detected substantial heterogeneity among studies; exclusion of the outlying study resulted in significant difference in verbal IQ of 4 points, 95% CI [-7.5, -0.4], P value 0.028. This meta-analysis suggests children with unilateral hearing loss have lower full-scale and performance IQ scores than children with normal hearing. There also may be disparity in verbal IQ scores. Laryngoscope, 126:746-754, 2016. © 2015 The American Laryngological, Rhinological and Otological Society, Inc.

Association between unilateral or bilateral mastectomy and breast cancer death in patients with unilateral ductal carcinoma.

PubMed

Agarwal, Shailesh; Pappas, Lisa; Agarwal, Jayant

2017-01-01

Utilization of bilateral mastectomy for unilateral breast cancer is increasing despite cost and surgical risks with conflicting reports of survival benefit. Current studies evaluating death after bilateral mastectomy have included patients treated both with breast conservation therapy and unilateral mastectomy. In this study, we directly compared breast cancer-specific death of patients who underwent bilateral or unilateral mastectomy for unilateral breast cancer using a matched cohort analysis. This was an observational study of women diagnosed with unilateral breast cancer from 1998 through 2002, using the Surveillance, Epidemiology, and End Results (SEER) database. A 4-to-1 matched cohort of patients was selected including 14,075 patients. Mortality of the groups was compared using Cox proportional hazards models for cause-specific death. A total of 41,510 patients diagnosed with unilateral breast cancer were included. Unilateral mastectomy was performed in 93% of patients, while bilateral mastectomy was performed in the remaining 7% of patients. When 4-to-1 matching was performed, 11,260 unilateral mastectomy and 2,815 bilateral mastectomy patients were included. Patients with bilateral mastectomy did not have a significantly lower hazard of breast cancer-specific death when compared with patients with unilateral mastectomy (hazard ratio: 0.92 vs 1.00, p =0.11). Bilateral mastectomy did not provide a clinically or statistically significant breast cancer-specific mortality benefit over unilateral mastectomy based on a matched cohort analysis of a nationwide population database. These findings should be interpreted in the context of patient preference and alternative benefits of bilateral mastectomy.

Association between unilateral or bilateral mastectomy and breast cancer death in patients with unilateral ductal carcinoma

PubMed Central

Agarwal, Shailesh; Pappas, Lisa; Agarwal, Jayant

2017-01-01

Background Utilization of bilateral mastectomy for unilateral breast cancer is increasing despite cost and surgical risks with conflicting reports of survival benefit. Current studies evaluating death after bilateral mastectomy have included patients treated both with breast conservation therapy and unilateral mastectomy. In this study, we directly compared breast cancer–specific death of patients who underwent bilateral or unilateral mastectomy for unilateral breast cancer using a matched cohort analysis. Methods This was an observational study of women diagnosed with unilateral breast cancer from 1998 through 2002, using the Surveillance, Epidemiology, and End Results (SEER) database. A 4-to-1 matched cohort of patients was selected including 14,075 patients. Mortality of the groups was compared using Cox proportional hazards models for cause-specific death. Results A total of 41,510 patients diagnosed with unilateral breast cancer were included. Unilateral mastectomy was performed in 93% of patients, while bilateral mastectomy was performed in the remaining 7% of patients. When 4-to-1 matching was performed, 11,260 unilateral mastectomy and 2,815 bilateral mastectomy patients were included. Patients with bilateral mastectomy did not have a significantly lower hazard of breast cancer–specific death when compared with patients with unilateral mastectomy (hazard ratio: 0.92 vs 1.00, p=0.11). Conclusion Bilateral mastectomy did not provide a clinically or statistically significant breast cancer–specific mortality benefit over unilateral mastectomy based on a matched cohort analysis of a nationwide population database. These findings should be interpreted in the context of patient preference and alternative benefits of bilateral mastectomy. PMID:29180900

Impact of unilateral conductive hearing loss due to aural atresia on academic performance in children.

PubMed

Kesser, Bradley W; Krook, Kaelyn; Gray, Lincoln C

2013-09-01

This study evaluates the effect of unilateral conductive hearing loss secondary to aural atresia on elementary school children's academic performance. Case control survey and review of audiometric data. One hundred thirty-two surveys were mailed to families of children with aural atresia, and 48 surveys were sent to families of children with unilateral sensorineural hearing loss (SNHL) to identify rates of grade retention, use of any resource, and behavioral problems. Audiometric data of the cohort were tabulated. Of the 40 atresia patients, none repeated a grade, but 65% needed some resources: 12.5% currently use a hearing aid, 32.5% use(d) a frequency-modulated system in school, 47.5% had an Individualized Education Plan, and 45% utilized speech therapy. Compared to the unilateral SNHL group and a cohort of children with unilateral SNHL in an earlier study, children with unilateral atresia were less likely to repeat a grade. Children in both unilateral atresia and SNHL groups were more likely to utilize some resource in the academic setting compared to the unilateral SNHL children in the prior study. Unilateral conductive hearing loss due to aural atresia has an impact on academic performance in children, although not as profound when compared to children with unilateral SNHL. The majority of these children with unilateral atresia utilize resources in the school setting. Parents, educators, and health care professionals should be aware of the impact of unilateral conductive hearing loss and offer appropriate habilitative services. Copyright © 2013 The American Laryngological, Rhinological and Otological Society, Inc.

A 0.18 micrometer CMOS Thermopile Readout ASIC Immune to 50 MRAD Total Ionizing Dose (SI) and Single Event Latchup to 174MeV-cm(exp 2)/mg

NASA Technical Reports Server (NTRS)

Quilligan, Gerard T.; Aslam, Shahid; Lakew, Brook; DuMonthier, Jeffery J.; Katz, Richard B.; Kleyner, Igor

2014-01-01

Radiation hardened by design (RHBD) techniques allow commercial CMOS circuits to operate in high total ionizing dose and particle fluence environments. Our radiation hard multi-channel digitizer (MCD) ASIC (Figure 1) is a versatile analog system on a chip (SoC) fabricated in 180nm CMOS. It provides 18 chopper stabilized amplifier channels, a 16- bit sigma-delta analog-digital converter (SDADC) and an on-chip controller. The MCD was evaluated at Goddard Space Flight Center and Texas A&M University's radiation effects facilities and found to be immune to single event latchup (SEL) and total ionizing dose (TID) at 174 MeV-cm(exp 2)/mg and 50 Mrad (Si) respectively.

Single Event Effects and Total Dose Testing of the Intersil ISL 70003SEH Integrated Point of Load Converter

NASA Astrophysics Data System (ADS)

van Vonno, N. W.; White, J. D.; Pearce, L. G.; Thomson, E. J.; Gill, J. S.; Mansilla, O. E.

2014-08-01

Single-event transient (SET) phenomena in power management applications has evolved into a key issue, particularly in point of load (POL) buck regulators, as the loads driven by these devices are sensitive to even short-term overvoltage conditions. We preface this paper by a discussion of earlier destructive and nondestructive SEE testing of Intersil integrated point of load regulators, with emphasis on SET phenomena and some of the lessons learned in this work. We then report recent results of SET and destructive SEE testing of the ISL70003SEH POL converter, together with a brief discussion of the part's electrical and radiation hardness specifications. We conclude with a brief overview of low and high dose rate total dose testing of the part.

A review of immunogenicity and tolerability of live attenuated Hepatitis A vaccine in children.

PubMed

Rao, Sameer; Mao, J S; Motlekar, Salman; Fangcheng, Zhuang; Kadhe, Ganesh

2016-12-01

Changing epidemiology of Hepatitis A virus (HAV) has led to an increased susceptibility of adolescents and adults to the infection. Vaccination can remarkably reduce the incidence and associated morbidity of HAV infection. This review is focused on the safety and efficacy of H2 strain derived live attenuated Hepatitis A vaccine. We found the vaccine to be highly immunogenic with minimal or negligible safety issues. Moreover, a single dose of live attenuated vaccine persists a long term immune response and can be a preferred option for developing countries. In 2014, Indian Academy of Paediatrics (IAP) also updated their recommendations for H2 vaccine as a single dose as against the previous 2 dose schedule. A focused approach to include the vaccine in national immunization program should be explored.

Fast, high-resolution 3D dosimetry utilizing a novel optical-CT scanner incorporating tertiary telecentric collimation

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

Sakhalkar, H. S.; Oldham, M.

2008-01-15

This study introduces a charge coupled device (CCD) area detector based optical-computed tomography (optical-CT) scanner for comprehensive verification of radiation dose distributions recorded in nonscattering radiochromic dosimeters. Defining characteristics include: (i) a very fast scanning time of {approx}5 min to acquire a complete three-dimensional (3D) dataset, (ii) improved image formation through the use of custom telecentric optics, which ensures accurate projection images and minimizes artifacts from scattered and stray-light sources, and (iii) high resolution (potentially 50 {mu}m) isotropic 3D dose readout. The performance of the CCD scanner for 3D dose readout was evaluated by comparison with independent 3D readout frommore » the single laser beam OCTOPUS-scanner for the same PRESAGE dosimeters. The OCTOPUS scanner was considered the 'gold standard' technique in light of prior studies demonstrating its accuracy. Additional comparisons were made against calculated dose distributions from the ECLIPSE treatment-planning system. Dose readout for the following treatments were investigated: (i) a single rectangular beam irradiation to investigate small field and very steep dose gradient dosimetry away from edge effects, (ii) a 2-field open beam parallel-opposed irradiation to investigate dosimetry along steep dose gradients, and (iii) a 7-field intensity modulated radiation therapy (IMRT) irradiation to investigate dosimetry for complex treatment delivery involving modulation of fluence and for dosimetry along moderate dose gradients. Dose profiles, dose-difference plots, and gamma maps were employed to evaluate quantitative estimates of agreement between independently measured and calculated dose distributions. Results indicated that dose readout from the CCD scanner was in agreement with independent gold-standard readout from the OCTOPUS-scanner as well as the calculated ECLIPSE dose distribution for all treatments, except in regions within a few millimeters of the edge of the dosimeter, where edge artifact is predominant. Agreement of line profiles was observed, even along steep dose gradients. Dose difference plots indicated that the CCD scanner dose readout differed from the OCTOPUSscanner readout and ECLIPSE calculations by {approx}10% along steep dose gradients and by {approx}5% along moderate dose gradients. Gamma maps (3% dose-difference and 3 mm distance-to-agreement acceptance criteria) revealed agreement, except for regions within 5 mm of the edge of the dosimeter where the edge artifact occurs. In summary, the data demonstrate feasibility of using the fast, high-resolution CCD scanner for comprehensive 3D dosimetry in all applications, except where dose readout is required close to the edges of the dosimeter. Further work is ongoing to reduce this artifact.« less

Single-Dose Pharmacokinetics and Safety of Ziprasidone in Children and Adolescents

ERIC Educational Resources Information Center

Sallee, Floyd R.; Miceli, Jeffrey J.; Tensfeldt, Thomas; Robarge, Lisa; Wilner, Keith; Patel, Nick C.

2006-01-01

Objective: The purpose of this study was to provide single-dose pharmacokinetic, safety, and tolerability data for ziprasidone in youths with tic disorder, for comparison to adult studies to discern whether ziprasidone pediatric dosing could be modeled from adult data. Method: A single-dose, open-label study of ziprasidone was conducted in youths…

Oxytocin efficacy is modulated by dosage and oxytocin receptor genotype in young adults with high-functioning autism: a 24-week randomized clinical trial

PubMed Central

Kosaka, H; Okamoto, Y; Munesue, T; Yamasue, H; Inohara, K; Fujioka, T; Anme, T; Orisaka, M; Ishitobi, M; Jung, M; Fujisawa, T X; Tanaka, S; Arai, S; Asano, M; Saito, D N; Sadato, N; Tomoda, A; Omori, M; Sato, M; Okazawa, H; Higashida, H; Wada, Y

2016-01-01

Recent studies have suggested that long-term oxytocin administration can alleviate the symptoms of autism spectrum disorder (ASD); however, factors influencing its efficacy are still unclear. We conducted a single-center phase 2, pilot, randomized, double-blind, placebo-controlled, parallel-group, clinical trial in young adults with high-functioning ASD, to determine whether oxytocin dosage and genetic background of the oxytocin receptor affects oxytocin efficacy. This trial consisted of double-blind (12 weeks), open-label (12 weeks) and follow-up phases (8 weeks). To examine dose dependency, 60 participants were randomly assigned to high-dose (32 IU per day) or low-dose intranasal oxytocin (16 IU per day), or placebo groups during the double-blind phase. Next, we measured single-nucleotide polymorphisms (SNPs) in the oxytocin receptor gene (OXTR). In the intention-to-treat population, no outcomes were improved after oxytocin administration. However, in male participants, Clinical Global Impression-Improvement (CGI-I) scores in the high-dose group, but not the low-dose group, were significantly higher than in the placebo group. Furthermore, we examined whether oxytocin efficacy, reflected in the CGI-I scores, is influenced by estimated daily dosage and OXTR polymorphisms in male participants. We found that >21 IU per day oxytocin was more effective than ⩽21 IU per day, and that a SNP in OXTR (rs6791619) predicted CGI-I scores for ⩽21 IU per day oxytocin treatment. No severe adverse events occurred. These results suggest that efficacy of long-term oxytocin administration in young men with high-functioning ASD depends on the oxytocin dosage and genetic background of the oxytocin receptor, which contributes to the effectiveness of oxytocin treatment of ASD. PMID:27552585

Oxytocin efficacy is modulated by dosage and oxytocin receptor genotype in young adults with high-functioning autism: a 24-week randomized clinical trial.

PubMed

Kosaka, H; Okamoto, Y; Munesue, T; Yamasue, H; Inohara, K; Fujioka, T; Anme, T; Orisaka, M; Ishitobi, M; Jung, M; Fujisawa, T X; Tanaka, S; Arai, S; Asano, M; Saito, D N; Sadato, N; Tomoda, A; Omori, M; Sato, M; Okazawa, H; Higashida, H; Wada, Y

2016-08-23

Recent studies have suggested that long-term oxytocin administration can alleviate the symptoms of autism spectrum disorder (ASD); however, factors influencing its efficacy are still unclear. We conducted a single-center phase 2, pilot, randomized, double-blind, placebo-controlled, parallel-group, clinical trial in young adults with high-functioning ASD, to determine whether oxytocin dosage and genetic background of the oxytocin receptor affects oxytocin efficacy. This trial consisted of double-blind (12 weeks), open-label (12 weeks) and follow-up phases (8 weeks). To examine dose dependency, 60 participants were randomly assigned to high-dose (32 IU per day) or low-dose intranasal oxytocin (16 IU per day), or placebo groups during the double-blind phase. Next, we measured single-nucleotide polymorphisms (SNPs) in the oxytocin receptor gene (OXTR). In the intention-to-treat population, no outcomes were improved after oxytocin administration. However, in male participants, Clinical Global Impression-Improvement (CGI-I) scores in the high-dose group, but not the low-dose group, were significantly higher than in the placebo group. Furthermore, we examined whether oxytocin efficacy, reflected in the CGI-I scores, is influenced by estimated daily dosage and OXTR polymorphisms in male participants. We found that >21 IU per day oxytocin was more effective than ⩽21 IU per day, and that a SNP in OXTR (rs6791619) predicted CGI-I scores for ⩽21 IU per day oxytocin treatment. No severe adverse events occurred. These results suggest that efficacy of long-term oxytocin administration in young men with high-functioning ASD depends on the oxytocin dosage and genetic background of the oxytocin receptor, which contributes to the effectiveness of oxytocin treatment of ASD.

SU-E-T-10: A Clinical Implementation and the Dosimetric Evidence in High Dose Rate Vaginal Multichannel Applicator Brachytherapy

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

Syh, J; Syh, J; Patel, B

2015-06-15

Purpose: The multichannel cylindrical applicator has a distinctive modification of the traditional single channel cylindrical applicator. The novel multichannel applicator has additional peripheral channels that provide more flexibility both in treatment planning process and outcomes. To protect by reducing doses to adjacent organ at risk (OAR) while maintaining target coverage with inverse plan optimization are the goals for such novel Brachytherapy device. Through a series of comparison and analysis of reults in more than forty patients who received HDR Brachytherapy using multichannel vaginal applicator, this procedure has been implemented in our institution. Methods: Multichannel planning was CT image based. Themore » CTV of 5mm vaginal cuff rind with prescribed length was well reconstructed as well as bladder and rectum. At least D95 of CTV coverage is 95% of prescribed dose. Multichannel inverse plan optimization algorithm not only shapes target dose cloud but set dose avoids to OAR’s exclusively. The doses of D2cc, D5cc and D5; volume of V2Gy in OAR’s were selected to compare with single channel results when sole central channel is only possibility. Results: Study demonstrates plan superiorly in OAR’s doe reduction in multi-channel plan. The D2cc of the rectum and bladder were showing a little lower for multichannel vs. single channel. The V2Gy of the rectum was 93.72% vs. 83.79% (p=0.007) for single channel vs. multichannel respectively. Absolute reduced mean dose of D5 by multichannel was 17 cGy (s.d.=6.4) and 44 cGy (s.d.=15.2) in bladder and rectum respectively. Conclusion: The optimization solution in multichannel was to maintain D95 CTV coverage while reducing the dose to OAR’s. Dosimetric advantage in sparing critical organs by using a multichannel applicator in HDR Brachytherapy treatment of the vaginal cuff is so promising and has been implemented clinically.« less

Single-dose Live Oral Cholera Vaccine CVD 103-HgR Protects Against Human Experimental Infection With Vibrio cholerae O1 El Tor.

PubMed

Chen, Wilbur H; Cohen, Mitchell B; Kirkpatrick, Beth D; Brady, Rebecca C; Galloway, David; Gurwith, Marc; Hall, Robert H; Kessler, Robert A; Lock, Michael; Haney, Douglas; Lyon, Caroline E; Pasetti, Marcela F; Simon, Jakub K; Szabo, Flora; Tennant, Sharon; Levine, Myron M

2016-06-01

No licensed cholera vaccine is presently available in the United States. Cholera vaccines available in other countries require 2 spaced doses. A single-dose cholera vaccine that can rapidly protect short-notice travelers to high-risk areas and help control explosive outbreaks where logistics render 2-dose immunization regimens impractical would be a major advance.PXVX0200, based on live attenuated Vibrio cholerae O1 classical Inaba vaccine strain CVD 103-HgR, elicits seroconversion of vibriocidal antibodies (a correlate of protection) within 10 days of a single oral dose. We investigated the protection conferred by this vaccine in a human cholera challenge model. Consenting healthy adult volunteers, 18-45 years old, were randomly allocated 1:1 to receive 1 oral dose of vaccine (approximately 5 × 10(8) colony-forming units [CFU]) or placebo in double-blind fashion. Volunteers ingested approximately 1 × 10(5) CFU of wild-type V. cholerae O1 El Tor Inaba strain N16961 10 days or 3 months after vaccination and were observed on an inpatient research ward for stool output measurement and management of hydration. The vaccine was well tolerated, with no difference in adverse event frequency among 95 vaccinees vs 102 placebo recipients. The primary endpoint, moderate (≥3.0 L) to severe (≥5.0 L) diarrheal purge, occurred in 39 of 66 (59.1%) placebo controls but only 2 of 35 (5.7%) vaccinees at 10 days (vaccine efficacy, 90.3%; P < .0001) and 4 of 33 (12.1%) vaccinees at 3 months (vaccine efficacy, 79.5%; P < .0001). The significant vaccine efficacy documented 10 days and 3 months after 1 oral dose of PXVX0200 supports further development as a single-dose cholera vaccine. NCT01895855. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Absolute Bioavailability and Effect of Food on the Disposition of Safinamide Immediate Release Tablets in Healthy Adult Subjects.

PubMed

Seithel-Keuth, Annick; Johne, Andreas; Freisleben, Achim; Kupas, Katrin; Lissy, Michael; Krösser, Sonja

2013-01-01

The objectives of this study were to establish the basic intravenous (IV) single-dose PK of safinamide and its major human metabolites, the absolute bioavailability (BA) and food effect on safinamide tablets. Fourteen healthy adult male and female subjects received 50 mg safinamide single-dose treatments according to a randomized, 3-period, 2-sequence crossover design: immediate release (IR) tablets, administered after an overnight fast and after a standardized high-fat, high-calorie breakfast, and IV solution, administered over 30 minutes. Treatments were separated by wash-out intervals of at least 17 days. Serial blood samples were collected for 240 hours postdosing to evaluate safinamide parent drug and metabolite concentrations for the determination of PK parameters. The absolute BA of safinamide 50 mg IR tablets was high, with geoMean AUC0-∞ ratios of about 95% (90% CI: 90-99%) indicating that safinamide is virtually completely absorbed after oral administration. Safinamide IR tablets did not display a food effect on exposure parameters; both 90% CIs for the ratios fed/fasted of AUC0-∞ and Cmax were entirely within the bioequivalence acceptance margins of 80-125%. Only tmax was delayed by about 30% in the fed state. Oral and IV safinamide 50 mg single-dose administrations were generally well tolerated. © The Author(s) 2013.

A study of dose-proportionality in the pharmacokinetics of the oral direct renin inhibitor aliskiren in healthy subjects.

PubMed

Limoges, D; Dieterich, H A; Yeh, C-M; Vaidyanathan, S; Howard, D; Dole, W P

2008-05-01

To evaluate the dose-proportionality of the pharmacokinetics of aliskiren, the first in a new class of orally active direct renin inhibitors approved for the treatment of hypertension. This was an open-label, single-center, single-dose, randomized, 4-period crossover study. Following a 21-day screening period, 32 healthy male or female subjects (ages 18 - 45 years) were randomized to 1 of 4 aliskiren dosing sequence groups (8 subjects per group): 75, 150, 300 and 600 mg. Blood samples were obtained for determination of plasma aliskiren concentrations (HPLC/MS/MS) for 96 h post dose. Log-transformed pharmacokinetic parameters AUC and C(max) were analyzed to determine dose-proportionality using the power model, parameter = A*(Dose)(beta), where A = intercept and beta = dose-proportionality coefficient. The predefined dose-proportionality criteria over the dose range 75 â 600 mg were 90% confidence intervals (CI) for beta contained within the range 0.89 - 1.11. AUC and Cmax values increased with increasing doses of aliskiren. Both AUC and C(max) were associated with high variability (coefficient of variation 55 - 64% for AUC and 59 - 117% for C(max)). The estimated proportionality coefficients (beta) for AUC(0-infiniti), AUC(0-t) and C(max) were 1.18 (90% CI 1.10, 1.25), 1.29 (90% CI 1.22, 1.36) and 1.42 (90% CI 1.31, 1.52), respectively. Dose-proportionality was, therefore, not demonstrated across the entire 8-fold dose range. For the clinical dose range of 150 â 300 mg, increases of 2.3- and 2.6-fold were observed for AUC and C(max), respectively. All doses of aliskiren were well tolerated. Exposure to aliskiren was greater than proportional over the dose range of 75 - 600 mg. Over the therapeutic dose range of 150 â 300 mg approved for the treatment of hypertension, AUC and Cmax increased by 2.3- and 2.6-fold, respectively. The pharmacokinetics of aliskiren show relatively high intersubject variability.