Dose finding study of granisetron in patients receiving high-dose cisplatin chemotherapy. The Granisetron Study Group.

Science.gov (United States)

Riviere, A.

1994-01-01

The efficacy and safety of three different doses of granisetron (2 micrograms kg-1, group A; 10 micrograms kg-1, group B; 40 micrograms kg-1, group C) were compared in a randomised, double-blind study of 157 patients due to receive high-dose cisplatin therapy (mean dose > 97 mg m-2). In each group, up to two 3 mg rescue doses of granisetron were allowed if more than mild nausea or vomiting occurred. In group A 30.8%, in group B 61.5% and in group C 67.9% of patients were complete responders (i.e. no vomiting or nothing worse than mild nausea) during the first 24 h. These differences are significant between groups A and B, and A and C. There were no statistically significant differences in any efficacy variable between the 10 micrograms kg-1 and 40 micrograms kg-1 groups, although in each case the trend favoured the higher dose. Additional rescue doses resulted in resolved or improved symptoms in 95.3% for the first rescue dose and 93.3% for the second. Over the 7 days of the study, 82.7%, 82.7% and 86.8% of patients in groups A, B and C respectively were treated with granisetron alone. Headache was the most common side-effect, reported by 9.6% of patients; the majority of headaches were mild. There was no difference between the treatment groups regarding the adverse event rate. We concluded that prophylactic doses of 10 or 40 micrograms kg-1 lead to a safe and satisfactory degree of control of nausea and vomiting induced by high-dose cisplatin. PMID:8180032

Neglectable benefit of searching for incidental findings in the Dutch-Belgian lung cancer screening trial (NELSON) using low-dose multidetector CT

International Nuclear Information System (INIS)

Wiel, J.C.M. van de; Wang, Y.; Xu, D.M.; Zaag-Loonen, H.J. van der; Jagt, E.J. van der; Oudkerk, M.; Klaveren, R.J. van

2007-01-01

The purpose of this study was to prospectively determine the frequency and spectrum of incidental findings (IFs) and their clinical implications in a high risk population for lung cancer undergoing low-dose multidetector computed tomography (MDCT) screening for lung cancer. Scans of 1,929 participants were evaluated for lung lesions and IFs by two radiologists. IFs were categorised as not clinically relevant or possibly clinically relevant. Findings were considered possibly clinically relevant if they could require further evaluation or could have substantial clinical implications. All possibly clinically relevant IFs were reviewed by a third radiologist, who determined its clinical relevance. Of all 1,929 participants, 1,410 (73%) had not clinically relevant IFs and 163 (8%) had possibly clinically relevant IFs of which 129 (79%) were indeed considered clinically relevant. Additional imaging was performed mainly by ultrasound (112 of 118, 96%). All but one lesion were concluded to be benign, mostly cysts (n = 115, 80%). Only 21 (1%) participants had findings with clinical implications. In one participant a malignancy was found, yet without any clinical benefit since no curative treatment was possible. Based on our results, we advise against systematically searching for and reporting of IFs in lung cancer screening studies using low-dose MDCT. (orig.)

Intradermal Inactivated Poliovirus Vaccine: A Preclinical Dose-Finding Study

OpenAIRE

Kouiavskaia, Diana; Mirochnitchenko, Olga; Dragunsky, Eugenia; Kochba, Efrat; Levin, Yotam; Troy, Stephanie; Chumakov, Konstantin

2014-01-01

Intradermal delivery of vaccines has been shown to result in dose sparing. We tested the ability of fractional doses of inactivated poliovirus vaccine (IPV) delivered intradermally to induce levels of serum poliovirus-neutralizing antibodies similar to immunization through the intramuscular route. Immunogenicity of fractional doses of IPV was studied by comparing intramuscular and intradermal immunization of Wistar rats using NanoPass MicronJet600 microneedles. Intradermal delivery of partial...

A Dose-Finding Study of Dexketoprofen in Patients Undergoing Laparoscopic Cholecystectomy: A Randomized Clinical Trial on Effects on the Analgesic Concentration of Oxycodone.

Science.gov (United States)

Piirainen, Annika; Kokki, Hannu; Immonen, Satu; Eskelinen, Matti; Häkkinen, Merja R; Hautajärvi, Heidi; Kokki, Merja

2015-12-01

Dexketoprofen has been shown to provide efficient analgesia and an opioid-sparing effect after orthopedic surgery. In this dose-finding study, we evaluated the analgesic efficacy and opioid-sparing effect of dexketoprofen administered intravenously (i.v.) after laparoscopic cholecystectomy (LCC). Twenty-four patients undergoing LCC were randomized to receive dexketoprofen 10 or 50 mg i.v. 15 min before the end of the surgery. Subjects were provided with 0.2 mg/kg of oxycodone at anesthesia induction. In the recovery room, pain was assessed with an 11-point numerical rating scale (NRS; score of 0 = no pain, score of 10 = most severe pain) every 10 min. When the NRS score was ≥3/10 at rest or ≥5/10 at wound compression, a plasma sample was taken for analysis of oxycodone [to determine the minimum effective concentration (MEC)], its metabolites, and dexketoprofen. After that, subjects were titrated with oxycodone 2 or 3 mg i.v. every 10 min until the NRS score was dexketoprofen. At the onset of pain, the plasma oxycodone concentrations (MEC) were similar in the two groups: median 60 ng/mL (range 37-73) in the 10 mg group and median 52 ng/mL (range 24-79) in the 50 mg group. At the time of pain relief, the MEACs were 98 ng/mL (range 59-150) in the 10 mg group and 80 ng/mL (range 45-128) in the 50 mg group. The total doses of oxycodone needed to achieve pain relief were similar: 0.11 mg/kg (range 0-0.33) in the 10 mg group and 0.08 mg/kg (range 0-0.24) in the 50 mg group. Eleven subjects developed mild desaturation or a decreased respiratory rate after oxycodone titration. In the present double-blinded, randomized clinical trial, the need for a rescue opioid analgesic, oxycodone, was similar with the two dose levels of dexketoprofen-10 and 50 mg i.v.-after LCC.

Evaluation of Mangosteen juice blend on biomarkers of inflammation in obese subjects: a pilot, dose finding study

Directory of Open Access Journals (Sweden)

Singh Betsy B

2009-10-01

Full Text Available Abstract Background The ability to reduce inflammation in overweight and obese individuals may be valuable in preventing the progression to metabolic syndrome with associated risks for heart disease and diabetes. The purpose of this study was to evaluate the effect of multiple dosages of a proprietary Mangosteen Juice blend on indicators of inflammation and antioxidant levels in obese patients with elevated C-reactive protein (CRP levels. Methods The study was an 8 week randomized, double-blind, placebo-controlled study with a pre-study 2 week washout period. The study included four groups including placebo and three difference doses of the test product, XanGo Juice™: 3, 6 or 9 oz twice daily. The primary outcome measure of this study was high-sensitivity (HS-CRP. Secondary outcome measures included other biochemical indicators of inflammation, anthropomorphic measures and a safety evaluation. Results One hundred twenty two (122 persons were screened for the study, 44 were randomized and 40 completed the study. HS-CRP measurements dropped after 8 weeks treatment compared to baseline in all 3 dose groups and increased in the placebo group. The changes from baseline were not significant but the comparison of change from baseline was significant for the 18 oz group when compared to placebo (p = 0.02. Other markers of inflammation (inflammatory cytokines and a marker for lipid peroxidation (F2 isoprostane did not show any significant differences when compared with placebo. There was a trend towards a decrease in BMI in the juice groups. There were no side effects reported in any of the groups and none of the laboratory or EKG safety assessments indicated clinically significant changes for any subject. Conclusion In this pilot, dose-finding study, a proprietary mangosteen juice blend (XanGo Juice™ reduced CRP levels (increased change from baseline compared to placebo for those taking the highest dose of 18 oz per day. Further studies with a

Evaluation of Mangosteen juice blend on biomarkers of inflammation in obese subjects: a pilot, dose finding study.

Science.gov (United States)

Udani, Jay K; Singh, Betsy B; Barrett, Marilyn L; Singh, Vijay J

2009-10-20

The ability to reduce inflammation in overweight and obese individuals may be valuable in preventing the progression to metabolic syndrome with associated risks for heart disease and diabetes. The purpose of this study was to evaluate the effect of multiple dosages of a proprietary Mangosteen Juice blend on indicators of inflammation and antioxidant levels in obese patients with elevated C-reactive protein (CRP) levels. The study was an 8 week randomized, double-blind, placebo-controlled study with a pre-study 2 week washout period. The study included four groups including placebo and three difference doses of the test product, XanGo Juice: 3, 6 or 9 oz twice daily. The primary outcome measure of this study was high-sensitivity (HS)-CRP. Secondary outcome measures included other biochemical indicators of inflammation, anthropomorphic measures and a safety evaluation. One hundred twenty two (122) persons were screened for the study, 44 were randomized and 40 completed the study. HS-CRP measurements dropped after 8 weeks treatment compared to baseline in all 3 dose groups and increased in the placebo group. The changes from baseline were not significant but the comparison of change from baseline was significant for the 18 oz group when compared to placebo (p = 0.02). Other markers of inflammation (inflammatory cytokines) and a marker for lipid peroxidation (F2 isoprostane) did not show any significant differences when compared with placebo. There was a trend towards a decrease in BMI in the juice groups. There were no side effects reported in any of the groups and none of the laboratory or EKG safety assessments indicated clinically significant changes for any subject. In this pilot, dose-finding study, a proprietary mangosteen juice blend (XanGo Juice) reduced CRP levels (increased change from baseline) compared to placebo for those taking the highest dose of 18 oz per day. Further studies with a larger population are required to confirm and further define the

Phase I dose-finding study of cabazitaxel administered weekly in patients with advanced solid tumours

International Nuclear Information System (INIS)

Fumoleau, Pierre; Trigo, Jose Manuel; Isambert, Nicolas; Sémiond, Dorothée; Gupta, Sunil; Campone, Mario

2013-01-01

Cabazitaxel is approved in patients with metastatic hormone-refractory prostate cancer previously treated with a docetaxel-containing regimen. This study evaluated a weekly cabazitaxel dosing regimen. Primary objectives were to report dose-limiting toxicities (DLTs) and to determine the maximum tolerated dose (MTD). Efficacy, safety and pharmacokinetics were secondary objectives. Cabazitaxel was administered weekly (1-hour intravenous infusion at 1.5–12 mg/m2 doses) for the first 4 weeks of a 5-week cycle in patients with solid tumours. Monitoring of DLTs was used to determine the MTD and the recommended weekly dose. Thirty-one patients were enrolled. Two of six patients experienced DLTs at 12 mg/m 2 , which was declared the MTD. Gastrointestinal disorders were the most common adverse event. Eight patients developed neutropenia (three ≥ Grade 3); one occurrence of febrile neutropenia was reported. There were two partial responses (in breast cancer) and 13 patients had stable disease (median duration of 3.3 months). Increases in C max and AUC 0–t were dose proportional for the 6–12 mg/m 2 doses. The MTD of weekly cabazitaxel was 12 mg/m 2 and the recommended weekly dose was 10 mg/m 2 . The observed safety profile and antitumour activity of cabazitaxel were consistent with those observed with other taxanes in similar dosing regimens. The study was registered with ClinicalTrials.gov as http://www.clinicaltrials.gov/ct2/show/NCT01755390

Prevalence of incidental or unexpected findings on low-dose CT performed during routine SPECT/CT nuclear medicine studies

International Nuclear Information System (INIS)

Yap, Kelvin Kwok-Ho; Sutherland, Tom; Shafik-Eid, Raymond; Taubman, Kim; Schlicht, Stephen; Ramaseshan, Ganeshan

2015-01-01

In nuclear medicine, single-photon-emission computed tomography (SPECT) is often combined with ‘simultaneous’ low-dose CT (LDCT) to provide complementary anatomical and functional correlation. As a consequence, numerous incidental and unexpected findings may be detected on LDCT. Recognition of these findings and appropriate determination of their relevance can add to the utility of SPECT/CT. We aimed to evaluate the prevalence and categorise the relevance of incidental and unexpected findings on LDCT scans performed as part of routine SPECT/CT studies. All available LDCT scans performed as part of SPECT/CT studies at St. Vincent's Hospital Melbourne in the year 2013 were retrospectively reviewed. Two qualified radiologists independently reviewed the studies and any previous available imaging and categorised any detected incidental findings. A total of 2447 LDCT studies were reviewed. The relevance of the findings was classified according to a modified version of a scale used in the Colonography Reporting and Data System: E1 = normal or normal variant (28.0%); E2 = clinically unimportant (63.5%); E3 = likely unimportant or incompletely characterised (6.2%); E4 = potentially important (2.5%). Imaging specialists need to be cognisant of incidental and unexpected findings present on LDCT studies performed as part of SPECT/CT. Appropriate categorisation of findings and communication of potentially important findings to referring clinicians should form part of routine practice. The overall prevalence of potentially significant incidental and unexpected findings in our series was 8.7% (E3, 6.2%; E4, 2.5%) and was comparable to rates in other published imaging series.

Radiation dose to children in diagnostic radiology. Measurements and methods for clinical optimisation studies

Energy Technology Data Exchange (ETDEWEB)

Almen, A J

1995-09-01

A method for estimating mean absorbed dose to different organs and tissues was developed for paediatric patients undergoing X-ray investigations. The absorbed dose distribution in water was measured for the specific X-ray beam used. Clinical images were studied to determine X-ray beam positions and field sizes. Size and position of organs in the patient were estimated using ORNL phantoms and complementary clinical information. Conversion factors between the mean absorbed dose to various organs and entrance surface dose for five different body sizes were calculated. Direct measurements on patients estimating entrance surface dose and energy imparted for common X-ray investigations were performed. The examination technique for a number of paediatric X-ray investigations used in 19 Swedish hospitals was studied. For a simulated pelvis investigation of a 1-year old child the entrance surface dose was measured and image quality was estimated using a contrast-detail phantom. Mean absorbed doses to organs and tissues in urography, lung, pelvis, thoracic spine, lumbar spine and scoliosis investigations was calculated. Calculations of effective dose were supplemented with risk calculations for special organs e g the female breast. The work shows that the examination technique in paediatric radiology is not yet optimised, and that the non-optimised procedures contribute to a considerable variation in radiation dose. In order to optimise paediatric radiology there is a need for more standardised methods in patient dosimetry. It is especially important to relate measured quantities to the size of the patient, using e g the patient weight and length. 91 refs, 17 figs, 8 tabs.

Radiation dose to children in diagnostic radiology. Measurements and methods for clinical optimisation studies

International Nuclear Information System (INIS)

Almen, A.J.

1995-09-01

A method for estimating mean absorbed dose to different organs and tissues was developed for paediatric patients undergoing X-ray investigations. The absorbed dose distribution in water was measured for the specific X-ray beam used. Clinical images were studied to determine X-ray beam positions and field sizes. Size and position of organs in the patient were estimated using ORNL phantoms and complementary clinical information. Conversion factors between the mean absorbed dose to various organs and entrance surface dose for five different body sizes were calculated. Direct measurements on patients estimating entrance surface dose and energy imparted for common X-ray investigations were performed. The examination technique for a number of paediatric X-ray investigations used in 19 Swedish hospitals was studied. For a simulated pelvis investigation of a 1-year old child the entrance surface dose was measured and image quality was estimated using a contrast-detail phantom. Mean absorbed doses to organs and tissues in urography, lung, pelvis, thoracic spine, lumbar spine and scoliosis investigations was calculated. Calculations of effective dose were supplemented with risk calculations for special organs e g the female breast. The work shows that the examination technique in paediatric radiology is not yet optimised, and that the non-optimised procedures contribute to a considerable variation in radiation dose. In order to optimise paediatric radiology there is a need for more standardised methods in patient dosimetry. It is especially important to relate measured quantities to the size of the patient, using e g the patient weight and length. 91 refs, 17 figs, 8 tabs

Clinical findings and survival time in dogs with advanced heart failure.

Science.gov (United States)

Beaumier, Amelie; Rush, John E; Yang, Vicky K; Freeman, Lisa M

2018-04-10

Dogs with advanced heart failure are a clinical challenge for veterinarians but there are no studies reporting clinical features and outcome of this population. To describe clinical findings and outcome of dogs with advanced heart failure caused by degenerative mitral valve disease (DMVD). Fifty-four dogs with advanced heart failure because of DMVD. For study purposes, advanced heart failure was defined as recurrence of congestive heart failure signs despite receiving the initially prescribed dose of pimobendan, angiotensin-converting-enzyme inhibitor (ACEI), and furosemide >4 mg/kg/day. Data were collected for the time of diagnosis of Stage C heart failure and time of diagnosis of advanced heart failure. Date of death was recorded. At the diagnosis of advanced heart failure, doses of pimobendan (n = 30), furosemide (n = 28), ACEI (n = 13), and spironolactone (n = 4) were increased, with ≥1 new medications added in most dogs. After initial diagnosis of advanced heart failure, 38 (70%) dogs had additional medications adjustments (median = 2 [range, 0-27]), with the final total medication number ranging from 2-10 (median = 5). Median survival time after diagnosis of advanced heart failure was 281 days (range, 3-885 days). Dogs receiving a furosemide dose >6.70 mg/kg/day had significantly longer median survival times (402 days [range, 3-885 days] versus 129 days [range 9-853 days]; P = .017). Dogs with advanced heart failure can have relatively long survival times. Higher furosemide dose and non-hospitalization were associated with longer survival. Copyright © 2018 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

The diagnostic efficacy of clinical findings and electrophysiological studies in carpal tunnel syndrome

OpenAIRE

Buyukkoyuncu Pekel, Nilufer; Nar Senol, Pelin; Yildiz, Demet; Kilic, Ahmet Kasim; Kamaci Sener, Deniz; Seferoglu, Meral; Gunes, Aygul

2017-01-01

Objective. The aim of the study was to examine the relation between clinical findings, neurological examination and electrophysiological studies in diagnosing carpal tunnel syndrome (CTS) and share our institutional experience in patients with CTS. Methods. Patients presenting with complaints of pain, paresthesia, and weakness in hands who diagnosed CTS between 2014 and 2015 were examined retrospectively. Demographic characteristics, clinical and neurological examination findings and electrod...

A step-up test procedure to find the minimum effective dose.

Science.gov (United States)

Wang, Weizhen; Peng, Jianan

2015-01-01

It is of great interest to find the minimum effective dose (MED) in dose-response studies. A sequence of decreasing null hypotheses to find the MED is formulated under the assumption of nondecreasing dose response means. A step-up multiple test procedure that controls the familywise error rate (FWER) is constructed based on the maximum likelihood estimators for the monotone normal means. When the MED is equal to one, the proposed test is uniformly more powerful than Hsu and Berger's test (1999). Also, a simulation study shows a substantial power improvement for the proposed test over four competitors. Three R-codes are provided in Supplemental Materials for this article. Go to the publishers online edition of Journal of Biopharmaceutical Statistics to view the files.

Dose-Finding Study of Omeprazole on Gastric pH in Neonates with Gastro-Esophageal Acid Reflux Using a Bayesian Sequential Approach.

Science.gov (United States)

Kaguelidou, Florentia; Alberti, Corinne; Biran, Valerie; Bourdon, Olivier; Farnoux, Caroline; Zohar, Sarah; Jacqz-Aigrain, Evelyne

2016-01-01

Proton pump inhibitors are frequently administered on clinical symptoms in neonates but benefit remains controversial. Clinical trials validating omeprazole dosage in neonates are limited. The objective of this trial was to determine the minimum effective dose (MED) of omeprazole to treat pathological acid reflux in neonates using reflux index as surrogate marker. Double blind dose-finding trial with continual reassessment method of individual dose administration using a Bayesian approach, aiming to select drug dose as close as possible to the predefined target level of efficacy (with a credibility interval of 95%). Neonatal Intensive Care unit of the Robert Debré University Hospital in Paris, France. Neonates with a postmenstrual age ≥ 35 weeks and a pathologic 24-hour intra-esophageal pH monitoring defined by a reflux index ≥ 5% over 24 hours were considered for participation. Recruitment was stratified to 3 groups according to gestational age at birth. Five preselected doses of oral omeprazole from 1 to 3 mg/kg/day. Primary outcome, measured at 35 weeks postmenstrual age or more, was a reflux index reflux index ranging from 5.06 to 27.7% were included. Median age was 37.5 days and median postmenstrual age was 36 weeks. In neonates born at less than 32 weeks of GA (n = 30), the MED was 2.5mg/kg/day with an estimated mean posterior probability of success of 97.7% (95% credibility interval: 90.3-99.7%). The MED was 1mg/kg/day for neonates born at more than 32 GA (n = 24). Omeprazole is extensively prescribed on clinical symptoms but efficacy is not demonstrated while safety concerns do exist. When treatment is required, the daily dose needs to be validated in preterm and term neonates. Optimal doses of omeprazole to increase gastric pH and decrease reflux index below 5% over 24 hours, determined using an adaptive Bayesian design differ among neonates. Both gestational and postnatal ages account for these differences but their differential impact on omeprazole

The study on clinical conditions and skin dose of upper-gastrointestinal x-ray fluoroscopy

International Nuclear Information System (INIS)

Kim, Sung Chul; Ahn, Sung Min; Jang, Sang Sup

2007-01-01

This study examined present conditions of upper-gastrointestinal X-ray fluoroscopy and patient skin dose. The authors elected 21 equipment to check the X-ray equipment and exposure factor of fluoroscopy and spot exposure in university hospitals, hospitals, and clinics where perform upper-gastrointestinal X-ray fluoroscopy more than five times every day in Incheon areas. The amount of patient's skin dose during upper-gastrointestinal X-ray fluoroscopy was measured by ionization chamber

Clinical study of double dose of valsartan combined with tacrolimus in treatment of diabetic nephropathy.

Science.gov (United States)

Jin, H; Zhang, H-N; Hou, X-L; Zhang, B; Wu, J; Zhang, H-B

2016-01-01

To investigate the clinical effect of double dose of valsartan combined with tacrolimus in the treatment of diabetic nephropathy (DN). HA total of 86 cases diagnosed with DN were selected from October 2013 to October 2014 in Zaozhuang Municipal Hospital, China. The study was approved by our hospital Ethics Committee and written consent was obtained from patients and their family members. Patients were randomly divided into three groups according to the sequence of admission, group A (conventional dose of valsartan group, n = 28 cases), group B (double dose of valsartan group, n = 29 cases) and group C (double dose of valsartan combined with tacrolimus group, n = 29). Clinical effects were compared by analyzing the renal function tests after 8 weeks. 24h urine protein, serum creatinine level of patients in group B and group C were significantly lower than that of group A. Those in group C was much lower. The glomerular filtration rates were significantly higher for group B and C than that of group A, and those in group C were much higher. The difference is statistically significant (p valsartan combined with tacrolimus treatment of DN patients can improve clinical symptoms, reducing inflammation, inhibiting or even reversing the interstitial fibrosis, which will improve the curative effect and reduce the recurrence, as to provide a new theoretical basis for the clinical treatment of the disease.

Evaluation of dose reduction versus standard dosing for maintenance of remission in patients with spondyloarthritis and clinical remission with anti-TNF (REDES-TNF): study protocol for a randomized controlled trial.

Science.gov (United States)

Pontes, Caridad; Gratacós, Jordi; Torres, Ferran; Avendaño, Cristina; Sanz, Jesús; Vallano, Antoni; Juanola, Xavier; de Miguel, Eugenio; Sanmartí, Raimon; Calvo, Gonzalo

2015-08-20

Dose reduction schedules of tumor necrosis factor antagonists (anti-TNF) as maintenance therapy in patients with spondyloarthritis are used empirically in clinical practice, despite the lack of clinical trials providing evidence for this practice. To address this issue the Spanish Society of Rheumatology (SER) and Spanish Society of Clinical Pharmacology (SEFC) designed a 3-year multicenter, randomized, open-label, controlled clinical trial (2 years for inclusion and 1 year of follow-up). The study is expected to include 190 patients with axial spondyloarthritis on stable maintenance treatment (≥4 months) with any anti-TNF agent at doses recommended in the summary of product characteristics. Patients will be randomized to either a dose reduction arm or maintenance of the dosing regimen as per the official labelling recommendations. Randomization will be stratified according to the anti-TNF agent received before study inclusion. Patient follow-up, visit schedule, and examinations will be maintained as per normal clinical practice recommendations according to SER guidelines. The study aims to test the hypothesis of noninferiority of the dose reduction strategy compared with standard treatment. The first patients were recruited in July 2012, and study completion is scheduled for the end of April 2015. The REDES-TNF study is a pragmatic clinical trial that aims to provide evidence to support a medical decision now made empirically. The study results may help inform clinical decisions relevant to both patients and healthcare decision makers. EudraCT 2011-005871-18 (21 December 2011).

Dose-Finding Study of Omeprazole on Gastric pH in Neonates with Gastro-Esophageal Acid Reflux Using a Bayesian Sequential Approach.

Directory of Open Access Journals (Sweden)

Florentia Kaguelidou

Full Text Available Proton pump inhibitors are frequently administered on clinical symptoms in neonates but benefit remains controversial. Clinical trials validating omeprazole dosage in neonates are limited. The objective of this trial was to determine the minimum effective dose (MED of omeprazole to treat pathological acid reflux in neonates using reflux index as surrogate marker.Double blind dose-finding trial with continual reassessment method of individual dose administration using a Bayesian approach, aiming to select drug dose as close as possible to the predefined target level of efficacy (with a credibility interval of 95%.Neonatal Intensive Care unit of the Robert Debré University Hospital in Paris, France.Neonates with a postmenstrual age ≥ 35 weeks and a pathologic 24-hour intra-esophageal pH monitoring defined by a reflux index ≥ 5% over 24 hours were considered for participation. Recruitment was stratified to 3 groups according to gestational age at birth.Five preselected doses of oral omeprazole from 1 to 3 mg/kg/day.Primary outcome, measured at 35 weeks postmenstrual age or more, was a reflux index <5% during the 24-h pH monitoring registered 72±24 hours after omeprazole initiation.Fifty-four neonates with a reflux index ranging from 5.06 to 27.7% were included. Median age was 37.5 days and median postmenstrual age was 36 weeks. In neonates born at less than 32 weeks of GA (n = 30, the MED was 2.5mg/kg/day with an estimated mean posterior probability of success of 97.7% (95% credibility interval: 90.3-99.7%. The MED was 1mg/kg/day for neonates born at more than 32 GA (n = 24.Omeprazole is extensively prescribed on clinical symptoms but efficacy is not demonstrated while safety concerns do exist. When treatment is required, the daily dose needs to be validated in preterm and term neonates. Optimal doses of omeprazole to increase gastric pH and decrease reflux index below 5% over 24 hours, determined using an adaptive Bayesian design differ

Renal MRI findings and their clinical associations in nephropathia epidemica: analysis of quantitative findings

Energy Technology Data Exchange (ETDEWEB)

Paakkala, A. [University of Tampere, Medical School, Tampere (Finland); Tampere University Hospital, Department of Radiology, Tampere (Finland); Dastidar, P.; Ryymin, P. [Tampere University Hospital, Department of Radiology, Tampere (Finland); Huhtala, H. [University of Tampere, School of Public Health, Tampere (Finland); Mustonen, J. [University of Tampere, Medical School, Tampere (Finland); Tampere University Hospital, Department of Medicine, Tampere (Finland)

2005-05-01

Morphologic renal magnetic resonance imaging (MRI) findings in patients with nephropathia epidemica (NE) were evaluated, and these findings were correlated with the clinical course of NE. Renal MRI was performed in 20 hospitalized NE patients during the acute phase of their disease. A repeat MRI study was made 5-8 months later. Renal parenchymal volume, renal length and parenchymal thickness were decreased in all patients in the repeat study. Edema/fluid collections were found bilaterally in 16 patients in the primary MRI study. Greater change in parenchymal volume, renal length and parenchymal thickness between the primary and the repeat MRI study as well as the presence of edema/fluid collections in the primary study evinced mild association with clinical fluid volume overload, high blood pressure level, inflammation, thrombocytopenia and severe clinical renal insufficiency. Change in parenchymal volume was associated with a severe clinical course more markedly than the other MRI findings. Measurable renal MRI changes occurred in every NE patient. The severity of the findings in MRI evinced mild association with clinical fluid volume overload, high blood pressure level, inflammation, thrombocytopenia and severe clinical renal insufficiency. Based on this study and our previous ultrasound (US) findings, we prefer US as the primary examination mode in NE patients. (orig.)

Renal MRI findings and their clinical associations in nephropathia epidemica: analysis of quantitative findings

International Nuclear Information System (INIS)

Paakkala, A.; Dastidar, P.; Ryymin, P.; Huhtala, H.; Mustonen, J.

2005-01-01

Morphologic renal magnetic resonance imaging (MRI) findings in patients with nephropathia epidemica (NE) were evaluated, and these findings were correlated with the clinical course of NE. Renal MRI was performed in 20 hospitalized NE patients during the acute phase of their disease. A repeat MRI study was made 5-8 months later. Renal parenchymal volume, renal length and parenchymal thickness were decreased in all patients in the repeat study. Edema/fluid collections were found bilaterally in 16 patients in the primary MRI study. Greater change in parenchymal volume, renal length and parenchymal thickness between the primary and the repeat MRI study as well as the presence of edema/fluid collections in the primary study evinced mild association with clinical fluid volume overload, high blood pressure level, inflammation, thrombocytopenia and severe clinical renal insufficiency. Change in parenchymal volume was associated with a severe clinical course more markedly than the other MRI findings. Measurable renal MRI changes occurred in every NE patient. The severity of the findings in MRI evinced mild association with clinical fluid volume overload, high blood pressure level, inflammation, thrombocytopenia and severe clinical renal insufficiency. Based on this study and our previous ultrasound (US) findings, we prefer US as the primary examination mode in NE patients. (orig.)

Clinical and symptomatological study of pigs subjected to a lethal dose of integral gamma irradiation

International Nuclear Information System (INIS)

Vaiman, M.; Guenet, J.-L.; Maas, J.; Nizza, P.

1966-05-01

Results are reported from a clinical and haematological study on a Corsican species of pigs wholly exposed to an approximately lethal dose of γ radiation. The aim of this work was to examine the changes in the irradiation syndrome of irradiation for pigs to make it thus possible to devise further experiments, in particular in the therapeutic field. The dose received was 285 rads (measured as the absorption in the vertical antero-posterior medial plane). Data are presented on cyto-haematological changes in the blood circulating immediately after irradiation, and followed up to death, and changes in the medullary cytology after irradiation. The clinical picture of lethal radiation injury in swine is described. (authors) [fr

Radiation dose monitoring in the clinical routine

Energy Technology Data Exchange (ETDEWEB)

Guberina, Nika [UK Essen (Germany). Radiology

2017-04-15

Here we describe the first clinical experiences regarding the use of an automated radiation dose management software to monitor the radiation dose of patients during routine examinations. Many software solutions for monitoring radiation dose have emerged in the last decade. The continuous progress in radiological techniques, new scan features, scanner generations and protocols are the primary challenge for radiation dose monitoring software systems. To simulate valid dose calculations, radiation dose monitoring systems have to follow current trends and stay constantly up-to-date. The dose management software is connected to all devices at our institute and conducts automatic data acquisition and radiation dose calculation. The system incorporates 18 virtual phantoms based on the Cristy phantom family, estimating doses in newborns to adults. Dose calculation relies on a Monte Carlo simulation engine. Our first practical experiences demonstrate that the software is capable of dose estimation in the clinical routine. Its implementation and use have some limitations that can be overcome. The software is promising and allows assessment of radiation doses, like organ and effective doses according to ICRP 60 and ICRP 103, patient radiation dose history and cumulative radiation doses. Furthermore, we are able to determine local diagnostic reference doses. The radiation dose monitoring software systems can facilitate networking between hospitals and radiological departments, thus refining radiation doses and implementing reference doses at substantially lower levels.

Phase I dose-finding study of sorafenib with FOLFOX4 as first-line treatment in patients with unresectable locally advanced or metastatic gastric cancer.

Science.gov (United States)

Chi, Yihebali; Yang, Jianliang; Yang, Sheng; Sun, Yongkun; Jia, Bo; Shi, Yuankai

2015-06-01

To determine the maximum tolerated dose (MTD), dose-limiting toxicity (DLT) and efficacy of sorafenib in combination with FOLFOX4 (oxaliplatin/leucovorin (LV)/5-fluorouracil) as first-line treatment for advanced gastric cancer, we performed a phase I dose-finding study in nine evaluable patients with unresectable locally advanced or metastatic gastric cancer or gastroesophageal junction adenocarcinoma. According to modified Fibonacci method, the design of this study was to guide elevation of the sorafenib dosage to the next level (from 200 mg twice daily to 400 mg twice daily and then, if tolerated, 600 mg twice daily). If the patient achieved complete response (CR), partial response (PR) or stable disease (SD) after eight cycles of treatment, combination chemotherapy was scheduled to be discontinued and sorafenib monotherapy continued at the original dose until either disease progression or unacceptable toxicity. In sorafenib 200 mg twice daily group, DLT was observed in 1 of 6 patients, and in 400 mg twice daily group, it was observed in 2 of 3 patients. Seven of 9 (77.8%) evaluable patients achieved PR, with a median overall survival (OS) of 11.8 [95% confidence interval (CI): 8.9-14.7] months. Common adverse effects include hand-foot syndrome, leukopenia, neutropenia, anorexia, and nausea. Twice-daily dosing of sorafenib 200 mg in combination with FOLFOX4 was proven effective and safe for the treatment of advanced gastric cancer, and could be an appropriate dosage for subsequent phase II clinical studies.

Dose Escalation Methods in Phase I Cancer Clinical Trials

OpenAIRE

Le Tourneau, Christophe; Lee, J. Jack; Siu, Lillian L.

2009-01-01

Phase I clinical trials are an essential step in the development of anticancer drugs. The main goal of these studies is to establish the recommended dose and/or schedule of new drugs or drug combinations for phase II trials. The guiding principle for dose escalation in phase I trials is to avoid exposing too many patients to subtherapeutic doses while preserving safety and maintaining rapid accrual. Here we review dose escalation methods for phase I trials, including the rule-based and model-...

Preliminary results for avelumab plus axitinib as first-line therapy in patients with advanced clear-cell renal-cell carcinoma (JAVELIN Renal 100): an open-label, dose-finding and dose-expansion, phase 1b trial.

Science.gov (United States)

Choueiri, Toni K; Larkin, James; Oya, Mototsugu; Thistlethwaite, Fiona; Martignoni, Marcella; Nathan, Paul; Powles, Thomas; McDermott, David; Robbins, Paul B; Chism, David D; Cho, Daniel; Atkins, Michael B; Gordon, Michael S; Gupta, Sumati; Uemura, Hirotsugu; Tomita, Yoshihiko; Compagnoni, Anna; Fowst, Camilla; di Pietro, Alessandra; Rini, Brian I

2018-04-01

The combination of an immune checkpoint inhibitor and a VEGF pathway inhibitor to treat patients with advanced renal-cell carcinoma might increase the clinical benefit of these drugs compared with their use alone. Here, we report preliminary results for the combination of avelumab, an IgG1 monoclonal antibody against the programmed cell death protein ligand PD-L1, and axitinib, a VEGF receptor inhibitor approved for second-line treatment of advanced renal-cell carcinoma, in treatment-naive patients with advanced renal-cell carcinoma. The JAVELIN Renal 100 study is an ongoing open-label, multicentre, dose-finding, and dose-expansion, phase 1b study, done in 14 centres in the USA, UK, and Japan. Eligible patients were aged 18 years or older (≥20 years in Japan) and had histologically or cytologically confirmed advanced renal-cell carcinoma with clear-cell component, life expectancy of at least 3 months, an Eastern Cooperative Oncology Group performance status of 1 or less, received no previous systemic treatment for advanced renal cell carcinoma, and had a resected primary tumour. Patients enrolled into the dose-finding phase received 5 mg axitinib orally twice daily for 7 days, followed by combination therapy with 10 mg/kg avelumab intravenously every 2 weeks and 5 mg axitinib orally twice daily. Based on the pharmacokinetic data from the dose-finding phase, ten additional patients were enrolled into the dose-expansion phase and assigned to this regimen. The other patients in the dose-expansion phase started taking combination therapy directly. The primary endpoint was dose-limiting toxicities in the first 4 weeks (two cycles) of treatment with avelumab plus axitinib. Safety and antitumour activity analyses were done in all patients who received at least one dose of avelumab or axitinib. This trial is registered with ClinicalTrials.gov, number NCT02493751. Between Oct 30, 2015, and Sept 30, 2016, we enrolled six patients into the dose-finding phase and 49 into the

A phase I dose-finding study of 5-azacytidine in combination with sodium phenylbutyrate in patients with refractory solid tumors.

Science.gov (United States)

Lin, Jianqing; Gilbert, Jill; Rudek, Michelle A; Zwiebel, James A; Gore, Steve; Jiemjit, Anchalee; Zhao, Ming; Baker, Sharyn D; Ambinder, Richard F; Herman, James G; Donehower, Ross C; Carducci, Michael A

2009-10-01

This was a phase I trial to determine the minimal effective dose and optimal dose schedule for 5-azacytidine (5-AC) in combination with sodium phenylbutyrate in patients with refractory solid tumors. The pharmacokinetics, pharmacodynamics, and antineoplastic effects were also studied. Three dosing regimens were studied in 27 patients with advanced solid tumors, and toxicity was recorded. The pharmacokinetics of the combination of drugs was evaluated. Repeat tumor biopsies and peripheral blood mononuclear cells (PBMC) were analyzed to evaluate epigenetic changes in response to therapy. EBV titers were evaluated as a surrogate measure for gene re-expression of epigenetic modulation in PBMC. The three dose regimens of 5-AC and phenylbutyrate were generally well tolerated and safe. A total of 48 cycles was administrated to 27 patients. The most common toxicities were bone marrow suppression-related neutropenia and anemia, which were minor. The clinical response rate was disappointing for the combination of agents. One patient showed stable disease for 5 months whereas 26 patients showed progressive disease as the best tumor response. The administration of phenylbutyrate and 5-AC did not seem to alter the pharmacokinetics of either drug. Although there were individual cases of targeted DNA methyltransferase activity and histone H3/4 acetylation changes from paired biopsy or PBMC, no conclusive statement can be made based on these limited correlative studies. The combination of 5-AC and phenylbutyrate across three dose schedules was generally well tolerated and safe, yet lacked any real evidence for clinical benefit.

Accuracy of Dose Calibrators for 68Ga PET Imaging: Unexpected Findings in a Multicenter Clinical Pretrial Assessment.

Science.gov (United States)

Bailey, Dale L; Hofman, Michael S; Forwood, Nicholas J; O'Keefe, Graeme J; Scott, Andrew M; van Wyngaardt, Winifred M; Howe, Bonnie; Kovacev, Olga; Francis, Roslyn J

2018-04-01

We report the discovery of a systematic miscalibration during the work-up process for site validation of a multicenter clinical PET imaging trial using 68 Ga, which manifested as a consistent and reproducible underestimation in the quantitative accuracy (assessed by SUV) of a range of PET systems from different manufacturers at several different facilities around Australia. Methods: Sites were asked to follow a strict preparation protocol to create a radioactive phantom with 68 Ga to be imaged using a standard clinical protocol before commencing imaging in the trial. All sites had routinely used 68 Ga for clinical PET imaging for many years. The reconstructed image data were transferred to an imaging core laboratory for analysis, along with information about ancillary equipment such as the radionuclide dose calibrator. Fourteen PET systems were assessed from 10 nuclear medicine facilities in Australia, with the aim for each PET system being to produce images within 5% of the true SUV. Results: At initial testing, 10 of the 14 PET systems underestimated the SUV by 15% on average (range, 13%-23%). Multiple PET systems at one site, from two different manufacturers, were all similarly affected, suggesting a common cause. We eventually identified an incorrect factory-shipped dose calibrator setting from a single manufacturer as being the cause. The calibrator setting for 68 Ga was subsequently adjusted by the users so that the reconstructed images produced accurate values. Conclusion: PET imaging involves a chain of measurements and calibrations to produce accurate quantitative performance. Testing of the entire chain is simple, however, and should form part of any quality assurance program or prequalifying site assessment before commencing a quantitative imaging trial or clinical imaging. © 2018 by the Society of Nuclear Medicine and Molecular Imaging.

Energy and integrated dose dependence of MOSFET dosimeter for clinical electron beams

International Nuclear Information System (INIS)

Manigandan, D.; Bharanidharan, G.; Aruna, P.; Ganesan, S.; Tamil Kumar, T.; Rai

2008-01-01

In this study, the sensitivity (mV/cGy) and integral dose dependence of a MOSFET detector for different clinical electron beams was studied. Calibrated clinical electron beams (Varian 2100) were used for the exposure. A Markus type parallel plate chamber was used for the absolute dose measurements. In order to study the sensitivity of a MOSFET, the response of the ion chamber and MOSFET for the absorbed dose of 100 cGy was measured. The sensitivity of the MOSFET was then expressed as mV/cGy. Sensitivity was measured for 4-18 MeV electron beams. (author)

Measuring pacemaker dose: A clinical perspective

Energy Technology Data Exchange (ETDEWEB)

Studenski, Matthew T., E-mail: matthew.studenski@jeffersonhospital.org [Department of Radiation Oncology at the Jefferson Medical College and Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA (United States); Xiao Ying; Harrison, Amy S. [Department of Radiation Oncology at the Jefferson Medical College and Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA (United States)

2012-07-01

Recently in our clinic, we have seen an increased number of patients presenting with pacemakers and defibrillators. Precautions are taken to develop a treatment plan that minimizes the dose to the pacemaker because of the adverse effects of radiation on the electronics. Here we analyze different dosimeters to determine which is the most accurate in measuring pacemaker or defibrillator dose while at the same time not requiring a significant investment in time to maintain an efficient workflow in the clinic. The dosimeters analyzed here were ion chambers, diodes, metal-oxide-semiconductor field effect transistor (MOSFETs), and optically stimulated luminescence (OSL) dosimeters. A simple phantom was used to quantify the angular and energy dependence of each dosimeter. Next, 8 patients plans were delivered to a Rando phantom with all the dosimeters located where the pacemaker would be, and the measurements were compared with the predicted dose. A cone beam computed tomography (CBCT) image was obtained to determine the dosimeter response in the kilovoltage energy range. In terms of the angular and energy dependence of the dosimeters, the ion chamber and diode were the most stable. For the clinical cases, all the dosimeters match relatively well with the predicted dose, although the ideal dosimeter to use is case dependent. The dosimeters, especially the MOSFETS, tend to be less accurate for the plans, with many lateral beams. Because of their efficiency, we recommend using a MOSFET or a diode to measure the dose. If a discrepancy is observed between the measured and expected dose (especially when the pacemaker to field edge is <10 cm), we recommend analyzing the treatment plan to see whether there are many lateral beams. Follow-up with another dosimeter rather than repeating multiple times with the same type of dosimeter. All dosimeters should be placed after the CBCT has been acquired.

Studies of health effects of low dose radiation and its application to medicare

International Nuclear Information System (INIS)

Yamaoka, Kiyonori; Ishida, Kenji; Iwasaki, Toshiyasu; Koana, Takao; Magae, Junji; Watanabe, Masami; Sakamoto, Kiyohiko

2008-01-01

The articles contain following 7 topics of low dose radiation effects. Studies of Health Effects of Low dose Radiation and Its Application to Medicare'', describes the indication of Rn therapy and investigations of its usefulness mechanism mainly in Misasa Spa, Okayama Pref. ''Challenges for the Paradigm Shift (CRIEPI Studies)'', introduces studies against the paradigm that radiation dose is linearly and proportionally hazardous. ''Studies of High Background Radiation Area (CRIEPI Studies)'', describes global HBRA studies on chromosome affection and effect of smoking in HBRA. ''Is the Radiation Effect on Man Proportional to Dose? (CRIEPI Studies)'', describes studies of immature sperm irradiated at low dose against Linear-Non-threshold Theory (LNT) hypothesis. ''Induction of Radiation Resistance by Low Dose Radiation and Assessment of Its Effect in Models of Human Diseases (CRIEPI Studies)'', explains the adoptive response in radiation effect, suppression of carcinogenesis and immune regulation by previous low dose radiation in the mouse, and improvement of diabetes in the db/db mouse. ''Modulation of Biological Effects of Low Dose Radiation: Adoptive Response, Bystander Effect, Genetic Instability and Radiation Hormesis'', summarizes findings of each item. ''Cancer Treatment with Low dose Radiation to the Whole Body'', describes basic studies in the mouse tumor in relation to suppression of carcinogenesis and metastasis, immune activation and treatment, and successful clinical studies in patients with ovary, colon cancers and malignant lymphoma where survival has been significantly improved: a base of recent European Organization for Research and Treatment of Cancer (EORTC) clinical trials. The mechanism is essentially based on immune activation of patients to cure the disease. (R.T.)

A clinical comparison of high dose and low dose of Suxamethonium

Directory of Open Access Journals (Sweden)

RK Yadav

2014-01-01

Full Text Available Background: Suxamethonium having its rapid onset and short duration of action makes this drug unique amongst the neuromuscular blocking drugs described so far. However, use of suxamethonium is associated with a large number of undesirable side effects. Objective: To evaluate clinical effects of high and low dose of suxamethonium and to determine whether lower dose of suxamethonium can be used for any beneficial effects in terms of its various adverse effects e.g. cardiovascular responses, post-operative muscle pains and intraocular pressure. Methods: A total of 100 patients were included in this prospective study. All these patients on preoperative clinical evaluation were assessed to have adequate airway. All the patients were divided in two groups, low dose group (group I and High dose group (group II with 50 patients in each at random. A standard anesthetic technique was adhered to all the patients and following parameters were observed on comparative basis: a. Fasciculation and post operative myalgia. b. Cardiovascular effects, c. Intraocular pressure. Observation: The incidence of post Suxamethonium pain was significantly greater in group II. Increase in heart rate from baseline was significant in both groups. There was no significant difference between the two groups in the diastolic pressure but rise in systolic blood pressure was significant at all assessment times in both groups. This rise from control was statistically significant. Conclusion: Suxamethonium can be used in lower doses (0.5 mg/kg in elective cases without airway compromise. It gives benefits of reduced muscle pains, cardiovascular responses and intraocular hypertension. Journal of College of Medical Sciences-Nepal, 2013, Vol-9, No-2, 1-8 DOI: http://dx.doi.org/10.3126/jcmsn.v9i2.9677

Bottlenecks in the development of topical analgesics: molecule, formulation, dose-finding, and phase III design

Directory of Open Access Journals (Sweden)

Keppel Hesselink JM

2017-03-01

Full Text Available Jan M Keppel Hesselink,1 David J Kopsky,2 Stephen M Stahl3 1Institute Neuropathic Pain, Bosch en Duin, the Netherlands; 2Institute Neuropathic Pain, Amsterdam, the Netherlands; 3University of California San Diego, La Jolla, CA, USA Abstract: Topical analgesics can be defined as topical formulations containing analgesics or co-analgesics. Since 2000, interest in such formulations has been on the rise. There are, however, four critical issues in the research and development phases of topical analgesics: 1 The selection of the active pharmaceutical ingredient. Analgesics and co-analgesics differ greatly in their mechanism of action, and it is required to find the most optimal fit between such mechanisms of action and the pathogenesis of the targeted (neuropathic pain. 2 Issues concerning the optimized formulation. For relevant clinical efficacy, specific characteristics for the selected vehicle (eg, cream base or gel base are required, depending on the physicochemical characteristics of the active pharmaceutical ingredient(s to be delivered. 3 Well-designed phase II dose-finding studies are required, and, unfortunately, such trials are missing. In fact, we will demonstrate that underdosing is one of the major hurdles to detect meaningful and statistically relevant clinical effects of topical analgesics. 4 Selection of clinical end points and innovatively designed phase III trials. End point selection can make or break a trial. For instance, to include numbness together with tingling as a composite end point for neuropathic pain seems stretching the therapeutic impact of an analgesic too far. Given the fast onset of action of topical analgesics (usually within 30 minutes, enrichment designs might enhance the chances for success, as the placebo response might decrease. Topical analgesics may become promising inroads for the treatment of neuropathic pain, once sufficient attention is given to these four key aspects. Keywords: topical, analgesics

An inter-hospital comparison of patient dose based on clinical indications

International Nuclear Information System (INIS)

Teeuwisse, W.; Geleijns, J.; Veldkamp, W.

2007-01-01

Patient dose is usually estimated for a single radiographic projection or computed tomography (CT) series. In this study, patient dose was calculated for predefined clinical indications (24 radiography, 11 CT). Members of the radiology staff of each of 11 hospitals were trained in dose measurement and calculation techniques. Based on clinical indications participants decided on imaging protocols and calculated cumulative effective dose for a complete examination. Effective dose ranged from <1 μSv to 0.6 mSv for examinations with radiographs and from 0.2 to 12 mSv for CT scans. Differences in the imaging protocols contributedd to a substantial variation in patient dose. For mammography, average glandular dose (AGD) was estimated for 32-, 53- and 90-mm compressed breast thicknesses, with a median value of 0.74, 1.74 and 3.40 mGy, respectively. The results presented here demonstrate that a pragmatic choice of dosimetry methods enables local staff to estimate effective dose. The inclusion of imaging protocols in the dose surveys provided a broader view on the variations in patient dose between hospitals. (orig.)

Clinical validation of a dose reduction study in paediatric abdomen MSCT scanning

International Nuclear Information System (INIS)

Ciccarone, A.; Fonda, C.; Zatelli, Giovanna; Mazzocchi, S.

2008-01-01

Full text: In our previous work an individual dose adaptation in abdomen of paediatric patients has been showed at the Meyer children hospital of Florence. For each kV really feasible in our MSCT scanner, a table of mAs versus abdomen thickness and width ratio has been developed only on the basis of water cylinder phantoms. The choice of the water arise by the fact that in pediatric patient the quantity of water inside the body is major than that of adult. In this way a reduction dose has showed with respect to the ordinary paediatric scanning protocol in use before and the same image quality has been preserved in the case of an optimized CT scanning technique of a standard adult patient of height 175 cm and weight 70 kg. However these results were only theoretical because relied on water phantoms. Now this work concerns the clinical validation of our dose reduction study on phantoms. So 50 examinations were acquired with the dose reduction scanning technique and scored randomly, without knowing weight and height of patient by three radiologists. These scores were compared with that of other 50 abdomen examination before dose reduction study. The scores refers to the noise perceived by radiologist and to the diagnostic quality of radiograph. As last, a score on the low contrast tissue separation between muscle and fat and a score on visibility of structure therein have been asked to the radiologists. The same work has concerned the abdomen examinations with iodine contrast medium. In this study the score of each radiographs has been catalogued in four range of age, 0 - 1; 1 - 3; 3 - 8; 8 - 13 years. Aligned rank and Wilcoxon's signed rank tests were used for statistical analyses. The table of modulating mAs with respect to the size of patient obtained with only water phantom study has been revised so that none reduced detection in low-visibility structures like fat or muscle or liver was evident. Nevertheless a reduction in CTDI of 30 % has been reached in our new

Non-clinical studies in the process of new drug development - Part II: Good laboratory practice, metabolism, pharmacokinetics, safety and dose translation to clinical studies.

Science.gov (United States)

Andrade, E L; Bento, A F; Cavalli, J; Oliveira, S K; Schwanke, R C; Siqueira, J M; Freitas, C S; Marcon, R; Calixto, J B

2016-12-12

The process of drug development involves non-clinical and clinical studies. Non-clinical studies are conducted using different protocols including animal studies, which mostly follow the Good Laboratory Practice (GLP) regulations. During the early pre-clinical development process, also known as Go/No-Go decision, a drug candidate needs to pass through several steps, such as determination of drug availability (studies on pharmacokinetics), absorption, distribution, metabolism and elimination (ADME) and preliminary studies that aim to investigate the candidate safety including genotoxicity, mutagenicity, safety pharmacology and general toxicology. These preliminary studies generally do not need to comply with GLP regulations. These studies aim at investigating the drug safety to obtain the first information about its tolerability in different systems that are relevant for further decisions. There are, however, other studies that should be performed according to GLP standards and are mandatory for the safe exposure to humans, such as repeated dose toxicity, genotoxicity and safety pharmacology. These studies must be conducted before the Investigational New Drug (IND) application. The package of non-clinical studies should cover all information needed for the safe transposition of drugs from animals to humans, generally based on the non-observed adverse effect level (NOAEL) obtained from general toxicity studies. After IND approval, other GLP experiments for the evaluation of chronic toxicity, reproductive and developmental toxicity, carcinogenicity and genotoxicity, are carried out during the clinical phase of development. However, the necessity of performing such studies depends on the new drug clinical application purpose.

Acute pancreatitis: clinical vs. CT findings

International Nuclear Information System (INIS)

Hill, M.C.; Barkin, J.; Isikoff, M.B.; Silver stein, W.; Kalser, M.

1982-01-01

In a prospective study of 91 patients with acute pancreatitis, computed tomographic (CT) findings were correlated with the clinical type of acute pancreatitis. In acute edematous pancreatitis (63 patients; 16 with repeat CT), CT was normal (28%) or showed inflammation limited to the pancreas (61%). Phlegmonous changes were present in 11%, including one patient with focal pancreatic hemorrhage, indicating that clinically unsuspected hemorrhagic pancreatitis can occur. In acute necrotizing (hemorrhagic, suppurative) pancreatitis (nine patients; eight with repeat CT), no patient had a normal CT scan and 89% had phlegmonous changes. One patient had hemorrhagic pancreatitis and three had abscesses. In acute exacerbation of chronic pancreatitis (10 patients; three with repeat CT), there were pancreatic calcifications (70%), a focal mass (40%), and pancreatic ductal dilation (30%). On follow-up CT, the findings of acute pancreatitis did not always disappear with resolution of the clinical symptons. This was especialy true of phlegmonous pancreatitis, where the CT findings could persist for months

Towards tracer dose reduction in PET studies: Simulation of dose reduction by retrospective randomized undersampling of list-mode data.

Science.gov (United States)

Gatidis, Sergios; Würslin, Christian; Seith, Ferdinand; Schäfer, Jürgen F; la Fougère, Christian; Nikolaou, Konstantin; Schwenzer, Nina F; Schmidt, Holger

2016-01-01

Optimization of tracer dose regimes in positron emission tomography (PET) imaging is a trade-off between diagnostic image quality and radiation exposure. The challenge lies in defining minimal tracer doses that still result in sufficient diagnostic image quality. In order to find such minimal doses, it would be useful to simulate tracer dose reduction as this would enable to study the effects of tracer dose reduction on image quality in single patients without repeated injections of different amounts of tracer. The aim of our study was to introduce and validate a method for simulation of low-dose PET images enabling direct comparison of different tracer doses in single patients and under constant influencing factors. (18)F-fluoride PET data were acquired on a combined PET/magnetic resonance imaging (MRI) scanner. PET data were stored together with the temporal information of the occurrence of single events (list-mode format). A predefined proportion of PET events were then randomly deleted resulting in undersampled PET data. These data sets were subsequently reconstructed resulting in simulated low-dose PET images (retrospective undersampling of list-mode data). This approach was validated in phantom experiments by visual inspection and by comparison of PET quality metrics contrast recovery coefficient (CRC), background-variability (BV) and signal-to-noise ratio (SNR) of measured and simulated PET images for different activity concentrations. In addition, reduced-dose PET images of a clinical (18)F-FDG PET dataset were simulated using the proposed approach. (18)F-PET image quality degraded with decreasing activity concentrations with comparable visual image characteristics in measured and in corresponding simulated PET images. This result was confirmed by quantification of image quality metrics. CRC, SNR and BV showed concordant behavior with decreasing activity concentrations for measured and for corresponding simulated PET images. Simulation of dose

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

Science.gov (United States)

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

2018-03-15

Human papillomavirus (HPV) vaccination is a major strategy for preventing cervical and other ano-genital cancers. Worldwide HPV vaccination introduction and coverage will be facilitated if a single dose of vaccine is as effective as two or three doses or demonstrates significant protective effect compared to 'no vaccination'. In a multi-centre cluster randomized trial of two vs three doses of quadrivalent HPV vaccination (Gardasil™) in India, suspension of the vaccination due to events unrelated to the study led to per protocol and partial vaccination of unmarried 10-18 year old girls leading to four study groups, two by design and two by default. They were followed up for the primary outcomes of immunogenicity in terms of L1 genotype-specific binding antibody titres, neutralising antibody titres, and antibody avidity for the vaccine-targeted HPV types and HPV infections. Analysis was per actual number of vaccine doses received. This study is registered with ISRCTN, number ISRCTN98283094; and with ClinicalTrials.gov, number NCT00923702. Of the 17,729 vaccinated girls, 4348 (25%) received three doses on days 1, 60, 180 or later, 4979 (28%) received two doses on days 1 and 180 or later, 3452 (19%) received two doses on days 1 and 60, and 4950 (28%) received one dose. One dose recipients demonstrated a robust and sustained immune response against HPV 16 and 18, albeit inferior to that of 3- or 2-doses and the antibody levels were stable over a 4 year period. The frequencies of cumulative incident and persistent HPV 16 and 18 infections up to 7 years of follow-up were similar and uniformly low in all the vaccinated study groups; the frequency of HPV 16 and 18 infections were significantly higher in unvaccinated age-matched control women than among vaccine recipients. The frequency of vaccine non-targeted HPV types was similar in the vaccinated groups but higher in the unvaccinated control women. Our results indicate that a single dose of quadrivalent HPV

Radiation doses to personnel in clinics for gynecologic oncology

International Nuclear Information System (INIS)

Forsberg, B.; Spanne, P.

1985-01-01

Radium or Cesium is used for radiotherapy of gynecologic cancer at six clinics in Sweden. This report gives a survey of the radiation doses the personnel is exposed to. The measurement were performed using TL-dosimeters. The dose equivalents for different parts of the body at specific working moments was deduced as well as the effective dose equivalent and the collective dose equivalent. 1983 the total collective dose equivalent for the six clinics was 1.3 manSv, which corresponds to 3.9 manmSv/g equivalent mass of Radium used at the treatments. (With 11 tables and 10 figures) (L.E.)

Postimplant Dosimetry Using a Monte Carlo Dose Calculation Engine: A New Clinical Standard

International Nuclear Information System (INIS)

Carrier, Jean-Francois; D'Amours, Michel; Verhaegen, Frank; Reniers, Brigitte; Martin, Andre-Guy; Vigneault, Eric; Beaulieu, Luc

2007-01-01

Purpose: To use the Monte Carlo (MC) method as a dose calculation engine for postimplant dosimetry. To compare the results with clinically approved data for a sample of 28 patients. Two effects not taken into account by the clinical calculation, interseed attenuation and tissue composition, are being specifically investigated. Methods and Materials: An automated MC program was developed. The dose distributions were calculated for the target volume and organs at risk (OAR) for 28 patients. Additional MC techniques were developed to focus specifically on the interseed attenuation and tissue effects. Results: For the clinical target volume (CTV) D 90 parameter, the mean difference between the clinical technique and the complete MC method is 10.7 Gy, with cases reaching up to 17 Gy. For all cases, the clinical technique overestimates the deposited dose in the CTV. This overestimation is mainly from a combination of two effects: the interseed attenuation (average, 6.8 Gy) and tissue composition (average, 4.1 Gy). The deposited dose in the OARs is also overestimated in the clinical calculation. Conclusions: The clinical technique systematically overestimates the deposited dose in the prostate and in the OARs. To reduce this systematic inaccuracy, the MC method should be considered in establishing a new standard for clinical postimplant dosimetry and dose-outcome studies in a near future

Temporal bone trauma: correlative study between CT findings and clinical manifestations

Energy Technology Data Exchange (ETDEWEB)

Kim, Jung Hee; Kim, Hyung Jin; Kim, Jae Hyoung [College of Medicine, Gyeongsang National University, Jinju (Korea, Republic of)

1994-11-15

To assess how accurately computed tomography (CT) can demonstrate the abnormal findings which are believed to cause the clinical signs and symptoms of hearing loss (HL), vertigo and facial paralysis (FP) in patients with temporal bone trauma. The authors studied CT scans of 39 ears in 35 patients with temporal bone trauma. CT scans were performed with 1-1.5 mm slice thickness and table incrementation. Both axial and coronal scans were obtained in 32 patients and in three patients only axial scans were obtained. We analyzed CT with special reference to the structural abnormalities of the external auditory canal, middle ear cavity, bony labyrinth, and facial nerve canal, and correlated these findings with the actual clinical signs and symptoms. As to hearing loss, we evaluated 32 ears in which pure tone audiometry or brainstem evoked response audiometry had been performed. With respect to the specific types of HL, CT accurately showed the abnormalities in 84% (16/19) in conductive HL, 100% (2/2) in sensorineural HL, and 25% (2/8) for mixed HL. When we categorized HL simply as conductive and sensorineural, assuming that mixed be the result of combined conductive and sensorineural HL, CT demonstrated the abnormalities in 89% (24/27) for conductive HL and 50% (5/10) for sensorineural HL. Concerning vertigo and FP, CT demonstrated abnormalities in 67%(4/6), and 29% (4/14), respectively. Except for conductive HL, CT seems to have a variable degree of limitation for the demonstration of the structural abnormalities resulting sensorineural HL, vertigo or facial paralysis. It is imperative to correlate the CT findings with the signs and symptoms in those clinical settings.

Temporal bone trauma: correlative study between CT findings and clinical manifestations

International Nuclear Information System (INIS)

Kim, Jung Hee; Kim, Hyung Jin; Kim, Jae Hyoung

1994-01-01

To assess how accurately computed tomography (CT) can demonstrate the abnormal findings which are believed to cause the clinical signs and symptoms of hearing loss (HL), vertigo and facial paralysis (FP) in patients with temporal bone trauma. The authors studied CT scans of 39 ears in 35 patients with temporal bone trauma. CT scans were performed with 1-1.5 mm slice thickness and table incrementation. Both axial and coronal scans were obtained in 32 patients and in three patients only axial scans were obtained. We analyzed CT with special reference to the structural abnormalities of the external auditory canal, middle ear cavity, bony labyrinth, and facial nerve canal, and correlated these findings with the actual clinical signs and symptoms. As to hearing loss, we evaluated 32 ears in which pure tone audiometry or brainstem evoked response audiometry had been performed. With respect to the specific types of HL, CT accurately showed the abnormalities in 84% (16/19) in conductive HL, 100% (2/2) in sensorineural HL, and 25% (2/8) for mixed HL. When we categorized HL simply as conductive and sensorineural, assuming that mixed be the result of combined conductive and sensorineural HL, CT demonstrated the abnormalities in 89% (24/27) for conductive HL and 50% (5/10) for sensorineural HL. Concerning vertigo and FP, CT demonstrated abnormalities in 67%(4/6), and 29% (4/14), respectively. Except for conductive HL, CT seems to have a variable degree of limitation for the demonstration of the structural abnormalities resulting sensorineural HL, vertigo or facial paralysis. It is imperative to correlate the CT findings with the signs and symptoms in those clinical settings

Clinical implementation and evaluation of the Acuros dose calculation algorithm.

Science.gov (United States)

Yan, Chenyu; Combine, Anthony G; Bednarz, Greg; Lalonde, Ronald J; Hu, Bin; Dickens, Kathy; Wynn, Raymond; Pavord, Daniel C; Saiful Huq, M

2017-09-01

The main aim of this study is to validate the Acuros XB dose calculation algorithm for a Varian Clinac iX linac in our clinics, and subsequently compare it with the wildely used AAA algorithm. The source models for both Acuros XB and AAA were configured by importing the same measured beam data into Eclipse treatment planning system. Both algorithms were validated by comparing calculated dose with measured dose on a homogeneous water phantom for field sizes ranging from 6 cm × 6 cm to 40 cm × 40 cm. Central axis and off-axis points with different depths were chosen for the comparison. In addition, the accuracy of Acuros was evaluated for wedge fields with wedge angles from 15 to 60°. Similarly, variable field sizes for an inhomogeneous phantom were chosen to validate the Acuros algorithm. In addition, doses calculated by Acuros and AAA at the center of lung equivalent tissue from three different VMAT plans were compared to the ion chamber measured doses in QUASAR phantom, and the calculated dose distributions by the two algorithms and their differences on patients were compared. Computation time on VMAT plans was also evaluated for Acuros and AAA. Differences between dose-to-water (calculated by AAA and Acuros XB) and dose-to-medium (calculated by Acuros XB) on patient plans were compared and evaluated. For open 6 MV photon beams on the homogeneous water phantom, both Acuros XB and AAA calculations were within 1% of measurements. For 23 MV photon beams, the calculated doses were within 1.5% of measured doses for Acuros XB and 2% for AAA. Testing on the inhomogeneous phantom demonstrated that AAA overestimated doses by up to 8.96% at a point close to lung/solid water interface, while Acuros XB reduced that to 1.64%. The test on QUASAR phantom showed that Acuros achieved better agreement in lung equivalent tissue while AAA underestimated dose for all VMAT plans by up to 2.7%. Acuros XB computation time was about three times faster than AAA for VMAT plans, and

Case study: Findings and lessons learned from investigating a uranium intake and the corresponding dose calculations

International Nuclear Information System (INIS)

Beeslaar, Frik; Niekerk, Santie van; Steenkamp, Harry; Visagie, Abrie

2008-01-01

Full text: Purpose: To discuss the findings of an investigation into uranium intake and to discuss the lessons learned from the subsequent bioassay monitoring and dose calculations. Method: An investigation was held to determine direct and root causes after elevated air concentration levels were reported during the execution of an ad-hoc task. A programme of bioassay monitoring (urine sampling and lung counts) was implemented for the involved staff and committed effective doses were calculated. Major findings of the investigation: a) Inadequate pre-task assessment led to hazards not being identified and subsequently proper control measures were not implemented; b) Inadequate localised control of contamination led to contamination of worker's clothes and faces and contamination of rest of area; c) Workers were complacent which led to a lapse in safety awareness and subsequently they removed their face masks during the task. Problems experienced with bioassay monitoring and dose calculations: a) Some bioassay samples were not taken or were given incorrectly; b) Calculating doses were difficult due to lack of information regarding date of intake; whether there were other possible intakes; and the physiochemical nature of the uranium; c) Weak correlation between predicted and actual bioassay data; d) Period between starting bioassay monitoring and the actual event was too long. Conclusions: a) Shortcomings in the control of contamination with protective clothing and during the execution of ad-hoc tasks; b) Identifying hazards and assessing it is extremely dependant on the skill and capabilities if the Radiation Protection Officers; c) Instructions to workers regarding sampling of urine and arrangements around the sampling should be very specific with only one person responsible for managing the process; d) Be aware of the psychological impact on the affected workers; e) 2 nd Independent dose calculation important for verifying doses; f) Detection capabilities and

Population pharmacokinetics of exendin-(9-39) and clinical dose selection in patients with congenital hyperinsulinism.

Science.gov (United States)

Ng, Chee M; Tang, Fei; Seeholzer, Steven H; Zou, Yixuan; De León, Diva D

2018-03-01

Congenital hyperinsulinism (HI) is the most common cause of persistent hypoglycaemia in infants and children. Exendin-(9-39), an inverse glucagon-like peptide 1 (GLP-1) agonist, is a novel therapeutic agent for HI that has demonstrated glucose-raising effect. We report the first population pharmacokinetic (PopPK) model of the exendin-(9-39) in patients with HI and propose the optimal dosing regimen for future clinical trials in neonates with HI. A total of 182 pharmacokinetic (PK) observations from 26 subjects in three clinical studies were included for constructing the PopPK model using first order conditional estimation (FOCE) with interaction method in nonlinear mixed-effects modelling (NONMEM). Exposure metrics (area under the curve [AUC] and maximum plasma concentration [C max ]) at no observed adverse effect levels (NOAELs) in rats and dogs were determined in toxicology studies. Observed concentration-time profiles of exendin-(9-39) were described by a linear two-compartmental PK model. Following allometric scaling of PK parameters, age and creatinine clearance did not significantly affect clearance. The calculated clearance and elimination half-life for adult subjects with median weight of 69 kg were 11.8 l h -1 and 1.81 h, respectively. The maximum recommended starting dose determined from modelling and simulation based on the AUC 0-last at the NOAEL and predicted AUC 0-inf using the PopPK model was 27 mg kg -1  day -1 intravenously. This is the first study to investigate the PopPK of exendin-(9-39) in humans. The final PopPK model was successfully used with preclinical toxicology findings to propose the optimal dosing regimen of exendin-(9-39) for clinical studies in neonates with HI, allowing for a more targeted dosing approach to achieve desired glycaemic response. © 2017 The British Pharmacological Society.

Effects of clinically relevant doses of methyphenidate on spatial memory, behavioral sensitization and open field habituation: a time related study.

Science.gov (United States)

Haleem, Darakhshan Jabeen; Inam, Qurrat-ul-Aen; Haleem, Muhammad Abdul

2015-03-15

The psychostimulant methylphenidate (MPD) is a first-line drug for the treatment of attention deficit hyperactivity disorder (ADHD). Despite acceptable therapeutic efficacy, there is limited data regarding the long-term consequences of MPD exposure over extended periods. The present study concerns effects of clinically relevant doses of MPD, administered orally to rats for an extended period, on spatial memory, behavioral sensitization and habituation to an open field. Water maze test was used to monitor memory acquisition (2 h after training), retention (day next to training), extinction (1 week after training) and reconsolidation (weekly for 4 weeks). Administration of MPD at doses of 0.25-1.0 mg/kg improved memory acquisition, retention, reconsolidation and impaired memory extinction. Treatment with 0.25 and 0.5 mg/kg MPD for 6 weeks produced a sustained increase in motor activity but higher dose (1.0 mg/kg) elicited behavioral sensitization. High as well as low doses MPD impaired open field habituation. We conclude that clinically relevant doses of MPD enhance memory even if used for extended period. It is suggested that higher (1.0 mg/kg) clinically relevant doses of MPD, if used for extended period, may exacerbate hyperactivity and impulsivity associated with the disease. Copyright © 2015 Elsevier B.V. All rights reserved.

Study on fatty liver diagnosed by abdominal ultrasonography and clinical laboratory findings

International Nuclear Information System (INIS)

Yang, Jeong Hwa

2006-01-01

The study obtained the following conclusions by making a comparative study on fatty liver diagnosed by abdominal ultrasonography and clinical laboratory findings. I surveyed the value of abdominal ultrasound in 400 patients without clinical symptoms at C Health Clinic Center, Seoul. Compare with blood pressure was high (systolic/diastolic) in 7.5%/4.5% on persons who were diagnosed fatty liver. At the time of the diagnosis, Total cholesterol level was increased in fatty liver patients, HDL-cholesterol level was high in fatty liver patients. And Trigryceride level was increased in fatty liver persons, LDL-cholesterol was high in fatty liver persons. SGOT level was increased in 5.5% on patients who were diagnosed fatty liver, 0% on persons who were normal and SGPT level was high in 29.5% on people who were diagnosed fatty liver, 0% on patients who were diagnosed normal

Study on fatty liver diagnosed by abdominal ultrasonography and clinical laboratory findings

Energy Technology Data Exchange (ETDEWEB)

Yang, Jeong Hwa [Cheju Halla College, Cheju (Korea, Republic of)

2006-03-15

The study obtained the following conclusions by making a comparative study on fatty liver diagnosed by abdominal ultrasonography and clinical laboratory findings. I surveyed the value of abdominal ultrasound in 400 patients without clinical symptoms at C Health Clinic Center, Seoul. Compare with blood pressure was high (systolic/diastolic) in 7.5%/4.5% on persons who were diagnosed fatty liver. At the time of the diagnosis, Total cholesterol level was increased in fatty liver patients, HDL-cholesterol level was high in fatty liver patients. And Trigryceride level was increased in fatty liver persons, LDL-cholesterol was high in fatty liver persons. SGOT level was increased in 5.5% on patients who were diagnosed fatty liver, 0% on persons who were normal and SGPT level was high in 29.5% on people who were diagnosed fatty liver, 0% on patients who were diagnosed normal.

MR findings of transverse myelitis and its clinical correlation

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Kim, Jae Seung; Chang, Kee Hyun; Na, Dong Gyu; Han, Moon Hee; Choi, Choong Gon; Kim, Ji Hye [Seoul National University College of Medicine, Seoul (Korea, Republic of)

1995-02-15

The purpose of this study is to correlate the MR findings with clinical stage and clinical outcome, and to describe the evolutional changes of abnormal MR findings of transverse myelitis. Medical records and spinal MR images of 23 patients with both clinical and radiological diagnosis of transverse myelitis were retrospectively reviewed. MR findings were correlated with clinical stages including interval between MR imaging and full development of clinical symptoms, and compared with the clinical outcome. Diffuse high signal intensity of the spinal cord on T2-weighted image with mild cord bulging (67%) and focal contrast enhancement of the cord (75%) were observed within the first four weeks after full development of clinical symptoms. The findings decreased in extent or vanished later than four weeks on either initial or follow-up MR images. Most patients with either cord atrophy or focal hemorrhage within the cord lesion had poor clinical outcome. The MR findings of transverse myelitis are nonspecific, which may be seen in a variety of diseases. Serial MRIs, especially follow-up examination over at least one month after full development of clinical symptoms are useful in the diagnosis of transverse myelitis and predicting its prognosis.

Clinical study of a new therapy for nerve agent poisoning: Ascending dose tolerance study of HI-6 + atropine

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Clement, J.G.; Bailey, D.G.; Madill, H.D.; Spence, J.D.

1993-05-13

HI-6 was rapidly absorbed from an IM injection site. Maximum HI-6 plasma concentrations of 1.88, 4.96, 8.31 15.0 ug/ml were found 28-36 min after administration and maintained above 4 ug/ml concentration for 0, 39, 112 172.5 min following administration of 62.5, 125, 250 or 500 mg HI-6 + atropine (2 mg), respectively. The calculated half life of HI-6 was 78.2 min following 62.5 mg HI-6 + atropine dose and approximately 64-67 min following 125-500 mg HI-6 + atropine doses. Approximately 50 % of the total dose of HI-6 was eliminated unchanged in the urine. There were significant changes (p < 0.05) in AST, CPK, creatinine and gamma GT following the 500 mg HI-6 + atropine dose but they were not considered to be clinically significant. Urinalysis, hematology and semen analysis over the 24 hr observation period was uneventful. There were no clinically significant changes in heart rate or ECG trace, respiration or blood pressure, visual and mental acuity following HI-6 + atropine.

Clinical use of carbon-loaded thermoluminescent dosimeters for skin dose determination

International Nuclear Information System (INIS)

Ostwald, Patricia M.; Kron, Tomas; Hamilton, Christopher S.; Denham, James W.

1995-01-01

Purpose: Carbon-loaded thermoluminescent dosimeters (TLDs) are designed for surface/skin dose measurements. Following 4 years in clinical use at the Mater Hospital, the accuracy and clinical usefulness of the carbon-loaded TLDs was assessed. Methods and Materials: Teflon-based carbon-loaded lithium fluoride (LiF) disks with a diameter of 13 mm were used in the present study. The TLDs were compared with ion chamber readings and TLD extrapolation to determine the effective depth of the TLD measurement. In vivo measurements were made on patients receiving open-field treatments to the chest, abdomen, and groin. Skin entry dose or entry and exit dose were assessed in comparison with doses estimated from phantom measurements. Results: The effective depth of measurement in a 6 MV therapeutic x-ray beam was found to be about 0.10 mm using TLD extrapolation as a comparison. Entrance surface dose measurements made on a solid water phantom agreed well with ion chamber and TLD extrapolation measurements, and black TLDs provide a more accurate exit dose than the other methods. Under clinical conditions, the black TLDs have an accuracy of ± 5% (± 2 SD). The dose predicted from black TLD readings correlate with observed skin reactions as assessed with reflectance spectroscopy. Conclusion: In vivo dosimetry with carbon-loaded TLDs proved to be a useful tool in assessing the dose delivered to the basal cell layer in the skin of patients undergoing radiotherapy

Doses of olanzapine, risperidone, and haloperidol used in clinical practice: results of a prospective pharmacoepidemiologic study. EFESO Study Group. Estudio Farmacoepidemiologico en la Esquizofrenia con Olanzapina.

Science.gov (United States)

Sacristán, J A; Gómez, J C; Montejo, A L; Vieta, E; Gregor, K J

2000-05-01

The objectives of this study were to determine the doses of olanzapine (OLZ), risperidone (RIS), and haloperidol (HAL) used in clinical practice in outpatients with schizophrenia and the rates of occurrence of extrapyramidal symptoms (EPS) and other adverse events, clinical response, and use of concomitant medications. The present study involved a subset of patients from a 6-month, open-label, prospective observational study. Data were collected by 293 psychiatrists at mental health centers and other outpatient treatment facilities in Spain. Medications and doses used, occurrence of EPS and other adverse events, and scores on the Clinical Global Impression (CGI) of Severity Scale and Global Assessment of Function (GAF) were recorded. Clinical response was defined as a decrease of > or = 2 points on the CGI, with a final CGI score or = 5 received significantly higher overall mean daily doses than did patients with an initial CGI score < 5 (P < 0.001). A significantly lower proportion of OLZ-treated patients (10.2%) were receiving concomitant anticholinergic medication at the end of the study (month 6) compared with RIS-treated (19.9%) and HAL-treated (44.0%) patients (P < 0.001). The mean daily doses recorded in this analysis based on data from a naturalistic setting are consistent with recommendations based on clinical trials. Compared with both RIS- and HAL-treated patients, OLZ-treated patients were less likely to experience EPS or other adverse events, and less likely to use concomitant anticholinergic medications. OLZ-treated patients were also more likely to respond to treatment than were RIS-treated patients.

Patient radiation dose in some dental radiography clinics in Khartoum, Sudan

International Nuclear Information System (INIS)

Mohamed, Aziza Hamed Abdelgadir

2016-01-01

Patient dose audit is an important tool for quality control and it is important for monitoring patient exposure. The DAP meter has proved to be an easy and accurate tool for patient dosimetry and for establishment of diagnostic reference levels in dental radiology. The objective of this study was measure patient dose in dental radiography in some dental radiography clinics in Khartoum. The study was performed in five dental clinics comprising six panoramic and six intraoral dental radiography devices in Khartoum state. The incident surface air kerma (k i ) and dose area product were measured for intraoral and panoramic dental examinations, respectively for digital and film imaging modalities. Incident surface air kerma (k i ) was measured using calibrated dose rate meter where dose area product were determined from dose width product (DWP) measured using 3 cc pencil type CT ionization chamber. For intraoral examinations, the maximum, average and minimum, (1.95, 1.48, and 1.24) mGy, (5.84, 4.54, and 3.6) mGy for digital and imaging, respectively. This result was lower in digital in traol and higher in film imaging. The result for panoramic examination calculated dose area product (DAP) mean value for adult and pediatric was (103, 70.42) mGy cm 2 , respectively, where the dose for digital imaging was highest in two centers, compared to previous study. Increased patient dose in intraoral dental radiography could partially be explained by the use of circular collimators. or intraoral x-ray equipment the downward trend in patient dose can only be continue, a through the adoption of digital imaging methods. Our results are relatively higher in digital panoramic dental examinations. It is important to point out that non of the dental units under study were covered by regular quality assurance programme.(Author)

Clinical indications and radiation doses to the conceptus associated with CT imaging in pregnancy: a retrospective study

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Woussen, S.; Vanbeckevoort, D.; Bosmans, H.; Oyen, R. [University Hospitals Leuven, Department of Radiology, Leuven (Belgium); Lopez-Rendon, X.; Zanca, F. [University Hospitals Leuven, Department of Imaging and Pathology, Leuven (Belgium)

2016-04-15

To perform an internal audit at a university hospital with the aim of evaluating the number, clinical indication and operating procedure of computed tomography (CT) performed on pregnant patients and of estimating the radiation doses to the conceptus. A retrospective review was conducted of all CT examinations performed in a single centre on pregnant patients between January 2008 and July 2013. The radiation doses to the conceptus were estimated. The results were compared with published data. The number of CT examinations during pregnancy increased from 3-4 per year in 2008-2011 to 11 per year in 2012. The mean estimated conceptus radiation dose was considered negligible for CT of the head and cervical spine, being less than 0.01 mGy, and for CT of the chest, less than 0.1 mGy. The estimated conceptus radiation dose from abdominopelvic CT was on average 28.7 mGy (range 6.7-60.5 mGy). The number of CT scans of pregnant patients increased threefold during the last few years. Most clinical indications and doses were in line with good clinical practice and literature; only in two cases the dose to the conceptus was higher than 50 mGy. (orig.)

Clinical Outcomes With Dose-Escalated Adaptive Radiation Therapy for Urinary Bladder Cancer: A Prospective Study

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Murthy, Vedang, E-mail: vmurthy@actrec.gov.in [Department of Radiation Oncology, Tata Memorial Centre, Parel, Mumbai (India); Masodkar, Renuka; Kalyani, Nikhil; Mahantshetty, Umesh [Department of Radiation Oncology, Tata Memorial Centre, Parel, Mumbai (India); Bakshi, Ganesh; Prakash, Gagan [Department of Surgical Oncology, Tata Memorial Centre, Parel, Mumbai (India); Joshi, Amit; Prabhash, Kumar [Department of Medical Oncology, Tata Memorial Centre, Parel, Mumbai (India); Ghonge, Sujata; Shrivastava, Shyamkishore [Department of Radiation Oncology, Tata Memorial Centre, Parel, Mumbai (India)

2016-01-01

Purpose: The purpose of this study was to assess feasibility, clinical outcomes, and toxicity in patients with bladder cancer treated with adaptive, image guided radiation therapy (IGRT) for bladder preservation as a part of trimodality treatment. The role of dose escalation was also studied. Methods and Materials: Forty-four patients with localized bladder cancer were enrolled in a prospective study. They underwent maximal safe resection of bladder tumor and concurrent platinum-based chemotherapy. Patients with large tumors were offered induction chemotherapy. Radiation therapy planning was done using either 3 (n=34) or 6 (n=10) concentrically grown planning target volumes (PTV). Patients received 64 Gy in 32 fractions to the whole bladder and 55 Gy to the pelvic nodes and, if appropriate, a simultaneous integrated boost to the tumor bed to 68 Gy (equivalent dose for 2-Gy fractions assuming α/β of 10 [EQD2]{sub 10} = 68.7 Gy). Daily megavoltage (MV) imaging helped to choose the most appropriate PTV encompassing bladder for the particular day (using plan-of-the-day approach). Results: Most patients (88%) had T2 disease. Sixteen patients (36%) received neoadjuvant chemotherapy. A majority of the patients (73%) received prophylactic nodal irradiation, whereas 55% of the patients received escalated dose to the tumor bed. With a median follow-up of 30 months, the 3-year locoregional control (LRC), disease-free survival, and overall survival (OS) were 78%, 66%, and 67%, respectively. The bladder preservation rate was 83%. LRC (87% vs 68%, respectively, P=.748) and OS (74% vs 60%, respectively, P=.36) rates were better in patients receiving dose escalation. Instances of acute and late Radiation Therapy Oncology Group (RTOG) grade 3 genitourinary toxicity was seen in 5 (11%) and 2 (4%) patients, respectively. There was no acute or late RTOG grade 3 or higher gastrointestinal toxicity. Conclusions: Adaptive IGRT using plan-of-the-day approach for bladder

Clinical Outcomes With Dose-Escalated Adaptive Radiation Therapy for Urinary Bladder Cancer: A Prospective Study

International Nuclear Information System (INIS)

Murthy, Vedang; Masodkar, Renuka; Kalyani, Nikhil; Mahantshetty, Umesh; Bakshi, Ganesh; Prakash, Gagan; Joshi, Amit; Prabhash, Kumar; Ghonge, Sujata; Shrivastava, Shyamkishore

2016-01-01

Purpose: The purpose of this study was to assess feasibility, clinical outcomes, and toxicity in patients with bladder cancer treated with adaptive, image guided radiation therapy (IGRT) for bladder preservation as a part of trimodality treatment. The role of dose escalation was also studied. Methods and Materials: Forty-four patients with localized bladder cancer were enrolled in a prospective study. They underwent maximal safe resection of bladder tumor and concurrent platinum-based chemotherapy. Patients with large tumors were offered induction chemotherapy. Radiation therapy planning was done using either 3 (n=34) or 6 (n=10) concentrically grown planning target volumes (PTV). Patients received 64 Gy in 32 fractions to the whole bladder and 55 Gy to the pelvic nodes and, if appropriate, a simultaneous integrated boost to the tumor bed to 68 Gy (equivalent dose for 2-Gy fractions assuming α/β of 10 [EQD2] 10  = 68.7 Gy). Daily megavoltage (MV) imaging helped to choose the most appropriate PTV encompassing bladder for the particular day (using plan-of-the-day approach). Results: Most patients (88%) had T2 disease. Sixteen patients (36%) received neoadjuvant chemotherapy. A majority of the patients (73%) received prophylactic nodal irradiation, whereas 55% of the patients received escalated dose to the tumor bed. With a median follow-up of 30 months, the 3-year locoregional control (LRC), disease-free survival, and overall survival (OS) were 78%, 66%, and 67%, respectively. The bladder preservation rate was 83%. LRC (87% vs 68%, respectively, P=.748) and OS (74% vs 60%, respectively, P=.36) rates were better in patients receiving dose escalation. Instances of acute and late Radiation Therapy Oncology Group (RTOG) grade 3 genitourinary toxicity was seen in 5 (11%) and 2 (4%) patients, respectively. There was no acute or late RTOG grade 3 or higher gastrointestinal toxicity. Conclusions: Adaptive IGRT using plan-of-the-day approach for bladder preservation

Dose-response relationship in the treatment of gastrointestinal disorders.

Science.gov (United States)

Weihrauch, T R; Demol, P

1989-08-01

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

Comparison of doses delivered in clinical trials of neutron capture therapy in the USA

International Nuclear Information System (INIS)

Albritton, J.R.; Binns, P.J.; Riley, K.J.; Coderre, J.A.; Harling, O.K.; Kiger, W.S. III

2006-01-01

A combined 81 brain tumor patients have been treated in dose escalation trials of Neutron Capture Therapy (NCT) at Harvard-MIT and Brookhaven National Laboratory (BNL). Pooling the clinical outcomes from these trials will permit evaluation with more statistical rigor. However, differences in physical and computational dosimetry between the institutions make direct comparison of the clinical dosimetry difficult. This paper describes work performed to normalize the BNL clinical dosimetry to that of Harvard-MIT for combined dose response analysis. This normalization involved analysis of MIT measurements and calculations using the BNL treatment planning system (TPS), BNCT - Rtpe, for two different phantoms. The BNL TPS was calibrated to dose measurements made by MIT at the BMRR in the BNL calibration phantom, a Lucite cube, and then validated by MIT dose measurements at the BMMR in an ellipsoidal water phantom. Treatment plans for all BNL patients were recomputed using the newly determined TPS calibration, yielding reductions in reported mean brain doses of 19% on average in the initial 15 patients and 31% in the latter 38 patients. These reductions in reported doses have clinically significant implications for those relying on reported BNL doses as a basis for initial dose selection in clinical studies. (author)

The continual reassessment method: comparison of Bayesian stopping rules for dose-ranging studies.

Science.gov (United States)

Zohar, S; Chevret, S

2001-10-15

The continual reassessment method (CRM) provides a Bayesian estimation of the maximum tolerated dose (MTD) in phase I clinical trials and is also used to estimate the minimal efficacy dose (MED) in phase II clinical trials. In this paper we propose Bayesian stopping rules for the CRM, based on either posterior or predictive probability distributions that can be applied sequentially during the trial. These rules aim at early detection of either the mis-choice of dose range or a prefixed gain in the point estimate or accuracy of estimated probability of response associated with the MTD (or MED). They were compared through a simulation study under six situations that could represent the underlying unknown dose-response (either toxicity or failure) relationship, in terms of sample size, probability of correct selection and bias of the response probability associated to the MTD (or MED). Our results show that the stopping rules act correctly, with early stopping by using the two first rules based on the posterior distribution when the actual underlying dose-response relationship is far from that initially supposed, while the rules based on predictive gain functions provide a discontinuation of inclusions whatever the actual dose-response curve after 20 patients on average, that is, depending mostly on the accumulated data. The stopping rules were then applied to a data set from a dose-ranging phase II clinical trial aiming at estimating the MED dose of midazolam in the sedation of infants during cardiac catheterization. All these findings suggest the early use of the two first rules to detect a mis-choice of dose range, while they confirm the requirement of including at least 20 patients at the same dose to reach an accurate estimate of MTD (MED). A two-stage design is under study. Copyright 2001 John Wiley & Sons, Ltd.

A study on correlation between CT findings and clinical course of meningitis in children

International Nuclear Information System (INIS)

Song, Chi Sung; Chang, Kee Hyun; Yeon, Kyung Mo; Hwang, Yong Seung

1984-01-01

63 cases of meningitis in children were reviewed to study correlated between brain CT findings and clinical course. We divided 63 cases into 3 groups according to clinical course, that is , Group I: Healed without significant sequelae. Group II: Discharged with sequelae such as neurologic deficit or complicated clinical course. Group III: Expired or considered to be expired after hopeless discharge. The CT findings were retrospectively analyzed and compared with each clinical group. We drawed several conclusions as follows: 1. The wrost prognostic CT findings is dirty basal cisternal enhancement. ( Group I only 5%, Group II 50%, Group III 45%). 2. Focal brain parenchymal lesion, especially multiple, such as granuloma and infarct shows unfavorable clinical outcome, that is , high rate of Group III and evident neurologic deficit, in contrast to only 7% of Group I. 3. In 7 case of which CT findings is only hydrocephalus, the prognosis is rather favorable, that is 57% were Group I, 43% were improved after V-P shunt (Group II) and no Group III. But hydrocephalus with dirty cisternal enhancement results in grave prognosis, that is, Group I only 8%, Group II 54%, Group III 38%. With regard to overall hydrocephalus, predilection for good or bad prognosis can't be mentioned. 4. No prognostic difference were noted between presence and absence of periventricular low density in hydrocephalus. 5. CSF pressure of hydrocephalus is mostly high (over 20 cm H 2 O), but normal pressure hydrocephalus were noted in 24%. CSF pressure of normal ventricle size is mostly under 18 cm H 2 O but high pressure were noted in 18 % of the normal sized ventricle (most of them shows intracranial space occupying lesion such as granuloma, accute infarct, subdural effusion, etc). 6. Most of diffuse brain swelling, diffuse brain atrophy and subdural effusion result in Group I , that is , favorable clinical outcome. 7. Normal CT findings are found in 29%, of which 61% belong to Group I and 31% to Group

Axitinib in combination with pembrolizumab in patients with advanced renal cell cancer: a non-randomised, open-label, dose-finding, and dose-expansion phase 1b trial.

Science.gov (United States)

Atkins, Michael B; Plimack, Elizabeth R; Puzanov, Igor; Fishman, Mayer N; McDermott, David F; Cho, Daniel C; Vaishampayan, Ulka; George, Saby; Olencki, Thomas E; Tarazi, Jamal C; Rosbrook, Brad; Fernandez, Kathrine C; Lechuga, Mariajose; Choueiri, Toni K

2018-03-01

Previous studies combining PD-1 checkpoint inhibitors with tyrosine kinase inhibitors of the VEGF pathway have been characterised by excess toxicity, precluding further development. We hypothesised that axitinib, a more selective VEGF inhibitor than others previously tested, could be combined safely with pembrolizumab (anti-PD-1) and yield antitumour activity in patients with treatment-naive advanced renal cell carcinoma. In this ongoing, open-label, phase 1b study, which was done at ten centres in the USA, we enrolled patients aged 18 years or older who had advanced renal cell carcinoma (predominantly clear cell subtype) with their primary tumour resected, and at least one measureable lesion, Eastern Cooperative Oncology Group performance status 0-1, controlled hypertension, and no previous systemic therapy for renal cell carcinoma. Eligible patients received axitinib plus pembrolizumab in a dose-finding phase to estimate the maximum tolerated dose, and additional patients were enrolled into a dose-expansion phase to further establish safety and determine preliminary efficacy. Axitinib 5 mg was administered orally twice per day with pembrolizumab 2 mg/kg given intravenously every 3 weeks. We assessed safety in all patients who received at least one dose of axitinib or pembrolizumab; antitumour activity was assessed in all patients who received study treatment and had an adequate baseline tumour assessment. The primary endpoint was investigator-assessed dose-limiting toxicity during the first two cycles (6 weeks) to estimate the maximum tolerated dose and recommended phase 2 dose. This study is registered with ClinicalTrials.gov, number NCT02133742. Between Sept 23, 2014, and March 25, 2015, we enrolled 11 patients with previously untreated advanced renal cell carcinoma to the dose-finding phase and between June 3, 2015, and Oct 13, 2015, we enrolled 41 patients to the dose-expansion phase. All 52 patients were analysed together. No unexpected toxicities were

Ocular pharmacokinetics and tolerability of bimatoprost ophthalmic solutions administered once or twice daily in rabbits, and clinical dosing implications

Directory of Open Access Journals (Sweden)

Shen J

2017-09-01

, especially in the iris-ciliary body. Key findings from previous clinical studies suggest that by varying the concentration of benzalkonium chloride (a preservative with corneal penetration-enhancing properties, formulations of bimatoprost 0.01% can be administered once or twice daily. These findings support development of bimatoprost 0.01%-based fixed-dose combination therapies administered twice daily for patients who require multiple adjunctive medications to control their IOP. Keywords: bimatoprost, pharmacokinetics, glaucoma, intraocular pressure, hyperemia

Determination of the optimal minimum radioiodine dose in patients with Graves' disease: a clinical outcome study

Energy Technology Data Exchange (ETDEWEB)

Howarth, D.; Tan, P.; Booker, J. [Pacific Medical Imaging, Newcastle, NSW (Australia); Epstein, M. [Dept. of Endocrinology, John Hunter Hospital, Newcastle, NSW (Australia); Lan, L. [High-Dependency Unit, St. George Hospital, Sydney, NSW (Australia)

2001-10-01

The study was performed under the auspices of the International Atomic Energy Commission, Vienna, Austria, with the aim of determining the optimal minimum therapeutic dose of iodine-131 for Graves' disease. The study was designed as a single-blinded randomised prospective outcome trial. Fifty-eight patients were enrolled, consisting of 50 females and 8 males aged from 17 to 75 years. Each patient was investigated by clinical assessment, biochemical and immunological assessment, thyroid ultrasound, technetium-99m thyroid scintigraphy and 24-h thyroid {sup 131}I uptake. Patients were then randomised into two treatment groups, one receiving 60 Gy and the other receiving 90 Gy thyroid tissue absorbed dose of radioiodine. The end-point markers were clinical and biochemical response to treatment. The median follow-up period was 37.5 months (range, 24-48 months). Among the 57 patients who completed final follow-up, a euthyroid state was achieved in 26 patients (46%), 27 patients (47%) were rendered hypothyroid and four patients (7%) remained hyperthyroid. Thirty-four patients (60%) remained hyperthyroid at 6 months after the initial radioiodine dose (median dose 126 MBq), and a total of 21 patients required additional radioiodine therapy (median total dose 640 MBq; range 370-1,485 MBq). At 6-month follow-up, of the 29 patients who received a thyroid tissue dose of 90 Gy, 17 (59%) remained hyperthyroid. By comparison, of the 28 patients who received a thyroid tissue dose of 60 Gy, 17 (61%) remained hyperthyroid. No significant difference in treatment response was found (P=0.881). At 6 months, five patients in the 90-Gy group were hypothyroid, compared to two patients in the 60-Gy group (P=0.246). Overall at 6 months, non-responders to low-dose therapy had a significantly larger thyroid gland mass (respective means: 35.9 ml vs 21.9 ml) and significantly higher levels of serum thyroglobulin (respective means: 597.6 {mu}g/l vs 96.9 {mu}g/l). Where low-dose radioiodine

Comparison of image quality and visibility of normal and abnormal findings at submillisievert chest CT using filtered back projection, iterative model reconstruction (IMR) and iDose{sup 4}™

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Laqmani, Azien, E-mail: a.laqmani@uke.de [Department of Diagnostic and Interventional Radiology and Nuclear Medicine, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg (Germany); Avanesov, Maxim; Butscheidt, Sebastian; Kurfürst, Maximilian [Department of Diagnostic and Interventional Radiology and Nuclear Medicine, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg (Germany); Sehner, Susanne [Department of Medical Biometry and Epidemiology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg (Germany); Schmidt-Holtz, Jakob; Derlin, Thorsten; Behzadi, Cyrus [Department of Diagnostic and Interventional Radiology and Nuclear Medicine, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg (Germany); Nagel, Hans D. [Science & Technology for Radiology, Fritz-Reuter-Weg 5f, 21244 Buchholz, Germany, (Germany); Adam, Gerhard; Regier, Marc [Department of Diagnostic and Interventional Radiology and Nuclear Medicine, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg (Germany)

2016-11-15

Objective: To compare both image quality and visibility of normal and abnormal findings at submillisievert chest CT (smSv-CT) using filtered back projection (FBP) and the two different iterative reconstruction (IR) techniques iterative model reconstruction (IMR) and iDose{sup 4}™. Materials and methods: This institutional review board approved study was based on retrospective interpretation of clinically indicated acquired data. The requirement to obtain informed consent was waived. 81 patients with suspected pneumonia underwent smSv-CT (Brilliance iCT, Philips Healthcare; mean effective dose: 0.86 ± 0.2 mSv). Data were reconstructed using FBP and two different IR techniques iDose{sup 4}™ and IMR (Philips Healthcare) at various iteration levels. Objective image noise (OIN) was measured. Two experienced readers independently assessed all images for image noise, image appearance and visibility of normal anatomic and abnormal findings. A random intercept model was used for statistical analysis. Results: Compared to FBP and iDose{sup 4}™, IMR reduced OIN up to 88% and 72%, respectively (p < 0.001). A mild blotchy image appearance was seen in IMR images, affecting diagnostic confidence. iDose{sup 4}™ images provided satisfactory to good image quality for visibility of normal and abnormal findings and were superior to FBP (p < 0.001). IMR images were significantly inferior for visibility of normal structures compared to iDose{sup 4}™, while being superior for visibility of abnormal findings except for reticular pattern (p < 0.001). Conclusion: IMR results for visibility of normal and abnormal lung findings are heterogeneous, indicating that IMR may not represent a priority technique for clinical routine. iDose{sup 4}™ represents a suitable method for evaluation of lung tissue at submillisievert chest CT.

Regulatory T Cell Responses in Participants with Type 1 Diabetes after a Single Dose of Interleukin-2: A Non-Randomised, Open Label, Adaptive Dose-Finding Trial

Science.gov (United States)

Todd, John A.; Porter, Linsey; Smyth, Deborah J.; Rainbow, Daniel B.; Ferreira, Ricardo C.; Yang, Jennie H.; Bell, Charles J. M.; Schuilenburg, Helen; Challis, Ben; Clarke, Pamela; Coleman, Gillian; Dawson, Sarah; Goymer, Donna; Kennet, Jane; Brown, Judy; Greatorex, Jane; Goodfellow, Ian; Evans, Mark; Mander, Adrian P.; Bond, Simon; Wicker, Linda S.

2016-01-01

Background Interleukin-2 (IL-2) has an essential role in the expansion and function of CD4+ regulatory T cells (Tregs). Tregs reduce tissue damage by limiting the immune response following infection and regulate autoreactive CD4+ effector T cells (Teffs) to prevent autoimmune diseases, such as type 1 diabetes (T1D). Genetic susceptibility to T1D causes alterations in the IL-2 pathway, a finding that supports Tregs as a cellular therapeutic target. Aldesleukin (Proleukin; recombinant human IL-2), which is administered at high doses to activate the immune system in cancer immunotherapy, is now being repositioned to treat inflammatory and autoimmune disorders at lower doses by targeting Tregs. Methods and Findings To define the aldesleukin dose response for Tregs and to find doses that increase Tregs physiologically for treatment of T1D, a statistical and systematic approach was taken by analysing the pharmacokinetics and pharmacodynamics of single doses of subcutaneous aldesleukin in the Adaptive Study of IL-2 Dose on Regulatory T Cells in Type 1 Diabetes (DILT1D), a single centre, non-randomised, open label, adaptive dose-finding trial with 40 adult participants with recently diagnosed T1D. The primary endpoint was the maximum percentage increase in Tregs (defined as CD3+CD4+CD25highCD127low) from the baseline frequency in each participant measured over the 7 d following treatment. There was an initial learning phase with five pairs of participants, each pair receiving one of five pre-assigned single doses from 0.04 × 106 to 1.5 × 106 IU/m2, in order to model the dose-response curve. Results from each participant were then incorporated into interim statistical modelling to target the two doses most likely to induce 10% and 20% increases in Treg frequencies. Primary analysis of the evaluable population (n = 39) found that the optimal doses of aldesleukin to induce 10% and 20% increases in Tregs were 0.101 × 106 IU/m2 (standard error [SE] = 0.078, 95% CI = −0

Clinical and imaging findings in spinal cord arteriovenous malformations

International Nuclear Information System (INIS)

Kim, Sang Heum; Kim, Dong Ik; Yoon, Pyeong Ho; Jeon, Pyoung; Ihn, Yeon Kwon

1997-01-01

The purpose of this study is to evaluate the findings of magnetic resonance (MR) imaging and selective spinal angiography of spinal cord arteriovenous malformations (SCAVMs) and to investigate the correlation of these findings with the development of clinical symptoms. In 16 patients diagnosed as suffering from SCAVMs, MR imaging and selective spinal angiograms were retrospectively analyzed and correlated with clinical symptoms. Clinical data were reviewed, especially concerning the mode of onset of clinical symptoms, and MR images of SCAVMs were evaluated with regard to the following parameters: spinal cord swelling with T2 hyperintensity, cord atrophy, intramedullary hemorrhage, and contrast enhancement of the spinal cord. Selective spinal angiographic findings of SCAVMs were also evaluated in terms of the following , parameters: type of SCAVM, presence of aneurysms, and patterns of venous drainage. Imaging findings were also correlated with the development of clinical symptoms. Systematic evaluation of the findings of MR imaging and angiography provides detailed information on the type of AVM and status of the spinal cord parenchyma, and this can be correlated with clinical manifestations of SCAVM. In patients suffering from this condition, spinal cord dysfunction due to venous congestion appears to be the main cause of clinical symptoms. (author). 18 refs., 2 tabs., 3 figs

Dose reduction with adaptive statistical iterative reconstruction for paediatric CT: phantom study and clinical experience on chest and abdomen CT

Energy Technology Data Exchange (ETDEWEB)

Gay, F.; Lasalle, S.; Neuenschwander, S.; Brisse, H.J. [Institut Curie, Imaging Department, Paris (France); Pavia, Y.; Pierrat, N. [Institut Curie, Medical Physics Department, Paris (France)

2014-01-15

To assess the benefit and limits of iterative reconstruction of paediatric chest and abdominal computed tomography (CT). The study compared adaptive statistical iterative reconstruction (ASIR) with filtered back projection (FBP) on 64-channel MDCT. A phantom study was first performed using variable tube potential, tube current and ASIR settings. The assessed image quality indices were the signal-to-noise ratio (SNR), the noise power spectrum, low contrast detectability (LCD) and spatial resolution. A clinical retrospective study of 26 children (M:F = 14/12, mean age: 4 years, range: 1-9 years) was secondarily performed allowing comparison of 18 chest and 14 abdominal CT pairs, one with a routine CT dose and FBP reconstruction, and the other with 30 % lower dose and 40 % ASIR reconstruction. Two radiologists independently compared the images for overall image quality, noise, sharpness and artefacts, and measured image noise. The phantom study demonstrated a significant increase in SNR without impairment of the LCD or spatial resolution, except for tube current values below 30-50 mA. On clinical images, no significant difference was observed between FBP and reduced dose ASIR images. Iterative reconstruction allows at least 30 % dose reduction in paediatric chest and abdominal CT, without impairment of image quality. (orig.)

Dose reduction with adaptive statistical iterative reconstruction for paediatric CT: phantom study and clinical experience on chest and abdomen CT

International Nuclear Information System (INIS)

Gay, F.; Lasalle, S.; Neuenschwander, S.; Brisse, H.J.; Pavia, Y.; Pierrat, N.

2014-01-01

To assess the benefit and limits of iterative reconstruction of paediatric chest and abdominal computed tomography (CT). The study compared adaptive statistical iterative reconstruction (ASIR) with filtered back projection (FBP) on 64-channel MDCT. A phantom study was first performed using variable tube potential, tube current and ASIR settings. The assessed image quality indices were the signal-to-noise ratio (SNR), the noise power spectrum, low contrast detectability (LCD) and spatial resolution. A clinical retrospective study of 26 children (M:F = 14/12, mean age: 4 years, range: 1-9 years) was secondarily performed allowing comparison of 18 chest and 14 abdominal CT pairs, one with a routine CT dose and FBP reconstruction, and the other with 30 % lower dose and 40 % ASIR reconstruction. Two radiologists independently compared the images for overall image quality, noise, sharpness and artefacts, and measured image noise. The phantom study demonstrated a significant increase in SNR without impairment of the LCD or spatial resolution, except for tube current values below 30-50 mA. On clinical images, no significant difference was observed between FBP and reduced dose ASIR images. Iterative reconstruction allows at least 30 % dose reduction in paediatric chest and abdominal CT, without impairment of image quality. (orig.)

Dose reconstruction in deforming lung anatomy: Dose grid size effects and clinical implications

International Nuclear Information System (INIS)

Rosu, Mihaela; Chetty, Indrin J.; Balter, James M.; Kessler, Marc L.; McShan, Daniel L.; Ten Haken, Randall K.

2005-01-01

In this study we investigated the accumulation of dose to a deforming anatomy (such as lung) based on voxel tracking and by using time weighting factors derived from a breathing probability distribution function (p.d.f.). A mutual information registration scheme (using thin-plate spline warping) provided a transformation that allows the tracking of points between exhale and inhale treatment planning datasets (and/or intermediate state scans). The dose distributions were computed at the same resolution on each dataset using the Dose Planning Method (DPM) Monte Carlo code. Two accumulation/interpolation approaches were assessed. The first maps exhale dose grid points onto the inhale scan, estimates the doses at the 'tracked' locations by trilinear interpolation and scores the accumulated doses (via the p.d.f.) on the original exhale data set. In the second approach, the 'volume' associated with each exhale dose grid point (exhale dose voxel) is first subdivided into octants, the center of each octant is mapped to locations on the inhale dose grid and doses are estimated by trilinear interpolation. The octant doses are then averaged to form the inhale voxel dose and scored at the original exhale dose grid point location. Differences between the interpolation schemes are voxel size and tissue density dependent, but in general appear primarily only in regions with steep dose gradients (e.g., penumbra). Their magnitude (small regions of few percent differences) is less than the alterations in dose due to positional and shape changes from breathing in the first place. Thus, for sufficiently small dose grid point spacing, and relative to organ motion and deformation, differences due solely to the interpolation are unlikely to result in clinically significant differences to volume-based evaluation metrics such as mean lung dose (MLD) and tumor equivalent uniform dose (gEUD). The overall effects of deformation vary among patients. They depend on the tumor location, field

The Protective Effect of Low-Dose Aspirin against Colorectal Cancer Is Unlikely Explained by Selection Bias: Results from Three Different Study Designs in Clinical Practice.

Directory of Open Access Journals (Sweden)

Lucía Cea Soriano

Full Text Available We conducted three differently designed nested case-control studies to evaluate whether the protective effect of low-dose aspirin against colorectal cancer (CRC is explained by selection bias.Using a large validated UK primary care database, we followed different cohorts of patients, who varied in their demographic and clinical characteristics, to identify first ever cases of CRC. In Studies 1 and 2, two cohorts were followed, i new users of low-dose aspirin at start of follow-up (N = 170,336 in Study 1, N = 171,527 in Study 2 and either ii non-users of low-dose aspirin (Study 1, N = 170,336 or new users of paracetamol (Study 2, N = 149,597 at start of follow-up. In Study 3 a single cohort of individuals näive to low-dose aspirin at the start of observation was followed. Controls were selected using incidence sampling and logistic regression used to obtain an unbiased estimate of the incidence rate ratio (RR with 95% confidence intervals (CIs. Low-dose aspirin exposure was analyzed 'as-treated' before the index date (CRC date for cases, random date for controls.In the three studies, median (maximum follow-up was 5.1 (12, 5.8 (12 and 7.5 (13 years, respectively. 3033 incident CRC cases were identified in Study 1, 3174 in Study 2, and 12,333 in Study 3. Current use of low-dose aspirin was associated with a significantly reduced risk of 34%, 29% and 31% in the three studies, respectively; corresponding RRs (95% CIs were 0.66 (0.60-0.73, 0.71 (0.63-0.80 and 0.69 (0.64-0.74. In each study, significantly reduced risks of CRC were seen when low-dose aspirin was used for primary or secondary cardiovascular disease prevention, in both sexes, and across all age groups evaluated.Low-dose aspirin is associated with a significantly reduced risk of CRC. The consistency of our findings across different studies makes selection bias an unlikely explanation.

Dose-finding study of carbamylated monomeric allergoid tablets in grass-allergic rhinoconjunctivitis patients.

Science.gov (United States)

Mösges, Ralph; Rohdenburg, Christina; Eichel, Andrea; Zadoyan, Gregor; Kasche, Elena-Manja; Shah-Hosseini, Kija; Lehmacher, Walter; Schmalz, Petra; Compalati, Enrico

2017-11-01

To determine the optimal effective and safe dose of sublingual immunotherapy tablets containing carbamylated monomeric allergoids in patients with grass pollen-induced allergic rhinoconjunctivitis. In this prospective, randomized, double-blind, active-controlled, multicenter, Phase II study, four different daily doses were applied preseasonally for 12 weeks. Of 158 randomized adults, 155 subjects (safety population) received 300 units of allergy (UA)/day (n = 36), 600 UA/day (n = 43), 1000 UA/day (n = 39), or 2000 UA/day (n = 37). After treatment, 54.3, 47.6, 59.0 and 51.4% of patients, respectively, ceased to react to the highest allergen concentration in a conjunctival provocation test. Furthermore, the response threshold improved in 70.4, 62.9, 76.7 and 66.7% of patients, respectively. No serious adverse events occurred. This study found 1000 UA/day to be the optimal effective and safe dose.

Phase I/II dose-finding study of nanoparticle albumin-bound paclitaxel (nab®-Paclitaxel) plus Cisplatin as Treatment for Metastatic Nasopharyngeal Carcinoma.

Science.gov (United States)

Huang, Yan; Liang, Wenhua; Yang, Yunpeng; Zhao, Liping; Zhao, Hongyun; Wu, Xuan; Zhao, Yuanyuan; Zhang, Yang; Zhang, Li

2016-07-13

This phase I/II study aimed to determine the maximum tolerated dose (MTD) of nanoparticle albumin-bound paclitaxel (nab (®)-paclitaxel) plus cisplatin as treatment for metastatic nasopharyngeal carcinoma (NPC). Patients were enrolled into 1 of 3 dose cohorts, each with 21-day treatment cycles: 1) intravenous (IV) nab-paclitaxel 260 mg/m(2) on day 1; 2) IV nab-paclitaxel 140 mg/m(2) on days 1 and 8; 3) IV nab-paclitaxel 100 mg/m(2) on days 1, 8, and 15. All patients received IV cisplatin 75 mg/m(2) on day 1. Treatment continued for 4-6 cycles, or until progression or unacceptable toxicity. If more than one-third of the patients in a cohort experienced a dose-limiting toxicity (DLT), the dose used in the previous cohort would be designated the MTD. Secreted protein acidic and rich in cysteine (SPARC) expression was detected by immunohistochemistry staining. Sixty-nine patients were enrolled, of whom 64 and 67 were eligible for efficacy and safety analysis, respectively. Two DLTs occurred in cohort 1 (grade 4 febrile neutropenia, grade 3 myalgia), none occurred in cohort 2, and 2 occurred in cohort 3 (both grade 3 fatigue). The MTD was not reached. Partial responses were achieved by 42 patients, 15 had stable disease, and 7 had progressive disease, giving an overall response rate of 66 %. Median progression-free survival was 9 months (95 % CI, 6-12 months). Grade ≥ 3 adverse events were mainly hematologic. There was no significant difference between the 3 cohorts with respect to efficacy or safety. Biomarker analyses indicated that stromal, rather than tumoral, SPARC may predict the response to nab-paclitaxel in NPC. Our findings suggest that nab-paclitaxel plus cisplatin is a highly active regimen with moderate toxicity for the treatment of metastatic NPC, which warrants further investigation in a phase III study. ClinicalTrials.gov ID: NCT01735409 . The trial was registered on November 20th, 2012.

Automatic recognition of disorders, findings, pharmaceuticals and body structures from clinical text: an annotation and machine learning study.

Science.gov (United States)

Skeppstedt, Maria; Kvist, Maria; Nilsson, Gunnar H; Dalianis, Hercules

2014-06-01

Automatic recognition of clinical entities in the narrative text of health records is useful for constructing applications for documentation of patient care, as well as for secondary usage in the form of medical knowledge extraction. There are a number of named entity recognition studies on English clinical text, but less work has been carried out on clinical text in other languages. This study was performed on Swedish health records, and focused on four entities that are highly relevant for constructing a patient overview and for medical hypothesis generation, namely the entities: Disorder, Finding, Pharmaceutical Drug and Body Structure. The study had two aims: to explore how well named entity recognition methods previously applied to English clinical text perform on similar texts written in Swedish; and to evaluate whether it is meaningful to divide the more general category Medical Problem, which has been used in a number of previous studies, into the two more granular entities, Disorder and Finding. Clinical notes from a Swedish internal medicine emergency unit were annotated for the four selected entity categories, and the inter-annotator agreement between two pairs of annotators was measured, resulting in an average F-score of 0.79 for Disorder, 0.66 for Finding, 0.90 for Pharmaceutical Drug and 0.80 for Body Structure. A subset of the developed corpus was thereafter used for finding suitable features for training a conditional random fields model. Finally, a new model was trained on this subset, using the best features and settings, and its ability to generalise to held-out data was evaluated. This final model obtained an F-score of 0.81 for Disorder, 0.69 for Finding, 0.88 for Pharmaceutical Drug, 0.85 for Body Structure and 0.78 for the combined category Disorder+Finding. The obtained results, which are in line with or slightly lower than those for similar studies on English clinical text, many of them conducted using a larger training data set, show that

A 12-week DBPC dose-finding study with sublingual monomeric allergoid tablets in house dust mite-allergic patients.

Science.gov (United States)

Hüser, C; Dieterich, P; Singh, J; Shah-Hosseini, K; Allekotte, S; Lehmacher, W; Compalati, E; Mösges, R

2017-01-01

In sublingual immunotherapy, optimal doses are a key factor for therapeutic outcomes. The aim of this study with tablets containing carbamylated monomeric house dust mite allergoids was to determine the most effective and safe dose. In this double-blind, placebo-controlled dose-finding study, 131 patients with house dust mite-induced allergic rhinoconjunctivitis were randomized to 12-week treatments with 300 UA/day, 1000 UA/day, 2000 UA/day, 3000 UA/day or placebo. Conjunctival provocation tests (CPT) were performed before, during and after treatment. The change in mean allergic severity (primary endpoint), calculated from the severity of the CPT reaction, and the proportion of patients with an improved CPT threshold (secondary endpoint) determined the treatment effect. The mean allergic severity decreased in all groups, including the placebo group. It was lower in all active treatment groups (300 UA/day: 0.14, 1000 UA/day: 0.15, 2000 UA/day: 0.10, 3000 UA/day: 0.15) than in the placebo group (0.30). However, this difference was not statistically significant (P allergoid sublingual tablets is well tolerated and reduces the CPT reaction in house dust mite-allergic patients. © 2016 The Authors. Allergy Published by John Wiley & Sons Ltd.

Clinical findings just after return to play predict hamstring re-injury, but baseline MRI findings do not

NARCIS (Netherlands)

de Vos, Robert-Jan; Reurink, Gustaaf; Goudswaard, Gert-Jan; Moen, Maarten H.; Weir, Adam; Tol, Johannes L.

2014-01-01

Acute hamstring re-injuries are common and hard to predict. The aim of this study was to investigate the association between clinical and imaging findings and the occurrence of hamstring re-injuries. We obtained baseline data (clinical and MRI findings) of athletes who sustained an acute hamstring

Clinical Effectiveness and Dose Titration in Pediatric Practice

Directory of Open Access Journals (Sweden)

Yu.V. Marushko

2016-02-01

Full Text Available The paper is devoted to the questions of usage of one of the popular antipyretic and anesthetic drug in pediatric practice — ibuprofen. In the article there are generalized literature data and own experience in ibuprofen dose titration in single dose 5 and 10 mg/kg depending on clinical situation.

Clinical and Laboratory Findings in Patients with Tramadol Intoxication Referred to Razi Hospital During 2005-06

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Morteza Rahbar Taromsari

2012-03-01

Full Text Available Introduction: Frequency of Tramadol intoxication is increasing as a result of its useas a drug for suppression of withdrawal symptoms by opioids abusers and its wideaccessibility of this drug. Tramadol intoxication can lead to death and, therefore, earlyidentification of its clinical manifestations is crucial since early detection of theintoxication and its treatment could improve patients' survival This study investigatedthe frequency of clinical and laboratory findings in Tramadol intoxication.Methods: In this cross-sectional study, patients with Tramadol intoxication whoreferred to Razi Hospital in Rasht, Iran, during 2005-06 were examined. Theirmedical records were surveyed for demographic data, past medical history,neurological examination, and routine laboratory tests. All data were statisticallyanalyzed by SPSS software version 14.Result: The majority of the 306 patients (83.3% male were in the age range of 20-40 years and 68.6% of them had been educated up to high school. The mean dose ofingested Tramadol was 746± 453mg (mean± SD. Agitation (25.2% and seizure(20.3% were the most frequent reported symptoms. Among laboratory abnormalities,the most common findings were prolonged PT (18.3% and increased ALT (5.6%.Conclusion: The most common clinical presentation was agitation and the mostcommon laboratory finding was prolonged PT. Of all the patients, 3 cases wereadmitted to ICU. Although Tramadol poisoning might lead to death, there was onlyone death after Tramadol poisoning in the current study.

An incidental case of biliary fascioliasis with subtle clinical findings: US and MRCP findings

International Nuclear Information System (INIS)

Önder, Hakan; Ekici, Faysal; Adin, Emin; Kuday, Suzan; Gümüş, Hatice; Bilici, Aslan

2013-01-01

Fascioliasis is a disease caused by the trematode Fasciola hepatica. Cholangitis is a common clinical manifestation. Although fascioliasis may show various radiological and clinical features, cases without biliary dilatation are rare. We present unique ultrasound (US) and magnetic resonance cholangiopancreatography (MRCP) findings of a biliary fascioliasis case which doesn’t have biliary obstruction or cholestasis. Radiologically, curvilinear parasites compatible with juvenile and mature Fasciola hepatica within the gallbladder and common bile duct were found. The parasites appear as bright echogenic structures with no acoustic shadow on US and hypo-intense curvilinear lesions on T2 weighted MRCP images. Imaging studies may significantly contribute to the diagnosis of patients with subtle clinical and laboratory findings, particularly in endemic regions

Dose reduction with adaptive statistical iterative reconstruction for paediatric CT: phantom study and clinical experience on chest and abdomen CT.

Science.gov (United States)

Gay, F; Pavia, Y; Pierrat, N; Lasalle, S; Neuenschwander, S; Brisse, H J

2014-01-01

To assess the benefit and limits of iterative reconstruction of paediatric chest and abdominal computed tomography (CT). The study compared adaptive statistical iterative reconstruction (ASIR) with filtered back projection (FBP) on 64-channel MDCT. A phantom study was first performed using variable tube potential, tube current and ASIR settings. The assessed image quality indices were the signal-to-noise ratio (SNR), the noise power spectrum, low contrast detectability (LCD) and spatial resolution. A clinical retrospective study of 26 children (M:F = 14/12, mean age: 4 years, range: 1-9 years) was secondarily performed allowing comparison of 18 chest and 14 abdominal CT pairs, one with a routine CT dose and FBP reconstruction, and the other with 30 % lower dose and 40 % ASIR reconstruction. Two radiologists independently compared the images for overall image quality, noise, sharpness and artefacts, and measured image noise. The phantom study demonstrated a significant increase in SNR without impairment of the LCD or spatial resolution, except for tube current values below 30-50 mA. On clinical images, no significant difference was observed between FBP and reduced dose ASIR images. Iterative reconstruction allows at least 30 % dose reduction in paediatric chest and abdominal CT, without impairment of image quality. • Iterative reconstruction helps lower radiation exposure levels in children undergoing CT. • Adaptive statistical iterative reconstruction (ASIR) significantly increases SNR without impairing spatial resolution. • For abdomen and chest CT, ASIR allows at least a 30 % dose reduction.

Clinically relevant incidental cardiovascular findings in CT examinations

International Nuclear Information System (INIS)

Voigt, P.; Fahnert, J.; Kahn, T.; Surov, A.; Schramm, D.; Bach, A.G.

2017-01-01

Incidental cardiovascular findings are a frequent phenomenon in computed tomography (CT) examinations. As the result of a dedicated PubMed search this article gives a systemic overview of the current literature on the most important incidental cardiovascular findings, their prevalence and clinical relevance. The majority of incidental cardiovascular findings are of only low clinical relevance; however, highly relevant incidental findings, such as aortic aneurysms, thromboses and thromboembolic events can also occasionally be found, especially in oncology patients. The scans from every CT examination should also be investigated for incidental findings as they can be of decisive importance for the further clinical management of patients, depending on their clinical relevance. (orig.) [de

Parkinson’s Disease: Low-Dose Haloperidol Increases Dopamine Receptor Sensitivity and Clinical Response

Directory of Open Access Journals (Sweden)

Craig J. Hudson

2014-01-01

Full Text Available Background. It is known that ultra-low doses of haloperidol can cause dopamine supersensitivity of dopamine D2 receptors and related behaviour in animals. Objective. The objective was to determine whether a daily ultra-low dose of 40 micrograms of haloperidol could enhance the clinical action of levodopa in Parkinson’s disease patients. Method. While continuing their daily treatment with levodopa, 16 patients with Parkinson’s disease were followed weekly for six weeks. They received an add-on daily dose of 40 micrograms of haloperidol for the first two weeks only. The SPES/SCOPA scale (short scale for assessment of motor impairments and disabilities in Parkinson’s disease was administered before treatment and weekly throughout the trial. Results. The results showed a mean decrease in SPES/SCOPA scores after one week of the add-on treatment. Conclusion. SCOPA scores decreased after the addition of low-dose haloperidol to the standard daily levodopa dose. This finding is consistent with an increase in sensitivity of dopamine D2 receptors induced by haloperidol. Such treatment for Parkinson’s disease may possibly permit the levodopa dose to be reduced and, thus, delay the onset of levodopa side effects.

Dose escalation methods in phase I cancer clinical trials.

Science.gov (United States)

Le Tourneau, Christophe; Lee, J Jack; Siu, Lillian L

2009-05-20

Phase I clinical trials are an essential step in the development of anticancer drugs. The main goal of these studies is to establish the recommended dose and/or schedule of new drugs or drug combinations for phase II trials. The guiding principle for dose escalation in phase I trials is to avoid exposing too many patients to subtherapeutic doses while preserving safety and maintaining rapid accrual. Here we review dose escalation methods for phase I trials, including the rule-based and model-based dose escalation methods that have been developed to evaluate new anticancer agents. Toxicity has traditionally been the primary endpoint for phase I trials involving cytotoxic agents. However, with the emergence of molecularly targeted anticancer agents, potential alternative endpoints to delineate optimal biological activity, such as plasma drug concentration and target inhibition in tumor or surrogate tissues, have been proposed along with new trial designs. We also describe specific methods for drug combinations as well as methods that use a time-to-event endpoint or both toxicity and efficacy as endpoints. Finally, we present the advantages and drawbacks of the various dose escalation methods and discuss specific applications of the methods in developmental oncotherapeutics.

Low-dose (10-Gy) total skin electron beam therapy for cutaneous T-cell lymphoma: an open clinical study and pooled data analysis.

Science.gov (United States)

Kamstrup, Maria R; Gniadecki, Robert; Iversen, Lars; Skov, Lone; Petersen, Peter Meidahl; Loft, Annika; Specht, Lena

2015-05-01

Cutaneous T-cell lymphomas (CTCLs) are dominated by mycosis fungoides (MF) and Sézary syndrome (SS), and durable disease control is a therapeutic challenge. Standard total skin electron beam therapy (TSEBT) is an effective skin-directed therapy, but the possibility of retreatments is limited to 2 to 3 courses in a lifetime due to skin toxicity. This study aimed to determine the clinical effect of low-dose TSEBT in patients with MF and SS. In an open clinical study, 21 patients with MF/SS stages IB to IV were treated with low-dose TSEBT over dose of 10 Gy in 10 fractions. Data from 10 of these patients were published previously but were included in the current pooled data analysis. Outcome measures were response rate, duration of response, and toxicity. The overall response rate was 95% with a complete cutaneous response or a very good partial response rate (dose (10-Gy) TSEBT offers a high overall response rate and is relatively safe. With this approach, reirradiation at times of relapse or progression is likely to be less toxic than standard dose TSEBT. It remains to be established whether adjuvant and combination treatments can prolong the beneficial effects of low-dose TSEBT. Copyright © 2015 Elsevier Inc. All rights reserved.

Single dose (400 mg) versus 7 day (200 mg) daily dose itraconazole in the treatment of tinea versicolor: a randomized clinical trial.

Science.gov (United States)

Wahab, M A; Ali, M E; Rahman, M H; Chowdhury, S A; Monamie, N S; Sultana, N; Khondoker, L

2010-01-01

Tinea (pityriasis) versicolor is a superficial fungal infection and one of the most commonly found pigmentary disorders of skin caused by the yeast Malassezia. Multiple topical as well as systemic therapies are available for treatment. Systemic therapies are used for extensive disease, frequent relapse or where topical agents have failed. The aim that translates the rationale of the study was to compare the efficacy, safety, tolerability and cost effectiveness of single dose 400mg versus 7 day 200 mg daily dose of itraconazole in the treatment of tinea versicolor. A clinical study was done to compare the efficacy of single dose (400 mg) of itraconazole and 7 day 200 mg daily dose of itraconazole in the treatment of extensive tinea versicolor. Total 60 patients (aged 18-50 years) were selected for the study during the period of June 2007 to May 2008 in the department of Dermatology of three different hospitals in Bangladesh. Cases having with extensive involvement, diagnosed clinically and confirmed by wood's lamp and KOH microscopy were taken. Patients were randomly allocated into equal groups. Group A was given single dose 400 mg itraconazole and Group B was given 7 day 200 mg daily itraconazole. Fifty three (88%) male and 7(12%) female were included in the study. The mean age of group A was 32.37+/-9 years and in group B 33.23+/-8 years. The mean duration of the disease in group A was 2.63+/-2 months and 2.76+/-2 months in group B. In group A clinical responders was found cure 22(73.33%) and improvement 5(16.33%) and in group B it was found cure 24(79.99%) and improvement 4(13.33%). The measure at the End point (EP1) equals to 90% response and in-group B it was found cure 24 (79.99%) and improvement 4(13.33%). (Here the End point EP2) equals to 93.33%. The EP clinical analysis however shows 91.66% response. Both single dose and 7 day daily dose of itraconazole can be effective in the treatment of tinea versicolor with extensive involvement but single dose appears

A Pilot Study on Single-dose Toxicity Testing of Scolopendrid Pharmacopuncture in Sprague-Dawley Rats

Directory of Open Access Journals (Sweden)

Ilhong Son

2014-06-01

Full Text Available Objectives:This study was performed to analyze single dose toxicity and the lethal dose of Scolopendrid Pharmacopuncture in rats. Methods:All experiments were conducted at the Korea Testing & Research Institute (KTR, an institution authorized to perform non-clinical studies, under the regulations of Good Laboratory Practice (GLP. Sprague-Dawley rats were chosen for the pilot study. Doses of Scolopendrid pharmacopuncture, 0.1, 0.5, and 1.0 mL, were administered to the experimental group, and 1.0 mL doses of normal saline solution were administered to the control group. This study was conducted under the approval of the Institutional Animal Ethic Committee. Results:No deaths or abnormalities occurred in any of the groups. No significant changes in the weight, hematological parameters or clinical chemistry were noted between the control group and the experimental group. To check for abnormalities in organs and tissues, we used microscopy to examine representative histological sections of each specified organ; the results showed no significant differences in any of the organs or tissues. Conclusion:The above findings suggest Scolopendrid Pharmacopuncture is a relatively safe to use for treatment. Further studies on the subject should be conducted to yield more concrete evidence.

Comparative Study of the CT Findings and Clinical Features in Pediatric and Adult Sialadenitis

International Nuclear Information System (INIS)

Han, Jong Kyu; Jo, Seong Shik; Kim, Sang Won; Kim, Young Tong; Shin, Hyeong Cheol; Kim, Il Young; Lee, Yong Man

2010-01-01

We wanted to compare the CT findings and clinical features of parotitis and submandibular sialadenitis in children and adults and to evaluate the statistical significance of these in different age groups and the usefulness of a CT scan. Ninety-seven adults and 36 pediatric patients with sialadenitis were included in this retrospective study. Regardless of the site of involvement, we evaluated the CT findings and clinical manifestations between the pediatric and adult groups, and between the pediatric and adult parotitis and submandibular sialadenitis groups. At last, all the patients were classified into seven age groups. Abscess formations were more prominent in the parotitis groups, and sialiths were more common in the submandibular sialadenitis group with the lowest incidence in the young children group (≤ 10 years). Cellulitis seen on a CT scan showed a higher incidence in the adult parotitis group, and this finding was closely connected with pain. A number of patients showed cervical lymphadenitis on a CT scan and this coincided with lymph node palpation. Tonsillitis associated sialadenitis was common in the pediatric group. The therapeutic durations were longer in the pediatric parotitis patient group and the adult submandibular sialadenitis group. CT scans were very helpful to evaluate for abscess, stone, lymphadenitis and estimating the associated clinical manifestations such as swelling, palpable lymph nodes, pain with operation and the therapeutic plan

Dose response of rat retinal microvessels to proton dose schedules used clinically: a pilot study

International Nuclear Information System (INIS)

Archambeau, John O.; Mao, Xiao W.; McMillan, Paul J.; Gouloumet, Vanessa L.; Oeinck, Steven C.; Grove, Roger; Yonemoto, Leslie T.; Slater, Jerry D.; Slater, James M.

2000-01-01

Purpose: This preclinical rat pilot study quantifies retinal microvessel, endothelial, and pericyte population changes produced by proton irradiation Methods and Materials: The left eyes of rats were irradiated with single doses of 8, 14, 20, and 28 Gy protons; right eyes, with two fractions. Animals were euthanized, and eyes were removed; elastase digests were prepared, and cell populations were counted in sample fields. Results were compared with unirradiated controls. Results: Progressive time- and dose-dependent endothelial cell loss occurred following all schedules. Cell loss was significantly different from control values (p 0 phase of the mitotic cycle. 28 Gy produced photoreceptor cell loss. Conclusion: The retinal digest is an elegant bioassay to quantify the microvessel population response. Single- and split-dose schedules appear to yield similar outcomes, in terms of endothelial cell density

Radiation dose of CT coronary angiography in clinical practice: Objective evaluation of strategies for dose optimization

International Nuclear Information System (INIS)

Yerramasu, Ajay; Venuraju, Shreenidhi; Atwal, Satvir; Goodman, Dennis; Lipkin, David; Lahiri, Avijit

2012-01-01

Background: CT coronary angiography (CTCA) is an evolving modality for the diagnosis of coronary artery disease. Radiation burden associated with CTCA has been a major concern in the wider application of this technique. It is important to reduce the radiation dose without compromising the image quality. Objectives: To estimate the radiation dose of CTCA in clinical practice and evaluate the effect of dose-saving algorithms on radiation dose and image quality. Methods: Effective radiation dose was measured from the dose-length product in 616 consecutive patients (mean age 58 ± 12 years; 70% males) who underwent clinically indicated CTCA at our institution over 1 year. Image quality was assessed subjectively using a 4-point scale and objectively by measuring the signal- and contrast-to-noise ratios in the coronary arteries. Multivariate linear regression analysis was used to identify factors independently associated with radiation dose. Results: Mean effective radiation dose of CTCA was 6.6 ± 3.3 mSv. Radiation dose was significantly reduced by dose saving algorithms such as 100 kV imaging (−47%; 95% CI, −44% to −50%), prospective gating (−35%; 95% CI, −29% to −40%) and ECG controlled tube current modulation (−23%; 95% CI, −9% to −34%). None of the dose saving algorithms were associated with a significant reduction in mean image quality or the frequency of diagnostic scans (P = non-significant for all comparisons). Conclusion: Careful application of radiation-dose saving algorithms in appropriately selected patients can reduce the radiation burden of CTCA significantly, without compromising the image quality.

Transfusional hemosiderosis; correlation of MR findings with clinical findings

Energy Technology Data Exchange (ETDEWEB)

Park, Mi Ok; Kim, Ju Heon; Jeon, Woo Jin; Lee, Sung Moon; Kim, Hong; Suh, Soo Jhi [School of Medicine, Keimyung University, Taegu (Korea, Republic of)

1994-08-15

Parenchymal iron deposition occurs in hemochromatosis, while iron is deposited in reticuloendothelial cells after blood transfusions(Hemosiderosis). We studied correlation between MR finding and clinical findings(serum ferritin, TSI, LFT, disease duration) of hemosiderosis. 12 patients with chronic renal failure and one patient with aplastic anemia, who have received multiple transfusion, were performed MRI with a 2.0 Tesla unit. In all of 13 patients(17 cases), the liver revealed low signal intensity equal to background noise. In 4 of 17 cases whose serum ferritin level was below 1000 ng/ml, pancreas, gastric wall, adrenal gland were involved in 1 case. In 4 cases with serum ferritin level between 1000 and 1500, pancreas was involved in 2 cases, and other organ was involved in 1 case. In 9 cases with serum ferritin level above 1500ng/ml, pancreas was involved in 9 cases, and other origin 4 cases. The MR findings are well correlated with serum ferritin level whereas the TSI, LFT, disease duration are not correlated with involved organ on MR.

A Study on the Single-dose Oral Toxicity of Super Key in Sprague-Dawley Rats

Directory of Open Access Journals (Sweden)

Jinhee Kim

2015-09-01

Full Text Available Objectives: This study was performed to analyze the single-dose oral toxicity of the super key (processed sulfur. Methods: All experiments were conducted at Medvill, an institution authorized to perform non-clinical studies, under the Good Laboratory Practice (GLP regulations. In order to investigate the oral toxicity of super key We administered it orally to Sprague-Dawley (SD rats. The SD rats were divided into four groups of five male and five female animals per group: group 1 being the control group and groups 2, 3, and 4 being the experimental groups. Doses of super key 500 mg/kg, 1,000 mg/kg and 2,000 mg/kg were administered to the experimental groups, and a dose of normal saline solution, 10 mL/kg, was administered to the control group. We examined the survival rates, weights, clinical signs, gross findings and necropsy findings. This study was conducted under the approval of the Institutional Animal Ethics Committee. (Approval number: A01-14018. Results: No deaths or abnormalities occurred in any of the four groups. Although slight decreases in the weights of some female rats were noted, no significant changes in weights or differences in the gross findings between the control group and the experimental groups were observed. To check for abnormalities in organs, we used microscopy to examine representative histological sections of each specified organ; the results showed no significant differences in any of the organs. Conclusion: The results of this research showed that administration of 500 ─ 2,000 mg/kg of super key did not cause any changes in the weights or in the results of necropsy examinations. Neither did it result in any mortalities. The above findings suggest that treatment with super key is relatively safe. Further studies on this subject are needed to yield more concrete evidence.

Modic changes and their associations with clinical findings

DEFF Research Database (Denmark)

Kjær, Per; Korsholm, Lars; Bendix, Tom

2006-01-01

It is believed that disc degeneration (DD) is, in general, only mildly associated with low back pain (LBP). MRI-identified Modic changes (MC), probably a late stage of DD, are relatively strongly associated with LBP but it is not known if people with MC also have a specific clinical profile. The ...... around the disc in relation to LBP, history, and clinical findings. People with DD and no MC only vaguely differ from those without. People with LBP and MC may deserve to be diagnosed as having specific LBP.......It is believed that disc degeneration (DD) is, in general, only mildly associated with low back pain (LBP). MRI-identified Modic changes (MC), probably a late stage of DD, are relatively strongly associated with LBP but it is not known if people with MC also have a specific clinical profile....... The purpose of this study was to investigate if the clinical findings differ in people with Modic changes (MC) as compared to those with only degenerative disc findings or none at all. In a population-based sample of 412 40-year-old Danes, information was collected independently with MRI, questionnaires...

Relationship between esophageal clinical symptoms and manometry findings in patients with esophageal motility disorders: a cross-sectional study.

Science.gov (United States)

FakhreYaseri, Hashem; FakhreYaseri, Ali Mohammad; Baradaran Moghaddam, Ali; Soltani Arabshhi, Seyed Kamran

2015-01-01

Manometry is the gold-standard diagnostic test for motility disorders in the esophagus. The development of high-resolution manometry catheters and software displays of manometry recordings in color-coded pressure plots have changed the diagnostic assessment of esophageal disease. The diagnostic value of particular esophageal clinical symptoms among patients suspected of esophageal motor disorders (EMDs) is still unknown. The aim of this study was to explore the sensitivity, specificity, and predictive accuracy of presenting esophageal symptoms between abnormal and normal esophageal manometry findings. We conducted a cross-sectional study of 623 patients aged 11-80 years. Data were collected from clinical examinations as well as patient questionnaires. The sensitivity, specificity, and accuracy were calculated after high-resolution manometry plots were reviewed according to the most recent Chicago Criteria. The clinical symptoms were not sensitive enough to discriminate between EMDs. Nevertheless, dysphagia, noncardiac chest pain, hoarseness, vomiting, and weight loss had high specificity and high accuracy to distinguish EMDs from normal findings. Regurgitation and heartburn did not have good accuracy for the diagnosis of EMDs. Clinical symptoms are not reliable enough to discriminate between EMDs. Clinical symptoms can, however, discriminate between normal findings and EMDs, especially achalasia.

ICRU reference dose in an era of intensity-modulated radiation therapy clinical trials: Correlation with planning target volume mean dose and suitability for intensity-modulated radiation therapy dose prescription

International Nuclear Information System (INIS)

Yaparpalvi, Ravindra; Hong, Linda; Mah, Dennis; Shen Jin; Mutyala, Subhakar; Spierer, Marnee; Garg, Madhur; Guha, Chandan; Kalnicki, Shalom

2008-01-01

Background and Purpose: IMRT clinical trials lack dose prescription and specification standards similar to ICRU standards for two- and three-dimensional external beam planning. In this study, we analyzed dose distributions for patients whose treatment plans incorporated IMRT, and compared the dose determined at the ICRU reference point to the PTV doses determined from dose-volume histograms. Additionally, we evaluated if ICRU reference type single-point dose prescriptions are suitable for IMRT dose prescriptions. Materials and methods: For this study, IMRT plans of 117 patients treated at our institution were randomly selected and analyzed. The treatment plans were clinically applied to the following disease sites: abdominal (11), anal (10), brain (11), gynecological (15), head and neck (25), lung (15), male pelvis (10) and prostate (20). The ICRU reference point was located in each treatment plan following ICRU Report 50 guidelines. The reference point was placed in the central part of the PTV and at or near the isocenter. In each case, the dose was calculated and recorded to this point. For each patient - volume and dose (PTV, PTV mean, median and modal) information was extracted from the planned dose-volume histogram. Results: The ICRU reference dose vs PTV mean dose relationship in IMRT exhibited a weak positive association (Pearson correlation coefficient 0.63). In approximately 65% of the cases studied, dose at the ICRU reference point was greater than the corresponding PTV mean dose. The dose difference between ICRU reference and PTV mean doses was ≤2% in approximately 79% of the cases studied (average 1.21% (±1.55), range -4% to +4%). Paired t-test analyses showed that the ICRU reference doses and PTV median doses were statistically similar (p = 0.42). The magnitude of PTV did not influence the difference between ICRU reference and PTV mean doses. Conclusions: The general relationship between ICRU reference and PTV mean doses in IMRT is similar to that

Correlation of MRI findings with clinical findings of trochanteric pain syndrome

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Blankenbaker, Donna G.; Ullrick, Steven R.; Davis, Kirkland W.; De Smet, Arthur A. [University of Wisconsin School of Medicine and Public Health, Department of Radiology, Madison, WI (United States); Haaland, Ben; Fine, Jason P. [University of Wisconsin School of Medicine and Public Health, Departments of Biostatistics and Medical Informatics and Statistics, Madison, WI (United States)

2008-10-15

Greater trochanter pain syndrome due to tendinopathy or bursitis is a common cause of hip pain. The previously reported magnetic resonance (MR) findings of trochanteric tendinopathy and bursitis are peritrochanteric fluid and abductor tendon abnormality. We have often noted peritrochanteric high T2 signal in patients without trochanteric symptoms. The purpose of this study was to determine whether the MR findings of peritrochanteric fluid or hip abductor tendon pathology correlate with trochanteric pain. We retrospectively reviewed 131 consecutive MR examinations of the pelvis (256 hips) for T2 peritrochanteric signal and abductor tendon abnormalities without knowledge of the clinical symptoms. Any T2 peritrochanteric abnormality was characterized by size as tiny, small, medium, or large; by morphology as feathery, crescentic, or round; and by location as bursal or intratendinous. The clinical symptoms of hip pain and trochanteric pain were compared to the MR findings on coronal, sagittal, and axial T2 sequences using chi-square or Fisher's exact test with significance assigned as p<0.05. Clinical symptoms of trochanteric pain syndrome were present in only 16 of the 256 hips. All 16 hips with trochanteric pain and 212 (88%) of 240 without trochanteric pain had peritrochanteric abnormalities (p=0.15). Eighty-eight percent of hips with trochanteric symptoms had gluteus tendinopathy while 50% of those without symptoms had such findings (p=0.004). Other than tendinopathy, there was no statistically significant difference between hips with or without trochanteric symptoms and the presence of peritrochanteric T2 abnormality, its size or shape, and the presence of gluteus medius or minimus partial thickness tears. Patients with trochanteric pain syndrome always have peritrochanteric T2 abnormalities and are significantly more likely to have abductor tendinopathy on magnetic resonance imaging (MRI). However, although the absence of peritrochanteric T2 MR abnormalities

Correlation of MRI findings with clinical findings of trochanteric pain syndrome

International Nuclear Information System (INIS)

Blankenbaker, Donna G.; Ullrick, Steven R.; Davis, Kirkland W.; De Smet, Arthur A.; Haaland, Ben; Fine, Jason P.

2008-01-01

Greater trochanter pain syndrome due to tendinopathy or bursitis is a common cause of hip pain. The previously reported magnetic resonance (MR) findings of trochanteric tendinopathy and bursitis are peritrochanteric fluid and abductor tendon abnormality. We have often noted peritrochanteric high T2 signal in patients without trochanteric symptoms. The purpose of this study was to determine whether the MR findings of peritrochanteric fluid or hip abductor tendon pathology correlate with trochanteric pain. We retrospectively reviewed 131 consecutive MR examinations of the pelvis (256 hips) for T2 peritrochanteric signal and abductor tendon abnormalities without knowledge of the clinical symptoms. Any T2 peritrochanteric abnormality was characterized by size as tiny, small, medium, or large; by morphology as feathery, crescentic, or round; and by location as bursal or intratendinous. The clinical symptoms of hip pain and trochanteric pain were compared to the MR findings on coronal, sagittal, and axial T2 sequences using chi-square or Fisher's exact test with significance assigned as p<0.05. Clinical symptoms of trochanteric pain syndrome were present in only 16 of the 256 hips. All 16 hips with trochanteric pain and 212 (88%) of 240 without trochanteric pain had peritrochanteric abnormalities (p=0.15). Eighty-eight percent of hips with trochanteric symptoms had gluteus tendinopathy while 50% of those without symptoms had such findings (p=0.004). Other than tendinopathy, there was no statistically significant difference between hips with or without trochanteric symptoms and the presence of peritrochanteric T2 abnormality, its size or shape, and the presence of gluteus medius or minimus partial thickness tears. Patients with trochanteric pain syndrome always have peritrochanteric T2 abnormalities and are significantly more likely to have abductor tendinopathy on magnetic resonance imaging (MRI). However, although the absence of peritrochanteric T2 MR abnormalities

Phase I/II dose-finding study of nanoparticle albumin-bound paclitaxel (nab®-Paclitaxel) plus Cisplatin as Treatment for Metastatic Nasopharyngeal Carcinoma

International Nuclear Information System (INIS)

Huang, Yan; Liang, Wenhua; Yang, Yunpeng; Zhao, Liping; Zhao, Hongyun; Wu, Xuan; Zhao, Yuanyuan; Zhang, Yang; Zhang, Li

2016-01-01

This phase I/II study aimed to determine the maximum tolerated dose (MTD) of nanoparticle albumin-bound paclitaxel (nab ® -paclitaxel) plus cisplatin as treatment for metastatic nasopharyngeal carcinoma (NPC). Patients were enrolled into 1 of 3 dose cohorts, each with 21-day treatment cycles: 1) intravenous (IV) nab-paclitaxel 260 mg/m 2 on day 1; 2) IV nab-paclitaxel 140 mg/m 2 on days 1 and 8; 3) IV nab-paclitaxel 100 mg/m 2 on days 1, 8, and 15. All patients received IV cisplatin 75 mg/m 2 on day 1. Treatment continued for 4–6 cycles, or until progression or unacceptable toxicity. If more than one-third of the patients in a cohort experienced a dose-limiting toxicity (DLT), the dose used in the previous cohort would be designated the MTD. Secreted protein acidic and rich in cysteine (SPARC) expression was detected by immunohistochemistry staining. Sixty-nine patients were enrolled, of whom 64 and 67 were eligible for efficacy and safety analysis, respectively. Two DLTs occurred in cohort 1 (grade 4 febrile neutropenia, grade 3 myalgia), none occurred in cohort 2, and 2 occurred in cohort 3 (both grade 3 fatigue). The MTD was not reached. Partial responses were achieved by 42 patients, 15 had stable disease, and 7 had progressive disease, giving an overall response rate of 66 %. Median progression-free survival was 9 months (95 % CI, 6–12 months). Grade ≥ 3 adverse events were mainly hematologic. There was no significant difference between the 3 cohorts with respect to efficacy or safety. Biomarker analyses indicated that stromal, rather than tumoral, SPARC may predict the response to nab-paclitaxel in NPC. Our findings suggest that nab-paclitaxel plus cisplatin is a highly active regimen with moderate toxicity for the treatment of metastatic NPC, which warrants further investigation in a phase III study. ClinicalTrials.gov ID: NCT01735409. The trial was registered on November 20th, 2012. The online version of this article (doi:10.1186/s12885

Comparison of ESD and major organ absorbed doses of 5 year old standard guidekines and clinical exposure conditions

Energy Technology Data Exchange (ETDEWEB)

Kang, A Ram; Ahn, Sung Min [Dept. of Radiological Science, The Graduate School, Gachon University, Incheon (Korea, Republic of); Lee, In Ja [Dept. of Radiologic technology, Dongnam health University, Suwon (Korea, Republic of)

2017-09-15

Pediatrics are more sensibility to radiation than adults and because they are organs that are not completely grown, they have a life expectancy that can be adversely affected by exposure. Therefore, the management of exposure dose is more important than the case of adult. The purpose of this study was to determine the suitability of the 10 year old phantom for the 5 year old pediatric's recommendation and the incident surface dose, and to measure the organ absorbed dose. This study is compared the organ absorbed dose and the entrance surface dose in the clinical conditions at 5 and 10 years old pediatric. Clinical 5 year old condition was slightly higher than recommendation condition and 10 year old condition was very high. In addition, recommendation condition ESD was found to be 43% higher than the ESD of the 5 year old group and the ESD of the 10 year old group was 126% higher than that of the 5 year old group. The recommended ESD at 5 years old and the ESD according to clinical imaging conditions were 31.6%. There was no significant difference between the 5 year old recommended exposure conditions and the organ absorbed dose due to clinical exposure conditions, but there was a large difference between the Chest and Pelvic. However, it was found that there was a remarkable difference when comparing the organ absorbed dose by 10 year clinical exposure conditions. Therefore, more detailed standard exposure dose for the recommended dose of pediatric should be studied.

Comparison of ESD and major organ absorbed doses of 5 year old standard guidekines and clinical exposure conditions

International Nuclear Information System (INIS)

Kang, A Ram; Ahn, Sung Min; Lee, In Ja

2017-01-01

Pediatrics are more sensibility to radiation than adults and because they are organs that are not completely grown, they have a life expectancy that can be adversely affected by exposure. Therefore, the management of exposure dose is more important than the case of adult. The purpose of this study was to determine the suitability of the 10 year old phantom for the 5 year old pediatric's recommendation and the incident surface dose, and to measure the organ absorbed dose. This study is compared the organ absorbed dose and the entrance surface dose in the clinical conditions at 5 and 10 years old pediatric. Clinical 5 year old condition was slightly higher than recommendation condition and 10 year old condition was very high. In addition, recommendation condition ESD was found to be 43% higher than the ESD of the 5 year old group and the ESD of the 10 year old group was 126% higher than that of the 5 year old group. The recommended ESD at 5 years old and the ESD according to clinical imaging conditions were 31.6%. There was no significant difference between the 5 year old recommended exposure conditions and the organ absorbed dose due to clinical exposure conditions, but there was a large difference between the Chest and Pelvic. However, it was found that there was a remarkable difference when comparing the organ absorbed dose by 10 year clinical exposure conditions. Therefore, more detailed standard exposure dose for the recommended dose of pediatric should be studied

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

Science.gov (United States)

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

2018-05-01

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. 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. 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. 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. © 2018 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.

The BioFIND study: Characteristics of a clinically typical Parkinson's disease biomarker cohort

Science.gov (United States)

Goldman, Jennifer G.; Alcalay, Roy N.; Xie, Tao; Tuite, Paul; Henchcliffe, Claire; Hogarth, Penelope; Amara, Amy W.; Frank, Samuel; Rudolph, Alice; Casaceli, Cynthia; Andrews, Howard; Gwinn, Katrina; Sutherland, Margaret; Kopil, Catherine; Vincent, Lona; Frasier, Mark

2016-01-01

ABSTRACT Background Identifying PD‐specific biomarkers in biofluids will greatly aid in diagnosis, monitoring progression, and therapeutic interventions. PD biomarkers have been limited by poor discriminatory power, partly driven by heterogeneity of the disease, variability of collection protocols, and focus on de novo, unmedicated patients. Thus, a platform for biomarker discovery and validation in well‐characterized, clinically typical, moderate to advanced PD cohorts is critically needed. Methods BioFIND (Fox Investigation for New Discovery of Biomarkers in Parkinson's Disease) is a cross‐sectional, multicenter biomarker study that established a repository of clinical data, blood, DNA, RNA, CSF, saliva, and urine samples from 118 moderate to advanced PD and 88 healthy control subjects. Inclusion criteria were designed to maximize diagnostic specificity by selecting participants with clinically typical PD symptoms, and clinical data and biospecimen collection utilized standardized procedures to minimize variability across sites. Results We present the study methodology and data on the cohort's clinical characteristics. Motor scores and biospecimen samples including plasma are available for practically defined off and on states and thus enable testing the effects of PD medications on biomarkers. Other biospecimens are available from off state PD assessments and from controls. Conclusion Our cohort provides a valuable resource for biomarker discovery and validation in PD. Clinical data and biospecimens, available through The Michael J. Fox Foundation for Parkinson's Research and the National Institute of Neurological Disorders and Stroke, can serve as a platform for discovering biomarkers in clinically typical PD and comparisons across PD's broad and heterogeneous spectrum. © 2016 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society PMID:27113479

Prophylactic Oral Dextrose Gel for Newborn Babies at Risk of Neonatal Hypoglycaemia: A Randomised Controlled Dose-Finding Trial (the Pre-hPOD Study).

Science.gov (United States)

Hegarty, Joanne Elizabeth; Harding, Jane Elizabeth; Gamble, Gregory David; Crowther, Caroline Anne; Edlin, Richard; Alsweiler, Jane Marie

2016-10-01

limitation of this study was that most of the babies in the trial were infants of mothers with diabetes (73%), which may reduce the applicability of the results to babies from other risk groups. The incidence of neonatal hypoglycaemia can be reduced with a single dose of buccal 40% dextrose gel 200 mg/kg. A large randomised trial (Hypoglycaemia Prevention with Oral Dextrose [hPOD]) is under way to determine the effects on NICU admission and later outcomes. Australian New Zealand Clinical Trials Registry ACTRN12613000322730.

Relationship between MRI and clinical findings in the acromioclavicular joint

International Nuclear Information System (INIS)

Jordan, L.K.; Griffiths, H.L.; Kenter, K.

2002-01-01

Objective: To determine the relationship between the magnetic resonance (MR) appearance of the acromioclavicular (AC) joint and the physical findings. Design: A total of 116 consecutive patients underwent routine MR imaging (MRI) of the shoulder over an 18-month period. All MR studies were interpreted by a blinded, experienced musculoskeletal radiologist. Eleven variables were studied: the presence of osteophytes; fluid in the joint; fluid outside the joint; high signal in the clavicle or in the acromion; fluid in the subacromial bursa; irregularity of the joint margins; bulging of the capsule; widening of the joint; the age of the patient; and the presence of a rotator cuff tear. The clinical information was supplied by an experienced shoulder surgeon blinded to the MRI findings. A control group of 23 normal volunteers was also studied. Results: The only statistically significant correlation (P=0.0249) was between high signal in the distal clavicle and degenerative changes found clinically. A weaker relationship existed between fluid in the joint and the clinical examination and between increasing degenerative changes and advancing age. Otherwise, no material relationship was found between any of the other MR abnormalities and the clinical picture. Conclusion: There appears to be no real correlation between the MR appearances and the clinical findings in the AC joint. (orig.)

Relationship between MRI and clinical findings in the acromioclavicular joint

Energy Technology Data Exchange (ETDEWEB)

Jordan, L.K.; Griffiths, H.L. [Department of Radiology, University of Missouri Health Care (United States); Kenter, K. [Department of Orthopedics, University of Missouri Health Care (United States)

2002-09-01

Objective: To determine the relationship between the magnetic resonance (MR) appearance of the acromioclavicular (AC) joint and the physical findings. Design: A total of 116 consecutive patients underwent routine MR imaging (MRI) of the shoulder over an 18-month period. All MR studies were interpreted by a blinded, experienced musculoskeletal radiologist. Eleven variables were studied: the presence of osteophytes; fluid in the joint; fluid outside the joint; high signal in the clavicle or in the acromion; fluid in the subacromial bursa; irregularity of the joint margins; bulging of the capsule; widening of the joint; the age of the patient; and the presence of a rotator cuff tear. The clinical information was supplied by an experienced shoulder surgeon blinded to the MRI findings. A control group of 23 normal volunteers was also studied. Results: The only statistically significant correlation (P=0.0249) was between high signal in the distal clavicle and degenerative changes found clinically. A weaker relationship existed between fluid in the joint and the clinical examination and between increasing degenerative changes and advancing age. Otherwise, no material relationship was found between any of the other MR abnormalities and the clinical picture. Conclusion: There appears to be no real correlation between the MR appearances and the clinical findings in the AC joint. (orig.)

A study of low-density areas, clinical findings, and angiographic findings in patients with cerebral infarction

International Nuclear Information System (INIS)

Saiki, Iwao; Sakai, Yoshiaki; Oikawa, Tadato; Koide, Kohji; Kanaya, Haruyuki.

1978-01-01

55 out of 62 patients with cerebral infarction were investigated in terms of CT scan findings, angiographic findings, and clinical symptoms. The results obtained were as follows: 1) The low-density areas of the CT scan findings were classified into the following four types: large hemispheric or lobular --Type I; wedge-shaped --Type II; small --Type III; and lacunar low-density area. --Type IV. 2) Almost all patients with angiographically occlusive findings showed low-density areas of Type I; however, one patient with ICA occlusion revealed only a lacunar low-density area. 3) The patients with lacunar low-density areas showed an angiographically delayed filling of the angular artery and posterior parietal artery of the middle cerebral artery. 4) The relationship between the types of low-density areas and the clinical conscious disorders was not clear. On the other hand, the patients with Type I low-density areas almost all had motor disturbances, while patients with other types of low-density areas showed only 60 - 70% motor disturbances. 5) In patients with speech disorders, total aphasia cases were found in patients with large hemispheric low-density areas on the left side. Although, motor aphasia cases were seen in patients with various low-density areas on the left inferior frontal and precentral gyri, dysarthria cases were found in the patients with several low-density areas on both sides. 6) The localization of lacunar low-density areas seemed to be near the caudate nucleus on the right side and in the putaminal regions on the left side. The mean and the standard deviation of CT numbers in the lacunar low-density areas showed higher values on the right side than on the left side. (author)

Infliximab Dose Reduction Sustains the Clinical Treatment Effect in Active HLAB27 Positive Ankylosing Spondylitis: A Two-Year Pilot Study

Directory of Open Access Journals (Sweden)

Boel Mörck

2013-01-01

Full Text Available The rationale of the study was to evaluate the efficacy of infliximab (IFX treatment in patients with ankylosing spondylitis (AS and to determine whether IFX dose reduction and interval extension sustains the treatment effect. Nineteen patients were included and treated with IFX 5 mg/kg every 6 weeks for 56 weeks. All patients concomitantly received MTX with median dose 7.5 mg/weekly. During the second year, the IFX dose was reduced to 3 mg/kg every 8 weeks. Eighteen patients completed the 1-year and 15 patients the 2-year trial. The ≥50% improvement at week 16 from baseline of BASDAI was achieved in 16/19 (84% patients. Significant reductions in BASDAI, BASFI, and BASMI scores, decrease in ESR and CRP, and improvement in SF-36 were observed at weeks 16 and 56. The MRI-defined inflammatory changes in the sacroiliac joints disappeared in 10/15 patients (67% already at 16 weeks. IFX treatment effect was sustained throughout the second year after IFX dose reduction and interval extension. We conclude that IFX treatment is effective in well-established active AS and a dose reduction sustains the treatment effect. These observations are of clinical importance and open the opportunity to reduce the drug costs. This trial is registered with ClinicalTrials.gov NCT01850121.

Clinical findings in 16 patients with tomographic diagnosis of schizencephaly

Energy Technology Data Exchange (ETDEWEB)

Rodrigues, Maria do Carmo de Souza [Universidade Federal do Espirito Santo, Vitoria, ES (Brazil). Hospital Universitario Cassiano Antonio Moraes]. E-mail: rodriguesmcs@yahoo.com.br; Monteiro, Alexandra Maria Vieira [Universidade do Estado do Rio de Janeiro, RJ (Brazil). Faculdade de Ciencias Medicas; Llerena Junior, Juan Clinton [Fundacao Oswaldo Cruz, Rio de Janeiro, RJ (Brazil). Instituto Fernandes Figueira. Centro de Genetica Medica; Fernandes, Alexandre Ribeiro [Universidade Gama Filho, Rio de Janeiro, RJ (Brazil). Dept. de Pediatria

2006-09-15

Objective: to establish a correlation between clinical features in a group of children with tomographic diagnosis of schizencephaly and clefts extent and localization. Materials and methods: retrospective study of dossiers from the archives of Neurology and Medical Genetics Services at Instituto Fernandes Figueira/FIOCRUZ and Hospital Municipal Jesus, Rio de Janeiro, RJ, Brazil, in the period between 2000 and 2003. The study included 16 patients, nine female and seven male, with tomographic diagnosis of schizencephaly investigated for clinical findings, psychomotor development, motor/cognitive deficits and epilepsy. Results: predominance of bilateral clefts in 10:16 patients, open-lip schizencephaly type in 23:27 patients, and small lips in 11:27 patients. As regards anomalies associated with schizencephaly, pellucid septum absence was the most frequent one (10:16 patients). As regards clinical findings, 15 patients presented with developmental delay and motor deficit, six patients with cognitive deficit and ten with epilepsy. In three patients, we observed discordant clinical findings and cleft sizes, although the clefts were small, the clinical features severity was high because of other cerebral anomalies. Conclusion: the clinical features of schizencephaly are related to the size of the clefts, regardless laterality, presenting higher severity when associated with other cerebral anomalies. (author)

Clinical findings in 16 patients with tomographic diagnosis of schizencephaly

International Nuclear Information System (INIS)

Rodrigues, Maria do Carmo de Souza; Monteiro, Alexandra Maria Vieira; Llerena Junior, Juan Clinton; Fernandes, Alexandre Ribeiro

2006-01-01

Objective: to establish a correlation between clinical features in a group of children with tomographic diagnosis of schizencephaly and clefts extent and localization. Materials and methods: retrospective study of dossiers from the archives of Neurology and Medical Genetics Services at Instituto Fernandes Figueira/FIOCRUZ and Hospital Municipal Jesus, Rio de Janeiro, RJ, Brazil, in the period between 2000 and 2003. The study included 16 patients, nine female and seven male, with tomographic diagnosis of schizencephaly investigated for clinical findings, psychomotor development, motor/cognitive deficits and epilepsy. Results: predominance of bilateral clefts in 10:16 patients, open-lip schizencephaly type in 23:27 patients, and small lips in 11:27 patients. As regards anomalies associated with schizencephaly, pellucid septum absence was the most frequent one (10:16 patients). As regards clinical findings, 15 patients presented with developmental delay and motor deficit, six patients with cognitive deficit and ten with epilepsy. In three patients, we observed discordant clinical findings and cleft sizes, although the clefts were small, the clinical features severity was high because of other cerebral anomalies. Conclusion: the clinical features of schizencephaly are related to the size of the clefts, regardless laterality, presenting higher severity when associated with other cerebral anomalies. (author)

Indeterminate findings on oncologic PET/CT: What difference dose PET/MRI make?

Energy Technology Data Exchange (ETDEWEB)

Fraum, Tyler J.; Fowler, Kathryn J.; McConathy, Jonathan; Dehdashti, Farokh [Mallinckrodt Institute of Radiology, Washington University School of Medicine, Saint Louis (United States)

2016-12-15

Positron emission tomography/computed tomography (PET/CT) with 2-deoxy-2-[{sup 18}F]fluoro-D-glucose (FDG) has become the standard of care for the initial staging and subsequent treatment response assessment of many different malignancies. Despite this success, PET/CT is often supplemented by MRI to improve assessment of local tumor invasion and to facilitate detection of lesions in organs with high background FDG uptake. Consequently, PET/MRI has the potential to expand the clinical value of PET examinations by increasing reader certainty and reducing the need for subsequent imaging. This study evaluates the ability of FDG-PET/MRI to clarify findings initially deemed indeterminate on clinical FDG-PET/CT studies. A total of 190 oncology patients underwent whole-body PET/CT, immediately followed by PET/MRI utilizing the same FDG administration. Each PET/CT was interpreted by our institution's nuclear medicine service as a standard-of-care clinical examination. Review of these PET/CT reports identified 31 patients (16 %) with indeterminate findings. Two readers evaluated all 31 PET/CT studies, followed by the corresponding PET/MRI studies. A consensus was reached for each case, and changes in interpretation directly resulting from PET/MRI review were recorded. Interpretations were then correlated with follow-up imaging, pathology results, and other diagnostic studies. In 18 of 31 cases with indeterminate findings on PET/CT, PET/MRI resulted in a more definitive interpretation by facilitating the differentiation of infection/inflammation from malignancy (15/18), the accurate localization of FDG-avid lesions (2/18), and the characterization of incidental non-FDG-avid solid organ lesions (1/18). Explanations for improved reader certainty with PET/MRI included the superior soft tissue contrast of MRI and the ability to assess cellular density with diffusion-weighted imaging. The majority (12/18) of such cases had an appropriate standard of reference; in all 12 cases

Indeterminate findings on oncologic PET/CT: What difference dose PET/MRI make?

International Nuclear Information System (INIS)

Fraum, Tyler J.; Fowler, Kathryn J.; McConathy, Jonathan; Dehdashti, Farokh

2016-01-01

Positron emission tomography/computed tomography (PET/CT) with 2-deoxy-2-["1"8F]fluoro-D-glucose (FDG) has become the standard of care for the initial staging and subsequent treatment response assessment of many different malignancies. Despite this success, PET/CT is often supplemented by MRI to improve assessment of local tumor invasion and to facilitate detection of lesions in organs with high background FDG uptake. Consequently, PET/MRI has the potential to expand the clinical value of PET examinations by increasing reader certainty and reducing the need for subsequent imaging. This study evaluates the ability of FDG-PET/MRI to clarify findings initially deemed indeterminate on clinical FDG-PET/CT studies. A total of 190 oncology patients underwent whole-body PET/CT, immediately followed by PET/MRI utilizing the same FDG administration. Each PET/CT was interpreted by our institution's nuclear medicine service as a standard-of-care clinical examination. Review of these PET/CT reports identified 31 patients (16 %) with indeterminate findings. Two readers evaluated all 31 PET/CT studies, followed by the corresponding PET/MRI studies. A consensus was reached for each case, and changes in interpretation directly resulting from PET/MRI review were recorded. Interpretations were then correlated with follow-up imaging, pathology results, and other diagnostic studies. In 18 of 31 cases with indeterminate findings on PET/CT, PET/MRI resulted in a more definitive interpretation by facilitating the differentiation of infection/inflammation from malignancy (15/18), the accurate localization of FDG-avid lesions (2/18), and the characterization of incidental non-FDG-avid solid organ lesions (1/18). Explanations for improved reader certainty with PET/MRI included the superior soft tissue contrast of MRI and the ability to assess cellular density with diffusion-weighted imaging. The majority (12/18) of such cases had an appropriate standard of reference; in all 12 cases, the

Clinical application of a OneDose MOSFET for skin dose measurements during internal mammary chain irradiation with high dose rate brachytherapy in carcinoma of the breast.

Science.gov (United States)

Kinhikar, Rajesh A; Sharma, Pramod K; Tambe, Chandrashekhar M; Mahantshetty, Umesh M; Sarin, Rajiv; Deshpande, Deepak D; Shrivastava, Shyam K

2006-07-21

In our earlier study, we experimentally evaluated the characteristics of a newly designed metal oxide semiconductor field effect transistor (MOSFET) OneDose in-vivo dosimetry system for Ir-192 (380 keV) energy and the results were compared with thermoluminescent dosimeters (TLDs). We have now extended the same study to the clinical application of this MOSFET as an in-vivo dosimetry system. The MOSFET was used during high dose rate brachytherapy (HDRBT) of internal mammary chain (IMC) irradiation for a carcinoma of the breast. The aim of this study was to measure the skin dose during IMC irradiation with a MOSFET and a TLD and compare it with the calculated dose with a treatment planning system (TPS). The skin dose was measured for ten patients. All the patients' treatment was planned on a PLATO treatment planning system. TLD measurements were performed to compare the accuracy of the measured results from the MOSFET. The mean doses measured with the MOSFET and the TLD were identical (0.5392 Gy, 15.85% of the prescribed dose). The mean dose was overestimated by the TPS and was 0.5923 Gy (17.42% of the prescribed dose). The TPS overestimated the skin dose by 9% as verified by the MOSFET and TLD. The MOSFET provides adequate in-vivo dosimetry for HDRBT. Immediate readout after irradiation, small size, permanent storage of dose and ease of use make the MOSFET a viable alternative for TLDs.

Canine dilated cardiomyopathy: a retrospective study of signalment, presentation and clinical findings in 369 cases.

Science.gov (United States)

Martin, M W S; Stafford Johnson, M J; Celona, B

2009-01-01

To review the clinical and diagnostic findings and survival of dilated cardiomyopathy from a large population of dogs in England. A retrospective study of the case records of dogs with dilated cardiomyopathy collected between January 1993 and May 2006. There were 369 dogs with dilated cardiomyopathy of which all were pure-bred dogs except for four. The most commonly affected breeds were dobermanns and boxers. Over 95 per cent of dogs weighed more than 15 kg and 73 per cent were male. The median duration of signs before referral was three weeks with 65 per cent presenting in stage 3 heart failure. The most common signs were breathlessness (67 per cent) and coughing (64 per cent). The majority of dogs (89 per cent) had an arrhythmia at presentation and 74 per cent of dogs had radiographic signs of pulmonary oedema or pleural effusion. The median survival time was 19 weeks. Dilated cardiomyopathy occurs primarily in medium to large breed pure-bred dogs, and males are more frequently affected than females. The duration of clinical signs before referral is often short and the survival times are poor. Greater awareness of affected breeds, clinical signs and diagnostic findings may help in early recognition of this disease which often has a short clinical phase.

SPECIAL CONSIDERATIONS REGARDING WARFARIN DOSE TITRATION IN PATIENTS WITH ATRIAL FIBRILLATION DEPENDING ON CLINICAL FACTORS

Directory of Open Access Journals (Sweden)

E. L. Artanova

2011-01-01

Full Text Available Aim. To study the relations of clinical characteristics and individual warfarin dose titration in patients with atrial fibrillation. Material and methods. Period of warfarin dose titration was analyzed in 68 patients with atrial fibrillation due to ischemic heart disease. Adjusted warfarin dose in milligram, duration of dose titration in days and maximal international normalized ratio (INR were taken into account. Sex, age, history of myocardial infarction and stroke, concomitant diseases, amiodarone therapy were considered among clinical characteristics. Results. Adjusted warfarin dose was significantly higher in obesity , and it was lower in case of experienced myocardial infarction. The INR highest levels and maximal amplitudes of its fluctuations were observed in patients with thyroid gland nodes and smokers. Period of warfarin dose titration was longer in patients treated with amiodarone. Conclusion. Warfarin dose titration in patients with atrial fibrillation depends on the presence of myocardial infarction, obesity , thyroid nodular changes, smoking and amiodarone treatment.

Correlation of clinical outcome to the estimated radiation dose from Boron Neutron Capture Therapy (BNCT)

Energy Technology Data Exchange (ETDEWEB)

Chadha, M. [Beth Israel Medical Center, NY (United States). Dept. of Radiation Oncology; Coderre, J.A.; Chanana, A.D. [Brookhaven National Lab., Upton, NY (United States)] [and others

1996-12-31

A phase I/II trial delivering a single fraction of BNCT using p-Boronophenylalanine-Fructose and epithermal neutrons at the the Brookhaven Medical Research Reactor was initiated in September 1994. The primary endpiont of the study was to evaluate the feasibility and safety of a given BNCT dose. The clinical outcome of the disease was a secondary endpoint of the study. The objective of this paper is to evaluate the correlation of the clinical outcome of patients to the estimated radiation dose from BNCT.

Correlation of clinical outcome to the estimated radiation dose from Boron Neutron Capture Therapy (BNCT)

International Nuclear Information System (INIS)

Chadha, M.

1996-01-01

A phase I/II trial delivering a single fraction of BNCT using p-Boronophenylalanine-Fructose and epithermal neutrons at the the Brookhaven Medical Research Reactor was initiated in September 1994. The primary endpiont of the study was to evaluate the feasibility and safety of a given BNCT dose. The clinical outcome of the disease was a secondary endpoint of the study. The objective of this paper is to evaluate the correlation of the clinical outcome of patients to the estimated radiation dose from BNCT

SPECIAL CONSIDERATIONS REGARDING WARFARIN DOSE TITRATION IN PATIENTS WITH ATRIAL FIBRILLATION DEPENDING ON CLINICAL FACTORS

OpenAIRE

E. L. Artanova; E. V. Saleeva; I. M. Sokolov; Y. G. Shvarts

2011-01-01

Aim. To study the relations of clinical characteristics and individual warfarin dose titration in patients with atrial fibrillation. Material and methods. Period of warfarin dose titration was analyzed in 68 patients with atrial fibrillation due to ischemic heart disease. Adjusted warfarin dose in milligram, duration of dose titration in days and maximal international normalized ratio (INR) were taken into account. Sex, age, history of myocardial infarction and stroke, concomitant diseases, a...

A method to adjust radiation dose-response relationships for clinical risk factors

DEFF Research Database (Denmark)

Appelt, Ane Lindegaard; Vogelius, Ivan R

2012-01-01

Several clinical risk factors for radiation induced toxicity have been identified in the literature. Here, we present a method to quantify the effect of clinical risk factors on radiation dose-response curves and apply the method to adjust the dose-response for radiation pneumonitis for patients...

Prevalence and clinical significance of extravascular incidental findings in patients undergoing CT cervico-cerebral angiography

International Nuclear Information System (INIS)

Crockett, Matthew Thomas; Murphy, Blathnaid; Smith, Jennifer; Kavanagh, Eoin Carl

2015-01-01

Highlights: • CT cervico-cerebral angiography (CTCCA) is a commonly performed study for assessment of vascular pathologies of head and neck. • This study assessed the prevalence, clinical significance and management of extravascular incidental findings detected on CTCCA. • This study demonstrated the presence of clinically significant incidental findings in 14% of patients undergoing CTCCA with 8% of these findings deemed to be highly significant. 19% of patients with highly clinically significant findings did not receive appropriate follow up. • A standardised method of reporting incidental findings, such as that used in this paper is suggested to aid radiologists and referring physicians in recording and communicating these findings. - Abstract: Introduction: CT cervico-cerebral angiography (CTCCA) is now the first line diagnostic imaging modality for the majority of vascular pathologies of the head and neck with diagnostic value comparable to or better than traditional angiographic techniques. The aim of this study was to assess the prevalence, clinical significance and management of extravascular incidental findings detected on CTCCA. Materials and methods: A retrospective review of the CTCCA reports of 302 consecutive patients from 2009 to 2013 was undertaken. Extravascular incidental findings were classified, according to an adaptation of the CT colonography data and reporting system (CRADS), as EV1–EV4. EV1 = no incidental findings, EV2 = clinically insignificant incidental finding, EV3 = incidental finding of intermediate clinical significance, EV4 = highly clinically significant finding. Follow up of the electronic medical records of patients with EV3 or EV4 findings was undertaken to determine subsequent management. Results: Potentially clinically significant findings were demonstrated in 14.2% of patients with 8.6% of patients having a highly clinically significant finding. 4 incidental findings were confirmed to be malignant lesions and 5

CT findings of pancreatic carcinoma. Evaluation with the combined method of early enhancement CT and high dose enhancement CT

International Nuclear Information System (INIS)

Itoh, Shigeki; Endo, Tokiko; Isomura, Takayuki; Ishigaki, Takeo; Ikeda, Mitsuru; Senda, Kouhei.

1995-01-01

Computed tomographic (CT) findings of pancreatic ductal adenocarcinoma were studied with the combined method of early enhancement CT and high dose enhancement CT in 72 carcinomas. Common Findings were change in pancreatic contour, abnormal attenuation in a tumor and dilatation of the main pancreatic duct. The incidence of abnormal attenuation and dilatation of the main pancreatic duct and bile duct was constant regardless of tumor size. The finding of hypoattenuation at early enhancement CT was most useful for demonstrating a carcinoma. However, this finding was negative in ten cases, five of which showed inhomogenous hyperattenuation at high dose enhancement CT. The detection of change in pancreatic contour and dilatation of the main pancreatic duct was most frequent at high dose enhancement CT. The finding of change in pancreatic contour and/or abnormal attenuation in a tumor could be detected in 47 cases at plain CT, 66 at early enhancement CT and 65 at high dose enhancement CT. Since the four cases in which neither finding was detected by any CT method showed dilatated main pancreatic duct, there was no case without abnormal CT findings. This combined CT method will be a reliable diagnostic technique in the imaging of pancreatic carcinoma. (author)

Spontaneously draining acute otitis media in children: an observational study of clinical findings, microbiology and clinical course.

Science.gov (United States)

Neumark, Thomas; Ekblom, Maria; Brudin, Lars; Groth, Anita; Eliasson, Ingvar; Mölstad, Sigvard; Petersson, Ann-Cathrine; Törngren, Annika

2011-12-01

To study the outcome of acute otitis media (AOM) with otorrhoea in children managed initially without antibiotics, in relation to bacterial and clinical findings, and to identify those who may benefit from antibiotics. Otherwise healthy, not otitis prone children aged 2-16 y, presenting with AOM with spontaneous otorrhoea, were recruited from primary care and followed at selected ear, nose and throat (ENT) clinics. Specimens for bacterial investigations were obtained; symptoms were registered on a daily basis. The main outcomes measured were the frequency of children treated with antibiotics due to persisting AOM within 9 days in relation to clinical and bacteriological findings, and new AOM within 3 months. Twelve of 71 children who completed the trial received antibiotics during the first 9 days due to lack of improvement. One received antibiotics after 16 days due to relapsing AOM and 6 received antibiotics after 30 days due to new AOM. At 2-4 days following inclusion, over 70% of children showed normalized eardrum status and markedly reduced secretion. Alloiococcus otitidis was found in 23 samples, Streptococcus pneumoniae in 12, Streptococcus pyogenes in 6, and Fusobacterium nucleatum in 5. Mycoplasma pneumoniae, Chlamydia pneumoniae, and Fusobacterium necrophorum were not detected. Antibiotics were prescribed more extensively to children with a pulsating eardrum and abundant purulent secretion. All children with S. pyogenes received antibiotics, whereas children with only A. otitidis did not. The results suggest that antibiotics are indicated in AOM with otorrhoea and the presence of abundant purulent secretion, a pulsating eardrum, or the presence of S. pyogenes. The presence of only A. otitidis was not associated with a more prolonged course or the need for antibiotics.

A study on gamma dose rate in Seoul (I)

International Nuclear Information System (INIS)

Kim, You Hyun; Kim, Chang Kyun; Choi, Jong Hak; Kim, Jeong Min

2001-01-01

This study was conducted to find out gamma dose rate in Seoul, from January to December in 2000, and the following results were achieved : The annual gamma dose rate in Seoul was 17.24 μR/hr as average. The annual gamma dose rate in subway of Seoul was 14.96 μR/hr as average. The highest annual gamma dose rate was Dong-daemon ku. Annual gamma dose rate in Seoul was higher autumn than winter

Clinical value of CARE dose 4D technique in decreasing CT scanning dose of adult chest

International Nuclear Information System (INIS)

Wu Aiqin; Zheng Wenlong; Xu Chongyong; Fang Bidong; Ge Wen

2011-01-01

Objective: To investigate the value of CARE Dose 4D technique in decreasing radiation dose and improving image quality of multi-slice spiral CT in adult chest scanning. Methods: 100 patients of chest CT scanning were equally divided into study group and control group randomly. CARE Dose 4D Technique was used in study group. Effective mAs value, volume CT dose index (CTDI vol ) and dose length product (DLP) were displayed automatically in machine while chest scanning; those values and actual mAs value of every image were recorded respectively. The image quality at apex of lung, lower edge of aorta arch, middle area of left atrium and base of lung on every image of 400 images was judged and classified as three level (excellent, good, poor) by two deputy chief physicians with double blind method, the image noise at corresponding parts was measured. Results: While setting 80 mAs for quality reference mAs, the effective mAs value in study group most decreased 44 mAs than control group with an average decrease of 9.60 (12.0%), CTDI vol with 4.75 mGy with an average decrease of 0.95 mCy (11.0%), DLP 99.50% in study group, with 98.0% in control group. But it was higher at apex of lung and base of lung, lower at middle area of left atrium, and similar at lower edge of aorta arch in study group than contrast group. The image noise were lower at apex of lung and base of lung in study group than control group (t =6.299 and 2.332, all P<0.05), higher at middle area of left atrium in study group than control group (t=3.078, P<0.05) and similar at lower edge of aorta arch in study group than control group (t=1.191, P>0.05). Conclusions: CARE Dose 4D technique provides a function regulated mAs real-time on line, it not only raises utilization rate of radiation and decreases radiation dose, but also promises and increases image quality in chest CT scanning, and has some clinical significance. (authors)

Low-dose single acquisition rest 99mTc/stress 201Tl myocardial perfusion SPECT protocol: phantom studies and clinical validation

International Nuclear Information System (INIS)

Dey, Thomas; Backus, Barbra E.; Romijn, R.Leo; Wieczorek, Herfried; Verzijlbergen, J.F.

2014-01-01

We developed and tested a single acquisition rest 99m Tc-sestamibi/stress 201 Tl dual isotope protocol (SDI) with the intention of improving the clinical workflow and patient comfort of myocardial perfusion single photon emission computed tomography (SPECT). The technical feasibility of SDI was evaluated by a series of anthropomorphic phantom studies on a standard SPECT camera. The attenuation map was created by a moving transmission line source. Iterative reconstruction including attenuation correction, resolution recovery and Monte Carlo simulation of scatter was used for simultaneous reconstruction of dual tracer distribution. For clinical evaluation, patient studies were compared to stress 99m Tc and rest 99m Tc reference images acquired in a 2-day protocol. Clinical follow-up examinations like coronary angiography (CAG) and fractional flow reserve (FFR) were included in the assessment if available. Phantom studies demonstrated the technical feasibility of SDI. Artificial lesions inserted in the phantom mimicking ischaemia could be clearly identified. In 51/53 patients, the image quality was adequate for clinical evaluation. For the remaining two obese patients with body mass index > 32 the injected 201 Tl dose of 74 MBq was insufficient for clinical assessment. In answer to this the 201 Tl dose was adapted for obese patients in the rest of the study. In 31 patients, SDI and 99m Tc reference images resulted in equivalent clinical assessment. Significant differences were found in 20 patients. In 18 of these 20 patients additional examinations were available. In 15 patients the diagnosis based on the SDI images was confirmed by the results of CAG or FFR. In these patients the SDI images were more accurate than the 99m Tc reference study. In three patients minor ischaemic lesions were detected by SDI but were not confirmed by CAG. In one of these cases this was probably caused by pronounced apical thinning. For two patients no relevant clinical follow

Clinical findings just after return to play predict hamstring re-injury, but baseline MRI findings do not

NARCIS (Netherlands)

R.J. de Vos (Robert-Jan); G. Reurink (Gustaaf); G.J. Goudswaard (Gert Jan); M.H. Moen (Maaike); A. Weir (Adam); J.L. Tol (Johannes)

2014-01-01

markdownabstract__Abstract__ Background Acute hamstring re-injuries are common and hard to predict. The aim of this study was to investigate the association between clinical and imaging findings and the occurrence of hamstring re-injuries. Methods We obtained baseline data (clinical and MRI

Clinical Utility and Safety of a Model-Based Patient-Tailored Dose of Vancomycin in Neonates.

Science.gov (United States)

Leroux, Stéphanie; Jacqz-Aigrain, Evelyne; Biran, Valérie; Lopez, Emmanuel; Madeleneau, Doriane; Wallon, Camille; Zana-Taïeb, Elodie; Virlouvet, Anne-Laure; Rioualen, Stéphane; Zhao, Wei

2016-04-01

Pharmacokinetic modeling has often been applied to evaluate vancomycin pharmacokinetics in neonates. However, clinical application of the model-based personalized vancomycin therapy is still limited. The objective of the present study was to evaluate the clinical utility and safety of a model-based patient-tailored dose of vancomycin in neonates. A model-based vancomycin dosing calculator, developed from a population pharmacokinetic study, has been integrated into the routine clinical care in 3 neonatal intensive care units (Robert Debré, Cochin Port Royal, and Clocheville hospitals) between 2012 and 2014. The target attainment rate, defined as the percentage of patients with a first therapeutic drug monitoring serum vancomycin concentration achieving the target window of 15 to 25 mg/liter, was selected as an endpoint for evaluating the clinical utility. The safety evaluation was focused on nephrotoxicity. The clinical application of the model-based patient-tailored dose of vancomycin has been demonstrated in 190 neonates. The mean (standard deviation) gestational and postnatal ages of the study population were 31.1 (4.9) weeks and 16.7 (21.7) days, respectively. The target attainment rate increased from 41% to 72% without any case of vancomycin-related nephrotoxicity. This proof-of-concept study provides evidence for integrating model-based antimicrobial therapy in neonatal routine care. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Reliability of dose volume constraint inference from clinical data

DEFF Research Database (Denmark)

Lutz, C M; Møller, D S; Hoffmann, L

2017-01-01

Dose volume histogram points (DVHPs) frequently serve as dose constraints in radiotherapy treatment planning. An experiment was designed to investigate the reliability of DVHP inference from clinical data for multiple cohort sizes and complication incidence rates. The experimental background...... was radiation pneumonitis in non-small cell lung cancer and the DVHP inference method was based on logistic regression. From 102 NSCLC real-life dose distributions and a postulated DVHP model, an 'ideal' cohort was generated where the most predictive model was equal to the postulated model. A bootstrap...

Clinical application of a OneDose(TM) MOSFET for skin dose measurements during internal mammary chain irradiation with high dose rate brachytherapy in carcinoma of the breast

International Nuclear Information System (INIS)

Kinhikar, Rajesh A; Sharma, Pramod K; Tambe, Chandrashekhar M; Mahantshetty, Umesh M; Sarin, Rajiv; Deshpande, Deepak D; Shrivastava, Shyam K

2006-01-01

In our earlier study, we experimentally evaluated the characteristics of a newly designed metal oxide semiconductor field effect transistor (MOSFET) OneDose(TM) in-vivo dosimetry system for Ir-192 (380 keV) energy and the results were compared with thermoluminescent dosimeters (TLDs). We have now extended the same study to the clinical application of this MOSFET as an in-vivo dosimetry system. The MOSFET was used during high dose rate brachytherapy (HDRBT) of internal mammary chain (IMC) irradiation for a carcinoma of the breast. The aim of this study was to measure the skin dose during IMC irradiation with a MOSFET and a TLD and compare it with the calculated dose with a treatment planning system (TPS). The skin dose was measured for ten patients. All the patients' treatment was planned on a PLATO treatment planning system. TLD measurements were performed to compare the accuracy of the measured results from the MOSFET. The mean doses measured with the MOSFET and the TLD were identical (0.5392 Gy, 15.85% of the prescribed dose). The mean dose was overestimated by the TPS and was 0.5923 Gy (17.42% of the prescribed dose). The TPS overestimated the skin dose by 9% as verified by the MOSFET and TLD. The MOSFET provides adequate in-vivo dosimetry for HDRBT. Immediate readout after irradiation, small size, permanent storage of dose and ease of use make the MOSFET a viable alternative for TLDs. (note)

A double-blind, randomized, pilot dose-finding study of maca root (L. meyenii) for the management of SSRI-induced sexual dysfunction.

Science.gov (United States)

Dording, Christina M; Fisher, Lauren; Papakostas, George; Farabaugh, Amy; Sonawalla, Shamsah; Fava, Maurizio; Mischoulon, David

2008-01-01

We sought to determine whether maca, a Peruvian plant, is effective for selective-serotonin reuptake inhibitor (SSRI)-induced sexual dysfunction. We conducted a double-blind, randomized, parallel group dose-finding pilot study comparing a low-dose (1.5 g/day) to a high-dose (3.0 g/day) maca regimen in 20 remitted depressed outpatients (mean age 36+/-13 years; 17 women) with SSRI-induced sexual dysfunction. The Arizona Sexual Experience Scale (ASEX) and the Massachusetts General Hospital Sexual Function Questionnaire (MGH-SFQ) were used to measure sexual dysfunction. Ten subjects completed the study, and 16 subjects (9 on 3.0 g/day; 7 on 1.5 g/day) were eligible for intent-to-treat (ITT) analyses on the basis of having had at least one postbaseline visit. ITT subjects on 3.0 g/day maca had a significant improvement in ASEX (from 22.8+/-3.8 to 16.9+/-6.2; z=-2.20, P=0.028) and in MGH-SFQ scores (from 24.1+/-1.9 to 17.0+/-5.7; z=-2.39, P=0.017), but subjects on 1.5 g/day maca did not. Libido improved significantly (PMaca was well tolerated. Maca root may alleviate SSRI-induced sexual dysfunction, and there may be a dose-related effect. Maca may also have a beneficial effect on libido.

Analgesic and sedative effects of perioperative gabapentin in total knee arthroplasty A randomized, double-blind, placebo-controlled, dose-finding study

DEFF Research Database (Denmark)

Lunn, Troels Haxholdt; Husted, Henrik; Laursen, Mogens Berg

2015-01-01

(1:1:1) to either gabapentin 1300 mg/d (group A), gabapentin 900 mg/d (group B), or placebo (group C) daily from 2 hours preoperatively to postoperative day 6 in addition to a standardized multimodal analgesic regime. The primary outcome was pain upon ambulation 24 hours after surgery......Gabapentin has shown acute postoperative analgesic effects, but the optimal dose and procedure-specific benefits vs harm have not been clarified. In this randomized, double-blind, placebo-controlled dose-finding study, 300 opioid-naive patients scheduled for total knee arthroplasty were randomized......, and the secondary outcome was sedation 6 hours after surgery. Other outcomes were overall pain during well-defined mobilizations and at rest and sedation during the first 48 hours and from days 2-6, morphine use, anxiety, depression, sleep quality, and nausea, vomiting, dizziness, concentration difficulty, headache...

Dosimetry investigation of MOSFET for clinical IMRT dose verification.

Science.gov (United States)

Deshpande, Sudesh; Kumar, Rajesh; Ghadi, Yogesh; Neharu, R M; Kannan, V

2013-06-01

In IMRT, patient-specific dose verification is followed regularly at each centre. Simple and efficient dosimetry techniques play a very important role in routine clinical dosimetry QA. The MOSFET dosimeter offers several advantages over the conventional dosimeters such as its small detector size, immediate readout, immediate reuse, multiple point dose measurements. To use the MOSFET as routine clinical dosimetry system for pre-treatment dose verification in IMRT, a comprehensive set of experiments has been conducted, to investigate its linearity, reproducibility, dose rate effect and angular dependence for 6 MV x-ray beam. The MOSFETs shows a linear response with linearity coefficient of 0.992 for a dose range of 35 cGy to 427 cGy. The reproducibility of the MOSFET was measured by irradiating the MOSFET for ten consecutive irradiations in the dose range of 35 cGy to 427 cGy. The measured reproducibility of MOSFET was found to be within 4% up to 70 cGy and within 1.4% above 70 cGy. The dose rate effect on the MOSFET was investigated in the dose rate range 100 MU/min to 600 MU/min. The response of the MOSFET varies from -1.7% to 2.1%. The angular responses of the MOSFETs were measured at 10 degrees intervals from 90 to 270 degrees in an anticlockwise direction and normalized at gantry angle zero and it was found to be in the range of 0.98 ± 0.014 to 1.01 ± 0.014. The MOSFETs were calibrated in a phantom which was later used for IMRT verification. The measured calibration coefficients were found to be 1 mV/cGy and 2.995 mV/cGy in standard and high sensitivity mode respectively. The MOSFETs were used for pre-treatment dose verification in IMRT. Nine dosimeters were used for each patient to measure the dose in different plane. The average variation between calculated and measured dose at any location was within 3%. Dose verification using MOSFET and IMRT phantom was found to quick and efficient and well suited for a busy radiotherapy

Low-Dose (10-Gy) Total Skin Electron Beam Therapy for Cutaneous T-Cell Lymphoma: An Open Clinical Study and Pooled Data Analysis

Energy Technology Data Exchange (ETDEWEB)

Kamstrup, Maria R., E-mail: mkam0004@bbh.regionh.dk [Department of Dermatology, Bispebjerg Hospital, University of Copenhagen, Copenhagen (Denmark); Gniadecki, Robert [Department of Dermatology, Bispebjerg Hospital, University of Copenhagen, Copenhagen (Denmark); Iversen, Lars [Department of Dermatology, Aarhus University Hospital, Aarhus (Denmark); Skov, Lone [Department of Dermatology, Gentofte Hospital, University of Copenhagen, Copenhagen (Denmark); Petersen, Peter Meidahl [Department of Oncology and Hematology, Rigshospitalet, University of Copenhagen, Copenhagen (Denmark); Loft, Annika [Department of Clinical Physiology, Nuclear Medicine and PET, Rigshospitalet, University of Copenhagen, Copenhagen (Denmark); Specht, Lena [Department of Oncology and Hematology, Rigshospitalet, University of Copenhagen, Copenhagen (Denmark)

2015-05-01

Purpose: Cutaneous T-cell lymphomas (CTCLs) are dominated by mycosis fungoides (MF) and Sézary syndrome (SS), and durable disease control is a therapeutic challenge. Standard total skin electron beam therapy (TSEBT) is an effective skin-directed therapy, but the possibility of retreatments is limited to 2 to 3 courses in a lifetime due to skin toxicity. This study aimed to determine the clinical effect of low-dose TSEBT in patients with MF and SS. Methods and Materials: In an open clinical study, 21 patients with MF/SS stages IB to IV were treated with low-dose TSEBT over <2.5 weeks, receiving a total dose of 10 Gy in 10 fractions. Data from 10 of these patients were published previously but were included in the current pooled data analysis. Outcome measures were response rate, duration of response, and toxicity. Results: The overall response rate was 95% with a complete cutaneous response or a very good partial response rate (<1% skin involvement with patches or plaques) documented in 57% of the patients. Median duration of overall cutaneous response was 174 days (5.8 months; range: 60-675 days). TSEBT-related acute adverse events (grade 1 or 2) were observed in 60% of patients. Conclusions: Low-dose (10-Gy) TSEBT offers a high overall response rate and is relatively safe. With this approach, reirradiation at times of relapse or progression is likely to be less toxic than standard dose TSEBT. It remains to be established whether adjuvant and combination treatments can prolong the beneficial effects of low-dose TSEBT.

Clinical findings versus imaging studies in the diagnosis of infantile ...

African Journals Online (AJOL)

Background: Infantile hypertrophic pyloric stenosis is the most common surgical cause of vomiting in early infancy and can be diagnosed clinically or by imaging studies. Objectives: The aim of this study was to assess the accuracy of clinical examination compared with ultrasound and upper gastrointestinal contrast imaging ...

The potential use of ultra-low radiation dose images in digital mammography-a clinical proof-of-concept study in craniocaudal views

NARCIS (Netherlands)

Bluekens, A. M. J.; Veldkamp, W. J. H.; Schuur, K. H.; Karssemeijer, N.; Broeders, M. J. M.; den Heeten, G. J.

2015-01-01

Objective: To estimate the potential of low-dose images in digital mammography by analysing the effect of substantial dose reduction in craniocaudal (CC) views on clinical performance. Methods: At routine mammography, additional CC views were obtained with about 10% of the standard dose. Five

The potential use of ultra-low radiation dose images in digital mammography--a clinical proof-of-concept study in craniocaudal views

NARCIS (Netherlands)

Bluekens, A.M.; Veldkamp, W.J.H.; Schuur, K.H.; Karssemeijer, N.; Broeders, M.J.; Heeten, GJ. den

2015-01-01

OBJECTIVE: To estimate the potential of low-dose images in digital mammography by analysing the effect of substantial dose reduction in craniocaudal (CC) views on clinical performance. METHODS: At routine mammography, additional CC views were obtained with about 10% of the standard dose. Five

Cerebral amyloid angiopathy-related inflammation: imaging findings and clinical outcome

Energy Technology Data Exchange (ETDEWEB)

Martucci, Matia [Vall d' Hebron University Hospital, Neuroradiology Unit, Radiology Department (IDI), Barcelona (Spain); Catholic University of Sacred Heart, ' ' A. Gemelli' ' University Hospital, Department of Radiological Sciences, Rome (Italy); Sarria, Silvana; Coscojuela, Pilar; Vert, Carla; Siurana, Sahyly; Auger, Cristina; Rovira, Alex [Vall d' Hebron University Hospital, Neuroradiology Unit, Radiology Department (IDI), Barcelona (Spain); Toledo, Manuel [Vall d' Hebron University Hospital, Epilepsy Unit, Neurology Department, Barcelona (Spain)

2014-04-15

We aim to investigate the clinical onset, computed tomography (CT) and magnetic resonance (MR) imaging findings, and follow-up of patients with cerebral amyloid angiopathy (CAA)-related inflammation, an uncommon but clinically striking presentation of CAA. We retrospectively reviewed the clinical manifestations, CT/MR imaging findings, and outcome of ten consecutive patients with CAA-related inflammation. In each patient, a brain CT study was performed at hospital admission, and brain MR imaging was carried out 2 to 4 days later. Clinical and radiologic follow-up findings were evaluated in all patients. The most common clinical onset was rapidly progressive cognitive decline, followed by focal neurological signs. Brain CT/MR showed unenhanced expansive subcortical lesions, corresponding to areas of vasogenic edema, associated with chronic lobar, cortical, or cortical-subcortical micro/macrohemorrhages. Clinical symptoms recovered in a few weeks under treatment in eight patients and spontaneously in the remaining two. MRI follow-up at 2 to 12 months after treatment showed resolution of the lesions. Three patients experienced symptomatic disease recurrence, with new lesions on CT/MR. In the absence of histological data, early recognition of the clinical symptoms and typical radiologic features of CAA-related inflammation is essential to enable timely establishment of proper treatment. (orig.)

Cerebral amyloid angiopathy-related inflammation: imaging findings and clinical outcome

International Nuclear Information System (INIS)

Martucci, Matia; Sarria, Silvana; Coscojuela, Pilar; Vert, Carla; Siurana, Sahyly; Auger, Cristina; Rovira, Alex; Toledo, Manuel

2014-01-01

We aim to investigate the clinical onset, computed tomography (CT) and magnetic resonance (MR) imaging findings, and follow-up of patients with cerebral amyloid angiopathy (CAA)-related inflammation, an uncommon but clinically striking presentation of CAA. We retrospectively reviewed the clinical manifestations, CT/MR imaging findings, and outcome of ten consecutive patients with CAA-related inflammation. In each patient, a brain CT study was performed at hospital admission, and brain MR imaging was carried out 2 to 4 days later. Clinical and radiologic follow-up findings were evaluated in all patients. The most common clinical onset was rapidly progressive cognitive decline, followed by focal neurological signs. Brain CT/MR showed unenhanced expansive subcortical lesions, corresponding to areas of vasogenic edema, associated with chronic lobar, cortical, or cortical-subcortical micro/macrohemorrhages. Clinical symptoms recovered in a few weeks under treatment in eight patients and spontaneously in the remaining two. MRI follow-up at 2 to 12 months after treatment showed resolution of the lesions. Three patients experienced symptomatic disease recurrence, with new lesions on CT/MR. In the absence of histological data, early recognition of the clinical symptoms and typical radiologic features of CAA-related inflammation is essential to enable timely establishment of proper treatment. (orig.)

From AAA to Acuros XB-clinical implications of selecting either Acuros XB dose-to-water or dose-to-medium.

Science.gov (United States)

Zifodya, Jackson M; Challens, Cameron H C; Hsieh, Wen-Long

2016-06-01

When implementing Acuros XB (AXB) as a substitute for anisotropic analytic algorithm (AAA) in the Eclipse Treatment Planning System, one is faced with a dilemma of reporting either dose to medium, AXB-Dm or dose to water, AXB-Dw. To assist with decision making on selecting either AXB-Dm or AXB-Dw for dose reporting, a retrospective study of treated patients for head & neck (H&N), prostate, breast and lung is presented. Ten patients, previously treated using AAA plans, were selected for each site and re-planned with AXB-Dm and AXB-Dw. Re-planning was done with fixed monitor units (MU) as well as non-fixed MUs. Dose volume histograms (DVH) of targets and organs at risk (OAR), were analyzed in conjunction with ICRU-83 recommended dose reporting metrics. Additionally, comparisons of plan homogeneity indices (HI) and MUs were done to further highlight the differences between the algorithms. Results showed that, on average AAA overestimated dose to the target volume and OARs by less than 2.0 %. Comparisons between AXB-Dw and AXB-Dm, for all sites, also showed overall dose differences to be small (135 % of prescription dose) for target volumes with high density materials. Homogeneity indices showed that AAA planning and optimization templates would need to be adjusted only for the H&N and Lung sites. MU comparison showed insignificant differences between AXB-Dw relative to AAA and between AXB-Dw relative to AXB-Dm. However AXB-Dm MUs relative to AAA, showed an average difference of about 1.3 % signifying an underdosage by AAA. In conclusion, when dose is reported as AXB-Dw, the effect that high density structures in the PTV has on the dose distribution should be carefully considered. As the results show overall small dose differences between the algorithms, when transitioning from AAA to AXB, no significant change to existing prescription protocols is expected. As most of the clinical experience is dose-to-water based and calibration protocols and clinical trials are

Adaptive designs for dose-finding in non-cancer phase II trials: influence of early unexpected outcomes.

Science.gov (United States)

Resche-Rigon, Matthieu; Zohar, Sarah; Chevret, Sylvie

2008-01-01

In non-cancer phase II trials, dose-finding trials are usually carried out using fixed designs, in which several doses including a placebo are randomly distributed to patients. However, in certain vulnerable populations, such as neonates or infants, there is an heightened requirement for safety, precluding randomization. To estimate the minimum effective dose of a new drug from a non-cancer phase II trial, we propose the use of adaptive designs like the Continual Reassessment Method (CRM). This approach estimates the dose closest to some target response, and has been shown to be unbiased and efficient in cancer phase I trials. Based on a motivating example, we point out the individual influence of first outliers in this setting. A weighted version of the CRM is proposed as a theoretical benchmark to control for these outliers. Using simulations, we illustrate how this approach provides further insight into the behavior of the CRM. When dealing with low targets like a 10% failure rate, the CRM appears unable to rapidly overcome an early unexpected outcome. This behavior persisted despite changing the inference (Bayesian or likelihood), underlying dose-response model (though slightly improved using the power model), and the number of patients enrolled at each dose level. The choices for initial guesses of failure rates, the vague prior for the model parameter, and the log-log shape of weights can appear somewhat arbitrary. In phase II dose-finding studies in which failure targets are below 20%, the CRM appears quite sensitive to first unexpected outcomes. Using a power model for dose-response improves some behavior if the trial is started at the first dose level and includes at least three to five patients at the starting dose before applying the CRM allocation rule.

From AAA to Acuros XB-clinical implications of selecting either Acuros XB dose-to-water or dose-to-medium

International Nuclear Information System (INIS)

Zifoyda, Jackson M.; Challens, Cameron H.C.; Hsieh, Wen-Long

2016-01-01

When implementing Acuros XB (AXB) as a substitute for anisotropic analytic algorithm (AAA) in the Eclipse Treatment Planning System, one is faced with a dilemma of reporting either dose to medium, AXB-Dm or dose to water, AXB-Dw. To assist with decision making on selecting either AXB-Dm or AXB-Dw for dose reporting, a retrospective study of treated patients for head & neck (H&N), prostate, breast and lung is presented. Ten patients, previously treated using AAA plans, were selected for each site and re-planned with AXB-Dm and AXB-Dw. Re-planning was done with fixed monitor units (MU) as well as non-fixed MUs. Dose volume histograms (DVH) of targets and organs at risk (OAR), were analyzed in conjunction with ICRU-83 recommended dose reporting metrics. Additionally, comparisons of plan homogeneity indices (HI) and MUs were done to further highlight the differences between the algorithms. Results showed that, on average AAA overestimated dose to the target volume and OARs by less than 2.0 %. Comparisons between AXB-Dw and AXB-Dm, for all sites, also showed overall dose differences to be small (<1.5 %). However, in non-water biological media, dose differences between AXB-Dw and AXB-Dm, as large as 4.6 % were observed. AXB-Dw also tended to have unexpectedly high 3D maximum dose values (>135 % of prescription dose) for target volumes with high density materials. Homogeneity indices showed that AAA planning and optimization templates would need to be adjusted only for the H&N and Lung sites. MU comparison showed insignificant differences between AXB-Dw relative to AAA and between AXB-Dw relative to AXB-Dm. However AXB-Dm MUs relative to AAA, showed an average difference of about 1.3 % signifying an underdosage by AAA. In conclusion, when dose is reported as AXB-Dw, the effect that high density structures in the PTV has on the dose distribution should be carefully considered. As the results show overall small dose differences between the algorithms, when transitioning

Reformulation of a clinical-dose system for carbon-ion radiotherapy treatment planning at the National Institute of Radiological Sciences, Japan

Science.gov (United States)

Inaniwa, Taku; Kanematsu, Nobuyuki; Matsufuji, Naruhiro; Kanai, Tatsuaki; Shirai, Toshiyuki; Noda, Koji; Tsuji, Hiroshi; Kamada, Tadashi; Tsujii, Hirohiko

2015-04-01

At the National Institute of Radiological Sciences (NIRS), more than 8,000 patients have been treated for various tumors with carbon-ion (C-ion) radiotherapy in the past 20 years based on a radiobiologically defined clinical-dose system. Through clinical experience, including extensive dose escalation studies, optimum dose-fractionation protocols have been established for respective tumors, which may be considered as the standards in C-ion radiotherapy. Although the therapeutic appropriateness of the clinical-dose system has been widely demonstrated by clinical results, the system incorporates several oversimplifications such as dose-independent relative biological effectiveness (RBE), empirical nuclear fragmentation model, and use of dose-averaged linear energy transfer to represent the spectrum of particles. We took the opportunity to update the clinical-dose system at the time we started clinical treatment with pencil beam scanning, a new beam delivery method, in 2011. The requirements for the updated system were to correct the oversimplifications made in the original system, while harmonizing with the original system to maintain the established dose-fractionation protocols. In the updated system, the radiation quality of the therapeutic C-ion beam was derived with Monte Carlo simulations, and its biological effectiveness was predicted with a theoretical model. We selected the most used C-ion beam with αr = 0.764 Gy-1 and β = 0.0615 Gy-2 as reference radiation for RBE. The C-equivalent biological dose distribution is designed to allow the prescribed survival of tumor cells of the human salivary gland (HSG) in entire spread-out Bragg peak (SOBP) region, with consideration to the dose dependence of the RBE. This C-equivalent biological dose distribution is scaled to a clinical dose distribution to harmonize with our clinical experiences with C-ion radiotherapy. Treatment plans were made with the original and the updated clinical-dose systems, and both

Using Virtual Social Networks for Case Finding in Clinical Studies: An Experiment from Adolescence, Brain, Cognition, and Diabetes Study

OpenAIRE

Pourabbasi, Ata; Farzami, Jalal; Shirvani, Mahbubeh-Sadat Ebrahimnegad; Shams, Amir Hossein; Larijani, Bagher

2017-01-01

Background: One of the main usages of social networks in clinical studies is facilitating the process of sampling and case finding for scientists. The main focus of this study is on comparing two different methods of sampling through phone calls and using social network, for study purposes. Methods: One of the researchers started calling 214 families of children with diabetes during 90 days. After this period, phone calls stopped, and the team started communicating with families through teleg...

Study of single dose toxic test of Sweet Bee Venom in Beagle Dogs

Directory of Open Access Journals (Sweden)

Hye-Chul, Yoon

2010-12-01

Full Text Available Objectives : This study was performed to analyse single dose toxicity of Sweet Bee Venom(Sweet BV extracted from the bee venom in Beagle dogs. Methods : All experiments were conducted under the regulations of Good Laboratory Practice (GLP at Biotoxtech Company, a non-clinical study authorized institution. Male and female Beagle dogs of 5-6 months old were chosen for the pilot study of single dose toxicity of Sweet BV which was administered at the level of 9.0 ㎎/㎏ body weight which is 1300 times higher than the clinical application dosage as the high dosage, followed by 3.0 and 1.0 ㎎/㎏ as midium and low dosage, respectively. Equal amount of excipient(normal saline to the Sweet BV experiment groups was administered as the control group. Results : 1. No mortality was witnessed in all of the experiment groups. 2. Hyperemia and movement disorder were observed around the area of administration in all the experiment groups, and higher occurrence in the higher dosage treatment. 3. For weight measurement, Neither male nor female groups showed significant changes. 4. To verify abnormalities of organs and tissues, thigh muscle which treated with Sweet BV, brain, liver, lung, kidney, and spinal cords were removed and histologocal observation using H-E staining was conducted. In the histologocal observation of thigh muscle, cell infiltration, inflammation, degeneration, necrosis of muscle fiber, and fibrosis were found in both thigh tissue. And the changes depend on the dose of Sweet BV. But the other organs did not showed in any abnormality. 5. The maximum dose of Sweet BV in Beagle dogs were over 9 ㎎/㎏ in this study. Conclusions : The above findings of this study suggest that Sweet BV is a relatively safe treatment medium. Further studies on the toxicity of Sweet BV should be conducted to yield more concrete evidences.

Biological effective dose studies in carcinoma of uterine cervix

International Nuclear Information System (INIS)

Yadav, Poonam; Ramasubramanian, V.

2008-01-01

Cancer of cervix is the second most common cancer worldwide among women. Several treatments related protocols of radiotherapy have been followed over few decades in its treatment for evaluating the response. These physical doses varying on the basics of fractionation size, dose rate and total dose needed to be indicated as biological effective dose (BED) to rationalize these treatments. The curative potential of radiation therapy in the management of carcinoma of the cervix is greatly enhanced by the use of intracavitary brachytherapy. Successful brachytherapy requires the high radiation dose to be delivered to the tumor where as minimum radiation dose reach to surrounding normal tissue. Present study is aimed to evaluate biologically effective dose in patients receiving high dose-rate brachytherapy plus external beam radiotherapy based on tumor cell proliferation values in cancer of the cervix patients. The study includes 30 patients' data as a retrospective analysis. In addition determine extent of a dose-response relationship existing between the biological effective dose at Point A and the bladder and rectum and the clinical outcomes

The clinic and pathologic picture in the lethal dose irradiated ewes

International Nuclear Information System (INIS)

Halagan, J.; Stanikova, A.; Maracek, I.

2004-01-01

The history of clinical symptoms as well as pathologic histological and morphological changes after long/lasting gamma irradiation were estimated in seven clinical healthy ewes. The animals were irradiated continually seven days with totally 6.7 Gy per ewe. Clinically recognizable symptoms of the radiation sickness were observed commencing the 4 th after last dose of irradiation. Sharp increase of the body temperature, heart and respiratory frequency rate as well as apathy, anorexia, arrhythmia, dyspnoe, diarrhea, dehydration, polyuria were prevalent in clinical founding . All of the animals were death in course of seven days after last irradiated dose. The gastrointestinal radiation syndrome was typical evidence of gastrointestinal tract and the general hemorrhagic enhancing of the gamma irradiation damage effects was confirmed. (authors)

The efficacy and safety of S-flurbiprofen plaster in the treatment of knee osteoarthritis: a phase II, randomized, double-blind, placebo-controlled, dose-finding study

Directory of Open Access Journals (Sweden)

Yataba I

2017-04-01

Full Text Available Ikuko Yataba,1 Noboru Otsuka,1 Isao Matsushita,1 Hideo Matsumoto,2 Yuichi Hoshino3 1Taisho Pharmaceutical Co, Ltd, 2Institute for Integrated Sports Medicine, School of Medicine, Keio University, Tokyo, 3Department of Orthopedics Surgery, School of Medicine, Jichi Medical University, Tochigi, Japan Background: Nonsteroidal anti-inflammatory drug (NSAID patches are convenient for use and show much less gastrointestinal side effects than oral NSAIDs, whereas its percutaneous absorption is not sufficient for the expression of clinical efficacy at satisfactory level. S-flurbiprofen plaster (SFPP has shown dramatic improvement in percutaneous absorption results from animal and clinical studies. In this study, the efficacy and safety of SFPP were compared with placebo in patients with knee osteoarthritis (OA to determine its optimal dose. This was a multicenter, randomized, double-blind, parallel-group comparative study. Patients and methods: Enrolled 509 knee OA patients were treated with placebo or SFPP at 10, 20, or 40 mg applied on the affected site once daily for 2 weeks. The primary endpoint for efficacy was improvement in knee pain on rising from the chair assessed by visual analog scale (VAS. The other endpoints were clinical symptoms, pain on walking, and global assessment by both investigator and patient. Safety was evaluated by observing adverse events (AEs. Results: VAS change in knee pain from baseline to trial end was dose-dependent, least squares mean was 29.5, 31.5, 32.0, and 35.6 mm in placebo and SFPP 10, 20, and 40 mg, respectively. A significant difference was observed between placebo and SFPP 40 mg (P=0.001. In contrast, the effect of SFPP at a dose ≤20 mg was not significantly different from that of placebo. The proportion of the patients who achieved 50% pain relief was 72.4% in 40 mg and 51.2% in placebo (P<0.001. In all other endpoints, SFPP 40 mg showed significant improvement compared with placebo. The incidence of AEs was

Reduction of uterus dose in clinical thoracic computed tomography

International Nuclear Information System (INIS)

Danova, D.; Keil, B.; Kaestner, B.; Klose, K.J.; Heverhagen, J.T.; Wulff, J.; Fiebich, M.; Zink, K.

2010-01-01

Purpose: The aim of this study was to investigate the potential dose reduction in the uterus as a result of lead apron protection during thoracic CT scans. Moreover, the distribution of the radiation dose in the uterus was determined in order to obtain information about the ratio of internally and externally scattered radiation. Materials and Methods: The uterus doses during thoracic CT were determined by measuring organ doses using an Alderson-RANDO registered -Phantom and thermoluminescent dosimeters. A 0.25 mm lead equivalent protective apron was used to shield the abdominal area. Three measurement conditions were evaluated: without lead apron, covered with lead apron and wrapped with lead apron. The uterus dose with and without shielding describes the mean value and standard deviation of all examinations and all measurement points in the organ. Results: The uterus dose by thoracic CT was measured to be approximately 66.5 ± 3.1 μGy. If the abdomen is covered with a 0.25 mm Pb equivalent lead apron in the front area and on both sides, the uterus dose is reduced to 49.4 ± 2.8 μGy (26 % reduction, p < 0.001). If a lead apron is wrapped around the abdomen, providing 0.50 mm Pb shielding in the anterior section due to overlap, and 0.25 mm Pb in the posterior section and on both sides, the uterus dose is reduced even more to 43.8 ± 2.5 μGy (34 % reduction, p < 0.001). The dose distribution when the lead apron covers the abdomen shows that the shielding is effective for the scatter radiation that comes from the anterior part. Moreover, the wrapped apron protects the uterus from all directions and is even more effective for dose reduction than the covering apron. Conclusion: Our findings demonstrate that protective aprons are an effective dose reduction technique without additional costs and little effect on patient examination time. (orig.)

The Correlation of Endoscopic Findings and Clinical Features in Korean Patients with Scrub Typhus: A Cohort Study.

Science.gov (United States)

Lee, Jun; Kim, Dong-Min; Yun, Na Ra; Kim, Young Dae; Park, Chan Guk; Kim, Man Woo

2016-01-01

Scrub typhus is an infectious disease caused by Orientia tsutsugamushi-induced systemic vasculitis, but the involvement of the gastrointestinal tract and the endoscopic findings associated with scrub typhus are not well understood. We performed a prospective study and recommend performing esophagogastroduodenoscopy (EGD) for all possible scrub typhus patients, regardless of gastrointestinal symptoms. Gastrointestinal symptoms, endoscopic findings and clinical severity based on organ involvement and ICU admission were analyzed. Gastrointestinal symptoms occurred in up to 76.4% of scrub typhus patients. The major endoscopic findings were ulcers (43/127, 33.9%). Interestingly, 7.1% (9/127) of the patients presented with esophageal candidiasis. There was no correlation between the presence or absence of gastrointestinal symptoms and the endoscopic grade (P = 0.995). However, there was a positive correlation between the clinical severity and the endoscopic findings (P = 0.001). Sixty-three percent of the patients presented with erosion or ulcers on prospectively performed endoscopic evaluations, irrespective of gastrointestinal symptoms. Gastrointestinal symptoms did not reflect the need for endoscopy. Scrub typhus patients could have significant endoscopic abnormalities even in the absence of gastrointestinal symptoms.

Saturated norepinephrine transporter occupancy by atomoxetine relevant to clinical doses: a rhesus monkey study with (S,S)-[18F]FMeNER-D2

International Nuclear Information System (INIS)

Takano, Akihiro; Gulyas, Balazs; Varrone, Andrea; Halldin, Christer; Maguire, Ralph Paul

2009-01-01

In a previous PET study on norepinephrine transporter (NET) occupancy in the nonhuman primate brain, the relationship between NET occupancy and atomoxetine plasma concentration, and occupancies among different brain regions, were not demonstrated adequately. It may therefore be difficult to translate the results to the clinical situations. In the present study, the detailed change of NET occupancy was investigated among a wider range of doses in a more advanced manner. Two rhesus monkeys were examined using a high-resolution PET system with (S,S)-[ 18 F]FMeNER-D 2 under baseline conditions and after steady-state infusion of different doses of atomoxetine (0.003 to 0.12 mg/kg per hour). NET occupancy of the thalamus, brainstem and anterior cingulate cortex was calculated using BP ND obtained with the simplified reference tissue model. NET occupancy increased regionally and uniformly as the plasma concentration of atomoxetine increased. The estimated Kd value (the amount to occupy 50% of NET) in the thalamus was 16 ng/ml. The results indicate that clinical doses of atomoxetine would occupy NET almost completely. (orig.)

Therapeutic effects of low radiation doses

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Trott, K.R. (Dept. of Radiation Biology, St. Bartholomew' s Medical College, London (United Kingdom))

1994-01-01

This editorial explores the scientific basis of radiotherapy with doses of < 1 Gy for various non-malignant conditions, in particular dose-effect relationships, risk-benefit considerations and biological mechanisms. A review of the literature, particularly clinical and experimental reports published more than 50 years ago was conducted to clarify the following problems. 1. The dose-response relationships for the therapeutic effects on three groups of conditions: non-malignant skin disease, arthrosis and other painful degenerative joint disorders and anti-inflammatory radiotherapy; 2. risks after radiotherapy and after the best alternative treatments; 3. the biological mechanisms of the different therapeutic effects. Radiotherapy is very effective in all three groups of disease. Few dose-finding studies have been performed, all demonstrating that the optimal doses are considerable lower than the generally recommended doses. In different conditions, risk-benefit analysis of radiotherapy versus the best alternative treatment yields very different results: whereas radiotherapy for acute postpartum mastitis may not be justified any more, the risk-benefit ratio of radiotherapy of other conditions and particularly so in dermatology and some anti-inflammatory radiotherapy appears to be more favourable than the risk-benefit ratio of the best alternative treatments. Radiotherapy can be very effective treatment for various non-malignant conditions such as eczema, psoriasis, periarthritis humeroscapularis, epicondylitis, knee arthrosis, hydradenitis, parotitis and panaritium and probably be associated with less acute and long-term side effects than similarly effective other treatments. Randomized clinical studies are required to find the optimal dosage which, at present, may be unnecessarily high.

European Academy of Allergy and Clinical Immunology task force report on 'dose-response relationship in allergen-specific immunotherapy'.

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Calderón, M A; Larenas, D; Kleine-Tebbe, J; Jacobsen, L; Passalacqua, G; Eng, P A; Varga, E M; Valovirta, E; Moreno, C; Malling, H J; Alvarez-Cuesta, E; Durham, S; Demoly, P

2011-10-01

For a century, allergen-specific immunotherapy (SIT) has proven to be an effective treatment for allergic rhinitis, asthma, and insect sting allergy. However, as allergen doses are frequently adapted to the individual patient, there are few data on dose-response relationship in SIT. Allergen products for SIT are being increasingly required to conform to regulatory requirements for human medicines, which include the need to demonstrate dose-dependent effects. This report, produced by a Task Force of the EAACI Immunotherapy Interest Group, evaluates the currently available data on dose-response relationships in SIT and aims to provide recommendations for the design of future studies. Fifteen dose-ranging studies fulfilled the inclusion criteria and twelve reported a dose-response relationship for clinical efficacy. Several studies also reported a dose-response relationship for immunological and safety endpoints. Due to the use of different reference materials and methodologies for the determination of allergen content, variations in study design, and choice of endpoints, no comparisons could be made between studies and, as a consequence, no general dosing recommendations can be made. Despite recently introduced guidelines on the standardization of allergen preparations and study design, the Task Force identified a need for universally accepted standards for the measurement of allergen content in SIT preparations, dosing protocols, and selection of clinical endpoints to enable dose-response effects to be compared across studies. © 2011 John Wiley & Sons A/S.

Relationship between clinical findings of temporomandibular disorders and magnetic resonance imaging

International Nuclear Information System (INIS)

Iizuka, Yasuyuki; Miura, Hiroyuki; Ishikawa, Fujiro; Kikuchi, Shiori; Konishi, Nobuhiro; Sakamaki, Kimio

1996-01-01

The present study was conducted to investigate the relationship between magnetic resonance imaging (MRI) of the temporomandibular joint (TMJ) and clinical findings of patients having symptoms of temporomandibular disorders, and to consider the possibility to grasp the internal derangement of the TMJ from clinical findings. Subjects were 80 patients who visited to ask orthodontic treatment 16 males and 64 females. The average age was 22 years and 4 months. We performed a investigation of both their previous and present illness. In addition, to decide the correct condition concerning the internal derangement of the TMJ, patients were given MRI examinations (G. E. medical system Signa 1.5 Tesla) before orthodontic treatment. Results were as follows: The three symptoms of temporomandibular disorders-noise, pain, and abnormal mandibular movement, were not related to constant disk displacement. It seemed difficult to infer and obtain the diagnosis of the condition of internal derangement of the TMJ only from clinical findings. In a dental clinics having no medical imaging instrument such as MRI, it was, however, considered that the following items will make it possible to define the condition of internal derangements of the TMJ from clinical findings. As to respects concerning clinical findings, it is necessary to consider the previous illness as well as present illness. TMJ noise indicates a higher relationship to the disk displacement in MRI findings. The temporomandibular joint with plural symptoms indicated a higher incidence of disk displacement examined by MR Imaging than that with a single symptom. (author)

Dose-dependent LDL-cholesterol lowering effect by plant stanol ester consumption: clinical evidence

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Laitinen Kirsi

2012-10-01

Full Text Available Abstract Elevated serum lipids are linked to cardiovascular diseases calling for effective therapeutic means to reduce particularly LDL-cholesterol (LDL-C levels. Plant stanols reduce levels of LDL-C by partly blocking cholesterol absorption. Accordingly the consumption of foods with added plant stanols, typically esterified with vegetable oil fatty acids in commercial food products, are recommended for lowering serum cholesterol levels. A daily intake of 1.5 to 2.4 g of plant stanols has been scientifically evaluated to lower LDL-C by 7 to 10% in different populations, ages and with different diseases. Based on earlier studies, a general understanding is that no further reduction may be achieved in intakes in excess of approximately 2.5 g/day. Recent studies however suggest that plant stanols show a continuous dose–response effect in serum LDL-C lowering. This review discusses the evidence for a dose-effect relationship between plant stanol ester consumption and reduction of LDL-C concentrations with daily intakes of plant stanols of 4 g/day or more. We identified five such studies and the overall data demonstrate a linear dose-effect relationship with the most pertinent LDL-Cholesterol lowering outcome, 18%, achieved by a daily intake of 9 to 10 g of plant stanols. Along with reduction in LDL-C, the studies demonstrated a decrease in cholesterol absorption markers, the serum plant sterol to cholesterol ratios, by increasing the dose of plant stanol intake. None of the studies with daily intakes up to 10 g of plant stanols reported adverse clinical or biochemical effects from plant stanols. In a like manner, the magnitude of decrease in serum antioxidant vitamins was not related to the dose of plant stanols consumed and the differences between plant stanol ester consumers and controls were minor and insignificant or nonexisting. Consumption of plant stanols in high doses is feasible as a range of food products are commercially available for

Migraine accompagnee: Clinical and neutroradiological findings

International Nuclear Information System (INIS)

Schaefer, E.M.

1981-01-01

This study analyses clinical data, EEC and X-ray findings of 102 stationary examined migraine patients, 62 of whom suffered from migraine accompagnee. Sex distribution, age at onset of disease, hereditary disease disposition and EEC findings largely correspond to the data given in literature. As it had been expected, the X-ray images of the skull and the cerebral angiographies performed in 46 patients suffering from migraine accompagnee did not show any pathological findings. The X-ray images were compared with those taken of patients without migraine anamnesis in order to detect non-pathologic variations. Neither differences in the intensity of vascular and diplovenous marking could be found in the native images of the skull nor any variations of the circle of Willisi. The dependency of the posterior cerebral artery on the carotid circulation existing in 41% of the migraine accompagnee does not lead to any particular alteration of the accompanying symptoms and signs. The idea is discussed to divide the migraine syndrome into simple, focal and complicated migraine on the basis of a uniform pathogenesis. (orig./MG) [de

In vitro study of dose rate effect on Leksell Gamma Knife Perfexion

International Nuclear Information System (INIS)

Pastykova, V.; Novotny, J. jr.; Vachelova, J.; Davidkova, M.; Liscak, R.

2018-01-01

The main purpose of the study is to evaluate the radiobiological effect of the dose rate changes in Leksell Gamma Knife (LGK) clinical conditions. In principle there are two reasons why dose rate on LGK is reduced during patient irradiation: 1) Co-60 sources decay with a half-life of 5.26 years and 2) using multiple iso-centers and conformal treatment plans (e.g. with blocked beams). This pilot study is an experimental work performed in vitro with medulloblastoma DAOY cells. Are there effects caused by low dose rate which could negatively influence the clinical outcome of the radiosurgery? (authors)

Single visit rabies pre-exposure priming induces a robust anamnestic antibody response after simulated post-exposure vaccination: results of a dose-finding study.

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Jonker, Emile F F; Visser, Leonardus G

2017-09-01

The current standard 3-dose intramuscular rabies PrEP schedule suffers from a number of disadvantages that severely limit accessibility and availability. The cost of is often prohibitive, it requires 3 visits to the clinic, and there are regular vaccine shortages. Volunteers ( N  = 30) were randomly assigned to 4 study arms: 1 standard dose intramuscular (IM) dose of PVRV (purified Vero cell rabies vaccine, Verorab), and 1/5th, 2/5th or 3/5th- fractional intradermal (ID) dose of PVRV in a single visit. All subjects received a simulated rabies post-exposure prophylaxis (D0, D3) 1 year later. Rabies virus neutralizing antibodies (RVNA) were determined by virus neutralization microtest (FAVN) on D0, D7, D28, Y1 and Y1 + D7. 28 out of 30 subjects (93%) seroconverted 1 month after primary vaccination; 1 subject in the 1-dose IM arm and 1 in the 1/5th-fractional dose ID arm did not. After 1 year, 22 out of 30 subjects (73%) no longer had RVNA above 0.5 IU/ml, with no discernible difference between study groups. After 1 year, all 30 subjects mounted a booster response within 7 days after simulated PEP, with the highest titers found in the single dose IM group ( P  rabies vaccine was sufficient to induce an adequate anamnestic antibody response to rabies PEP in all subjects 1 year later, even in those in whom the RVNA threshold of 0.5 IU/ml was not reached after priming. © International Society of Travel Medicine, 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

Privacy in Pharmacogenetics: An End-to-End Case Study of Personalized Warfarin Dosing.

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Fredrikson, Matthew; Lantz, Eric; Jha, Somesh; Lin, Simon; Page, David; Ristenpart, Thomas

2014-08-01

We initiate the study of privacy in pharmacogenetics, wherein machine learning models are used to guide medical treatments based on a patient's genotype and background. Performing an in-depth case study on privacy in personalized warfarin dosing, we show that suggested models carry privacy risks, in particular because attackers can perform what we call model inversion : an attacker, given the model and some demographic information about a patient, can predict the patient's genetic markers. As differential privacy (DP) is an oft-proposed solution for medical settings such as this, we evaluate its effectiveness for building private versions of pharmacogenetic models. We show that DP mechanisms prevent our model inversion attacks when the privacy budget is carefully selected . We go on to analyze the impact on utility by performing simulated clinical trials with DP dosing models. We find that for privacy budgets effective at preventing attacks, patients would be exposed to increased risk of stroke, bleeding events, and mortality . We conclude that current DP mechanisms do not simultaneously improve genomic privacy while retaining desirable clinical efficacy, highlighting the need for new mechanisms that should be evaluated in situ using the general methodology introduced by our work.

Clinical outcomes with alternative dosing strategies for piperacillin/tazobactam: a systematic review and meta-analysis.

Directory of Open Access Journals (Sweden)

Hui Yang

Full Text Available A better dosing strategy can improve clinical outcomes for patients. We sought to compare the extended or continuous infusion with conventional intermittent infusion of piperacillin/tazobactam, investigating which approach is better and worthy of recommendation for clinical use.Articles were gathered from PubMed, Web of Science, ProQuest, Science Direct, Cochrane, two Chinese literature databases (CNKI, Wan Fang Data and related ICAAC and ACCP conferences. Randomized controlled and observational studies that compared extended or continuous infusion with conventional intermittent infusion of piperacillin/tazobactam were identified from the databases above and analyzed. Two reviewers independently extracted and investigated the data. A meta-analysis was performed using Revman 5.2 software. The quality of each study was assessed. Sensitivity analysis and publication bias were evaluated.Five randomized controlled trials and nine observational studies were included in this study. All included studies had high quality and no publication bias was found. Compared to the conventional intermittent infusion approach, the extended or continuous infusion group had a significantly higher clinical cure rate (OR 1.88, 95% CI 1.29-2.73, P = 0.0009 and a lower mortality rate (OR 0.67, 95% CI 0.50-0.89, P = 0.005. No statistical difference was observed for bacteriologic cure (OR 1.40, 95% CI 0.82-2.37, P = 0.22 between the two dosing regimens. The sensitivity analysis showed the results were stable.Our systematic review and meta-analysis suggested that the extended or continuous infusion strategy of piperacillin/tazobactam should be recommended for clinical use considering its higher clinical cure rate and lower mortality rate in comparison with conventional intermittent strategy. Data from this study could be extrapolated for other β-lactam antimicrobials. Therefore, this dosing strategy could be considered in clinical practice.

An oracle: antituberculosis pharmacokinetics-pharmacodynamics, clinical correlation, and clinical trial simulations to predict the future.

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Pasipanodya, Jotam; Gumbo, Tawanda

2011-01-01

Antimicrobial pharmacokinetic-pharmacodynamic (PK/PD) science and clinical trial simulations have not been adequately applied to the design of doses and dose schedules of antituberculosis regimens because many researchers are skeptical about their clinical applicability. We compared findings of preclinical PK/PD studies of current first-line antituberculosis drugs to findings from several clinical publications that included microbiologic outcome and pharmacokinetic data or had a dose-scheduling design. Without exception, the antimicrobial PK/PD parameters linked to optimal effect were similar in preclinical models and in tuberculosis patients. Thus, exposure-effect relationships derived in the preclinical models can be used in the design of optimal antituberculosis doses, by incorporating population pharmacokinetics of the drugs and MIC distributions in Monte Carlo simulations. When this has been performed, doses and dose schedules of rifampin, isoniazid, pyrazinamide, and moxifloxacin with the potential to shorten antituberculosis therapy have been identified. In addition, different susceptibility breakpoints than those in current use have been identified. These steps outline a more rational approach than that of current methods for designing regimens and predicting outcome so that both new and older antituberculosis agents can shorten therapy duration.

Neuromuscular dose-response studies: determining sample size.

Science.gov (United States)

Kopman, A F; Lien, C A; Naguib, M

2011-02-01

Investigators planning dose-response studies of neuromuscular blockers have rarely used a priori power analysis to determine the minimal sample size their protocols require. Institutional Review Boards and peer-reviewed journals now generally ask for this information. This study outlines a proposed method for meeting these requirements. The slopes of the dose-response relationships of eight neuromuscular blocking agents were determined using regression analysis. These values were substituted for γ in the Hill equation. When this is done, the coefficient of variation (COV) around the mean value of the ED₅₀ for each drug is easily calculated. Using these values, we performed an a priori one-sample two-tailed t-test of the means to determine the required sample size when the allowable error in the ED₅₀ was varied from ±10-20%. The COV averaged 22% (range 15-27%). We used a COV value of 25% in determining the sample size. If the allowable error in finding the mean ED₅₀ is ±15%, a sample size of 24 is needed to achieve a power of 80%. Increasing 'accuracy' beyond this point requires increasing greater sample sizes (e.g. an 'n' of 37 for a ±12% error). On the basis of the results of this retrospective analysis, a total sample size of not less than 24 subjects should be adequate for determining a neuromuscular blocking drug's clinical potency with a reasonable degree of assurance.

Bone marrow abnormality associated with painful osteoarthritis of the knee. A cross-sectional study of magnetic resonance imaging findings with the radiographic stage and clinical findings

International Nuclear Information System (INIS)

Kubota, Mitsuaki; Kurosawa, Hisashi; Ikeda, Hiroshi; Takazawa, Yuji; Kawasaki, Takayuki; Ishijima, Muneaki; Kim, Song-Gon; Seto, Hiroaki

2009-01-01

Bone marrow abnormalities (BMAs) are frequently found in osteoarthritis (OA) of the knee with magnetic resonance imaging (MRI). Some reports have suggested BMA was correlated with the X-ray stage of OA and also with knee pain, but the reports depended on two-dimensional images without considering the spatial expansion of BMAs. To determine whether three-dimensional expansion of a BMA with MRI in patient with medial-type OA of the knee is correlated with the radiographic stage of OA and clinical findings using a semi-quantitative method. Cross-sectional study. This study enrolled 238 patients with medial-type OA. Radiography and MRI of the knee were taken in all participants. X-rays were graded using the Kellgren-Lawrence (K/L) grade (1-4). T2-weighted fat-suppressed MRI images were used to score the size of the BMA according to the whole-organ MRI score (WORMS). A new scoring system defined as the spatial BMA score (s-score), which specifically addressed the spatial expansion of BMAs, was examined to assess the size of the BMA. BMA frequency was examined in subdivisions of the articular surfaces of the knee according to the X-ray stages of the K/L grade and the correlation of the s-score to the clinical findings. BMA frequency in the medial femorotibial joint (MFTJ; 74%) was significantly higher than in the lateral femorotibial joint (LFTJ; 14%) and patellofemoral joint (PFJ; 14%; P<0.01). The s-score of the MFTJ was strongly correlated with the X-ray stage assessed by the K/L grade. The s-score of the MFTJ was also correlated with the clinical findings. The frequency and spatial expansion of BMAs in the MFTJ are strongly correlated with the X-ray stage of medial-type OA as well as the clinical findings. (author)

Pneumatosis intestinalis: CT findings and clinical features

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Kim, Hye Lin; Lee, Hae Kyung; Park, Seong Jin; Yi, Boem Ha; Ko, Bong Min; Hong, Hyun Sook; Paik, Sang Hyun [Soonchunhyang University Hospital Bucheon, Bucheon (Korea, Republic of)

2008-02-15

The purpose of this study is to evaluate the CT findings and clinical features of patients with pneumatosis intestinalis. From January 2001 to October 2007, 15 patients with pneumatosis intestinalis were diagnosed by the use of CT. We analyzed the clinical features and CT findings to assess the involvement site, the presence of portal and mesenteric vein gas, and the existence of accompanied ischemic change. Of the 15 patients, five patients had end stage renal disease (33.3%), two patients underwent a gastrectomy, one patient underwent a laminectomy, one patient had tuberculous enteritis, one patient had lung cancer and one patient had pneumonia. Four patients presented with no specific disease. There was portal or mesenteric venous gas in six cases, and strangulation or an ischemic change of the bowel in five cases. Otherwise, pneumatosis intestinalis was associated with hydropneumoperitoneum in two cases, pneumoperitoneum in one case and a single case of perforated appendicitis. Nine patients underwent surgery for ischemic change of the bowel, pneumoperitoneum, appendicitis, and a clinical sign of panperitonitis. Among the remaining six patients, three patients recovered and were discharged, and three patients expired during progression of the disease. End stage renal disease is the most common condition associated with pneumatosis intestinalis. The presence of portomesenteric venous gas, ischemic change of the bowel, and linear pneumatosis intestinalis are indicative of a poor prognosis.

Optimal medication dosing from suboptimal clinical examples: a deep reinforcement learning approach.

Science.gov (United States)

Nemati, Shamim; Ghassemi, Mohammad M; Clifford, Gari D

2016-08-01

Misdosing medications with sensitive therapeutic windows, such as heparin, can place patients at unnecessary risk, increase length of hospital stay, and lead to wasted hospital resources. In this work, we present a clinician-in-the-loop sequential decision making framework, which provides an individualized dosing policy adapted to each patient's evolving clinical phenotype. We employed retrospective data from the publicly available MIMIC II intensive care unit database, and developed a deep reinforcement learning algorithm that learns an optimal heparin dosing policy from sample dosing trails and their associated outcomes in large electronic medical records. Using separate training and testing datasets, our model was observed to be effective in proposing heparin doses that resulted in better expected outcomes than the clinical guidelines. Our results demonstrate that a sequential modeling approach, learned from retrospective data, could potentially be used at the bedside to derive individualized patient dosing policies.

Reformulation of a clinical-dose system for carbon-ion radiotherapy treatment planning at the National Institute of Radiological Sciences, Japan

International Nuclear Information System (INIS)

Inaniwa, Taku; Kanematsu, Nobuyuki; Matsufuji, Naruhiro; Shirai, Toshiyuki; Noda, Koji; Kanai, Tatsuaki; Tsuji, Hiroshi; Kamada, Tadashi; Tsujii, Hirohiko

2015-01-01

At the National Institute of Radiological Sciences (NIRS), more than 8,000 patients have been treated for various tumors with carbon-ion (C-ion) radiotherapy in the past 20 years based on a radiobiologically defined clinical-dose system. Through clinical experience, including extensive dose escalation studies, optimum dose-fractionation protocols have been established for respective tumors, which may be considered as the standards in C-ion radiotherapy. Although the therapeutic appropriateness of the clinical-dose system has been widely demonstrated by clinical results, the system incorporates several oversimplifications such as dose-independent relative biological effectiveness (RBE), empirical nuclear fragmentation model, and use of dose-averaged linear energy transfer to represent the spectrum of particles. We took the opportunity to update the clinical-dose system at the time we started clinical treatment with pencil beam scanning, a new beam delivery method, in 2011. The requirements for the updated system were to correct the oversimplifications made in the original system, while harmonizing with the original system to maintain the established dose-fractionation protocols. In the updated system, the radiation quality of the therapeutic C-ion beam was derived with Monte Carlo simulations, and its biological effectiveness was predicted with a theoretical model. We selected the most used C-ion beam with α r = 0.764 Gy −1 and β = 0.0615 Gy −2 as reference radiation for RBE. The C-equivalent biological dose distribution is designed to allow the prescribed survival of tumor cells of the human salivary gland (HSG) in entire spread-out Bragg peak (SOBP) region, with consideration to the dose dependence of the RBE. This C-equivalent biological dose distribution is scaled to a clinical dose distribution to harmonize with our clinical experiences with C-ion radiotherapy. Treatment plans were made with the original and the updated clinical-dose systems, and both

17DD yellow fever vaccine: a double blind, randomized clinical trial of immunogenicity and safety on a dose-response study.

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Martins, Reinaldo M; Maia, Maria de Lourdes S; Farias, Roberto Henrique G; Camacho, Luiz Antonio B; Freire, Marcos S; Galler, Ricardo; Yamamura, Anna Maya Yoshida; Almeida, Luiz Fernando C; Lima, Sheila Maria B; Nogueira, Rita Maria R; Sá, Gloria Regina S; Hokama, Darcy A; de Carvalho, Ricardo; Freire, Ricardo Aguiar V; Pereira Filho, Edson; Leal, Maria da Luz Fernandes; Homma, Akira

2013-04-01

To verify if the Bio-Manguinhos 17DD yellow fever vaccine (17DD-YFV) used in lower doses is as immunogenic and safe as the current formulation. Doses from 27,476 IU to 587 IU induced similar seroconversion rates and neutralizing antibodies geometric mean titers (GMTs). Immunity of those who seroconverted to YF was maintained for 10 mo. Reactogenicity was low for all groups. Young and healthy adult males (n = 900) were recruited and randomized into 6 groups, to receive de-escalating doses of 17DD-YFV, from 27,476 IU to 31 IU. Blood samples were collected before vaccination (for neutralization tests to yellow fever, serology for dengue and clinical chemistry), 3 to 7 d after vaccination (for viremia and clinical chemistry) and 30 d after vaccination (for new yellow fever serology and clinical chemistry). Adverse events diaries were filled out by volunteers during 10 d after vaccination. Volunteers were retested for yellow fever and dengue antibodies 10 mo later. Seropositivity for dengue was found in 87.6% of volunteers before vaccination, but this had no significant influence on conclusions. In young healthy adults Bio-Manguinhos/Fiocruz yellow fever vaccine can be used in much lower doses than usual. INTERNATIONAL REGISTER: ISRCTN 38082350.

Atopy patch tests in young adult patients with atopic dermatitis and controls: dose-response relationship, objective reading, reproducibility and clinical interpretation.

Science.gov (United States)

Bygum, Anette; Mortz, Charlotte Gotthard; Andersen, Klaus Ejner

2003-01-01

The clinical interpretation and reproducibility of atopy patch tests was studied in 23 selected young adult patients with atopic dermatitis and 25 healthy controls using standard inhalant allergens. Non-invasive measurements were used for objective assessment of test reactions and the participants were retested after 6 weeks. Ten of 19 (53%) evaluable patients with atopic dermatitis had at least one positive atopy patch test. However, there was no clear clinical relevance of the atopy patch test results when related to patient history and distribution of dermatitis. Reproducible and dose-dependent results were obtained with Dermatophagoides pteronyssinus, grass and cat with a reproducibility rate of 0.69 to 0.81 in patients and 0.60-0.96 in controls. A unique finding was a significant positive correlation between a positive atopy patch test, allergen dose and increase in transepidermal water loss and erythema, while measurement of capacitance did not distinguish between positive and negative reactions. The results of the present study do not support the routine use of atopy patch tests in the evaluation of adult patients with atopic dermatitis.

Evidence for single-dose protection by the bivalent HPV vaccine-Review of the Costa Rica HPV vaccine trial and future research studies.

Science.gov (United States)

Kreimer, Aimée R; Herrero, Rolando; Sampson, Joshua N; Porras, Carolina; Lowy, Douglas R; Schiller, John T; Schiffman, Mark; Rodriguez, Ana Cecilia; Chanock, Stephen; Jimenez, Silvia; Schussler, John; Gail, Mitchell H; Safaeian, Mahboobeh; Kemp, Troy J; Cortes, Bernal; Pinto, Ligia A; Hildesheim, Allan; Gonzalez, Paula

2018-01-20

The Costa Rica Vaccine Trial (CVT), a phase III randomized clinical trial, provided the initial data that one dose of the HPV vaccine could provide durable protection against HPV infection. Although the study design was to administer all participants three doses of HPV or control vaccine, 20% of women did not receive the three-dose regimens, mostly due to involuntary reasons unrelated to vaccination. In 2011, we reported that a single dose of the bivalent HPV vaccine could be as efficacious as three doses of the vaccine using the endpoint of persistent HPV infection accumulated over the first four years of the trial; findings independently confirmed in the GSK-sponsored PATRICIA trial. Antibody levels after one dose, although lower than levels elicited by three doses, were 9-times higher than levels elicited by natural infection. Importantly, levels remained essentially constant over at least seven years, suggesting that the observed protection provided by a single dose might be durable. Much work has been done to assure these non-randomized findings are valid. Yet, the group of recipients who received one dose of the bivalent HPV vaccine in the CVT and PATRICIA trials was small and not randomly selected nor blinded to the number of doses received. The next phase of research is to conduct a formal randomized, controlled trial to evaluate the protection afforded by a single dose of HPV vaccine. Complementary studies are in progress to bridge our findings to other populations, and to further document the long-term durability of antibody response following a single dose. Published by Elsevier Ltd.

Research design considerations for single-dose analgesic clinical trials in acute pain

DEFF Research Database (Denmark)

Cooper, Stephen A; Desjardins, Paul J; Turk, Dennis C

2016-01-01

This article summarizes the results of a meeting convened by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) on key considerations and best practices governing the design of acute pain clinical trials. We discuss the role of early phase clinical trials......, including pharmacokinetic-pharmacodynamic (PK-PD) trials, and the value of including both placebo and active standards of comparison in acute pain trials. This article focuses on single-dose and short-duration trials with emphasis on the perioperative and study design factors that influence assay...... sensitivity. Recommendations are presented on assessment measures, study designs, and operational factors. Although most of the methodological advances have come from studies of postoperative pain after dental impaction, bunionectomy, and other surgeries, the design considerations discussed are applicable...

Chronic Meningitis: A study on epidemiological and clinical findings, treatment results and prognosis of 97 patients

Directory of Open Access Journals (Sweden)

"Ahmadinejad Z

2001-08-01

Full Text Available Central nervous system’s disorders including chronic meningitis (CM have considerable mortality and irreversible complications, and diagnosis and treatment of CM is difficult. In this retrospective study we reviwed epidemiological and clinical findings, treatment results and prognostic factors of 97 patients with CM admitted in Imam Khomeini hospital for the last 10 years. Important etiological factors in this study included: Mycobacterium Tuberculousis (8.2% Brucellae SP (5.2%, malignancies (1% and unknown (85.5%; the sexual ratio was 2:1 (Male/Female and the most common clinical manifestations were: fever, headache, cranial and motor neuron involvement, seizure and ataxia. Treatment regimens used included antituberculosis agents with or witout corticosteroids, in which the prognosis was better in patients who had been treated with antituberculosis agents alone. The mortality rate was 22.7%, which was in accordance with other studies. We suggest using of antituberculosis treatment alone in comparison with antituberculosis and corticosteroid. Last but not least a double blind randomized clinical trial for a longer period is needed to further substantiate the results of this study.

Methylphenidate dose optimization for ADHD treatment: review of safety, efficacy, and clinical necessity

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Huss M

2017-07-01

Full Text Available Michael Huss,1 Praveen Duhan,2 Preetam Gandhi,3 Chien-Wei Chen,4 Carsten Spannhuth,3 Vinod Kumar5 1Child and Adolescent Psychiatry, University Medicine, Mainz, Germany; 2Global Medical Affairs, Novartis Healthcare Pvt. Ltd., Hyderabad, India; 3Development Franchise, Established Medicine Neuroscience, Novartis Pharma AG, Basel, Switzerland; 4Biostatistics Cardio-Metabolic & Established Medicine, Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA; 5Established Medicines, Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA Abstract: Attention-deficit/hyperactivity disorder (ADHD is a chronic psychiatric disorder characterized by hyperactivity and/or inattention and is often associated with a substantial impact on psychosocial functioning. Methylphenidate (MPH, a central nervous system stimulant, is commonly used for pharmacological treatment of adults and children with ADHD. Current practice guidelines recommend optimizing MPH dosage to individual patient needs; however, the clinical benefits of individual dose optimization compared with fixed-dose regimens remain unclear. Here we review the available literature on MPH dose optimization from clinical trials and real-world experience on ADHD management. In addition, we report safety and efficacy data from the largest MPH modified-release long-acting Phase III clinical trial conducted to examine benefits of dose optimization in adults with ADHD. Overall, MPH is an effective ADHD treatment with a good safety profile; data suggest that dose optimization may enhance the safety and efficacy of treatment. Further research is required to establish the extent to which short-term clinical benefits of MPH dose optimization translate into improved long-term outcomes for patients with ADHD. Keywords: methylphenidate, dose optimization, attention-deficit/hyperactivity disorder, ADHD

SU-E-T-135: Assessing the Clinical Impact of Approximations in Analytical Dose Calculations for Proton Therapy

Energy Technology Data Exchange (ETDEWEB)

Schuemann, J; Giantsoudi, D; Grassberger, C; Paganetti, H [Massachusetts General Hospital, Boston, MA (United States)

2015-06-15

Purpose: To estimate the clinical relevance of approximations made in analytical dose calculation methods (ADCs) used for treatment planning on tumor coverage and tumor control probability (TCP) in proton therapy. Methods: We compared dose distributions planned with ADC to delivered dose distributions (as determined by TOPAS Monte Carlo (MC) simulations). We investigated 10 patients per site for 5 treatment sites (head-and-neck, lung, breast, prostate, liver). We evaluated differences between the two dose distributions analyzing dosimetric indices based on the dose-volume-histograms, the γ-index and the TCP. The normal tissue complication probability (NTCP) was estimated for the bladder and anterior rectum for the prostate patients. Results: We find that the target doses are overestimated by the ADC by 1–2% on average for all patients considered. All dosimetric indices (the mean dose, D95, D50 and D02, the dose values covering 95%, 50% and 2% of the target volume, respectively) are predicted within 5% of the delivered dose. A γ-index with a 3%/3mm criteria had a passing rate for target volumes above 96% for all patients. The TCP predicted by the two algorithms was up to 2%, 2.5%, 6%, 6.5%, and 11% for liver and breast, prostate, head-and-neck and lung patients, respectively. Differences in NTCP for anterior-rectum and bladder for prostate patients were less than 3%. Conclusion: We show that ADC provide adequate dose distributions for most patients, however, they can Result in underdosage of the target by as much as 5%. The TCP was found to be up to 11% lower than predicted. Advanced dose-calculation methods like MC simulations may be necessary in proton therapy to ensure target coverage for heterogeneous patient geometries, in clinical trials comparing proton therapy to conventional radiotherapy to avoid biases due to systematic discrepancies in calculated dose distributions, and, if tighter range margins are considered. Fully funded by NIH grants.

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

Science.gov (United States)

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

2015-07-01

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

Clinical benefit of fixed-dose dual bronchodilation with glycopyrronium and indacaterol once daily in patients with chronic obstructive pulmonary disease

DEFF Research Database (Denmark)

Ulrik, Charlotte Suppli

2014-01-01

BACKGROUND AND AIM: Long-acting bronchodilators are the preferred option for maintenance therapy of patients with chronic obstructive pulmonary disease (COPD). The aim of this review is to provide an overview of the clinical studies evaluating the clinical efficacy of the once-daily fixed-dose du...... for chronic Obstructive Lung Disease [GOLD] spirometric criteria). Furthermore, a very recent study has shown that fixed-dose indacaterol/glycopyrronium improves exercise endurance time compared with placebo, although no significant difference was observed between fixed-dose indacaterol...

Albinism: classification, clinical characteristics, and recent findings.

Science.gov (United States)

Summers, C Gail

2009-06-01

To describe the clinical characteristics and recent findings in the heterogeneous group of inherited disorders of melanin biosynthesis grouped as "albinism." The current classification of albinism, and the cutaneous, ocular, and central nervous system characteristics are presented. Recent clinical findings are summarized. Albinism is now classified based on genes known to be responsible for albinism. Foveal hypoplasia is invariably present and individuals with albinism often have delayed visual development, reduced vision, nystagmus, a positive angle kappa, strabismus, iris transillumination, and absent or reduced melanin pigment in the fundi. A visual-evoked potential can document the excessive retinostriate decussation seen in albinism. Grating acuity can be used to document delayed visual development in preverbal children. Glasses are often needed to improve visual acuity and binocular alignment. Albinism is caused by several different genes. Heterogeneity in clinical phenotype indicates that expressivity is variable.

SU-G-BRC-15: The Potential Clinical Significance of Dose Mapping Error for Intra- Fraction Dose Mapping for Lung Cancer Patients

Energy Technology Data Exchange (ETDEWEB)

Sayah, N [Thomas Cancer Center, Richmond, VA (United States); Weiss, E [Virginia Commonwealth University, Richmond, Virginia (United States); Watkins, W [University of Virginia, Charlottesville, VA (United States); Siebers, J [University of Virginia Health System, Charlottesville, VA (United States)

2016-06-15

Purpose: To evaluate the dose-mapping error (DME) inherent to conventional dose-mapping algorithms as a function of dose-matrix resolution. Methods: As DME has been reported to be greatest where dose-gradients overlap tissue-density gradients, non-clinical 66 Gy IMRT plans were generated for 11 lung patients with the target edge defined as the maximum 3D density gradient on the 0% (end of inhale) breathing phase. Post-optimization, Beams were copied to 9 breathing phases. Monte Carlo dose computed (with 2*2*2 mm{sup 3} resolution) on all 10 breathing phases was deformably mapped to phase 0% using the Monte Carlo energy-transfer method with congruent mass-mapping (EMCM); an externally implemented tri-linear interpolation method with voxel sub-division; Pinnacle’s internal (tri-linear) method; and a post-processing energy-mass voxel-warping method (dTransform). All methods used the same base displacement-vector-field (or it’s pseudo-inverse as appropriate) for the dose mapping. Mapping was also performed at 4*4*4 mm{sup 3} by merging adjacent dose voxels. Results: Using EMCM as the reference standard, no clinically significant (>1 Gy) DMEs were found for the mean lung dose (MLD), lung V20Gy, or esophagus dose-volume indices, although MLD and V20Gy were statistically different (2*2*2 mm{sup 3}). Pinnacle-to-EMCM target D98% DMEs of 4.4 and 1.2 Gy were observed ( 2*2*2 mm{sup 3}). However dTransform, which like EMCM conserves integral dose, had DME >1 Gy for one case. The root mean square RMS of the DME for the tri-linear-to- EMCM methods was lower for the smaller voxel volume for the tumor 4D-D98%, lung V20Gy, and cord D1%. Conclusion: When tissue gradients overlap with dose gradients, organs-at-risk DME was statistically significant but not clinically significant. Target-D98%-DME was deemed clinically significant for 2/11 patients (2*2*2 mm{sup 3}). Since tri-linear RMS-DME between EMCM and tri-linear was reduced at 2*2*2 mm{sup 3}, use of this resolution is

A clinical study of lung cancer dose calculation accuracy with Monte Carlo simulation.

Science.gov (United States)

Zhao, Yanqun; Qi, Guohai; Yin, Gang; Wang, Xianliang; Wang, Pei; Li, Jian; Xiao, Mingyong; Li, Jie; Kang, Shengwei; Liao, Xiongfei

2014-12-16

The accuracy of dose calculation is crucial to the quality of treatment planning and, consequently, to the dose delivered to patients undergoing radiation therapy. Current general calculation algorithms such as Pencil Beam Convolution (PBC) and Collapsed Cone Convolution (CCC) have shortcomings in regard to severe inhomogeneities, particularly in those regions where charged particle equilibrium does not hold. The aim of this study was to evaluate the accuracy of the PBC and CCC algorithms in lung cancer radiotherapy using Monte Carlo (MC) technology. Four treatment plans were designed using Oncentra Masterplan TPS for each patient. Two intensity-modulated radiation therapy (IMRT) plans were developed using the PBC and CCC algorithms, and two three-dimensional conformal therapy (3DCRT) plans were developed using the PBC and CCC algorithms. The DICOM-RT files of the treatment plans were exported to the Monte Carlo system to recalculate. The dose distributions of GTV, PTV and ipsilateral lung calculated by the TPS and MC were compared. For 3DCRT and IMRT plans, the mean dose differences for GTV between the CCC and MC increased with decreasing of the GTV volume. For IMRT, the mean dose differences were found to be higher than that of 3DCRT. The CCC algorithm overestimated the GTV mean dose by approximately 3% for IMRT. For 3DCRT plans, when the volume of the GTV was greater than 100 cm(3), the mean doses calculated by CCC and MC almost have no difference. PBC shows large deviations from the MC algorithm. For the dose to the ipsilateral lung, the CCC algorithm overestimated the dose to the entire lung, and the PBC algorithm overestimated V20 but underestimated V5; the difference in V10 was not statistically significant. PBC substantially overestimates the dose to the tumour, but the CCC is similar to the MC simulation. It is recommended that the treatment plans for lung cancer be developed using an advanced dose calculation algorithm other than PBC. MC can accurately

Pilot study in the treatment of endometrial carcinoma with 3D image-based high-dose-rate brachytherapy using modified Heyman packing: Clinical experience and dose-volume histogram analysis

International Nuclear Information System (INIS)

Weitmann, Hajo Dirk; Poetter, Richard; Waldhaeusl, Claudia; Nechvile, Elisabeth; Kirisits, Christian; Knocke, Tomas Hendrik

2005-01-01

Purpose: The aim of this study was to evaluate dose distribution within uterus (clinical target volume [CTV]) and tumor (gross tumor volume [GTV]) and the resulting clinical outcome based on systematic three-dimensional treatment planning with dose-volume adaptation. Dose-volume assessment and adaptation in organs at risk and its impact on side effects were investigated in parallel. Methods and Materials: Sixteen patients with either locally confined endometrial carcinoma (n = 15) or adenocarcinoma of uterus and ovaries after bilateral salpingo-oophorectomy (n = 1) were included. Heyman packing was performed with mean 11 Norman-Simon applicators (3-18). Three-dimensional treatment planning based on computed tomography (n = 29) or magnetic resonance imaging (n = 18) was done in all patients with contouring of CTV, GTV, and organs at risk. Dose-volume adaptation was achieved by dwell location and time variation (intensity modulation). Twelve patients treated with curative intent received five to seven fractions of high-dose-rate brachytherapy (7 Gy per fraction) corresponding to a total dose of 60 Gy (2 Gy per fraction and α/β of 10 Gy) to the CTV. Four patients had additional external beam radiotherapy (range, 10-40 Gy). One patient had salvage brachytherapy and 3 patients were treated with palliative intent. A dose-volume histogram analysis was performed in all patients. On average, 68% of the CTV and 92% of the GTV were encompassed by the 60 Gy reference volume. Median minimum dose to 90% of CTV and GTV (D90) was 35.3 Gy and 74 Gy, respectively. Results: All patients treated with curative intent had complete remission (12/12). After a median follow-up of 47 months, 5 patients are alive without tumor. Seven patients died without tumor from intercurrent disease after median 22 months. The patient with salvage treatment had a second local recurrence after 27 months and died of endometrial carcinoma after 57 months. In patients treated with palliative intent

Islet Oxygen Consumption Rate (OCR) Dose Predicts Insulin Independence in Clinical Islet Autotransplantation.

Science.gov (United States)

Papas, Klearchos K; Bellin, Melena D; Sutherland, David E R; Suszynski, Thomas M; Kitzmann, Jennifer P; Avgoustiniatos, Efstathios S; Gruessner, Angelika C; Mueller, Kathryn R; Beilman, Gregory J; Balamurugan, Appakalai N; Loganathan, Gopalakrishnan; Colton, Clark K; Koulmanda, Maria; Weir, Gordon C; Wilhelm, Josh J; Qian, Dajun; Niland, Joyce C; Hering, Bernhard J

2015-01-01

Reliable in vitro islet quality assessment assays that can be performed routinely, prospectively, and are able to predict clinical transplant outcomes are needed. In this paper we present data on the utility of an assay based on cellular oxygen consumption rate (OCR) in predicting clinical islet autotransplant (IAT) insulin independence (II). IAT is an attractive model for evaluating characterization assays regarding their utility in predicting II due to an absence of confounding factors such as immune rejection and immunosuppressant toxicity. Membrane integrity staining (FDA/PI), OCR normalized to DNA (OCR/DNA), islet equivalent (IE) and OCR (viable IE) normalized to recipient body weight (IE dose and OCR dose), and OCR/DNA normalized to islet size index (ISI) were used to characterize autoislet preparations (n = 35). Correlation between pre-IAT islet product characteristics and II was determined using receiver operating characteristic analysis. Preparations that resulted in II had significantly higher OCR dose and IE dose (p<0.001). These islet characterization methods were highly correlated with II at 6-12 months post-IAT (area-under-the-curve (AUC) = 0.94 for IE dose and 0.96 for OCR dose). FDA/PI (AUC = 0.49) and OCR/DNA (AUC = 0.58) did not correlate with II. OCR/DNA/ISI may have some utility in predicting outcome (AUC = 0.72). Commonly used assays to determine whether a clinical islet preparation is of high quality prior to transplantation are greatly lacking in sensitivity and specificity. While IE dose is highly predictive, it does not take into account islet cell quality. OCR dose, which takes into consideration both islet cell quality and quantity, may enable a more accurate and prospective evaluation of clinical islet preparations.

Islet Oxygen Consumption Rate (OCR Dose Predicts Insulin Independence in Clinical Islet Autotransplantation.

Directory of Open Access Journals (Sweden)

Klearchos K Papas

Full Text Available Reliable in vitro islet quality assessment assays that can be performed routinely, prospectively, and are able to predict clinical transplant outcomes are needed. In this paper we present data on the utility of an assay based on cellular oxygen consumption rate (OCR in predicting clinical islet autotransplant (IAT insulin independence (II. IAT is an attractive model for evaluating characterization assays regarding their utility in predicting II due to an absence of confounding factors such as immune rejection and immunosuppressant toxicity.Membrane integrity staining (FDA/PI, OCR normalized to DNA (OCR/DNA, islet equivalent (IE and OCR (viable IE normalized to recipient body weight (IE dose and OCR dose, and OCR/DNA normalized to islet size index (ISI were used to characterize autoislet preparations (n = 35. Correlation between pre-IAT islet product characteristics and II was determined using receiver operating characteristic analysis.Preparations that resulted in II had significantly higher OCR dose and IE dose (p<0.001. These islet characterization methods were highly correlated with II at 6-12 months post-IAT (area-under-the-curve (AUC = 0.94 for IE dose and 0.96 for OCR dose. FDA/PI (AUC = 0.49 and OCR/DNA (AUC = 0.58 did not correlate with II. OCR/DNA/ISI may have some utility in predicting outcome (AUC = 0.72.Commonly used assays to determine whether a clinical islet preparation is of high quality prior to transplantation are greatly lacking in sensitivity and specificity. While IE dose is highly predictive, it does not take into account islet cell quality. OCR dose, which takes into consideration both islet cell quality and quantity, may enable a more accurate and prospective evaluation of clinical islet preparations.

Treatment Dosing Patterns and Clinical Outcomes for Patients with Type 2 Diabetes Starting or Switching to Treatment with Insulin Glargine (300 Units per Milliliter) in a Real-World Setting: A Retrospective Observational Study.

Science.gov (United States)

Gupta, Shaloo; Wang, Hongwei; Skolnik, Neil; Tong, Liyue; Liebert, Ryan M; Lee, Lulu K; Stella, Peter; Cali, Anna; Preblick, Ronald

2018-01-01

Usage patterns and effectiveness of a longer-acting formulation of insulin glargine at a strength of 300 units per milliliter (Gla-300) have not been studied in real-world clinical practice. This study evaluated differences in dosing and clinical outcomes before and after Gla-300 treatment initiation in patients with type 2 diabetes starting or switching to treatment with Gla-300 to assess whether the benefits observed in clinical trials translate into real-world settings. This was a retrospective observational study using medical record data obtained by physician survey for patients starting treatment with insulin glargine at a strength of 100 units per milliliter (Gla-100) or Gla-300, or switching to treatment with Gla-300 from treatment with another basal insulin (BI). Differences in dosing and clinical outcomes before versus after treatment initiation or switching were examined by generalized linear mixed-effects models. Among insulin-naive patients starting BI treatment, no difference in the final titrated dose was observed in patients starting Gla-300 treatment versus those starting Gla-100 treatment [least-squares (LS) mean 0.43 units per kilogram vs 0.44 units per kilogram; P = 0.77]. Both groups had significant hemoglobin A 1c level reductions (LS mean 1.21 percentage points for Gla-300 and 1.12 percentage points for Gla-100 ; both P per kilogram before switch vs 0.58 units per kilogram after switch; P = 0.02). The mean hemoglobin A 1c level was significantly lower after switching than before switching (adjusted difference - 0.95 percentage points, 95% CI - 1.13 to - 0.78 percentage points ; P per patient-year were significantly lower (relative risk 0.17, 95% CI 0.11-0.26; P < 0.0001). Insulin-naive patients starting Gla-300 treatment had fewer hypoglycemic events, a similar hemoglobin A 1c level reduction, and no difference in insulin dose versus patients starting Gla-100 treatment. Patients switching to Gla-300 treatment from treatment with

Clinical menifestations and CT findings of lacunar infarction

International Nuclear Information System (INIS)

Shimada, Tsutomu; Kaneko, Mitsuo; Tanaka, Keisei; Sato, Kengo; Yamamoto, Toshiki

1983-01-01

Since the introduction of the CT scanner, the present authors have experienced 111 cases of lacunar infarction which were diagnosed on the basis of clinical manifestations and/or CT findings, being 35 % of total 318 cases of acute cerebral infarction in our series. The clinical features and their correlation with the CT findings were studied in the cases of lacunar infarction. The results were as follows. 1) Seventy-four per cent of the patients were hypertensive. 2) Fifty per cent of the patients had only motor deficit. 3) The patients who revealed small deep infarctions in the posterior two-thirds of the posterior limb of the internal capsule on CT scan had more marked motor impariment with more involvement of the upper extremity than the lower extremity. 4) The recovery of the motor deficit was generally good, but unsatisfactory when the patient had a larger lesion than 10 mm in diameter. (author)

MO-F-304-01: Applying PDSA to a Practical Clinical Problem: Variation in Procedural Doses Among Interventional Radiologists

Energy Technology Data Exchange (ETDEWEB)

Jones, A. [UT MD Anderson Cancer Center (United States)

2015-06-15

With the current Maintenance of Certification (MOC) requirement for a practice quality improvement (PQI) project every 3 years, we all (well, most of us) find ourselves searching for projects that are both manageable and likely to have a positive impact on our clinical practice. In this session we will walk through the use of the Plan, Do, Study, Act (PDSA) cycle to address a common finding in practices where fluoroscopically guided interventions (FGI) are performed: variation in procedural doses among physicians. We will also examine strategies to secure physician support using carrots, not sticks. Learning Objectives: Review the PDSA cycle and its application to PQI. Discuss strategies for action in the example presented. Examine strategies for successful group PQI projects. A. Kyle Jones: Owner, FluoroSafety Joseph R. Steele: Consultant, FluoroSafety.

MO-F-304-01: Applying PDSA to a Practical Clinical Problem: Variation in Procedural Doses Among Interventional Radiologists

International Nuclear Information System (INIS)

Jones, A.

2015-01-01

With the current Maintenance of Certification (MOC) requirement for a practice quality improvement (PQI) project every 3 years, we all (well, most of us) find ourselves searching for projects that are both manageable and likely to have a positive impact on our clinical practice. In this session we will walk through the use of the Plan, Do, Study, Act (PDSA) cycle to address a common finding in practices where fluoroscopically guided interventions (FGI) are performed: variation in procedural doses among physicians. We will also examine strategies to secure physician support using carrots, not sticks. Learning Objectives: Review the PDSA cycle and its application to PQI. Discuss strategies for action in the example presented. Examine strategies for successful group PQI projects. A. Kyle Jones: Owner, FluoroSafety Joseph R. Steele: Consultant, FluoroSafety

A neurophysiological study of facial numbness in multiple sclerosis: Integration with clinical data and imaging findings.

Science.gov (United States)

Koutsis, Georgios; Kokotis, Panagiotis; Papagianni, Aikaterini E; Evangelopoulos, Maria-Eleftheria; Kilidireas, Constantinos; Karandreas, Nikolaos

2016-09-01

To integrate neurophysiological findings with clinical and imaging data in a consecutive series of multiple sclerosis (MS) patients developing facial numbness during the course of an MS attack. Nine consecutive patients with MS and recent-onset facial numbness were studied clinically, imaged with routine MRI, and assessed neurophysiologically with trigeminal somatosensory evoked potential (TSEP), blink reflex (BR), masseter reflex (MR), facial nerve conduction, facial muscle and masseter EMG studies. All patients had unilateral facial hypoesthesia on examination and lesions in the ipsilateral pontine tegmentum on MRI. All patients had abnormal TSEPs upon stimulation of the affected side, excepting one that was tested following remission of numbness. BR was the second most sensitive neurophysiological method with 6/9 examinations exhibiting an abnormal R1 component. The MR was abnormal in 3/6 patients, always on the affected side. Facial conduction and EMG studies were normal in all patients but one. Facial numbness was always related to abnormal TSEPs. A concomitant R1 abnormality on BR allowed localization of the responsible pontine lesion, which closely corresponded with MRI findings. We conclude that neurophysiological assessment of MS patients with facial numbness is a sensitive tool, which complements MRI, and can improve lesion localization. Copyright © 2016 Elsevier B.V. All rights reserved.

Low-dose single acquisition rest {sup 99m}Tc/stress {sup 201}Tl myocardial perfusion SPECT protocol: phantom studies and clinical validation

Energy Technology Data Exchange (ETDEWEB)

Dey, Thomas [RWTH Aachen University, Institute of Imaging and Computer Vision, Aachen (Germany); Backus, Barbra E.; Romijn, R.Leo [St. Antonius Hospital, Department of Nuclear Medicine, Nieuwegein (Netherlands); Wieczorek, Herfried [Philips Research, Eindhoven (Netherlands); Verzijlbergen, J.F. [St. Antonius Hospital, Department of Nuclear Medicine, Nieuwegein (Netherlands); Erasmus Medical Center, Department of Nuclear Medicine, Rotterdam (Netherlands)

2014-03-15

We developed and tested a single acquisition rest {sup 99m}Tc-sestamibi/stress {sup 201}Tl dual isotope protocol (SDI) with the intention of improving the clinical workflow and patient comfort of myocardial perfusion single photon emission computed tomography (SPECT). The technical feasibility of SDI was evaluated by a series of anthropomorphic phantom studies on a standard SPECT camera. The attenuation map was created by a moving transmission line source. Iterative reconstruction including attenuation correction, resolution recovery and Monte Carlo simulation of scatter was used for simultaneous reconstruction of dual tracer distribution. For clinical evaluation, patient studies were compared to stress {sup 99m}Tc and rest {sup 99m}Tc reference images acquired in a 2-day protocol. Clinical follow-up examinations like coronary angiography (CAG) and fractional flow reserve (FFR) were included in the assessment if available. Phantom studies demonstrated the technical feasibility of SDI. Artificial lesions inserted in the phantom mimicking ischaemia could be clearly identified. In 51/53 patients, the image quality was adequate for clinical evaluation. For the remaining two obese patients with body mass index > 32 the injected {sup 201}Tl dose of 74 MBq was insufficient for clinical assessment. In answer to this the {sup 201}Tl dose was adapted for obese patients in the rest of the study. In 31 patients, SDI and {sup 99m}Tc reference images resulted in equivalent clinical assessment. Significant differences were found in 20 patients. In 18 of these 20 patients additional examinations were available. In 15 patients the diagnosis based on the SDI images was confirmed by the results of CAG or FFR. In these patients the SDI images were more accurate than the {sup 99m}Tc reference study. In three patients minor ischaemic lesions were detected by SDI but were not confirmed by CAG. In one of these cases this was probably caused by pronounced apical thinning. For two patients

Clinical relevance and scope of accidental extracoronary findings in coronary computed tomography angiography: A cardiac versus thoracic FOV study

International Nuclear Information System (INIS)

Aglan, Iman; Jodocy, Daniel; Hiehs, Stefan; Soegner, Peter; Frank, Renate; Haberfellner, Berhard; Klauser, Andrea; Jaschke, Werner; Feuchtner, Gudrun M.

2010-01-01

Objective: To assess the spectrum and clinical relevance of extracoronary findings in coronary CT angiography (CCTA), and to compare a small (cardiac) field of view (FOV) to a large (thoracic) FOV setting. Material and methods: 1084 consecutive patients (mean 57 years) with low-to-intermediate risk of coronary artery disease were enrolled. 542 CCTA scans were interpreted with small FOV (160-190 mm 2 ) encompassing the cardiac region. In another 542 CCTA (patients matched for age and gender), read-out of an additional full FOV (>320 mm 2 ) covering the thorax was performed. Clinical relevance of extracoronary findings was considered as either 'significant' or 'non-significant'. 'Significant' findings were subclassified as either score 1: findings necessitating immediate therapeutic actions, or score 2: findings with undoubted clinical or prognostic relevance, requiring clinical awareness, follow-up or further investigations (non-urgent). 'Non-significant' findings were assigned to either score 3: findings not requiring follow-up or further tests, or as score 4: irrelevant incidental findings. Results: Significantly more patients with extracoronary findings were identified by using a full FOV with 43.2% (234/542) compared to a small FOV with 33.6% (182/542) (p = 0.001). Similarly, a higher total number of extracoronary findings (n = 394) was found on full FOV compared to small FOV (n = 250) (p 2 aortic valve orifice area. Conclusions: The interpretation of extracoronary findings on CCTA scans is mandatory given high prevalence of clinically significant findings by using a full 'thoracic' FOV.

Impact of Penicillin Allergy on Time to First Dose of Antimicrobial Therapy and Clinical Outcomes.

Science.gov (United States)

Conway, Erin L; Lin, Ken; Sellick, John A; Kurtzhalts, Kari; Carbo, James; Ott, Michael C; Mergenhagen, Kari A

2017-11-01

The objective of this study was to evaluate the impact of a listed penicillin allergy on the time to first dose of antibiotic in a Veterans Affairs hospital. Additional clinical outcomes of patients with penicillin allergies were compared with those of patients without a penicillin allergy. A retrospective chart review of veterans admitted through the emergency department with a diagnosis of pneumonia, urinary tract infection, bacteremia, and sepsis from January 2006 to December 2015 was conducted. The primary outcome was time to first dose of antibiotic treatment, defined as the time from when the patient presented to the emergency department to the medication administration time. Secondary outcomes included total antibiotic therapy duration and treatment outcomes, including mortality, length of stay, and 30-day readmission rate. A total of 403 patients were included in the final analysis; 57 patients (14.1%) had a listed penicillin allergy. The average age of the population was 75 years and 99% of the population was male. The mean time to first dose of antibiotic treatment for patients with a penicillin allergy was prolonged compared with those without a penicillin allergy (236.1 vs 186.6 minutes; P = 0.03), resulting in an approximately 50-minute delay. Penicillin-allergic patients were more likely to receive a carbapenem or fluoroquinolone antibiotic (P penicillin allergy had a prolonged time to first dose of antibiotic therapy. No significant differences were found in total antibiotic duration, length of stay, or 30-day readmission rate. The small sample size, older population, and single-center nature of this study may limit the generalizability of the present findings to other populations. Published by Elsevier Inc.

Open-label comparative clinical study of chlorproguanil-dapsone fixed dose combination (Lapdap alone or with three different doses of artesunate for uncomplicated Plasmodium falciparum malaria.

Directory of Open Access Journals (Sweden)

Daniel G Wootton

2008-03-01

Full Text Available The objective of this study was to determine the appropriate dose of artesunate for use in a fixed dose combination therapy with chlorproguanil-dapsone (CPG-DDS for the treatment of uncomplicated falciparum malaria.Open-label clinical trial comparing CPG-DDS alone or with artesunate 4, 2, or 1 mg/kg at medical centers in Blantyre, Malawi and Farafenni, The Gambia. The trial was conducted between June 2002 and February 2005, including 116 adults (median age 27 years and 107 children (median age 38 months with acute uncomplicated Plasmodium falciparum malaria. Subjects were randomized into 4 groups to receive CPG-DDS alone or plus 4, 2 or 1 mg/kg of artesunate once daily for 3 days. Assessments took place on Days 0-3 in hospital and follow-up on Days 7 and 14 as out-patients. Efficacy was evaluated in the Day 3 per-protocol (PP population using mean time to reduce baseline parasitemia by 90% (PC90. A number of secondary outcomes were also included. Appropriate artesunate dose was determined using a pre-defined decision matrix based on primary and secondary outcomes. Treatment emergent adverse events were recorded from clinical assessments and blood parameters. Safety was evaluated in the intent to treat (ITT population.In the Day 3 PP population for the adult group (N = 85, mean time to PC90 was 19.1 h in the CPG-DDS group, significantly longer than for the +artesunate 1 mg/kg (12.5 h; treatment difference -6.6 h [95%CI -11.8, -1.5], 2 mg/kg (10.7 h; -8.4 h [95%CI -13.6, -3.2] and 4 mg/kg (10.3 h; -8.7 h [95%CI -14.1, -3.2] groups. For children in the Day 3 PP population (N = 92, mean time to PC90 was 21.1 h in the CPG-DDS group, similar to the +artesunate 1 mg/kg group (17.7 h; -3.3 h [95%CI -8.6, 2.0], though the +artesunate 2 mg/kg and 4 mg/kg groups had significantly shorter mean times to PC90 versus CPG-DDS; 14.4 h (treatment difference -6.4 h [95%CI -11.7, -1.0] and 12.8 h (-7.4 h [95%CI -12.9, -1.8], respectively. An analysis of mean time

Dose proportionality and pharmacokinetics of carvedilol sustained-release formulation: a single dose-ascending 10-sequence incomplete block study

Directory of Open Access Journals (Sweden)

Kim YH

2015-06-01

Full Text Available Yo Han Kim,1 Hee Youn Choi,1 Yook-Hwan Noh,1 Shi Hyang Lee,1 Hyeong-Seok Lim,1 Chin Kim,2 Kyun-Seop Bae11Department of Clinical Pharmacology and Therapeutics, College of Medicine, University of Ulsan, Asan Medical Center, 2Chong Kun Dang Clinical Research and Clinical Epidemiology and Medical Information, CKD Pharmaceuticals, Seoul, Republic of KoreaBackground: Carvedilol is a third-generation β-blocker indicated for congestive heart failure and high blood pressure. The aim of this study was to investigate the dose proportionality of the carvedilol sustained-release (SR formulation in healthy male subjects.Methods: An open-label, single dose-ascending, 10-sequence, 3-period balanced incomplete block study was performed using healthy male subjects. In varying sequences, each subject received three of five carvedilol SR formulations (8, 16, 32, 64, or 128 mg once. The treatment periods were separated by a washout period of 7 days. Serial blood samples were collected up to 48 h after dosing. The plasma concentrations of carvedilol were determined by using validated liquid chromatography–tandem mass spectrometry. Pharmacokinetic parameters including the area under the plasma concentration–time curve (AUC from time 0 to the last measurable time (AUClast, AUC extrapolated to infinity (AUCinf, and the measured peak plasma concentration (Cmax were obtained by noncompartmental analysis. Dose proportionality was evaluated if the ln–ln plots of AUClast, AUCinf, and Cmax versus dose were linear and the 90% confidence intervals (CIs of the slopes were within 0.9195 and 1.0805. Tolerability was assessed by vital signs, electrocardiogram, clinical laboratory tests, and monitoring of adverse events (AEs throughout the study.Results: A total of 31 subjects were enrolled, and 30 completed the study. The assessment of dose proportionality meets the statistical criteria; the point estimates of slope were 1.0104 (90% CI: 0.9849–1.0359 for AUClast, 1

Prospective Evaluation to Establish a Dose Response for Clinical Oral Mucositis in Patients Undergoing Head-and-Neck Conformal Radiotherapy

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Narayan, Samir; Lehmann, Joerg; Coleman, Matthew A.; Vaughan, Andrew; Yang, Claus Chunli; Enepekides, Danny; Farwell, Gregory; Purdy, James A.; Laredo, Grace; Nolan, Kerry A.S.; Pearson, Francesca S.; Vijayakumar, Srinivasan

2008-01-01

Purpose: We conducted a clinical study to correlate oral cavity dose with clinical mucositis, perform in vivo dosimetry, and determine the feasibility of obtaining buccal mucosal cell samples in patients undergoing head-and-neck radiation therapy. The main objective is to establish a quantitative dose response for clinical oral mucositis. Methods and Materials: Twelve patients undergoing radiation therapy for head-and-neck cancer were prospectively studied. Four points were chosen in separate quadrants of the oral cavity. Calculated dose distributions were generated by using AcQPlan and Eclipse treatment planning systems. MOSFET dosimeters were used to measure dose at each sampled point. Each patient underwent buccal sampling for future RNA analysis before and after the first radiation treatment at the four selected points. Clinical and functional mucositis were assessed weekly according to National Cancer Institute Common Toxicity Criteria, Version 3. Results: Maximum and average doses for sampled sites ranged from 7.4-62.3 and 3.0-54.3 Gy, respectively. A cumulative point dose of 39.1 Gy resulted in mucositis for 3 weeks or longer. Mild severity (Grade ≤ 1) and short duration (≤1 week) of mucositis were found at cumulative point doses less than 32 Gy. Polymerase chain reaction consistently was able to detect basal levels of two known radiation responsive genes. Conclusions: In our sample, cumulative doses to the oral cavity of less than 32 Gy were associated with minimal acute mucositis. A dose greater than 39 Gy was associated with longer duration of mucositis. Our technique for sampling buccal mucosa yielded sufficient cells for RNA analysis using polymerase chain reaction

Epidemiology, etiology and study of clinical findings of headache

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Ghaffarpoor M

1998-09-01

Full Text Available In a cross-sectional epidemiological study of headache disorders in neurology clinic of Fatemieh hospital of Semnan (August 22-November 20.1996, information on types of headaches, quality, severity, location, duration, frequency, precipitating factors, age of onset, influence of menstruation and pregnancy, positive familial history, use of oral contraceptive pills and other epidemiological factors including socioeconomic and age/sex composition was collected. The presence of any types of headaches was ascertained by a clinical interview and examination using the operational diagnostic criteria of the International Headaches Society. The prevalence of migraine and tension type headache was also analysed in relation to variables of life style (physical activity and sleep pattern and associated signs and symptoms (nausea, vomiting, photophobia and phonophobia. In this study migraine and tension headache were also compared in variable aspects with each other. 1 Headache was more prevalent in women than men (F/M=3/1. 2 The most common types of headache included: tension type headache (41.4%, migraine (31.2% and unclassified headaches (17.2%. 3 Migraine and T.T.H were more prevalent in early adult life and middle ages. 4 In both migraine and tension type headache the time profiles (duration, frequency, age of onset, quality and location were like that noted in textbook and previous studies. 5 In both migraine and tension type headache the most conspicuous precipitating factor was stress and mental tension and frequent headaches were accompanied with psychiatric problems (e.g depression and or anxiety. 6 Nausea, vomiting, phonophobia and photophobia were the most common associated symptoms in both of them. 7 Positive familial history and aggravation of headache in perimenstual period were more commonly seen in patients with migraine than tension type headache. In conclusion using the operational diagnostic criteria of International Headache Society in

Clinical Coenurosis (Coenurus Cerebralis and Associated Pathological Findings in a Calf

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Cumali Özkan*, Serkan Yildirim1 and Abdullah Kaya

2011-06-01

Full Text Available This study aims to investigate clinical and pathological findings of a clinical Coenurus cerebralis case in a 10-month-old Simmental male calf. Clinical examination of the calf revealed incoordination, irregular gait, failure to hold the head straight, leftward head tilt, and circling. The animal was diagnosed with C. cerebralis and euthanazia was recommended. The autopsy demonstrated a cyst (9x7 cm in the caudal of the left cerebral hemisphere within the cranium. The cyst caused compression over the ventral portion of the left cerebral hemisphere, while a marked perforation of 3-4 cm diameter was found on the sphenoid bone. Histopathologically, hyperemia and perivascular mononuclear cell infiltration were observed. In conclusion, we found it beneficial to present the clinical and pathological findings of this calf infected with C. cerebralis which is known to be a rare clinical entity among cattle.

Clinical review: Optimal dose of continuous renal replacement therapy in acute kidney injury.

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Prowle, John R; Schneider, Antoine; Bellomo, Rinaldo

2011-01-01

Continuous renal replacement therapy (CRRT) is the preferred treatment for acute kidney injury in intensive care units (ICUs) throughout much of the world. Despite the widespread use of CRRT, controversy and center-specific practice variation in the clinical application of CRRT continue. In particular, whereas two single-center studies have suggested survival benefit from delivery of higher-intensity CRRT to patients with acute kidney injury in the ICU, other studies have been inconsistent in their results. Now, however, two large multi-center randomized controlled trials - the Veterans Affairs/National Institutes of Health Acute Renal Failure Trial Network (ATN) study and the Randomized Evaluation of Normal versus Augmented Level (RENAL) Replacement Therapy Study - have provided level 1 evidence that effluent flow rates above 25 mL/kg per hour do not improve outcomes in patients in the ICU. In this review, we discuss the concept of dose of CRRT, its relationship with clinical outcomes, and what target optimal dose of CRRT should be pursued in light of the high-quality evidence now available.

Central image archiving and managements system for multicenter clinical studies: Lessons from low-dose CT for appendicitis trial

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Ko, You Sun; Lee, Kyong Joon; Lee, Kyoung Ho [Dept. of Radiology, Seoul National University Bundang Hospital, Seongnam (Korea, Republic of); and others

2017-03-15

This special report aimed to document our experiences in implementing the Central Imaging Archiving and Management System (CIAMS) for a multicenter clinical trial, Low-dose CT for Appendicitis Trial (LOCAT), supported by the Korean Society of Radiology and Radiology Imaging Network of Korea for Clinical Research. LOCAT was a randomized controlled trial to determine whether low-dose CT is non-inferior to standard-dose CT with respect to the negative appendectomy rate in patients aged from 15 to 44 years. Site investigators downloaded the CT images from the site picture archiving and communication system servers, and uploaded the anonymized images to the primary server. CIAMS administrators inspected the images routed to the secondary server by a cross-check against image submission worksheets provided by the site investigators. The secondary server was automatically synchronized to the tertiary backup server. Up to June 2016, 2715 patients from 20 sites participated in LOCAT for 30 months. A total of 2539 patients' images (93.5%, 2539/2715) were uploaded to the primary server, 2193 patients' worksheets (80.8%, 2193/2715) were submitted, and 2163 patients' data (79.7%, 2163/2715) were finally monitored. No data error occurred.

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

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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.

A comparison of entrance skin dose delivered by clinical angiographic c-arms using the real-time dosimeter: the MOSkin

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Thorpe, Nathan K.; Cutajar, Dean; Lian, Cheryl; Rosenfeld, Anatoly; Pitney, Mark; Friedman, Daniel; Perevertaylo, Vladimir

2016-01-01

Coronary angiography is a procedure used in the diagnosis and intervention of coronary heart disease. The procedure is often considered one of the highest dose diagnostic procedures in clinical use. Despite this, there is minimal use of dosimeters within angiographic catheterisation laboratories due to challenges resulting from their implementation. The aim of this study was to compare entrance dose delivery across locally commissioned c-arms to assess the need for real-time dosimetry solutions during angiographic procedures. The secondary aim of this study was to establish a calibration method for the MOSkin dosimeter that accurately produces entrance dose values from the clinically sampled beam qualities and energies. The MOSkin is a real-time dosimeter used to measure the skin dose delivered by external radiation beams. The suitability of the MOSkin for measurements in the angiographic catheterisation laboratory was assessed. Measurements were performed using a 30 × 30 × 30cm 3 PMMA phantom positioned at the rotational isocenter of the c-arm gantry. The MOSkin calibration factor was established through comparison of the MOSkin response to EBT2 film response. Irradiation of the dosimeters was performed using several clinical beam qualities ranging in energy from 70 to 105 kVp. A total of four different interventional c-arm machines were surveyed and compared using the MOSkin dosimeter. The phantom was irradiated from a normal angle of incidence using clinically relevant protocols, field sizes and source to image detector distance values. The MOSkin was observed to be radiotranslucent to the c-arm beam in all clinical environments. The MOSkin response was reproducible to within 2 % of the average value across repeated measurements for each beam setting. There were large variations in entrance dose delivery to the phantom between the different c-arm machines with the highest observed cine-acquisition entrance dose rate measuring 326 % higher than the lowest

Ocular pharmacokinetics and tolerability of bimatoprost ophthalmic solutions administered once or twice daily in rabbits, and clinical dosing implications

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Shen, Jie; Goodkin, Margot L; Tong, Warren; Attar, Mayssa

2017-01-01

Purpose Fixed-combination medications can benefit patients requiring multiple agents to lower their intraocular pressure (IOP), but combining agents with complementary mechanisms of action is challenging if their dosing frequency differs. This study compares in vivo pharmacokinetic and ocular tolerability of bimatoprost 0.01% ophthalmic solutions dosed once or twice daily. Reports of twice-daily dosing in glaucoma patients are also reviewed. Methods New Zealand White rabbits were administered bimatoprost 0.01% monotherapy or fixed-combination bimatoprost 0.01%/brimonidine 0.1%, once or twice daily in both eyes for 4 days. Ocular tissues were harvested and analyzed by liquid chromatography-tandem mass spectrometry. The pharmacokinetic parameters calculated included maximum observed concentration, time to maximum concentration, and area under the concentration-time curve. Results Due to extensive metabolism, bimatoprost concentration was below the quantitation limit by 1 hour post-dose in all samples. Bimatoprost acid exposure, however, could be measured up to 6–8 hours post-dose and was similar in the aqueous humor and iris-ciliary body (pharmacological site of action) of animals treated once or twice daily with either bimatoprost 0.01% or fixed-combination bimatoprost 0.01%/brimonidine 0.1%. Increasing dosage frequency in rabbits did not raise the incidence of drug-related conjunctival hyperemia (most common adverse event associated with bimatoprost use in humans), suggesting comparable ocular tolerability of the once- and twice-daily regimens for each formulation. Conclusion Bimatoprost 0.01% administered once or twice daily as monotherapy and in fixed-combination with brimonidine 0.1% in rabbits show similar pharmacokinetic profiles of bimatoprost acid, especially in the iris-ciliary body. Key findings from previous clinical studies suggest that by varying the concentration of benzalkonium chloride (a preservative with corneal penetration-enhancing properties

Polysomnographic Findings and Clinical Correlates in Huntington Disease: A Cross-Sectional Cohort Study

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Piano, Carla; Losurdo, Anna; Della Marca, Giacomo; Solito, Marcella; Calandra-Buonaura, Giovanna; Provini, Federica; Bentivoglio, Anna Rita; Cortelli, Pietro

2015-01-01

Study Objectives: To evaluate the sleep pattern and the motor activity during sleep in a cohort of patients affected by Huntington disease (HD). Design: Cross-sectional cohort study. Setting: Sleep laboratory. Patients: Thirty HD patients, 16 women and 14 men (mean age 57.3 ± 12.2 y); 30 matched healthy controls (mean age 56.5 ± 11.8 y). Interventions: Subjective sleep evaluation: Epworth Sleepiness Scale (ESS); Berlin's Questionnaire, interview for restless legs syndrome (RLS), questionnaire for REM sleep behavior disorder (RBD). Clinical evaluation: disease duration, clinical severity (unified Huntington disease motor rating scale [UHDMRS]), genetic tests. Laboratory-based full-night attended video-polysomnography (V-PSG). Measurements and Results: The duration of the disease was 9.4 ± 4.4 y, UHMDRS score was 55.5 ± 23.4, CAG repeats were 44.3 ± 4.1. Body mass index was 21.9 ± 4.0 kg/m2. No patients or caregivers reported poor sleep quality. Two patients reported symptoms of RLS. Eight patients had an ESS score ≥ 9. Eight patients had high risk of obstructive sleep apnea. At the RBD questionnaire, two patients had a pathological score. HD patients, compared to controls, showed shorter sleep, reduced sleep efficiency index, and increased arousals and awakenings. Four patients presented with sleep disordered breathing (SDB). Periodic limb movements (PLMs) during wake and sleep were observed in all patients. No episode of RBD was observed in the V-PSG recordings, and no patients showed rapid eye movement (REM) sleep without atonia. The disease duration correlated with ESS score (P Marca G, Solito M, Calandra-Buonaura G, Provini F, Bentivoglio AR, Cortelli P. Polysomnographic findings and clinical correlates in Huntington disease: a cross-sectional cohort study. SLEEP 2015;38(9):1489–1495. PMID:25845698

ACCEPTABILITY OF ULTRA LOW-DOSE ORAL CONTRACEPTIVES CONTAINING 20 µg ETHINYL ESTRADIOL AND 75 µg GESTODENE IN YOUNG FEMALES IN A MULTICENTER CLINICAL STUDY

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Bojana Pinter

2004-06-01

Full Text Available Background. The acceptability of ultra low-dose oral contraception (OC among young females after three and six cycles of treatment was assessed.Methods. In the clinical prospective study, carried out in 10 outpatient clinics in Slovenia, 240 healthy women aged 16– 30 years choosing ultra low-dose OC (20 µg ethinyl estradiol and 75 µg gestodene were included.Results. The average age was 20.6 (± 3.5 years. After three cycles (N = 228 there were no changes in body weight or blood pressure; one tenth (9.6% of women reported irregular bleeding and 3.9% weight gain while other side effects occurred rarely. After three cycles 88.3% of the women initially included continued OC use (5% discontinued the use due to side effects. After six cycles (N = 195 there were no changes in blood pressure; body weight statistically significantly increased for 0.5 kg providing the weight changes during the time were not considered. Fewer women reported side effects (3.6% irregular bleeding, 2.6% weight gain and rarely other side effects. After six cycles 75.0% of the women initially included continued the OC use (7.5% discontinued the use due to the side effects.Conclusions. The study has shown good clinical acceptability of ultra low-dose OC by young females.

Clinical, laboratory, and hemostatic findings in cats with naturally occurring sepsis.

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Klainbart, Sigal; Agi, Limor; Bdolah-Abram, Tali; Kelmer, Efrat; Aroch, Itamar

2017-11-01

OBJECTIVE To characterize clinical and laboratory findings in cats with naturally occurring sepsis, emphasizing hemostasis-related findings, and evaluate these variables for associations with patient outcomes. DESIGN Prospective, observational, clinical study. ANIMALS 31 cats with sepsis and 33 healthy control cats. PROCEDURES Data collected included history; clinical signs; results of hematologic, serum biochemical, and hemostatic tests; diagnosis; and outcome (survival vs death during hospitalization or ≤ 30 days after hospital discharge). Differences between cats with and without sepsis and associations between variables of interest and death were analyzed statistically. RESULTS The sepsis group included cats with pyothorax (n = 10), septic peritonitis (7), panleukopenia virus infection (5), bite wounds (5), abscesses and diffuse cellulitis (3), and pyometra (1). Common clinical abnormalities included dehydration (21 cats), lethargy (21), anorexia (18), pale mucous membranes (15), and dullness (15). Numerous clinicopathologic abnormalities were identified in cats with sepsis; novel findings included metarubricytosis, hypertriglyceridemia, and high circulating muscle enzyme activities. Median activated partial thromboplastin time and plasma D-dimer concentrations were significantly higher, and total protein C and antithrombin activities were significantly lower, in the sepsis group than in healthy control cats. Disseminated intravascular coagulopathy was uncommon (4/22 [18%] cats with sepsis). None of the clinicopathologic abnormalities were significantly associated with death on multivariate analysis. CONCLUSIONS AND CLINICAL RELEVANCE Cats with sepsis had multiple hematologic, biochemical, and hemostatic abnormalities on hospital admission, including several findings suggestive of hemostatic derangement. Additional research including larger numbers of cats is needed to further investigate these findings and explore associations with outcome.

Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for Pharmacogenetics-Guided Warfarin Dosing: 2017 Update.

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Johnson, J A; Caudle, K E; Gong, L; Whirl-Carrillo, M; Stein, C M; Scott, S A; Lee, M T; Gage, B F; Kimmel, S E; Perera, M A; Anderson, J L; Pirmohamed, M; Klein, T E; Limdi, N A; Cavallari, L H; Wadelius, M

2017-09-01

This document is an update to the 2011 Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for CYP2C9 and VKORC1 genotypes and warfarin dosing. Evidence from the published literature is presented for CYP2C9, VKORC1, CYP4F2, and rs12777823 genotype-guided warfarin dosing to achieve a target international normalized ratio of 2-3 when clinical genotype results are available. In addition, this updated guideline incorporates recommendations for adult and pediatric patients that are specific to continental ancestry. © 2017 American Society for Clinical Pharmacology and Therapeutics.

Tg.rasH2 Mice and not CByB6F1 Mice Should Be Used for 28-Day Dose Range Finding Studies Prior to 26-Week Tg.rasH2 Carcinogenicity Studies.

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Paranjpe, Madhav G; Belich, Jessica; Vidmar, Tom J; Elbekai, Reem H; McKeon, Marie; Brown, Caren

Our recent retrospective analysis of data, collected from 29 Tg.rasH2 mouse carcinogenicity studies, determined how successful the strategy of choosing the high dose for the 26-week studies was based on the estimated maximum tolerated dose (EMTD) derived from earlier 28-day dose range finding (DRF) studies conducted in CByB6F1 mice. Our analysis demonstrated that the high doses applied at EMTD in the 26-week Tg.rasH2 studies failed to detect carcinogenic effects. To investigate why the dose selection process failed in the 26-week carcinogenicity studies, the initial body weights, terminal body weights, body weight gains, food consumption, and mortality from the first 4 weeks of 26-week studies with Tg.rasH2 mice were compared with 28-day DRF studies conducted with CByB6F1 mice. Both the 26-week and the earlier respective 28-day studies were conducted with the exact same vehicle, test article, and similar dose levels. The analysis of our results further emphasizes that the EMTD and subsequent lower doses, determined on the basis of the 28-day studies in CByB6F1 mice, may not be an accurate strategy for selecting appropriate dose levels for the 26-week carcinogenicity studies in Tg.rasH2 mice. Based on the analysis presented in this article, we propose that the Tg.rasH2 mice and not the CByB6F1 mice should be used in future DRF studies. The Tg.rasH2 mice demonstrate more toxicity than the CByB6F1 mice, possibly because of their smaller size compared to CByB6F1 mice. Also, the Tg.rasH2 males appear to be more sensitive than the female Tg.rasH2 mice.

Clinical relevance and scope of accidental extracoronary findings in coronary computed tomography angiography: A cardiac versus thoracic FOV study

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Aglan, Iman; Jodocy, Daniel; Hiehs, Stefan; Soegner, Peter; Frank, Renate; Haberfellner, Berhard; Klauser, Andrea; Jaschke, Werner [Department of Radiology II, Innsbruck Medical University, Innsbruck (Austria); Feuchtner, Gudrun M. [Department of Radiology II, Innsbruck Medical University, Innsbruck (Austria)], E-mail: Gudrun.Feuchtner@i-med.ac.at

2010-04-15

Objective: To assess the spectrum and clinical relevance of extracoronary findings in coronary CT angiography (CCTA), and to compare a small (cardiac) field of view (FOV) to a large (thoracic) FOV setting. Material and methods: 1084 consecutive patients (mean 57 years) with low-to-intermediate risk of coronary artery disease were enrolled. 542 CCTA scans were interpreted with small FOV (160-190 mm{sup 2}) encompassing the cardiac region. In another 542 CCTA (patients matched for age and gender), read-out of an additional full FOV (>320 mm{sup 2}) covering the thorax was performed. Clinical relevance of extracoronary findings was considered as either 'significant' or 'non-significant'. 'Significant' findings were subclassified as either score 1: findings necessitating immediate therapeutic actions, or score 2: findings with undoubted clinical or prognostic relevance, requiring clinical awareness, follow-up or further investigations (non-urgent). 'Non-significant' findings were assigned to either score 3: findings not requiring follow-up or further tests, or as score 4: irrelevant incidental findings. Results: Significantly more patients with extracoronary findings were identified by using a full FOV with 43.2% (234/542) compared to a small FOV with 33.6% (182/542) (p = 0.001). Similarly, a higher total number of extracoronary findings (n = 394) was found on full FOV compared to small FOV (n = 250) (p < 0.001). The detection rate of clinically significant findings was higher by using full FOV compared to small FOV (25.6% versus 15.4%) (p < 0.001), out of those 2.2% versus 1.8% of findings required immediate actions (score 1), and 23.4% versus 13.6% (p = 0.0001), respectively were of clinical relevance (non-urgent, score 2). The rate of malign findings was 0.2%, and of acute pulmonary embolism 0.1%. More lung pathologies were observed by using full FOV compared to small FOV (22% versus 7%) (p < 0.0001), and the detection rate of

Comparison of antiplatelet activity of garlic tablets with cardio-protective dose of aspirin in healthy volunteers: a randomized clinical trial

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Mojtaba Shafiekhani

2016-08-01

Full Text Available Objective: Some of the adverse effects of aspirin including peptic ulcers, gastrointestinal bleeding and aspirin resistance compelled researchers to find a suitable alternative with fewer adverse effects. In this clinical trial, we aimed to find the effective antiplatelet dose of garlic. Materials and Methods: This randomized controlled clinical trial (RCT was conducted on 62 healthy volunteers of 20-50 years old. All volunteers used 80 mg aspirin per day for 1 week and at the end of this time, platelet aggregation (PA induced by 4 agonists acting in aggregation pathway including adenosinediphosphate (20 μmol/l, epinephrine (20 μmol/l, collagen(0.19 mg/ ml and arachidonic acid (0.5mg/ ml was measured by Light Transmittance Aggregometry (LTA in all participants. After one month washout period, volunteers were randomized into 3 groups and each received 1, 2 or 3 garlic tablets (1250 mg a day for 1 month. After one month, PA was examined in all groups. Results: The mean ±SD of the age of all volunteers was 28.60 ± 9.00 years. In addition, 52.00 % of our volunteers were male and 48.00% of them were female. Garlic tablet didnot have significant effect on PA at any dose. However, 30% of volunteers in the group that used 3 garlic tablets/day reported adverse effect (i.e. bleeding. No significant association between sex, age and PA was observed. Conclusion:  In this study, we were unable to determine the effective anti-platelet dose of garlic which that could be equal to that of aspirin anti-platelet activity, as assessed LTA method.

Water syphon test and gastrooesophageal reflux during childhood (correlation with the clinical findings and oesophageal manometry)

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Fotter, R.; Hoellwarth, M.

1981-07-01

The water syphon test is a simple and easily performed method for demonstrating gastro-oesophageal reflux with a high degree of reliability. It is carried out following a conventional barium swallow. Compared with clinical findings and oesophageal manometry, the water syphon test is very reliable for demonstrating gastro-oesophageal reflux during childhood. Prolonged irradiation in order to see spontaneous reflux becomes unnecessary. This results in a significant reduction in radiation dose. Barium swallow and the water syphon test are the most useful initial examinations in children with symptoms which suggest reflux.

Clinical diagnosis versus autopsy findings in polytrauma fatalities

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Fakler Johannes K

2010-10-01

Full Text Available Abstract Objectives The aim of the study was to determine if differences in clinical diagnosis versus autopsy findings concerning the cause of death in polytrauma fatalities would be detected in 19 cases of fatal polytrauma from a Level 1 trauma centre. Methods Clinical diagnoses determining the cause of death in 19 cases of fatal polytrauma (2007 - 2008 from a Level 1 trauma centre were correlated with autopsy findings. Results In 13 cases (68%, the clinical cause of death and the cause of death as determined by autopsy were congruent. Marginal differences occurred in three (16% patients while obvious differences in interpreting the cause of death were found in another three (16% cases. Five fatalities (three with obvious differences and two with marginal differences were remarked as early death (1-4 h after trauma and one fatality with marginal differences as late death (>1 week after trauma. Obvious and marginal discrepancies mostly occurred in the early phase of treatment, especially when severely injured patients were admitted to the emergency room undergoing continued cardiopulmonary resuscitation, i. e. limiting diagnostic procedures, and thus the clinical cause of death was essentially determined by basic emergency diagnostics. Conclusions Autopsy as golden standard to define the cause of death in fatal polytrauma varies from the clinical point of view, depending on the patient's pre-existing condition, mechanism of polytrauma, necessity of traumatic cardiopulmonary resuscitation, survival time, and thus the possibility to perform emergency diagnostics. An autopsy should be performed at least in cases of early fatal polytrauma to help establishing the definite cause of death. Moreover, autopsy data should be included in trauma registries as a quality assessment tool.

Efficacy and Safety of Daikenchuto for Constipation and Dose-Dependent Differences in Clinical Effects

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Tatsuya Hirose

2018-01-01

Full Text Available Background. Daikenchuto (DKT is a Kampo medicine used for the treatment of constipation. In this study, we evaluated the effectiveness of DKT against constipation. Patients and Methods. Thirty-three patients administered DKT for constipation were selected and divided into low-dose (7.5 g DKT; n=22 and high-dose (15 g DKT; n=11 groups. We retrospectively evaluated weekly defaecation frequency, side effects, and clinical laboratory data. Results. Median defaecation frequencies after DKT administration (5, 5.5, 5, and 8 for the first, second, third, and fourth weeks, resp. were significantly higher than that before DKT administration (2 in all 33 cases (P<0.01. One case (3% of watery stool, one case of loose stools (3%, and no cases of abdominal pain (0% were observed. Median defaecation frequencies in the high-dose group (7 and 9 were significantly higher than those in the low-dose group (4 and 3 in the first (P=0.0133 and second (P=0.0101 weeks, respectively. There was no significant change in clinical laboratory values. Conclusion. We suggest that DKT increases defaecation frequency and is safe for treating constipation.

Peritoneal Nebulization of Ropivacaine during Laparoscopic Cholecystectomy: Dose Finding and Pharmacokinetic Study

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Massimo Allegri

2017-01-01

Full Text Available Background. Intraperitoneal nebulization of ropivacaine reduces postoperative pain and morphine consumption after laparoscopic surgery. The aim of this multicenter double-blind randomized controlled trial was to assess the efficacy of different doses and dose-related absorption of ropivacaine when nebulized in the peritoneal cavity during laparoscopic cholecystectomy. Methods. Patients were randomized to receive 50, 100, or 150 mg of ropivacaine 1% by peritoneal nebulization through a nebulizer. Morphine consumption, pain intensity in the abdomen, wound and shoulder, time to unassisted ambulation, discharge time, and adverse effects were collected during the first 48 hours after surgery. The pharmacokinetics of ropivacaine was evaluated using high performance liquid chromatography. Results. Nebulization of 50 mg of ropivacaine had the same effect of 100 or 150 mg in terms of postoperative morphine consumption, shoulder pain, postoperative nausea and vomiting, activity resumption, and hospital discharge timing (>0.05. Plasma concentrations did not reach toxic levels in any patient, and no significant differences were observed between groups (P>0.05. Conclusions. There is no enhancement in analgesic efficacy with higher doses of nebulized ropivacaine during laparoscopic cholecystectomy. When administered with a microvibration-based aerosol humidification system, the pharmacokinetics of ropivacaine is constant and maintains an adequate safety profile for each dosage tested.

Saturated norepinephrine transporter occupancy by atomoxetine relevant to clinical doses: a rhesus monkey study with (S,S)-[{sup 18}F]FMeNER-D{sub 2}

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Takano, Akihiro; Gulyas, Balazs; Varrone, Andrea; Halldin, Christer [Karolinska Institutet, Department of Clinical Neuroscience, Psychiatry Section, Stockholm (Sweden); Maguire, Ralph Paul [Pfizer Global Research and Development, New London, CT (United States); Novartis Institutes for BioMedical Research, Basel (Switzerland)

2009-08-15

In a previous PET study on norepinephrine transporter (NET) occupancy in the nonhuman primate brain, the relationship between NET occupancy and atomoxetine plasma concentration, and occupancies among different brain regions, were not demonstrated adequately. It may therefore be difficult to translate the results to the clinical situations. In the present study, the detailed change of NET occupancy was investigated among a wider range of doses in a more advanced manner. Two rhesus monkeys were examined using a high-resolution PET system with (S,S)-[{sup 18}F]FMeNER-D{sub 2} under baseline conditions and after steady-state infusion of different doses of atomoxetine (0.003 to 0.12 mg/kg per hour). NET occupancy of the thalamus, brainstem and anterior cingulate cortex was calculated using BP{sub ND} obtained with the simplified reference tissue model. NET occupancy increased regionally and uniformly as the plasma concentration of atomoxetine increased. The estimated Kd value (the amount to occupy 50% of NET) in the thalamus was 16 ng/ml. The results indicate that clinical doses of atomoxetine would occupy NET almost completely. (orig.)

Clinical and symptomatological study of pigs subjected to a lethal dose of integral gamma irradiation; Etude clinique et symptomatologique chez le porc soumis a une irradiation gamma totale a dose letale

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Vaiman, M; Guenet, J -L; Maas, J; Nizza, P

1966-05-01

Results are reported from a clinical and haematological study on a Corsican species of pigs wholly exposed to an approximately lethal dose of {gamma} radiation. The aim of this work was to examine the changes in the irradiation syndrome of irradiation for pigs to make it thus possible to devise further experiments, in particular in the therapeutic field. The dose received was 285 rads (measured as the absorption in the vertical antero-posterior medial plane). Data are presented on cyto-haematological changes in the blood circulating immediately after irradiation, and followed up to death, and changes in the medullary cytology after irradiation. The clinical picture of lethal radiation injury in swine is described. (authors) [French] Les auteurs rapportent les resultats d'une etude clinique et hematologique chez des porcs de race corse irradies in toto a dose sensiblement letale. Le but de cette etude etait de connaitre l'evolution du syndrome aigu d'irradiation chez le porc et de permettre ainsi le developpement d'experimentations ulterieures, en particulier dans le domaine therapeutique. La dose delivree etait de 285 rad (en dose absorbee au niveau du plan median vertical anteroposterieur. L'etude a porte essentiellement: 1. Sur les modifications cyclo-hematologiques du sang circulant immediatement apres l'irradiation, pour les differentes lignees cellulaires; l'evolution de ces modifications a ete notee jusqu'a la mort; 2. Sur les modifications de la cytologie medullaire apres irradiation (evolution du myelogramme et essai d'evaluation de la cellularite de la moelle osseuse);: 3. Sur les signes cliniques, d'ailleurs tres discrets, observes chez les porcs apres irradiation. (auteurs)

Clinical and symptomatological study of pigs subjected to a lethal dose of integral gamma irradiation; Etude clinique et symptomatologique chez le porc soumis a une irradiation gamma totale a dose letale

Energy Technology Data Exchange (ETDEWEB)

Vaiman, M.; Guenet, J.-L.; Maas, J.; Nizza, P

1966-05-01

Results are reported from a clinical and haematological study on a Corsican species of pigs wholly exposed to an approximately lethal dose of {gamma} radiation. The aim of this work was to examine the changes in the irradiation syndrome of irradiation for pigs to make it thus possible to devise further experiments, in particular in the therapeutic field. The dose received was 285 rads (measured as the absorption in the vertical antero-posterior medial plane). Data are presented on cyto-haematological changes in the blood circulating immediately after irradiation, and followed up to death, and changes in the medullary cytology after irradiation. The clinical picture of lethal radiation injury in swine is described. (authors) [French] Les auteurs rapportent les resultats d'une etude clinique et hematologique chez des porcs de race corse irradies in toto a dose sensiblement letale. Le but de cette etude etait de connaitre l'evolution du syndrome aigu d'irradiation chez le porc et de permettre ainsi le developpement d'experimentations ulterieures, en particulier dans le domaine therapeutique. La dose delivree etait de 285 rad (en dose absorbee au niveau du plan median vertical anteroposterieur. L'etude a porte essentiellement: 1. Sur les modifications cyclo-hematologiques du sang circulant immediatement apres l'irradiation, pour les differentes lignees cellulaires; l'evolution de ces modifications a ete notee jusqu'a la mort; 2. Sur les modifications de la cytologie medullaire apres irradiation (evolution du myelogramme et essai d'evaluation de la cellularite de la moelle osseuse);: 3. Sur les signes cliniques, d'ailleurs tres discrets, observes chez les porcs apres irradiation. (auteurs)

Optimizing adaptive design for Phase 2 dose-finding trials incorporating long-term success and financial considerations: A case study for neuropathic pain.

Science.gov (United States)

Gao, Jingjing; Nangia, Narinder; Jia, Jia; Bolognese, James; Bhattacharyya, Jaydeep; Patel, Nitin

2017-06-01

In this paper, we propose an adaptive randomization design for Phase 2 dose-finding trials to optimize Net Present Value (NPV) for an experimental drug. We replace the traditional fixed sample size design (Patel, et al., 2012) by this new design to see if NPV from the original paper can be improved. Comparison of the proposed design to the previous design is made via simulations using a hypothetical example based on a Diabetic Neuropathic Pain Study. Copyright © 2017 Elsevier Inc. All rights reserved.

Sugammadex and neostigmine dose-finding study for reversal of residual neuromuscular block at a train-of-four ratio of 0.2 (SUNDRO20)†,.

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Kaufhold, N; Schaller, S J; Stäuble, C G; Baumüller, E; Ulm, K; Blobner, M; Fink, H

2016-02-01

The aim of this dose-finding study was to evaluate the dose-response relationship of sugammadex and neostigmine to reverse a commonly observed level of incomplete recovery from rocuronium-induced neuromuscular block, that is, a train-of-four ratio (TOFR) ≥0.2. Ninety-nine anaesthetized patients received rocuronium 0.6 mg kg(-1) i.v. for tracheal intubation and, if necessary, incremental doses of 0.1-0.2 mg kg(-1). Neuromuscular monitoring was performed by calibrated electromyography. Once the TOFR recovered to 0.2, patients were randomized to receive sugammadex (0.25, 0.5, 0.75, 1.0, or 1.25 mg kg(-1) i.v.), neostigmine (10, 25, 40, 55, or 70 µg kg(-1) i.v.), or saline (n=9 per group). Primary and secondary end points were the doses necessary to restore neuromuscular function to a TOFR≥0.9 with an upper limit of 5 and 10 min for 95% of patients, respectively. Neostigmine was not able to fulfil the end points. Based on the best-fitting model, the sugammadex dose estimation for recovery to a TOFR≥0.9 for 95% of patients within 5 and 10 min was 0.49 and 0.26 mg kg(-1), respectively. A residual neuromuscular block of a TOFR of 0.2 cannot be reversed reliably with neostigmine within 10 min. In the conditions studied, substantially lower doses of sugammadex than the approved dose of 2.0 mg kg(-1) may be sufficient to reverse residual rocuronium-induced neuromuscular block at a recovery of TOFR≥0.2. NCT01006720. © The Author 2016. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Retrospective Dosimetric Comparison of Low-Dose-Rate and Pulsed-Dose-Rate Intracavitary Brachytherapy Using a Tandem and Mini-Ovoids

International Nuclear Information System (INIS)

Mourtada, Firas; Gifford, Kent A.; Berner, Paula A.; Horton, John L.; Price, Michael J.; Lawyer, Ann A.; Eifel, Patricia J.

2007-01-01

The purpose of this study was to compare the dose distribution of Iridium-192 ( 192 Ir) pulsed-dose-rate (PDR) brachytherapy to that of Cesium-137 ( 137 Cs) low-dose-rate (LDR) brachytherapy around mini-ovoids and an intrauterine tandem. Ten patient treatment plans were selected from our clinical database, all of which used mini-ovoids and an intrauterine tandem. A commercial treatment planning system using AAPM TG43 formalism was used to calculate the dose in water for both the 137 Cs and 192 Ir sources. For equivalent system loadings, we compared the dose distributions in relevant clinical planes, points A and B, and to the ICRU bladder and rectal reference points. The mean PDR doses to points A and B were 3% ± 1% and 6% ± 1% higher than the LDR doses, respectively. For the rectum point, the PDR dose was 4% ± 3% lower than the LDR dose, mainly because of the 192 Ir PDR source anisotropy. For the bladder point, the PDR dose was 1% ± 4% higher than the LDR dose. We conclude that the PDR and LDR dose distributions are equivalent for intracavitary brachytherapy with a tandem and mini-ovoids. These findings will aid in the transfer from the current practice of LDR intracavitary brachytherapy to PDR for the treatment of gynecologic cancers

Clinical implementation of full Monte Carlo dose calculation in proton beam therapy

International Nuclear Information System (INIS)

Paganetti, Harald; Jiang, Hongyu; Parodi, Katia; Slopsema, Roelf; Engelsman, Martijn

2008-01-01

The goal of this work was to facilitate the clinical use of Monte Carlo proton dose calculation to support routine treatment planning and delivery. The Monte Carlo code Geant4 was used to simulate the treatment head setup, including a time-dependent simulation of modulator wheels (for broad beam modulation) and magnetic field settings (for beam scanning). Any patient-field-specific setup can be modeled according to the treatment control system of the facility. The code was benchmarked against phantom measurements. Using a simulation of the ionization chamber reading in the treatment head allows the Monte Carlo dose to be specified in absolute units (Gy per ionization chamber reading). Next, the capability of reading CT data information was implemented into the Monte Carlo code to model patient anatomy. To allow time-efficient dose calculation, the standard Geant4 tracking algorithm was modified. Finally, a software link of the Monte Carlo dose engine to the patient database and the commercial planning system was established to allow data exchange, thus completing the implementation of the proton Monte Carlo dose calculation engine ('DoC++'). Monte Carlo re-calculated plans are a valuable tool to revisit decisions in the planning process. Identification of clinically significant differences between Monte Carlo and pencil-beam-based dose calculations may also drive improvements of current pencil-beam methods. As an example, four patients (29 fields in total) with tumors in the head and neck regions were analyzed. Differences between the pencil-beam algorithm and Monte Carlo were identified in particular near the end of range, both due to dose degradation and overall differences in range prediction due to bony anatomy in the beam path. Further, the Monte Carlo reports dose-to-tissue as compared to dose-to-water by the planning system. Our implementation is tailored to a specific Monte Carlo code and the treatment planning system XiO (Computerized Medical Systems Inc

Increased apoptotic potential and dose-enhancing effect of gold nanoparticles in combination with single-dose clinical electron beams on tumor-bearing mice

International Nuclear Information System (INIS)

Chang Mengya; Chen Yuhung; Chang Chihjui; Chen Helen H-W; Wu Chaoliang; Shiau Aili

2008-01-01

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. (author)

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

International Nuclear Information System (INIS)

Dang, Y.

2005-01-01

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

Clinical manifestations and laboratory findings of 496 children with brucellosis in Van, Turkey.

Science.gov (United States)

Parlak, Mehmet; Akbayram, Sinan; Doğan, Murat; Tuncer, Oğuz; Bayram, Yasemin; Ceylan, Nesrin; Özlük, Suat; Akbayram, Hatice Tuba; Öner, Abdurrahman

2015-08-01

Brucellosis is the most common zoonotic disease worldwide and remains an important human disease especially in developing countries. The aim of the present study was to evaluate clinical manifestations and laboratory findings of childhood brucellosis in Van province of Eastern Turkey. To our knowledge, this is the largest series of childhood brucellosis reported in the literature. In this retrospective study, 496 children with brucellosis were assessed for the clinical manifestations and laboratory findings from July 2009 through December 2013. The diagnosis of brucellosis was based on clinical findings and a standard tube agglutination test (titer ≥ 1:160). Data were analyzed using Minitab version 16. The study included 496 children (boys, 60.5%) with a mean age of 10.0 ± 3.95 years (range, 1-16 years). The most frequent clinical symptoms were arthralgia (46.2%), fever (32.1%), and abdominal pain (17.1%) and the most common clinical signs were peripheral arthritis (10.1%), splenomegaly (2.2%) and hepatomegaly (1.8%). The most contagious seasons were summer and autumn (63.3%). Elevated lactate dehydrogenase and C-reactive protein and erythrocyte sedimentation rate were reported in 63.1%, 58.7%, and 55.2% of the patients, respectively. Anemia (20.4%), thrombocytopenia (15.5%), and leukopenia (12.1%) were the most common hematologic findings. Brucellosis remains a serious public health problem in Turkey. The clinical and laboratory characteristics of childhood brucellosis have been described in order to assist clinicians in diagnosing and monitoring the disease. © 2015 Japan Pediatric Society.

Efficacy, safety and tolerability of escitalopram in doses up to 50 mg in Major Depressive Disorder (MDD: an open-label, pilot study

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Crawford Gordon M

2011-03-01

Full Text Available Abstract Background Escitalopram is licensed for use at doses up to 20 mg but is used clinically at higher doses. There is limited published data at higher doses and none in the treatment of Major Depressive Disorder (MDD. Methods This open-label, pilot study was designed to investigate the efficacy, safety and tolerability of escitalopram in doses up to 50 mg in MDD. It was conducted in 60 primary care patients with MDD who had not responded to adequate treatment with citalopram. Patients were treated with escalating doses of escitalopram up to 50 mg for up to 32 weeks until they achieved remission (Montgomery-Asberg Depression Rating Scale [MADRS] ≤8 or failed to tolerate the dose. Results Forty-two patients (70% completed the study. Twenty-one patients (35% achieved remission with 8 of the 21 patients (38% needing the 50 mg dose to achieve remission. Median time to remission was 24 weeks and median dose in remission was 30 mg. No significant safety issues were identified although tolerability appeared to decline above a dose of 40 mg with 26% of patients unable to tolerate 50 mg. Twelve (20% patients had adverse events leading to discontinuation. The most common adverse events were headache (35%, nausea, diarrhoea and nasopharyngitis (all 25%. Minor mean weight gain was found during the study, which did not appear to be dose-related. Half of the patients who completed the study chose to continue treatment with escitalopram rather than taper down the dose at 32 weeks. Conclusions Dose escalation with escitalopram above 20 mg may have a useful role in the management of patients with MDD, although further studies are needed to confirm this finding. Trial Registration ClinicalTrials.gov: NCT00785434

A comparative study for image quality and radiation dose of a cone beam computed tomography scanner and a multislice computed tomography scanner for paranasal sinus imaging.

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De Cock, Jens; Zanca, Federica; Canning, John; Pauwels, Ruben; Hermans, Robert

2015-07-01

To evaluate image quality and radiation dose of a state of the art cone beam computed tomography (CBCT) system and a multislice computed tomography (MSCT) system in patients with sinonasal poliposis. In this retrospective study two radiologists evaluated 57 patients with sinonasal poliposis who underwent a CBCT or MSCT sinus examination, along with a control group of 90 patients with normal radiological findings. Tissue doses were measured using a phantom model with thermoluminescent dosimeters (TLD). Overall image quality in CBCT was scored significantly higher than in MSCT in patients with normal radiologic findings (p-value: 0.00001). In patients with sinonasal poliposis, MSCT scored significantly higher than CBCT (p-value: 0.00001). The average effective dose for MSCT was 42% higher compared to CBCT (108 μSv vs 63 μSv). CBCT and MSCT are both suited for the evaluation of sinonasal poliposis. In patients with sinonasal poliposis, clinically important structures of the paranasal sinuses can be better delineated with MSCT, whereas in patients without sinonasal poliposis, CBCT turns out to define the important structures of the sinonasal region better. However, given the lower radiation dose, CBCT can be considered for the evaluation of the sinonasal structures in patients with sinonasal poliposis. • CBCT and MSCT are both suited for evaluation of sinonasal poliposis. • Effective dose for MSCT was 42% higher compared to CBCT. • In patients with sinonasal poliposis, clinically important anatomical structures are better delineated with MSCT. • In patients with normal radiological findings, clinically important anatomical structures are better delineated with CBCT.

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

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Mould, Diane R; Dubinsky, Marla C

2015-03-01

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

Clinical outcome of one-third-dose depot triptorelin is the same as half-dose depot triptorelin in the long protocol of controlled ovarian stimulation

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Yu Li

2012-01-01

Full Text Available Objective: Appropriate dosage of the long-acting depot gonadotrophin releasing hormone (GnRH agonist has not been determined in long protocol for IVF, and one-third-dose depot triptorelin was compared with half-dose in a luteal long protocol of in-vitro fertilization/ intra cytoplasmic sperm injection (IVF/ICSI treatment in this study. Materials and Methods: This is a prospective, randomized, open clinical trial. 100 patients were randomized into two groups. Group I received one-third-dose (1.25 mg depot triptorelin. Group II received half-dose (1.87 mg. The clinical and experimental parameters were compared between the two groups. Results: There was no premature luteinizing hormone (LH surge in both groups. On Day 3-5 of menstrual cycle after down-regulation, fewer patients showed low-level LH (<1.0 IU/L and estradiol (<30 pg/mL in group I (P <0.05. There were fewer oocytes retrieved (P =0.086, fewer total embryos and available embryos for cryopreservation in Group I (P <0.05, while good-quality embryo rate was higher in group I (P <0.05. The length and dose of ovarian stimulation was lower in Group I, but not significantly. The clinical pregnancy (52% versus 40%, implantation (48% versus 37.5%, delivery (46% versus 32%, or live birth (42% versus 32% rates and the abortion (8% versus 20% rates showed no significant differences. Conclusion: Depot triptorelin 1.25 mg can be successfully used with reduced pituitary suppression and lower cost in a long protocol for in-vitro fertilization.

Islet oxygen consumption rate (OCR) dose predicts insulin independence for first clinical islet allotransplants

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Kitzmann, JP; O’Gorman, D; Kin, T; Gruessner, AC; Senior, P; Imes, S; Gruessner, RW; Shapiro, AMJ; Papas, KK

2014-01-01

Human islet allotransplant (ITx) for the treatment of type 1 diabetes is in phase III clinical registration trials in the US and standard of care in several other countries. Current islet product release criteria include viability based on cell membrane integrity stains, glucose stimulated insulin release (GSIR), and islet equivalent (IE) dose based on counts. However, only a fraction of patients transplanted with islets that meet or exceed these release criteria become insulin independent following one transplant. Measurements of islet oxygen consumption rate (OCR) have been reported as highly predictive of transplant outcome in many models. In this paper we report on the assessment of clinical islet allograft preparations using islet oxygen consumption rate (OCR) dose (or viable IE dose) and current product release assays in a series of 13 first transplant recipients. The predictive capability of each assay was examined and successful graft function was defined as 100% insulin independence within 45 days post-transplant. Results showed that OCR dose was most predictive of CTO. IE dose was also highly predictive, while GSIR and membrane integrity stains were not. In conclusion, OCR dose can predict CTO with high specificity and sensitivity and is a useful tool for evaluating islet preparations prior to clinical ITx. PMID:25131089

Correlation of 111In-labeled leukocyte scintigraphy with clinical and laboratory findings

International Nuclear Information System (INIS)

Uchida, Yoshitaka; Kitakata, Yuusuke; Uno, Kimiichi; Minoshima, Satoshi; Arimizu, Noboru.

1993-01-01

This study evaluated the relationship between 111 In-labeled leukocyte scintigraphy and clinical information and laboratory findings in 24 patients with bone infection and 35 patients with abdominal infection. Fifty-nine scintigrams were retrospectively reviewed and classified into positive or negative results. As the laboratory findings, C-reactive protein (CRP) level, erythrocyte sedimentation rate (ESR) at 60 minutes, and peripheral blood leukocyte counts (WBCC) were evaluated. Clinical information such as presence of fever and administration of antibiotics was also compared. No significant relationship between the scintigraphic results and clinical as well as laboratory findings was observed in bone infection patients. CRP levels in positive scintigraphic patients were significantly higher than those in negative scintigraphic patients in the abdominal infection group, otherwise the other indices were not correlated with the scintigraphic results. A few patients with slightly increased CRP (mostly chronic cases) did not show positive scintigrams, suggesting an increased false negative rate of leukocyte scintigraphy in such circumstances. These results suggest that it is inappropriate to determine the application of leukocyte scintigraphy depending on clinical as well as laboratory findings, and leukocyte scintigraphy would yield additional information different from other indices when evaluating inflammatory foci. (author)

Prevention of laryngospasm with rocuronium in cats: a dose-finding study.

Science.gov (United States)

Martin-Flores, Manuel; Sakai, Daniel M; Portela, Diego A; Borlle, Lucia; Campoy, Luis; Gleed, Robin D

2016-09-01

To identify the dose of rocuronium that will prevent a laryngeal response to water spraying of the glottis in anesthetized cats. Randomized crossover study. Eight healthy, adult, short-haired cats, aged 1-4 years, weighing 3.2-6.0 kg. Each cat was anesthetized four times and administered one of four doses of rocuronium (0.1, 0.2, 0.3 and 0.6 mg kg(-1) ) in random order. The larynx was observed with a video-endoscope inserted through a laryngeal mask airway. Video-clips of the laryngeal response to a sterile water spray (0.2 mL) were obtained at baseline (without rocuronium) and at maximal effect of each treatment. Glottal closure score (0-2), duration of glottal closure, and number of adductive arytenoid movements were obtained from video-clips of laryngeal responses (reproduced in slow motion) at baseline and after treatment. Two observers blinded to treatment allocation scored the vigor of the laryngeal response on a visual analog scale (VAS). The duration of apnea (up to 5 minutes) was recorded for each treatment. Compared with baseline, rocuronium 0.3 mg kg(-1) and 0.6 mg kg(-1) significantly decreased all glottal scores obtained from the videos (all p rocuronium 0.1, 0.2, 0.3 and 0.6 mg kg(-1) , respectively. Rocuronium 0.3 mg kg(-1) and 0.6 mg kg(-1) consistently decreased the completeness and duration of the laryngeal response to water spray, and reduced the number of arytenoid adductive movements in response to that stimulus. However, a laryngeal response was never completely prevented. Rocuronium 0.3 mg kg(-1) may be useful for facilitating tracheal intubation. Positive pressure ventilation must be available for cats administered rocuronium. © 2016 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.

No-threshold dose-response curves for nongenotoxic chemicals: Findings and applications for risk assessment

International Nuclear Information System (INIS)

Sheehan, Daniel M.

2006-01-01

We tested the hypothesis that no threshold exists when estradiol acts through the same mechanism as an active endogenous estrogen. A Michaelis-Menten (MM) equation accounting for response saturation, background effects, and endogenous estrogen level fit a turtle sex-reversal data set with no threshold and estimated the endogenous dose. Additionally, 31 diverse literature dose-response data sets were analyzed by adding a term for nonhormonal background; good fits were obtained but endogenous dose estimations were not significant due to low resolving power. No thresholds were observed. Data sets were plotted using a normalized MM equation; all 178 data points were accommodated on a single graph. Response rates from ∼1% to >95% were well fit. The findings contradict the threshold assumption and low-dose safety. Calculating risk and assuming additivity of effects from multiple chemicals acting through the same mechanism rather than assuming a safe dose for nonthresholded curves is appropriate

Scrub typhus: radiological and clinical findings in abdominopelvic involvement.

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Kim, Kun Yung; Song, Ji Soo; Park, Eun Hae; Jin, Gong Yong

2017-03-01

To describe the clinical and radiological findings of abdominopelvic involvement in scrub typhus. Abdominopelvic computed tomography (CT) of 78 patients with scrub typhus were evaluated by two readers. The presence of gallbladder wall thickening, arterial inhomogeneous enhancement of the liver, periportal edema, splenic infarction, hepatomegaly, splenomegaly, ascites, pleural effusion, and sites of lymphadenopathy were evaluated. Patients were divided into four clinical subgroups according to laboratory findings. Association between imaging findings and subgroups was analyzed by Chi squared test or Fisher's exact test. The most common CT finding was hepatomegaly (74.4%), followed by splenomegaly (66.7%). The majority of patients had at least three areas of abdominopelvic lymphadenopathy (71.8%). Pelvic lymphadenopathy was most commonly seen when eschar was found in the ipsilateral lower extremity (left, n = 5/7; right, n = 8/13). Significant association between hepatic dysfunction and perigastric lymphadenopathy was documented (p = 0.03). Scrub typhus has a spectrum of variable clinical and radiological findings mimicking those of acute hepatitis. Diffuse abdominopelvic lymphadenopathy involving the retroperitoneum and pelvic area may aid in early diagnosis of scrub typhus. Perigastric lymphadenopathy could be a sign of severe scrub typhus combined with hepatic dysfunction.

Clinical and MRI findings of brucellar spondylodiscitis

International Nuclear Information System (INIS)

Bozgeyik, Zulkif; Ozdemir, Huseyin; Demirdag, Kutbettin; Ozden, Mehmet; Sonmezgoz, Fitnet; Ozgocmen, Salih

2008-01-01

Objective: The aim of this retrospective study was to report the clinical features and MR imaging findings of patients with brucellar spondylodiscitis. Materials and methods: Twenty-two patients with spondylodiscitis, recruited among 152 patients with brucellosis referred from the Department of Infectious Diseases. Patients were diagnosed based on positive clinical findings, ≥1/160 titers of brucella agglutination tests and/or positive blood cultures. Magnetic resonance imaging (MRI) was performed to all of the patients with spondylodiscitis. Signal changes and enhancement of vertebral bodies, involvement of paravertebral soft tissues and epidural spaces, nerve root and cord compression and abscess formation were assessed. Results: All of the patients (n = 22; 7 F, 15 M) had ≥1/160 titers of brucella agglutination test and blood culture was positive in 9. A great majority of the patients had involvement at only one vertebrae level (n = 21, 95.5%), whereas one patient (4.5%) had multilevel involvement. In MRI, eight patients had soft tissue involvement and three had abscess formation. All cases had vertebral and discal enhancement. Additionally epidural extension was detected in four cases, posterior longitudinal ligament (PLL) elevation in five cases and root compression in two cases. Conclusion: Brucella is still a public health problem in endemic areas. MRI is a highly sensitive and non-invasive imaging technique which should be first choice of imaging in the early diagnosis of spondylodiscitis

Clinical and MRI findings of brucellar spondylodiscitis

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Bozgeyik, Zulkif [Department of Radiology, Faculty of Medicine, Firat University, 23119 Elazig (Turkey)], E-mail: bozgeyik4@hotmail.com; Ozdemir, Huseyin [Department of Radiology, Faculty of Medicine, Firat University, 23119 Elazig (Turkey); Demirdag, Kutbettin; Ozden, Mehmet [Department of Infection Disease, Faculty of Medicine, Firat University, Elazig (Turkey); Sonmezgoz, Fitnet [Department of Radiology, Faculty of Medicine, Firat University, 23119 Elazig (Turkey); Ozgocmen, Salih [Division of Rheumatology, Department of PMR, Faculty of Medicine, Firat University, Elazig (Turkey)

2008-07-15

Objective: The aim of this retrospective study was to report the clinical features and MR imaging findings of patients with brucellar spondylodiscitis. Materials and methods: Twenty-two patients with spondylodiscitis, recruited among 152 patients with brucellosis referred from the Department of Infectious Diseases. Patients were diagnosed based on positive clinical findings, {>=}1/160 titers of brucella agglutination tests and/or positive blood cultures. Magnetic resonance imaging (MRI) was performed to all of the patients with spondylodiscitis. Signal changes and enhancement of vertebral bodies, involvement of paravertebral soft tissues and epidural spaces, nerve root and cord compression and abscess formation were assessed. Results: All of the patients (n = 22; 7 F, 15 M) had {>=}1/160 titers of brucella agglutination test and blood culture was positive in 9. A great majority of the patients had involvement at only one vertebrae level (n = 21, 95.5%), whereas one patient (4.5%) had multilevel involvement. In MRI, eight patients had soft tissue involvement and three had abscess formation. All cases had vertebral and discal enhancement. Additionally epidural extension was detected in four cases, posterior longitudinal ligament (PLL) elevation in five cases and root compression in two cases. Conclusion: Brucella is still a public health problem in endemic areas. MRI is a highly sensitive and non-invasive imaging technique which should be first choice of imaging in the early diagnosis of spondylodiscitis.

Determining clinical photon beam spectra from measured depth dose with the Cimmino algorithm

International Nuclear Information System (INIS)

Bloch, P.; Altschuler, M.D.; Bjaerngard, B.E.; Kassaee, A.; McDonough, J.

2000-01-01

A method to determine the spectrum of a clinical photon beam from measured depth-dose data is described. At shallow depths, where the range of Compton-generated electrons increases rapidly with photon energy, the depth dose provides the information to discriminate the spectral contributions. To minimize the influence of contaminating electrons, small (6x6cm2 ) fields were used. The measured depth dose is represented as a linear combination of basis functions, namely the depth doses of monoenergetic photon beams derived by Monte Carlo simulations. The weights of the basis functions were obtained with the Cimmino feasibility algorithm, which examines in each iteration the discrepancy between predicted and measured depth dose. For 6 and 15 MV photon beams of a clinical accelerator, the depth dose obtained from the derived spectral weights was within about 1% of the measured depth dose at all depths. Because the problem is ill conditioned, solutions for the spectrum can fluctuate with energy. Physically realistic smooth spectra for these photon beams appeared when a small margin (about ±1%) was attributed to the measured depth dose. The maximum energy of both derived spectra agreed with the measured energy of the electrons striking the target to within 1 MeV. The use of a feasibility method on minimally relaxed constraints provides realistic spectra quickly and interactively. (author)

Clinical Trials

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Full Text Available ... at the smallest dose and for the shortest time possible. Clinical trials, like the two described above, ... in a clinical trial, find out ahead of time about costs and coverage. You should learn about ...

Depth dose curves from 90Sr+90Y clinical applicators using the thermoluminescent technique

International Nuclear Information System (INIS)

Antonio, Patricia L.; Caldas, Linda V.E.; Oliveira, Mercia L.

2009-01-01

The 90 Sr+ 90 Y beta-ray sources widely used in brachytherapy applications were developed in the 1950's. Many of these sources, called clinical applicators, are still routinely used in several Brazilian radiotherapy clinics for the treatment of superficial lesions in the skin and eyes, although they are not commercialized anymore. These applicators have to be periodically calibrated, according to international recommendations, because these sources have to be very well specified in order to reach the traceability of calibration standards. In the case of beta-ray sources, the recommended quantity is the absorbed dose rate in water at a reference distance from the source. Moreover, there are other important quantities, as the depth dose curves and the source uniformity for beta-ray plaque sources. In this work, depth dose curves were obtained and studied of five dermatological applicators, using thin thermoluminescent dosimeters of CaSO 4 :Dy and phantoms of PMMA with different thicknesses (between 1.0 mm and 5.0 mm) positioned between each applicator and the TL pellets. The depth dose curves obtained presented the expected attenuation response in PMMA, and the results were compared with data obtained for a 90 Sr+ 90 Y standard source reported by the IAEA, and they were considered satisfactory. (author)

Radiographic findings of gastrointestinal anisakiasis: clinical and pathologic correlation

International Nuclear Information System (INIS)

Chung, Tae Woong; Kang, Heoung Keun; Jeong, Yong Yeon; And Others

2000-01-01

To evaluate the radiographic findings of gastrointestinal anisakiasis with clinical and pathologic correlation. In ten patients, findings were retrospectively analysed. There were two cases of the gastric variety of gastrointestinal anisakiasis and eight of the intestinal, and they were diagnosed during gastroscopy, by resection during surgery, and on the basis of typical clinical findings. All ten patients underwent both plain radiography and CT scanning of the abdomen. US was performed in five patients and an upper gastrointestinal series in one. Clinical data were evaluated with regard to a history of raw fish ingestion, time from ingestion of raw fish to onset of symptoms, location of abdominal pain, and laboratory data. Radiologic findings were analysed in terms of wall thickening and appearance, mesenteric infiltration, bowel dilatation proximal to lesion, and ascites. All patients had a history of recent ingestion of raw fish and complained of severe abdominal pain that occurred approximately 7-48 hours later. Pain occurred in the lower abdomen in five patients, the epigastrium in four, and the right lower abdomen in two. Laboratory test disclosed the leukocytosis in eight patients and eosinophilia in three. In all cases of intestinal anisakiasis, ileus was demonstrated on plain radiographs of the abdomen, while the upper gastrointestinal series showed mucosal thickening and multiple filling defects. US findings were bowel thickening and dilation, and on CT images, wall thickening revealed a target sign. Mesenteric infiltration and ascites were seen in seven patients. In four who underwent surgery, a cross-section through the lesion revealed submucosal eosinophilic granuloma with anisakis larva. Although the CT findings are non-specific, taken in conjunction with characteristic clinical findings, they may be helpful in the diagnosis of gastrointestinal anisakiasis. (author)

Radiographic findings of gastrointestinal anisakiasis: clinical and pathologic correlation

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Chung, Tae Woong; Kang, Heoung Keun; Jeong, Yong Yeon [Medical School, Chonnam University, Kwangju (Korea, Republic of); And Others

2000-08-01

To evaluate the radiographic findings of gastrointestinal anisakiasis with clinical and pathologic correlation. In ten patients, findings were retrospectively analysed. There were two cases of the gastric variety of gastrointestinal anisakiasis and eight of the intestinal, and they were diagnosed during gastroscopy, by resection during surgery, and on the basis of typical clinical findings. All ten patients underwent both plain radiography and CT scanning of the abdomen. US was performed in five patients and an upper gastrointestinal series in one. Clinical data were evaluated with regard to a history of raw fish ingestion, time from ingestion of raw fish to onset of symptoms, location of abdominal pain, and laboratory data. Radiologic findings were analysed in terms of wall thickening and appearance, mesenteric infiltration, bowel dilatation proximal to lesion, and ascites. All patients had a history of recent ingestion of raw fish and complained of severe abdominal pain that occurred approximately 7-48 hours later. Pain occurred in the lower abdomen in five patients, the epigastrium in four, and the right lower abdomen in two. Laboratory test disclosed the leukocytosis in eight patients and eosinophilia in three. In all cases of intestinal anisakiasis, ileus was demonstrated on plain radiographs of the abdomen, while the upper gastrointestinal series showed mucosal thickening and multiple filling defects. US findings were bowel thickening and dilation, and on CT images, wall thickening revealed a target sign. Mesenteric infiltration and ascites were seen in seven patients. In four who underwent surgery, a cross-section through the lesion revealed submucosal eosinophilic granuloma with anisakis larva. Although the CT findings are non-specific, taken in conjunction with characteristic clinical findings, they may be helpful in the diagnosis of gastrointestinal anisakiasis. (author)

Combination chemotherapy with intermittent erlotinib and pemetrexed for pretreated patients with advanced non-small cell lung cancer: a phase I dose-finding study

International Nuclear Information System (INIS)

Minami, Seigo; Tachibana, Isao; Komuta, Kiyoshi; Kawase, Ichiro; Kijima, Takashi; Takahashi, Ryo; Kida, Hiroshi; Nakatani, Takeshi; Hamaguchi, Masanari; Takeuchi, Yoshiko; Nagatomo, Izumi; Yamamoto, Suguru

2012-01-01

Erlotinib and pemetrexed have been approved for the second-line treatment of non-small cell lung cancer (NSCLC). These two agents have different mechanisms of action. Combined treatment with erlotinib and pemetrexed could potentially augment the antitumor activity of either agent alone. In the present study, we investigated the safety profile of combined administration of the two agents in pretreated NSCLC patients. A phase I dose-finding study (Trial registration: UMIN000002900) was performed in patients with stage III/IV nonsquamous NSCLC whose disease had progressed on or after receiving first-line chemotherapy. Patients received 500 mg/m 2 of pemetrexed intravenously every 21 days and erlotinib (100 mg at Level 1 and 150 mg at Level 2) orally on days 2–16. Twelve patients, nine males and three females, were recruited. Patient characteristics included a median age of 66 years (range, 48–78 years), stage IV disease (nine cases), adenocarcinoma (seven cases) and activating mutation-positives in the epidermal growth factor receptor gene (two cases). Treatment was well-tolerated, and the recommended dose of erlotinib was fixed at 150 mg. Dose-limiting toxicities were experienced in three patients and included: grade 3 elevation of serum alanine aminotransferase, repetitive grade 4 neutropenia that required reduction of the second dose of pemetrexed and grade 3 diarrhea. No patient experienced drug-induced interstitial lung disease. Three patients achieved a partial response and stable disease was maintained in five patients. Combination chemotherapy of intermittent erlotinib with pemetrexed was well-tolerated, with promising efficacy against pretreated advanced nonsquamous NSCLC

Nonpalpable breast cancer : mammographic and clinical findings

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Seo, Jae Seung; Kim, Eun Kyung; Oh, Ki Keun; Cheon, Young Jik; Lee, Byung Chan [Yonsei Univ. College of Medicine, Seoul (Korea, Republic of)

1998-08-01

To evaluate the mammographic and clinical findings of nonpalpable breast cancer. Materials and Methods : In 28 of 607 breast cancer patients examined between January 1994 and April 1997, lesions were nonpalpable. We retrospectively analyzed the mammographic, clinical and pathologic features of 25 patients (28 lesions) whose mammograms we obtained. Results : Among these 25 patients (28 lesions) screening was abnormal in 22; other symptoms were bloody nipple discharge(n=4), and nipple eczema(n=2). The patients were 34-62 (mean 52)years old. Invasive ductal carcinoma(n=13), DCIS(ductal carcinoma in situ, n-12), Paget's disease (n=2), and LCIS(lobular carcinoma in situ, n=1) were found during surgery. Six of 28 lesions(21%) showed evidence of axillary nodal metastasis;the majority arose from the upper outer quadrant of the breast (n=21). The mammographic findings were mass (50%), (and mass with microcalcification, 11%); microcalcification(29%); asymmetrical density(14%); and normal (7%). According to the mammographic density of breast parenchyma, the major finding in the low density group(N1+P1) was mass(9/9), and in the high density group(P2+DY) was microcalcification (12/19). Conclusion : The most common mammographic findings of nonpalpable breast cancer were mass (50%) and microcalcification(29%). Its features varied according to the mammographic density of breast parenchyma;mass was the main finding in the low density group and microcalcification in the high density group.

Nonpalpable breast cancer : mammographic and clinical findings

International Nuclear Information System (INIS)

Seo, Jae Seung; Kim, Eun Kyung; Oh, Ki Keun; Cheon, Young Jik; Lee, Byung Chan

1998-01-01

To evaluate the mammographic and clinical findings of nonpalpable breast cancer. Materials and Methods : In 28 of 607 breast cancer patients examined between January 1994 and April 1997, lesions were nonpalpable. We retrospectively analyzed the mammographic, clinical and pathologic features of 25 patients (28 lesions) whose mammograms we obtained. Results : Among these 25 patients (28 lesions) screening was abnormal in 22; other symptoms were bloody nipple discharge(n=4), and nipple eczema(n=2). The patients were 34-62 (mean 52)years old. Invasive ductal carcinoma(n=13), DCIS(ductal carcinoma in situ, n-12), Paget's disease (n=2), and LCIS(lobular carcinoma in situ, n=1) were found during surgery. Six of 28 lesions(21%) showed evidence of axillary nodal metastasis;the majority arose from the upper outer quadrant of the breast (n=21). The mammographic findings were mass (50%), (and mass with microcalcification, 11%); microcalcification(29%); asymmetrical density(14%); and normal (7%). According to the mammographic density of breast parenchyma, the major finding in the low density group(N1+P1) was mass(9/9), and in the high density group(P2+DY) was microcalcification (12/19). Conclusion : The most common mammographic findings of nonpalpable breast cancer were mass (50%) and microcalcification(29%). Its features varied according to the mammographic density of breast parenchyma;mass was the main finding in the low density group and microcalcification in the high density group

When are night shifts effective for nursing student clinical learning? Findings from a mixed-method study design.

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Palese, Alvisa; Basso, Felix; Del Negro, Elena; Achil, Illarj; Ferraresi, Annamaria; Morandini, Marzia; Moreale, Renzo; Mansutti, Irene

2017-05-01

Some nursing programmes offer night shifts for students while others do not, mainly due to the lack of evidence regarding their effectiveness on clinical learning. The principal aims of the study were to describe nursing students' perceptions and to explore conditions influencing effectiveness on learning processes during night shifts. An explanatory mixed-method study design composed of a cross-sectional study (primary method, first phase) followed by a descriptive phenomenological study design (secondary method, second phase) in 2015. Two bachelor of nursing degree programmes located in Northern Italy, three years in length and requiring night shifts for students starting in the second semester of the 1st year, were involved. First phase: all nursing students ending their last clinical placement of the academic year attended were eligible; 352 out the 370 participated. Second phase: a purposeful sample of nine students among those included in the first phase and who attended the highest amount of night shifts were interviewed. First phase: a questionnaire composed of closed and open-ended questions was adopted; data was analyzed through descriptive statistical methods. Second phase: an open-ended face-to-face audio-recorded interview was adopted and data was analyzed through content analysis. Findings from the quantitative phase, showed that students who attended night shifts reported satisfaction (44.7%) less frequently than those who attended only day shifts (55.9%). They also reported boredom (23.5%) significantly more often compared to day shift students (p=0001). Understanding of the nursing role and learning competence was significantly inferior among night shift students as compared to day shift students, while the perception of wasting time was significantly higher among night shift students compared to their counterparts. Night shift students performed nursing rounds (288; 98.2%), non-nursing tasks (247; 84.3%) and/or less often managed clinical problems

Single and multiple dose Fluconazole in the treatment of candidia vulvovaginitis: a prospective comparative study

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Ashrafinia M

2007-09-01

Full Text Available  Background: Vulvovaginal candidiasis, the most common type of vaginitis, is usually caused by Candidia albicans. Patients experience a variety of symptoms. There are many types of vulvovaginal candidiasis with various microbial causes, symptoms, host circumstances, recurrence rates, and responses to treatment. The purpose of this study was to find the best method of treatment of complicated vaginitis as determined by its high prevalence, varying symptoms and signs and patient complaints.Methods: In this open clinical trial without placebo control, we studied all patients aged 18 to 65 years, suffering from vaginitis symptoms that presented at the gynecological clinic of Arash Hospital, Tehran, Iran, during the year 2004. After obtaining informed consent, we assessed the response to a treatment of single 150 mg dose of fluconazole in one group, and sequential 150 mg doses of fluconazole in the other. The analysis was performed using SPSS statistical software (version 11.Results: With regard to symptom severity, no significant difference was found between the groups. The rate of excoriation and fissure formation demonstrated significant difference between the two groups (p=0.048. Assessment of clinical and mycological response proved that patients with severe vaginitis treated with sequential doses of fluconazole had a better general status than those in the other group. The difference between the severity of vaginitis and positive response to the treatment in culture was not significant among patients with recurrent vaginitis.Conclusion: Patients with mild to moderate recurrent vaginitis show better response to treatment. The high rate of positive culture on day 35 reconfirms the limitation of fluconazole and other azoles as fungistatic drugs.

Cytogenetics findings at Turner Syndrome and their correlation with clinical findings

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Amra Ćatović

2005-08-01

Full Text Available Turner Syndrome is a genetic condition in females that results from an abnormal chromosome. One of the X chromosomes is missing or misshapen in the most cells of the body. Three classics clinical symptoms of the syndrome are: incomplete sexual maturation, short stature and pterygium colli. Turner Syndrome is diagnosed by karyotyping. In the retrospective study for a twelve years period (1991-2002 correlation between clinical and cytogenetics findings was established in our Center among 47 examinees from all parts of Federation of Bosnia and Herzegovina, who had suspect clinical diagnosis of Turner Syndrome. The syndrome was demonstrated by cytogeneticsexaminations in 30(63,8% examinees and excluded in 17 (36,2% examinees. The most frequent karyotype is monosomy of X chromosome (45,X found at 63,3%, than isochromosome of Xq (46,XisoXq found at 16,7%, mosaic form (46,XX/45,X and deletion of Xp (46,XdelXp both at 6,7%, than deletion of Xq (46,XdelXq and ring of Xp (46,XX/46,XringXp both at 3,3%. Our results suggest that promptly and exactly diagnosis of Turner syndrome is very important due to introducing growth hormone therapy and estrogen therapy at a very young age.

TH-AB-201-01: A Feasibility Study of Independent Dose Verification for CyberKnife

International Nuclear Information System (INIS)

Sato, A; Noda, T; Keduka, Y; Kawajiri, T; Itano, M; Yamazaki, T; Tachibana, H

2016-01-01

Purpose: CyberKnife irradiation is composed of tiny-size, multiple and intensity-modulated beams compared to conventional linacs. Few of the publications for Independent dose calculation verification for CyberKnife have been reported. In this study, we evaluated the feasibility of independent dose verification for CyberKnife treatment as Secondary check. Methods: The followings were measured: test plans using some static and single beams, clinical plans in a phantom and using patient’s CT. 75 patient plans were collected from several treatment sites of brain, lung, liver and bone. In the test plans and the phantom plans, a pinpoint ion-chamber measurement was performed to assess dose deviation for a treatment planning system (TPS) and an independent verification program of Simple MU Analysis (SMU). In the clinical plans, dose deviation between the SMU and the TPS was performed. Results: In test plan, the dose deviations were 3.3±4.5%, and 4.1±4.4% for the TPS and the SMU, respectively. In the phantom measurements for the clinical plans, the dose deviations were −0.2±3.6% for the TPS and −2.3±4.8% for the SMU. In the clinical plans using the patient’s CT, the dose deviations were −3.0±2.1% (Mean±1SD). The systematic difference was partially derived from inverse square law and penumbra calculation. Conclusion: The independent dose calculation for CyberKnife shows −3.0±4.2% (Mean±2SD) and our study, the confidence limit was achieved within 5% of the tolerance level from AAPM task group 114 for non-IMRT treatment. Thus, it may be feasible to use independent dose calculation verification for CyberKnife treatment as the secondary check. This research is partially supported by Japan Agency for Medical Research and Development (AMED)

Are high doses of carbidopa a concern? A randomized clinical trial in Parkinson’s disease

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Brod, Lissa S.; Aldred, Jason L.; Nutt, John G.

2013-01-01

Background Recommended doses of carbidopa are 75–200 mg/day. Higher doses could inhibit brain aromatic amino acid decarboxylase and reduce clinical effects. Methods We compared 4-week outpatient treatments with carbidopa 75 mg and 450 mg/day administered with levodopa on the subjects’ normal schedule. After each treatment phase subjects had two 2-hour levodopa infusions. The first infusion examined the effects of carbidopa doses administered the preceding four weeks and the second infusion determined the acute effects of the two dosages of carbidopa. The antiparkinsonian effects and levodopa and carbidopa plasma concentrations were monitored during the infusions. Results Twelve subjects completed the study. Carbidopa concentrations were eight times higher after the high carbidopa phase. Area under the curve (AUC) for clinical ratings did not differ for the four levodopa infusions although AUC for plasma levodopa was modestly increased with 450 mg of carbidopa. Nine subjects reported the high carbidopa outpatient phase was associated with greater response to levodopa. Conclusion Doses of 450 mg/day of carbidopa did not reduce the responses to levodopa infusion, extending the safe range of carbidopa to 450 mg/day. PMID:22508376

Clinical dosimetry with plastic scintillators - Almost energy independent, direct absorbed dose reading with high resolution

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Quast, U; Fluehs, D [Department of Radiotherapy, Essen (Germany). Div. of Clinical Radiation Physics; Fluehs, D; Kolanoski, H [Dortmund Univ. (Germany). Inst. fuer Physik

1996-08-01

Clinical dosimetry is still far behind the goal to measure any spatial or temporal distribution of absorbed dose fast and precise without disturbing the physical situation by the dosimetry procedure. NE 102A plastic scintillators overcome this border. These tissue substituting dosemeter probes open a wide range of new clinical applications of dosimetry. This versatile new dosimetry system enables fast measurement of the absorbed dose to water in water also in regions with a steep dose gradient, close to interfaces, or in partly shielded regions. It allows direct reading dosimetry in the energy range of all clinically used external photon and electron beams, or around all branchytherapy sources. Thin detector arrays permit fast and high resolution measurements in quality assurance, such as in-vivo dosimetry or even afterloading dose monitoring. A main field of application is the dosimetric treatment planning, the individual optimization of brachytherapy applicators. Thus, plastic scintillator dosemeters cover optimally all difficult fields of clinical dosimetry. An overview about its characteristics and applications is given here. 20 refs, 1 fig.

MRI findings in the patients with the presumptive clinical diagnosis of Tolosa-Hunt syndrome

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Cakirer, Sinan [Department of Radiology, Neuroradiology Section, Istanbul Sisli Etfal Hospital, 81120 Istanbul (Turkey)

2003-01-01

The aim of this study was to present our experience in MRI diagnosis of 23 patients with the clinical findings suggesting Tolosa-Hunt syndrome (THS). Cranial MRI studies of the patients with a clinical history of at least one episode of unilateral or bilateral orbital and periorbital pain, and associated paresis of one or more of third to sixth cranial nerves, were performed on a 1.5-T MRI scanner. Whereas 5 patients had the diagnosis of THS, paracavernous meningiomas in 4 patients, pituitary macroadenomas with cavernous sinus infiltration in 3 patients, Meckel's cave neurinoma in 1 patient, and suprasellar epidermoid in 1 patient were surgically proven MRI findings. Other pathological MRI findings were leptomeningeal metastases in 3 patients, granulomatous pachymeningitis sequelae in 2 patients, and aneurysm with compression on cavernous sinus in 1 patient. Three patients had normal MRI findings. The incidence of radiologically proven diagnosis of THS among the patients with the clinical findings suggesting THS seemed to be low in our study. In conclusion, MRI is the most valuable imaging technique to distinguish THS from other THS-like entities, and permits a precise assessment, management, and therapeutic planning of the underlying pathological conditions. (orig.)

A study on clinical findings about vertebral disease diagnosed with MRI

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Kim, Ham-Gyum [Ansan College, Seoul (Korea, Republic of)

2006-09-15

In order to analyze clinical characteristics like sex-and age-based onset frequency and onset region from vertebral disease cases, this study investigated total 1,291 cases of vertebral disease that were diagnosed via magnetic resonance imaging (MRI) from January to December 2004 at B University Hospital in metropolitan area. For higher diagnostic accuracy in cases of spinal disorder diagnosed, this study analyzed findings from data reading conducted by veteran specialists in diagnostic radiology. But this study excluded uncertain lesion cases, the cases requiring differential diagnosis from other disorders and so on from subjects under analysis. This study employed superconductive 1.5 Tesla SIGNA MR/i for MRI test and basically received resulting images via FSE (fast spin echo). In particular, this study obtained T1 and T2 myelogram with regard to regional characteristics (such as cervical vertebrae, thoracic vertebrae and lumbar vertebra) and imaging characteristics for sagittal and transverse section. As a result, this study came to the following conclusions: 1. In terms of general characteristics of subjects under analysis, male group comprised 53.5% and female 46.5% out of total 1,291 subjects. 2. The regional onset frequency of spinal disorders was converged primarily on lumbar vertebra (65.5%), which was followed by cervical vertebrae (27.3%) and thoracic vertebrae (7.0%) respectively. 3. Top 10 cases with high onset frequency of spinal disorders can be listed as follows: 1) posterior bulging disc 65.8% 2) narrowing of neural foramen 23.8% 3) herniated intervertebral disc (HIVD) 22.4% 4) spinal stenosis 16.7% 5) osteochondrosis 6.4% 6) compression fracture 6.4% 7) facet joint arthropathy 6.2% 8) spondylolisthesis 6.0% 9) spinal cord tumor 3.5% 10) inter body fusion 2.6%.

A study on clinical findings about vertebral disease diagnosed with MRI

International Nuclear Information System (INIS)

Kim, Ham-Gyum

2006-01-01

In order to analyze clinical characteristics like sex-and age-based onset frequency and onset region from vertebral disease cases, this study investigated total 1,291 cases of vertebral disease that were diagnosed via magnetic resonance imaging (MRI) from January to December 2004 at B University Hospital in metropolitan area. For higher diagnostic accuracy in cases of spinal disorder diagnosed, this study analyzed findings from data reading conducted by veteran specialists in diagnostic radiology. But this study excluded uncertain lesion cases, the cases requiring differential diagnosis from other disorders and so on from subjects under analysis. This study employed superconductive 1.5 Tesla SIGNA MR/i for MRI test and basically received resulting images via FSE (fast spin echo). In particular, this study obtained T1 and T2 myelogram with regard to regional characteristics (such as cervical vertebrae, thoracic vertebrae and lumbar vertebra) and imaging characteristics for sagittal and transverse section. As a result, this study came to the following conclusions: 1. In terms of general characteristics of subjects under analysis, male group comprised 53.5% and female 46.5% out of total 1,291 subjects. 2. The regional onset frequency of spinal disorders was converged primarily on lumbar vertebra (65.5%), which was followed by cervical vertebrae (27.3%) and thoracic vertebrae (7.0%) respectively. 3. Top 10 cases with high onset frequency of spinal disorders can be listed as follows: 1) posterior bulging disc 65.8% 2) narrowing of neural foramen 23.8% 3) herniated intervertebral disc (HIVD) 22.4% 4) spinal stenosis 16.7% 5) osteochondrosis 6.4% 6) compression fracture 6.4% 7) facet joint arthropathy 6.2% 8) spondylolisthesis 6.0% 9) spinal cord tumor 3.5% 10) inter body fusion 2.6%

G-CSF in acute myocardial infarction - experimental and clinical findings.

Science.gov (United States)

Ince, Hüseyin; Petzsch, Michael; Rehders, Tim C; Dunkelmann, Simone; Nienaber, Christoph A

2006-09-01

Early data from clinical studies suggest that intracoronary injection of autologous progenitor cells may beneficially affect postinfarction remodeling and perfusion. Beyond intracoronary infusion of autologous bone marrow mononuclear CD34+ cells (MNCCD34+), mobilization of stem cells by G-CSF has recently attracted attention because of various advantages such as the noninvasive nature of MNCCD34+ mobilization by subcutaneous injections. It is the aim of the present work to give an overview about the current experimental and clinical findings of G-CSF treatment in acute myocardial infarction.

MR findings of cerebral palsy and clinical correlation

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Kim, Sun Ho; Kim, In One; Kim, Woo Sun; Yeon, Kyung Mo [Seoul National Univ. College of Medicine, Seoul (Korea, Republic of)

1997-04-01

To demonstrate MR findings of cerebral palsy (CP), correlation with clinical findings, and differences between the full-term and pre-term group. Brain MRI of 94 patients with cerebral palsy (CP) were reviewed. The frequency of each MR finding, statistical correlation with clinical findings including type, severity and extent of CP, and differences between the full-term and pre-term group were analyzed. Abnormal MR findings were found in 83 patients(88%), and were as follows : diffuse brain atrophy(30%); periventricular leukomalacia(PVL)(28%); infarction(11%), basal ganglia abnormality(11%); delayed myelination(10%); nonspecific tissue loss or encephalomalacia(9%); and cortical dysplasia(7%). Hemiplegia was the most common condition among patients with infarction, and was found in 80% of this group; diplegia was found in 50% of cases with diffuse brain atrophy, while paraplegia was found in 36% of those with normal MR findings (p < .05). Mild symptoms were dominant in patients with normal MR findings(82%) and in those with infarctions(90%)(p < .05). PVL was the dominant finding in the pre-term group (65%) whereas findings in the full-term group varied; in this group, 38% of MR findings suggested prenatal insults. Possible causative factors were found in 66% of the full-term and 80% of the pre-term group. Perinatal factors were dominant in the pre-term group(81%), whereas prenatal and postnatal factors showed relatively higher frequencies in the full-term group(30% and 24%, respectively). Diffuse brain atrophy and PVL were the most common MR findings. The extent of CP the pre-term correlated well with MR findings. PVL and perinatal factors were dominant in the pre-term group, whereas variable MR findings and relatively higher frequencies of pre- and postnatal factors were found in the full-term group.

MR findings of cerebral palsy and clinical correlation

International Nuclear Information System (INIS)

Kim, Sun Ho; Kim, In One; Kim, Woo Sun; Yeon, Kyung Mo

1997-01-01

To demonstrate MR findings of cerebral palsy (CP), correlation with clinical findings, and differences between the full-term and pre-term group. Brain MRI of 94 patients with cerebral palsy (CP) were reviewed. The frequency of each MR finding, statistical correlation with clinical findings including type, severity and extent of CP, and differences between the full-term and pre-term group were analyzed. Abnormal MR findings were found in 83 patients(88%), and were as follows : diffuse brain atrophy(30%); periventricular leukomalacia(PVL)(28%); infarction(11%), basal ganglia abnormality(11%); delayed myelination(10%); nonspecific tissue loss or encephalomalacia(9%); and cortical dysplasia(7%). Hemiplegia was the most common condition among patients with infarction, and was found in 80% of this group; diplegia was found in 50% of cases with diffuse brain atrophy, while paraplegia was found in 36% of those with normal MR findings (p < .05). Mild symptoms were dominant in patients with normal MR findings(82%) and in those with infarctions(90%)(p < .05). PVL was the dominant finding in the pre-term group (65%) whereas findings in the full-term group varied; in this group, 38% of MR findings suggested prenatal insults. Possible causative factors were found in 66% of the full-term and 80% of the pre-term group. Perinatal factors were dominant in the pre-term group(81%), whereas prenatal and postnatal factors showed relatively higher frequencies in the full-term group(30% and 24%, respectively). Diffuse brain atrophy and PVL were the most common MR findings. The extent of CP the pre-term correlated well with MR findings. PVL and perinatal factors were dominant in the pre-term group, whereas variable MR findings and relatively higher frequencies of pre- and postnatal factors were found in the full-term group

[Clinical studies on flomoxef in the perinatal period infections].

Science.gov (United States)

Chimura, T; Morisaki, N; Funayama, T

1991-06-01

We conducted clinical efficacy and safety tests of flomoxef (FMOX, 6315-S) in the perinatal infections and obtained the following results. 1. A total of 25 patients was treated: 16 patients with intrauterine infections, 2 patients with pelvioperitonitis, 4 patients with urinary tract infections and 3 patients with other infections. FMOX was injected at a daily dose of 2-4 g for 3-15 days (6-60 g for total dose) by intravenous drip infusion, intravenous injection or their combination. 2. The clinical efficacy rate was 96.0% of 25 patients: excellent in 4 cases (16.0%), good in 20 cases (80.0%) and poor in 1 case (4.0%). Bacteriological effects obtained were: eradicated in 14/16 cases (87.5%) replaced in 3 cases. 3. There were no subjective or objective side effects, nor were any abnormal laboratory test values attributable to the drug. From these findings, we consider that FMOX treatment appears to obtain good clinical and bacteriological responses and in safe in perinatal period infections.

Dose conversion of radon exposure according to new epidemiological findings

International Nuclear Information System (INIS)

Tomasek, L.; Rogel, A.; Laurier, D.; Tirmarche, M.

2008-01-01

In 1993, ICRP-65 recommended that dose conversion of radon exposure should be based on the comparison of detriments between radon exposure and effective dose. The lifetime detriment from the radon exposure was projected according to the epidemiological studies of uranium miners then available. The projection model (GSF) was multiplicative with temporal and age-at-exposure modification. Since 1993, new studies of uranium miners have appeared and many original studies were updated. In addition, projections of the risk have been improved by including further modifying factors as for instance in BEIR VI. New analyses were completed in the Czech and French studies of uranium miners with accurate estimates of exposures based on extensive radon measurements. The resulting estimates of excess absolute lifetime risk per unit exposure in working level months (WLM) from these models lead to dose conversion of 10 mSv WLM -1 for the BEIR VI model and 8 mSv WLM -1 for the joint Czech-French model in contrast to the conversion of 5 mSv WLM -1 for the GSF model. (authors)

A simplified approach for exit dose in vivo measurements in radiotherapy and its clinical application

International Nuclear Information System (INIS)

Banjade, D.P.; Shukri, A.; Tajuddin, A.A.; Shrestha, S.L.; Bhat, M.

2002-01-01

This is a study using LiF:Mg;Ti thermoluminescent dosimeter (TLD) rods in phantoms to investigate the effect of lack of backscatter on exit dose. Comparing the measured dose with anticipated dose calculated using tissue maximum ratio (TMR) or percentage depth dose (PDD) gives rise to a correction factor. This correction factor may be applied to in-vivo dosimetry results to derive true dose to a point within the patient. Measurements in a specially designed humanoid breast phantom as well as patients undergoing radiotherapy treatment were also been done. TLDs with reproducibility of within ±3% (1 SD) are irradiated in a series of measurements for 6 and 10 MV photon beams from a medical linear accelerator. The measured exit doses for the different phantom thickness for 6 MV beams are found to be lowered by 10.9 to 14.0% compared to the dose derived from theoretical estimation (normalized dose at d max ). The same measurements for 10 MV beams are lowered by 9.0 to 13.5%. The variations of measured exit dose for different field sizes are found to be within 2.5%. The exit doses with added backscatter material from 2 mm up to 15 cm, shows gradual increase and the saturated values agreed within 1.5% with the expected results for both beams. The measured exit doses in humanoid breast phantom as well as in the clinical trial on patients undergoing radiotherapy also agreed with the predicted results based on phantom measurements. The authors' viewpoint is that this technique provides sufficient information to design exit surface bolus to restore build down effect in cases where part of the exit surface is being considered as a target volume. It indicates that the technique could be translated for in vivo dose measurements, which may be a conspicuous step of quality assurance in clinical practice. Copyright (2002) Australasian College of Physical Scientists and Engineers in Medicine

Unexpected MRI findings in clinically suspected Legg-Calve-Perthes disease

Energy Technology Data Exchange (ETDEWEB)

Lobert, Philip F.; Dillman, Jonathan R.; Strouse, Peter J.; Hernandez, Ramiro J. [University of Michigan Health System, Department of Radiology, Section of Pediatric Radiology, C.S. Mott Children' s Hospital/F3503, Ann Arbor, MI (United States)

2011-03-15

In the setting of clinically suspected Legg-Calve-Perthes (LCP) disease and negative/equivocal radiographs, contrast-enhanced MRI can be performed to confirm the diagnosis. To determine the frequency of unexpected causes of hip pain as identified by MRI in children with clinically suspected LCP disease and negative/equivocal radiographs. All pediatric contrast-enhanced MRI examinations of the pelvis and hips performed between January 2000 and February 2009 to evaluate for possible LCP disease in the setting of negative/equivocal radiographs were identified. MRI examinations performed to evaluate for secondary avascular necrosis were excluded. Imaging reports were retrospectively reviewed for unexpected clinically important causes of hip pain. Thirty-six pediatric patients underwent contrast-enhanced MRI examinations for clinically suspected LCP disease in the setting of negative/equivocal radiographs. Twenty-two (61%) imaging studies were normal, while four (11%) imaging studies demonstrated findings consistent with LCP disease. Ten (28%) imaging studies revealed unexpected clinically important causes of hip pain, including nonspecific unilateral joint effusion and synovitis (n = 7, juvenile chronic arthritis was eventually diagnosed in 3 patients), sacral fracture (n = 1), apophyseal injury (n = 1), and femoral head subluxation (n = 1). MRI frequently reveals unexpected clinically important causes of hip pain in children with suspected LCP disease and negative/equivocal radiographs. (orig.)

Radiation dose responses for chemoradiation therapy of pancreatic cancer: an analysis of compiled clinical data using biophysical models.

Science.gov (United States)

Moraru, Ion C; Tai, An; Erickson, Beth; Li, X Allen

2014-01-01

We analyzed recent clinical data obtained from chemoradiation of unresectable, locally advanced pancreatic cancer (LAPC) in order to examine possible benefits from radiation therapy dose escalation. A modified linear quadratic model was used to fit clinical tumor response and survival data of chemoradiation treatments for LAPC reported from 20 institutions. Biophysical radiosensitivity parameters were extracted from the fits. Examination of the clinical data demonstrated an enhancement in tumor response with higher irradiation dose, an important clinical result for palliation and quality of life. Little indication of improvement in 1-year survival with increased radiation dose was observed. Possible dose escalation schemes are proposed based on calculations of the biologically effective dose required for a 50% tumor response rate. Based on the evaluation of tumor response data, the escalation of radiation dose presents potential clinical benefits which when combined with normal tissue complication analyses may result in improved treatment outcome for locally advanced pancreatic cancer patients. Copyright © 2014 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.

Study of correlation between clinical, magnetic resonance imaging, and arthroscopic findings in meniscal and anterior cruciate ligament injuries

Directory of Open Access Journals (Sweden)

Subhash R Puri

2013-01-01

Full Text Available Background: Approx. 28% of patients presents to orthopedic OPD with complaints of knee pain. Common medical complications include an unstable knee, chronic knee pain, and post traumatic arthritis. Aim: To study the correlation between clinical, magnetic resonance imaging (MRI, and arthroscopic findings in knee injuries. Materials and Methods: About 30 cases with history of rotational injury having knee pain and recurrent swelling were subjected to study. Results: MRI had better sensitivity (0.95 vs. 0.85 and specificity (1.0 vs. 0.5 in comparison with clinical examination for medial meniscus. In lateral meniscus injury (sensitivity 0.65 vs. 0.61 and specificity 0.95 vs. 0.92 and in ACL injury (Sensitivity 0.77 vs. 0.8 and specificity 1.0 vs. 0.96 the sensitivity and specificity of MRI versus clinical examination showed minimal difference. Conclusion: Our conclusion is that carefully performed clinical examination can give equal or better diagnosis of meniscal and ACL injuries in comparison with MRI scan. MRI may be used as an additional tool for diagnosis.

Proposed Rectal Dose Constraints for Patients Undergoing Definitive Whole Pelvic Radiotherapy for Clinically Localized Prostate Cancer

International Nuclear Information System (INIS)

Chan, Linda W.; Xia Ping; Gottschalk, Alexander R.; Akazawa, Michelle; Scala, Matthew; Pickett, Barby M.S.; Hsu, I-C.; Speight, Joycelyn; Roach, Mack

2008-01-01

Purpose: Although several institutions have reported rectal dose constraints according to threshold toxicity, the plethora of trials has resulted in multiple, confusing dose-volume histogram recommendations. A set of standardized, literature-based constraints for patients undergoing whole pelvic radiotherapy (RT) for prostate cancer would help guide the practice of prostate RT. The purpose of this study was to develop these constraints, demonstrate that they are achievable, and assess the corresponding rectal toxicity. Methods and Materials: An extensive literature search identified eight key studies relating dose-volume histogram data to rectal toxicity. A correction factor was developed to address differences in the anatomic definition of the rectum across studies. The dose-volume histogram constraints recommended by each study were combined to generate the constraints. The data from all patients treated with definitive intensity-modulated RT were then compared against these constraints. Acute rectal toxicity was assessed. Results: A continuous, proposed rectal dose-constraint curve was generated. Intensity-modulated RT not only met this constraint curve, but also was able to achieve at least 30-40% lower dose to the rectum. The preliminary clinical results were also positive: 50% of patients reported no acute bowel toxicity, 33% reported Grade 1 toxicity, and 17% reported Grade 2 toxicity. No patients reported Grade 3-4 acute rectal toxicity. Conclusions: In this study, we developed a set of proposed rectal dose constraints. This allowed for volumetric assessment of the dose-volume relationship compared with single dose-volume histogram points. Additional research will be performed to validate this threshold as a class solution for rectal dose constraints

Effect of Genotype-Guided Warfarin Dosing on Clinical Events and Anticoagulation Control Among Patients Undergoing Hip or Knee Arthroplasty: The GIFT Randomized Clinical Trial.

Science.gov (United States)

Gage, Brian F; Bass, Anne R; Lin, Hannah; Woller, Scott C; Stevens, Scott M; Al-Hammadi, Noor; Li, Juan; Rodríguez, Tomás; Miller, J Philip; McMillin, Gwendolyn A; Pendleton, Robert C; Jaffer, Amir K; King, Cristi R; Whipple, Brandi DeVore; Porche-Sorbet, Rhonda; Napoli, Lynnae; Merritt, Kerri; Thompson, Anna M; Hyun, Gina; Anderson, Jeffrey L; Hollomon, Wesley; Barrack, Robert L; Nunley, Ryan M; Moskowitz, Gerard; Dávila-Román, Victor; Eby, Charles S

2017-09-26

Warfarin use accounts for more medication-related emergency department visits among older patients than any other drug. Whether genotype-guided warfarin dosing can prevent these adverse events is unknown. To determine whether genotype-guided dosing improves the safety of warfarin initiation. The randomized clinical Genetic Informatics Trial (GIFT) of Warfarin to Prevent Deep Vein Thrombosis included patients aged 65 years or older initiating warfarin for elective hip or knee arthroplasty and was conducted at 6 US medical centers. Enrollment began in April 2011 and follow-up concluded in October 2016. Patients were genotyped for the following polymorphisms: VKORC1-1639G>A, CYP2C9*2, CYP2C9*3, and CYP4F2 V433M. In a 2 × 2 factorial design, patients were randomized to genotype-guided (n = 831) or clinically guided (n = 819) warfarin dosing on days 1 through 11 of therapy and to a target international normalized ratio (INR) of either 1.8 or 2.5. The recommended doses of warfarin were open label, but the patients and clinicians were blinded to study group assignment. The primary end point was the composite of major bleeding, INR of 4 or greater, venous thromboembolism, or death. Patients underwent a screening lower-extremity duplex ultrasound approximately 1 month after arthroplasty. Among 1650 randomized patients (mean age, 72.1 years [SD, 5.4 years]; 63.6% women; 91.0% white), 1597 (96.8%) received at least 1 dose of warfarin therapy and completed the trial (n = 808 in genotype-guided group vs n = 789 in clinically guided group). A total of 87 patients (10.8%) in the genotype-guided group vs 116 patients (14.7%) in the clinically guided warfarin dosing group met at least 1 of the end points (absolute difference, 3.9% [95% CI, 0.7%-7.2%], P = .02; relative rate [RR], 0.73 [95% CI, 0.56-0.95]). The numbers of individual events in the genotype-guided group vs the clinically guided group were 2 vs 8 for major bleeding (RR, 0.24; 95% CI, 0

Consolidating duodenal and small bowel toxicity data via isoeffective dose calculations based on compiled clinical data.

Science.gov (United States)

Prior, Phillip; Tai, An; Erickson, Beth; Li, X Allen

2014-01-01

To consolidate duodenum and small bowel toxicity data from clinical studies with different dose fractionation schedules using the modified linear quadratic (MLQ) model. A methodology of adjusting the dose-volume (D,v) parameters to different levels of normal tissue complication probability (NTCP) was presented. A set of NTCP model parameters for duodenum toxicity were estimated by the χ(2) fitting method using literature-based tolerance dose and generalized equivalent uniform dose (gEUD) data. These model parameters were then used to convert (D,v) data into the isoeffective dose in 2 Gy per fraction, (D(MLQED2),v) and convert these parameters to an isoeffective dose at another NTCP (D(MLQED2'),v). The literature search yielded 5 reports useful in making estimates of duodenum and small bowel toxicity. The NTCP model parameters were found to be TD50(1)(model) = 60.9 ± 7.9 Gy, m = 0.21 ± 0.05, and δ = 0.09 ± 0.03 Gy(-1). Isoeffective dose calculations and toxicity rates associated with hypofractionated radiation therapy reports were found to be consistent with clinical data having different fractionation schedules. Values of (D(MLQED2'),v) between different NTCP levels remain consistent over a range of 5%-20%. MLQ-based isoeffective calculations of dose-response data corresponding to grade ≥2 duodenum toxicity were found to be consistent with one another within the calculation uncertainty. The (D(MLQED2),v) data could be used to determine duodenum and small bowel dose-volume constraints for new dose escalation strategies. Copyright © 2014 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.

Esophageal Lichen Planus: Clinical and Radiographic Findings in Eight Patients.

Science.gov (United States)

Rauschecker, Andreas M; Levine, Marc S; Whitson, Matthew J; Tondon, Rashmi; Rubesin, Stephen E; Furth, Emma E; Metz, David C

2017-01-01

The purpose of this study is to present the clinical and radiographic findings of esophageal lichen planus. A search of computerized medical records identified 15 patients with pathologic findings of esophageal lichen planus on endoscopic biopsy specimens. Three other patients had presumed esophageal lichen planus, although no biopsy specimens were obtained. Twelve of these 18 patients (67%) had double-contrast esophagography performed at our institution; for eight of the 12 patients (67%), the studies revealed abnormalities in the esophagus. These eight patients constituted our study group. The barium esophagrams and medical records of these eight patients were reviewed to determine the clinical, radiographic, and endoscopic findings of esophageal lichen planus as well as the treatment and patient outcome. All eight patients were women (median age, 66.5 years), and all eight presented with dysphagia (mean duration, 3.2 years). Four patients had previous lichen planus that involved the skin (n = 1), the oral cavity (n = 2), or both (n = 1), and one patient later had lichen planus that involved the vagina. Five patients had a small-caliber esophagus with diffuse esophageal narrowing. The remaining three patients had segmental strictures in the cervical (n = 1), upper thoracic (n = 1), and distal thoracic (n = 1) esophagus. Esophageal lichen planus typically occurs in older women with longstanding dysphagia and often develops in the absence of extraesophageal disease. Barium esophagrams may reveal a small-caliber esophagus or, less commonly, segmental esophageal strictures. Greater awareness of the radiographic findings of esophageal lichen planus hopefully will lead to earlier diagnosis and better management of this condition.

Disparity between ultrasound and clinical findings in psoriatic arthritis.

Science.gov (United States)

Husic, Rusmir; Gretler, Judith; Felber, Anja; Graninger, Winfried B; Duftner, Christina; Hermann, Josef; Dejaco, Christian

2014-08-01

To investigate the association between psoriatic arthritis (PsA)-specific clinical composite scores and ultrasound-verified pathology as well as comparison of clinical and ultrasound definitions of remission. We performed a prospective study on 70 consecutive PsA patients. Clinical assessments included components of Disease Activity Index for Psoriatic Arthritis (DAPSA) and the Composite Psoriatic Disease Activity Index (CPDAI). Minimal disease activity (MDA) and the following remission criteria were applied: CPDAI joint, entheses and dactylitis domains (CPDAI-JED)=0, DAPSA≤3.3, Boolean's remission definition and physician-judged remission (rem-phys). B-mode and power Doppler (PD-) ultrasound findings were semiquantitatively scored at 68 joints (evaluating synovia, peritendinous tissue, tendons and bony changes) and 14 entheses. Ultrasound remission and minimal ultrasound disease activity (MUDA) were defined as PD-score=0 and PD-score ≤1, respectively, at joints, peritendinous tissue, tendons and entheses. DAPSA but not CPDAI correlated with B-mode and PD-synovitis. Ultrasound signs of enthesitis, dactylitis, tenosynovitis and perisynovitis were not linked with clinical composites. Clinical remission or MDA was observed in 15.7% to 47.1% of PsA patients. Ultrasound remission and MUDA were present in 4.3% and 20.0% of patients, respectively. Joint and tendon-related PD-scores were higher in patients with active versus inactive disease according to CPDAI-JED, DAPSA, Boolean's and rem-phys, whereas no difference was observed regarding enthesitis and perisynovitis. DAPSA≤3.3 (OR 3.9, p=0.049) and Boolean's definition (OR 4.6, p=0.03) were more useful to predict MUDA than other remission criteria. PsA-specific composite scores partially reflect ultrasound findings. DAPSA and Boolean's remission definitions better identify MUDA patients than other clinical criteria. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted

Diagnosis of cerebral metastases by means of standard doses of Gadobutrol versus a high-dose protocol. Intraindividual evaluation of a phase-II high-dose study

International Nuclear Information System (INIS)

Vogl, T.J.; Friebe, C.E.; Balzer, T.; Mack, M.G.; Steiner, S.; Schedel, H.; Pegios, W.; Lanksch, W.; Banzer, D.; Felix, R.

1995-01-01

In a clinical phase-II study 20 patients who had been diagnosed as having brain metastases with CT or MRT were studied prospectively with Gadobutrol, a new nonionic, low osmolality contrast agent. Each patient received an initial injection of 0.1 mmol/kg body weight and an additional dose of 0.2 mmol/kg Gadobutrol 10 min later. Spinecho images were obtained before and after the two applications of Gadobutrol. Dynamic scanning (Turbo-FLASH) was performed for 3 min after each injection of the contrast agent. Both quantitative and qualitative data were intraindividually evaluated. The primary tumor was a bronchial carcinoma in 11 cases; in 9 other cases there were different primary tumors. Forty-eight hours after the use of Gadobutrol there were no adverse signs in the clinical examination, vital signs or blood and urine chemistry. Statistical analysis (Friedman test and Wilcoxon test) of the C/N ratios between tumor and white matter, percentage enhancement, and visual assessment rating revealed statistically significant superiority of high-dose Gadobutrol injection in comparison to the standard dose. The percentage enhancement increased on average from 104% after 0.1 mmol/kg to 162% after 0.3 mmol/kg Gadobutrol. Qualitative delineation and contrast of the lesions increased significantly. The use of high-dose Gadobutrol improved the detection of 36 additional lesions in 6 patients. (orig./VHE) [de

Ketosis in buffalo (Bubalus bubalis): clinical findings and the associated oxidative stress level.

Science.gov (United States)

Youssef, Mohamed A; El-Khodery, Sabry Ahmed; El-deeb, Wael M; Abou El-Amaiem, Waleed E E

2010-12-01

As little is known about the oxidant/antioxidant status in buffalo with ketosis, the present study was delineated to assess the oxidative stress level associated with clinical ketosis in water buffalo. A total of 91 parturient buffalo at smallholder farms were studied (61 suspected to be ketotic and 30 healthy). Clinical and biochemical investigations were carried out for each buffalo. Based on clinical findings and the level of beta-hydroxybutyrate (BHB), buffalo were allocated into ketotic (42), subclinical cases (19). Clinically, there was an association between clinical ketosis and anorexia (pketosis compared with subclinical and control cases, there was a significant increase (pketosis.

A dose error evaluation study for 4D dose calculations

Science.gov (United States)

Milz, Stefan; Wilkens, Jan J.; Ullrich, Wolfgang

2014-10-01

Previous studies have shown that respiration induced motion is not negligible for Stereotactic Body Radiation Therapy. The intrafractional breathing induced motion influences the delivered dose distribution on the underlying patient geometry such as the lung or the abdomen. If a static geometry is used, a planning process for these indications does not represent the entire dynamic process. The quality of a full 4D dose calculation approach depends on the dose coordinate transformation process between deformable geometries. This article provides an evaluation study that introduces an advanced method to verify the quality of numerical dose transformation generated by four different algorithms. The used transformation metric value is based on the deviation of the dose mass histogram (DMH) and the mean dose throughout dose transformation. The study compares the results of four algorithms. In general, two elementary approaches are used: dose mapping and energy transformation. Dose interpolation (DIM) and an advanced concept, so called divergent dose mapping model (dDMM), are used for dose mapping. The algorithms are compared to the basic energy transformation model (bETM) and the energy mass congruent mapping (EMCM). For evaluation 900 small sample regions of interest (ROI) are generated inside an exemplary lung geometry (4DCT). A homogeneous fluence distribution is assumed for dose calculation inside the ROIs. The dose transformations are performed with the four different algorithms. The study investigates the DMH-metric and the mean dose metric for different scenarios (voxel sizes: 8 mm, 4 mm, 2 mm, 1 mm 9 different breathing phases). dDMM achieves the best transformation accuracy in all measured test cases with 3-5% lower errors than the other models. The results of dDMM are reasonable and most efficient in this study, although the model is simple and easy to implement. The EMCM model also achieved suitable results, but the approach requires a more complex

Exposure to low dose ionising radiation: Molecular and clinical consequences.

LENUS (Irish Health Repository)

Martin, Lynn M

2014-07-10

This review article provides a comprehensive overview of the experimental data detailing the incidence, mechanism and significance of low dose hyper-radiosensitivity (HRS). Important discoveries gained from past and present studies are mapped and highlighted to illustrate the pathway to our current understanding of HRS and the impact of HRS on the cellular response to radiation in mammalian cells. Particular attention is paid to the balance of evidence suggesting a role for DNA repair processes in the response, evidence suggesting a role for the cell cycle checkpoint processes, and evidence investigating the clinical implications\\/relevance of the effect.

Effect of infliximab dose increase in rheumatoid arthritis at different trough concentrations: a cohort study in clinical practice conditions

Directory of Open Access Journals (Sweden)

Chamaida ePlasencia

2015-10-01

Full Text Available BackgroundEvidence supporting treatment intensification in rheumatoid arthritis is limited and controversial. We explored outcomes of infliximab dose increases and accounted for pre-existing trough levels in patients with active rheumatoid arthritis (RA.MethodsThis study was a retrospective study of 42 RA patients who received increased infliximab following an insufficient response (DAS28 > 3.2. Serum concentrations of infliximab and antibodies to infliximab (ATI and DAS28 and EULAR clinical response parameters were recorded for one year. Analyses were performed in three patient groups that were defined by infliximab serum concentration prior to treatment enhancement: No detectable, Low (< 1.1 µg/mL or High (≥ 1.1 µg/mL drug levels. Results No circulating infliximab was detected in 20 patients (47.6 %, but 13 (30.9 % and 9 (21.4 % patients exhibited Low and High levels, respectively. ATI were only detected in patients with No detectable drug levels because the drug interferes with ELISA. DAS28 disease activity globally showed a modest improvement after dose escalation, but this improvement did not persist after 6 and 12 months. Infliximab serum levels increased significantly in the High group (p=0.016, but no increase was achieved in the Low and No detectable groups. The three study groups exhibited similar disease activity over time, and no improvement was observed in the non-responder EULAR rates. ConclusionsThese results suggest that the efficacy of an infliximab dose increase is limited, and the response is independent of the infliximab trough serum concentration that is achieved prior to escalation.

Biologically effective dose distribution based on the linear quadratic model and its clinical relevance

International Nuclear Information System (INIS)

Lee, Steve P.; Leu, Min Y.; Smathers, James B.; McBride, William H.; Parker, Robert G.; Withers, H. Rodney

1995-01-01

Purpose: Radiotherapy plans based on physical dose distributions do not necessarily entirely reflect the biological effects under various fractionation schemes. Over the past decade, the linear-quadratic (LQ) model has emerged as a convenient tool to quantify biological effects for radiotherapy. In this work, we set out to construct a mechanism to display biologically oriented dose distribution based on the LQ model. Methods and Materials: A computer program that converts a physical dose distribution calculated by a commercially available treatment planning system to a biologically effective dose (BED) distribution has been developed and verified against theoretical calculations. This software accepts a user's input of biological parameters for each structure of interest (linear and quadratic dose-response and repopulation kinetic parameters), as well as treatment scheme factors (number of fractions, fractional dose, and treatment time). It then presents a two-dimensional BED display in conjunction with anatomical structures. Furthermore, to facilitate clinicians' intuitive comparison with conventional fractionation regimen, a conversion of BED to normalized isoeffective dose (NID) is also allowed. Results: Two sample cases serve to illustrate the application of our tool in clinical practice. (a) For an orthogonal wedged pair of x-ray beams treating a maxillary sinus tumor, the biological effect at the ipsilateral mandible can be quantified, thus illustrates the so-called 'double-trouble' effects very well. (b) For a typical four-field, evenly weighted prostate treatment using 10 MV x-rays, physical dosimetry predicts a comparable dose at the femoral necks between an alternate two-fields/day and four-fields/day schups. However, our BED display reveals an approximate 21% higher BED for the two-fields/day scheme. This excessive dose to the femoral necks can be eliminated if the treatment is delivered with a 3:2 (anterio-posterior/posterio-anterior (AP

A Negative Finding from a Single Center Study Led to Re-Design of a Large-Scale Clinical Trial of Phytotherapy for Benign Prostatic Hyperplasia: the CAMUS study

Science.gov (United States)

Lee, Jeannette Y.; Andriole, Gerald; Avins, Andrew; Crawford, E. David; Foster, Harris; Kaplan, Steven; Kreder, Karl; Kusek, John W.; McCullough, Andrew; McVary, Kevin; Meleth, Sreelatha; Naslund, Michael; Nickel, J. Curtis; Nyberg, Leroy M.; Roehrborn, Claus; Williams, O. Dale; Barry, Michael J.

2010-01-01

Background Benign prostatic hyperplasia (BPH), a common condition among older men, confers its morbidity through potentially bothersome lower urinary tract symptoms. Treatments for BPH include drugs such as alpha adrenergic receptor blockers and 5-alpha reductase inhibitors, minimally invasive therapies that use heat to damage or destroy prostate tissue, and surgery including transurethral resection of the prostate. Complementary and alternative medicines are gaining popularity in the U.S. Two phytotherapies commonly used for BPH are extracts of the fruit of Serenoa repens, the Saw palmetto dwarf palm that grows in the Southeastern U.S., and extracts of the bark of Pygeum africanum, the African plum tree. Purpose The objective of the Complementary and Alternative Medicines for Urological Symptoms (CAMUS) clinical trial is to determine if phytotherapy is superior to placebo in the treatment of BPH. Methods CAMUS was originally designed as a 3300-participant, four-arm trial of Serenoa repens, Pygeum africanum, an alpha adrenergic blocking drug, and placebo with time to clinical progression of BPH, a measure of long-term efficacy, as the primary endpoint. Before enrollment started, a randomized, double-blind, placebo-controlled, single institution clinical trial showed that Serenoa repens at the usual dose did not demonstrate any benefit over placebo with respect to symptom relief at one year. Consequently, the focus of CAMUS shifted from evaluating long-term efficacy to determining if any short-term (6-18 month) symptom relief could be achieved with increasing doses of Serenoa repens, the phytotherapy most commonly used in the U.S. for BPH. Results Results are anticipated in 2011. Conclusions Trial design occurs in an environment of continually evolving information. In this case, emerging results from another trial suggested that a study of long-term efficacy was premature, and that an effective dose and preparation of Serenoa repens had to be established before

Reversal of rocuronium-induced neuromuscular block by the selective relaxant binding agent sugammadex: a dose-finding and safety study

DEFF Research Database (Denmark)

Sorgenfrei, Iben F; Norrild, Kathrine; Larsen, Per Bo

2006-01-01

Sugammadex (Org 25969) forms a complex with steroidal neuromuscular blocking agents, thereby reversing neuromuscular block. This study investigated the dose-response relation, safety, and pharmacokinetics of sugammadex to reverse rocuronium-induced block.......Sugammadex (Org 25969) forms a complex with steroidal neuromuscular blocking agents, thereby reversing neuromuscular block. This study investigated the dose-response relation, safety, and pharmacokinetics of sugammadex to reverse rocuronium-induced block....

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.

Science.gov (United States)

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.

Axitinib dose titration: analyses of exposure, blood pressure and clinical response from a randomized phase II study in metastatic renal cell carcinoma.

Science.gov (United States)

Rini, B I; Melichar, B; Fishman, M N; Oya, M; Pithavala, Y K; Chen, Y; Bair, A H; Grünwald, V

2015-07-01

In a randomized, double-blind phase II trial in patients with metastatic renal cell carcinoma (mRCC), axitinib versus placebo titration yielded a significantly higher objective response rate. We evaluated pharmacokinetic and blood pressure (BP) data from this study to elucidate relationships among axitinib exposure, BP change, and efficacy. Patients received axitinib 5 mg twice daily during a lead-in period. Patients who met dose-titration criteria were randomized 1:1 to stepwise dose increases with axitinib or placebo. Patients ineligible for randomization continued without dose increases. Serial 6-h and sparse pharmacokinetic sampling were carried out; BP was measured at clinic visits and at home in all patients, and by 24-h ambulatory BP monitoring (ABPM) in a subset of patients. Area under the plasma concentration-time curve from 0 to 24 h throughout the course of treatment (AUCstudy) was higher in patients with complete or partial responses than those with stable or progressive disease in the axitinib-titration arm, but comparable between these groups in the placebo-titration and nonrandomized arms. In the overall population, AUCstudy and efficacy outcomes were not strongly correlated. Mean BP across the population was similar when measured in clinic, at home, or by 24-h ABPM. Weak correlations were observed between axitinib steady-state exposure and diastolic BP. When grouped by change in diastolic BP from baseline, patients in the ≥10 and ≥15 mmHg groups had longer progression-free survival. Optimal axitinib exposure may differ among patients with mRCC. Pharmacokinetic or BP measurements cannot be used exclusively to guide axitinib dosing. Individualization of treatment with vascular endothelial growth factor receptor tyrosine kinase inhibitors, including axitinib, is thus more complex than anticipated and cannot be limited to a single clinical factor. © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical

Clinical and Proctosigmoidoscopic findings in Patients with ...

African Journals Online (AJOL)

Background: Anorectal sepsis is a distressing condition which is sometimes inadequately treated. Objectives: To determine the clinical and prostosigmoidoscopic findings in patients with anorectal sepsis seen by the authors over a 5 year period as well as identifying the commonly performed procedures. Method: A review of ...

Case report: clinical and postmortem findings in four cows with rib fracture

OpenAIRE

Braun, Ueli; Warislohner, Sonja; Hetzel, Udo; Nuss, Karl

2017-01-01

BACKGROUND: Published reports of rib fractures in adult cattle are limited to the occurrence of chronic rib swellings caused by calluses, which are unremarkable from a clinical standpoint, whereas studies identifying clinical signs of rib fractures were not found in a literature search. This report describes the clinical and postmortem findings in four cows with rib fractures. CASE PRESENTATION: The 13th rib was fractured in three cows and the 11th rib in the remaining cow; three fractures...

Repeated dose titration versus age-based method in electroconvulsive therapy: a pilot study.

Science.gov (United States)

Aten, Jan Jaap; Oudega, Mardien; van Exel, Eric; Stek, Max L; van Waarde, Jeroen A

2015-06-01

In electroconvulsive therapy (ECT), a dose titration method (DTM) was suggested to be more individualized and therefore more accurate than formula-based dosing methods. A repeated DTM (every sixth session and dose adjustment accordingly) was compared to an age-based method (ABM) regarding treatment characteristics, clinical outcome, and cognitive functioning after ECT. Thirty-nine unipolar depressed patients dosed using repeated DTM and 40 matched patients treated with ABM were compared. Montgomery-Åsberg Depression Rating Scale (MADRS) and Mini-Mental State Examination (MMSE) were assessed at baseline and at the end of the index course, as well as the total number of ECT sessions. Both groups were similar regarding age, sex, psychotic features, mean baseline MADRS, and median baseline MMSE. At the end of the index course, the two methods showed equal outcome (mean end MADRS, 11.6 ± 8.3 in DTM and 9.5 ± 7.6 in ABM (P = 0.26); median end MMSE, 28 (25-29) and 28 (25-29.8), respectively (P = 0.81). However, the median number of all ECT sessions differed 16 (11-22) in DTM versus 12 (10-14.8) in ABM; P = 0.02]. Using regression analysis, dosing method and age were independently associated with the total number of ECT sessions, with less sessions needed in ABM (P = 0.02) and in older patients (P = 0.001). In this comparative cohort study, ABM and DTM showed equal outcome for depression and cognition. However, the median ECT course duration in repeated DTM appeared longer. Additionally, higher age was associated with shorter ECT courses regardless of the dosing method. Further prospective studies are needed to confirm these findings.

Clinical relevance of findings in trials of CBT for depression.

Science.gov (United States)

Lepping, P; Whittington, R; Sambhi, R S; Lane, S; Poole, R; Leucht, S; Cuijpers, P; McCabe, R; Waheed, W

2017-09-01

Cognitive behavioural therapy (CBT) is beneficial in depression. Symptom scores can be translated into Clinical Global Impression (CGI) scale scores to indicate clinical relevance. We aimed to assess the clinical relevance of findings of randomised controlled trials (RCTs) of CBT in depression. We identified RCTs of CBT that used the Hamilton Rating Scale for Depression (HAMD). HAMD scores were translated into Clinical Global Impression - Change scale (CGI-I) scores to measure clinical relevance. One hundred and seventy datasets from 82 studies were included. The mean percentage HAMD change for treatment arms was 53.66%, and 29.81% for control arms, a statistically significant difference. Combined active therapies showed the biggest improvement on CGI-I score, followed by CBT alone. All active treatments had better than expected HAMD percentage reduction and CGI-I scores. CBT has a clinically relevant effect in depression, with a notional CGI-I score of 2.2, indicating a significant clinical response. The non-specific or placebo effect of being in a psychotherapy trial was a 29% reduction of HAMD. Copyright © 2017. Published by Elsevier Masson SAS.

A clinical and pathological study of acute rectal injury by the radiation therapy of uterine cervix cancer

International Nuclear Information System (INIS)

Honke, Yoshifumi; Katsuta, Shizutomo; Katayama, Hiroshi; Haruma, Ken; Fujiwara, Atsushi; Suenaga, Kenji.

1983-01-01

The clinical features, magnifying colonoscopic findings and pathological findings of acute radiation proctitis were investigated in 40 cases of uterine cervix cancer and the following results were obtained. 1)As a clinical simptom, diarrhea was observed in about half of all cases. 2)The value of serum total protein and number of leukocyte decreased until the dose of 30 Gy (3000 rads) and no remarkable change of them were observed afterwards. Hemoglobin value did not change throughout the whole clinical course. 3)Magnifying colonoscopic findings showed remarkable change with increase of the dose and especially irregularity of pit was observed in all cases. 4)In pathological findings, edema, degenerative change of epitherial cells and decreased number of goblet cells were observed from the beginning. In cases that received more than 50 Gy (5000 rads), fibrosis developed and the epithelium showed strong regeneration. Also Paneth cells were observed in 5 out of 40 cases. 5)Remarkable change was not observed before or after the radiation by barium enema. (author)

Epithelioid sarcoma: clinical, MR imaging and pathologic findings

International Nuclear Information System (INIS)

Hanna, S.L.; Kaste, S.; Jenkins, J.J.; Hewan-Lowe, K.; Spence, J.V.; Gupta, M.; Monson, D.; Fletcher, B.D.

2002-01-01

Objective. To report and describe the MR imaging features of eight new cases of this rare soft tissue sarcoma and correlate them with the clinical and histologic findings.Design and patients. Retrospective analysis was carried out for the MR imaging characteristics and histologic findings of eight patients with pathologically proven epithelioid sarcoma and the literature was reviewed. Findings were correlated in each case with the patient's clinical presentation and eventual outcome.Results. The patients, whose primary tumors ranged from 2.5 cm to 19 cm in maximum dimension, were 1 to 90 years of age. Tumors involved the extremities (n=5), the scalp (n=2) and the paraspinal muscles (n=1). Five tumors presented as well-defined, frequently painful, deeply situated masses and three as subcutaneous nodules or cutaneous ulcers with no palpable mass. Four patients had associated regional lymphadenopathy and one had distant metastases at diagnosis. MR imaging showed tumor infiltration of adjacent tissues in seven patients. Signal characteristics reflected varying degrees of cellularity, and the presence of necrosis, hemorrhage, fibrosis, hyalinization and inflammation. Bone marrow involvement was demonstrated in one patient. Clinical outcomes were generally poor.Conclusions. Epithelioid sarcoma is an aggressive soft tissue sarcoma with a varied clinical presentation, growth pattern, MR signal characteristics and histologic picture. The tumor favors the distal extremities and is commonly infiltrative and accompanied by enlarged regional lymph nodes. This neoplasm may present as an intramuscular mass but should also be suspected in patients with ulcerating cutaneous nodules with or without regional lymphadenopathy. (orig.)

THE STUDY OF CLINICAL VARIATIONS AND HISTOPATHOLOGICAL FINDINGS IN POLYMORPHOUS LIGHT ERUPTION

Directory of Open Access Journals (Sweden)

Banoth Mohan Lal

2016-07-01

Full Text Available BACKGROUND Epstein. S in 1942 described PMLE under the name of Prurigo aestivalis. He first hypothesised that PMLE represents a form of delayed-type hypersensitivity response to an endogenous, cutaneous UV-induced antigen, because of the hours or days delay between sun exposure and manifestation of symptoms, and the histological appearance of lesional skin. Firm evidence; however, has been lacking and the responsible allergen has not been identified. PMLE a specific entity encompassing six clinical manifestations: Small erythematous papulovesicles, eczematous lesions, large papules, oedematous plaques, prurigo nodules and erythema multiforme-like lesions. The histological features of PMLE are characteristic, but not pathognomonic and vary with the different clinical presentation. A sincere effort has been put in this study to understand the clinical and histopathological features of polymorphic light lesions. The study is intended to help the practising physicians and dermatologists to diagnose the pathology on time and intervene before it develops into complications. METHODS Material for the present study consisted of 100 cases of clinically diagnosed untreated cases of polymorphous light eruption, who were attending the skin and STD and Leprosy Department, Kakatiya Medical College, Warangal, during January 2014 to Dec 2014 were selected for this study. The patients were selected randomly irrespective of age, sex, socioeconomic status. RESULTS Histopathology showed perivascular lymphocytic infiltration in the dermis in majority of our cases (93.33% and clinicohistopathological correlation was observed in most cases; hence apart from clinical examination, histopathological examination plays an important role in diagnosing PMLE. CONCLUSION 56 percent of the patients complained pruritus followed by burning. The study was similar to other studies in comparison.

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

International Nuclear Information System (INIS)

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

2007-01-01

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

The clinical significance of equivocal findings on spinal MRI in children with medulloblastoma.

Science.gov (United States)

Bennett, Julie; Ashmawy, Ramy; Ramaswamy, Vijay; Stephens, Derek; Bouffet, Eric; Laperriere, Normand; Taylor, Michael; Shroff, Manohar; Bartels, Ute

2017-08-01

Medulloblastoma (MB) is the most common malignant brain tumor of childhood, with cerebrospinal fluid spread the most common site of metastasis. Currently, children diagnosed with MB and evidence of spinal metastasis are treated with an increased dose of craniospinal radiation (CSI). This report reviewed equivocal abnormalities including nerve root clumping, linear vascular enhancement, nerve root enhancement and/or other vague findings on spinal magnetic resonance imaging (MRI) to elucidate their prognostic significance and aid in risk stratification. This retrospective cohort study identified children (≥3 years) diagnosed with MB between 1988 and 2012. Children treated with upfront CSI were included, and staging spine MRI must have been done preoperatively or within 72 hr of primary tumor resection. Initial MRI of the spine was assessed by two independent reviewers blinded to outcome to evaluate for equivocal findings. Survival analysis was done to determine impact on prognosis. One hundred of 157 patients were eligible for the analysis. Equivocal findings were identified in 48 (48%) patients, with MRI done preoperatively in 45 (94%) patients. Analysis by subgroup identified a higher proportion of equivocal findings in the sonic hedgehog (SHH) subgroup (P = 0.007). Five-year overall survival (OS) in children with equivocal findings compared to those with normal MRI was not different, 80 vs. 84.8% respectively, while OS in M3 patients was worse at 54.7% (P = 0.02). A higher proportion of equivocal findings was identified in the SHH subgroup. This institutional retrospective review demonstrates equivocal findings are common, not associated with decreased OS and should not prompt increased dose of CSI. © 2017 Wiley Periodicals, Inc.

Nationwide Study of Humidifier Disinfectant Lung Injury in South Korea, 1994-2011. Incidence and Dose-Response Relationships.

Science.gov (United States)

Paek, Domyung; Koh, Younsuck; Park, Dong-Uk; Cheong, Hae-Kwan; Do, Kyung-Hyun; Lim, Chae-Man; Hong, Soo-Jong; Kim, Yong-Hwa; Leem, Jong-Han; Chung, Kyu Hyuck; Choi, Ye-Yong; Lee, Jong-Hyeon; Lim, Sin-Ye; Chung, Eun-Hee; Cho, Young Ah; Chae, Eun Jin; Joh, Joon-Sung; Yoon, Yup; Lee, Kyu-Hong; Choi, Bo Youl; Gwack, Jin

2015-12-01

Humidifier disinfectant lung injury is an acute lung disease attributed to recurrent inhalation of certain disinfectant aerosols emitted from room humidifiers. An outbreak of this toxic lung injury occurred in South Korea from 1995 until all humidifier disinfectant products were recalled from the consumer market by the government in 2011. A nationwide study was conducted to ascertain and classify all potential cases of humidifier disinfectant lung injury in Korea and to assess dose-response relationships. By several mechanisms, clinicians and the general public were invited to report all suspected cases of humidifier disinfectant lung injury to public health officials in South Korea. A committee was convened to define diagnostic criteria based on pathologic, radiologic, and clinical findings for index cases, combined with assessment of environmental exposure to humidifier disinfectants. Clinical review and environmental assessments were performed and later combined to determine overall likelihood of disease for each study participant, classified as definite, probable, possible, or unlikely. Survival time from exposure to onset of symptoms was analyzed to assess dose-response relationships. Three broad categories of risk factors were examined: (1) biological susceptibility, (2) temporal cycle of exposure and recovery, and (3) spatial conditions and density of disinfectant. Of 374 possible cases identified and reviewed, 329 were unanimously classified by the diagnostic committee, as follows: 117 definite, 34 probable, 38 possible and 140 unlikely cases. A total of 62 individuals with definite or probable disease died. Risk factors examined for polyhexamethyleneguanidine phosphate exposure that were found to be significant in shortening survival included age 4 years or younger at onset, use of disinfectant for 7 days per week, airborne density of 800 μg/m(3) or more of disinfectant, and daily exposure 11 or more hours in duration. Dose-response analysis indicated

Clinical and pulmonary thin-section CT findings in acute Klebsiella Pneumoniae pneumonia

International Nuclear Information System (INIS)

Okada, Fumito; Ando, Yumiko; Honda, Koichi; Nakayama, Tomoko; Kiyonaga, Maki; Ono, Asami; Tanoue, Shuichi; Maeda, Toru; Mori, Hiromu

2009-01-01

The aim of this study was to assess the clinical and pulmonary thin-section CT findings in patients with acute Klebsiella pneumoniae pneumonia. We retrospectively evaluated thin-section CT examinations performed between January 1991 and December 2007 from 962 patients with acute Klebsiella pneumoniae pneumonia. Seven hundred and sixty-four cases with concurrent infectious diseases were excluded. Thus, our study group comprised 198 patients (118 male, 80 female; age range 18-97 years, mean age 61.5). Underlying diseases and clinical findings were assessed. Parenchymal abnormalities were evaluated along with the presence of enlarged lymph nodes and pleural effusion. CT findings in patients with acute Klebsiella pneumoniae pneumonia consisted mainly of ground-glass attenuation (100%), consolidation (91.4%), and intralobular reticular opacity (85.9%), which were found in the periphery (96%) of both sides of the lungs (72.2%) and were often associated with pleural effusion (53%). The underlying conditions in patients with Klebsiella pneumoniae pneumonia were alcoholism or smoking habit. (orig.)

Clinical and pulmonary thin-section CT findings in acute Klebsiella Pneumoniae pneumonia

Energy Technology Data Exchange (ETDEWEB)

Okada, Fumito [Oita University Faculty of Medicine, Department of Diagnostic and Interventional Radiology, Oita (Japan); Oita University Faculty of Medicine, Department of Radiology, Oita (Japan); Ando, Yumiko; Honda, Koichi; Nakayama, Tomoko; Kiyonaga, Maki; Ono, Asami; Tanoue, Shuichi; Maeda, Toru; Mori, Hiromu [Oita University Faculty of Medicine, Department of Diagnostic and Interventional Radiology, Oita (Japan)

2009-04-15

The aim of this study was to assess the clinical and pulmonary thin-section CT findings in patients with acute Klebsiella pneumoniae pneumonia. We retrospectively evaluated thin-section CT examinations performed between January 1991 and December 2007 from 962 patients with acute Klebsiella pneumoniae pneumonia. Seven hundred and sixty-four cases with concurrent infectious diseases were excluded. Thus, our study group comprised 198 patients (118 male, 80 female; age range 18-97 years, mean age 61.5). Underlying diseases and clinical findings were assessed. Parenchymal abnormalities were evaluated along with the presence of enlarged lymph nodes and pleural effusion. CT findings in patients with acute Klebsiella pneumoniae pneumonia consisted mainly of ground-glass attenuation (100%), consolidation (91.4%), and intralobular reticular opacity (85.9%), which were found in the periphery (96%) of both sides of the lungs (72.2%) and were often associated with pleural effusion (53%). The underlying conditions in patients with Klebsiella pneumoniae pneumonia were alcoholism or smoking habit. (orig.)

Dose-dependent effects of the clinical anesthetic isoflurane on Octopus vulgaris: a contribution to cephalopod welfare.

Science.gov (United States)

Polese, Gianluca; Winlow, William; Di Cosmo, Anna

2014-12-01

Recent progress in animal welfare legislation relating to invertebrates has provoked interest in methods for the anesthesia of cephalopods, for which different approaches to anesthesia have been tried but in most cases without truly anesthetizing the animals. For example, several workers have used muscle relaxants or hypothermia as forms of "anesthesia." Several inhalational anesthetics are known to act in a dose-dependent manner on the great pond snail Lymnaea stagnalis, a pulmonate mollusk. Here we report, for the first time, on the effects of clinical doses of the well-known inhalational clinical anesthetic isoflurane on the behavioral responses of the common octopus Octopus vulgaris. In each experiment, isoflurane was equilibrated into a well-aerated seawater bath containing a single adult O. vulgaris. Using a web camera, we recorded each animal's response to touch stimuli eliciting withdrawal of the arms and siphon and observed changes in the respiratory rate and the chromatophore pattern over time (before, during, and after application of the anesthetic). We found that different animals of the same size responded with similar behavioral changes as the isoflurane concentration was gradually increased. After gradual application of 2% isoflurane for a maximum of 5 min (at which time all the responses indicated deep anesthesia), the animals recovered within 45-60 min in fresh aerated seawater. Based on previous findings in gastropods, we believe that the process of anesthesia induced by isoflurane is similar to that previously observed in Lymnaea. In this study we showed that isoflurane is a good, reversible anesthetic for O. vulgaris, and we developed a method for its use.

Clinical relevance of findings in trials of CBT for depression

NARCIS (Netherlands)

Lepping, P.; Whittington, R.; Sambhi, R.S.; Lane, S.; Poole, R.; Leucht, S.; Cuijpers, P.; McCabe, R.; Waheed, W.

2017-01-01

Cognitive behavioural therapy (CBT) is beneficial in depression. Symptom scores can be translated into Clinical Global Impression (CGI) scale scores to indicate clinical relevance. We aimed to assess the clinical relevance of findings of randomised controlled trials (RCTs) of CBT in depression. We

A phase 2 clinical study of 99mTc-MAG3 injectable, a dynamic renal imaging agent

International Nuclear Information System (INIS)

Torizuka, Kanji; Yamamoto, Kazutaka; Nishibuchi, Shigeo; Ishibashi, Akira; Ikekubo, Katsuji.

1993-01-01

A phase 2 clinical study of 99m Tc-mercapto acetyl glycylglycylglycine ( 99m Tc-MAG3) injectable, a new dynamic renal imaging agent, was performed in 110 patients with renal and/or urinary disorders to evaluate the safety, efficacy and optimal dose of this agent. Neither adverse reactions nor abnormal laboratory findings due to intravenous administration of 99m Tc-MAG3 were observed. The investigators evaluated the clinical efficacy of 99m Tc-MAG3 was to be effective in 96 of 97 cases. Among the doses of 92.5 MBq, 370 MBq and 555 MBq, the dose of 92.5 MBq was not large enough to provide adequate-quality blood flow images or reliable information for evaluation of the renal blood flow. It was concluded that the optimal dose range of 99m Tc-MAG3 was 185-555 MBq with 370 MBq as the standard dose. Also, we summarize that 555 MBq is especially recommendable when detailed blood flow information is required. These results indicate that 99m Tc-MAG3 injectable is useful for the diagnosis of renal and urinary disorders. (author)

Randomised clinical trial: study of escalating doses of NRL001 given in rectal suppositories of different weights.

Science.gov (United States)

Bell, D; Pediconi, C; Jacobs, A

2014-03-01

The application of α-adrenoceptor agonists can improve faecal incontinence symptoms. The aim of this study was to investigate the pharmacokinetic and systemic effects of NRL001 administered as different strengths in 1 or 2 g suppositories. This randomised, double-blind, placebo controlled study included 48 healthy subjects. Group 1 consisted of two cohorts of 12 subjects administered either four single doses of 1 or 2 g rectal suppository with either 5, 7.5 or 10 mg NRL001, or matching placebo. Group 2 consisted of two cohorts of 12 subjects administered either four single doses of 1 or 2 g rectal suppository with either 10, 12.5 or 15 mg NRL001, or matching placebo. Doses were given in an escalating manner with placebo at a random position within the sequence. Tmax was at ~4.5 h post-dose for all NRL001 doses. Median AUC0-tz , AUC0-∞ and Cmax increased with increasing dose for both suppository sizes. The estimate of ratios of geometric means comparing 2 g with 1 g suppository, and regression analysis for dose proportionality, was close to 1 for the variables AUC0-tz , AUC0-∞ and Cmax (P > 0.05). For both suppository sizes, 20-min mean pulse rate was significantly decreased compared with placebo with all doses (P < 0.05). Blood pressure decreased overall. There were 144 adverse events (AEs) and no serious AEs reported during the study. All AEs were mild in severity. The regression analysis concluded that the doses were dose proportional. Colorectal Disease © 2014 The Association of Coloproctology of Great Britain and Ireland.

Clinical radiation doses for spinal cord: the 1988 international questionnaire

International Nuclear Information System (INIS)

Fowler, J.F.; Bogaert, W. vanden; Scheuren, E. van der; Bentzen, S.M.; Bond, S.J.; Ang, K.K.; Kogel, A.J. van der

2000-01-01

Emmanuel van der Schueren gave a keynote lecture at the 1988 ASTRO annual conference pointing out that the spinal cord 'tolerance doses' then prescribed were probably unnecessarily cautious, resulting in probable underdosing of some tumours. This lecture was supported both by an international questionnaire which he and two of the present authors had conducted, and by animal experimental data. In 1997 he initiated a 10-year follow-up questionnaire, the results of which are summarised here. The present report analyses the chance in prescriptions from 1988 to 1998 and the variation in prescriptions among various regions of the World. The main conclusion is that prescribed dose levels have increased significantly in this period. Large geographical variations still exist. Among responders who use a formula to correct for changed dose per fraction, 90% are now using the linear-quadratic model vs. 33% in 1988. The current status of clinically acceptable doses to spinal cord in 2-Gy fractions is discussed briefly. Further details from the responses to the 1998 questionnaire will be presented in another publication. (author)

Bacterial meningitis in newborn and infant: correlation between organism, CT findings and clinical outcome

International Nuclear Information System (INIS)

Choi, Hye Young; Park, Young Seo; Yoo, Shi Joon; Suh, Dae Chul; Chung, Young Kyo

1993-01-01

Acute bacterial meningitis often results in significant neurologic complications regardless of the antibiotics treatment Computed tomographic (CT) finding of tuberculous meningitis is fairly well known but not the findings of bacterial meningitis. This study was performed to determine the incidence of causative organisms and to correlate between the organisms and computed tomographic (CT) findings with clinical outcome of bacterial meningitis in newborns and infants. We analyzed the brain CT and clinical records of 15 infants who had been diagnosed as bacterial meningitis by CSF culture. We found that the most common organisms were Group B streptococcus in neonates without no neurologic complications in all but one and Hemophilus influenza in infants whose clinical outcomes were poor in all except one. CT findings related with poor prognosis in this study were cerebral edema, basal cisternal obliteration and enhancement, and cerebral infarction on initial CT and ventriculomegaly on follow-up CT. We concluded that CT diagnosed intracranial complications of bacterial meningitis well and could contributed to better treatment of bacterial meningitis

Gastrointestinal toxicity of vorinostat: reanalysis of phase 1 study results with emphasis on dose-volume effects of pelvic radiotherapy

LENUS (Irish Health Repository)

Bratland, Ase

2011-04-08

Abstract Background In early-phase studies with targeted therapeutics and radiotherapy, it may be difficult to decide whether an adverse event should be considered a dose-limiting toxicity (DLT) of the investigational systemic agent, as acute normal tissue toxicity is frequently encountered with radiation alone. We have reanalyzed the toxicity data from a recently conducted phase 1 study on vorinostat, a histone deacetylase inhibitor, in combination with pelvic palliative radiotherapy, with emphasis on the dose distribution within the irradiated bowel volume to the development of DLT. Findings Of 14 eligible patients, three individuals experienced Common Terminology Criteria of Adverse Events grade 3 gastrointestinal and related toxicities, representing a toxicity profile vorinostat has in common with radiotherapy to pelvic target volumes. For each study patient, the relative volumes of small bowel receiving radiation doses between 6 Gy and 30 Gy at 6-Gy intervals (V6-V30) were determined from the treatment-planning computed tomography scans. The single patient that experienced a DLT at the second highest dose level of vorinostat, which was determined as the maximum-tolerated dose, had V6-V30 dose-volume estimates that were considerably higher than any other study patient. This patient may have experienced an adverse radiation dose-volume effect rather than a toxic effect of the investigational drug. Conclusions When reporting early-phase trial results on the tolerability of a systemic targeted therapeutic used as potential radiosensitizing agent, radiation dose-volume effects should be quantified to enable full interpretation of the study toxicity profile. Trial registration ClinicalTrials.gov: NCT00455351

Phase I (or phase II) dose-ranging clinical trials: proposal of a two-stage Bayesian design.

Science.gov (United States)

Zohar, Sarah; Chevret, Sylvie

2003-02-01

We propose a new design for phase I (or phase II) dose-ranging clinical trials aiming at determining a dose of an experimental treatment to satisfy safety (respectively efficacy) requirements, at treating a sufficiently large number of patients to estimate the toxicity (respectively failure) probability of the dose level with a given reliability, and at stopping the trial early if it is likely that no dose is safe (respectively efficacious). A two-stage design was derived from the Continual Reassessment Method (CRM), with implementation of Bayesian criteria to generate stopping rules. A simulation study was conducted to compare the operating characteristics of the proposed two-stage design to those reached by the traditional CRM. Finally, two applications to real data sets are provided.

Randomised clinical trial: a dose-ranging study of vonoprazan, a novel potassium-competitive acid blocker, vs. lansoprazole for the treatment of erosive oesophagitis.

Science.gov (United States)

Ashida, K; Sakurai, Y; Nishimura, A; Kudou, K; Hiramatsu, N; Umegaki, E; Iwakiri, K; Chiba, T

2015-09-01

The potassium-competitive acid blocker vonoprazan (VPZ) has potent acid-inhibitory effects and may offer clinical advantages over conventional therapy for acid-related disorders. To investigate the efficacy and safety of VPZ in patients with erosive oesophagitis (EO). In this multicentre, randomised, double-blind, parallel-group, dose-ranging study, patients ≥20 years with endoscopically confirmed EO [Los Angeles (LA) grades A-D] received VPZ 5, 10, 20 or 40 mg, or lansoprazole (LPZ) 30 mg once daily for 8 weeks. The primary endpoint was the proportion of healed EO subjects as shown by endoscopy at week 4. A total of 732 subjects received VPZ or LPZ. The proportion of healed EO subjects at week 4 was 92.3%, 92.5%, 94.4%, 97.0% and 93.2%, respectively, with VPZ 5, 10, 20 and 40 mg and LPZ 30 mg. All VPZ doses were non-inferior to LPZ when adjusted for baseline LA grades A/B and C/D. Among those with LA grades C/D, the proportions of healed EO subjects were 87.3%, 86.4%, 100%, 96.0% and 87.0%, respectively, with VPZ 5, 10, 20 and 40 mg and LPZ 30 mg. The incidence of adverse events was similar across the groups. Vonoprazan was effective and non-inferior to LPZ in healing EO. VPZ 20 mg or higher was highly efficacious for severe EO (LA grades C/D). VPZ was associated with no safety concern during this 8-week study, while there was a dose-dependent increase in serum gastrin. Once-daily VPZ 20 mg is the recommended clinical dose for treating EO. © 2015 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.

Field study to evaluate radiation doses in dental practices

International Nuclear Information System (INIS)

Panzer, W.; Scheurer, C.

1984-05-01

An inexpensive and simple test device was developed and used in a field study to evaluate entrance dose, dose to an intra-oral film, filtration and field size under routine conditions in more than 150 dental practices. The test device consists of two films of different speed and a set of 5 thin copper filters for a filter analytical determination of the radiation quality. Dentists voluntarily participating in the study were asked to expose the test device like they usually do when examining a molar tooth. The main result was the evidence of a significant dose reduction compared to the findings of similar studies performed in 1970 and 1976. This reduction is due to a general shift to lower values and a complete disappearance of values above 45 mGy (5 R) which in 1970 were still more than 15%. In the same way the number of facilities showing insufficient filtration or collimation had decreased. Nevertheless, a large spread of dose values could still be observed, ranging from less than 0.45 mGy (50 mR) to more than 26 mGy (3 R), for the entrance dose. The most striking result, however, was that such an important parameter like the speed of the films used at the respective unit turned out to have no impact on the entrance dose. (orig./HP)

Multi-walled carbon nanotubes: A cytotoxicity study in relation to functionalization, dose and dispersion.

Science.gov (United States)

Zhou, Lulu; Forman, Henry Jay; Ge, Yi; Lunec, Joseph

2017-08-01

Chemical functionalization broadens carbon nanotube (CNT) applications, conferring new functions, but at the same time potentially altering toxicity. Although considerable experimental data related to CNT toxicity, at the molecular and cellular levels, have been reported, there is very limited information available for the corresponding mechanism involved (e.g. cell apoptosis and genotoxicity). The threshold dose for safe medical application in relation to both pristine and functionalized carbon nanotubes remains ambiguous. In this study, we evaluated the in vitro cytotoxicity of pristine and functionalized (OH, COOH) multi-walled carbon nanotubes (MWCNTs) for cell viability, oxidant detection, apoptosis and DNA mutations, to determine the non-toxic dose and influence of functional group in a human lung-cancer cell line exposed to 1-1000μg/ml MWCNTs for 24, 48 and 72h. The findings suggest that pristine MWCNTs induced more cell death than functionalized MWCNTs while functionalized MWCNTs are more genotoxic compared to their pristine form. The level of both dose and dispersion in the matrix used should be taken into consideration before applying further clinical applications of MWCNTs. Copyright © 2017 Elsevier Ltd. All rights reserved.

Association between clinical and cone-beam computed tomography findings in patients with temporomandibular disorders

Directory of Open Access Journals (Sweden)

Mahrokh Imanimoghaddam

2017-08-01

Full Text Available BACKGROUND AND AIM: The aim of this study was to assess the association between the clinical and cone-beam computed tomography (CBCT findings in relation to bony changes in patients with temporomandibular disorders (TMD. METHODS: According to the research diagnostic criteria for temporomandibular disorder (RDC/TMD, forty-one patients with type II TMD (42 TM joints and type III TMD (40 TM joints were recruited for this study. Condylar position and bony changes including flattening, sclerosis, osteophytes, resorption, and erosion of joint were evaluated by CBCT and compared with clinical findings. Data were analyzed by SPSS software. RESULTS: Condylar flattening, sclerosis, resorption, and erosion were not significantly associated with joint/masticatory muscles pain or crepitus sound. The vertical or horizontal position of the condyle showed no significant relationship with the clinical findings. Condylar osteophyte was significantly associated with pain in masticatory muscles and crepitus (P = 0.030 and P = 0.010, respectively. There was no association between the condylar range of motion and pain in joint or masticatory muscles. CONCLUSION: Condylar osteophyte was significantly associated with both masticatory muscles pain and crepitus sound. No significant relationship was found between the other temporomandibular joint (TMJ radiographic and clinical findings in patients with TMD.

Clinical Effects and Antivenom Dosing in Brown Snake (Pseudonaja spp.) Envenoming — Australian Snakebite Project (ASP-14)

Science.gov (United States)

Allen, George E.; Brown, Simon G. A.; Buckley, Nicholas A.; O’Leary, Margaret A.; Page, Colin B.; Currie, Bart J.; White, Julian; Isbister, Geoffrey K.

2012-01-01

Background Snakebite is a global health issue and treatment with antivenom continues to be problematic. Brown snakes (genus Pseudonaja) are the most medically important group of Australian snakes and there is controversy over the dose of brown snake antivenom. We aimed to investigate the clinical and laboratory features of definite brown snake (Pseudonaja spp.) envenoming, and determine the dose of antivenom required. Methods and Finding This was a prospective observational study of definite brown snake envenoming from the Australian Snakebite Project (ASP) based on snake identification or specific enzyme immunoassay for Pseudonaja venom. From January 2004 to January 2012 there were 149 definite brown snake bites [median age 42y (2–81y); 100 males]. Systemic envenoming occurred in 136 (88%) cases. All envenomed patients developed venom induced consumption coagulopathy (VICC), with complete VICC in 109 (80%) and partial VICC in 27 (20%). Systemic symptoms occurred in 61 (45%) and mild neurotoxicity in 2 (1%). Myotoxicity did not occur. Severe envenoming occurred in 51 patients (38%) and was characterised by collapse or hypotension (37), thrombotic microangiopathy (15), major haemorrhage (5), cardiac arrest (7) and death (6). The median peak venom concentration in 118 envenomed patients was 1.6 ng/mL (Range: 0.15–210 ng/mL). The median initial antivenom dose was 2 vials (Range: 1–40) in 128 patients receiving antivenom. There was no difference in INR recovery or clinical outcome between patients receiving one or more than one vial of antivenom. Free venom was not detected in 112/115 patients post-antivenom with only low concentrations (0.4 to 0.9 ng/ml) in three patients. Conclusions Envenoming by brown snakes causes VICC and over a third of patients had serious complications including major haemorrhage, collapse and microangiopathy. The results of this study support accumulating evidence that giving more than one vial of antivenom is unnecessary in brown snake

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

Science.gov (United States)

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

2012-01-01

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

Skin dose reduction by a clinically viable magnetic deflector

International Nuclear Information System (INIS)

Butson, M.J.; Carolan, M.; Metcalfe, J.N.; University of Wollongong, NSW; Mathur, J.N.; Yu, P.; Young, E.; Kan, M.; City University of Hong Kong, Kowloon

1997-01-01

A variable magnetic deflector which attaches onto the treatment head of a linear accelerator has reduced skin dose by as much as 65% for 6MV x-rays. The magnetic deflector is constructed from Neodymium Iron Boron (NdFeB) rare earth magnets. It weighs approximately 15 kg and is designed to easily fit onto the accessory mount of a clinical linear accelerator. All field sizes are attainable up to 35 cm x 35 cm at 100 cm SSD. The gap between the magnetic poles can be adjusted, providing the highest field strength for each field size. Magnetic field strengths up to 0.55 Tesla are attainable. For a 6MV x-ray beam with a 10 mm perspex block tray, surface dose is reduced from 29% to 14% and from 59% to 37% for a 20 cm x 20 cm and 35 cm x 35 cm field size, respectively. Results at varying SSD's have shown at least 10 cm of space must be allowed between the magnets and patient for adequate reduction of skin dose through removal of electron contaminants. (authors)

A study of 60 patients with percutaneous trigger finger releases: clinical and ultrasonographic findings.

Science.gov (United States)

Gulabi, D; Cecen, G S; Bekler, H I; Saglam, F; Tanju, N

2014-09-01

We present the clinical results and ultrasonographic findings of 61 trigger digits treated with percutaneous A1 pulley release. An endoscopic carpal tunnel knife was used for the release in the outpatient department. The mean follow-up period was 3.5 months. A total of 55 digits (90%) had complete relief of their triggering postoperatively. Six digits (10%) had Grade 2 triggering clinically in the early postoperative period.The complications included six cases of insufficient release (10%), scar sensitivity in one patient, short-term hypoaesthesia in three digits (5%), and flexor tendon laceration noted on postoperative ultrasonography in eight digits (13%). No neurovascular damage was noted on the postoperative ultrasonography. Ultrasonograpy provides information about tendon laceration and changes in thickness of the pulleys and confirm A1 pulley release after surgery, but it does not alter clinical decision-making. We believe that pre- and postoperative ultrasonograpy does not need to be included as a routine examination. © The Author(s) 2014.

Non-cardiovascular findings in clinical cardiovascular magnetic resonance imaging in children

International Nuclear Information System (INIS)

Ghadimi Mahani, Maryam; Morani, Ajaykumar C.; Lu, Jimmy C.; Dorfman, Adam L.; Fazeli Dehkordy, Soudabeh; Jeph, Sunil; Agarwal, Prachi P.

2016-01-01

With increasing use of pediatric cardiovascular MRI, it is important for all imagers to become familiar with the spectrum of non-cardiovascular imaging findings that can be encountered. This study aims to ascertain the prevalence and nature of these findings in pediatric cardiovascular MRIs performed at our institution. We retrospectively evaluated reports of all cardiovascular MRI studies performed at our institute from January 2008 to October 2012 in patients younger than18 years. Most studies (98%) were jointly interpreted by a pediatric cardiologist and a radiologist. We reviewed the electronic medical records of all cases with non-cardiovascular findings, defined as any imaging finding outside the cardiovascular system. Non-cardiovascular findings were classified into significant and non-significant, based on whether they were known at the time of imaging or they required additional workup or a change in management. In 849 consecutive studies (mean age 9.7 ± 6.3 years), 145 non-cardiovascular findings were found in 140 studies (16.5% of total studies). Overall, 51.0% (74/145) of non-cardiovascular findings were in the abdomen, 30.3% (44/145) were in the chest, and 18.6% (27/145) were in the spine. A total of 19 significant non-cardiovascular findings were observed in 19 studies in individual patients (2.2% of total studies, 47% male, mean age 5.9 ± 6.7 years). Significant non-cardiovascular findings included hepatic adenoma, arterially enhancing focal liver lesions, asplenia, solitary kidney, pelvicaliectasis, renal cystic diseases, gastric distention, adrenal hemorrhage, lung hypoplasia, air space disease, bronchial narrowing, pneumomediastinum and retained surgical sponge. Non-cardiovascular findings were seen in 16.5% of cardiovascular MRI studies in children, of which 2.2% were clinically significant findings. Prevalence and nature of these non-cardiovascular findings are different from those reported in adults. Attention to these findings is important

Non-cardiovascular findings in clinical cardiovascular magnetic resonance imaging in children

Energy Technology Data Exchange (ETDEWEB)

Ghadimi Mahani, Maryam [University of Michigan Health System, C.S. Mott Children' s Hospital, Department of Radiology, Section of Pediatric Radiology, Ann Arbor, MI (United States); Morani, Ajaykumar C. [The University of Texas MD Anderson Cancer Center, Department of Diagnostic Radiology, Houston, TX (United States); Lu, Jimmy C.; Dorfman, Adam L. [University of Michigan Health System, C.S. Mott Children' s Hospital, Department of Pediatrics and Communicable Diseases, Division of Pediatric Cardiology, Ann Arbor, MI (United States); Fazeli Dehkordy, Soudabeh [University of Michigan Health System, C.S. Mott Children' s Hospital, Department of Radiology, Section of Pediatric Radiology, Ann Arbor, MI (United States); Providence Hospital and Medical Centers, Department of Graduate Medical Education, Southfield, MI (United States); Jeph, Sunil [The University of Texas MD Anderson Cancer Center, Department of Diagnostic Radiology, Houston, TX (United States); Geisinger Medical Center, Department of Radiology, Danville, PA (United States); Agarwal, Prachi P. [University of Michigan Health System, Department of Radiology, Division of Cardiothoracic Radiology, Ann Arbor, MI (United States)

2016-04-15

With increasing use of pediatric cardiovascular MRI, it is important for all imagers to become familiar with the spectrum of non-cardiovascular imaging findings that can be encountered. This study aims to ascertain the prevalence and nature of these findings in pediatric cardiovascular MRIs performed at our institution. We retrospectively evaluated reports of all cardiovascular MRI studies performed at our institute from January 2008 to October 2012 in patients younger than18 years. Most studies (98%) were jointly interpreted by a pediatric cardiologist and a radiologist. We reviewed the electronic medical records of all cases with non-cardiovascular findings, defined as any imaging finding outside the cardiovascular system. Non-cardiovascular findings were classified into significant and non-significant, based on whether they were known at the time of imaging or they required additional workup or a change in management. In 849 consecutive studies (mean age 9.7 ± 6.3 years), 145 non-cardiovascular findings were found in 140 studies (16.5% of total studies). Overall, 51.0% (74/145) of non-cardiovascular findings were in the abdomen, 30.3% (44/145) were in the chest, and 18.6% (27/145) were in the spine. A total of 19 significant non-cardiovascular findings were observed in 19 studies in individual patients (2.2% of total studies, 47% male, mean age 5.9 ± 6.7 years). Significant non-cardiovascular findings included hepatic adenoma, arterially enhancing focal liver lesions, asplenia, solitary kidney, pelvicaliectasis, renal cystic diseases, gastric distention, adrenal hemorrhage, lung hypoplasia, air space disease, bronchial narrowing, pneumomediastinum and retained surgical sponge. Non-cardiovascular findings were seen in 16.5% of cardiovascular MRI studies in children, of which 2.2% were clinically significant findings. Prevalence and nature of these non-cardiovascular findings are different from those reported in adults. Attention to these findings is important

First clinical tests using a liquid-filled electronic portal imaging device and a convolution model for the verification of the midplane dose

International Nuclear Information System (INIS)

Boellaard, R.; Herk, M. van; Uiterwaal, H.; Mijnheer, B.

1998-01-01

Background and purpose: Recently, algorithms have been developed to derive the patient dose from portal dose measurements using a liquid-filled electronic portal imaging device. These algorithms have already been validated for several phantom geometries irradiated under clinical conditions. It is the aim of the present study to investigate the applicability of a liquid-filled electronic portal imaging device in combination with these algorithms for two-dimensional midplane dose verification in clinical practice. Measurements and methods: Portal dose images were obtained during several patient treatments under routine clinical conditions. Measurements were performed to verify the midplane dose during radiotherapy of larynx cancer with 4 MV beams, breast and lung cancer with 8 MV beams and prostate cancer with both 8 and 18 MV beams. Midplane doses, determined from portal dose measurements and analyzed with our algorithms, were compared with midplane doses calculated with our three-dimensional (3D) treatment planning system (TPS). Results: For the larynx treatment the measured 2D midplane dose agreed within 2.0% with TPS calculations in most parts of the field. Larger differences were found in a small region below the skin due to the absence of electron equilibrium, which is not taken into account in our portal dose analysis. For breast irradiations the measured midplane dose showed a homogeneous distribution in the AP direction in the axial plane, while high dose regions were observed in the cranial and caudal part of the breast. Portal dose measurements and TPS calculations agreed within 2.5% for most of the prostate and lung irradiations. For a few of the prostate and lung treatments larger local differences were found due to differences between the actual patient anatomy and the planning CT data, e.g. as a result of variable gas filling in the rectum and anatomical changes in the lung. Conclusions: Portal dose measurements with a liquid-filled electronic portal

Clinical evaluation of a dose monitoring software tool based on Monte Carlo Simulation in assessment of eye lens doses for cranial CT scans

Energy Technology Data Exchange (ETDEWEB)

Guberina, Nika; Suntharalingam, Saravanabavaan; Nassenstein, Kai; Forsting, Michael; Theysohn, Jens; Wetter, Axel; Ringelstein, Adrian [University Hospital Essen, Institute of Diagnostic and Interventional Radiology and Neuroradiology, Essen (Germany)

2016-10-15

The aim of this study was to verify the results of a dose monitoring software tool based on Monte Carlo Simulation (MCS) in assessment of eye lens doses for cranial CT scans. In cooperation with the Federal Office for Radiation Protection (Neuherberg, Germany), phantom measurements were performed with thermoluminescence dosimeters (TLD LiF:Mg,Ti) using cranial CT protocols: (I) CT angiography; (II) unenhanced, cranial CT scans with gantry angulation at a single and (III) without gantry angulation at a dual source CT scanner. Eye lens doses calculated by the dose monitoring tool based on MCS and assessed with TLDs were compared. Eye lens doses are summarized as follows: (I) CT angiography (a) MCS 7 mSv, (b) TLD 5 mSv; (II) unenhanced, cranial CT scan with gantry angulation, (c) MCS 45 mSv, (d) TLD 5 mSv; (III) unenhanced, cranial CT scan without gantry angulation (e) MCS 38 mSv, (f) TLD 35 mSv. Intermodality comparison shows an inaccurate calculation of eye lens doses in unenhanced cranial CT protocols at the single source CT scanner due to the disregard of gantry angulation. On the contrary, the dose monitoring tool showed an accurate calculation of eye lens doses at the dual source CT scanner without gantry angulation and for CT angiography examinations. The dose monitoring software tool based on MCS gave accurate estimates of eye lens doses in cranial CT protocols. However, knowledge of protocol and software specific influences is crucial for correct assessment of eye lens doses in routine clinical use. (orig.)

Clinical evaluation of a dose monitoring software tool based on Monte Carlo Simulation in assessment of eye lens doses for cranial CT scans

International Nuclear Information System (INIS)

Guberina, Nika; Suntharalingam, Saravanabavaan; Nassenstein, Kai; Forsting, Michael; Theysohn, Jens; Wetter, Axel; Ringelstein, Adrian

2016-01-01

The aim of this study was to verify the results of a dose monitoring software tool based on Monte Carlo Simulation (MCS) in assessment of eye lens doses for cranial CT scans. In cooperation with the Federal Office for Radiation Protection (Neuherberg, Germany), phantom measurements were performed with thermoluminescence dosimeters (TLD LiF:Mg,Ti) using cranial CT protocols: (I) CT angiography; (II) unenhanced, cranial CT scans with gantry angulation at a single and (III) without gantry angulation at a dual source CT scanner. Eye lens doses calculated by the dose monitoring tool based on MCS and assessed with TLDs were compared. Eye lens doses are summarized as follows: (I) CT angiography (a) MCS 7 mSv, (b) TLD 5 mSv; (II) unenhanced, cranial CT scan with gantry angulation, (c) MCS 45 mSv, (d) TLD 5 mSv; (III) unenhanced, cranial CT scan without gantry angulation (e) MCS 38 mSv, (f) TLD 35 mSv. Intermodality comparison shows an inaccurate calculation of eye lens doses in unenhanced cranial CT protocols at the single source CT scanner due to the disregard of gantry angulation. On the contrary, the dose monitoring tool showed an accurate calculation of eye lens doses at the dual source CT scanner without gantry angulation and for CT angiography examinations. The dose monitoring software tool based on MCS gave accurate estimates of eye lens doses in cranial CT protocols. However, knowledge of protocol and software specific influences is crucial for correct assessment of eye lens doses in routine clinical use. (orig.)

Clinical and Imaging Findings in Childhood Posterior Reversible Encephalopathy Syndrome

Science.gov (United States)

GUNGOR, Serdal; KILIC, Betul; TABEL, Yilmaz; SELIMOGLU, Ayse; OZGEN, Unsal; YILMAZ, Sezai

2018-01-01

Objective Posterior reversible encephalopathy syndrome (PRES) is characterized by typical radiologic findings in the posterior regions of the cerebral hemispheres and cerebellum. The symptoms include headache, nausea, vomiting, visual disturbances, focal neurologic deficits, and seizures. The aim of this study is to evaluate the clinical and radiological features of PRES in children and to emphasize the recognition of atypical features. Materials & Methods We retrospectively examined 23 children with PRES from Mar 2010-Apr 2015 in Inonu University Turgut Ozal Medical Center in Turkey. We compared the clinical features and cranial MRI findings between underlying diseases of PRES. Results The most common precipitating factors were hypertension (78.2%) and medications, namely immunosuppressive and antineoplastic agents (60.8%). Manifestations included mental changes (100%), seizures (95.6%), headache (60.8%), and visual disturbances (21.7%) of mean 3.6 (range 1-10) days' duration. Cranial magnetic resonance imaging (MRI) showed bilateral occipital lesions in all patients, associated in 82.6% with less typical distribution of lesions in frontal, temporal or parietal lobes, cerebellum, corpus callosum, basal ganglia, thalamus, and brain stem. Frontal involvement was predominant, observed in 56.5% of patients. Clinical recovery was followed by radiologic resolution in all patients. Conclusion PRES is often unsuspected by the clinician, thus radiologists may be the first to suggest this diagnosis on an MRI obtained for seizures or encephalopathy. Atypical MRI finding is seen quite often. Rapid diagnosis and treatment are required to avoid a devastating outcome. PMID:29379559

SU-F-T-433: Evaluation of a New Dose Mimicking Application for Clinical Flexibility and Reliability

International Nuclear Information System (INIS)

Hoffman, D; Nair, C Kumaran; Wright, C; Yamamoto, T; Mayadev, J; Valicenti, R; Benedict, S; Rong, Y; Markham, J

2016-01-01

Purpose: Clinical workflow and machine down time occasionally require patients to be temporarily treated on a system other than the initial treatment machine. A new commercial dose mimicking application provides automated cross-platform treatment planning to expedite this clinical flexibility. The aim of this work is to evaluate the feasibility of automatic plan creation and establish a robust clinical workflow for prostate and pelvis patients. Methods: Five prostate and five pelvis patients treated with helical plans were selected for re-planning with the dose mimicking application, covering both simple and complex scenarios. Two-arc VMAT and 7- and 9-field IMRT plans were generated for each case, with the objective function of achieving similar dose volume histogram from the initial helical plans. Dosimetric comparisons include target volumes and organs at risk (OARs) (rectum, bladder, small bowel, femoral heads, etc.). Dose mimicked plans were evaluated by a radiation oncologist, and patient-specific QAs were performed to validate delivery. Results: Overall plan generation and transfer required around 30 minutes of dosimetrist’s time once the dose-mimicking protocol is setup for each site. The resulting VMAT and 7- and 9-field IMRT plans achieved equivalent PTV coverage and homogeneity (D99/DRx = 97.3%, 97.2%, 97.2% and HI = 6.0, 5.8, and 5.9, respectively), compared to helical plans (97.6% and 4.6). The OAR dose discrepancies were up to 6% in rectum Dmean, but generally lower in bladder, femoral heads, bowel and penile bulb. In the context of 1–5 fractions, the radiation oncologist evaluated the dosimetric changes as not clinically significant. All delivery QAs achieved >90% pass with a 3%/3mm gamma criteria. Conclusion: The automated dose-mimicking workflow offers a strategy to avoid missing treatment fractions due to machine down time with non-clinically significant changes in dosimetry. Future work will further optimize dose mimicking plans and

SU-F-T-433: Evaluation of a New Dose Mimicking Application for Clinical Flexibility and Reliability

Energy Technology Data Exchange (ETDEWEB)

Hoffman, D; Nair, C Kumaran; Wright, C; Yamamoto, T; Mayadev, J; Valicenti, R; Benedict, S; Rong, Y [University of California Davis Medical Center, Sacramento, CA (United States); Markham, J [Raysearch Laboratories, Garden City, NY (United States)

2016-06-15

Purpose: Clinical workflow and machine down time occasionally require patients to be temporarily treated on a system other than the initial treatment machine. A new commercial dose mimicking application provides automated cross-platform treatment planning to expedite this clinical flexibility. The aim of this work is to evaluate the feasibility of automatic plan creation and establish a robust clinical workflow for prostate and pelvis patients. Methods: Five prostate and five pelvis patients treated with helical plans were selected for re-planning with the dose mimicking application, covering both simple and complex scenarios. Two-arc VMAT and 7- and 9-field IMRT plans were generated for each case, with the objective function of achieving similar dose volume histogram from the initial helical plans. Dosimetric comparisons include target volumes and organs at risk (OARs) (rectum, bladder, small bowel, femoral heads, etc.). Dose mimicked plans were evaluated by a radiation oncologist, and patient-specific QAs were performed to validate delivery. Results: Overall plan generation and transfer required around 30 minutes of dosimetrist’s time once the dose-mimicking protocol is setup for each site. The resulting VMAT and 7- and 9-field IMRT plans achieved equivalent PTV coverage and homogeneity (D99/DRx = 97.3%, 97.2%, 97.2% and HI = 6.0, 5.8, and 5.9, respectively), compared to helical plans (97.6% and 4.6). The OAR dose discrepancies were up to 6% in rectum Dmean, but generally lower in bladder, femoral heads, bowel and penile bulb. In the context of 1–5 fractions, the radiation oncologist evaluated the dosimetric changes as not clinically significant. All delivery QAs achieved >90% pass with a 3%/3mm gamma criteria. Conclusion: The automated dose-mimicking workflow offers a strategy to avoid missing treatment fractions due to machine down time with non-clinically significant changes in dosimetry. Future work will further optimize dose mimicking plans and

Advance of study on hormesis of low dose radiation

International Nuclear Information System (INIS)

Su Liaoyuan

2003-01-01

There have been growing interests in recent years over the effects of low doses of ionizing radiation on human. The paper gives a brief review on the LDR studies, which include LDR-induced hormesis and adaptive response, LDR experiments in vivo or in vitro and epidemiologic investigation, and clinical applications of LDR as well

CT of jejunal diverticulitis: imaging findings, differential diagnosis, and clinical management

International Nuclear Information System (INIS)

Macari, M.; Faust, M.; Liang, H.; Pachter, H.L.

2007-01-01

Aim: To describe the imaging findings of jejunal diverticulitis as depicted at contrast-enhanced computed tomography (CT) and review the differential diagnosis and clinical management. Materials and Methods: CT and pathology databases were searched for the diagnosis of jejunal diverticulitis. Three cases were identified and the imaging and clinical findings correlated. Results: Jejunal diverticulitis presents as a focal inflammatory mass involving the proximal small bowel. A trial of medical management with antibiotics may be attempted. Surgical resection may be required if medical management is unsuccessful. Conclusion: The imaging findings at MDCT may allow a specific diagnosis of jejunal diverticulitis to be considered and may affect the clinical management of the patient

CT findings of transfusional hemosiderosis in patients with chronic renal failure : clinical correlation

International Nuclear Information System (INIS)

Park, Tae Joon; Lee, Hae Kyung; Hong, Hyun Sook; Kim, Gun Woo; Kim, Hyung Hwan; Choi, Gyo Chang; Kwon, Kui Hyang; Choi, Deuk Lin

1997-01-01

The purpose of this study is to evaluate whether there is any correlation between the CT features of hemosiderosis and clinical findings in patients with chronic renal failure who have received multiple blood transfusion. Among chronic renal failure patients who had undergone long-tern dialysis and received multiple blood transfusions, CT findings in 16 cases in which increased liver attenuation was seen on images obtained for other purpose, were analyzed by three radiologic specialists. The attenuation values of liver, spleen and pancreas compared with that of back muscle were correlated with the amount and duration of transfusion, and blood ferritin level. There is no correlation between the CT features of hemosiderosis and clinical findings. In patients with chronic renal failure and no clinical symptoms, the status of iron overload was relatively easily detected on CT. Close observation of CT findings is thus thought to prevent significant permanent functional deformity of organs in patients with chronic renal failure who have received multiple blood transfusions. (author). 14 refs., 1 tab., 1 fig

Inverse optimization of objective function weights for treatment planning using clinical dose-volume histograms

Science.gov (United States)

Babier, Aaron; Boutilier, Justin J.; Sharpe, Michael B.; McNiven, Andrea L.; Chan, Timothy C. Y.

2018-05-01

We developed and evaluated a novel inverse optimization (IO) model to estimate objective function weights from clinical dose-volume histograms (DVHs). These weights were used to solve a treatment planning problem to generate ‘inverse plans’ that had similar DVHs to the original clinical DVHs. Our methodology was applied to 217 clinical head and neck cancer treatment plans that were previously delivered at Princess Margaret Cancer Centre in Canada. Inverse plan DVHs were compared to the clinical DVHs using objective function values, dose-volume differences, and frequency of clinical planning criteria satisfaction. Median differences between the clinical and inverse DVHs were within 1.1 Gy. For most structures, the difference in clinical planning criteria satisfaction between the clinical and inverse plans was at most 1.4%. For structures where the two plans differed by more than 1.4% in planning criteria satisfaction, the difference in average criterion violation was less than 0.5 Gy. Overall, the inverse plans were very similar to the clinical plans. Compared with a previous inverse optimization method from the literature, our new inverse plans typically satisfied the same or more clinical criteria, and had consistently lower fluence heterogeneity. Overall, this paper demonstrates that DVHs, which are essentially summary statistics, provide sufficient information to estimate objective function weights that result in high quality treatment plans. However, as with any summary statistic that compresses three-dimensional dose information, care must be taken to avoid generating plans with undesirable features such as hotspots; our computational results suggest that such undesirable spatial features were uncommon. Our IO-based approach can be integrated into the current clinical planning paradigm to better initialize the planning process and improve planning efficiency. It could also be embedded in a knowledge-based planning or adaptive radiation therapy framework to

Comparison of image quality in head CT studies with different dose-reduction strategies

DEFF Research Database (Denmark)

Johansen, Jeppe; Nielsen, Rikke; Fink-Jensen, Vibeke

The number of multi-detector CT examinations is increasing rapidly. They allow high quality reformatted images providing accurate and precise diagnosis at maximum speed. Brain examinations are the most commonly requested studies, and although they come at a lower effective dose than body CT, can...... account to a considerable radiation dose as many patients undergo repeated studies. Therefore, various dose-reduction strategies are applied such as automated tube current and voltage modulation and recently different iterative reconstruction algorithms. However, the trade-off of all dose......-reduction maneuvers is reduction of image quality due to image noise or artifacts. The aim of our study was therefore to find the best diagnostic images with lowest possible dose. We present results of dose- and image quality optimizing strategies of brain CT examinations at our institution. We compare sequential...

[Immunological and clinical study on therapeutic efficacy of inosine pranobex].

Science.gov (United States)

Gołebiowska-Wawrzyniak, Maria; Markiewicz, Katarzyna; Kozar, Agata; Derentowicz, Piotr; Czerwińska-Kartowicz, Iwona; Jastrzebska-Janas, Krystyna; Wacławek, Jolanta; Wawrzyniak, Zbigniew M; Siwińska-Gołebiowska, Henryka

2005-09-01

Many studies in vitro and in vivo have shown immunomodulating and antiviral activities of inosine pranobex. The object of this research was to examine the potential beneficial effects of inosine pranobex (Groprinosin) on immune system in children with cellular immunodeficiency as a prophylaxis of recurrent infections, mainly of viral origin. 50 mg/kg b.w/day of inosine pranobex in divided doses was given to the group of 30 children aged 3-15 years for 10 days in 3 following months. Clinical and immunological investigations were done before and after the treatment. Statistically significant rise of CD3T lymphocytes number (p = 0.02) and in this CD4T lymphocytes number (p = 0.02) as well as statistically significant improvement of their function (p = 0.005) evaluated with blastic transformation method were found. These laboratory findings were parallel to clinical benefits. Control study was performed in the group of children completed by randomization and treated in the same way with garlic (Alliofil).

Efficacy and Safety of Daikenchuto for Constipation and Dose-Dependent Differences in Clinical Effects.

Science.gov (United States)

Hirose, Tatsuya; Shinoda, Yasutaka; Kuroda, Ayaka; Yoshida, Aya; Mitsuoka, Machiko; Mori, Kouki; Kawachi, Yuki; Moriya, Akihiro; Tanaka, Kouji; Takeda, Atsuko; Yoshimura, Tomoaki; Sugiyama, Tadashi

2018-01-01

Daikenchuto (DKT) is a Kampo medicine used for the treatment of constipation. In this study, we evaluated the effectiveness of DKT against constipation. Thirty-three patients administered DKT for constipation were selected and divided into low-dose (7.5 g DKT; n = 22) and high-dose (15 g DKT; n = 11) groups. We retrospectively evaluated weekly defaecation frequency, side effects, and clinical laboratory data. Median defaecation frequencies after DKT administration (5, 5.5, 5, and 8 for the first, second, third, and fourth weeks, resp.) were significantly higher than that before DKT administration (2) in all 33 cases ( P DKT increases defaecation frequency and is safe for treating constipation.

Low dose irradiation facilitates hepatocellular carcinoma genesis involving HULC.

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Li, Yuan; Ge, Chang; Feng, Guoxing; Xiao, Huiwen; Dong, Jiali; Zhu, Changchun; Jiang, Mian; Cui, Ming; Fan, Saijun

2018-03-24

Irradiation exposure positive correlates with tumor formation, such as breast cancer and lung cancer. However, whether low dose irradiation induces hepatocarcinogenesis and the underlying mechanism remain poorly defined. In the present study, we reported that low dose irradiation facilitated the proliferation of hepatocyte through up-regulating HULC in vitro and in vivo. Low dose irradiation exposure elevated HULC expression level in hepatocyte. Deletion of heightened HULC erased the cells growth accelerated following low dose irradiation exposure. CDKN1, the neighbor gene of HULC, was down-regulated by overexpression of HULC following low dose irradiation exposure via complementary base pairing, resulting in promoting cell cycle process. Thus, our findings provide new insights into the mechanism of low dose irradiation-induced hepatocarcinogenesis through HULC/CDKN1 signaling, and shed light on the potential risk of low dose irradiation for the development of hepatocellular carcinoma in pre-clinical settings. © 2018 Wiley Periodicals, Inc.

Nonconcordance between Clinical and Head CT Findings: The Specter of Overdiagnosis

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Kelli N. O'Laughlin

2013-01-01

Full Text Available Background. It is unclear whether history and physical examination findings can predict abnormalities on head computed tomography (CT believed to indicate increased risk of lumbar-puncture- (LP- induced brain herniation. The objectives of this study were to (1 identify head CT findings felt to be associated with increased risk of brain herniation and (2 to assess the ability of history and physical examination to predict those findings. Methods. Using a modified Delphi survey technique, an expert panel defined CT abnormalities felt to predict increased risk of LP-induced brain herniation. Presence of such findings on CT was compared with history and physical examination (H&P variables in 47 patients. Results. No H&P variable predicted “high-risk” CT; combining H&P variables to improve sensitivity led to extremely low specificity and still failed to identify all patients with high-risk CT. Conclusions. “High-risk” CT is not uncommon in patients with clinical characteristics known to predict an absence of actual risk from LP, and thus it may not be clinically relevant. “Overdiagnosis” will be increasingly problematic as technological advances identify increasingly subtle deviations from “normal.”

Dosimetric and Clinical Analysis of Spatial Distribution of the Radiation Dose in Gamma Knife Radiosurgery for Vestibular Schwannoma

International Nuclear Information System (INIS)

Massager, Nicolas; Lonneville, Sarah; Delbrouck, Carine; Benmebarek, Nadir; Desmedt, Françoise; Devriendt, Daniel

2011-01-01

Objectives: We investigated variations in the distribution of radiation dose inside (dose inhomogeneity) and outside (dose falloff) the target volume during Gamma Knife (GK) irradiation of vestibular schwannoma (VS). We analyzed the relationship between some parameters of dose distribution and the clinical and radiological outcome of patients. Methods and Materials: Data from dose plans of 203 patients treated for a vestibular schwannoma by GK C using same prescription dose (12 Gy at the 50% isodose) were collected. Four different dosimetric indexes were defined and calculated retrospectively in all plannings on the basis of dose–volume histograms: Paddick conformity index (PI), gradient index (GI), homogeneity index (HI), and unit isocenter (UI). The different measures related to distribution of the radiation dose were compared with hearing and tumor outcome of 203 patients with clinical and radiological follow-up of minimum 2 years. Results: Mean, median, SD, and ranges of the four indexes of dose distribution analyzed were calculated; large variations were found between dose plans. We found a high correlation between the target volume and PI, GI, and UI. No significant association was found between the indexes of dose distribution calculated in this study and tumor control, tumor volume shrinkage, hearing worsening, loss of functional hearing, or complete hearing loss at last follow-up. Conclusions: Parameters of distribution of the radiation dose during GK radiosurgery for VS can be highly variable between dose plans. The tumor and hearing outcome of patients treated is not significantly related to these global indexes of dose distribution inside and around target volume. In GK radiosurgery for VS, the outcome seems more to be influenced by local radiation dose delivered to specific structures or volumes than by global dose gradients.

Clinical responses after total body irradiation by over permissible dose of γ-rays in one time

International Nuclear Information System (INIS)

Jiang Benrong; Wang Guilin; Liu Huilan; Tang Xingsheng; Ai Huisheng

1990-01-01

The clinical responses of patients after total body over permissilbe dose γ-ray irradiation were observed and analysed. The results showed: when the dose was above 5 cGy, there was some immunological depression, but no significant change in hematopoietic functions. 5 cases showed some transient changes of ECG, perhaps due to vagotonia caused by psychological imbalance, One case vomitted 3-4 times after 28 cGy irradiation, this suggested that a few times of vomitting had no significance in the estimation of the irradiated dose and the whole clinical manifestations must be concretely analysed

The validity of clinical findings for diagnosing temporomandibular disorders in patients from different age and gender groups

International Nuclear Information System (INIS)

Igarashi, Chinami

2008-01-01

This study was to clarify the diagnostic accuracy of clinical findings for internal derangement of the temporomandibular joint (TMJ) compared with that of magnetic resonance imaging. A series of 4559 patients (879 male and 3680 female, mean age 32.7 years; range 8-85 years;) with temporomandibular disorders were clinically examined by un unspecified number of dentists. All patients underwent magnetic resonance imaging (MRI). The clinical findings that characterize disc displacement, anterior disc displacement with reduction (ADDwR) and anterior disc displacement without reduction (ADDwoR) are pain, clicking sound and limitation of maximum mouth opening. These clinical findings were compared to the MRI interpretation, which was used as the gold standard for diagnosis of temporomandibular disorders to define the diagnostic accuracy, specificity, sensitivity, positive predictive value and negative predictive value of clinical findings. The prevalence of clinical finding was 3990 joints (43%) with pain, 2775 joints (30%) with clicking sound and 1731 patients (38%) with limitation of opening. Three thousands forty seven joints were diagnosed as having a normal disc position, 510 joints with sideways disc displacement, 2312 joints with ADDwR, 3239 joints with ADDwoR on MR image. The sensitivity of clinical findings was considerably low: sensitivity was 0.48 for pain versus internal derangement, 0.51 for clicking sound versus ADDwR, 0.62 for limitation of opening versus ADDwoR. The sensitivity was higher in the younger group for clicking sound versus ADDwR, but sensitivity was higher in the older group for limitation of opening versus ADDwoR. The diagnostic accuracy based on clinical findings of internal derangement of TMJ was found to be correlated with age. This study has been that the overall diagnostic accuracy of the clinical findings to determine the status of the joint is about 50-60%. The status of the joint could not be accurately determined by clinical findings

Per-beam, planar IMRT QA passing rates do not predict clinically relevant patient dose errors

International Nuclear Information System (INIS)

Nelms, Benjamin E.; Zhen Heming; Tome, Wolfgang A.

2011-01-01

Purpose: The purpose of this work is to determine the statistical correlation between per-beam, planar IMRT QA passing rates and several clinically relevant, anatomy-based dose errors for per-patient IMRT QA. The intent is to assess the predictive power of a common conventional IMRT QA performance metric, the Gamma passing rate per beam. Methods: Ninety-six unique data sets were created by inducing four types of dose errors in 24 clinical head and neck IMRT plans, each planned with 6 MV Varian 120-leaf MLC linear accelerators using a commercial treatment planning system and step-and-shoot delivery. The error-free beams/plans were used as ''simulated measurements'' (for generating the IMRT QA dose planes and the anatomy dose metrics) to compare to the corresponding data calculated by the error-induced plans. The degree of the induced errors was tuned to mimic IMRT QA passing rates that are commonly achieved using conventional methods. Results: Analysis of clinical metrics (parotid mean doses, spinal cord max and D1cc, CTV D95, and larynx mean) vs IMRT QA Gamma analysis (3%/3 mm, 2/2, 1/1) showed that in all cases, there were only weak to moderate correlations (range of Pearson's r-values: -0.295 to 0.653). Moreover, the moderate correlations actually had positive Pearson's r-values (i.e., clinically relevant metric differences increased with increasing IMRT QA passing rate), indicating that some of the largest anatomy-based dose differences occurred in the cases of high IMRT QA passing rates, which may be called ''false negatives.'' The results also show numerous instances of false positives or cases where low IMRT QA passing rates do not imply large errors in anatomy dose metrics. In none of the cases was there correlation consistent with high predictive power of planar IMRT passing rates, i.e., in none of the cases did high IMRT QA Gamma passing rates predict low errors in anatomy dose metrics or vice versa. Conclusions: There is a lack of correlation between

A dose-finding, placebo-controlled study on extended-release felodipine once daily in treatment of hypertension.

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Cambell, L M; Ross, J R; Goves, J R; Lees, C T; McCullagh, A; Barnes, P; Timerick, S J; Richardson, P D

1989-12-01

Hypertensive patients received a beta-blocker plus placebo once daily for 4 weeks. If their diastolic blood pressure (DBP) was then 95-115 mm Hg, they were randomized to receive, in addition to the beta-blocker, placebo (n = 36), felodipine-extended release (ER) 10 mg (n = 36), or felodipine-ER 20 mg (n = 37) in a 4-week double-blind parallel-group trial. All medication was administered once daily and, when BP was measured 24 h after the last dose, felodipine-ER 10 mg reduced DBP by 14 +/- 9 mm Hg (mean +/- SD) from a mean of 103 mm Hg and felodipine-ER 20 mg reduced DBP by 18 +/- 9 mm Gg from 101 mm Hg. The reductions in DBP with both doses of felodipine were greater than reductions with placebo (5 +/- 8 mm Hg, from 102 mm Hg--both p less than 0.001). At the end of the study, 21% of patients receiving placebo had a DBP less than or equal to 90 mm Hg. In contrast, 69% of patients receiving felodipine-ER 10 mg and 82% receiving 20 mg attained this level. More than 90% of patients receiving 10 mg felodipine-ER once daily had a reduction in DBP greater than 5 mm Hg 24 h postdose. Felodipine-ER was well tolerated. Felodipine-ER once daily is an effective antihypertensive drug for patients who require therapy in addition to a beta-blocker; the tolerability in this study was good, and a starting dose greater than 10 mg once daily is not indicated.

Clinical study on the adriamycin induced cardiomyopathy using the cardiac magnetic resonance imaging. Total dose and cardiac dysfunction

International Nuclear Information System (INIS)

Yamaguchi, Kyoko; Teraoka, Kunihiko; Hirano, Masaharu

2001-01-01

We studied cardiac functional disorders caused by Adoriamycin using gadolinium (Gd) contrast cine MRI. Forty-eight patients were given ACT (31 men and 17 women; mean age, 52±15 years). First, the relationship between dose and the left ventricular volume, cardiac function, left ventricular cardiac mass and localized wall motion were examined in all patients. Patients given a total dose of 300 mg/m 2 or higher were assigned to the high dose group and those given doses under 300 mg/m 2 to the low dose group. The same parameters were studied in both groups and compared. A 1.5-Tesla superconductive MRI was used for all studies. Cine images of the long and short axes at the papillary muscle level were obtained by ECG R-wave synchronized Gd contrast cine MRI. Left ventricular volume and cardiac function were analyzed using the long-axis cine images and the wall thickness in diastole and systole was measured at each site using the short-axis cine images. The percentage of wall thickness was calculated at each site. The mean ACT dose was 273.3±218.2 mg/m 2 . In all patients the total dose directly correlated with ESVI and inversely correlated with the ejection fraction (EF). In the high dose group, the total dose and EF were inversely correlated, but no significant differences were observed in the low dose group. In the high dose group, the ESVI was significantly greater and the SVI and EF were more significantly reduced than in the low dose group. In the high dose group, the thickness of the anterior, lateral and posterior walls, excluding the septum, was significantly lower than in the low dose group. However, changes in wall thickness were not significantly different between the groups. Gd contrast cine MRI was useful in examining cardiac functional disorders caused by anthracyclines. The total dose of anthracycline correlated directly with the ESVI, and inversely with the EF. A total dose of 300 mg/m 2 appeared to be the borderline dose beyond which there were

Clinical study on the adriamycin induced cardiomyopathy using the cardiac magnetic resonance imaging. Total dose and cardiac dysfunction

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Yamaguchi, Kyoko; Teraoka, Kunihiko; Hirano, Masaharu [Tokyo Medical Coll. (Japan)

2001-05-01

We studied cardiac functional disorders caused by Adoriamycin using gadolinium (Gd) contrast cine MRI. Forty-eight patients were given ACT (31 men and 17 women; mean age, 52{+-}15 years). First, the relationship between dose and the left ventricular volume, cardiac function, left ventricular cardiac mass and localized wall motion were examined in all patients. Patients given a total dose of 300 mg/m{sup 2} or higher were assigned to the high dose group and those given doses under 300 mg/m{sup 2} to the low dose group. The same parameters were studied in both groups and compared. A 1.5-Tesla superconductive MRI was used for all studies. Cine images of the long and short axes at the papillary muscle level were obtained by ECG R-wave synchronized Gd contrast cine MRI. Left ventricular volume and cardiac function were analyzed using the long-axis cine images and the wall thickness in diastole and systole was measured at each site using the short-axis cine images. The percentage of wall thickness was calculated at each site. The mean ACT dose was 273.3{+-}218.2 mg/m{sup 2}. In all patients the total dose directly correlated with ESVI and inversely correlated with the ejection fraction (EF). In the high dose group, the total dose and EF were inversely correlated, but no significant differences were observed in the low dose group. In the high dose group, the ESVI was significantly greater and the SVI and EF were more significantly reduced than in the low dose group. In the high dose group, the thickness of the anterior, lateral and posterior walls, excluding the septum, was significantly lower than in the low dose group. However, changes in wall thickness were not significantly different between the groups. Gd contrast cine MRI was useful in examining cardiac functional disorders caused by anthracyclines. The total dose of anthracycline correlated directly with the ESVI, and inversely with the EF. A total dose of 300 mg/m{sup 2} appeared to be the borderline dose beyond