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Sample records for intensive lipid-lowering therapy

  1. Cardiovascular pharmacogenetics of antihypertensive and lipid- lowering therapies.

    PubMed

    Vanichakarn, P; Hwa, J; Stitham, J

    2014-01-01

    Recent changes to the clinical management guidelines for hypertension and hyperlipidemia have placed emphasis on prevention through the pharmacological control and reduction of cardiovascular risk factors. In conjunction with proper diet and lifestyle changes, such risk factor control necessitates the use of safe and effective pharmacotherapy. However, many patients fail to reach or maintain therapeutic goals due to inadequacy and/or variability in response to antihypertensive and lipid-lowering medications. Thus, given the contribution of both hypertension and hyperlipidemia in the development and progression of cardiovascular disease, a personalized approach to pharmacotherapy, as well as disease prevention, seems particularly prudent. With the advancement of cardiovascular pharmacogenetics, the aim is to identify genetic biomarkers of drug-response and disease-susceptibility in order to make informed and individualized decisions, improving patient care through proper drug selection and dosing.

  2. PCSK9 inhibitors: A new era of lipid lowering therapy

    PubMed Central

    Chaudhary, Rahul; Garg, Jalaj; Shah, Neeraj; Sumner, Andrew

    2017-01-01

    Hyperlipidemia is a well-established risk factor for developing cardiovascular disease (CVD). The recent American College of Cardiology and American Heart Association guidelines on lipid management emphasize treatment of individuals at increased risk for developing CVD events with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) at doses proven to reduce CVD events. However, there are limited options for patients who are either intolerant to statin therapy, develop CVD despite being on maximally tolerated statin therapy, or have severe hypercholesterolemia. Recently the Food and Drug Administration approved two novel medications for low-density lipoprotein (LDL)-cholesterol reduction: Evolocumab and Alirocumab. These agents target and inactivate proprotein convertase subtilsin-kexin type 9 (PCSK9), a hepatic protease that attaches and internalizes LDL receptors into lysosomes hence promoting their destruction. By preventing LDL receptor destruction, LDL-C levels can be lowered 50%-60% above that achieved by statin therapy alone. This review explores PCSK-9 biology and the mechanisms available to alter it; clinical trials targeting PCSK9 activity, and the current state of clinically available inhibitors of PCSK9. PMID:28289523

  3. Differences in synthesis and absorption of cholesterol of two effective lipid-lowering therapies

    PubMed Central

    Kasmas, S.H.; Izar, M.C.; França, C.N.; Ramos, S.C.; Moreira, F.T.; Helfenstein, T.; Moreno, R.A.; Borges, N.C.; Figueiredo-Neto, A.M.; Fonseca, F.A.

    2012-01-01

    Effective statin therapy is associated with a marked reduction of cardiovascular events. However, the explanation for full benefits obtained for LDL cholesterol targets by combined lipid-lowering therapy is controversial. Our study compared the effects of two equally effective lipid-lowering strategies on markers of cholesterol synthesis and absorption. A prospective, open label, randomized, parallel design study, with blinded endpoints, included 116 subjects. We compared the effects of a 12-week treatment with 40 mg rosuvastatin or the combination of 40 mg simvastatin/10 mg ezetimibe on markers of cholesterol absorption (campesterol and β-sitosterol), synthesis (desmosterol), and their ratios to cholesterol. Both therapies similarly decreased total and LDL cholesterol, triglycerides and apolipoprotein B, and increased apolipoprotein A1 (P < 0.05 vs baseline for all). Simvastatin/ezetimibe increased plasma desmosterol (P = 0.012 vs baseline), and decreased campesterol and β-sitosterol (P < 0.0001 vs baseline for both), with higher desmosterol (P = 0.007) and lower campesterol and β-sitosterol compared to rosuvastatin, (P < 0.0001, for both). In addition, rosuvastatin increased the ratios of these markers to cholesterol (P < 0.002 vs baseline for all), whereas simvastatin/ezetimibe significantly decreased the campesterol/cholesterol ratio (P = 0.008 vs baseline) and tripled the desmosterol/cholesterol ratio (P < 0.0001 vs baseline). The campesterol/cholesterol and β-sitosterol/cholesterol ratios were lower, whereas the desmosterol/cholesterol ratio was higher in patients receiving simvastatin/ezetimibe (P < 0.0001 vs rosuvastatin, for all). Pronounced differences in markers of cholesterol absorption and synthesis were observed between two equally effective lipid-lowering strategies. PMID:22801416

  4. Challenges in Oral Lipid-lowering Therapy: Position Document of the Spanish Society of Cardiology.

    PubMed

    Anguita Sánchez, Manuel; Castro Conde, Almudena; Cordero Fort, Alberto; García-Moll Marimón, Xavier; Gómez Doblas, Juan José; González-Juanatey, José R; Lidón Corbi, Rosa María; López-Sendón, José Luis; Mostaza Prieto, José; Rodríguez Padial, Luis

    2016-11-01

    Lipid-lowering therapy is one of the cornerstones of cardiovascular prevention and is one of the most effective strategies in the secondary prevention of ischemic heart disease. Nevertheless, the current treatment of lipid disorders, together with lifestyle changes, fails to achieve the targets recommended in clinical guidelines in a substantial proportion of patients. PCSK9 inhibitors have demonstrated safety and efficacy in the treatment of dyslipidemia. Due to their ability to reduce low-density lipoprotein cholesterol levels, these drugs have recently been approved for clinical use by Spanish regulatory agencies, with the aim of reducing cardiovascular risk in selected patient groups.

  5. Overcoming toxicity and side-effects of lipid-lowering therapies.

    PubMed

    Wilkinson, Michael J; Laffin, Luke J; Davidson, Michael H

    2014-06-01

    Lowering serum lipid levels is part of the foundation of treating and preventing clinically significant cardiovascular disease. Recently, the American Heart Association/American College of Cardiology released cholesterol guidelines which advocate for high efficacy statins rather than LDL-c goals for five patient subgroups at high risk for cardiovascular disease. Therefore, it is critical that clinicians have an approach for managing side-effects of statin therapy. Statins are associated with myopathy, transaminase elevations, and an increased risk of incident diabetes mellitus among some patients; connections between statins and other processes, such as renal and neurologic function, have also been studied with mixed results. Statin-related adverse effects might be minimized by careful assessment of patient risk factors. Strategies to continue statin therapy despite adverse effects include switching to another statin at a lower dose and titrating up, giving intermittent doses of statins, and adding non-statin agents. Non-statin lipid-lowering drugs have their own unique limitations. Management strategies and algorithms for statin-associated toxicities are available to help guide clinicians. Clinical practice should emphasize tailoring therapy to address each individual's cholesterol goals and risk of developing adverse effects on lipid-lowering drugs.

  6. Early Effects of Intensive Lipid-Lowering Treatment on Plaque Characteristics Assessed by Virtual Histology Intravascular Ultrasound

    PubMed Central

    Lee, Jung-Hee; Shin, Dong-Ho; Kim, Byeong-Keuk; Ko, Young-Guk; Choi, Donghoon; Jang, Yangsoo

    2016-01-01

    Purpose The effects of short-term intensive lipid-lowering treatment on coronary plaque composition have not yet been sufficiently evaluated. We investigated the influence of short-term intensive lipid-lowering treatment on quantitative and qualitative changes in plaque components of non-culprit lesions in patients with acute coronary syndrome. Materials and Methods This was a prospective, randomized, open-label, single-center trial. Seventy patients who underwent both baseline and three-month follow-up virtual histology intravascular ultrasound were randomly assigned to either an intensive lipid-lowering treatment group (ezetimibe/simvastatin 10/40 mg, n=34) or a control statin treatment group (pravastatin 20 mg, n=36). Using virtual histology intravascular ultrasound, plaque was characterized as fibrous, fibro-fatty, dense calcium, or necrotic core. Changes in plaque components during the three-month lipid-lowering treatment were compared between the two groups. Results Compared with the control statin treatment group, there was a significant reduction in low-density lipoprotein cholesterol in the intensive lipid-lowering treatment group (-20.4±17.1 mg/dL vs. -36.8±17.4 mg/dL, respectively; p<0.001). There were no statistically significant differences in baseline, three-month follow-up, or serial changes of gray-scale intravascular ultrasound parameters between the two groups. The absolute volume of fibro-fatty plaque was significantly reduced in the intensive lipid-lowering treatment group compared with the control group (-1.5±3.4 mm3 vs. 0.8±4.7 mm3, respectively; p=0.024). A linear correlation was found between changes in low-density lipoprotein cholesterol levels and changes in the absolute volumes of fibro-fatty plaque (p<0.001, R2=0.209). Conclusion Modification of coronary plaque may be attainable after only three months of intensive lipid-lowering treatment. PMID:27401638

  7. Myotoxic reactions to lipid-lowering therapy are associated with altered oxidation of fatty acids.

    PubMed

    Phillips, Paul S; Ciaraldi, Theodore P; Kim, Dong-Lim; Verity, M Anthony; Wolfson, Tanya; Henry, Robert R

    2009-02-01

    Despite exceptional efficacy and safety, fear of muscle toxicity remains a major reason statins are underutilized. Evidence suggests that statin muscle toxicity may be mediated by abnormalities in lipid metabolism. To test the hypothesis that myotubes from patients intolerant of lipid-lowering therapies have abnormal fatty acid oxidation (FAO) responses we compared muscle from 11 subjects with statin intolerance (Intolerant) with muscle from seven statin-naive volunteers undergoing knee arthroplasty (Comparator). Gross muscle pathology was graded and skeletal muscle cell cultures were produced from each subject. FAO was assessed following treatment with increasing statin concentrations. There was no difference in muscle biopsy myopathy scores between the groups. Basal octanoate oxidation was greater in Intolerant than in Comparator subjects (P = 0.03). Lovastatin-stimulated palmitate oxidation tended to be greater for Intolerant compared to Control subjects' myotubes (P = 0.07 for 5 microM and P = 0.06 for 20 microM lovastatin). In conclusion abnormalities in FAO of Intolerant subjects appear to be an intrinsic characteristic of these subjects that can be measured in their cultured myotubes.

  8. Lipid lowering and imaging protease activation in atherosclerosis Lipid therapy and MMP imaging in atherosclerosis

    PubMed Central

    Challa, Azariyas; Zhang, Jiasheng; Golestani, Reza; Jung, Jae-Joon; Robinson, Simon; Sadeghi, Mehran M.

    2014-01-01

    Background Lipid lowering is a mainstay of modern therapeutic approach to atherosclerosis. We sought to evaluate matrix metalloproteinase (MMP)-targeted microSPECT imaging for tracking of the effect of lipid-lowering interventions on plaque biology in atherosclerotic mice in vivo. Methods and Results ApoE−/− mice fed on a high fat diet (HFD) for 2 months were randomly assigned to continuation of HFD, HFD plus simvastatin, HFD plus fenofibrate and high fat withdrawal (HFW). The animals underwent serial microSPECT/CT imaging using RP805, a 99mTc-labeled MMP-targeted tracer at 1 and 4 weeks after randomization. All three interventions reduced total blood cholesterol by 4 weeks. In animals on HFD, aortic arch RP805 uptake significantly increased from 1 week to 4 weeks. Tracer uptake in fenofibrate and HFW groups was significantly lower than uptake in the HFD group at 4 weeks. Similarly, CD 68 gene expression, reflecting plaque inflammation, was significantly lower in fenofibrate and HFW groups compared to HFD group. MMP tracer uptake significantly correlated with aortic CD68, but not VE-cadherin or smooth muscle α-actin expression. Conclusions MMP tracer uptake paralleled the effect of lipid-lowering interventions on plaque inflammation in atherosclerotic mice. MMP-targeted imaging may be used to track the effect of therapeutic interventions in atherosclerosis. PMID:24368425

  9. The economics of hypercholesterolemia and lipid-lowering therapy: a brief historical tour.

    PubMed

    Oster, G

    1998-09-01

    The first formal economic evaluation of a lipid-lowering intervention was conducted almost 20 years ago. The field exploded in the mid-1980s following the publication of findings from the Lipid Research Clinics Coronary Primary Prevention Trial (LRC-CPPT), in which the bile-acid sequestrant, cholestyramine, was reported to reduce the incidence of coronary artery disease in adults with significant elevations in cholesterol. Almost all of the early pharmacoeconomic studies that followed focused on this agent. Later in the decade, the introduction of lovastatin, the first 3-hydroxy-3 methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor (or "statin"), revolutionized the treatment of hypercholesterolemia, as it was significantly more effective than earlier agents (as were the other statins that followed it). Pharmacoeconomic studies of the statins generally have reported that, despite their higher cost, they are significantly more cost-effective than bile acid sequestrants. Recent long-term clinical trials, such as the West of Scotland Coronary Prevention Study (WOSCOPS) and the Scandinavian Simvastatin Survival Study (4S), have provided firm evidence of the benefits of the statins in both the primary and secondary prevention of coronary artery disease. Formal economic evaluations were incorporated into most of these end-point studies-in contrast to morbidity and mortality trials of earlier lipid-lowering agents-and results from these evaluations are just now becoming available. The availability of primary economic data derived directly from large-scale, long-term clinical trials raises important questions about the future role of modeling in this area.

  10. Intensive versus Guideline Blood Pressure and Lipid Lowering in Patients with Previous Stroke: Main Results from the Pilot ‘Prevention of Decline in Cognition after Stroke Trial’ (PODCAST) Randomised Controlled Trial

    PubMed Central

    Scutt, Polly; Blackburn, Daniel J.; Ankolekar, Sandeep; Krishnan, Kailash; Ballard, Clive; Burns, Alistair; Mant, Jonathan; Passmore, Peter; Pocock, Stuart; Reckless, John; Sprigg, Nikola; Stewart, Rob; Wardlaw, Joanna M.; Ford, Gary A.

    2017-01-01

    Background Stroke is associated with the development of cognitive impairment and dementia. We assessed the effect of intensive blood pressure (BP) and/or lipid lowering on cognitive outcomes in patients with recent stroke in a pilot trial. Methods In a multicentre, partial-factorial trial, patients with recent stroke, absence of dementia, and systolic BP (SBP) 125–170 mmHg were assigned randomly to at least 6 months of intensive (target SBP <125 mmHg) or guideline (target SBP <140 mmHg) BP lowering. The subset of patients with ischaemic stroke and total cholesterol 3.0–8.0 mmol/l were also assigned randomly to intensive (target LDL-cholesterol <1.3 mmol/l) or guideline (target LDL-c <3.0 mmol/l) lipid lowering. The primary outcome was the Addenbrooke’s Cognitive Examination-Revised (ACE-R). Results We enrolled 83 patients, mean age 74.0 (6.8) years, and median 4.5 months after stroke. The median follow-up was 24 months (range 1–48). Mean BP was significantly reduced with intensive compared to guideline treatment (difference –10·6/–5·5 mmHg; p<0·01), as was total/LDL-cholesterol with intensive lipid lowering compared to guideline (difference –0·54/–0·44 mmol/l; p<0·01). The ACE-R score during treatment did not differ for either treatment comparison; mean difference for BP lowering -3.6 (95% CI -9.7 to 2.4), and lipid lowering 4.4 (95% CI -2.1 to 10.9). However, intensive lipid lowering therapy was significantly associated with improved scores for ACE-R at 6 months, trail making A, modified Rankin Scale and Euro-Qol Visual Analogue Scale. There was no difference in rates of dementia or serious adverse events for either comparison. Conclusion In patients with recent stroke and normal cognition, intensive BP and lipid lowering were feasible and safe, but did not alter cognition over two years. The association between intensive lipid lowering and improved scores for some secondary outcomes suggests further trials are warranted. Trial Registration

  11. Randomized, Placebo-Controlled Trial of Mipomersen in Patients with Severe Hypercholesterolemia Receiving Maximally Tolerated Lipid-Lowering Therapy

    PubMed Central

    McGowan, Mary P.; Tardif, Jean-Claude; Ceska, Richard; Burgess, Lesley J.; Soran, Handrean; Gouni-Berthold, Ioanna; Wagener, Gilbert; Chasan-Taber, Scott

    2012-01-01

    Objectives Mipomersen, an antisense oligonucleotide targeting apolipoprotein B synthesis, significantly reduces LDL-C and other atherogenic lipoproteins in familial hypercholesterolemia when added to ongoing maximally tolerated lipid-lowering therapy. Safety and efficacy of mipomersen in patients with severe hypercholesterolemia was evaluated. Methods and Results Randomized, double-blind, placebo-controlled, multicenter trial. Patients (n  = 58) were ≥18 years with LDL-C ≥7.8 mmol/L or LDL-C ≥5.1 mmol/L plus CHD disease, on maximally tolerated lipid-lowering therapy that excluded apheresis. Weekly subcutaneous injections of mipomersen 200 mg (n  = 39) or placebo (n  = 19) were added to lipid-lowering therapy for 26 weeks. Main outcome: percent reduction in LDL-C from baseline to 2 weeks after the last dose of treatment. Mipomersen (n = 27) reduced LDL-C by 36%, from a baseline of 7.2 mmol/L, for a mean absolute reduction of 2.6 mmol/L. Conversely, mean LDL-C increased 13% in placebo (n = 18) from a baseline of 6.5 mmol/L (mipomersen vs placebo p<0.001). Mipomersen produced statistically significant (p<0.001) reductions in apolipoprotein B and lipoprotein(a), with no change in high-density lipoprotein cholesterol. Mild-to-moderate injection site reactions were the most frequently reported adverse events with mipomersen. Mild-to-moderate flu-like symptoms were reported more often with mipomersen. Alanine transaminase increase, aspartate transaminase increase, and hepatic steatosis occurred in 21%, 13% and 13% of mipomersen treated patients, respectively. Adverse events by category for the placebo and mipomersen groups respectively were: total adverse events, 16(84.2%), 39(100%); serious adverse events, 0(0%), 6(15.4%); discontinuations due to adverse events, 1(5.3%), 8(20.5%) and cardiac adverse events, 1(5.3%), 5(12.8%). Conclusion Mipomersen significantly reduced LDL-C, apolipoprotein B, total cholesterol and non-HDL-cholesterol, and

  12. High dose simvastatin exhibits enhanced lipid lowering effects relative to simvastatin/ezetimibe combination therapy

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Technical Abstract: Background: Statins are the frontline in cholesterol reduction therapies; however use in combination with agents that possess complimentary mechanisms of action may achieve further reduce in LDL-C. Methods and Results: Thirty-nine patients were treated with either 80mg simvasta...

  13. Is Lipid Lowering Therapy an Independent Risk Factor for Venous Thromboembolism? A Population-Based Case-Control Study

    PubMed Central

    Ashrani, Aneel A.; Barsoum, Michel K.; Crusan, Daniel J.; Petterson, Tanya M.; Bailey, Kent R.; Heit, John A.

    2015-01-01

    Introduction The independent effect of lipid lowering therapy (LLT) on venous thromboembolism (VTE) risk is uncertain. Objective To test statin and non-statin LLT as potential VTE risk factors. Methods Using Rochester Epidemiology Project resources, we identified all Olmsted County, MN residents with objectively diagnosed incident VTE (cases) over the 13-year period, 1988–2000 (n=1340), and one to two matched controls (n=1538). We reviewed their complete medical records for baseline characteristics previously identified as independent VTE risk factors, and for statin and non-statin LLT. Using conditional logistic regression, we tested the overall effect of LLT on VTE risk and also separately explored the role of statin versus that of non-statin LLT, adjusting for other baseline characteristics. Results Among cases and controls, 74 and 111 received statin LLT, and 32 and 50 received non-statin LLT, respectively. Univariately, and after individually controlling for other potential VTE risk factors (i.e., BMI, trauma/fracture, leg paresis, hospitalization for surgery or medical illness, nursing home residence, active cancer, central venous catheter, varicose veins, prior superficial vein thrombosis, diabetes, congestive heart failure, angina/myocardial infarction, stroke, peripheral vascular disease, smoking, anticoagulation), LLT was associated with decreased odds of VTE (unadjusted OR= 0.73; p= 0.03). When considered separately, statin and non-statin LLT were each associated with moderate, non-significant lower odds of VTE. After adjusting for angina/myocardial infarction, each was significantly associated with decreased odds of VTE (OR= 0.63, p< 0.01 and OR= 0.61, p=0.04, respectively). Conclusions LLT is associated with decreased VTE risk after adjusting for known risk factors. PMID:25891841

  14. The MYLIP p.N342S polymorphism is associated with response to lipid-lowering therapy in Brazilian patients with familial hypercholesterolemia

    PubMed Central

    Santos, Paulo C.J.L.; Morgan, Aline C.; Jannes, Cinthia E.; Krieger, José E.; Santos, Raul D.

    2014-01-01

    Background A previous study reported that the myosin regulatory light chain interacting protein (MYLIP) might serve as a novel therapeutic class for treating dyslipidemia. It contributes to variations in the levels of circulating low-density lipoprotein cholesterol (LDL-C), promoting the degradation of LDL–LDLR, thus limiting absorption. The effect of genetic variation in the MYLIP gene in a disease scenario characterized by mutations in the LDLR gene has not been previously evaluated. Objective The aim of this study was to assess the effect of the p.N342S variant on the response to lipid-lowering therapy in Brazilian patients with heterozygous familial hypercholesterolemia (FH). Patients and methods A total of 156 patients with heterozygous FH were followed up for 12 months and received lipid-lowering therapy (different doses of atorvastatin with the addition of ezetimibe in over half the patients of each genotype group). Cholesterol data were assessed, and analysis of the MYLIP rs9370867 (p.N342S) genotypes was carried out by melting curve analysis. Results Baseline total cholesterol and baseline LDL-C levels were not different between genotypes. After 1 year of treatment, LDL-C responses (expressed as mg/dl and as %) were significantly different among genotypes (AA: −79±68 and −39±27, GA: −60±79 and −27±32, and GG: −30±83 and −15±38; P=0.02 and 0.005, respectively). In addition, FH patients carrying the AA genotype were more likely to achieve LDL-C levels of less than 130 mg/dl after 1 year of treatment (75.0%) compared with patients with the GG and GA genotypes (34.5 and 34.8%, respectively; P=0.001). Conclusion Our study indicates that MYLIP p.N342S might be a pharmacogenetic marker for lipid-lowering therapy in patients with FH. PMID:25171759

  15. Adherence to lipid-lowering therapy and the use of preventive health services: an investigation of the healthy user effect.

    PubMed

    Brookhart, M Alan; Patrick, Amanda R; Dormuth, Colin; Avorn, Jerry; Shrank, William; Cadarette, Suzanne M; Solomon, Daniel H

    2007-08-01

    Patients who adhere to preventive therapies may be more likely to engage in a broad spectrum of behaviors consistent with a healthy lifestyle. Because many of these behaviors cannot be measured easily, observational studies of outcomes associated with the long-term use of preventive therapies are subject to the so-called "healthy user bias." To better understand this effect, the authors examined the association between adherence to statin therapy and the use of preventive health services in a Pennsylvania cohort of 20,783 new users of statins between 1996 and 2004. After adjustment for age, gender, and various comorbid conditions, patients who filled two or more prescriptions for a statin during a 1-year ascertainment period were more likely than patients who filled only one prescription to receive prostate-specific antigen tests (hazard ratio (HR)=1.57, 95% confidence interval (CI): 1.17, 2.19), fecal occult blood tests (HR=1.31, 95% CI: 1.12, 1.53), screening mammograms (HR=1.22, 95% CI: 1.09, 1.38), influenza vaccinations (HR=1.21, 95% CI: 1.12, 1.31), and pneumococcal vaccinations (HR=1.46, 95% CI: 1.17, 1.83) during follow-up. These results suggest that patients who adhere to chronic therapies are more likely to seek out preventive health services, such as screening tests and vaccinations. Further work is needed to identify study design and analysis methods that can be used to minimize the healthy user bias in studies of preventive therapies.

  16. The Interpretation of Cholesterol Balance Derived Synthesis Data and Surrogate Noncholesterol Plasma Markers for Cholesterol Synthesis under Lipid Lowering Therapies

    PubMed Central

    Stellaard, Frans

    2017-01-01

    The cholesterol balance procedure allows the calculation of cholesterol synthesis based on the assumption that loss of endogenous cholesterol via fecal excretion and bile acid synthesis is compensated by de novo synthesis. Under ezetimibe therapy hepatic cholesterol is diminished which can be compensated by hepatic de novo synthesis and hepatic extraction of plasma cholesterol. The plasma lathosterol concentration corrected for total cholesterol concentration (R_Lath) as a marker of de novo cholesterol synthesis is increased during ezetimibe treatment but unchanged under treatment with ezetimibe and simvastatin. Cholesterol balance derived synthesis data increase during both therapies. We hypothesize the following. (1) The cholesterol balance data must be applied to the hepatobiliary cholesterol pool. (2) The calculated cholesterol synthesis value is the sum of hepatic de novo synthesis and the net plasma—liver cholesterol exchange rate. (3) The reduced rate of biliary cholesterol absorption is the major trigger for the regulation of hepatic cholesterol metabolism under ezetimibe treatment. Supportive experimental and literature data are presented that describe changes of cholesterol fluxes under ezetimibe, statin, and combined treatments in omnivores and vegans, link plasma R_Lath to liver function, and define hepatic de novo synthesis as target for regulation of synthesis. An ezetimibe dependent direct hepatic drug effect cannot be excluded. PMID:28321334

  17. Common variants of HMGCR, CETP, APOAI, ABCB1, CYP3A4, and CYP7A1 genes as predictors of lipid-lowering response to atorvastatin therapy.

    PubMed

    Poduri, Aruna; Khullar, Madhu; Bahl, Ajay; Sehrawat, B S; Sharma, Yashpaul; Talwar, Kewal K

    2010-10-01

    There is interindividual variation in lipid-lowering response to statins. The objective of this study was to investigate whether common variation in genes involved in lipid and statin metabolism modify the effect of statins on serum total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), and high-density lipoprotein-cholesterol concentration in coronary artery disease (CAD) patients. We studied the association between 18 single-nucleotide polymorphisms (SNPs) in six genes (HMGCR, CETP, APOAI, ABCB1, CYP3A4, CYP7A1) in response to atorvastatin therapy (20 mg/day) in 265 newly diagnosed CAD patients using multivariable adjusted general linear regression. Variant alleles of ABCB1 (-41A/G), HMGCR SNP29 G/T, rs5908A/G, rs12916C/T, and CYP7A1-204A/C polymorphisms were significantly associated with attenuated LDL-C reduction and variant alleles of CETP TaqI, -629C/A, and APOAI PstI polymorphisms were associated with higher increase in high-density lipoprotein-cholesterol. A three-loci interaction model consisting of CYP7A1rs892871AA/APOAIPstIP1P1/HMGCR rs12916CT was a better predictor for LDL-C lowering, when compared with single polymorphisms analysis on statin response. Variant genotypes of APOAI -2500C/T, CETP 405I/V, and ABCB1 3435C/T showed higher risk of myocardial infarction events (p < 0.05) in a 1-year follow-up of CAD patients. These results suggest that SNPs in lipid and statin pathway genes are associated with reduced LDL-C lowering by statins and identify individuals who may be resistant to maximal LDL-C lowering by statins.

  18. Gemfibrozil, stretching arms beyond lipid lowering

    PubMed Central

    Roy, Avik; Pahan, Kalipada

    2009-01-01

    Gemfibrozil is long known for its ability to reduce the level of triglycerides in the blood circulation and to decrease the risk of hyperlipidemia. However, a number of recent studies reveal that apart from its lipid-lowering effects, gemfibrozil can also regulate many other signaling pathways responsible for inflammation, switching of T-helper cells, cell-to-cell contact, migration, and oxidative stress. In this review, we have made an honest attempt to analyze various biological activities of gemfibrozil and associated mechanisms that may help to consider this drug for different human disorders as primary or adjunct therapy. PMID:19694602

  19. Neoatherosclerosis causing occlusive in-stent restenosis: Impact of intracoronary imaging in the intensity of lipid-lowering therapy.

    PubMed

    Martí, David; López, Edurne; Álvarez, Salvador; Palazuelos, Jorge; Rada, Ignacio; Alfonso, Fernando

    2016-12-01

    The unique physical properties of optical coherence tomography (OCT) make it a useful technique in the study of restenosis mechanisms. In fact, OCT is able to differentiate between neointimal proliferation and neoatherosclerosis within the stent. We report a rare case of occlusive neoatherosclerosis presenting beyond one year after a successful drug-eluting stent implantation. The impact of OCT findings in the clinical decision making process is emphasized.

  20. Intensity modulated proton therapy

    PubMed Central

    Grassberger, C

    2015-01-01

    Intensity modulated proton therapy (IMPT) implies the electromagnetic spatial control of well-circumscribed “pencil beams” of protons of variable energy and intensity. Proton pencil beams take advantage of the charged-particle Bragg peak—the characteristic peak of dose at the end of range—combined with the modulation of pencil beam variables to create target-local modulations in dose that achieves the dose objectives. IMPT improves on X-ray intensity modulated beams (intensity modulated radiotherapy or volumetric modulated arc therapy) with dose modulation along the beam axis as well as lateral, in-field, dose modulation. The clinical practice of IMPT further improves the healthy tissue vs target dose differential in comparison with X-rays and thus allows increased target dose with dose reduction elsewhere. In addition, heavy-charged-particle beams allow for the modulation of biological effects, which is of active interest in combination with dose “painting” within a target. The clinical utilization of IMPT is actively pursued but technical, physical and clinical questions remain. Technical questions pertain to control processes for manipulating pencil beams from the creation of the proton beam to delivery within the patient within the accuracy requirement. Physical questions pertain to the interplay between the proton penetration and variations between planned and actual patient anatomical representation and the intrinsic uncertainty in tissue stopping powers (the measure of energy loss per unit distance). Clinical questions remain concerning the impact and management of the technical and physical questions within the context of the daily treatment delivery, the clinical benefit of IMPT and the biological response differential compared with X-rays against which clinical benefit will be judged. It is expected that IMPT will replace other modes of proton field delivery. Proton radiotherapy, since its first practice 50 years ago, always required the

  1. Coumarin and Derivates as Lipid Lowering Agents.

    PubMed

    Tejada, Silvia; Martorell, Miquel; Capo, Xavier; Tur, Josep A; Pons, Antoni; Sureda, Antoni

    2017-01-01

    Cardiovascular disease is the main cause of death in the developed countries. Dyslipidaemia is one of the risk factors associated to cardiovascular disease and it is characterised by abnormal amounts of lipids (i.e. cholesterol and fatty acids) and/or circulating lipoproteins in the blood. Oxidative stress has been implicated in the pathogenesis of various illnesses including cardiovascular disease. In this way, the potential therapeutic or preventive effects of antioxidant mediators have recently drawn much attention. Coumarin (1,2-benzopyrone) is a natural phenolic compound found in many plants such as citrus fruits, tomatoes, vegetables and green tea. Coumarin and derivates are proposed as lipid lowering agents due to its broad pharmacological activities, mainly the implicated in vasodilator and antioxidant effect. Several studies have evidenced a promising role of coumarin and several of its derivates as lipid lowering agents. In the current work, the available reports related to the promising function of these compounds are reviewed.

  2. Intensity-Modulated Radiation Therapy (IMRT)

    MedlinePlus

    ... Resources Professions Site Index A-Z Intensity-Modulated Radiation Therapy (IMRT) Intensity-modulated radiotherapy (IMRT) uses linear ... and after this procedure? What is Intensity-Modulated Radiation Therapy and how is it used? Intensity-modulated ...

  3. Role of phytosterols in lipid-lowering: current perspectives.

    PubMed

    Gupta, A K; Savopoulos, C G; Ahuja, J; Hatzitolios, A I

    2011-04-01

    The cholesterol-lowering effect of plant sterols was first discovered in the early 1950s. However, it is only recently that plant sterols have become clinically important, when advances in food-technology have made it possible to combine sterols with a variety of food products including margarines, yogurts, fruit juices and cereal bars. We review the clinical trial evidence of lipid-lowering efficacy of plant sterols and discuss their implications in routine clinical practice. To generate the evidence we searched the Pubmed database for English language literature, using relevant keywords and medical subject heading (MeSH) terms, and extracted the findings from recently published studies and meta-analyses on this topic. Our findings suggest that the short-term use of food supplements rich in plant sterols is a safe and effective strategy; to maximize the benefits of dietary and lifestyle therapy, either with or without statin therapy, among majority of dyslipidemic patients with need for additional lipid-lowering.

  4. [Lipid-lowering drugs and PCSK9].

    PubMed

    Millán Núñez-Cortés, Jesús; Mostaza Prieto, José M

    2016-05-01

    PCSK9 is a protease, synthesized mainly in the liver, which promotes the hepatic degradation of the LDL receptor and consequently decreases LDL receptor density and clearance of LDL particles. Statins inhibit HMG-CoA-reductase activity, an enzyme that catalyses an important step in hepatic cholesterol biosynthesis. The decrease of the hepatic intracellular cholesterol pool produced by these drugs upregulates the activity of the SREBP2 transcription factor, which subsequently stimulates the expression of the LDL receptor gene, an effect that is followed by an increase in the serum concentration of PCSK9. This article aims to review the effects of different lipid-lowering drugs on plasma PCSK9 concentrations. Overall, statins increase blood PCSK9 levels, an effect that is enhanced by ezetimibe. In contrast, others drugs, such as fibrates and niacin, could decrease PCSK9 levels.

  5. Intensive Insulin Therapy: Tight Blood Sugar Control

    MedlinePlus

    ... insulin therapy can help you achieve desired blood sugar control and what intensive insulin therapy requires of ... aggressive treatment approach designed to control your blood sugar levels. Intensive insulin therapy requires close monitoring of ...

  6. Lipid-lowering update 2001. Aggressive new goals.

    PubMed Central

    Fenske, T. K.

    2001-01-01

    OBJECTIVE: To review the central role of cholesterol in coronary artery disease (CAD), underscore the need for identifying patients at high risk of CAD, and discuss treatment of dyslipidemias. QUALITY OF EVIDENCE: Current literature (1995-2000) was searched via MEDLINE using the MeSH headings "cholesterol," "risk reduction," and "statins." Recommendations in this paper are based mainly on the results of large randomized controlled trials. Preference was given to more recent articles, clinically relevant articles, and landmark clinical trials. MAIN MESSAGE: Lipid lowering, and specifically low-density lipoprotein lowering, has been repeatedly shown in large clinical trials to improve survival dramatically and reduce cardiac events in both primary and secondary prevention. Identifying those at highest risk for future cardiac events is critical because these patients will benefit most from aggressive modification of risk factors. The definition of high risk has been expanded to include patients with diabetes mellitus and peripheral vascular disease, as well as those with established CAD. A full lipid profile is required for these patients to assess risk and develop a lipid-lowering strategy with proven effectiveness. CONCLUSION: With the advent of powerful, efficacious, and well tolerated cholesterol-modifying therapies, lipid normalization should be a mandate for all physicians caring for patients with established CAD and patients at risk of developing CAD. PMID:11228031

  7. Intensity-modulated radiation therapy.

    PubMed

    Goffman, Thomas E; Glatstein, Eli

    2002-07-01

    Intensity-modulated radiation therapy (IMRT) is an increasingly popular technical means of tightly focusing the radiation dose around a cancer. As with stereotactic radiotherapy, IMRT uses multiple fields and angles to converge on the target. The potential for total dose escalation and for escalation of daily fraction size to the gross cancer is exciting. The excitement, however, has greatly overshadowed a range of radiobiological and clinical concerns.

  8. New Era of Lipid-Lowering Drugs

    PubMed Central

    Rye, Kerry-Anne

    2016-01-01

    There are several established lipid-modifying agents, including statins, fibrates, niacin, and ezetimibe, that have been shown in randomized clinical outcome trials to reduce the risk of having an atherosclerotic cardiovascular event. However, in many people, the risk of having an event remains unacceptably high despite treatment with these established agents. This has stimulated the search for new therapies designed to reduce residual cardiovascular risk. New approaches that target atherogenic lipoproteins include: 1) inhibition of proprotein convertase subtilisin/kexin type 9 to increase removal of atherogenic lipoproteins from plasma; 2) inhibition of the synthesis of apolipoprotein (apo) B, the main protein component of atherogenic lipoproteins; 3) inhibition of microsomal triglyceride transfer protein to block the formation of atherogenic lipoproteins; 4) inhibition of adenosine triphosphate citrate lyase to inhibit the synthesis of cholesterol; 5) inhibition of the synthesis of lipoprotein(a), a factor known to cause atherosclerosis; 6) inhibition of apoC-III to reduce triglyceride-rich lipoproteins and to enhance high-density lipoprotein (HDL) functionality; and 7) inhibition of cholesteryl ester transfer protein, which not only reduces the concentration of atherogenic lipoproteins but also increases the level and function of the potentially antiatherogenic HDL fraction. Other new therapies that specifically target HDLs include infusions of reconstituted HDLs, HDL delipidation, and infusions of apoA-I mimetic peptides that mimic some of the functions of HDLs. This review describes the scientific basis and rationale for developing these new therapies and provides a brief summary of established therapies. PMID:26983688

  9. Intensive insulin therapy in the intensive cardiac care unit.

    PubMed

    Hasin, Tal; Eldor, Roy; Hammerman, Haim

    2006-01-01

    Treatment in the intensive cardiac care unit (ICCU) enables rigorous control of vital parameters such as heart rate, blood pressure, body temperature, oxygen saturation, serum electrolyte levels, urine output and many others. The importance of controlling the metabolic status of the acute cardiac patient and specifically the level of serum glucose was recently put in focus but is still underscored. This review aims to explain the rationale for providing intensive control of serum glucose levels in the ICCU, especially using intensive insulin therapy and summarizes the available clinical evidence suggesting its effectiveness.

  10. Nutraceuticals in lipid-lowering treatment: a narrative review on the role of chitosan.

    PubMed

    Patti, Angelo Maria; Katsiki, Niki; Nikolic, Dragana; Al-Rasadi, Khalid; Rizzo, Manfredi

    2015-05-01

    Lipid-lowering drugs may cause adverse effects and, although lipid targets may be achieved, a substantial residual cardiovascular (CV) risk remains. Treatment with agents mimicking proteins present in the body, such as incretin-based therapies, provided promising results. However, in order to improve lipids and CV risk, lifestyle measures remain important. Some researchers focused on nutraceuticals that may beneficially affect metabolic parameters and minimize CV risk. Chitosan, a dietary fiber, can regulate lipids with benefit on anthropometric parameters. The beneficial properties of dietary supplements (such as green tea extract, prebiotics, plant sterols, and stanols) on plasma lipids, lipoproteins, blood pressure, glucose, and insulin levels and their anti-inflammatory and anti-oxidant effects are documented. However, larger, prospective clinical trials are required to confirm such benefits. Such treatments may be recommended when lipid-lowering drugs are neither indicated nor tolerated as well as in order to achieve therapeutic targets and/or overcome residual CV risk.

  11. [Dyslipidemia - when are lipid lowering medications useful in clinical practice?].

    PubMed

    Blum, Manuel R; Stanga, Zeno; Rodondi, Nicolas

    2013-05-08

    Dyslipidemia is one of the main modifiable cardiovascular risk factors. There is strong evidence for the efficacy of lipid-lowering drugs in secondary prevention, as well as in primary prevention for patients at high cardiovascular risk. In primary prevention, indication for lipid-lowering interventions should be based on an individual assessment of the cardiovascular risk and on the LDL cholesterol level, despite less strong evidence for the efficacy of drug-based interventions in low risk patients. Treatment consists of statins, as well as lifestyle modifications such as body weight control and increased physical exercise. The latter constitute the primary intervention in patients at low cardiovascular risk. Secondary dyslipidemias due to an underlying medical condition and familial dyslipidemias such as Familial Hypercholesterolemia and Familial Combined Hyperlipidemia should be identified and treated accordingly, taking into account that the risk scoring systems are not appropriate in these situations.

  12. [Special recommendations for lipid-lowering treatment: efficacy and safety].

    PubMed

    Martinez, Tania Leme da Rocha; Nascimento, Helena Maria do

    2005-10-01

    Pharmacologic lipid-lowering interventions should be monitored periodically to assess efficacy and safety parameters. Statins are usually well-tolerated drugs and major side effects include increased serum liver and muscle enzymes (AST, ALT, CK). Treatment should be stopped or diminished in case of significant increase of AST or ALT (> 3x ULN), or CK (> 10x ULN). Other lipid lowering agents may also produce hepatotoxicity or myositis, especially in association with statins (fibrates and nicotinic acid) or in presence of metabolic abnormalities (thyroid, liver or renal disorders). Nicotinic acid can also increase glucose and uric acid plasma levels. Laboratory tests might be performed prior to hypolipidemic drug treatment and should be repeated every three months during the first year and then at 6-mo intervals. Shorter intervals should be recommended in individual cases.

  13. A Metaanalysis of Interventions to Improve Adherence to Lipid-Lowering Medication

    PubMed Central

    Deichmann, Richard E.; Morledge, Michael D.; Ulep, Robin; Shaffer, Johnathon P.; Davies, Philippa; van Driel, Mieke L.

    2016-01-01

    Background: Inadequate patient adherence to a medication regimen is a major factor in the lack of success in treating hyperlipidemia. Improved adherence rates may result in significantly improved cardiovascular outcomes in populations treated with lipid-lowering therapy. The purpose of this metaanalysis was to evaluate the effectiveness of interventions aimed at improving adherence to lipid-lowering drugs, focusing on measures of adherence and clinical outcomes. Methods: We searched the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, PsycINFO, and the Cumulative Index to Nursing and Allied Health Literature databases through January 14, 2015, and also used the results from previous Cochrane reviews of this title. Randomized controlled trials of adherence-enhancing interventions for lipid-lowering medication in adults in an ambulatory setting with measurable outcomes were evaluated with criteria outlined by the Cochrane Handbook for Systematic Reviews of Interventions. Results: Twenty-seven studies randomly assigning 899,068 participants to a variety of interventions were analyzed. One group of interventions categorized as intensified patient care showed significant improvement in adherence rates when compared to usual care (odds ratio 1.93; 95% confidence interval [CI] 1.29-2.88). Additionally, after <6 months of follow-up, total cholesterol decreased by a mean of 17.15 mg/dL (95% CI 1.17-33.14), while after >6 months total cholesterol decreased by a mean of 17.57 mg/dL (95% CI 14.95-20.19). Conclusion: Healthcare systems that can implement team-based intensified patient care interventions, such as electronic reminders, pharmacist-led interventions, and healthcare professional education of patients, may be successful in improving adherence rates to lipid-lowering medicines. PMID:27660570

  14. Cardiovascular effects of statins, beyond lipid-lowering properties.

    PubMed

    Mihos, Christos G; Pineda, Andres M; Santana, Orlando

    2014-10-01

    The 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors, better known as 'statins', are amongst the most widely used medications in the world. They have become a pivotal component in the primary and secondary prevention of coronary artery and vascular disease. However, a growing amount of evidence has suggested that statins also possess strong pleiotropic effects irrespective of their lipid-lowering properties, which include enhancement of endothelial function, anti-inflammatory and anti-atherothrombotic properties, and immunomodulation. The following provides a comprehensive and updated review of the clinical evidence regarding the pleiotropic effects of statins in cardiovascular disorders and their potential therapeutic benefits.

  15. Virtual micro-intensity modulated radiation therapy.

    PubMed

    Siochi, R A

    2000-11-01

    Virtual micro-intensity modulated radiation therapy (VMIMRT) combines a 10 x 5 mm2 intensity map with a 5 x 10 mm2 intensity map, delivered at orthogonal collimator settings. The superposition of these component maps (CM) yields a 5 x 5 mm2 virtual micro-intensity map (VMIM) that can be delivered with a 1 cm leaf width MLC. A pair of CMs with optimal delivery efficiency and quality must be chosen, since a given VMIM can be delivered using several different pairs. This is possible since, for each group of four VMIM cells that can be covered by an MLC leaf in either collimator orientation, the minimum intensity can be delivered from either collimator setting. By varying the proportions of the minimum values that go into each CM, one can simultaneously minimize the number of potential junction effects and the number of segments required to deliver the VMIM. The minimization is achieved by reducing high leaf direction gradients in the CMs. Several pseudoclinical and random VMIMs were studied to determine the applicability of this new technique. A nine level boost map was also studied to investigate dosimetric and spatial resolution issues. Finally, clinical issues for this technique are discussed.

  16. D-003 (Saccharum officinarum): The forgotten lipid-lowering agent.

    PubMed

    Awad, Kamal; Penson, Peter; Banach, Maciej

    2016-12-01

    Reduction of elevated cholesterol levels, particularly low-density lipoprotein cholesterol (LDL-C), is essential in primary and secondary prevention of cardiovascular disease (CVD). Therefore there is still a large need for new effective drugs, which would be able to essentially reduce LDL-C and in the consequence CV residual risk. D-003 is a mixture of high aliphatic primary acids purified from sugarcane (Saccharum officinarum) wax. It showed promising hypocholesterolemic effects in both animal and human studies; it significantly lowers both serum total cholesterol (TC) and LDL-C, and increases high-density lipoprotein cholesterol (HDL-C). In addition, it showed a favorable safety profile. In this review, we evaluated the profile of D-003 as a lipid-lowering agent based on data from available preclinical and clinical studies.

  17. Fan-beam intensity modulated proton therapy

    PubMed Central

    Hill, Patrick; Westerly, David; Mackie, Thomas

    2013-01-01

    Purpose: This paper presents a concept for a proton therapy system capable of delivering intensity modulated proton therapy using a fan beam of protons. This system would allow present and future gantry-based facilities to deliver state-of-the-art proton therapy with the greater normal tissue sparing made possible by intensity modulation techniques. Methods: A method for producing a divergent fan beam of protons using a pair of electromagnetic quadrupoles is described and particle transport through the quadrupole doublet is simulated using a commercially available software package. To manipulate the fan beam of protons, a modulation device is developed. This modulator inserts or retracts acrylic leaves of varying thickness from subsections of the fan beam. Each subsection, or beam channel, creates what effectively becomes a beam spot within the fan area. Each channel is able to provide 0–255 mm of range shift for its associated beam spot, or stop the beam and act as an intensity modulator. Results of particle transport simulations through the quadrupole system are incorporated into the MCNPX Monte Carlo transport code along with a model of the range and intensity modulation device. Several design parameters were investigated and optimized, culminating in the ability to create topotherapy treatment plans using distal-edge tracking on both phantom and patient datasets. Results: Beam transport calculations show that a pair of electromagnetic quadrupoles can be used to create a divergent fan beam of 200 MeV protons over a distance of 2.1 m. The quadrupole lengths were 30 and 48 cm, respectively, with transverse field gradients less than 20 T/m, which is within the range of water-cooled magnets for the quadrupole radii used. MCNPX simulations of topotherapy treatment plans suggest that, when using the distal edge tracking delivery method, many delivery angles are more important than insisting on narrow beam channel widths in order to obtain conformal target coverage

  18. Fan-beam intensity modulated proton therapy

    SciTech Connect

    Hill, Patrick; Westerly, David; Mackie, Thomas

    2013-11-15

    Purpose: This paper presents a concept for a proton therapy system capable of delivering intensity modulated proton therapy using a fan beam of protons. This system would allow present and future gantry-based facilities to deliver state-of-the-art proton therapy with the greater normal tissue sparing made possible by intensity modulation techniques.Methods: A method for producing a divergent fan beam of protons using a pair of electromagnetic quadrupoles is described and particle transport through the quadrupole doublet is simulated using a commercially available software package. To manipulate the fan beam of protons, a modulation device is developed. This modulator inserts or retracts acrylic leaves of varying thickness from subsections of the fan beam. Each subsection, or beam channel, creates what effectively becomes a beam spot within the fan area. Each channel is able to provide 0–255 mm of range shift for its associated beam spot, or stop the beam and act as an intensity modulator. Results of particle transport simulations through the quadrupole system are incorporated into the MCNPX Monte Carlo transport code along with a model of the range and intensity modulation device. Several design parameters were investigated and optimized, culminating in the ability to create topotherapy treatment plans using distal-edge tracking on both phantom and patient datasets.Results: Beam transport calculations show that a pair of electromagnetic quadrupoles can be used to create a divergent fan beam of 200 MeV protons over a distance of 2.1 m. The quadrupole lengths were 30 and 48 cm, respectively, with transverse field gradients less than 20 T/m, which is within the range of water-cooled magnets for the quadrupole radii used. MCNPX simulations of topotherapy treatment plans suggest that, when using the distal edge tracking delivery method, many delivery angles are more important than insisting on narrow beam channel widths in order to obtain conformal target coverage

  19. Rhabdomyolysis: a case study exploring the possible side effect of lipid lowering medication by a HIV positive patient taking a protease inhibitor.

    PubMed

    De Carvalho, Diana; Citro, Mark; Tibbles, Anthony

    2008-12-01

    This case study explores the incidence of rhabdomyolysis in a HIV positive patient that was taking a lipid lowering drug and a protease inhibitor concurrently while under chiropractic treatment for generalized muscular soreness. Dyslipidemia is a very common problem both in the general and HIV population, with many patients being prescribed lipid lowering drugs. While extremely rare, adverse effects of lipid lowering drugs have been documented to include myopathy such as rhabdomyolysis. It is imperative that chiropractors are aware of the possible adverse side effect of lipid lowering drug therapy in their patients complaining of musculoskeletal pain. It is even more important that chiropractors treating the HIV population are aware of the potential interactions between these medications and protease inhibitors to cause myopathy.

  20. Formulation and Evaluation of Nanocrystals of a Lipid Lowering Agent.

    PubMed

    Louis, Dina

    2016-01-01

    Atorvastatin calcium, the lipid lowering agent, is taken as a model drug characterized by poor water solubility and bioavailability. In this study an attempt was made for preparation of nanocrystals using high pressure homogenization. A number of stabilizers were included as well as polymers at different concentrations, and the formulations were homogenized for ten cycles at a pressure of 1000 bars. The obtained nano crystals were evaluated by determining their size, zeta potential, saturated solubility and dissolution rate. Results revealed that Formulation 3, containing (10: 1) drug to sodium lauryl sulphate ratio, possessed the highest saturated solubility and dissolution rate, and hence was analyzed by X-ray diffraction analysis, differential scanning calorimetry, Fourrier transform infrared spectroscopy and scanning electron microscopy. An in-vivo study was carried out on the successful formulation in comparison to drug powder using rats as experimental animals. A significant increase in the area under the concentration-time curve Cpmax and MRT for nanocrystals was observed in comparison to the untreated atorvastatin calcium.

  1. Formulation and Evaluation of Nanocrystals of a Lipid Lowering Agent

    PubMed Central

    Louis, Dina

    2016-01-01

    Atorvastatin calcium, the lipid lowering agent, is taken as a model drug characterized by poor water solubility and bioavailability. In this study an attempt was made for preparation of nanocrystals using high pressure homogenization. A number of stabilizers were included as well as polymers at different concentrations, and the formulations were homogenized for ten cycles at a pressure of 1000 bars. The obtained nano crystals were evaluated by determining their size, zeta potential, saturated solubility and dissolution rate. Results revealed that Formulation 3, containing (10: 1) drug to sodium lauryl sulphate ratio, possessed the highest saturated solubility and dissolution rate, and hence was analyzed by X-ray diffraction analysis, differential scanning calorimetry, Fourrier transform infrared spectroscopy and scanning electron microscopy. An in-vivo study was carried out on the successful formulation in comparison to drug powder using rats as experimental animals. A significant increase in the area under the concentration-time curve Cpmax and MRT for nanocrystals was observed in comparison to the untreated atorvastatin calcium. PMID:27610148

  2. Film Dosimetry for Intensity Modulated Radiation Therapy

    NASA Astrophysics Data System (ADS)

    Benites-Rengifo, J.; Martínez-Dávalos, A.; Celis, M.; Lárraga, J.

    2004-09-01

    Intensity Modulated Radiation Therapy (IMRT) is an oncology treatment technique that employs non-uniform beam intensities to deliver highly conformal radiation to the targets while minimizing doses to normal tissues and critical organs. A key element for a successful clinical implementation of IMRT is establishing a dosimetric verification process that can ensure that delivered doses are consistent with calculated ones for each patient. To this end we are developing a fast quality control procedure, based on film dosimetry techniques, to be applied to the 6 MV Novalis linear accelerator for IMRT of the Instituto Nacional de Neurología y Neurocirugía (INNN) in Mexico City. The procedure includes measurements of individual fluence maps for a limited number of fields and dose distributions in 3D using extended dose-range radiographic film. However, the film response to radiation might depend on depth, energy and field size, and therefore compromise the accuracy of measurements. In this work we present a study of the dependence of Kodak EDR2 film's response on the depth, field size and energy, compared with those of Kodak XV2 film. The first aim is to devise a fast and accurate method to determine the calibration curve of film (optical density vs. doses) commonly called a sensitometric curve. This was accomplished by using three types of irradiation techniques: Step-and-shoot, dynamic and static fields.

  3. [Palliative therapy concepts in intensive care medicine].

    PubMed

    Schuster, M; Ferner, M; Bodenstein, M; Laufenberg-Feldmann, R

    2017-04-01

    Involvement of palliative care is so far not common practice for critically ill patients on surgical intensive care units (ICUs) in Germany. The objectives of palliative care concepts are improvement of patient quality of life by relief of disease-related symptoms using an interdisciplinary approach and support of patients and their relatives considering their current physical, psychological, social and spiritual needs. The need for palliative care can be identified via defined screening criteria. Integration of palliative care can either be realized using a consultative model which focusses on involvement of palliative care consultants or an integrative model which embeds palliative care principles into the routine daily practice by the ICU team. Early integration of palliative care in terms of advance care planning (ACP) can lead to an increase in goals of care discussions and quality of life as well as a decrease of mortality and length of stay on the ICU. Moreover, stress reactions of relatives and ICU staff can be reduced and higher satisfaction with therapy can be achieved. The core of goal of care discussions is professional and well-structured communication between patients, relatives and staff. Consideration of palliative care principles by model-based integration into ICU practice can improve complex intensive care courses of disease in a productive but dignified way without neglecting curative attempts.

  4. Intensity of Therapy Services: What Are the Considerations?

    ERIC Educational Resources Information Center

    Palisano, Robert J.; Murr, Susan

    2009-01-01

    Research on intensity of therapy services is limited and perspectives often vary considerably among families, therapists, administrators, policy makers, and health insurers. In this commentary, the authors share their perspectives on intensity of physical therapy and/or occupational therapy services for children with developmental conditions. Five…

  5. Lipid lowering effect of Cinnamomum zeylanicum in hyperlipidaemic albino rabbits.

    PubMed

    Javed, Ijaz; Faisal, Imran; Rahman, Ziaur; Khan, Muhammad Zargham; Muhammad, Faqir; Aslam, Bilal; Ahmad, Mahmood; Shahzadi, Andleeb

    2012-01-01

    The purpose of the present study was to investigate the lipid lowering effect of Cinnamomum zeylanicum (Cinnamon) in hyperlipidaemic albino rabbits. For this purpose, forty eight albino rabbits were randomly divided into eight equal groups; untreated control on normal routine feed, untreated control on butter and cholesterol, treated control on synthetic cholesterol lowering drug simvastatin (Tablet survive (R) 20 mg), three treated groups on three respective doses of C. zeylanicum bark powder and two treated groups on water and methanol extracts of C. zeylanicum bark powder. Butter ad lib and cholesterol powder 500 mg/kg body weight were used to induce experimental hyperlipidaemia in all groups except untreated control group. The results suggested that C. zeylanicum bark powder at the rate of 0.50 g/kg, 0.75 g/kg and methanol extract equivalent to 0.75 g/kg powder produced respective percent reductions in total lipids by 45, 49 and 64; triglycerides by 38, 53 and 60; total cholesterol by 53, 64 and 69 and LDL-cholesterol by 50, 59 and 62. However, at these dosage levels HDL-cholesterol showed respective percent increase of 42, 48 and 53. Nonetheless, C. zeylanicum bark powder at the level of 0.25g/kg and C. zeylanicum extract in water could not significantly reduce lipid profile indicators. Based on these studies, it can safely be said that C. zeylanicum bark powder methanol extract equivalent to 0.75g/kg bark powder and simvastatin (0.6 mg/kg b. wt.) were equieffective in treating hyperlipidaemia.

  6. Combination of simvastatin with berberine improves the lipid-lowering efficacy.

    PubMed

    Kong, Wei-Jia; Wei, Jin; Zuo, Zeng-Yan; Wang, Yue-Ming; Song, Dan-Qing; You, Xue-Fu; Zhao, Li-Xun; Pan, Huai-Ning; Jiang, Jian-Dong

    2008-08-01

    We have identified berberine (BBR) as a novel cholesterol-lowering drug acting through stabilization of the low-density lipoprotein receptor (LDLR) messenger RNA. Because the mechanism differs from that of statins, it is of great interest to examine the lipid-lowering activity of BBR in combination with statins. Our results showed that combination of BBR with simvastatin (SIMVA) increased the LDLR gene expression to a level significantly higher than that in monotherapies. In the treatment of food-induced hyperlipidemic rats, combination of BBR (90 mg/[kg d], oral) with SIMVA (6 mg/[kg d], oral) reduced serum LDL cholesterol by 46.2%, which was more effective than that of the SIMVA (28.3%) or BBR (26.8%) monotherapy (P < .01 for both) and similar to that of SIMVA at 12 mg/(kg d) (43.4%). More effective reduction of serum triglyceride was also achieved with the combination as compared with either monotherapy. Combination of BBR with SIMVA up-regulated the LDLR messenger RNA in rat livers to a level about 1.6-fold higher than the monotherapies did. Significant reduction of liver fat storage and improved liver histology were found after the combination therapy. The therapeutic efficacy of the combination was then evaluated in 63 hypercholesterolemic patients. As compared with monotherapies, the combination showed an improved lipid-lowering effect with 31.8% reduction of serum LDL cholesterol (P < .05 vs BBR alone, P < .01 vs SIMVA alone). Similar efficacies were observed in the reduction of total cholesterol as well as triglyceride in the patients. Our results display the rationale, effectiveness, and safety of the combination therapy for hyperlipidemia using BBR and SIMVA. It could be a new regimen for hypercholesterolemia.

  7. Low intensity laser therapy: the clinical approach

    NASA Astrophysics Data System (ADS)

    Kahn, Fred

    2006-02-01

    Recently, there has been significant improvement in the process of research and application of Low Intensity Laser Therapy (LILT). Despite this positive direction, a wide discrepancy between the research component and clinical understanding of the technology remains. In our efforts to achieve better clinical results and more fully comprehend the mechanisms of interaction between light and cells, further studies are required. The clinical results presented in this paper are extrapolated from a wide range of musculoskeletal problems including degenerative osteoarthritis, repetitive motion injuries, sports injuries, etc. The paper includes three separate clinical studies comprising 151, 286 and 576 consecutive patient discharges at our clinic. Each patient studied received a specific course of treatment that was designed for that individual and was modified on a continuing basis as the healing process advanced. On each visit, clinical status correlation with the duration, dosage and other parameters was carried out. The essentials of the treatment consisted of a three stage approach. This involved a photon stream emanating from a number of specified gallium-aluminum-arsenide diodes; stage one, red light array, stage two consisting of an array of infrared diodes and stage three consisting of the application of an infrared laser diode probe. On average, each of these groups required less than 10 treatments per patient and resulted in a significant improvement / cure rate greater than 90% in all conditions treated. This report clearly demonstrates the benefits of LILT, indicating that it should be more widely adapted in all medical therapeutic settings.

  8. Robust optimization of intensity modulated proton therapy

    SciTech Connect

    Liu Wei; Zhang Xiaodong; Li Yupeng; Mohan, Radhe

    2012-02-15

    Purpose: Intensity modulated proton therapy (IMPT) is highly sensitive to range uncertainties and uncertainties caused by setup variation. The conventional inverse treatment planning of IMPT optimized based on the planning target volume (PTV) is not often sufficient to ensure robustness of treatment plans. In this paper, a method that takes the uncertainties into account during plan optimization is used to mitigate the influence of uncertainties in IMPT. Methods: The authors use the so-called ''worst-case robust optimization'' to render IMPT plans robust in the face of uncertainties. For each iteration, nine different dose distributions are computed--one each for {+-} setup uncertainties along anteroposterior (A-P), lateral (R-L) and superior-inferior (S-I) directions, for {+-} range uncertainty, and the nominal dose distribution. The worst-case dose distribution is obtained by assigning the lowest dose among the nine doses to each voxel in the clinical target volume (CTV) and the highest dose to each voxel outside the CTV. Conceptually, the use of worst-case dose distribution is similar to the dose distribution achieved based on the use of PTV in traditional planning. The objective function value for a given iteration is computed using this worst-case dose distribution. The objective function used has been extended to further constrain the target dose inhomogeneity. Results: The worst-case robust optimization method is applied to a lung case, a skull base case, and a prostate case. Compared with IMPT plans optimized using conventional methods based on the PTV, our method yields plans that are considerably less sensitive to range and setup uncertainties. An interesting finding of the work presented here is that, in addition to reducing sensitivity to uncertainties, robust optimization also leads to improved optimality of treatment plans compared to the PTV-based optimization. This is reflected in reduction in plan scores and in the lower normal tissue doses for the

  9. The lipid lowering effect of plant sterol ester capsules in hypercholesterolemic subjects

    PubMed Central

    Acuff, Robert V; Cai, David J; Dong, Zhi-Ping; Bell, Doris

    2007-01-01

    Background Foods enriched with phytosterols have been proven to be an effective therapy to improve blood lipid profiles. However, none of the studies have investigated the efficacy in lipid lowering of plant sterol esters (PSE) in capsule form. The objective of this study is to determine if the plant sterol esters (PSE) in capsule form (1.3 grams of PSE/day) lowered plasma cholesterol levels and lipid ratios in free-living hypercholesterolemic subjects during a 4-week intervention period. Methods Sixteen subjects participated in a double-blind, placebo-controlled, sequential study with a 4-week placebo phase followed by a 2-week wash-out period and a 4-week treatment phase. Subjects were instructed to maintain stable diet pattern and physical activities. Blood samples were collected at 7, 21 and 28 days of each phase. The primary measurements were change in plasma total cholesterol (TC), HDL-cholesterol (HDL) and LDL-cholesterol (LDL) between phases and within each phase. The secondary measurements were change in triglycerides, lipoprotein ratios (TC/HDL, LDL/HDL) and C-reactive protein (CRP). Results In comparison to placebo, LDL-cholesterol was significantly reduced by 7% and 4% (P < 0.05) at both week 3 and week 4; HDL at week 3 of the treatment was significantly increased by 9% (P < 0.01), but not at week 4 (4%); total cholesterol was not significantly different from placebo throughout the period, TC/HDL and LDL/HDL were significantly reduced by (8%, 8%, 6%, 10%, respectively) (P < 0.01) at both week 3 and week 4. CRP and triglycerides did not differ either between the two phases or during the treatment phase. Conclusion In conclusion, plant sterol ester capsule is effective in improving lipid profiles among hypercholesterolemic subjects in a free-living setting at the minimum dosage recommended by FDA. The significant improved lipid profiles were reached after three weeks of administration. To achieve better lipid lowering results, higher dosages and

  10. Physical Therapy Intervention in the Neonatal Intensive Care Unit

    ERIC Educational Resources Information Center

    Byrne, Eilish; Garber, June

    2013-01-01

    This article presents the elements of the Intervention section of the Infant Care Path for Physical Therapy in the Neonatal Intensive Care Unit (NICU). The types of physical therapy interventions presented in this path are evidence-based and the suggested timing of these interventions is primarily based on practice knowledge from expert…

  11. [Intensive therapy for patients with Guillian-Barré syndrome].

    PubMed

    Buus, Lone; Tønnesen, Else K

    2014-10-13

    Guillain-Barré syndrome is the leading cause of acute flaccid paralysis in the industrialized world. Approximately 25% of the patients suffering from Guillain-Barré syndrome develop respiratory failure requiring mechanical ventilation and intensive therapy. We seek answers to when it is optimal to start respiratory supportive therapy and review various complications associated with Guillain-Barré syndrome.

  12. Insulin therapy in the pediatric intensive care unit

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Hyperglycemia is a major risk factor for increased morbidity and mortality in the intensive care unit. Insulin therapy has emerged in adult intensive care units, and several pediatric studies are currently being conducted. This review discusses hyperglycemia and the effects of insulin on metabolic a...

  13. A REVIEW OF LOW-INTENSITY ULTRASOUND FOR CANCER THERAPY

    PubMed Central

    WOOD, ANDREW K. W.; SEHGAL, CHANDRA M.

    2015-01-01

    The literature describing the use of low-intensity ultrasound in four major areas of cancer therapy was reviewed - sonodynamic therapy, ultrasound mediated chemotherapy, ultrasound mediated gene delivery and antivascular ultrasound therapy. Each technique consistently resulted in the death of cancer cells and the bioeffects of ultrasound were primarily attributed to thermal actions and inertial cavitation. In each therapeutic modality, theranostic contrast agents composed of microbubbles played a role in both therapy and vascular imaging. The development of these agents is important as it establishes a therapeutic-diagnostic platform which can monitor the success of anti-cancer therapy. Little attention, however, has been given to either the direct assessment of the underlying mechanisms of the observed bioeffects or to the viability of these therapies in naturally occurring cancers in larger mammals; if such investigations provided encouraging data there could be a prompt application of a therapy technique in treating cancer patients. PMID:25728459

  14. Physical therapy intervention in the neonatal intensive care unit.

    PubMed

    Byrne, Eilish; Garber, June

    2013-02-01

    This article presents the elements of the Intervention section of the Infant Care Path for Physical Therapy in the Neonatal Intensive Care Unit (NICU). The types of physical therapy interventions presented in this path are evidence-based and the suggested timing of these interventions is primarily based on practice knowledge from expert therapists, with supporting evidence cited. Physical therapy intervention in the NICU is infant-driven and focuses on providing family-centered care. In this context, interventions to facilitate a calm behavioral state and motor organization in the infant, address positioning and handling of the infant, and provide movement therapy are presented.

  15. Intensive Cognitive Therapy for PTSD: A Feasibility Study

    PubMed Central

    Ehlers, Anke; Clark, David M.; Hackmann, Ann; Grey, Nick; Liness, Sheena; Wild, Jennifer; Manley, John; Waddington, Louise; McManus, Freda

    2010-01-01

    Background: Cognitive Behaviour Therapy (CBT) of anxiety disorders is usually delivered in weekly or biweekly sessions. There is evidence that intensive CBT can be effective in phobias and obsessive compulsive disorder. Studies of intensive CBT for posttraumatic stress disorder (PTSD) are lacking. Method: A feasibility study tested the acceptability and efficacy of an intensive version of Cognitive Therapy for PTSD (CT-PTSD) in 14 patients drawn from consecutive referrals. Patients received up to 18 hours of therapy over a period of 5 to 7 working days, followed by 1 session a week later and up to 3 follow-up sessions. Results: Intensive CT-PTSD was well tolerated and 85.7 % of patients no longer had PTSD at the end of treatment. Patients treated with intensive CT-PTSD achieved similar overall outcomes as a comparable group of patients treated with weekly CT-PTSD in an earlier study, but the intensive treatment improved PTSD symptoms over a shorter period of time and led to greater reductions in depression. Conclusions: The results suggest that intensive CT-PTSD is a feasible and promising alternative to weekly treatment that warrants further evaluation in randomized trials. PMID:20573292

  16. Plasma Coenzyme Q10 Predicts Lipid-lowering Response to High-Dose Atorvastatin

    PubMed Central

    Pacanowski, Michael A.; Frye, Reginald F.; Enogieru, Osatohanmen; Schofield, Richard S.; Zineh, Issam

    2008-01-01

    Background Coenzyme Q10 (CoQ10) is a provitamin synthesized via the HMG-CoA reductase pathway, and thus may serve as a potential marker of intrinsic HMG-CoA reductase activity. HMG-CoA reductase inhibitors (statins) decrease CoQ10, although it is unclear whether this is due to reductions in lipoproteins, which transport CoQ10. Objectives We evaluated whether baseline plasma CoQ10 concentrations predict the lipid-lowering response to high-dose atorvastatin, and to what extent CoQ10 changes following atorvastatin therapy depend on lipoprotein changes. Methods Individuals without dyslipidemia or known cardiovascular disease (n=84) received atorvastatin 80 mg daily for 16 weeks. Blood samples collected at baseline and after 4, 8, and 16 weeks of treatment were assayed for CoQ10. Results Individuals with higher baseline CoQ10:LDL-C ratios displayed diminished absolute and percent LDL-C reductions at 8 and 16 weeks of atorvastatin treatment (P<0.001 to 0.01). After 16 weeks of atorvastatin, plasma CoQ10 decreased 45% from 762±301 ng/ml to 374±150 ng/ml (P<0.001). CoQ10 changes were correlated with LDL-C and apolipoprotein B changes (r=0.27-0.38, P=0.001-0.02), but remained significant when normalized to all lipoproteins. CoQ10 changes were not associated with adverse drug reactions. Conclusion Baseline CoQ10:LDL-C ratio was associated with the degree of LDL-C response to atorvastatin. Atorvastatin decreased CoQ10 concentrations in a manner that was not completely dependent on lipoprotein changes. The utility of CoQ10 as a predictor of atorvastatin response should be further explored in patients with dyslipidemia. PMID:19649137

  17. Effects of Intensive versus Non-Intensive Physical Therapy on Children with Cerebral Palsy.

    PubMed

    Rahman, M A; Zaman, M M; Rahman, M M; Moniruzzaman, M; Ahmed, B; Chhobi, F K; Rahman, N; Akter, M R

    2016-07-01

    Cerebral Palsy (CP) is one of the most common causes of all childhood disorders. There are tone, posture and movements difficulty due to non-progressive damage to the immature brain in CP. The hallmark of CP is a disability in the development of gross motor function (GMF). The influence of gross motor development on fine motor development is more important in early developmental period, specially under three years old and in children with CP. Various therapeutic interventions have been used in the management of GMF development. Among them physical therapy is the most common intervention in CP and is usually a component of mandated programs. Physical therapy means physical stimulations in the form of various therapeutic exercises, touch, massage, limbs and trunk movement, balancing and coordination training, gait and ambulation training, cognitive stimulation as well as speech, language and occupational therapy. Our study focused to see the effect by short term intensive versus non-intensive physical therapy on children GMF development by using gross motor function measure (GMFM) Score sheet, GMFM-88, version 1.0. Study provides the information that physical therapy intervention is effective in GMF development and intensive interventions are more effective in children with spastic CP than non-intensive one. Study also inform that the more early treatment the more effective result.

  18. A US Claims-Based Analysis of Real-World Lipid-Lowering Treatment Patterns in Patients With High Cardiovascular Disease Risk or a Previous Coronary Event.

    PubMed

    Quek, Ruben G W; Fox, Kathleen M; Wang, Li; Li, Lu; Gandra, Shravanthi R; Wong, Nathan D

    2016-02-15

    The objective was to examine real-world treatment patterns of lipid-lowering therapies and their possible associated intolerance and/or ineffectiveness in patients with high cardiovascular disease (CVD) risk initiating statins and/or ezetimibe. Patients aged ≥18 years who initiated statins and/or ezetimibe from January 01, 2007, to June 30, 2011, were retrospectively identified from the IMS LifeLink PharMetrics Plus commercial claims database. Patients were further classified into 2 cohorts: (1) history of cardiovascular event (CVE) and (2) history of coronary heart disease risk equivalent (CHD RE). Patients had continuous health plan enrollment ≥1 year pre- and post-index date (statin and/or ezetimibe initiation date). Primary outcomes were index statin intensity, treatment modifications, possible associated statin/nonstatin intolerance and/or ineffectiveness issues (based on treatment modification), and time-to-treatment modifications. Analyses for each cohort were stratified by age group (<65 and ≥65 years). A total of 41,934 (history of CVE) and 170,344 patients (history of CHD RE) were included. On the index date, 8.8% to 25.1% of patients were initiated on high-intensity statin. Among patients aged <65, 79.2% and 48.8% of those with history of CVE and 78.6% and 47.3% of those with a history of CHD RE had ≥1 and 2 treatment modifications, respectively. Among all patients, 24.6% to 25.6% had possible statin intolerance and/or ineffectiveness issues after accounting for second treatment modification (if any). In conclusion, in patients with high CVD risk, index statin treatment modifications that imply possible statin intolerance and/or ineffectiveness were frequent; low use of high-intensity statins indicates unmet need in the management of hyperlipidemia and possible remaining unaccounted CVD residual risk.

  19. Clinical implementation of intensity-modulated arc therapy.

    PubMed

    Shepard, David M; Cao, Daliang

    2011-01-01

    Intensity-modulated arc therapy (IMAT) is a rotational approach to radiation therapy delivered on a conventional linear accelerator using a conventional multileaf collimator. There are 2 key advantages of IMAT. First, the rotational nature of the delivery provides great flexibility in shaping each dose distribution. As a result, IMAT can provide dosimetric advantages relative to fixed-field intensity-modulated radiation therapy (IMRT). The second advantage is the highly efficient nature of the delivery. For centers with an active IMRT program, the clinical implementation of IMAT should be relatively straightforward. For clinical implementation of IMAT, it is important to fully characterize the accuracy of the dose model used, and the performance of the quality assurance equipment.

  20. [Lipid-lowering effect of seven traditional Chinese medicine monomers in zebrafish system].

    PubMed

    Chen, Kan; Wang, Chang-Qian; Fan, Yu-Qi; Han, Zhi-Hua; Wang, Yue; Gao, Lin; Zeng, Hua-Su

    2017-02-25

    The present study aimed to study lipid-lowering effect of seven traditional Chinese medicine monomers in zebrafish system. Zebrafish were fed with high fat diet to establish a hyperlipemia model, then fasted and bathed with seven traditional Chinese medicine monomers stigmasterol, triacontanol, chrysophanol, vanillic acid, shikimic acid, polydatin and oleanolic acid respectively. The oil red O staining was used to detect the blood lipids of zebrafish. Serum total cholesterol and triglyceride levels were detected to validate the lipid-lowering effect. The result showed that a zebrafish model of hyperlipemia could be established by feeding larvae zebrafish with high fat diet. Among the seven traditional Chinese medicine monomers, chrysophanol had lipid-lowering effect. Chrysophanol significantly reduced serum total cholesterol and triglyceride levels in adult zebrafish fed with high fat diet. Chrysophanol accelerated peristalsis frequency of zebrafish intestine and the excretion of high fat food. It is concluded that chrysophanol has lipid- lowering effect in zebrafish, and the mechanism of the effect may be due to the roles of chrysophanol in reducing lipid absorption from gastrointestinal tract and accelerating the excretion of food.

  1. The lipid lowering drug lovastatin protects against doxorubicin-induced hepatotoxicity

    SciTech Connect

    Henninger, Christian; Huelsenbeck, Johannes; Huelsenbeck, Stefanie; Grösch, Sabine; Lackner, Karl J.; Kaina, Bernd; Fritz, Gerhard

    2012-05-15

    Liver is the main detoxifying organ and therefore the target of high concentrations of genotoxic compounds, such as environmental carcinogens and anticancer drugs. Here, we investigated the usefulness of lovastatin, which is nowadays widely used for lipid lowering purpose, as a hepatoprotective drug following the administration of the anthracycline derivative doxorubicin in vivo. To this end, BALB/c mice were exposed to either a single high dose or three consecutive low doses of doxorubicin. Acute and subacute hepatotoxicities were analyzed with or without lovastatin co-treatment. Lovastatin protected the liver against doxorubicin-induced acute pro-inflammatory and pro-fibrotic stress responses as indicated by an attenuated mRNA expression of tumor necrosis factor alpha (TNFα) and connective tissue growth factor (CTGF), respectively. Hepatoprotection by lovastatin was due to a reduced induction of DNA damage following doxorubicin treatment. The statin also mitigated subacute anthracycline-provoked hepatotoxicity as shown on the level of doxorubicin- and epirubicin-stimulated CTGF mRNA expression as well as histopathologically detectable fibrosis and serum concentration of marker enzymes of hepatotoxicity (GPT/GLDH). Kidney damage following doxorubicin exposure was not detectable under our experimental conditions. Moreover, lovastatin showed multiple inhibitory effects on doxorubicin-triggered hepatic expression of genes involved in oxidative stress response, drug transport, DNA repair, cell cycle progression and cell death. Doxorubicin also stimulated the formation of ceramides. Ceramide production, however, was not blocked by lovastatin, indicating that hepatoprotection by lovastatin is independent of the sphingolipid metabolism. Overall, the data show that lovastatin is hepatoprotective following genotoxic stress induced by anthracyclines. Based on the data, we hypothesize that statins might be suitable to lower hepatic injury following anthracycline

  2. High Intensity Focused Ultrasound Tumor Therapy System and Its Application

    NASA Astrophysics Data System (ADS)

    Sun, Fucheng; He, Ye; Li, Rui

    2007-05-01

    At the end of last century, a High Intensity Focused Ultrasound (HIFU) tumor therapy system was successfully developed and manufactured in China, which has been already applied to clinical therapy. This article aims to discuss the HIFU therapy system and its application. Detailed research includes the following: power amplifiers for high-power ultrasound, ultrasound transducers with large apertures, accurate 3-D mechanical drives, a software control system (both high-voltage control and low-voltage control), and the B-mode ultrasonic diagnostic equipment used for treatment monitoring. Research on the dosage of ultrasound required for tumour therapy in multiple human cases has made it possible to relate a dosage formula, presented in this paper, to other significant parameters such as the volume of thermal tumor solidification, the acoustic intensity (I), and the ultrasound emission time (tn). Moreover, the HIFU therapy system can be applied to the clinical treatment of both benign and malignant tumors in the pelvic and abdominal cavity, such as uterine fibroids, liver cancer and pancreatic carcinoma.

  3. Optimizing antibiotic therapy in the intensive care unit setting

    PubMed Central

    Kollef, Marin H

    2001-01-01

    Antibiotics are one of the most common therapies administered in the intensive care unit setting. In addition to treating infections, antibiotic use contributes to the emergence of resistance among pathogenic microorganisms. Therefore, avoiding unnecessary antibiotic use and optimizing the administration of antimicrobial agents will help to improve patient outcomes while minimizing further pressures for resistance. This review will present several strategies aimed at achieving optimal use of antimicrobial agents. It is important to note that each intensive care unit should have a program in place which monitors antibiotic utilization and its effectiveness. Only in this way can the impact of interventions aimed at improving antibiotic use (e.g. antibiotic rotation, de-escalation therapy) be evaluated at the local level. PMID:11511331

  4. Arc binary intensity modulated radiation therapy (AB IMRT)

    NASA Astrophysics Data System (ADS)

    Yang, Jun

    The state of the art Intensity Modulate Radiation Therapy (IMRT) has been one of the most significant breakthroughs in the cancer treatment in the past 30 years. There are two types of IMRT systems. The first system is the binary-based tomotherapy, represented by the Peacock (Nomos Corp) and Tomo unit (TomoTherapy Inc.), adopting specific binary collimator leafs to deliver intensity modulated radiation fields in a serial or helical fashion. The other uses the conventional dynamic multileaf collimator (MLC) to deliver intensity modulated fields through a number of gantry positions. The proposed Arc Binary IMRT attempts to deliver Tomo-like IMRT with conventional dynamic MLC and combines the advantages of the two types of IMRT techniques: (1) maximizing the number of pencil beams for better dose optimization, (2) enabling conventional linear accelerator with dynamic MLC to deliver Tomo-like IMRT. In order to deliver IMRT with conventional dynamic MLC in a binary fashion, the slice-by-slice treatment with limited slice thickness has been proposed in the thesis to accommodate the limited MLC traveling speed. Instead of moving the patient to subsequent treatment slices, the proposed method offsets MLC to carry out the whole treatment, slice by slice sequentially, thus avoid patient position error. By denoting one arc pencil beam set as a gene, genetic algorithm (GA) is used as the searching engine for the dose optimization process. The selection of GA parameters is a crucial step and has been studied in depth so that the optimization process will converge with reasonable speed. Several hypothetical and clinical cases have been tested with the proposed IMRT method. The comparison of the dose distribution with other commercially available IMRT systems demonstrates the clear advantage of the new method. The proposed Arc Binary Intensity Modulated Radiation Therapy is not only theoretically sound but practically feasible. The implementation of this method would expand the

  5. [Intensive therapy in complicated forms of purulent gestational pyelonephritis].

    PubMed

    Dovlatian, A A

    2008-01-01

    The experience with 65 cases of purulent gestational pyelonephritis (PGP) is reviewed. The efficacy of PGP intensive therapy depends on early surgical elimination of the source of bacteriemia and sepsis. Choice of the surgical technique should be based both on extension of destructive changes in the kidney and severity of the complications. In some cases it is necessary to perform nephrostomy with sanation of the pyonecrotic foci in the kidney, in the other--it is necessary to perform urgent nephrectomy. Three basic components of pre- and postoperative intensive care should be considered: antibacterial treatment, infusion-transfusion therapy and efferent detoxication. Etiotropic therapy is conducted with three antibiotics injected intravenously and intramuscularly to provide effective concentrations of the drugs in the blood, urine and affected organs. PGP medication is based on inhibitor-defended penicillines and cephalosporines of the third-forth generation. Combined use of these antibiotics is effective in 95% cases. If the condition is life-threatening, carbapenems, fluoroguinolones, aminoglycosides and metronidasol can be applied. Detoxication is provided by 24-h infusion of crystalloids, concentrated glucose solutions (10-20%) with insulin, transfusion of fresh frozen plasm, albumin, protein. Plasmapheresis accelerates recovery, diminished nephrectomy rate by 14% and obstetric complications 1.8 fold, enables physiological term of delivery (37-39 weeks) in significant reduction of postnatal complications. Lethal outcomes were absent.

  6. Planning and delivery of intensity-modulated radiation therapy.

    PubMed

    Yu, Cedric X; Amies, Christopher J; Svatos, Michelle

    2008-12-01

    Intensity modulated radiation therapy (IMRT) is an advanced form of external beam radiation therapy. IMRT offers an additional dimension of freedom as compared with field shaping in three-dimensional conformal radiation therapy because the radiation intensities within a radiation field can be varied according to the preferences of locations within a given beam direction from which the radiation is directed to the tumor. This added freedom allows the treatment planning system to better shape the radiation doses to conform to the target volume while sparing surrounding normal structures. The resulting dosimetric advantage has shown to translate into clinical advantages of improving local and regional tumor control. It also offers a valuable mechanism for dose escalation to tumors while simultaneously reducing radiation toxicities to the surrounding normal tissue and sensitive structures. In less than a decade, IMRT has become common practice in radiation oncology. Looking forward, the authors wonder if IMRT has matured to such a point that the room for further improvement has diminished and so it is pertinent to ask what the future will hold for IMRT. This article attempts to look from the perspective of the current state of the technology to predict the immediate trends and the future directions. This article will (1) review the clinical experience of IMRT; (2) review what we learned in IMRT planning; (3) review different treatment delivery techniques; and finally, (4) predict the areas of advancements in the years to come.

  7. Advances in endonasal low intensity laser irradiation therapy

    NASA Astrophysics Data System (ADS)

    Jiao, Jian-Ling; Liu, Timon C.; Liu, Jiang; Cui, Li-Ping; Liu, Song-hao

    2005-07-01

    Endonasal low intensity laser therapy (ELILT) began in China in 1998. Now in China it is widely applied to treat hyperlipidemia and brain diseases such as Alzheimer's disease, Parkinson's disease, insomnia, poststroke depression, intractable headache, ache in head or face, cerebral thrombosis, acute ischemic cerebrovascular disease, migraine, brain lesion and mild cognitive impairment. There are four pathways mediating EILILT, Yangming channel, autonomic nervous systems and blood cells. Two unhealth acupoints of Yangming channal inside nose might mediate the one as is low intensity laser acupuncture. Unbalance autonomic nervous systems might be modulated. Blood cells might mediate the one as is intravascular low intensity laser therapy. These three pathways are integrated in ELILT so that serum amyloid β protein, malformation rate of erythrocyte, CCK-8, the level of viscosity at lower shear rates and hematocrit, or serum lipid might decrease, and melanin production/SOD activity or β endorphin might increase after ELILT treatment. These results indicate ELILT might work, but it need to be verified by randomized placebo-controlled trial.

  8. Major Long-Term Benefits of Intensive Therapy for Type 1 Diabetes

    MedlinePlus

    ... A Listen Major Long-Term Benefits of Intensive Therapy for Type 1 Diabetes: Study Reports Near-Normal ... Stroke Chicago, June 22, 2013 Long-term, intensive therapy for people with type 1 diabetes helps them ...

  9. [The doctor-patient relationship in intensive therapy].

    PubMed

    Szulc, Roman

    2008-01-01

    The doctor-patient and doctor-patient's family relationships require skills of interpersonal communication, which is particularly important in intensive therapy. Unfortunately, such skills are not routinely taught and inadequacies are enormous. Communication skills are essential for decision-making and outcomes of therapy. The communication-related education should be obligatory and include abilities to use the linguistic and extra-linguistic signs suitable for the given circumstances. The former ought to have linguistic, psychological and social effects. The latter should involve gestures, voice modulation, facial expressions or even silence, if need be. ITU patients and their families expect physicians to behave appropriately and to provide them with competent emotional support and cooperation.

  10. Linear algebraic methods applied to intensity modulated radiation therapy.

    PubMed

    Crooks, S M; Xing, L

    2001-10-01

    Methods of linear algebra are applied to the choice of beam weights for intensity modulated radiation therapy (IMRT). It is shown that the physical interpretation of the beam weights, target homogeneity and ratios of deposited energy can be given in terms of matrix equations and quadratic forms. The methodology of fitting using linear algebra as applied to IMRT is examined. Results are compared with IMRT plans that had been prepared using a commercially available IMRT treatment planning system and previously delivered to cancer patients.

  11. [Low persistence of simvastatin and ezetimibe fixed combination in the lipid lowering therapy].

    PubMed

    Simonyi, Gábor; Ferenci, Tamás

    2015-01-25

    Bevezetés: Jól ismert, hogy a magas koleszterinszint fontos módosítható cardiovascularis kockázati tényező. A lipidcsökkentő kezelés során a cardiovascularis kockázat csökkentése miatt fontos a betegek terápiahűsége. Célkitűzés: A szerzők célja a simvastatin/ezetimib szabad és fix kombinációk, illetve a leghatékonyabb statin, a rozuvastatin egyéves perzisztenciájának összehasonlítása volt. Módszer: Az Országos Egészségbiztosítási Pénztár vényforgalmi adataira támaszkodva 2012. október 1. és 2013. szeptember 30. között első alkalommal a simvastatin/ezetimib szabad és fix kombinációi és a rozuvastatinmonoterápia receptjeit kiváltó betegeket választották ki, akik az ezt megelőző egy évben hasonló hatóanyaggal végzett antilipaemiás terápiában nem részesültek. A perzisztenciagörbéket Kaplan–Meier-becsléssel határozták meg, 95%-os, log-skálán számolt pontonkénti konfidenciaintervallummal. Cenzoráltnak azokat a betegeket vették, akik a vizsgálat záró időpontjában is perzisztensek voltak. A görbék modellezéséhez félparaméteres eljárást, Cox-regressziót használtak, ahol az egyetlen – kategoriális – magyarázó változó a terápia volt; referenciacsoportnak a simvastatin/ezetimib fix kombinációt vették. Eredmények: A bevonási kritériumoknak összesen 204 699 beteg felelt meg. E betegek közül 10 030 beteg kezdett simvastatin/ezetimib szabad, 7613 beteg simvastatin/ezetimib fix, illetve 187 056 beteg rozuvastatinmonoterápiát. Az egyéves perzisztencia a simvastatin/ezetimib szabad kombináció esetében 10,97%, a simvastatin/ezetimib fix kombinációt szedőkben 24,35%, míg a rozuvastatinmonoterápián lévők esetében 30,47% volt. A simvastatin/ezetimib fix kombinációhoz képest a simvastatin/ezetimib szabad kombináció elhagyásának az esélye 73%-kal volt nagyobb (kockázatarány = 1,73 [95% konfidenciaintervallum: 1,61–1,85], p<0,0001), míg a rozuvastatiné 20%-kal volt alacsonyabb (kockázatarány = 0,80 [95% konfidenciaintervallum: 0,78–0,82], p<0,0001). A 360. napra számított átlagos perzisztencia a simvastatin/ezetimib szabad kombináció esetén 107 nap, a simvastatin/ezetimib fix kombináció szedésekor 164 nap, míg a rozuvastatint szedőknél 185 nap volt. Következtetések: Vizsgálatukban igazolták, hogy a simvastatin/ezetimib szabad és fix kombináció egyéves perzisztenciája szignifikánsan alacsonyabb a rozuvastatinéhoz képest. Orv. Hetil., 2015, 156(4), 141–145.

  12. [Lipid-lowering therapy and patient adherence in the MULTI GAP 2013 trial].

    PubMed

    Simonyi, Gábor

    2014-04-27

    Bevezetés: A dyslipidaemia ismert cardiovascularis kockázati tényező. A lipidterápiában a célértékek elérésének fontos tényezője a megfelelő betegadherencia. Célkitűzés: A MULTI GAP (MULTI Goal Attainment Problem) 2013-as vizsgálatban atheroscleroticus betegségben szenvedő betegek esetében a statinterápia adherenciájának és perzisztenciájának felmérése, amely részben a vizsgálatban részt vevő orvosok becslésén, illetve 319, a megelőző évben elvégzett MULTI GAP vizsgálatban részt vett beteg esetében az Országos Egészségbiztosítási Pénztár vénykiváltási adatbázisán alapult. Módszer: A MULTI GAP 2013 vizsgálatban standard, strukturált kérdőívek segítségével 1519 beteg adatai kerültek feldolgozásra. Az elemzésben kiértékelésre kerültek az egyes ellátási szinteken elért lipidértékek, a kezelőorvos által vélt betegadherencia, a 319 beteg Országos Egészségbiztosítási Pénztár vénykiváltási adataira támaszkodó valós adherencia, a kezelőorvosok elégedettsége a statinterápia eredményeivel, illetve az adherencia és a lipideredmények összevetése. Eredmények: Az elmúlt 7 év felméréseinek adatait is figyelembe véve előtérbe kerültek a hatékonyabb statinok; az atorvastatin és rozuvastatin alkalmazásának összesített aránya 49%-ról 83%-ra, azaz mintegy 70%-kal nőtt. A betegadherencia vonatkozásában kimutatták, hogy a 2,5 mmol/l alatti LDL-koleszterin-értékeket elért betegeknél az 1 év alatt kiváltott receptek száma mintegy nyolc gyógyszertári beváltást jelentett. Ehhez képest a 2,5 mmol/l feletti LDL-koleszterin-értékű csoportban a gyógyszerkiváltás lényegesen alacsonyabb volt (5,3 és 6,3 közötti). Éves szinten a 10–12 és a 7–9 gyógyszerkiváltás szignifikánsan alacsonyabb LDL-koleszterin-szintet jelentett a semennyit (0), illetve az 1–3 receptet éves szinten kiváltók csoportjaihoz képest. A kezelőorvosok által 100%-os perzisztenciájúnak értékelt betegek valódi perzisztenciája 74%-os volt az Országos Egészségbiztosítási Pénztár adatbázisa szerint, amely mintegy 25%-kal alacsonyabb, mint a valóság. A kezelőorvosok a lipidcsökkentő terápia adherenciáját a betegek mintegy felében ítélték 100%-nak, ezzel szemben az Országos Egészségbiztosítási Pénztár adatai 36%-ot mutattak. A jobb adherenciájú betegek (90–100%) nagyobb arányban (59,5%) értek el 2,5 mmol/l alatti LDL-koleszterin-értékeket, mint az alacsonyabb adherenciájúnak tartott betegek. A kezelőorvosok elégedettsége a lipidértékekkel a 4,5–6 mmol/l közötti összkoleszterin-értékű csoportban 69–80%-ig terjedt, azonban igen magas, 53–54%-os elégedettséget mutattak a 7 feletti összkoleszterin-szintű betegek csoportjában. Következtetések: A vizsgálat eredményei szerint a vélt adherencia lényegesen magasabb az Országos Egészségbiztosítási Pénztár adatain alapuló elemzéshez viszonyítva. Ugyanakkor a magas lipidértékű betegekkel szemben a kezelőorvosok megelégedettsége is igen magasnak bizonyult. Mindezek arra utalnak, hogy nemcsak a betegek, hanem az orvosok adherenciáját is javítani kell a lipidcsökkentő irányelvekhez. Orv. Hetil., 2014, 155(17), 669–675.

  13. Segmentation and leaf sequencing for intensity modulated arc therapy

    SciTech Connect

    Gladwish, Adam; Oliver, Mike; Craig, Jeff; Chen, Jeff; Bauman, Glenn; Fisher, Barbara; Wong, Eugene

    2007-05-15

    A common method in generating intensity modulated radiation therapy (IMRT) plans consists of a three step process: an optimized fluence intensity map (IM) for each beam is generated via inverse planning, this IM is then segmented into discrete levels, and finally, the segmented map is translated into a set of MLC apertures via a leaf sequencing algorithm. To date, limited work has been done on this approach as it pertains to intensity modulated arc therapy (IMAT), specifically in regards to the latter two steps. There are two determining factors that separate IMAT segmentation and leaf sequencing from their IMRT equivalents: (1) the intrinsic 3D nature of the intensity maps (standard 2D maps plus the angular component), and (2) that the dynamic multileaf collimator (MLC) constraints be met using a minimum number of arcs. In this work, we illustrate a technique to create an IMAT plan that replicates Tomotherapy deliveries by applying IMAT specific segmentation and leaf-sequencing algorithms to Tomotherapy output sinograms. We propose and compare two alternative segmentation techniques, a clustering method, and a bottom-up segmentation method (BUS). We also introduce a novel IMAT leaf-sequencing algorithm that explicitly takes leaf movement constraints into consideration. These algorithms were tested with 51 angular projections of the output leaf-open sinograms generated on the Hi-ART II treatment planning system (Tomotherapy Inc.). We present two geometric phantoms and 2 clinical scenarios as sample test cases. In each case 12 IMAT plans were created, ranging from 2 to 7 intensity levels. Half were generated using the BUS segmentation and half with the clustering method. We report on the number of arcs produced as well as differences between Tomotherapy output sinograms and segmented IMAT intensity maps. For each case one plan for each segmentation method is chosen for full Monte Carlo dose calculation (NumeriX LLC) and dose volume histograms (DVH) are calculated

  14. [Hospital infections caused by Pseudomonas aeruginosa. Significance in intensive therapy].

    PubMed

    Sidorenko, S V; Gel'fand, E B; Mamontova, O A

    1999-01-01

    The significance of P. aeruginosa as an agent of hospital infections in intensive care departments is determined by high prevalence of this microorganism, its natural and acquired resistance to antibiotics of various groups, and severity of the infection it induces. The resistance of P. aeruginosa to antibiotics is different in different regions. Among the strains isolated in Moscow in intensive care wards for newborns 9% were resistant to meropenem, 10% to amicacine, 15% to imipramine, 16% to cefepime, 37% to ceftasidime, 45% to piperacylline/tasobactam, 45% to ciprofloxacine, and 60% to gentamicin; 1.5% of these strains were resistant to all tested antibiotics. High prevalence of antibiotic resistance among P. aeruginosa impedes the choice of drugs for empirical antibiotic therapy and increases the significance of microbiological diagnosis. Even if an agent is sensitive to such antibiotics as semisynthetic penicillines and aminoglycosides, their use as monotherapy in infections caused by P. aeruginosa is ineffective. Carbapenemes, III- IV generations cefalosporines, and fluoroquinolones can be used as mono therapy.

  15. Intensity-modulated arc therapy: principles, technologies and clinical implementation

    NASA Astrophysics Data System (ADS)

    Yu, Cedric X.; Tang, Grace

    2011-03-01

    Intensity-modulated arc therapy (IMAT) was proposed by Yu (1995 Phys. Med. Biol. 40 1435-49) as an alternative to tomotherapy. Over more than a decade, much progress has been made. The advantages and limitations of the IMAT technique have also been better understood. In recent years, single-arc forms of IMAT have emerged and become commercially adopted. The leading example is the volumetric-modulated arc therapy (VMAT), a single-arc form of IMAT that delivers apertures of varying weights with a single-arc rotation that uses dose-rate variation of the treatment machine. With commercial implementation of VMAT, wide clinical adoption has quickly taken root. However, there remains a lack of general understanding for the planning of such arc treatments, as well as what delivery limitations and compromises are made. Commercial promotion and competition add further confusion for the end users. It is therefore necessary to provide a summary of this technology and some guidelines on its clinical implementation. The purpose of this review is to provide a summary of the works from the radiotherapy community that led to wide clinical adoption, and point out the issues that still remain, providing some perspective on its further developments. Because there has been vast experience in IMRT using multiple intensity-modulated fields, comparisons between IMAT and IMRT are also made in the review within the areas of planning, delivery and quality assurance.

  16. Prone Breast Intensity Modulated Radiation Therapy: 5-Year Results

    SciTech Connect

    Osa, Etin-Osa O.; DeWyngaert, Keith; Roses, Daniel; Speyer, James; Guth, Amber; Axelrod, Deborah; Fenton Kerimian, Maria; Goldberg, Judith D.; Formenti, Silvia C.

    2014-07-15

    Purpose: To report the 5-year results of a technique of prone breast radiation therapy delivered by a regimen of accelerated intensity modulated radiation therapy with a concurrent boost to the tumor bed. Methods and Materials: Between 2003 and 2006, 404 patients with stage I-II breast cancer were prospectively enrolled into 2 consecutive protocols, institutional trials 03-30 and 05-181, that used the same regimen of 40.5 Gy/15 fractions delivered to the index breast over 3 weeks, with a concomitant daily boost to the tumor bed of 0.5 Gy (total dose 48 Gy). All patients were treated after segmental mastectomy and had negative margins and nodal assessment. Patients were set up prone: only if lung or heart volumes were in the field was a supine setup attempted and chosen if found to better spare these organs. Results: Ninety-two percent of patients were treated prone, 8% supine. Seventy-two percent had stage I, 28% stage II invasive breast cancer. In-field lung volume ranged from 0 to 228.27 cm{sup 3}, mean 19.65 cm{sup 3}. In-field heart volume for left breast cancer patients ranged from 0 to 21.24 cm{sup 3}, mean 1.59 cm{sup 3}. There was no heart in the field for right breast cancer patients. At a median follow-up of 5 years, the 5-year cumulative incidence of isolated ipsilateral breast tumor recurrence was 0.82% (95% confidence interval [CI] 0.65%-1.04%). The 5-year cumulative incidence of regional recurrence was 0.53% (95% CI 0.41%-0.69%), and the 5-year overall cumulative death rate was 1.28% (95% CI 0.48%-3.38%). Eighty-two percent (95% CI 77%-85%) of patients judged their final cosmetic result as excellent/good. Conclusions: Prone accelerated intensity modulated radiation therapy with a concomitant boost results in excellent local control and optimal sparing of heart and lung, with good cosmesis. Radiation Therapy Oncology Group protocol 1005, a phase 3, multi-institutional, randomized trial is ongoing and is evaluating the equivalence of a similar dose and

  17. Influence Of Low Intensity Laser Therapy On Diabetic Polyneuropathy

    NASA Astrophysics Data System (ADS)

    Abdel-Raoof, N. A.; Elnhas, N. G.; Elsayed, I. M.

    2011-09-01

    Diabetic peripheral neuropathy is a consequence of diabetes-mediated impairment of blood flow, and resultant hypoxia of nerves that may develop within 10 years of the onset of diabetes in 40-50% of people with type 1 or type 2 diabetes. Low Intensity Laser Therapy (LILT) has been advocated for the treatment of chronic pain disorders as blood flow is an important determinant for pain relief. Comparing the effect of Helium-Neon Laser therapy versus Infrared laser therapy on blood vessels diameter and flow as well as level of sensation for neuropathy. Twenty diabetic patients suffering from neuropathy were enrolled in the study with age 45-55 years. They were assigned randomly into two equal groups in number; Group A underwent an application of He-Neon laser while Group B underwent an application of Infrared laser. Both groups received laser for 2 months. Blood flow velocity, and blood vessel diameter were investigated by using duplex Doppler ultrasound and peripheral neuropathy parameters were investigated by Semmes-Weinstein monofilament assessment. The results revealed that He-Neon laser as well as Infrared laser groups showed significant improvement in blood flow velocity, blood vessel diameter & neuropathy tested parameters after treatment but there was no significance difference between the two types of LILT. LILT is a safe, non-invasive and drug free method for improving blood flow & sensation in patients suffering from diabetic polyneuropathy in addition to preventing one of the most threatening microvascular complications of diabetes.

  18. Randomized trial comparing exercise therapy, alternating cold and hot therapy, and low intensity laser therapy for chronic lumbar muscle strain

    NASA Astrophysics Data System (ADS)

    Liu, Xiaoguang; Li, Jie; Liu, Timon Chengyi; Yuan, Jianqin; Luo, Qingming

    2008-12-01

    The purpose of this study was to compare the effects of exercise therapy, alternating cold and hot (ACH) therapy and low intensity laser (LIL) therapy in patients with chronic lumbar muscle strain (CLMS). Thirty-two patients were randomly allocated to four groups: exercise group, ACH group, LIL group, and combination group of exercise, ACH and LIL, eight in each group. Sixteen treatments were given over the course of 4 weeks. Lumbar muscle endurance, flexion and lateral flexion measures, visual analogue scale (VAS) and lumbar disability questionnaire (LDQ) were used in the clinical and functional evaluations before, immediately after, and 4 weeks after treatment. It was found that the values of endurance, VAS and LDQ in all groups were significantly improved from before to after treatment (P < 0.01). The combination group showed significantly larger reduction on pain level and functional disability than the other groups immediately and 4 weeks after treatment (P < 0.01). Pain level reduced significantly more in the ACH group than in the exercise group or the LIL group immediately and 4 weeks after treatment (P < 0.05). Lumbar muscle endurance and spinal ranges of motion in all groups were improved after treatment but there was no significant difference between any therapy groups. In conclusion, exercise therapy, ACH therapy and LIL therapy were effective in the treatment of CLMS. ACH therapy was more effective than exercise therapy or LIL therapy. The combination therapy of exercise, ACH and LIL had still better rehabilitative effects on CLMS.

  19. 3D treatment planning and intensity-modulated radiation therapy.

    PubMed

    Purdy, J A

    1999-10-01

    Three-dimensional (3D) image-based treatment planning and new delivery technologies have spurred the implementation of external beam radiation therapy techniques, in which the high-dose region is conformed much more closely to the target volume than previously possible, thus reducing the volume of normal tissues receiving a high dose. This form of external beam irradiation is referred to as 3D conformal radiation therapy (3DCRT). 3DCRT is not just an add-on to the current radiation oncology process; it represents a radical change in practice, particularly for the radiation oncologist. Defining target volumes and organs at risk in 3D by drawing contours on CT images on a slice-by-slice basis, as opposed to drawing beam portals on a simulator radiograph, can be challenging, because radiation oncologists are generally not well trained in cross-sectional imaging. Currently, the 3DCRT approach will increase the time and effort required by physicians inexperienced with 3D treatment planning. Intensity-modulated radiation therapy (IMRT) is a more advanced form of 3DCRT, but there is considerable developmental work remaining. The instrumentation and methods used for IMRT quality assurance procedures and testing are not well established. Computer optimization cost functions are too simplistic, and thus time-consuming. Subjective plan evaluation by the radiation oncologist is still the norm. In addition, many fundamental questions regarding IMRT remain unanswered. For example, the radiobiophysical consequences of altered time-dose-fraction are unknown. Also, the fact that there is much greater dose heterogeneity for both the target and normal critical structures with IMRT compared to traditional irradiation techniques challenges current radiation oncology planning principles. However, this new process of planning and treatment delivery shows significant potential for improving the therapeutic ratio. In addition, while inefficient today, these systems, when fully developed

  20. Palliative intensity modulated radiation therapy for symptomatic adrenal metastasis.

    PubMed

    Mod, H; Patel, V

    2013-05-01

    Metastasis to the adrenal glands is quite common; especially from melanomas, breast, lung, renal and gastro-intestinal tumours. The most common tumour found in the adrenals in post mortem series is a metastatic tumour; incidence ranging from 13 to 27%. The diagnosis of adrenal metastasis is now more common and easier due to staging and subsequent follow up with Computed tomography /Magnetic resonance imaging and or positron emission tomography-computed tomography imaging studies. Most of the times these metastatic lesions are clinically occult and those that do have clinical symptoms complain of pain, nausea, vomiting and early satiety. We irradiated a patient of non small cell lung cancer with adrenal metastasis with palliative Intensity Modulated Radiation Therapy and achieved a good response in terms of pain relief, stable disease and no side effects of the treatment.

  1. Basic studies on intravascular low-intensity laser therapy

    NASA Astrophysics Data System (ADS)

    Liu, Timon Cheng-Yi; Duan, Rui; Wang, Shuang-Xi; Liu, Jiang; Cui, Li-Ping; Jin, Hua; Liu, Song-Hao

    2006-09-01

    Intravascular low intensity laser therapy (ILILT) was originally put forward in USA in 1982, but popularized in Russia in 1980s and in China in 1990s, respectively. A randomized placebo-controlled study has shown ILILT clinical efficacy in patients suffering from rheumatoid arthritis. As Chinese therapeutic applications of ILILT were the most widely in the world, its basic research, such as intracellular signal transduction research, blood research in vitro, animal blood research in vivo, human blood research in vivo and traditional Chinese medicine research, was also very progressive in China. Its basic studies will be reviewed in terms of the biological information model of photobiomodulation in this paper. ILILT might work in view of its basic studies, but the further randomized placebo-controlled trial and the further safety research should be done.

  2. Low Intensity Laser Therapy Applied in the Healing of Wounds

    NASA Astrophysics Data System (ADS)

    Kahn, Fred; Matthews, Jeffrey

    2009-06-01

    Objective: The aim of this study was to determine the outcomes of Low Intensity Laser Therapy (LILT) on wound healing for patients presenting with pain, compromised neurological and physical function and tissue damage associated with vascular/diabetic ulcerations of the lower extremity. Methods: A retrospective case review of six patients treated with LILT (GaAlAs SLD, 660 nm, 750 mW, 3.6 J/cm2; GaAlAs SLD, 840 nm, 1,500 mW, 6.48 J/cm2; GaAlAs laser, 830 nm, 75 mW, 270 J/cm2) was conducted of clinical features including pain, measured by visual analogue scale (VAS), motor function, measured by range of motion (ROM) and visual outcome, measured by wound dimensions for six patients (n = 6; 5 males, 1 female; age = 67.83 years). Results: Significant progress with regard to alleviation of pain (ΔVAS = -5), improvements in motor function (ΔROM = +40%), epithelialization (wound closure rate = 3%/week) and complete wound closure was achieved. No recurrence of pathology at least one month post cessation of therapy was evident (x¯% reduction in wound area = 100%). Conclusions: LILT achieved consistent, effective and clear endpoints, was cost effective, created no adverse effects and ultimately led to the salvage of extremities.

  3. Pitfalls in normalization for intensity-modulated radiation therapy planning

    SciTech Connect

    Williams, Greg . E-mail: greg.williams@hci.utah.edu; Tobler, Matt; Leavitt, Dennis

    2005-01-01

    Three-dimensional (3D) treatment planning often involves complex combinations of beam energies, treatment fields, and beam modifying devices. Even when a plan is devised that meets many treatment-planning objectives, limitations in the planner's ability to further adjust beam characteristics may require the radiation dose prescription to be normalized to an isodose level that best covers the target volume. While these normalizations help meet the volume coverage goals, they also result in adjustment of the dose delivered to the normal tissues and must be carefully evaluated. Intensity-modulated radiation therapy (IMRT) treatment planning allows combinations of complex dose patterns, in order to achieve the desired treatment planning goals. These dose patterns are created by defining a set of treatment planning objectives and then allowing the treatment planning computer to create intensity patterns, through the use of moving multileaf collimation that will meet the requested goals. Often, when an IMRT treatment plan is created that meets many of the treatment planning goals but falls short of volume coverage requirements, the planner is tempted to apply normalization principles similar to those utilized with 3D treatment planning. Again, these normalizations help meet the volume coverage goals, but unlike 3D planning situations, may result in avoidable delivery of additional doses to the normal tissues. The focus of this study is to evaluate the effect of application of normalization for IMRT planning using multiple patient situations. Recommendations would favor re-optimization over normalization in most planning situations.

  4. Lipid lowering activity of hydrosoluble chitosan and association with Aloe vera L. and Brassica olearaceae L.

    PubMed

    Geremias, R; Pedrosa, R C; Locatelli, C; de Fávere, V T; Coury-Pedrosa, R; Laranjeira, M C M

    2006-04-01

    The lipid lowering activity of chitosan associated with Aloe vera L. or hydrosoluble chitosan with Brassica olearaceae L. has been studied in rats. In this study, rats were submitted to different treatments with hydrosoluble chitosan alone (4% diet), hydrosoluble chitosan associated with Aloe vera L. or hydrosoluble chitosan with Brassica olearaceae L. (1:4, 4% diet) for 35 days, to identify the formula with the highest hypolipaemic potential. The results showed that all treatments reduced blood lipid levels but that hydrosoluble chitosan associated with Brassica olearaceae L. proved most efficient, because it decreased the levels of total cholesterol, LDL-cholesterol, VLDL-cholesterol and triglycerides in blood serum. The overall results suggest that the hydrosoluble chitosan/Brassica olearaceae L. association is a therapeutic alternative for hyperlipidaemia, and in this way may contribute to the prevention of atherogenic processes.

  5. Effect of vitamin D on bioavailability and lipid lowering efficacy of simvastatin.

    PubMed

    Al-Asmari, Abdulrahman K; Ullah, Zabih; Al-Sabaan, Fahad; Tariq, Mohammad; Al-Eid, Ahmed; Al-Omani, Saud F

    2015-03-01

    The 3-hydroxy 3-methylglutaryl coenzyme A reductase (HMG-CoA reductase) inhibitors known as "statins" are widely prescribed for the management of dyslipidemia. In spite of their muscle toxicity, use of statins has alarmingly increased worldwide. A recent report suggests that vitamin D (VD) levels are closely associated with lipid lowering activity and muscular toxicity of statins. However, data are limited and inconclusive. The present study was undertaken to investigate the effect of VD supplementation on the bioavailability and lipid lowering effect of simvastatin (ST). Adult Sprague-Dawley male rats (250 ± 10 g) were divided into four groups including control, ST (100 mg/kg/day), VD (100 μg/kg/day) and ST + VD group, respectively. After the dosing period of 8 days the animals were sacrificed and the blood was collected for the analysis of ST, its active metabolite simvastatin acid (STA), total cholesterol, triglyceride and liver enzymes including aspartate transaminase and alanine transaminase. The result of this study showed a significant decrease in the level of cholesterol and triglyceride in ST alone treated group, whereas VD alone failed to alter the blood lipid levels. Concomitant treatment with VD produced significant decrease in the bioavailability of ST and STA. However, there was no significant difference in the level of cholesterol in ST alone and in ST + VD treated group. Our results on the liver enzyme suggest that ST alone or in combination with VD does not produce any hepatotoxicity. Further studies using VD along with various statins for a longer duration are suggested.

  6. Muscle Mass and Body Fat in Relation to Cardiovascular Risk Estimation and Lipid-Lowering Eligibility.

    PubMed

    Lee, Kayoung

    2016-12-06

    This cross-sectional population-based study aimed to evaluate the relationships of muscle-mass and body-fat phenotypes to 10-yr risk of cardiovascular disease (CVD) events and eligibility for lipid management. Participants were Korean adults (N = 7315; 3163 men, 4152 women) aged 40-79 yr, free from stroke and coronary heart disease, who provided complete data for estimating 10-yr CVD risk and body composition during the Fifth Korea National Health and Nutrition Examination Survey (2009-2010). Four levels of combined muscle mass and body fat were determined using sex-specific quintiles of appendicular skeletal muscle mass divided by height squared, and sex-specific quintiles of total body fat percentage. Ten-year CVD risk was calculated using Pooled Cohort Equations and Framingham risk scores. Lipid-lowering medication eligibility was determined using American College of Cardiology/American Heart Association (ACC/AHA) and Adult Treatment Panel (ATP) III guidelines. Compared with the reference group, the risk of CVD events was higher in men with low muscle mass, high body fat, or the 2 factors combined. CVD risk was lower in women with low muscle mass, higher in women with high body fat, and nonsignificant in women with the 2 factors. Participants with low muscle mass and high body fat had higher odds for medication eligibility using the ACC/AHA guidelines but not the ATP III guidelines. Higher estimated 10-yr CVD risk was associated with combined phenotypes of low muscle mass and high fat in men but not in women. Also, the relationship of these phenotypes to lipid-lowering medication eligibility was guideline-specific.

  7. Assessment of ADRs associated with lipid-lowering agents recorded in the Department of Internal Medicine, University Hospital, Jena.

    PubMed

    Hippius, M; Farker, K; Helble, S; Hoffmann, A

    2002-03-01

    Drug-related illness is an important cause of admission to hospital. Little information is available regarding the frequency of ADRs caused by antilipidemic agents classified as HMG-CoA reductase inhibitors (statins). Treatment with statins has been associated with the occurrence of myopathy or liver toxicity in case reports. Recent lipid intervention studies have involved the implementation of lipid lowering therapy with HMG-CoA reductase inhibitors in cardiovascular risk management. Since January 1997 we have been involved in a study, the aim of which was to improve the spontaneous drug information reporting system in Germany. The study was supported by the German Federal Institute for Drugs and Medical Devices, the "Bundesinstitut für Arzneimittel und Medizinprodukte", Berlin BfArM. Between early 1997 and late 2000, as a result of this monitoring of ADRs, we analyzed all patient histories concerning therapy with statins. A total of 550 ADR patients were evaluated, (209 male, 341 female) with a mean age of 66.4 years. 27 (4.9%) of all patients had received statins (atorvastatin = 12, fluvastatin = 7, simvastatin as well as pravastatin = 3, lovastatin = 2). Only 2 of the 27 patients admitted to hospital for typical ADRs of statins such as skeletal muscle toxicity (e.g. myalgia, rhabdomyolysis) or disorders involving hepatic structure or function were receiving statins (atorvastatin). An increased risk of rhabdomyolysis has been reported in the case of several statins, following concomitant use with erythromycin, cyclosporine or itraconazole, all of which are potent inhibitors of CYP3A4 enzyme. But only 1 atorvastatin patient had received cyclosporine as a CYP3A4 inhibitor. After discontinuing medication, signs of intoxication disappeared. The antihyperlipidemic drugs available are generally safe and effective, and rate of ADRs is low if concomitant intake of other drugs and the differing pharmacokinetic profiles of the statins are considered.

  8. Residual cardiovascular risk in patients who received lipid-lowering treatment in a real-life setting: retrospective study

    PubMed Central

    Perrone, Valentina; Sangiorgi, Diego; Buda, Stefano; Degli Esposti, Luca

    2016-01-01

    Introduction The objective of this study was twofold: 1) to assess the residual cardiovascular (CV) risk among patients treated with statins according to guidelines and at the recommended dosages; and 2) to assess the difference, if any, in the frequency of CV events when patients were treated with other lipid-lowering agents alongside statins. Methods A retrospective observational study including one local health unit was conducted. Administrative databases were linked to laboratory test database in order to collect cholesterol values at baseline. Patients were included if they had filled at least one prescription for statins between January 1, 2009 and December 31, 2011; patients’ records were considered for a 12-month time span. Results A total of 27,330 patients treated with statins were included (50% male, mean age 68.0±11.5 years). Among them, 770 were treated with statins according to guidelines and at the recommended dosages and had a low density lipoprotein-cholesterol value below the therapeutic target. Nevertheless, the risk of myocardial infarction or stroke remained: incidence rates were 1.3±1.0 per patient per year for moderate CV risk, 4.1±2.6 for high risk, and 12.5±11.0 for very high risk. This incremental risk was confirmed further using the Cox model, by correcting for age, sex, use of antiplatelet and/or antihypertensive therapy, and adherence to treatment. As a second analysis, we compared, after a propensity score matching, patients extracted from the overall sample who were treated with fibrates. Based on the Cox model, patients on fibrates had a risk for myocardial infarction or stroke lower than patients on statins. Conclusion Among patients treated with statins according to guidelines and at the recommended dosages, a residual CV risk was observed. We concluded that intervention for managing residual CV risk during statin therapy should be implemented. PMID:27822076

  9. Bamboo Leaf Flavones and Tea Polyphenols Show a Lipid-lowering Effect in a Rat Model of Hyperlipidemia.

    PubMed

    Yang, C; Yifan, L; Dan, L; Qian, Y; Ming-yan, J

    2015-12-01

    At present, most of the lipid-lowering drugs are western medicines, which have a lot of adverse reactions. Zhucha, an age-old Uyghur medicine, is made up of bamboo leaves and tea (green tea), which has good efficacy and lipid-lowering effect. The purpose of this study was to undertake a pharmacodynamic examination of the optimal proportions of bamboo leaf flavones and tea polyphenols required to achieve lipid lowering in rats. A hyperlipidemia rat model was used to examine the lipid lowering effects of bamboo leaf flavones and tea polyphenols. Wistar rats were divided into 13 groups including one hyperlipidemia model group and 2 positive drug groups as well as experimental groups (9 groups dosed with different proportions of bamboo leaf flavones and tea polyphenols, the 3 dosages of bamboo leaf flavones were 75 mg/kg/d, 50 mg/kg/d and 25 mg/kg/d respectively, the 3 dosages of tea polyphenol were 750 mg/kg/d, 500 mg/kg/d and 250 mg/kg/d). The weight, the levels of triglyceride (TG) and high-density lipoprotein cholesterol (HDL) were determined. A high dose of bamboo leaf flavones (75 mg/kg/d) combined with a medium dose of tea polyphenols (500 mg/kg/d) was deemed to be optimal for achieving a lipid-lowering effect, the weight had the smallest increase and the level of TG and HDL was similar to positive control. The bamboo leaf flavones and tea polyphenols were mixed according to a certain proportion (1:6.7), and the mixture achieved a lipid-lowering effect and might prove to be useful as a natural lipid-lowering agent.

  10. Dosimetrically Triggered Adaptive Intensity Modulated Radiation Therapy for Cervical Cancer

    SciTech Connect

    Lim, Karen; Stewart, James; Kelly, Valerie; Xie, Jason; Brock, Kristy K.; Moseley, Joanne; Cho, Young-Bin; Fyles, Anthony; Lundin, Anna; Rehbinder, Henrik; Löf, Johan; Jaffray, David A.; Milosevic, Michael

    2014-09-01

    Purpose: The widespread use of intensity modulated radiation therapy (IMRT) for cervical cancer has been limited by internal target and normal tissue motion. Such motion increases the risk of underdosing the target, especially as planning margins are reduced in an effort to reduce toxicity. This study explored 2 adaptive strategies to mitigate this risk and proposes a new, automated method that minimizes replanning workload. Methods and Materials: Thirty patients with cervical cancer participated in a prospective clinical study and underwent pretreatment and weekly magnetic resonance (MR) scans over a 5-week course of daily external beam radiation therapy. Target volumes and organs at risk (OARs) were contoured on each of the scans. Deformable image registration was used to model the accumulated dose (the real dose delivered to the target and OARs) for 2 adaptive replanning scenarios that assumed a very small PTV margin of only 3 mm to account for setup and internal interfractional motion: (1) a preprogrammed, anatomy-driven midtreatment replan (A-IMRT); and (2) a dosimetry-triggered replan driven by target dose accumulation over time (D-IMRT). Results: Across all 30 patients, clinically relevant target dose thresholds failed for 8 patients (27%) if 3-mm margins were used without replanning. A-IMRT failed in only 3 patients and also yielded an additional small reduction in OAR doses at the cost of 30 replans. D-IMRT assured adequate target coverage in all patients, with only 23 replans in 16 patients. Conclusions: A novel, dosimetry-triggered adaptive IMRT strategy for patients with cervical cancer can minimize the risk of target underdosing in the setting of very small margins and substantial interfractional motion while minimizing programmatic workload and cost.

  11. Commissioning of Peacock System for intensity-modulated radiation therapy.

    PubMed

    Saw, C B; Ayyangar, K M; Thompson, R B; Zhen, W; Enke, C A

    2001-01-01

    The Peacock System was introduced to perform tomographic intensity-modulated radiation therapy (IMRT). Commissioning of the Peacock System included the alignment of the multileaf intensity-modulating collimator (MIMiC) to the beam axis, the alignment of the RTA device for immobilization, and checking the integrity of the CRANE for indexing the treatment couch. In addition, the secondary jaw settings, couch step size, and transmission through the leaves were determined. The dosimetric data required for the CORVUS planning system were divided into linear accelerator-specific and MIMiC-specific. The linear accelerator-specific dosimetric data were relative output in air, relative output in phantom, percent depth dose for a range of field sizes, and diagonal dose profiles for a large field size. The MIMiC-specific dosimetric data were the in-plane and cross-plane dose profiles of a small and a large field size to derive the penumbra fit. For each treatment unit, the Beam Utility software requires the data be entered into the CORVUS planning system in modular forms. These modules were treatment unit information, angle definition, configuration, gantry and couch angles range, dosimetry, results, and verification plans. After the appropriate machine data were entered, CORVUS created a dose model. The dose model was used to create known simple dose distribution for evaluation using the verification tools of the CORVUS. The planned doses for phantoms were confirmed using an ion chamber for point dose measurement and film for relative dose measurement. The planning system calibration factor was initially set at 1.0 and will be changed after data on clinical cases are acquired. The treatment unit was released for clinical use after the approval icon was checked in the verification plans module.

  12. High Intensity Laser Therapy (HILT) versus TENS and NSAIDs in low back pain: clinical study

    NASA Astrophysics Data System (ADS)

    Zati, Allesandro; Fortuna, Damiano; Valent, A.; Filippi, M. V.; Bilotta, Teresa W.

    2004-09-01

    Low back pain, caused by lumbar disc herniation, is prevalently treated with a conservative approach. In this study we valued the efficacy of High Intensity Laser Therapy (HILT), compared with accepted therapies such as TENS and NSAIDs. Laser therapy obtained similar results in the short term, but better clinical effect over time than TENS and NSAIDs. In conclusion high intensity laser therapy appears to be a interesting new treatment, worthy of further research.

  13. [The intensive care gallbladder as shock organ: symptoms and therapy].

    PubMed

    Rimkus, C; Kalff, J C

    2013-03-01

    Acute acalculous cholecystitis (AAC) represents a severe disease in critically ill patients. The pathogenesis of acute necroinflammatory gallbladder disease is multifactorial and intensive care unit (ICU) patients show multiple risk factors. In addition AAC is difficult to diagnose because of the vague physical and non-specific technical findings. Only the combination of clinical and technical findings including the challenging physical examination of critically ill patients, laboratory results and ultrasound or computed tomography (CT) scan, will lead to the diagnosis. The condition of AAC has a rapid progress to gallbladder necrosis, gangrene and perforation and these complications are reflected in the high morbidity and mortality rates, therefore, therapy should be promptly initiated. If there are no clinical contraindications for an operative approach cholecystectomy is the definitive treatment and both open and laparoscopic procedures have been used. In unstable, critically ill patients percutaneous cholecystostomy should be immediately performed. In addition, transpapillary endoscopic drainage is also possible if there are contraindications for percutaneous cholecystostomy. Patients who fail to improve or deteriorate following interventional drainage should be reconsidered for cholecystectomy. Due to the fact that more than 90 % of patients treated with percutaneous cholecystostomy showed no recurrence of symptoms during a period of more than 1 year, it is still unclear if percutaneous cholecystostomy is the definitive treatment of AAC for unstable patients or if delayed cholecystectomy is still necessary.

  14. Intensity modulated radiation therapy for breast cancer: current perspectives

    PubMed Central

    Buwenge, Milly; Cammelli, Silvia; Ammendolia, Ilario; Tolento, Giorgio; Zamagni, Alice; Arcelli, Alessandra; Macchia, Gabriella; Deodato, Francesco; Cilla, Savino; Morganti, Alessio G

    2017-01-01

    Background Owing to highly conformed dose distribution, intensity modulated radiation therapy (IMRT) has the potential to improve treatment results of radiotherapy (RT). Postoperative RT is a standard adjuvant treatment in conservative treatment of breast cancer (BC). The aim of this review is to analyze available evidence from randomized controlled trials (RCTs) on IMRT in BC, particularly in terms of reduction of side effects. Methods A literature search of the bibliographic database PubMed, from January 1990 through November 2016, was performed. Only RCTs published in English were included. Results Ten articles reporting data from 5 RCTs fulfilled the selection criteria and were included in our review. Three out of 5 studies enrolled only selected patients in terms of increased risk of toxicity. Three studies compared IMRT with standard tangential RT. One study compared the results of IMRT in the supine versus the prone position, and one study compared standard treatment with accelerated partial breast IMRT. Three studies reported reduced acute and/or late toxicity using IMRT compared with standard RT. No study reported improved quality of life. Conclusion IMRT seems able to reduce toxicity in selected patients treated with postoperative RT for BC. Further analyses are needed to better define patients who are candidates for this treatment modality. PMID:28293119

  15. Intensity-Modulated Radiation Therapy in Childhood Ependymoma

    SciTech Connect

    Schroeder, Thomas M.; Chintagumpala, Murali; Okcu, M. Fatih; Chiu, J. Kam; Teh, Bin S.; Woo, Shiao Y.; Paulino, Arnold C.

    2008-07-15

    Purpose: To determine the patterns of failure after intensity-modulated radiation therapy (IMRT) for localized intracranial ependymoma. Methods and Materials: From 1994 to 2005, 22 children with pathologically proven, localized, intracranial ependymoma were treated with adjuvant IMRT. Of the patients, 12 (55%) had an infratentorial tumor and 14 (64%) had anaplastic histology. Five patients had a subtotal resection (STR), as evidenced by postoperative magnetic resonance imaging. The clinical target volume encompassed the tumor bed and any residual disease plus margin (median dose 54 Gy). Median follow-up for surviving patients was 39.8 months. Results: The 3-year overall survival rate was 87% {+-} 9%. The 3-year local control rate was 68% {+-} 12%. There were six local recurrences, all in the high-dose region of the treatment field. Median time to recurrence was 21.7 months. Of the 5 STR patients, 4 experienced recurrence and 3 died. Patients with a gross total resection had significantly better local control (p = 0.024) and overall survival (p = 0.008) than those with an STR. At last follow-up, no patient had developed visual loss, brain necrosis, myelitis, or a second malignancy. Conclusions: Treatment with IMRT provides local control and survival rates comparable with those in historic publications using larger treatment volumes. All failures were within the high-dose region, suggesting that IMRT does not diminish local control. The degree of surgical resection was shown to be significant for local control and survival.

  16. Monte Carlo dose verification for intensity-modulated arc therapy

    NASA Astrophysics Data System (ADS)

    Li, X. Allen; Ma, Lijun; Naqvi, Shahid; Shih, Rompin; Yu, Cedric

    2001-09-01

    Intensity-modulated arc therapy (IMAT), a technique which combines beam rotation and dynamic multileaf collimation, has been implemented in our clinic. Dosimetric errors can be created by the inability of the planning system to accurately account for the effects of tissue inhomogeneities and physical characteristics of the multileaf collimator (MLC). The objective of this study is to explore the use of Monte Carlo (MC) simulation for IMAT dose verification. The BEAM/DOSXYZ Monte Carlo system was implemented to perform dose verification for the IMAT treatment. The implementation includes the simulation of the linac head/MLC (Elekta SL20), the conversion of patient CT images and beam arrangement for 3D dose calculation, the calculation of gantry rotation and leaf motion by a series of static beams and the development of software to automate the entire MC process. The MC calculations were verified by measurements for conventional beam settings. The agreement was within 2%. The IMAT dose distributions generated by a commercial forward planning system (RenderPlan, Elekta) were compared with those calculated by the MC package. For the cases studied, discrepancies of over 10% were found between the MC and the RenderPlan dose calculations. These discrepancies were due in part to the inaccurate dose calculation of the RenderPlan system. The computation time for the IMAT MC calculation was in the range of 20-80 min on 15 Pentium-III computers. The MC method was also useful in verifying the beam apertures used in the IMAT treatments.

  17. Low intensity laser therapy accelerates muscle regeneration in aged rats

    PubMed Central

    Vatansever, Fatma; Rodrigues, Natalia C.; Assis, Livia L.; Peviani, Sabrina S.; Durigan, Joao L.; Moreira, Fernando M.A.; Hamblin, Michael R.; Parizotto, Nivaldo A.

    2013-01-01

    Background Elderly people suffer from skeletal muscle disorders that undermine their daily activity and quality of life; some of these problems can be listed as but not limited to: sarcopenia, changes in central and peripheral nervous system, blood hypoperfusion, regenerative changes contributing to atrophy, and muscle weakness. Determination, proliferation and differentiation of satellite cells in the regenerative process are regulated by specific transcription factors, known as myogenic regulatory factors (MRFs). In the elderly, the activation of MRFs is inefficient which hampers the regenerative process. Recent studies found that low intensity laser therapy (LILT) has a stimulatory effect in the muscle regeneration process. However, the effects of this therapy when associated with aging are still unknown. Objective This study aimed to evaluate the effects of LILT (λ=830 nm) on the tibialis anterior (TA) muscle of aged rats. Subjects and methods The total of 56 male Wistar rats formed two population sets: old and young, with 28 animals in each set. Each of these sets were randomly divided into four groups of young rats (3 months of age) with n=7 per group and four groups of aged rats (10 months of age) with n=7 per group. These groups were submitted to cryoinjury + laser irradiation, cryoinjury only, laser irradiation only and the control group (no cryoinjury/no laser irradiation). The laser treatment was performed for 5 consecutive days. The first laser application was done 24 h after the injury (on day 2) and on the seventh day, the TA muscle was dissected and removed under anesthesia. After this the animals were euthanized. Histological analyses with toluidine blue as well as hematoxylin-eosin staining (for counting the blood capillaries) were performed for the lesion areas. In addition, MyoD and VEGF mRNA was assessed by quantitative polymerase chain reaction. Results The results showed significant elevation (p<0.05) in MyoD and VEGF genes expression levels

  18. Prioritized efficiency optimization for intensity modulated proton therapy.

    PubMed

    Müller, Birgit S; Wilkens, Jan J

    2016-12-07

    A high dosimetric quality and short treatment time are major goals in radiotherapy planning. Intensity modulated proton therapy (IMPT) plans obtain dose distributions of great conformity but often result in long delivery times which are typically not incorporated into the optimization process. We present an algorithm to optimize delivery efficiency of IMPT plans while maintaining plan quality, and study the potential trade-offs of these interdependent objectives. The algorithm is based on prioritized optimization, a stepwise approach to implemented objectives. First the quality of the plan is optimized. The second step of the prioritized efficiency optimization (PrEfOpt) routine offers four alternatives for reducing delivery time: minimization of the total spot weight sum (A), maximization of the lowest spot intensity of each energy layer (B), elimination of low-weighted spots (C) or energy layers (D). The trade-off between dosimetric quality (step I) and treatment time (step II) is controlled during the optimization by option-dependent parameters. PrEfOpt was applied to a clinical patient case, and plans for different trade-offs were calculated. Delivery times were simulated for two virtual facilities with constant and variable proton current, i.e. independent and dependent on the optimized spot weight distributions. Delivery times decreased without major degradation of plan quality; absolute time reductions varied with the applied method and facility type. Minimizing the total spot weight sum (A) reduced times by 28% for a similar plan quality at a constant current (changes of minimum dose in the target  <1%). For a variable proton current, eliminating low-weighted spots (C) led to remarkably faster delivery (16%). The implementation of an efficiency-optimization step into the optimization process can yield reduced delivery times with similar plan qualities. A potential clinical application of PrEfOpt is the generation of multiple plans with different trade

  19. Prioritized efficiency optimization for intensity modulated proton therapy

    NASA Astrophysics Data System (ADS)

    Müller, Birgit S.; Wilkens, Jan J.

    2016-12-01

    A high dosimetric quality and short treatment time are major goals in radiotherapy planning. Intensity modulated proton therapy (IMPT) plans obtain dose distributions of great conformity but often result in long delivery times which are typically not incorporated into the optimization process. We present an algorithm to optimize delivery efficiency of IMPT plans while maintaining plan quality, and study the potential trade-offs of these interdependent objectives. The algorithm is based on prioritized optimization, a stepwise approach to implemented objectives. First the quality of the plan is optimized. The second step of the prioritized efficiency optimization (PrEfOpt) routine offers four alternatives for reducing delivery time: minimization of the total spot weight sum (A), maximization of the lowest spot intensity of each energy layer (B), elimination of low-weighted spots (C) or energy layers (D). The trade-off between dosimetric quality (step I) and treatment time (step II) is controlled during the optimization by option-dependent parameters. PrEfOpt was applied to a clinical patient case, and plans for different trade-offs were calculated. Delivery times were simulated for two virtual facilities with constant and variable proton current, i.e. independent and dependent on the optimized spot weight distributions. Delivery times decreased without major degradation of plan quality; absolute time reductions varied with the applied method and facility type. Minimizing the total spot weight sum (A) reduced times by 28% for a similar plan quality at a constant current (changes of minimum dose in the target  <1%). For a variable proton current, eliminating low-weighted spots (C) led to remarkably faster delivery (16%). The implementation of an efficiency-optimization step into the optimization process can yield reduced delivery times with similar plan qualities. A potential clinical application of PrEfOpt is the generation of multiple plans with different trade

  20. Lipid-lowering treatment patterns among patients with type 2 diabetes mellitus with high cardiovascular disease risk

    PubMed Central

    Quek, Ruben G W; Fox, Kathleen M; Wang, Li; Li, Lu; Gandra, Shravanthi R; Wong, Nathan D

    2015-01-01

    Objective To examine real-world treatment patterns of lipid-lowering treatment and their possible associated intolerance and/or ineffectiveness among patients with type 2 diabetes mellitus initiating statins and/or ezetimibe. Research design and methods Adult (aged ≥18 years) patients diagnosed with type 2 diabetes who initiated statins and/or ezetimibe from January 1, 2007 to June 30, 2011 were retrospectively identified from the IMS LifeLink Pharmetrics Plus commercial claims database. Patients were further classified into 3 high-risk cohorts: (1) history of cardiovascular event (CVE); (2) two risk factors (age and hypertension); (3) aged ≥40 years. Patients had continuous health plan enrolment ≥1 year preindex and postindex date (statin and/or ezetimibe initiation date). Primary outcomes were index statin intensity, treatment modification(s), possible associated statin/non-statin intolerance and/or ineffectiveness issues (based on treatment modification type), and time-to-treatment modification(s). Analyses for each cohort were stratified by age groups (<65 and ≥65 years). Results A total of 9823 (history of CVE), 62 049 (2 risk factors), and 128 691 (aged ≥40 years) patients were included. Among patients aged <65 years, 81.4% and 51.8% of those with history of CVE, 75.6% and 44.4% of those with 2 risk factors, and 77.9% and 47.1% of those aged ≥40 years had ≥1 and 2 treatment modification(s), respectively. Among all patients, 23.2–28.4% had possible statin intolerance and/or ineffectiveness issues after accounting for second treatment modification (if any). Conclusions Among patients with type 2 diabetes with high cardiovascular disease risk, index statin treatment modifications that potentially imply possible statin intolerance and/or ineffectiveness were frequent. PMID:26435839

  1. Intensity Modulated Radiation Therapy With Dose Painting to Treat Rhabdomyosarcoma

    SciTech Connect

    Yang, Joanna C.; Dharmarajan, Kavita V.; Wexler, Leonard H.; La Quaglia, Michael P.; Happersett, Laura; Wolden, Suzanne L.

    2012-11-01

    Purpose: To examine local control and patterns of failure in rhabdomyosarcoma patients treated with intensity modulated radiation therapy (RT) with dose painting (DP-IMRT). Patients and Methods: A total of 41 patients underwent DP-IMRT with chemotherapy for definitive treatment. Nineteen also underwent surgery with or without intraoperative RT. Fifty-six percent had alveolar histologic features. The median interval from beginning chemotherapy to RT was 17 weeks (range, 4-25). Very young children who underwent second-look procedures with or without intraoperative RT received reduced doses of 24-36 Gy in 1.4-1.8-Gy fractions. Young adults received 50.4 Gy to the primary tumor and lower doses of 36 Gy in 1.8-Gy fractions to at-risk lymph node chains. Results: With 22 months of median follow-up, the actuarial local control rate was 90%. Patients aged {<=}7 years who received reduced overall and fractional doses had 100% local control, and young adults had 79% (P=.07) local control. Three local failures were identified in young adults whose primary target volumes had received 50.4 Gy in 1.8-Gy fractions. Conclusions: DP-IMRT with lower fractional and cumulative doses is feasible for very young children after second-look procedures with or without intraoperative RT. DP-IMRT is also feasible in adolescents and young adults with aggressive disease who would benefit from prophylactic RT to high-risk lymph node chains, although dose escalation might be warranted for improved local control. With limited follow-up, it appears that DP-IMRT produces local control rates comparable to those of sequential IMRT in patients with rhabdomyosarcoma.

  2. [Modalities of breast cancer irradiation in 2016: Aims and indications of intensity modulated radiation therapy].

    PubMed

    Bourgier, C; Fenoglietto, P; Lemanski, C; Ducteil, A; Charissoux, M; Draghici, R; Azria, D

    2016-10-01

    Irradiation techniques for breast cancer (arctherapy, tomotherapy) are evolving and intensity-modulated radiation therapy is being increasingly considered for the management of these tumours. Here, we propose a review of intensity-modulated radiation therapy planning issues, clinical toxicities and indications for breast cancer.

  3. Changes in N400 Topography Following Intensive Speech Language Therapy for Individuals with Aphasia

    ERIC Educational Resources Information Center

    Wilson, K. Ryan; O'Rourke, Heather; Wozniak, Linda A.; Kostopoulos, Ellina; Marchand, Yannick; Newman, Aaron J.

    2012-01-01

    Our goal was to characterize the effects of intensive aphasia therapy on the N400, an electrophysiological index of lexical-semantic processing. Immediately before and after 4 weeks of intensive speech-language therapy, people with aphasia performed a task in which they had to determine whether spoken words were a "match" or a "mismatch" to…

  4. Lipid lowering effects of iodothyronines: In vivo and in vitro studies on rat liver

    PubMed Central

    Vergani, Laura

    2014-01-01

    Non-alcoholic fatty liver disease (NAFLD) is emerging as one of the most common liver diseases, leading to the increasing interest for new therapeutic approaches for its treatment. NAFLD primarily depends on a hypercaloric and/or unbalanced diet leading to overweight and obesity. The liver, in fact, plays a central role in lipid metabolism by importing free fatty acids from the blood and synthesizing, storing, oxidizing and exporting lipids. Furthermore, the liver is the target for the thyroid hormones, thyroxine (T4) and 3,3’,5-triiodo-L-thyronine (T3), that stimulate the basal metabolic rate and lead to body weight loss. In the last decade, other iodothyronines have been shown to possess biological relevance and play some thyromimetic activities; in particular, 3,5-diiodo-L-thyronine (T2) gained large interest. The global effect of iodothyronines on liver lipid metabolism results from the balance between direct and indirect actions on the hepatocyte, leading to stimulation of lipid synthesis, oxidation and autophagy. In this review, the results so far obtained on both in vivo and in vitro models of hepatosteatosis are summarized in order to obtain an updated picture of the lipid-lowering effects of iodothyronines on mammalian liver. PMID:24799985

  5. Lipid-lowering Activity of Natural and Semi-Synthetic Sterols and Stanols.

    PubMed

    Taha, Dhiaa A; Wasan, Ellen K; Wasan, Kishor M; Gershkovich, Pavel

    2015-01-01

    Consumption of plant sterols/ stanols has long been demonstrated to reduce plasma cholesterol levels. The objective of this review is to demonstrate the lipid-lowering activity and anti-atherogenic effects of natural and semi-synthetic plant sterols/ stanols based on evidence from cell-culture studies, animal studies and clinical trials. Additionally, this review highlights certain molecular mechanisms by which plant sterols/ stanols lower plasma cholesterol levels with a special emphasis on factors that affect the cholesterol-lowering activity of plant sterols/stanols. The crystalline nature and the poor oil solubility of these natural products could be important factors that limit their cholesterol-lowering efficiency. Several attempts have been made to improve the cholesterol-lowering activity by enhancing the bioavailability of crystalline sterols and stanols. Approaches involved reduction of the crystal size and/or esterification with fatty acids from vegetable or fish oils. However, the most promising approach in this context is the chemical modification of plant sterols /stanols into water soluble disodium ascorbyl phytostanyl phosphates analogue by esterification with ascorbic acid. This novel semi-synthetic stanol derivative has improved efficacy over natural plant sterols/ stanols and can provide additional benefits by combining the cholesterol-lowering properties of plant stanols with the antioxidant potential of ascorbic acid. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.

  6. Role of lipid-lowering agents in the management of diabetic retinopathy

    PubMed Central

    Ioannidou, Estelle; Tseriotis, Vasilis-Spyridon; Tziomalos, Konstantinos

    2017-01-01

    Diabetic retinopathy affects a substantial proportion of patients with diabetes mellitus (DM) and is the leading cause of blindness in working-aged adults. Even though the incidence of diabetic retinopathy has declined in the last decades, its prevalence increased and is expected to rise further as a result of the increasing incidence of type 2 DM (T2DM) and the longer life expectancy of patients with DM. The pathogenesis of diabetic retinopathy is multifactorial. Some observational studies suggested an association between dyslipidemia and the development and progression of retinopathy in patients with DM but others did not confirm this association. Regarding lipid-lowering agents, studies that evaluated the role of statins in the management of these patients are mostly small and yielded discrepant results. Large randomized studies with statins in patients with T2DM showed no benefit of these agents on diabetic retinopathy but were not designed to address this effect. In contrast, both preclinical data and two large randomized controlled studies, the FIELD and the ACCORD trial, showed that fenofibrate delays the progression of diabetic retinopathy. Even though the mechanisms underpinning this favorable effect are not entirely clear, these findings suggest that fenofibrate might represent a useful tool for the management of diabetic retinopathy. PMID:28138358

  7. The JUPITER lipid lowering trial and vitamin D: Is there a connection?

    PubMed

    Ware, William R

    2010-04-01

    There is growing evidence that vitamin D deficiency significantly increases the risk of adverse cardiovascular events and that a vitamin D status representing sufficiency or optimum is protective. Unfortunately, in clinical trials that address interventions for reducing risk of adverse cardiovascular events, vitamin D status is not generally measured. Failure to do this has now assumed greater importance with the report of a study that found rosuvastatin at doses at the level used in a recent large randomized lipid lowering trial (JUPITER) had a large and significant impact on vitamin D levels as measured by the metabolite 25-hydroxyvitamin D. The statin alone appears to have increased this marker such that the participants on average went from deficient to sufficient in two months. The difference in cardiovascular risk between those deficient and sufficient in vitamin D in observational studies was similar to the risk reduction found in JUPITER. Thus it appears that this pleiotropic effect of rosuvastatin may be responsible for part of its unusual effectiveness in reducing the risk of various cardiovascular endpoints found in JUPITER and calls into question the interpretation based only on LDL cholesterol and CRP changes. In addition, vitamin D status is a cardiovascular risk factor which up until now has not been considered in adjusting study results or in multivariate analysis, and even statistical analysis using only baseline values may be inadequate.

  8. Whole-brain hippocampal sparing radiation therapy: Volume-modulated arc therapy vs intensity-modulated radiation therapy case study

    SciTech Connect

    Lee, Katrina Lenards, Nishele; Holson, Janice

    2016-04-01

    The hippocampus is responsible for memory and cognitive function. An ongoing phase II clinical trial suggests that sparing dose to the hippocampus during whole-brain radiation therapy can help preserve a patient's neurocognitive function. Progressive research and advancements in treatment techniques have made treatment planning more sophisticated but beneficial for patients undergoing treatment. The aim of this study is to evaluate and compare hippocampal sparing whole-brain (HS-WB) radiation therapy treatment planning techniques using volume-modulated arc therapy (VMAT) and intensity-modulated radiation therapy (IMRT). We randomly selected 3 patients to compare different treatment techniques that could be used for reducing dose to the hippocampal region. We created 2 treatment plans, a VMAT and an IMRT, from each patient's data set and planned on the Eclipse 11.0 treatment planning system (TPS). A total of 6 plans (3 IMRT and 3 VMAT) were created and evaluated for this case study. The physician contoured the hippocampus as per the Radiation Therapy Oncology Group (RTOG) 0933 protocol atlas. The organs at risk (OR) were contoured and evaluated for the plan comparison, which included the spinal cord, optic chiasm, the right and left eyes, lenses, and optic nerves. Both treatment plans produced adequate coverage on the planning target volume (PTV) while significantly reducing dose to the hippocampal region. The VMAT treatment plans produced a more homogenous dose distribution throughout the PTV while decreasing the maximum point dose to the target. However, both treatment techniques demonstrated hippocampal sparing when irradiating the whole brain.

  9. Extrapleural pneumonectomy, photodynamic therapy and intensity modulated radiation therapy for the treatment of malignant pleural mesothelioma.

    PubMed

    Du, Kevin L; Both, Stefan; Friedberg, Joseph S; Rengan, Ramesh; Hahn, Stephen M; Cengel, Keith A

    2010-09-01

    Intensity modulated radiation therapy (IMRT) has recently been proposed for the treatment of malignant pleural mesothelioma (MPM). Here, we describe our experience with a multimodality approach for the treatment of mesothelioma, incorporating extrapleural pneumonectomy, intraoperative photodynamic therapy and postoperative hemithoracic IMRT. From 2004-2007, we treated 11 MPM patients with hemithoracic IMRT, 7 of whom had undergone porfimer sodium-mediated PDT as an intraoperative adjuvant to surgical debulking. The median radiation dose to the planning treatment volume (PTV) ranged from 45.4-54.5 Gy. For the contralateral lung, V20 ranged from 1.4-28.5%, V5 from 42-100% and MLD from 6.8-16.5 Gy. In our series, 1 patient experienced respiratory failure secondary to radiation pneumonitis that did not require mechanical ventilation. Multimodality therapy combining surgery with increased doses of radiation using IMRT, and newer treatment modalities such as PDT , appears safe. Future prospective analysis will be needed to demonstrate efficacy of this approach in the treatment of malignant mesothelioma. Efforts to reduce lung toxicity and improve dose delivery are needed and provide the promise of improved local control and quality of life in a carefully chosen multidisciplinary approach.

  10. The Long Term Effectiveness of Intensive Stuttering Therapy: A Mixed Methods Study

    ERIC Educational Resources Information Center

    Irani, Farzan; Gabel, Rodney; Daniels, Derek; Hughes, Stephanie

    2012-01-01

    Purpose: The purpose of this study was to gain a deeper understanding of client perceptions of an intensive stuttering therapy program that utilizes a multi-faceted approach to therapy. The study also proposed to gain a deeper understanding about the process involved in long-term maintenance of meaningful changes made in therapy. Methods: The…

  11. [Study on lipid-lowering traditional Chinese medicines based on pharmacophore technology and patent retrieval].

    PubMed

    Huo, Xiao-qian; He, Yu-su; Qiao, Lian-sheng; Sun, Zhi-yi; Zhang, Yan-ling

    2014-12-01

    The combined application of statins that inhibit HMG-CoA reductase and fibrates that activate PPAR-α can produce a better lipid-lowering effect than the simple application, but with stronger adverse reactions at the same time. In the treatment of hyperlipidemia, the combined administration of TCMs and HMG-CoA reductase inhibitor in treating hyperlipidemia shows stable efficacy and less adverse reactions, and provides a new option for the combined application of drugs. In this article, the pharmacophore technology was used to search chemical components of TCMs, trace their source herbs, and determine the potential common TCMs that could activate PPAR-α. Because there is no hyperlipidemia-related medication reference in modern TCM classics, to ensure the high safety and efficacy of all selected TCMs, we selected TCMs that are proved to be combined with statins in the World Traditional/Natural Medicine Patent Database, analyzed corresponding drugs in pharmacophore results based on that, and finally obtained common TCMs that can be applied in PPAR-α and combined with statins. Specifically, the pharmacophore model was based on eight receptor-ligand complexes of PPAR-α. The Receptor-Ligand Pharmacophore Generation module in the DS program was used to build the model, optimize with the Screen Library module, and get the best sub-pharmacophore, which consisted of two hydrogen bond acceptor, three hydrophobic groups and 19 excluded volumes, with the identification effectiveness index value N of 2. 82 and the comprehensive evaluation index CAI value of 1. 84. The model was used to screen the TCMD database, hit 5,235 kinds of chemical components and 1 193 natural animals and plants, and finally determine 62 TCMs. Through patent retrieval, we found 38 TCMs; After comparing with the virtual screening results, we finally got seven TCMs.

  12. Nutritional therapy in paediatric intensive care units: a consensus statement of the Section of Paediatric Anaesthesia and Intensive Therapy the Polish Society of Anaesthesiology and Intensive Therapy, Polish Society of Neonatology and Polish Society for.

    PubMed

    Bartkowska-Śniatkowska, Alicja; Zielińska, Marzena; Świder, Magdalena; Bittner, Grażyna; Sarnowska-Wroczyńska, Irena; Witulska, Katarzyna; Migdał, Marek; Piotrowski, Andrzej; Bober-Olesińska, Krystyna; Kęsiak, Marcin; Lauterbach, Ryszard; Gawecka, Agnieszka; Danko, Mikołaj; Popińska, Katarzyna; Romanowska, Hanna; Szlagatys-Sidorkiewicz, Agnieszka; Toporowska-Kowalska, Ewa; Żyła, Aleksandra; Książyk, Janusz

    2015-01-01

    Providing nutritional therapy via the gastrointestinal tract in patients in paediatric intensive care units (PICUs) is an effective method for delivering energy and other nutrients. In the event of contraindications to using this method, it is necessary to commence parenteral nutrition. In the present study, methods for nutritional treatments in critically ill children are presented, depending on the clinical situation.

  13. The psychophysiological effects of music therapy in intensive care units.

    PubMed

    Austin, Donna

    2010-04-01

    This article reviews the evidence for using music therapy with young people who are supported by mechanical ventilation. The author argues that music therapy is essential for developing a holistic approach focusing on the developmental level of a child or young person, as well as being an inexpensive, non-pharmacological, non-invasive therapy, with significant physiological and psychological benefits. She argues that more research is needed in this area to develop a sound evidence base on which guidelines to inform practice could be based.

  14. Simvastatin preserves diastolic function in experimental hypercholesterolemia independently of its lipid lowering effect

    PubMed Central

    Mannheim, Dallit; Herrmann, Joerg; Bonetti, Piero O.; Lavi, Ronit; Lerman, Lilach O.; Lerman, Amir

    2013-01-01

    Objective: Isolated diastolic dysfunction is present in 40% of heart failure patients. It has been attributed to myocardial fibrosis and related to cardiovascular risk factor exposure. We hypothesized that simvastatin will improve these dynamics in experimental hypercholesterolemia (HC). Methods: Three groups of pigs were studied after 12 weeks of normal (N) diet, HC diet, or HC diet with simvastatin (80 mg/day) treatment. Cardiac function was assessed by electron beam computed tomography (EBCT) and percentage of myocardium occupied by microvessels (myocardial vascular fraction) was calculated by micro-CT. Collagen content was determined by Sirius red staining and confirmed by a quantitative, hydroxyoproline-based assay. Results: Compared with N, LDL serum concentration was higher in HC and HC + simvastatin (1.0 ± 0.1 vs. 7.9 ± 1.7 and 9.6 ± 1.2 mmol/L, p < 0.05 for both). Cardiac early diastolic filling was reduced in HC compared with N (102.4 ± 11.3 vs. 151.1 ± 12.1 mL/s; p < 0.05) but restored in HC + simvastatin (176.8 ± 21.3 mL/s, p < 0.05 vs. HC). Compared with N, myocardial vascular fraction was higher in HC but not in HC + simvastatin (1.98 ± 0.84 vs. 4.48 ± 0.31 and 2.95 ± 0.95%; p < 0.05 for HC vs. N). Myocardial collagen content was higher in HC than in HC + simvastatin and N (4.72 ± 1.03 vs. 1.62 ± 0.12 and 1.21 ± 0.24% area staining; p < 0.05 for HC vs. N), which was attributable mainly to an increase in collagen III (2.90 ± 0.48 vs. 1.62 ± 0.12 and 1.21 ± 0.24% area staining; p < 0.05 for HC vs. N). Conclusions: Simvastatin is able to prevent diastolic dysfunction in experimental HC independent of its lipid lowering effect. This beneficial effect is, at least partially, due to a decrease in myocardial fibrosis and angiogenesis. PMID:21414623

  15. Effectiveness of Intensive, Group Therapy for Teenagers Who Stutter

    ERIC Educational Resources Information Center

    Fry, Jane; Millard, Sharon; Botterill, Willie

    2014-01-01

    Background: Treatment of adolescents who stutter is an under-researched area that would benefit from greater attention. Aims: To investigate whether an intensive treatment programme for older teenagers who stutter, aged over 16 years of age, is effective in reducing overt and covert aspects of stuttering. Methods & Procedures: A…

  16. Intensive Stuttering Modification Therapy: A Multidimensional Assessment of Treatment Outcomes

    ERIC Educational Resources Information Center

    Blomgren, Michael; Roy, Nelson; Callister, Thomas; Merrill, Ray M.

    2005-01-01

    Nineteen adults who stutter participated in a 3-week intensive stuttering modification treatment program (the Successful Stuttering Management Program [SSMP]). A series of 14 fluency and affective-based measures were assessed before treatment, immediately after treatment, and 6 months after treatment. Measures included stuttering frequency; the…

  17. Effects of intensive insulin therapy combined with low molecular weight heparin anticoagulant therapy on severe pancreatitis

    PubMed Central

    DU, JUN-DONG; ZHENG, XI; HUANG, ZHI-QIANG; CAI, SHOU-WANG; TAN, JING-WANG; LI, ZHAN-LIANG; YAO, YONG-MING; JIAO, HUA-BO; YIN, HUI-NAN; ZHU, ZI-MAN

    2014-01-01

    The current study explored the effects of intensive insulin therapy (IIT) combined with low molecular weight heparin (LMWH) anticoagulant therapy on severe acute pancreatitis (SAP). A total of 134 patients with SAP that received treatment between June 2008 and June 2012 were divided randomly into groups A (control; n=33), B (IIT; n=33), C (LMWH; n=34) and D (IIT + LMWH; n=34). Group A were treated routinely. Group B received continuous pumped insulin, as well as the routine treatment, to maintain the blood sugar level between 4.4 and 6.1 mmol/l. Group C received a subcutaneous injection of LMWH every 12 h in addition to the routine treatment. Group D received IIT + LMWH and the routine treatment. The white blood cell count, hemodiastase, serum albumin, arterial partial pressure of oxygen and prothrombin time were recorded prior to treatment and 1, 3, 5, 7 and 14 days after the initiation of treatment. The intestinal function recovery time, incidence rate of multiple organ failure (MOF), length of hospitalization and fatality rates were observed. IIT + LMWH noticeably increased the white blood cell count, hemodiastase level, serum albumin level and the arterial partial pressure of oxygen in the patients with SAP (P<0.05). It markedly shortened the intestinal recovery time and the length of stay and reduced the incidence rate of MOF, the surgery rate and the fatality rate (P<0.05). It did not aggravate the hemorrhagic tendency of SAP (P>0.05). IIT + LMWH had a noticeably improved clinical curative effect on SAP compared with that of the other treatments. PMID:24944612

  18. Physical Therapy Observation and Assessment in the Neonatal Intensive Care Unit

    ERIC Educational Resources Information Center

    Byrne, Eilish; Campbell, Suzann K.

    2013-01-01

    This article presents the elements of the Observation and Assessment section of the Infant Care Path for Physical Therapy in the Neonatal Intensive Care Unit (NICU). The types of physical therapy assessments presented in this path are evidence-based and the suggested timing of these assessments is primarily based on practice knowledge from expert…

  19. Description of an Intensive Dialectical Behavior Therapy Program for Multidiagnostic Clients with Eating Disorders

    ERIC Educational Resources Information Center

    Federici, Anita; Wisniewski, Lucene; Ben-Porath, Denise

    2012-01-01

    The authors describe an intensive outpatient dialectical behavior therapy (DBT) program for multidiagnostic clients with eating disorders who had not responded adequately to standard, empirically supported treatments for eating disorders. The program integrates DBT with empirically supported cognitive behavior therapy approaches that are well…

  20. Delivery confirmation of bolus electron conformal therapy combined with intensity modulated x-ray therapy

    SciTech Connect

    Kavanaugh, James A.; Hogstrom, Kenneth R.; Fontenot, Jonas P.; Henkelmann, Gregory; Chu, Connel; Carver, Robert A.

    2013-02-15

    Purpose: The purpose of this study was to demonstrate that a bolus electron conformal therapy (ECT) dose plan and a mixed beam plan, composed of an intensity modulated x-ray therapy (IMXT) dose plan optimized on top of the bolus ECT plan, can be accurately delivered. Methods: Calculated dose distributions were compared with measured dose distributions for parotid and chest wall (CW) bolus ECT and mixed beam plans, each simulated in a cylindrical polystyrene phantom that allowed film dose measurements. Bolus ECT plans were created for both parotid and CW PTVs (planning target volumes) using 20 and 16 MeV beams, respectively, whose 90% dose surface conformed to the PTV. Mixed beam plans consisted of an IMXT dose plan optimized on top of the bolus ECT dose plan. The bolus ECT, IMXT, and mixed beam dose distributions were measured using radiographic films in five transverse and one sagittal planes for a total of 36 measurement conditions. Corrections for film dose response, effects of edge-on photon irradiation, and effects of irregular phantom optical properties on the Cerenkov component of the film signal resulted in high precision measurements. Data set consistency was verified by agreement of depth dose at the intersections of the sagittal plane with the five measured transverse planes. For these same depth doses, results for the mixed beam plan agreed with the sum of the individual depth doses for the bolus ECT and IMXT plans. The six mean measured planar dose distributions were compared with those calculated by the treatment planning system for all modalities. Dose agreement was assessed using the 4% dose difference and 0.2 cm distance to agreement. Results: For the combined high-dose region and low-dose region, pass rates for the parotid and CW plans were 98.7% and 96.2%, respectively, for the bolus ECT plans and 97.9% and 97.4%, respectively, for the mixed beam plans. For the high-dose gradient region, pass rates for the parotid and CW plans were 93.1% and 94

  1. The effects of high intensity laser therapy on pain and function in patients with knee osteoarthritis.

    PubMed

    Kim, Gook-Joo; Choi, Jioun; Lee, Sangyong; Jeon, Chunbae; Lee, Kwansub

    2016-11-01

    [Purpose] The purpose of this study was to examine the effects of high intensity laser therapy (HILT) on pain and function in patients with knee osteoarthritis. [Subjects and Methods] In this study, an experiment was conducted on 20 subjects who were divided into the control group (n=10), which would receive conservative physical therapy (CPT), and the experimental group (n=10), which would receive effects of high intensity laser therapy after conservative physical therapy. All patients received their respective therapies three times each week over a four-week period. In terms of the intensity of the high intensity laser therapy, it was applied to each patient in the tibia and femoral epicondyle for five minutes while the patient's knee joint was bent at around 30° and the separation distance between the handpiece and the skin was maintained at around 1 cm. The visual analogue scale was used to measure pain, and the Korean Western Ontario and McMaster Universities Osteoarthritis Index was used for functional evaluations. [Results] The comparison of differences in the measurements taken before and after the experiment within each group showed a statistically significant decline in both the VAS and the K-WOMAC. The comparison of the two groups showed that the high intensity laser therapy group had statistically significant lower scores in both the visual analogue scale and the Korean Western Ontario and McMaster Universities Osteoarthritis Index than the conservative physical therapy group. [Conclusion] High intensity laser therapy is considered an effective non-surgical intervention for reducing pain in patients with knee osteoarthritis and helping them to perform daily activities.

  2. The effects of high intensity laser therapy on pain and function in patients with knee osteoarthritis

    PubMed Central

    Kim, Gook-Joo; Choi, Jioun; Lee, Sangyong; Jeon, Chunbae; Lee, Kwansub

    2016-01-01

    [Purpose] The purpose of this study was to examine the effects of high intensity laser therapy (HILT) on pain and function in patients with knee osteoarthritis. [Subjects and Methods] In this study, an experiment was conducted on 20 subjects who were divided into the control group (n=10), which would receive conservative physical therapy (CPT), and the experimental group (n=10), which would receive effects of high intensity laser therapy after conservative physical therapy. All patients received their respective therapies three times each week over a four-week period. In terms of the intensity of the high intensity laser therapy, it was applied to each patient in the tibia and femoral epicondyle for five minutes while the patient’s knee joint was bent at around 30° and the separation distance between the handpiece and the skin was maintained at around 1 cm. The visual analogue scale was used to measure pain, and the Korean Western Ontario and McMaster Universities Osteoarthritis Index was used for functional evaluations. [Results] The comparison of differences in the measurements taken before and after the experiment within each group showed a statistically significant decline in both the VAS and the K-WOMAC. The comparison of the two groups showed that the high intensity laser therapy group had statistically significant lower scores in both the visual analogue scale and the Korean Western Ontario and McMaster Universities Osteoarthritis Index than the conservative physical therapy group. [Conclusion] High intensity laser therapy is considered an effective non-surgical intervention for reducing pain in patients with knee osteoarthritis and helping them to perform daily activities. PMID:27942148

  3. Application of Histogram Analysis in Radiation Therapy (HART) in Intensity Modulation Radiation Therapy (IMRT) Treatments

    NASA Astrophysics Data System (ADS)

    Pyakuryal, Anil

    2009-03-01

    A carcinoma is a malignant cancer that emerges from epithelial cells in structures through out the body.It invades the critical organs, could metastasize or spread to lymph nodes.IMRT is an advanced mode of radiation therapy treatment for cancer. It delivers more conformal doses to malignant tumors sparing the critical organs by modulating the intensity of radiation beam.An automated software, HART (S. Jang et al.,2008,Med Phys 35,p.2812) was used for efficient analysis of dose volume histograms (DVH) for multiple targets and critical organs in four IMRT treatment plans for each patient. IMRT data for ten head and neck cancer patients were exported as AAPM/RTOG format files from a commercial treatment planning system at Northwestern Memorial Hospital (NMH).HART extracted DVH statistics were used to evaluate plan indices and to analyze dose tolerance of critical structures at prescription dose (PD) for each patient. Mean plan indices (n=10) were found to be in good agreement with published results for Linac based plans. The least irradiated volume at tolerance dose (TD50) was observed for brainstem and the highest volume for larynx in SIB treatment techniques. Thus HART, an open source platform, has extensive clinical implications in IMRT treatments.

  4. [Significance of measuring family satisfaction in the intensive therapy unit].

    PubMed

    Suchorzewska, Janina; Basińska, Krystyna

    2011-01-01

    Recently, numerous studies have been devoted to the issues of satisfaction of ITU patients and their families. Good relationships between the medical personnel and family members are essential for interpersonal communication built by both parties. The knowledge of rules ensuring proper relations with patients and their families is an important element of the medical staff education. To date, neither the medical curriculum nor additional training have focused on this issue. Good communication between the patients` families and physicians, thus the feeling of safety and satisfaction with the intensive care provided, should be based on controlled paternalism, provision of reliable information, confidence moulded, by mutual understanding and respect, elimination of impulsive reactions.

  5. Strategies for quality assurance of intensity modulated radiation therapy

    NASA Astrophysics Data System (ADS)

    Benedek, Hunor; Isacsson, Ulf; Olevik-Dunder, Maria; Westermark, Mathias; Hållström, Per; Olofsson, Jörgen; Gustafsson, Magnus

    2015-01-01

    In late 2011 The Swedish Society of Radiation Physics formed a working group to concentrate on the Quality Assurance of modern radiation therapy techniques. The given task was to identify and summarise the different QA strategies in Sweden and also the international recommendations. This was used to formulate recommendations for practical guidelines within Sweden. In this paper a brief summery of the group's work is presented. All the Swedish radiation therapy centres do a pre treatment verification measurement as QA for every new IMRT and VMAT plan. Physicists do it and they believe it to be time consuming. A general standpoint from all the centres was that new guidelines and legislation is needed to allow QA that does not require a measurement. Based on various international publications and recommendations the working group has presented two strategies, one where all new plans are checked through measurement and one where no measurement is needed. The measurement- based strategy is basically the same as the one used today with an extended machine QA part. The other presented strategy is process oriented where all the different parts of the treatment chain are checked separately. The final report can be found in Swedish on http://www.radiofysik.org.

  6. Intensive Insulin Therapy is Associated with Reduced Infectious Complications in Burn Patients

    PubMed Central

    Hemmila, Mark R.; Taddonio, Michael A.; Arbabi, Saman; Maggio, Paul M.; Wahl, Wendy L.

    2013-01-01

    Background Intensive insulin therapy to control blood glucose levels has reduced mortality in surgical, but not medical intensive care unit (ICU) patients. Control of blood glucose levels has also been shown to reduce morbidity in surgical ICU patients. There is very little data for use of intensive insulin therapy in the burn patient population. We sought to evaluate our experience with intensive insulin therapy in burn injured ICU patients with regard to mortality, morbidity, and use of hospital resources. Study Design Burn patients admitted to our American College of Surgeons Level 1 verified Burn Center ICU from 7/1/2004 to 6/30/2006 were studied. An intensive insulin therapy protocol was initiated for ICU patients admitted starting 7/1/2005 with a blood glucose target of 100–140 mg/dL. The two groups of patients studied were control (7/1/2004 to 6/30/2005) and intensive insulin therapy (7/1/2005 to 6/30/2006). All glucose values for the hospitalization were analyzed. Univariate and multivariate analyses were performed. Results 152 ICU patients admitted with burn injury were available for study. No difference in mortality was evident between the control and intensive insulin therapy groups. After adjusting for patient risk, the intensive insulin therapy group was found to have a decreased rate of pneumonia, ventilator-associated pneumonia, and urinary tract infection. In patients with a maximum glucose value > 140 mg/dL, the risk for an infection was significantly increased (OR 11.3, 95% CI 4–32, p-value <0.001). Presence of a maximum glucose value > 140 mg/dL was associated with a sensitivity of 91% and specificity of 62% for an infectious complication. Conclusion Intensive insulin therapy for burn injured patients admitted to the ICU was associated with a reduced incidence of pneumonia, ventilator associated pneumonia, and urinary tract infection. Intensive insulin therapy did not result in a change in mortality or length of stay when adjusting for

  7. Dosimetric comparison of volumetric modulated arc therapy and intensity-modulated radiation therapy for pancreatic malignancies

    SciTech Connect

    Ali, Arif N.; Dhabaan, Anees H.; Jarrio, Christie S.; Siddiqi, Arsalan K.; Landry, Jerome C.

    2012-10-01

    Volumetric-modulated arc therapy (VMAT) has been previously evaluated for several tumor sites and has been shown to provide significant dosimetric and delivery benefits when compared with intensity-modulated radiation therapy (IMRT). To date, there have been no published full reports on the benefits of VMAT use in pancreatic patients compared with IMRT. Ten patients with pancreatic malignancies treated with either IMRT or VMAT were retrospectively identified. Both a double-arc VMAT and a 7-field IMRT plan were generated for each of the 10 patients using the same defined tumor volumes, organs at risk (OAR) volumes, dose, fractionation, and optimization constraints. The planning tumor volume (PTV) maximum dose (55.8 Gy vs. 54.4 Gy), PTV mean dose (53.9 Gy vs. 52.1 Gy), and conformality index (1.11 vs. 0.99) were statistically similar between the IMRT and VMAT plans, respectively. The VMAT plans had a statistically significant reduction in monitor units compared with the IMRT plans (1109 vs. 498, p < 0.001). In addition, the doses to the liver, small bowel, and spinal cord were comparable between the IMRT and VMAT plans. However, the VMAT plans demonstrated a statistically significant reduction in the mean left kidney V{sub 25} (9.4 Gy vs. 2.3 Gy, p = 0.018), mean right kidney V{sub 15} (53.4 Gy vs. 45.9 Gy, p = 0.035), V{sub 20} (32.2 Gy vs. 25.5 Gy, p = 0.016), and V{sub 25} (21.7 Gy vs. 14.9 Gy, p = 0.001). VMAT was investigated in patients with pancreatic malignancies and compared with the current standard of IMRT. VMAT was found to have similar or improved dosimetric parameters for all endpoints considered. Specifically, VMAT provided reduced monitor units and improved bilateral kidney normal tissue dose. The clinical relevance of these benefits in the context of pancreatic cancer patients, however, is currently unclear and requires further investigation.

  8. Cell-stimulation therapy of lateral epicondylitis with frequency-modulated low-intensity electric current.

    PubMed

    Aliyev, R M; Geiger, G

    2012-03-01

    In addition to the routine therapy, the patients with lateral epicondylitis included into experimental group were subjected to a 12-week cell-stimulation therapy with low-intensity frequency-modulated electric current. The control group received the same routine therapy and sham stimulation (the therapeutic apparatus was not energized). The efficiency of this microcurrent therapy was estimated by comparing medical indices before therapy and at the end of a 12-week therapeutic course using a 10-point pain severity numeric rating scale (NRS) and Roles-Maudsley pain score. The study revealed high therapeutic efficiency of cell-stimulation with low-intensity electric current resulting probably from up-regulation of intracellular transmitters, interleukins, and prostaglandins playing the key role in the regulation of inflammation.

  9. [Complications of resuscitation and intensive therapy in infants (proceedings)].

    PubMed

    Ivanovskaia, T E; Kogoĭ, T F; Pokrovskaia, L Ia; Larina, T M

    1980-01-01

    Most frequent complications of infusion therapy in children include thrombosis and thrombophlebitis of the umbilical and subclavian veins. In the perinatal period thrombophlebitis of the umbilical vein is due to exogenous infection and becomes the source of umbilical sepsis. Thrombophlebitis of the subclavian vein in nurslings results more frequently from endogenous infection. Because of morpho-functional immaturity in infancy, hyperhydration of tissues is extreme, with vacuolar dystrophy of cells up to their necrosis, particularly in the liver and kidneys. Artificial pulmonary ventilation (APV), particularly in premature newborns, is frequently accompanied by breaks of alveolar septae, development of bullous and interstitial emphysema, pneumothorax. In deeply premature infants APV may be ineffective because of immaturity of the lung tissue.

  10. [Solcoseryl in intensive therapy in severe craniocerebral trauma].

    PubMed

    Marusanov, V E; Miroshnichenko, A G; Nikolau, S A; Petrova, N V; Bichun, A B

    2000-01-01

    The state of processes of lipid peroxidation and antioxidant defense was studied in patients with severe isolated craniocerebral closed injury. It was found that starting from the first days in the hospital the patients demonstrated marked alterations in the thiol-disulfide and ascorbate metabolism, activation of lipid peroxidation processes and lower antioxidant defense. The use of Solcoseryl as a component of the antioxidant therapy in treatment of the above mentioned category of patients resulted in considerably better indices of the thiol-disulfide metabolism. The isolated use of Solcoseryl failed to influence the ascorbate metabolism and lipid peroxidation. Solcoseryl used in combination with the ascorbic acid led to normalization of the thiol-disulfide and ascorbade metabolism without influencing the lipid peroxidation processes. Combined use of Solcoseryl and ascorbic acid promoted normalization of the neurological status and stabilization of the arterial pressure level.

  11. Physical therapy in critically ill adult patients: recommendations from the Brazilian Association of Intensive Care Medicine Department of Physical Therapy.

    PubMed

    França, Eduardo Ériko Tenório de; Ferrari, Francimar; Fernandes, Patrícia; Cavalcanti, Renata; Duarte, Antonio; Martinez, Bruno Prata; Aquim, Esperidião Elias; Damasceno, Marta Cristina Paulete

    2012-03-01

    Complications from immobility in intensive care unit patients contribute to functional decline, increased healthcare costs, reduced quality of life and higher post-discharge mortality. Physical therapy focuses on promoting recovery and preserving function, and it may minimize the impact of these complications. A group of Brazilian Association of Intensive Care Medicine physical therapy experts developed this document that contains minimal physical therapy recommendations appropriate to the Brazilian real-world clinical situation. Prevention and treatment of atelectasis, procedures related to the removal of secretions and treatment of conditions related to physical deconditioning and functional decline are discussed. Equally important is the consideration that prescribing and executing activities, mobilizations and exercises are roles of the physical therapist, whose diagnosis should precede any intervention.

  12. A Randomized Controlled Trial of 7-Day Intensive and Standard Weekly Cognitive Therapy for PTSD and Emotion-Focused Supportive Therapy

    PubMed Central

    Ehlers, Anke; Hackmann, Ann; Grey, Nick; Wild, Jennifer; Liness, Sheena; Albert, Idit; Deale, Alicia; Stott, Richard; Clark, David M.

    2014-01-01

    Objective Psychological treatments for posttraumatic stress disorder (PTSD) are usually delivered once or twice weekly over several months. It is unclear whether they can be successfully delivered over a shorter period of time. This clinical trial had two goals, (1) to investigate the acceptability and efficacy of a 7-day intensive version of cognitive therapy for PTSD, and (2) to investigate whether cognitive therapy has specific treatment effects by comparing intensive and standard weekly cognitive therapy with an equally credible alternative treatment. Method Patients with chronic PTSD (N=121) were randomly allocated to 7-day intensive or standard 3-month weekly cognitive therapy for PTSD, 3-month weekly emotion-focused supportive therapy, or a 14-week waitlist condition. Primary outcomes were PTSD symptoms and diagnosis as assessed by independent assessors and self-report. Secondary outcomes were disability, anxiety, depression, and quality of life. Measures were taken at initial assessment, 6 weeks and 14 weeks (post-treatment/wait). For groups receiving treatment, measures were also taken at 3 weeks, and follow-ups at 27 and 40 weeks after randomization. All analyses were intent-to-treat. Results At post-treatment/wait assessment, 73%, 77%, 43%, 7% of the intensive cognitive therapy, standard cognitive therapy, supportive therapy, and waitlist groups, respectively, had recovered from PTSD. All treatments were well tolerated and were superior to waitlist on all outcome measures, with the exception of no difference between supportive therapy and waitlist on quality of life. For primary outcomes, disability and general anxiety, intensive and standard cognitive therapy were superior to supportive therapy. Intensive cognitive therapy achieved faster symptom reduction and comparable overall outcomes to standard cognitive therapy. Conclusions Cognitive therapy for PTSD delivered intensively over little more than a week is as effective as cognitive therapy delivered

  13. An individualized intermittent intensive physical therapy schedule for a child with spastic quadriparesis.

    PubMed

    Rahlin, Mary

    2011-10-01

    Current research literature supports the use of intensive physical therapy (PT) for children with cerebral palsy (CP) but lacks consensus on the selection of a specific therapy schedule. The purpose of this case report was to describe the use of an individualized intermittent intensive PT schedule for a child with CP who was otherwise seen following a traditional, two times per week, schedule. The patient was a 4.5-year-old girl with spastic quadriparesis, GMFCS level III. The new schedule was tried over a 3-month period. Each of the 3 months included a 2-week, five times per week intensive therapy phase, followed by a 2-week resting phase. Outcomes were assessed by using the GMFM-66 and by documenting the attainment of functional gross motor skills related to the patient's PT goals. Intervention included TAMO therapy and family instruction. The patient demonstrated a gradual increase in GMFM-66 scores throughout the 9-month period covered by this case report, with the greatest mean change score obtained when the intermittent intensive therapy schedule was used. Acquired skills were retained and even improved during the resting phases. The child's parents expressed their interest in using the new PT schedule in the future.

  14. Hypercalcemia in the Intensive Care Unit: A Review of Pathophysiology, Diagnosis, and Modern Therapy.

    PubMed

    Maier, Joshua D; Levine, Steven N

    2015-07-01

    Hypercalcemia may be seen in a variety of clinical settings and often requires intensive management when serum calcium levels are dramatically elevated. All of the many etiologies of mild hypercalcemia can lead to severe hypercalcemia. Knowledge of the physiologic mechanisms involved in maintaining normocalcemia and basic pathophysiology is essential for making a timely diagnosis and hence prompt institution of etiology-specific therapy. The development of new medications and critical reviews of traditional therapies have changed the treatment paradigm for severe hypercalcemia, calling for a more limited role for aggressive isotonic fluid administration and furosemide and an expanded role for calcitonin and the bisphosphonates. Experimental therapies such as denosumab show promise.

  15. [Intensity-modulated radiation therapy and stereotactic body radiation therapy for head and neck tumors: evidence-based medicine].

    PubMed

    Lapierre, A; Martin, F; Lapeyre, M

    2014-10-01

    Over the last decade, there have been many technical advances in radiation therapy, such as the spread of intensity-modulated conformal radiotherapy, and the rise of stereotactic body radiation therapy. By allowing better dose-to-target conformation and thus better organs at risk-sparing, these techniques seem very promising, particularly in the field of head and neck tumors. The present work aims at analyzing the level of evidence and recommendation supporting the use of high-technology radiotherapy in head and neck neoplasms, by reviewing the available literature.

  16. Comparison of High-Intensity Laser Therapy and Ultrasound Treatment in the Patients with Lumbar Discopathy

    PubMed Central

    Boyraz, Ismail; Yildiz, Ahmet; Koc, Bunyamin

    2015-01-01

    The aim of the present study was to evaluate the efficiency of high intensity laser and ultrasound therapy in patients who were diagnosed with lumbar disc herniation and who were capable of performing physical exercises. 65 patients diagnosed with lumbar disc were included in the study. The patients were randomly divided into three groups: Group 1 received 10 sessions of high intensity laser to the lumbar region, Group 2 received 10 sessions of ultrasound, and Group 3 received medical therapy for 10 days and isometric lumbar exercises. The efficacy of the treatment modalities was compared with the assessment of the patients before the therapy at the end of the therapy, and in third month after the therapy. Comparing the changes between groups, statically significant difference was observed in MH (mental health) parameter before treatment between Groups 1 and 2 and in MH parameter and VAS score in third month of the therapy between Groups 2 and 3. However, the evaluation of the patients after ten days of treatment did not show significant differences between the groups compared to baseline values. We found that HILT, ultrasound, and exercise were efficient therapies for lumbar discopathy but HILT and ultrasound had longer effect on some parameters. PMID:25883952

  17. Two-Day, Intensive Cognitive-Behavioral Therapy for Panic Disorder: A Case Study

    ERIC Educational Resources Information Center

    Deacon, Brett

    2007-01-01

    Cognitive-behavioral therapy (CBT) is a highly effective treatment for panic disorder. However, few patients have access to this treatment, particularly those living in rural areas. In a pilot study, the author previously described the efficacy of a 2-day, intensive, exposure-based CBT intervention that was developed for the purpose of delivering…

  18. Intense pulsed light therapy (IPL) induced iritis following treatment for a medial canthal capillary malformation.

    PubMed

    Crabb, Matthew; Chan, Weng Onn; Taranath, Deepa; Huilgol, Shyamala C

    2014-11-01

    The popularity of intense pulsed light (IPL) therapy continues to increase due to its relative safety, high skin coverage rate and ability to treat both vascular and pigmented lesions. An often-overlooked risk is the potential for IPL-induced ocular damage. The damage sustained can cause significant, persistent morbidity and can occur even with very limited IPL exposure to the eye.

  19. Increased Intensity of Physical Therapy for a Child with Gross Motor Developmental Delay: A Case Report

    ERIC Educational Resources Information Center

    Schreiber, Joe

    2004-01-01

    Background and Purpose: The intensity of physical therapy provided for children in early intervention (EI) programs may be influenced by a number of factors. In an individualized program, however, some children and families may benefit from an increased frequency of services. The purpose of this case report was to systematically document and…

  20. Bioactive vegetable proteins and peptides in lipid-lowering; nutraceutical potential.

    PubMed

    Ruiz Ruiz, Jorge Carlos; Betancur Ancona, David Abram; Segura Campos, Maira Rubi

    2014-04-01

    As the last century saw a decline in the burden of nutritional deficiency and infectious disease, the global burden of chronic disease, cardiovascular disease (CVD) in particular, is increasing. CVD is the leading cause of death in the developed countries. Significant research efforts on the prevention and treatment of this disease have identified elevated plasma cholesterol as a primary risk factor for CVD. Although CVD progresses with hypercholesterolemia, it seems possibility to delay and prevent its development through improvement of diet. Recent findings demonstrate that protein concentrates, protein hydrolysates, and peptides derived from vegetables may promote a significant decrease in blood cholesterol concentration. This reduction in cholesterol and lipid levels by protein, protein hydrolysates, and peptides can be the result of dietary changes, reduced cholesterol biosynthesis, changes in bile acid synthesis, and reduced absorption of lipid cholesterol and bile acid. Combination drug/diet therapies may reduce the number of drug prescriptions, the progressive rise in "optimal" drug dosage and costs associated with pharmaceutical management of disease. These bioactive vegetable proteins, hydrolysates and peptides may be used in formulation of functional foods, nutraceuticals, and natural drugs because of their health benefit effects suggesting their use as an alternative in treatment of various dyslipidemias, and a potential agent for reducing cardiovascular diseases risk factors.

  1. Ethanolic Extract of Vitis thunbergii Exhibits Lipid Lowering Properties via Modulation of the AMPK-ACC Pathway in Hypercholesterolemic Rabbits

    PubMed Central

    Pan, Chun-Hsu; Tsai, Chia-Hua; Lin, Wen-Hsin; Chen, Guo-Yan; Wu, Chieh-Hsi

    2012-01-01

    Vitis thunbergii (VT) is a wild grape that has been shown to provide various cardioprotective effects. The present study was designed to examine whether a VT extract could reduce serum lipid levels and prevent atherogenesis in a hypercholesterolemic rabbit model. At the end of an 8-week study, our results showed that a VT extract supplement markedly suppressed the serum levels of cholesterol and low-density lipoprotein, reduced lipid accumulation in liver tissues, and limited aortic fatty streaks. Our findings suggest that the VT extract activated AMPK (5′-adenosine monophosphate-activated protein kinase) with subsequent inhibition of the activation of ACC (acetyl-CoA carboxylase). Our results suggest that this VT extract could be further developed as a potential lipid-lowering agent and as a natural health food to prevent atherogenesis. PMID:22536284

  2. Electrocardiographic measures of left ventricular hypertrophy in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial.

    PubMed

    Ernst, Michael E; Davis, Barry R; Soliman, Elsayed Z; Prineas, Ronald J; Okin, Peter M; Ghosh, Alokananda; Cushman, William C; Einhorn, Paula T; Oparil, Suzanne; Grimm, Richard H

    2016-12-01

    Left ventricular hypertrophy (LVH) predicts cardiovascular risk in hypertensive patients. We analyzed baseline/follow-up electrocardiographies in 26,376 Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial participants randomized to amlodipine (A), lisinopril (L), or chlorthalidone (C). Prevalent/incident LVH was examined using continuous and categorical classifications of Cornell voltage. At 2 and 4 years, prevalence of LVH in the C group (5.57%; 6.14%) was not statistically different from A group (2 years: 5.47%; P = .806, 4 years: 6.54%; P = .857) or L group (2 years: 5.64%; P = .857, 4 years: 6.50%; P = .430). Incident LVH followed similarly, with no difference at 2 years for C (2.99%) compared to A (2.57%; P = .173) or L (3.16%; P = .605) and at 4 years (C = 3.52%, A = 3.29%, L = 3.71%; P = .521 C vs. A, P = .618 C vs. L). Mean Cornell voltage decreased comparably across treatment groups (Δ baseline, 2 years = +3 to -27 μV, analysis of variance P = .8612; 4 years = +10 to -17 μV, analysis of variance P = .9692). We conclude that risk reductions associated with C treatment in secondary end points of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial cannot be attributed to differential improvements in electrocardiography LVH.

  3. Long-term administration of inulin-type fructans has no significant lipid-lowering effect in normolipidemic humans.

    PubMed

    Forcheron, Fabien; Beylot, Michel

    2007-08-01

    Short-term studies have shown that the addition to diet of inulin-type fructans, a nondigestible carbohydrate, may have a plasma lipid-lowering effect in humans. Whether this beneficial effect persists during long-term administration has not been determined. The study was aimed at determining whether a prolonged (6 months) administration of inulin-type fructans to healthy subjects has a lipid-lowering action. In a double-blind, randomized, placebo-controlled study, 17 healthy subjects were studied before and after 6 months of daily administration of placebo (8 subjects) or 10 g of a mix of inulin and oligofructose (9 subjects). During this 6-month period, they consumed their usual diet and did not modify their everyday way of life. We measured plasma lipid concentrations; cholesterol synthesis and hepatic lipogenesis; and adipose tissue and circulating mononuclear cell messenger RNA concentrations of key regulatory genes of cholesterol metabolism. Compared with the administration of placebo, the administration of inulin-type fructans had no effect on plasma triacylglycerol concentrations and hepatic lipogenesis and induced only a nonsignificant trend for decreased plasma total and low-density lipoprotein cholesterol levels and increased high-density lipoprotein cholesterol concentration. Cholesterol synthesis was not significantly modified. Of all the messenger RNA concentrations measured, none was significantly modified by the administration of inulin-type fructans. In conclusion, contrary to what was observed in short-term studies, we observed no significant beneficial effect of a long-term (6-month) administration of inulin-type fructans on plasma lipids in healthy human subjects.

  4. Correlation between Ultrasound Reflection Intensity and Tumor Ablation Ratio of Late-Stage Pancreatic Carcinoma in HIFU Therapy: Dynamic Observation on Ultrasound Reflection Intensity

    PubMed Central

    Ge, Hui-Yu; Miao, Li-Ying; Wang, Jin-Rui; Xiong, Liu-Lin; Yan, Fang; Zheng, Cui-Shan; Jia, Jian-Wen; Cui, Li-Gang; Chen, Wen

    2013-01-01

    The minimally invasive high-intensity focused ultrasound (HIFU) therapy is thermal ablation treatment for late-stage pancreatic carcinoma with widely recognized safety and effectiveness, but there are currently no instant assessment methods for its ablation effect. It is vital to find a real-time high-sensitive assessment method. This research aims to dynamically observe the variation rules of ultrasound reflection intensity, analyze the correlation between ultrasound reflection intensity and tumor ablation ratio, and find out the value of ultrasound reflection intensity in prognosis of HIFU ablation effect. HIFU intermittent therapies were retrospectively analyzed for 31 subjects with late-stage pancreatic carcinoma from March 2007 to December 2009 in the study. The variation rules of the ultrasound reflection intensity during HIFU therapy were summarized and the correlation between ultrasound reflection intensity and tumor ablation ratio was analyzed based on the tumor ablation ratio indicated by CT scanning. The conclusion is that variation of ultrasound reflection intensity can be used for initial assessment of tumor ablation in HIFU therapy and early prognosis of overall HIFU ablation, providing important clinical basis for improving safety and effectiveness of HIFU therapy. Ultrasound can work as a real-time imaging instrument for observation of HIFU ablation effect in treating late-stage pancreatic carcinoma. PMID:24453916

  5. Correlation between ultrasound reflection intensity and tumor ablation ratio of late-stage pancreatic carcinoma in HIFU therapy: dynamic observation on ultrasound reflection intensity.

    PubMed

    Ge, Hui-Yu; Miao, Li-Ying; Wang, Jin-Rui; Xiong, Liu-Lin; Yan, Fang; Zheng, Cui-Shan; Jia, Jian-Wen; Cui, Li-Gang; Chen, Wen

    2013-01-01

    The minimally invasive high-intensity focused ultrasound (HIFU) therapy is thermal ablation treatment for late-stage pancreatic carcinoma with widely recognized safety and effectiveness, but there are currently no instant assessment methods for its ablation effect. It is vital to find a real-time high-sensitive assessment method. This research aims to dynamically observe the variation rules of ultrasound reflection intensity, analyze the correlation between ultrasound reflection intensity and tumor ablation ratio, and find out the value of ultrasound reflection intensity in prognosis of HIFU ablation effect. HIFU intermittent therapies were retrospectively analyzed for 31 subjects with late-stage pancreatic carcinoma from March 2007 to December 2009 in the study. The variation rules of the ultrasound reflection intensity during HIFU therapy were summarized and the correlation between ultrasound reflection intensity and tumor ablation ratio was analyzed based on the tumor ablation ratio indicated by CT scanning. The conclusion is that variation of ultrasound reflection intensity can be used for initial assessment of tumor ablation in HIFU therapy and early prognosis of overall HIFU ablation, providing important clinical basis for improving safety and effectiveness of HIFU therapy. Ultrasound can work as a real-time imaging instrument for observation of HIFU ablation effect in treating late-stage pancreatic carcinoma.

  6. Radiation-Induced Cancers From Modern Radiotherapy Techniques: Intensity-Modulated Radiotherapy Versus Proton Therapy

    SciTech Connect

    Yoon, Myonggeun; Ahn, Sung Hwan; Kim, Jinsung; Shin, Dong Ho; Park, Sung Yong; Lee, Se Byeong; Shin, Kyung Hwan; Cho, Kwan Ho

    2010-08-01

    Purpose: To assess and compare secondary cancer risk resulting from intensity-modulated radiotherapy (IMRT) and proton therapy in patients with prostate and head-and-neck cancer. Methods and Materials: Intensity-modulated radiotherapy and proton therapy in the scattering mode were planned for 5 prostate caner patients and 5 head-and-neck cancer patients. The secondary doses during irradiation were measured using ion chamber and CR-39 detectors for IMRT and proton therapy, respectively. Organ-specific radiation-induced cancer risk was estimated by applying organ equivalent dose to dose distributions. Results: The average secondary doses of proton therapy for prostate cancer patients, measured 20-60cm from the isocenter, ranged from 0.4 mSv/Gy to 0.1 mSv/Gy. The average secondary doses of IMRT for prostate patients, however, ranged between 3 mSv/Gy and 1 mSv/Gy, approximately one order of magnitude higher than for proton therapy. Although the average secondary doses of IMRT were higher than those of proton therapy for head-and-neck cancers, these differences were not significant. Organ equivalent dose calculations showed that, for prostate cancer patients, the risk of secondary cancers in out-of-field organs, such as the stomach, lungs, and thyroid, was at least 5 times higher for IMRT than for proton therapy, whereas the difference was lower for head-and-neck cancer patients. Conclusions: Comparisons of organ-specific organ equivalent dose showed that the estimated secondary cancer risk using scattering mode in proton therapy is either significantly lower than the cases in IMRT treatment or, at least, does not exceed the risk induced by conventional IMRT treatment.

  7. Defining and Treating Older Adults with Acute Myeloid Leukemia Who Are Ineligible for Intensive Therapies

    PubMed Central

    Pettit, Kristen; Odenike, Olatoyosi

    2015-01-01

    Although acute myeloid leukemia (AML) is primarily a disease of older adults (age ≥60 years), the optimal treatment for older adults remains largely undefined. Intensive chemotherapy is rarely beneficial for frail older adults or those with poor-risk disease, but criteria that define fitness and/or appropriateness for intensive chemotherapy remain to be standardized. Evaluation of disease-related and patient-specific factors in the context of clinical decision making has therefore been largely subjective. A uniform approach to identify those patients most likely to benefit from intensive therapies is needed. Here, we review currently available objective measures to define older adults with AML who are ineligible for intensive chemotherapy, and discuss promising investigational approaches. PMID:26697412

  8. Robust plan optimization using edge-enhanced intensity for intrafraction organ deformation in prostate intensity-modulated radiation therapy

    PubMed Central

    Kizaki, Hisao; Aboshi, Keiko; Tsujii, Mari; Yamada, Yuji; Tamari, Keisuke; Seo, Yuji; Isohashi, Fumiaki; Yoshioka, Yasuo; Ogawa, Kazuhiko

    2017-01-01

    This study evaluated a method for prostate intensity-modulated radiation therapy (IMRT) based on edge-enhanced (EE) intensity in the presence of intrafraction organ deformation using the data of 37 patients treated with step-and-shoot IMRT. On the assumption that the patient setup error was already accounted for by image guidance, only organ deformation over the treatment course was considered. Once the clinical target volume (CTV), rectum, and bladder were delineated and assigned dose constraints for dose optimization, each voxel in the CTV derived from the DICOM RT-dose grid could have a stochastic dose from the different voxel location according to the probability density function as an organ deformation. The stochastic dose for the CTV was calculated as the mean dose at the location through changing the voxel location randomly 1000 times. In the EE approach, the underdose region in the CTV was delineated and optimized with higher dose constraints that resulted in an edge-enhanced intensity beam to the CTV. This was compared to a planning target volume (PTV) margin (PM) approach in which a CTV to PTV margin equivalent to the magnitude of organ deformation was added to obtain an optimized dose distribution. The total monitor units, number of segments, and conformity index were compared between the two approaches, and the dose based on the organ deformation of the CTV, rectum, and bladder was evaluated. The total monitor units, number of segments, and conformity index were significantly lower with the EE approach than with the PM approach, while maintaining the dose coverage to the CTV with organ deformation. The dose to the rectum and bladder were significantly reduced in the EE approach compared with the PM approach. We conclude that the EE approach is superior to the PM with regard to intrafraction organ deformation. PMID:28282417

  9. The Effectiveness of Cervical Spondylosis Therapy with Saunders Traction Device and High-Intensity Laser Therapy: A Randomized Controlled Trial

    PubMed Central

    Haładaj, Robert; Pingot, Mariusz; Topol, Mirosław

    2017-01-01

    Background Among all spinal therapies, treatment of the cervical segment is the most difficult. The cervical segment is particularly sensitive to injuries and pain, and it also requires special care due to its great mobility and most delicate construction. The aim of this research was to evaluate analgesic efficacy and improvement of active mobility of the cervical spine after traction therapy with the Saunders device and high-intensity laser therapy (HILT) immediately after therapy, and in short-, medium-, and long-term follow-up in patients with cervical spondylosis. Material/Methods The study included 174 patients (114 women and 60 men) aged 24–67 years. The patients were divided into two randomized groups. In group I (88 subjects) traction therapy with the Saunders device was applied, and in group II (86 subjects) HILT was applied. The measurement of the range of cervical spine movement, a subjective visual scale for pain (Visual Analog Scale [VAS]), and the Neck Disability Index-Polish Version (NDI) questionnaire were used. Results The results obtained by the Saunders and HILT methods were similar immediately after the therapy and after 4 weeks (the medium-term follow-up). However, in long-term follow-up, there was a significant increase in the maintenance of positive therapeutic effects with the HILT method. Conclusions Both therapeutic methods improved the efficiency and demonstrated analgesic efficacy in patients with cervical spondylosis immediately and in the medium term after the therapy. HILT was more effective than the Saunders method in long-term follow-up. PMID:28104903

  10. A comparison of intensity modulated x-ray therapy to intensity modulated proton therapy for the delivery of non-uniform dose distributions

    NASA Astrophysics Data System (ADS)

    Flynn, Ryan

    2007-12-01

    The distribution of biological characteristics such as clonogen density, proliferation, and hypoxia throughout tumors is generally non-uniform, therefore it follows that the optimal dose prescriptions should also be non-uniform and tumor-specific. Advances in intensity modulated x-ray therapy (IMXT) technology have made the delivery of custom-made non-uniform dose distributions possible in practice. Intensity modulated proton therapy (IMPT) has the potential to deliver non-uniform dose distributions as well, while significantly reducing normal tissue and organ at risk dose relative to IMXT. In this work, a specialized treatment planning system was developed for the purpose of optimizing and comparing biologically based IMXT and IMPT plans. The IMXT systems of step-and-shoot (IMXT-SAS) and helical tomotherapy (IMXT-HT) and the IMPT systems of intensity modulated spot scanning (IMPT-SS) and distal gradient tracking (IMPT-DGT), were simulated. A thorough phantom study was conducted in which several subvolumes, which were contained within a base tumor region, were boosted or avoided with IMXT and IMPT. Different boosting situations were simulated by varying the size, proximity, and the doses prescribed to the subvolumes, and the size of the phantom. IMXT and IMPT were also compared for a whole brain radiation therapy (WBRT) case, in which a brain metastasis was simultaneously boosted and the hippocampus was avoided. Finally, IMXT and IMPT dose distributions were compared for the case of non-uniform dose prescription in a head and neck cancer patient that was based on PET imaging with the Cu(II)-diacetyl-bis(N4-methylthiosemicarbazone (Cu-ATSM) hypoxia marker. The non-uniform dose distributions within the tumor region were comparable for IMXT and IMPT. IMPT, however, was capable of delivering the same non-uniform dose distributions within a tumor using a 180° arc as for a full 360° rotation, which resulted in the reduction of normal tissue integral dose by a factor of

  11. Proton therapy versus intensity modulated x-ray therapy in the treatment of prostate cancer: Estimating secondary cancer risks

    NASA Astrophysics Data System (ADS)

    Fontenot, Jonas David

    External beam radiation therapy is used to treat nearly half of the more than 200,000 new cases of prostate cancer diagnosed in the United States each year. During a radiation therapy treatment, healthy tissues in the path of the therapeutic beam are exposed to high doses. In addition, the whole body is exposed to a low-dose bath of unwanted scatter radiation from the pelvis and leakage radiation from the treatment unit. As a result, survivors of radiation therapy for prostate cancer face an elevated risk of developing a radiogenic second cancer. Recently, proton therapy has been shown to reduce the dose delivered by the therapeutic beam to normal tissues during treatment compared to intensity modulated x-ray therapy (IMXT, the current standard of care). However, the magnitude of stray radiation doses from proton therapy, and their impact on this incidence of radiogenic second cancers, was not known. The risk of a radiogenic second cancer following proton therapy for prostate cancer relative to IMXT was determined for 3 patients of large, median, and small anatomical stature. Doses delivered to healthy tissues from the therapeutic beam were obtained from treatment planning system calculations. Stray doses from IMXT were taken from the literature, while stray doses from proton therapy were simulated using a Monte Carlo model of a passive scattering treatment unit and an anthropomorphic phantom. Baseline risk models were taken from the Biological Effects of Ionizing Radiation VII report. A sensitivity analysis was conducted to characterize the uncertainty of risk calculations to uncertainties in the risk model, the relative biological effectiveness (RBE) of neutrons for carcinogenesis, and inter-patient anatomical variations. The risk projections revealed that proton therapy carries a lower risk for radiogenic second cancer incidence following prostate irradiation compared to IMXT. The sensitivity analysis revealed that the results of the risk analysis depended only

  12. Cost considerations for the use of low-air-loss bed therapy in adult intensive care.

    PubMed

    Hibbert, C L; Edbrooke, D L; Corcoran, M; Bright, N N; Kingsley, J N

    1999-06-01

    The aim of this study was to consider the costs of low-air-loss bed therapy in the adult intensive care unit (ICU). A retrospective cost analysis was performed on 269 consecutive patients, 63 of whom had received low-air-loss bed therapy. Patients' APACHE II scores, length of stay (LOS), average daily TISS and ICU outcomes were also collected. Patients' APACHE II and LOS were further studied using odds ratios to test for an association between these factors and likelihood of receiving bed therapy. A prospective 10-week study to identify the amount of nursing time spent repositioning patients was also performed. The results of this study found the bed therapy to represent approximately 3% of the total average cost of care per patient. Patients requiring the bed therapy had higher APACHE II scores on admission, higher average daily TISS points and a longer length of ICU stay. Study of the odds ratios would suggest that the likelihood of patients receiving low-air-loss bed therapy increases if their APACHE II score on admission is between 11 and 20 and they stay > 4.5 days in the ICU. The results of the prospective study found the daily cost of repositioning patients to be 172.80 Pounds per patient.

  13. Hypocaloric enteral nutrition protects against hypoglycemia associated with intensive insulin therapy better than intravenous dextrose.

    PubMed

    Kauffmann, Rondi M; Hayes, Rachel M; VanLaeken, Amanda H; Norris, Patrick R; Diaz, Jose J; May, Addison K; Collier, Bryan R

    2014-11-01

    Intensive insulin therapy treats hyperglycemia but increases the risk of hypoglycemia. Typically, intravenous dextrose is given to prevent hypoglycemia; however, enteral nutrition is preferred. We hypothesized that the provision of hypocaloric enteral nutrition would protect against hypoglycemia. A retrospective analysis was performed evaluating patients treated with intensive insulin therapy comparing the use of enteral nutrition versus a dextrose-only intravenous solution. Nutrition in the 2 hours before each blood glucose test was assessed, and the association with hypoglycemia (50 mg/dL or less) evaluated. Risk of hypoglycemia as a function of nutrition type and rate was estimated by multivariable regression. A total of 26,140 blood glucose tests were collected on 1289 patients. Hypoglycemia occurred in 6.4 per cent of patients. In regression models, enteral nutrition was the strongest protective factor against hypoglycemia (P < 0.001) with the largest risk reduction (steepest portion of the curve) occurring at 60 per cent goal. Hypocaloric enteral nutrition showed a greater risk reduction than a peripheral dextrose-only intravenous solution alone. In the setting of intensive insulin therapy, the provision of enteral nutrition, even if hypocaloric, is sufficient to protect against hypoglycemia. Future prospective studies should evaluate the efficacy of enteral nutrition in reducing the risk of hypoglycemia and whether lower rates of hypoglycemia correspond to improved outcomes.

  14. Effectiveness of High Intensity Laser Therapy for Reduction of Pain in Knee Osteoarthritis

    PubMed Central

    2016-01-01

    Introduction. Osteoarthritis is the most common type of arthritis. It is the main cause of chronic musculoskeletal pain and disability among the elderly population. Aim. This is a pilot, randomized clinical study about the effect of high intensity laser therapy in patients with osteoarthritis of the knee (OA of the knee). Material and Method. 72 patients (aged between 39 and 83 years) with (clinically and radiographically proved) OA of the knee were included in the study. They were randomized in two groups: therapeutic (test) one (n = 37, 65,11 ± 1,40 (mean ± SD) years old; patients were treated with HILT) and control group (n = 35, 64,71 ± 1,98; patients receive sham laser). Both groups had seven sessions of treatment. VAS and dolorimetry were used for assessment of pain before and after the therapy. Pedobarometric analysis (static and dynamic) was used to assess comparatively the contact surface area and maximum pressure under the heel. Results. Pain levels measured by VAS and dolorimetry decreased significantly in the therapeutic group after seven days of treatment (p< 0,001). Conclusion. The results after seven days of treatment show more intensive and cumulative effect after the application of high intensity laser therapy in comparison to sham laser. This is the reason why HILT can be a method of choice in the treatment of gonarthrosis. PMID:28096711

  15. Nonlinear 3-D simulation of high-intensity focused ultrasound therapy in the Kidney.

    PubMed

    Suomi, Visa; Jaros, Jiri; Treeby, Bradley; Cleveland, Robin

    2016-08-01

    Kidney cancer is a severe disease which can be treated non-invasively using high-intensity focused ultrasound (HIFU) therapy. However, tissue in front of the transducer and the deep location of kidney can cause significant losses to the efficiency of the treatment. The effect of attenuation, refraction and reflection due to different tissue types on HIFU therapy of the kidney was studied using a nonlinear ultrasound simulation model. The geometry of the tissue was derived from a computed tomography (CT) dataset of a patient which had been segmented for water, bone, soft tissue, fat and kidney. The combined effect of inhomogeneous attenuation and soundspeed was found to result in an 11.0 dB drop in spatial peak-temporal average (SPTA) intensity in the kidney compared to pure water. The simulation without refraction effects showed a 6.3 dB decrease indicating that both attenuation and refraction contribute to the loss in focal intensity. The losses due to reflections at soft tissue interfaces were less than 0.1 dB. Focal point shifting due to refraction effects resulted in -1.3, 2.6 and 1.3 mm displacements in x-, y- and z-directions respectively. Furthermore, focal point splitting into several smaller subvolumes was observed. The total volume of the secondary focal points was approximately 46% of the largest primary focal point. This could potentially lead to undesired heating outside the target location and longer therapy times.

  16. Hypocaloric Enteral Nutrition Protects Against Hypoglycemia Associated with Intensive Insulin Therapy Better Than Intravenous Dextrose

    PubMed Central

    Kauffmann, Rondi M.; Hayes, Rachel M.; Vanlaeken, Amanda H.; Norris, Patrick R.; Diaz, Jose J.; May, Addison K.; Collier, Bryan R.

    2015-01-01

    Intensive insulin therapy treats hyperglycemia but increases the risk of hypoglycemia. Typically, intravenous dextrose is given to prevent hypoglycemia; however, enteral nutrition is preferred. We hypothesized that the provision of hypocaloric enteral nutrition would protect against hypoglycemia. A retrospective analysis was performed evaluating patients treated with intensive insulin therapy comparing the use of enteral nutrition versus a dextrose-only intravenous solution. Nutrition in the 2 hours before each blood glucose test was assessed, and the association with hypoglycemia (50 mg/dL or less) evaluated. Risk of hypoglycemia as a function of nutrition type and rate was estimated by multivariable regression. A total of 26,140 blood glucose tests were collected on 1289 patients. Hypoglycemia occurred in 6.4 per cent of patients. In regression models, enteral nutrition was the strongest protective factor against hypoglycemia (P < 0.001) with the largest risk reduction (steepest portion of the curve) occurring at 60 per cent goal. Hypocaloric enteral nutrition showed a greater risk reduction than a peripheral dextrose-only intravenous solution alone. In the setting of intensive insulin therapy, the provision of enteral nutrition, even if hypocaloric, is sufficient to protect against hypoglycemia. Future prospective studies should evaluate the efficacy of enteral nutrition in reducing the risk of hypoglycemia and whether lower rates of hypoglycemia correspond to improved outcomes. PMID:25347500

  17. Physical therapy observation and assessment in the neonatal intensive care unit.

    PubMed

    Byrne, Eilish; Campbell, Suzann K

    2013-02-01

    This article presents the elements of the Observation and Assessment section of the Infant Care Path for Physical Therapy in the Neonatal Intensive Care Unit (NICU). The types of physical therapy assessments presented in this path are evidence-based and the suggested timing of these assessments is primarily based on practice knowledge from expert therapists, with supporting evidence cited. Assessment in the NICU begins with a thorough review of the health care record. Assessment proceeds by using the least invasive methods of gathering the behavioral, developmental, physiologic, and musculoskeletal information needed to implement a physical therapy plan of care. As the neonate matures and can better tolerate handling, assessment methods include lengthier standardized tests with the psychometric properties needed for informing diagnosis and intervention planning. Standardized tests and measures for screening, diagnosis, and developmental assessment are appraised and special considerations for assessment of neonates in the NICU are discussed.

  18. Intensive sleep deprivation and cognitive behavioral therapy for pharmacotherapy refractory insomnia in a hospitalized patient.

    PubMed

    Breitstein, Joshua; Penix, Brandon; Roth, Bernard J; Baxter, Tristin; Mysliwiec, Vincent

    2014-06-15

    The case of a 59-year-old woman psychiatrically hospitalized with comorbid insomnia, suicidal ideation, and generalized anxiety disorder is presented. Pharmacologic therapies were unsuccessful for treating insomnia prior to and during hospitalization. Intensive sleep deprivation was initiated for 40 consecutive hours followed by a recovery sleep period of 8 hours. Traditional components of cognitive behavioral therapy for insomnia (CBTi), sleep restriction, and stimulus control therapies, were initiated on the ward. After two consecutive nights with improved sleep, anxiety, and absence of suicidal ideation, the patient was discharged. She was followed in the sleep clinic for two months engaging in CBTi. Treatment resulted in substantial improvement in her insomnia, daytime sleepiness, and anxiety about sleep. Sleep deprivation regimens followed by a restricted sleep recovery period have shown antidepressant effects in depressed patients. Similar treatment protocols have not been investigated in patients with pharmacotherapy refractory insomnia and generalized anxiety disorder.

  19. [Long-term intermittent renal replacement therapy at an intensive care unit].

    PubMed

    Bellomo, R; Baldwin, I; Toshio, N; Wan, L; Fealy, N; Ronco, C

    2005-01-01

    Standard intermittent hemodialysis (IHD) used for the treatment of acute renal failure (ARF) at an intensive care unit has significant biochemical and physiological drawbacks. In the past 20 years, these drawbacks have stimulated the development of continuous renal replacement therapy (CRRT) and its ever-increasing use. However, CRRT is technically complicated and requires 24-hour monitoring. In some clinics, the use of CRRT leads to that each patient is under his/her nurse's surveillance, instead 1 nurse per 2 patients as before; this change has economic consequences and may limit nursing accessibility to other patients. The procedures prolonging intermittent therapy do not require 24-hour monitoring may benefit the treatment of ARF at the intensive care therapy. In this paper the authors call such procedures for continuous intermittent renal replacement therapy. They are characterized by a number of basic principles: (1) the use of modified or standard dialysis apparatuses; (2) the application of diffuse, convection, or both; (3) a certain reduction in the rate of elimination of dissolved substances as compared with IHD; (4) more prolonged treatment: above usual 3 or 4 hours of IHD, but not more than 8-12 hours (hence the term "intermittent"); (5) the use of on-line generation dialysate or substituting fluid. Information on the effectiveness and safety of this procedure is being now compiled.

  20. Intensive Sleep Deprivation and Cognitive Behavioral Therapy for Pharmacotherapy Refractory Insomnia in a Hospitalized Patient

    PubMed Central

    Breitstein, Joshua; Penix, Brandon; Roth, Bernard J.; Baxter, Tristin; Mysliwiec, Vincent

    2014-01-01

    The case of a 59-year-old woman psychiatrically hospitalized with comorbid insomnia, suicidal ideation, and generalized anxiety disorder is presented. Pharmacologic therapies were unsuccessful for treating insomnia prior to and during hospitalization. Intensive sleep deprivation was initiated for 40 consecutive hours followed by a recovery sleep period of 8 hours. Traditional components of cognitive behavioral therapy for insomnia (CBTi), sleep restriction, and stimulus control therapies, were initiated on the ward. After two consecutive nights with improved sleep, anxiety, and absence of suicidal ideation, the patient was discharged. She was followed in the sleep clinic for two months engaging in CBTi. Treatment resulted in substantial improvement in her insomnia, daytime sleepiness, and anxiety about sleep. Sleep deprivation regimens followed by a restricted sleep recovery period have shown antidepressant effects in depressed patients. Similar treatment protocols have not been investigated in patients with pharmacotherapy refractory insomnia and generalized anxiety disorder. Citation: Breitstein J, Penix B, Roth BJ, Baxter T, Mysliwiec V. Intensive sleep deprivation and cognitive behavioral therapy for pharmacotherapy refractory insomnia in a hospitalized patient. J Clin Sleep Med 2014;10(6):689-690. PMID:24932151

  1. Constraint therapy versus intensive training: implications for motor control and brain plasticity after stroke.

    PubMed

    Medée, Béatrice; Bellaiche, Soline; Revol, Patrice; Jacquin-Courtois, Sophie; Arsenault, Lisette; Guichard-Mayel, Audrey; Delporte, Ludovic; Rode, Gilles; Rossetti, Yves; Boisson, Dominique; Luauté, Jacques

    2010-12-01

    Many studies have demonstrated that constraint induced movement therapy (CIMT) improves upper limb motor impairment following stroke. This rehabilitation method combines constraint of the less-affected upperlimb with intensive training of the paretic limb. The aim of the present study was to evaluate, in a single case study, the respective effects of each of these two therapeutic interventions. The patient selected was a 32-year-old right-handed woman. Three and a half years prior to inclusion, she suffered a left capsular infarct responsible for a right hemiparesis. Several assessments were carried out before and after constraint therapy and then after intensive training. Each assessment included measures of hand function as well as a three-dimensional (3D) analysis of prehension. Results showed a significant improvement of motor performance after the constraint period and an additional amelioration after the intensive training period. Kinematic analysis showed that the transport phase of movement (movement time and velocity peaks) was improved after the constraint period, whereas the grasping phase (maximum grip aperture) was modified after intensive training. These data could reflect a specific effect of treatment on each phase of the prehension task, or a more general proximal-to-distal gradient of recovery. Although firm conclusions are not warranted on the basis of this single case study, we confirm the utility of 3D motion analysis to evaluate objectively the effectiveness of a therapeutic intervention. We also discuss the implications of our findings for understanding processes of motor control reorganisation.

  2. Incorporating deliverable monitor unit constraints into spot intensity optimization in intensity-modulated proton therapy treatment planning

    NASA Astrophysics Data System (ADS)

    Cao, Wenhua; Lim, Gino; Li, Xiaoqiang; Li, Yupeng; Zhu, X. Ronald; Zhang, Xiaodong

    2013-08-01

    The purpose of this study is to investigate the feasibility and impact of incorporating deliverable monitor unit (MU) constraints into spot intensity optimization (SIO) in intensity-modulated proton therapy (IMPT) treatment planning. The current treatment planning system (TPS) for IMPT disregards deliverable MU constraints in the SIO routine. It performs a post-processing procedure on an optimized plan to enforce deliverable MU values that are required by the spot scanning proton delivery system. This procedure can create a significant dose distribution deviation between the optimized and post-processed deliverable plans, especially when small spot spacings are used. In this study, we introduce a two-stage linear programming approach to optimize spot intensities and constrain deliverable MU values simultaneously, i.e., a deliverable SIO (DSIO) model. Thus, the post-processing procedure is eliminated and the associated optimized plan deterioration can be avoided. Four prostate cancer cases at our institution were selected for study and two parallel opposed beam angles were planned for all cases. A quadratic programming based model without MU constraints, i.e., a conventional SIO (CSIO) model, was also implemented to emulate commercial TPS. Plans optimized by both the DSIO and CSIO models were evaluated for five different settings of spot spacing from 3 to 7 mm. For all spot spacings, the DSIO-optimized plans yielded better uniformity for the target dose coverage and critical structure sparing than did the CSIO-optimized plans. With reduced spot spacings, more significant improvements in target dose uniformity and critical structure sparing were observed in the DSIO than in the CSIO-optimized plans. Additionally, better sparing of the rectum and bladder was achieved when reduced spacings were used for the DSIO-optimized plans. The proposed DSIO approach ensures the deliverability of optimized IMPT plans that take into account MU constraints. This eliminates the post

  3. Validation of Heart Failure Events in the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) Participants Assigned to Doxazosin and Chlorthalidone

    PubMed Central

    Piller, Linda B; Davis, Barry R; Cutler, Jeffrey A; Cushman, William C; Wright, Jackson T; Williamson, Jeff D; Leenen, Frans HH; Einhorn, Paula T; Randall, Otelio S; Golden, John S; Haywood, L Julian

    2002-01-01

    Background The Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) is a randomized, double-blind, active-controlled trial designed to compare the rate of coronary heart disease events in high-risk hypertensive participants initially randomized to a diuretic (chlorthalidone) versus each of three alternative antihypertensive drugs: alpha-adrenergic blocker (doxazosin), ACE-inhibitor (lisinopril), and calcium-channel blocker (amlodipine). Combined cardiovascular disease risk was significantly increased in the doxazosin arm compared to the chlorthalidone arm (RR 1.25; 95% CI, 1.17–1.33; P < .001), with a doubling of heart failure (fatal, hospitalized, or non-hospitalized but treated) (RR 2.04; 95% CI, 1.79–2.32; P < .001). Questions about heart failure diagnostic criteria led to steps to validate these events further. Methods and Results Baseline characteristics (age, race, sex, blood pressure) did not differ significantly between treatment groups (P < .05) for participants with heart failure events. Post-event pharmacologic management was similar in both groups and generally conformed to accepted heart failure therapy. Central review of a small sample of cases showed high adherence to ALLHAT heart failure criteria. Of 105 participants with quantitative ejection fraction measurements provided, (67% by echocardiogram, 31% by catheterization), 29/46 (63%) from the chlorthalidone group and 41/59 (70%) from the doxazosin group were at or below 40%. Two-year heart failure case-fatalities (22% and 19% in the doxazosin and chlorthalidone groups, respectively) were as expected and did not differ significantly (RR 0.96; 95% CI, 0.67–1.38; P = 0.83). Conclusion Results of the validation process supported findings of increased heart failure in the ALLHAT doxazosin treatment arm compared to the chlorthalidone treatment arm. PMID:12459039

  4. Treatment planning, optimization, and beam delivery technqiues for intensity modulated proton therapy

    NASA Astrophysics Data System (ADS)

    Sengbusch, Evan R.

    , beamlet weight, the number of delivered beamlets, and the number of delivery angles. These methods are evaluated via treatment planning studies including left-sided whole breast irradiation, lung stereotactic body radiotherapy, nasopharyngeal carcinoma, and whole brain radiotherapy with hippocampal avoidance. Improvements in efficiency and efficacy relative to traditional proton therapy and intensity modulated photon radiation therapy are discussed.

  5. Clinical Outcomes of Intensity-Modulated Pelvic Radiation Therapy for Carcinoma of the Cervix

    SciTech Connect

    Hasselle, Michael D.; Rose, Brent S.; Kochanski, Joel D.; Nath, Sameer K.; Bafana, Rounak; Yashar, Catheryn M.; Hasan, Yasmin; Roeske, John C.; Mundt, Arno J.; Mell, Loren K.

    2011-08-01

    Purpose: To evaluate disease outcomes and toxicity in cervical cancer patients treated with pelvic intensity-modulated radiation therapy (IMRT). Methods and Materials: We included all patients with Stage I-IVA cervical carcinoma treated with IMRT at three different institutions from 2000-2007. Patients treated with extended field or conventional techniques were excluded. Intensity-modulated radiation therapy plans were designed to deliver 45 Gy in 1.8-Gy daily fractions to the planning target volume while minimizing dose to the bowel, bladder, and rectum. Toxicity was graded according to the Radiation Therapy Oncology Group system. Overall survival and disease-free survival were estimated by use of the Kaplan-Meier method. Pelvic failure, distant failure, and late toxicity were estimated by use of cumulative incidence functions. Results: The study included 111 patients. Of these, 22 were treated with postoperative IMRT, 8 with IMRT followed by intracavitary brachytherapy and adjuvant hysterectomy, and 81 with IMRT followed by planned intracavitary brachytherapy. Of the patients, 63 had Stage I-IIA disease and 48 had Stage IIB-IVA disease. The median follow-up time was 27 months. The 3-year overall survival rate and the disease-free survival rate were 78% (95% confidence interval [CI], 68-88%) and 69% (95% CI, 59-81%), respectively. The 3-year pelvic failure rate and the distant failure rate were 14% (95% CI, 6-22%) and 17% (95% CI, 8-25%), respectively. Estimates of acute and late Grade 3 toxicity or higher were 2% (95% CI, 0-7%) and 7% (95% CI, 2-13%), respectively. Conclusions: Intensity-modulated radiation therapy is associated with low toxicity and favorable outcomes, supporting its safety and efficacy for cervical cancer. Prospective clinical trials are needed to evaluate the comparative efficacy of IMRT vs. conventional techniques.

  6. [Prognosis improvements in children with acute myelocytic leucemia after more intensive induction therapy (author's transl)].

    PubMed

    Scheer, U; Schellong, G; Riehm, H

    1979-03-01

    Between October 1974 and October 1978 23 children with acute myelocytic leucemia (AML) received intensive therapy in the Univ.-Kinderklinik Münster: 4 children were treated according to the ALGB-protocol consisting of 5-7 day courses of ARA-C-infusion and 3 DNR-injections. 19 patients received the West-Berlin-protocol: The first 7 the original ALL protocol, 11 the modified form of AML, which will be presented here as AML-therapy-study BFM 78. 4 of the 23 patients died with early acute cerebral bleeding. 2 patients were nonresponders. 17 children went into remission. One girl died in remission of septicemic aspergillosis. 4 children had a relapse. In November 1978 there were still 12 patients in continuous complete remission, 3 of them already without therapy. 13 of the 19 patients, who were treated with the West-Berlin-protocol went into remission. 1 had a relapse. At present there are 11 patients in continuous complete remission. The above results and those found in the literature could signify that the long term prognosis of children with AML will be improved. To coordinate efforts toward this goal a cooperative AML-therapy-study in the "Deutsche Arbeitsgemeinschaft für Leukämieforschung" (BFM-group) using the here presented therapy protocol was formed in November 1978.

  7. Implementation of a procalcitonin-guided algorithm for antibiotic therapy in the burn intensive care unit

    PubMed Central

    Lavrentieva, A.; Kontou, P.; Soulountsi, V.; Kioumis, J.; Chrysou, O.; Bitzani, M.

    2015-01-01

    Summary The purpose of this study was to examine the hypothesis that an algorithm based on serial measurements of procalcitonin (PCT) allows reduction in the duration of antibiotic therapy compared with empirical rules, and does not result in more adverse outcomes in burn patients with infectious complications. All burn patients requiring antibiotic therapy based on confirmed or highly suspected bacterial infections were eligible. Patients were assigned to either a procalcitonin-guided (study group) or a standard (control group) antibiotic regimen. The following variables were analyzed and compared in both groups: duration of antibiotic treatment, mortality rate, percentage of patients with relapse or superinfection, maximum SOFA score (days 1-28), length of ICU and hospital stay. A total of 46 Burn ICU patients receiving antibiotic therapy were enrolled in this study. In 24 patients antibiotic therapy was guided by daily procalcitonin and clinical assessment. PCT guidance resulted in a smaller antibiotic exposure (10.1±4 vs. 15.3±8 days, p=0.034) without negative effects on clinical outcome characteristics such as mortality rate, percentage of patients with relapse or superinfection, maximum SOFA score, length of ICU and hospital stay. The findings thus show that use of a procalcitonin-guided algorithm for antibiotic therapy in the burn intensive care unit may contribute to the reduction of antibiotic exposure without compromising clinical outcome parameters. PMID:27279801

  8. Green tea as inhibitor of the intestinal absorption of lipids: potential mechanism for its lipid-lowering effect.

    PubMed

    Koo, Sung I; Noh, Sang K

    2007-03-01

    Animal and epidemiological studies suggest that green tea catechins may reduce the risk of cardiovascular diseases [e.g., coronary heart disease (CHD)]. The health benefit of green tea has been attributed to its antioxidant and anti-inflammatory properties; however, considerable evidence suggests that green tea and its catechins may reduce the risk of CHD by lowering the plasma levels of cholesterol and triglyceride. Although the mechanism underlying such effect of green tea is yet to be determined, it is evident from in vitro and in vivo studies that green tea or catechins inhibit the intestinal absorption of dietary lipids. Studies in vitro indicate that green tea catechins, particularly (-)-epigallocatechin gallate, interfere with the emulsification, digestion, and micellar solubilization of lipids, critical steps involved in the intestinal absorption of dietary fat, cholesterol, and other lipids. Based on the observations, it is likely that green tea or its catechins lower the absorption and tissue accumulation of other lipophilic organic compounds. The available information strongly suggests that green tea or its catechins may be used as safe and effective lipid-lowering therapeutic agents.

  9. Green Tea as Inhibitor of the Intestinal Absorption of Lipids: Potential Mechanism for its Lipid-Lowering Effect1

    PubMed Central

    Koo, Sung I.; Noh, Sang K.

    2007-01-01

    Animal and epidemiological studies suggest that green tea catechins may reduce the risk of cardiovascular diseases (CHD). The health benefit of green tea has been attributed to its antioxidant and anti-inflammatory properties; however, considerable evidence suggests that green tea and its catechins may reduce the risk of CHD by lowering the plasma levels of cholesterol and triglyceride. Although the mechanism underlying such effect of green tea is yet to be determined, it is evident from in vitro and in vivo studies that green tea or catechins inhibit the intestinal absorption of dietary lipids. Studies in vitro indicate that green tea catechins, particularly EGCG, interfere with the emulsification, digestion, and micellar solubilization of lipids, critical steps involved in the intestinal absorption of dietary fat, cholesterol, and other lipids. Based on the observations, it is likely that green tea or its catechins lower the absorption and tissue accumulation of other lipophilic organic compounds. The available information strongly suggests that green tea or its catechins may be used as safe and effective lipid-lowering therapeutic agents. PMID:17296491

  10. A modular approach to intensity-modulated arc therapy optimization with noncoplanar trajectories

    NASA Astrophysics Data System (ADS)

    Papp, Dávid; Bortfeld, Thomas; Unkelbach, Jan

    2015-07-01

    Utilizing noncoplanar beam angles in volumetric modulated arc therapy (VMAT) has the potential to combine the benefits of arc therapy, such as short treatment times, with the benefits of noncoplanar intensity modulated radiotherapy (IMRT) plans, such as improved organ sparing. Recently, vendors introduced treatment machines that allow for simultaneous couch and gantry motion during beam delivery to make noncoplanar VMAT treatments possible. Our aim is to provide a reliable optimization method for noncoplanar isocentric arc therapy plan optimization. The proposed solution is modular in the sense that it can incorporate different existing beam angle selection and coplanar arc therapy optimization methods. Treatment planning is performed in three steps. First, a number of promising noncoplanar beam directions are selected using an iterative beam selection heuristic; these beams serve as anchor points of the arc therapy trajectory. In the second step, continuous gantry/couch angle trajectories are optimized using a simple combinatorial optimization model to define a beam trajectory that efficiently visits each of the anchor points. Treatment time is controlled by limiting the time the beam needs to trace the prescribed trajectory. In the third and final step, an optimal arc therapy plan is found along the prescribed beam trajectory. In principle any existing arc therapy optimization method could be incorporated into this step; for this work we use a sliding window VMAT algorithm. The approach is demonstrated using two particularly challenging cases. The first one is a lung SBRT patient whose planning goals could not be satisfied with fewer than nine noncoplanar IMRT fields when the patient was treated in the clinic. The second one is a brain tumor patient, where the target volume overlaps with the optic nerves and the chiasm and it is directly adjacent to the brainstem. Both cases illustrate that the large number of angles utilized by isocentric noncoplanar VMAT plans

  11. Intensive combined modality therapy including low-dose TBI in high-risk Ewing's sarcoma patients

    SciTech Connect

    Kinsella, T.J.; Glaubiger, D.; Diesseroth, A.; Makuch, R.; Waller, B.; Pizzo, P.; Glatstein, E.

    1983-12-01

    Twenty-four high-risk Ewing's sarcoma patients were treated on an intensive combined modality protocol including low-dose fractionated total body irradiaiton (TBI) and autologous bone marrow infusion (ABMI). Twenty patients (83%) achieved a complete clinical response to the primary and/or metastatic sites following induction therapy. The median disease-free interval was 18 months, and nine patients remain disease-free with a follow-up of 22 to 72 months. Local failure as a manifestation of initial relapse occurred in only three patients (15%), each having synchronous distant failure. Eight patients failed initially with only distant metastases, usually within 1-2 years following a complete clinical response. Two patterns of granulocyte recovery following consolidative therapy (including TBI and ABMI) were recognized. The time to platelet recovery was different for the groups with early and late granulocyte recovery. Patients with late recovery did not tolerate maintenance chemotherapy. However, there was no difference in disease-free and overall survival, when comparing the groups with early and late granulocyte recovery. It is concluded that these high-risk Ewing's sarcoma patients remain a poor-prognosis group in spite of intensive combined modality therapy including low-dose TBI. The control of microscopic systemic disease remains the major challenge to improving the cure rate. A new combined modality protocol with high-dose 'therapeutic' TBI (800 rad/2 fractions) is being used and the protocol design is outlined.

  12. Short-term intensive family therapy for adolescent eating disorders: 30-month outcome.

    PubMed

    Marzola, Enrica; Knatz, Stephanie; Murray, Stuart B; Rockwell, Roxanne; Boutelle, Kerri; Eisler, Ivan; Kaye, Walter H

    2015-05-01

    Family therapy approaches have generated impressive empirical evidence in the treatment of adolescent eating disorders (EDs). However, the paucity of specialist treatment providers limits treatment uptake; therefore, our group developed the intensive family therapy (IFT)-a 5-day treatment based on the principles of family-based therapy for EDs. We retrospectively examined the long-term efficacy of IFT in both single-family (S-IFT) and multi-family (M-IFT) settings evaluating 74 eating disordered adolescents who underwent IFT at the University of California, San Diego, between 2006 and 2013. Full remission was defined as normal weight (≥ 95% of expected for sex, age, and height), Eating Disorder Examination Questionnaire (EDE-Q) global score within 1 SD of norms, and absence of binge-purging behaviours. Partial remission was defined as weight ≥ 85% of expected or ≥ 95% but with elevated EDE-Q global score and presence of binge-purging symptoms (<1/week). Over a mean follow-up period of 30 months, 87.8% of participants achieved either full (60.8%) or partial remission (27%), while 12.2% reported a poor outcome, with both S-IFT and M-IFT showing comparable outcomes. Short-term, intensive treatments may be cost-effective and clinically useful where access to regular specialist treatment is limited.

  13. Compact Dielectric Wall Accelerator Development For Intensity Modulated Proton Therapy And Homeland Security Applications

    SciTech Connect

    Chen, Y -; Caporaso, G J; Guethlein, G; Sampayan, S; Akana, G; Anaya, R; Blackfield, D; Cook, E; Falabella, S; Gower, E; Harris, J; Hawkins, S; Hickman, B; Holmes, C; Horner, A; Nelson, S; Paul, A; Pearson, D; Poole, B; Richardson, R; Sanders, D; Stanley, J; Sullivan, J; Wang, L; Watson, J; Weir, J

    2009-06-17

    Compact dielectric wall (DWA) accelerator technology is being developed at the Lawrence Livermore National Laboratory. The DWA accelerator uses fast switched high voltage transmission lines to generate pulsed electric fields on the inside of a high gradient insulating (HGI) acceleration tube. Its high electric field gradients are achieved by the use of alternating insulators and conductors and short pulse times. The DWA concept can be applied to accelerate charge particle beams with any charge to mass ratio and energy. Based on the DWA system, a novel compact proton therapy accelerator is being developed. This proton therapy system will produce individual pulses that can be varied in intensity, energy and spot width. The system will be capable of being sited in a conventional linac vault and provide intensity modulated rotational therapy. The status of the developmental new technologies that make the compact system possible will be reviewed. These include, high gradient vacuum insulators, solid dielectric materials, SiC photoconductive switches and compact proton sources. Applications of the DWA accelerator to problems in homeland security will also be discussed.

  14. SU-E-T-503: Intensity Modulated Proton Therapy (IMPT) Versus Intensity Modulated X-Ray Therapy (IMRT) for Patient with Hepatocellular Carcinoma: A Dosimetric Comparison

    SciTech Connect

    Singh, H; Zhao, L; Prabhu, K; Rana, S; Zheng, Y

    2015-06-15

    Purpose This study compares the dosimetric parameters in treatment of unresectable hepatocellular carcinoma between intensity modulated proton therapy (IMPT) and intensity modulated x-ray radiation therapy (IMRT). Methods and Materials: We studied four patients treated at our institution. All patients were simulated supine with 4D-CT using a GE light speed simulator with a maximum slice thickness of 3mm. The average CT and an internal target volume to account for respiration motion were used for planning. Both IMRT and IMPT plans were created using Elekta’s CMSXiO treatment planning system (TPS). The prescription dose was 58.05 CGE in 15 fractions. The IMRT plans had five beams with combination of co-planar and non-co-planar. The IMPT plans had 2 to 3 beams. Dose comparison was performed based on the averaged results of the four patients. Results The mean dose and V95% to PTV were 58.24CGE, 98.57% for IMPT, versus 57.34CGE and 96.68% for IMRT, respectively. The V10, V20, V30 and mean dose of the normal liver for IMPT were 23.10%, 18.61%, 13.75% and 9.78 CGE; and 47.19%, 37.55%, 22.73% and 17.12CGE for IMRT. The spinal cord didn’t receive any dose in IMPT technique, but received a maximum of 18.77CGE for IMRT. The IMPT gave lower maximum dose to the stomach as compared to IMRT (19.26 vs 26.35CGE). V14 for left and right kidney was 0% and 2.32% for IMPT and 3.89% and 29.54% for IMRT. The mean dose, V35, V40 and V45 for small bowl were similar in both techniques, 0.74CGE, 6.27cc, 4.85cc and 3.53 cc for IMPT, 3.47CGE, 9.73cc, 7.61cc 5.35cc for IMRT. Conclusion Based on this study, IMPT plans gave less dose to the critical structures such as normal liver, kidney, stomach and spinal cord as compared to IMRT plans, potentially leading to less toxicity and providing better quality of life for patients.

  15. Extracorporeal liver support therapy with Prometheus in patients with liver failure in the intensive care unit.

    PubMed

    Oppert, Michael; Rademacher, Sibylle; Petrasch, Kathrin; Jörres, Achim

    2009-10-01

    Acute liver failure (ALF) and acute-on-chronic liver failure (AoCLF) are associated with a high mortality. In these patients an accumulation of both water-soluble and water-insoluble, protein-bound, metabolic waste products occurs. Conventional extracorporeal blood purification techniques based on diffusion and/or convection such as hemodialysis or hemofiltration may only eliminate small molecular weight, water-soluble compounds. In recent years, fractionated plasma separation and adsorption (FPSA) with the Prometheus system has been introduced for extracorporeal liver support therapy. To date, however, only limited data is available regarding the effect of this treatment on mortality and outcome of patients with advanced liver disease. Here we report on our experience with 23 patients with severe liver failure who were treated with Prometheus in our medical intensive care unit. Fourteen patients had AoCLF, and nine patients experienced ALF. The median bilirubin level at the start of Prometheus therapy was 30.5 mg/dL and the median Acute Physiology and Chronic Health Evaluation II (APACHE II) score was 26. During 40 individual treatment sessions lasting 5-6 h, Prometheus therapy reduced serum bilirubin levels from 23.7 mg/dL to 15.0 mg/dL (median values) (P < 0.001), and the overall survival was 26%. ALF patients had a better survival compared to AoCLF patients (44% vs. 22%; P = 0.022). Apart from one patient who developed hemodynamic instability during a treatment session, Prometheus therapy was well tolerated without relevant side-effects. In conclusion, extracorporeal liver support therapy with Prometheus is a novel and safe treatment option in patients with severe liver failure. In this series, patients with ALF showed a significantly better outcome with Prometheus therapy compared to AoCLF patients.

  16. Optimization of intensity-modulated very high energy (50-250 MeV) electron therapy

    NASA Astrophysics Data System (ADS)

    Yeboah, C.; Sandison, G. A.; Moskvin, V.

    2002-04-01

    This work evaluates the potential of very high energy (50-250 MeV) electron beams for dose conformation and identifies those variables that influence optimized dose distributions for this modality. Intensity-modulated plans for a prostate cancer model were optimized as a function of the importance factors, beam energy and number of energy bins, number of beams, and the beam orientations. A trial-and-error-derived constellation of importance factors for target and sensitive structures to achieve good conformal dose distributions was 500, 50, 10 and 1 for the target, rectum, bladder and normal tissues respectively. Electron energies greater than 100 MeV were found to be desirable for intensity-modulated very high energy electron therapy (VHEET) of prostate cancer. Plans generated for lower energy beams had relatively poor conformal dose distributions about the target region and delivered high doses to sensitive structures. Fixed angle beam treatments utilizing a large number of fields in the range 9-21 provided acceptable plans. Using more than 21 beams at fixed gantry angles had an insignificant effect on target coverage, but resulted in an increased dose to sensitive structures and an increased normal tissue integral dose. Minor improvements in VHEET plans utilizing a `small' number (=<9) of beams may be achieved if, in addition to intensity modulation, energy modulation is implemented using a small number (=<3) of beam energies separated by 50 to 100 MeV. Rotation therapy provided better target dose homogeneity but unfortunately resulted in increased rectal dose, bladder dose and normal tissue integral dose relative to the 21-field fixed angle treatment plan. Modulation of the beam energy for rotation therapy had no beneficial consequences on the optimized dose distributions. Lastly, selection of beam orientations influenced the optimized treatment plan even when a large number of beams (approximately 15) were employed.

  17. Perturbative diffusion theory formalism for interpreting temporal light intensity changes during laser interstitial thermal therapy.

    PubMed

    Chin, Lee C L; Whelan, William M; Vitkin, I Alex

    2007-03-21

    In an effort to understand dynamic optical changes during laser interstitial thermal therapy (LITT), we utilize the perturbative solution of the diffusion equation in heterogeneous media to formulate scattering weight functions for cylindrical line sources. The analysis explicitly shows how changes in detected interstitial light intensity are associated with the extent and location of the volume of thermal coagulation during treatment. Explanations for previously reported increases in optical intensity observed early during laser heating are clarified using the model and demonstrated with experimental measurements in ex vivo bovine liver tissue. This work provides an improved understanding of interstitial optical signal changes during LITT and indicates the sensitivity and potential of interstitial optical monitoring of thermal damage.

  18. High-intensity laser therapy during chronic degenerative tenosynovitis experimentally induced in broiler chickens

    NASA Astrophysics Data System (ADS)

    Fortuna, Damiano; Rossi, Giacomo; Bilotta, Teresa W.; Zati, Allesandro; Gazzotti, Valeria; Venturini, Antonio; Pinna, Stefania; Serra, Christian; Masotti, Leonardo

    2002-10-01

    The aims of this study was the safety and the efficacy of High Intensity Laser Therapy (HILT) on chronic degenerative tenosynovitis. We have effectuated the histological evaluation and seroassay (C reactive protein) on 18 chickens affect by chronic degenerative tenosynovitis experimentally induced. We have been employed a Nd:YAG laser pulsed wave; all irradiated subjects received the same total energy (270 Joule) with a fluence of 7,7 J/cm2 and intensity of 10,7 W/cm2. The histological findings revealed a distinct reduction of the mineralization of the choral matrix, the anti-inflammatory effect of the laser, the hyperplasia of the synoviocytes and ectasia of the lymphatic vessels.

  19. The Future Is Now: Software-Guided Intensive Insulin Therapy in the Critically Ill

    PubMed Central

    Rattan, Rishi; Nasraway, Stanley A.

    2013-01-01

    Since the development of intensive insulin therapy for the critically ill adult, tight glycemic control (TGC) has become increasingly complicated to apply and achieve. Software-guided (SG) algorithms for insulin dosing represent a new method to achieve euglycemia in critical illness. We provide an overview of the state of SG TGC with an eye to the future. The current milieu is disorganized, with little research that incorporates newer variables of dysglycemia, such as glycemic variability. To develop and implement better algorithms, scientists, programmers, and clinicians need to standardize measurements and variables. PMID:23567013

  20. TH-A-BRE-01: The Status of Intensity Modulated Proton and Ion Therapy

    SciTech Connect

    Dong, L; Zhu, X; Unkelbach, J; Schulte, R

    2014-06-15

    IMRT with photons has become a radiation therapy standard of care for many cancer treatment sites. The situation is quite different with intensity modulated particle (protons and ion) radiation therapy (IMPT). With the rapid development of beam scanning techniques and many of the newer proton facilities exclusively offering active beam scanning as their radiation delivery technique, it is timely to give an update on the status and challenges of IMPT. The leading principle in IMPT is to aim at the target from several, not necessarily coplanar, directions with multiple pencil beams that are modulated in their intensity and adjusted in their energy such that a desired dose distribution or, more generally, a desired bio-effective dose distribution is achieved. Different from low-LET photons, the varying relative biological effectiveness (RBE) along the beam path adds an additional dimension to the treatment planning process and will require biophysical modeling at least for carbon ion therapy. IMPT involves computationally challenging tasks, yet it needs to be very fast in order to be clinically relevant. To make IMPT computationally tractable, robust and efficient optimization methods are required. Lastly, IMPT planning is very sensitive to accurate knowledge of relative stopping and scattering powers of the intervening tissues as well as intra- and inter-fraction motion. Robust planning methods are being developed in order to obtain IMPT plans that are less sensitive against such uncertainties. This therapy symposium will present an update on the current status and emerging developments of IMPT from the medical physics perspective. Learning Objectives: Become familiar with current delivery techniques for IMPT and their limitations. Understand the basics of dose calculational algorithms and commissioning of IMPT. Learn how to assess the accuracy of planning and delivery of IMPT treatments. Get an overview of currently used and emerging optimization techniques. Learn

  1. A compact linac for intensity modulated proton therapy based on a dielectric wall accelerator.

    PubMed

    Caporaso, G J; Mackie, T R; Sampayan, S; Chen, Y-J; Blackfield, D; Harris, J; Hawkins, S; Holmes, C; Nelson, S; Paul, A; Poole, B; Rhodes, M; Sanders, D; Sullivan, J; Wang, L; Watson, J; Reckwerdt, P J; Schmidt, R; Pearson, D; Flynn, R W; Matthews, D; Purdy, J

    2008-06-01

    A novel compact CT-guided intensity modulated proton radiotherapy (IMPT) system is described. The system is being designed to deliver fast IMPT so that larger target volumes and motion management can be accomplished. The system will be ideal for large and complex target volumes in young patients. The basis of the design is the dielectric wall accelerator (DWA) system being developed at the Lawrence Livermore National Laboratory (LLNL). The DWA uses fast switched high voltage transmission lines to generate pulsed electric fields on the inside of a high gradient insulating (HGI) acceleration tube. High electric field gradients are achieved by the use of alternating insulators and conductors and short pulse times. The system will produce individual pulses that can be varied in intensity, energy and spot width. The IMPT planning system will optimize delivery characteristics. The system will be capable of being sited in a conventional linac vault and provide intensity modulated rotational therapy. Feasibility tests of an optimization system for selecting the position, energy, intensity and spot size for a collection of spots comprising the treatment are underway. A prototype is being designed and concept designs of the envelope and environmental needs of the unit are beginning. The status of the developmental new technologies that make the compact system possible will be reviewed. These include, high gradient vacuum insulators, solid dielectric materials, SiC photoconductive switches and compact proton sources.

  2. Mortality and morbidity during and after Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial: results by sex.

    PubMed

    Oparil, Suzanne; Davis, Barry R; Cushman, William C; Ford, Charles E; Furberg, Curt D; Habib, Gabriel B; Haywood, L Julian; Margolis, Karen; Probstfield, Jeffrey L; Whelton, Paul K; Wright, Jackson T

    2013-05-01

    To determine whether an angiotensin-converting enzyme inhibitor (lisinopril) or calcium channel blocker (amlodipine) is superior to a diuretic (chlorthalidone) in reducing cardiovascular disease incidence in sex subgroups, we carried out a prespecified subgroup analysis of 15 638 women and 17 719 men in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). Total follow-up (active treatment + passive surveillance using national administrative databases to ascertain deaths and hospitalizations) was 8 to 13 years. The primary outcome was fatal coronary heart disease or nonfatal myocardial infarction. Secondary outcomes included all-cause mortality, stroke, combined cardiovascular disease (coronary heart disease death, nonfatal myocardial infarction, stroke, angina, coronary revascularization, heart failure [HF], or peripheral vascular disease), and end-stage renal disease. In-trial rates of HF, stroke, and combined cardiovascular disease were significantly higher for lisinopril compared with chlorthalidone, and rates of HF were significantly higher for amlodipine compared with chlorthalidone in both men and women. There were no significant treatment sex interactions. These findings did not persist through the extension period with the exception of the HF result for amlodipine versus chlorthalidone, which did not differ significantly by sex. For both women and men, rates were not lower in the amlodipine or lisinopril groups than in the chlorthalidone group for either the primary coronary heart disease outcome or any other cardiovascular disease outcome, and chlorthalidone-based treatment resulted in the lowest risk of HF. Neither lisinopril nor amlodipine is superior to chlorthalidone for initial treatment of hypertension in either women or men. Clinical Trial Registration- clinicaltrials.gov; Identifier: NCT00000542.

  3. Gemfibrozil, a Lipid-lowering Drug, Increases Myelin Genes in Human Oligodendrocytes via Peroxisome Proliferator-activated Receptor-β*

    PubMed Central

    Jana, Malabendu; Mondal, Susanta; Gonzalez, Frank J.; Pahan, Kalipada

    2012-01-01

    An increase in CNS remyelination and a decrease in CNS inflammation are important steps to halt the progression of multiple sclerosis. Earlier studies have shown that gemfibrozil, a lipid-lowering drug, has anti-inflammatory properties. The current study identified another novel property of gemfibrozil in stimulating the expression of myelin-specific genes (myelin basic protein, myelin oligodendrocyte glycoprotein, 2′,3′-cyclic-nucleotide 3′-phosphodiesterase, and proteolipid protein (PLP)) in primary human oligodendrocytes, mixed glial cells, and spinal cord organotypic cultures. Although gemfibrozil is a known activator of peroxisome proliferator-activated receptor-α (PPAR-α), we were unable to detect PPAR-α in either gemfibrozil-treated or untreated human oligodendrocytes, and gemfibrozil increased the expression of myelin genes in oligodendrocytes isolated from both wild type and PPAR-α(−/−) mice. On the other hand, gemfibrozil markedly increased the expression of PPAR-β but not PPAR-γ. Consistently, antisense knockdown of PPAR-β, but not PPAR-γ, abrogated the stimulatory effect of gemfibrozil on myelin genes in human oligodendrocytes. Gemfibrozil also did not up-regulate myelin genes in oligodendroglia isolated from PPAR-β(−/−) mice. Chromatin immunoprecipitation analysis showed that gemfibrozil induced the recruitment of PPAR-β to the promoter of PLP and myelin oligodendrocyte glycoprotein genes in human oligodendrocytes. Furthermore, gemfibrozil treatment also led to the recruitment of PPAR-β to the PLP promoter in vivo in the spinal cord of experimental autoimmune encephalomyelitis mice and suppression of experimental autoimmune encephalomyelitis symptoms in PLP-T cell receptor transgenic mice. These results suggest that gemfibrozil stimulates the expression of myelin genes via PPAR-β and that gemfibrozil, a prescribed drug for humans, may find further therapeutic use in demyelinating diseases. PMID:22879602

  4. Dose-Volume Comparison of Proton Therapy and Intensity-Modulated Radiotherapy for Prostate Cancer

    SciTech Connect

    Vargas, Carlos Fryer, Amber; Mahajan, Chaitali; Indelicato, Daniel; Horne, David C.; Chellini, Angela; McKenzie, Craig C.; Lawlor, Paula C.; Henderson, Randal; Li Zuofeng; Lin Liyong; Olivier, Kenneth; Keole, Sameer

    2008-03-01

    Purpose: The contrast in dose distribution between proton radiotherapy (RT) and intensity-modulated RT (IMRT) is unclear, particularly in regard to critical structures such as the rectum and bladder. Methods and Materials: Between August and November 2006, the first 10 consecutive patients treated in our Phase II low-risk prostate proton protocol (University of Florida Proton Therapy Institute protocol 0001) were reviewed. The double-scatter proton beam plans used in treatment were analyzed for various dosimetric endpoints. For all plans, each beam dose distribution, angle, smearing, and aperture margin were optimized. IMRT plans were created for all patients and simultaneously analyzed. The IMRT plans were optimized through multiple volume objectives, beam weighting, and individual leaf movement. The patients were treated to 78 Gray-equivalents (GE) in 2-GE fractions with a biologically equivalent dose of 1.1. Results: All rectal and rectal wall volumes treated to 10-80 GE (percentage of volume receiving 10-80 GE [V{sub 10}-V{sub 80}]) were significantly lower with proton therapy (p < 0.05). The rectal V{sub 50} was reduced from 31.3% {+-} 4.1% with IMRT to 14.6% {+-} 3.0% with proton therapy for a relative improvement of 53.4% and an absolute benefit of 16.7% (p < 0.001). The mean rectal dose decreased 59% with proton therapy (p < 0.001). For the bladder and bladder wall, proton therapy produced significantly smaller volumes treated to doses of 10-35 GE (p < 0.05) with a nonsignificant advantage demonstrated for the volume receiving {<=}60 GE. The bladder V{sub 30} was reduced with proton therapy for a relative improvement of 35.3% and an absolute benefit of 15.1% (p = 0.02). The mean bladder dose decreased 35% with proton therapy (p = 0.002). Conclusion: Compared with IMRT, proton therapy reduced the dose to the dose-limiting normal structures while maintaining excellent planning target volume coverage.

  5. Carcinoma of the anal canal: Intensity modulated radiation therapy (IMRT) versus three-dimensional conformal radiation therapy (3DCRT)

    SciTech Connect

    Sale, Charlotte; Moloney, Phillip; Mathlum, Maitham

    2013-12-15

    Patients with anal canal carcinoma treated with standard conformal radiotherapy frequently experience severe acute and late toxicity reactions to the treatment area. Roohipour et al. (Dis Colon Rectum 2008; 51: 147–53) stated a patient's tolerance of chemoradiation to be an important prediction of treatment success. A new intensity modulated radiation therapy (IMRT) technique for anal carcinoma cases has been developed at the Andrew Love Cancer Centre aimed at reducing radiation to surrounding healthy tissue. A same-subject repeated measures design was used for this study, where five anal carcinoma cases at the Andrew Love Cancer Centre were selected. Conformal and IMRT plans were generated and dosimetric evaluations were performed. Each plan was prescribed a total of 54 Gray (Gy) over a course of 30 fractions to the primary site. The IMRT plans resulted in improved dosimetry to the planning target volume (PTV) and reduction in radiation to the critical structures (bladder, external genitalia and femoral heads). Statistically there was no difference between the IMRT and conformal plans in the dose to the small and large bowel; however, the bowel IMRT dose–volume histogram (DVH) doses were consistently lower. The IMRT plans were superior to the conformal plans with improved dose conformity and reduced radiation to the surrounding healthy tissue. Anecdotally it was found that patients tolerated the IMRT treatment better than the three-dimensional (3D) conformal radiation therapy. This study describes and compares the planning techniques.

  6. Imaging Changes in Pediatric Intracranial Ependymoma Patients Treated With Proton Beam Radiation Therapy Compared to Intensity Modulated Radiation Therapy

    SciTech Connect

    Gunther, Jillian R.; Sato, Mariko; Chintagumpala, Murali; Ketonen, Leena; Jones, Jeremy Y.; Allen, Pamela K.; Paulino, Arnold C.; Okcu, M. Fatih; Su, Jack M.; Weinberg, Jeffrey; Boehling, Nicholas S.; Khatua, Soumen; Adesina, Adekunle; Dauser, Robert; Whitehead, William E.; Mahajan, Anita

    2015-09-01

    Purpose: The clinical significance of magnetic resonance imaging (MRI) changes after radiation therapy (RT) in children with ependymoma is not well defined. We compared imaging changes following proton beam radiation therapy (PBRT) to those after photon-based intensity modulated RT (IMRT). Methods and Materials: Seventy-two patients with nonmetastatic intracranial ependymoma who received postoperative RT (37 PBRT, 35 IMRT) were analyzed retrospectively. MRI images were reviewed by 2 neuroradiologists. Results: Sixteen PBRT patients (43%) developed postradiation MRI changes at 3.8 months (median) with resolution by 6.1 months. Six IMRT patients (17%) developed changes at 5.3 months (median) with 8.3 months to resolution. Mean age at radiation was 4.4 and 6.9 years for PBRT and IMRT, respectively (P=.06). Age at diagnosis (>3 years) and time of radiation (≥3 years) was associated with fewer imaging changes on univariate analysis (odds ratio [OR]: 0.35, P=.048; OR: 0.36, P=.05). PBRT (compared to IMRT) was associated with more frequent imaging changes, both on univariate (OR: 3.68, P=.019) and multivariate (OR: 3.89, P=.024) analyses. Seven (3 IMRT, 4 PBRT) of 22 patients with changes had symptoms requiring intervention. Most patients were treated with steroids; some PBRT patients also received bevacizumab and hyperbaric oxygen therapy. None of the IMRT patients had lasting deficits, but 2 patients died from recurrent disease. Three PBRT patients had persistent neurological deficits, and 1 child died secondarily to complications from radiation necrosis. Conclusions: Postradiation MRI changes are more common with PBRT and in patients less than 3 years of age at diagnosis and treatment. It is difficult to predict causes for development of imaging changes that progress to clinical significance. These changes are usually self-limiting, but some require medical intervention, especially those involving the brainstem.

  7. Acupuncture and Traditional Herbal Medicine Therapy Prevent Deliriumin Patients with Cardiovascular Disease in Intensive Care Units.

    PubMed

    Matsumoto-Miyazaki, Jun; Ushikoshi, Hiroaki; Miyata, Shusaku; Miyazaki, Nagisa; Nawa, Takahide; Okada, Hideshi; Ojio, Shinsuke; Ogura, Shinji; Minatoguchi, Shinya

    2017-02-23

    The aim of this study was to determine the effect of combination therapy consisting of acupuncture and traditional herbal medicine (Kampo medicine) for reducing the incidence rate of delirium in patients with cardiovascular (CV) disease in ICUs. Twenty-nine patients who had been urgently admitted to the ICU in the control period were treated with conventional intensive care. Thirty patients in the treatment period received conventional therapy plus a combination therapy consisting of acupuncture and herbal medicine. Acupuncture treatment was performed once a day, and the herbal formula was administered orally three times a day during the first week of the ICU stay. The standard acupuncture points were GV20, Ex-HN3, HT7, LI4, Liv3, and KI3, and the main herbal preparation was Kamikihito. The incident rates of delirium, assessed using the confusion assessment method for ICU, in the treatment and control period were compared. The incidence rate of delirium was significantly lower in the treatment group than in the control group (6.6% vs. 37.9%, [Formula: see text]). Moreover, sedative drugs and non-pharmacological approaches against aggressive behavior of patients who were delirious were used less in the treatment group than in the control group. No serious adverse events were observed in the treatment group. Combination therapy consisting of acupuncture and herbal medicine was found to be effective in lowering the incidence of delirium in patients with CV disease in ICUs. Further studies with a large sample size and parallel randomized controlled design would be required to establish the effects of this therapy.

  8. Family-Based Cognitive-Behavioral Therapy for Pediatric Obsessive-Compulsive Disorder: Comparison of Intensive and Weekly Approaches

    ERIC Educational Resources Information Center

    Storch, Eric A.; Geffken, Gary R.; Merlo, Lisa J.; Mann, Giselle; Duke, Danny; Munson, Melissa; Adkins, Jennifer; Grabill, Kristen M.; Murphy, Tanya K.; Goodman, Wayne K.

    2007-01-01

    Objective: To examine the relative efficacy of intensive versus weekly cognitive-behavioral therapy (CBT) for children and adolescents with obsessive-compulsive disorder (OCD). Method: Forty children and adolescents with OCD (range 7-17 years) were randomized to receive 14 sessions of weekly or intensive (daily psychotherapy sessions) family-based…

  9. Intensity modulated radiation therapy with field rotation--a time-varying fractionation study.

    PubMed

    Dink, Delal; Langer, Mark P; Rardin, Ronald L; Pekny, Joseph F; Reklaitis, Gintaras V; Saka, Behlul

    2012-06-01

    This paper proposes a novel mathematical approach to the beam selection problem in intensity modulated radiation therapy (IMRT) planning. The approach allows more beams to be used over the course of therapy while limiting the number of beams required in any one session. In the proposed field rotation method, several sets of beams are interchanged throughout the treatment to allow a wider selection of beam angles than would be possible with fixed beam orientations. The choice of beamlet intensities and the number of identical fractions for each set are determined by a mixed integer linear program that controls jointly for the distribution per fraction and the cumulative dose distribution delivered to targets and critical structures. Trials showed the method allowed substantial increases in the dose objective and/or sparing of normal tissues while maintaining cumulative and fraction size limits. Trials for a head and neck site showed gains of 25%-35% in the objective (average tumor dose) and for a thoracic site gains were 7%-13%, depending on how strict the fraction size limits were set. The objective did not rise for a prostate site significantly, but the tolerance limits on normal tissues could be strengthened with the use of multiple beam sets.

  10. Intensive insulin therapy for preventing postoperative infection in patients with traumatic brain injury

    PubMed Central

    Wang, Yan; Li, Jin-ping; Song, Ying-lun; Zhao, Qi-huang

    2017-01-01

    Abstract Objective: To assess the effect of intensive insulin therapy (IIT) for preventing postoperative infection in patients with traumatic brain injury (TBI). Methods: In total, 88 patients with TBI were randomly divided into 2 groups, 44 in each group. One group (group ITT) received IIT and the other group (group CIT) received conventional insulin therapy (CIT). This study was conducted between February 2013 and January 2016. Outcomes included infection rate, mortality, and neurological outcome (measured by the Glasgow Outcome Scale [GOS]). Results: A total of 81 patients completed the study. IIT showed greater efficacy than CIT, with a decreased infection rate in the IIT group compared to the CIT group (31.9% vs 52.3%, P = 0.03), and also a reduced duration of stay in intensive care unit (ICU) (IIT group, 4.5 ± 2.1 days vs CIT group, 5.7 ± 2.8 days, P = 0.02). In addition, a significant difference in scores on the GOS scale was observed between the 2 groups (P = 0.04). The mortality rates in hospital and at the 26-week follow-up were similar between the 2 groups. Conclusion: IIT leads to a reduced infection rate, shorter stays in ICU, and improved neurological outcome. PMID:28353579

  11. Intensive Statin Therapy in NSTE-ACS Patients Undergoing PCI: Clinical and Biochemical Effects

    PubMed Central

    Fayez, George; Nassar, Ahmed

    2015-01-01

    Early initiation of statin therapy in acute coronary syndrome patients has a favorable prognostic impact because of its anti-inflammatory and antithrombotic properties. In this study, we explored the effect of atorvastatin-loading, followed by intensive atorvastatin therapy, on clinical and biochemical outcomes in non-ST-segment-elevation acute coronary syndrome patients who were scheduled for percutaneous coronary intervention. We prospectively enrolled 140 patients (mean age, 56 ± 9 years, 68% men). Once eligible, patients were randomly assigned to receive either a moderate 20-mg daily dose of atorvastatin (Group A) or a 160-mg loading dose followed by an intensified 80-mg daily dose (Group B). High-sensitivity C-reactive protein (hs-CRP) levels were recorded before and after intervention. Evaluation after 6 months included hs-CRP levels, left ventricular systolic function, and major adverse cardiac events. We found no significant difference between the 2 groups in regard to the interventional data. However, blood sampling after coronary intervention, and again 6 months later, revealed a significant decline in mean hs-CRP level among Group B patients (P <0.001). Moreover, patients in Group B manifested a higher left ventricular ejection fraction than did patients in Group A (P <0.05). After 6 months, we found no significant difference between groups in the incidence of major adverse cardiac events. We conclude that intensive atorvastatin therapy in non-ST-segment-elevation acute coronary syndrome patients is associated with lower hs-CRP levels and with higher left ventricular ejection fraction after 6 months, with no significant impact on adverse cardiac events. PMID:26664304

  12. Treatment of extensive scalp lesions with segmental intensity-modulated photon therapy

    SciTech Connect

    Bedford, James L. . E-mail: James.Bedford@icr.ac.uk; Childs, Peter J.; Hansen, Vibeke Nordmark; Warrington, Alan P.; Mendes, Ruheena L.; Glees, John P.

    2005-08-01

    Purpose: To compare static electron therapy, electron arc therapy, and photon intensity-modulated radiation therapy (IMRT) for treatment of extensive scalp lesions and to examine the dosimetric accuracy of the techniques. Methods and Materials: A retrospective treatment-planning study was performed to evaluate the relative merits of static electron fields, arcing electron fields, and five-field photon IMRT. Thermoluminescent dosimeters (TLD) were used to verify the accuracy of the techniques. The required thickness of bolus was investigated, and an anthropomorphic phantom was also used to examine the effects of air gaps between the wax bolus used for the IMRT technique and the patient's scalp. Results: Neither static nor arcing electron techniques were able to provide a reliable coverage of the planning target volume (PTV), owing to obliquity of the fields in relation to the scalp. The IMRT technique considerably improved PTV dose uniformity, though it irradiated a larger volume of brain. Either 0.5 cm or 1.0 cm of wax bolus was found to be suitable. Air gaps of up to 1 cm between the bolus and the patient's scalp were correctly handled by the treatment-planning system and had negligible influence on the dose to the scalp. Conclusions: Photon IMRT provides a feasible alternative to electron techniques for treatment of large scalp lesions, resulting in improved homogeneity of dose to the PTV but with a moderate increase in dose to the brain.

  13. Improved outcomes with intensity modulated radiation therapy combined with temozolomide for newly diagnosed glioblastoma multiforme.

    PubMed

    Aherne, Noel J; Benjamin, Linus C; Horsley, Patrick J; Silva, Thomaz; Wilcox, Shea; Amalaseelan, Julan; Dwyer, Patrick; Tahir, Abdul M R; Hill, Jacques; Last, Andrew; Hansen, Carmen; McLachlan, Craig S; Lee, Yvonne L; McKay, Michael J; Shakespeare, Thomas P

    2014-01-01

    Purpose. Glioblastoma multiforme (GBM) is optimally treated by maximal debulking followed by combined chemoradiation. Intensity modulated radiation therapy (IMRT) is gaining widespread acceptance in other tumour sites, although evidence to support its use over three-dimensional conformal radiation therapy (3DCRT) in the treatment of gliomas is currently lacking. We examined the survival outcomes for patients with GBM treated with IMRT and Temozolomide. Methods and Materials. In all, 31 patients with GBM were treated with IMRT and 23 of these received chemoradiation with Temozolomide. We correlated survival outcomes with patient functional status, extent of surgery, radiation dose, and use of chemotherapy. Results. Median survival for all patients was 11.3 months, with a median survival of 7.2 months for patients receiving 40.05 Gray (Gy) and a median survival of 17.4 months for patients receiving 60 Gy. Conclusions. We report one of the few series of IMRT in patients with GBM. In our group, median survival for those receiving 60 Gy with Temozolomide compared favourably to the combined therapy arm of the largest randomised trial of chemoradiation versus radiation to date (17.4 months versus 14.6 months). We propose that IMRT should be considered as an alternative to 3DCRT for patients with GBM.

  14. [Bacterial contamination as a complication of intravenous therapy in intensive care (author's transl)].

    PubMed

    Kilian, J; Hösch, A; Ahnefeld, F W; Schmitz, J E; Vanek, E

    1980-10-01

    Intravenous infusion therapy has become an indispensible part of intensive care. Problems of bacterial contamination during this therapy are well known. To check on the possible routes of contamination we examined the infusion system in its several parts (infusion solution, infusion system, connection between infusion system and catheter and content of syringes). The highest rate of contamination was found at the connection between the infusion system and the catheter after use for 24 h (26.7%, 39 out of 146 probes); just at the beginning of the infusion we found bacterial growth in 7.1% (10 out of 141 probes). After injection of drugs into the system the infusion solution was contaminated in 1.9% (6 of 320 probes). The system for measuring the central venous pressure was contaminated in 2.7% (4 of 148 probes). At the end of infusion the infusion solutions were contaminated in 3.1% (9 of 287 probes). Different drugs in syringes in no case were contaminated. In most cases (59 probes) we found gram-positive bacteria (87.3%), in only seven cases (9.7%) gram-negative bacterias and in two cases Candida tropicalis. Our results show that the extrinsic or in use contamination plays the most important part in bacterial contamination of the infusion system. Infection control of intravenous therapy necessitates care in the hygienic standard adopted during the infusion and injection procedures.

  15. Intensity-modulated radiation therapy to bilateral lower limb extremities concurrently: a planning case study

    SciTech Connect

    Fitzgerald, Emma Miles, Wesley; Fenton, Paul; Frantzis, Jim

    2014-09-15

    Non-melanomatous skin cancers represent 80% of all newly diagnosed cancers in Australia with basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) being the most common. A previously healthy 71-year-old woman presented with widespread and tender superficial skin cancers on the lower bilateral limbs. External beam radiation therapy through the use of intensity-modulated radiation therapy (IMRT) was employed as the treatment modality of choice as this technique provides conformal dose distribution to a three-dimensional treatment volume while reducing toxicity to surrounding tissues. The patient was prescribed a dose of 60 Gy to the planning target volume (PTV) with 1.0 cm bolus over the ventral surface of each limb. The beam arrangement consisted of six treatment fields that avoided entry and exit through the contralateral limb. The treatment plans met the International Commission on Radiation Units and Measurements (ICRU) guidelines and produced highly conformal dosimetric results. Skin toxicity was measured against the National Cancer Institute: Common Terminology Criteria for Adverse Events (NCI: CTCAE) version 3. A well-tolerated treatment was delivered with excellent results given the initial extent of the disease. This case study has demonstrated the feasibility and effectiveness of IMRT for skin cancers as an alternative to surgery and traditional superficial radiation therapy, utilising a complex PTV of the extremities for patients with similar presentations.

  16. [Overview and perspectives of mesenchymal stem cell therapy in intensive care medicine].

    PubMed

    Espinoza, Francisco; Aliaga, Felipe; Crawford, Patricia Luz

    2016-02-01

    Development of innovative therapies in intensive care medicine is particularly important since diseases as sepsis, acute respiratory distress syndrome (ARDS) and acute renal injury (AKI) have an elevated morbidity and mortality in spite of current gold-standard approaches. Mesenchymal stem cells (MSC) may have a promising role due to their properties in immunomodulation, tissue reparation and microbial clearance. Preclinical data and results of a systematic review of PubMed, PMC and ClinicalTrials.gov have been included to review the role of MSC therapy in sepsis, ARDS and AKI. A description of MSC biology, sources and benefits in preclinical models was included. A phase I/II clinical trial (RCT) is recruiting neutropenic patients with septic shock. In ARDS, the START trial (Stem cells in ARDS Treatment) is a phase I/II study of bone marrow-derived human MSC (hMSC) that is currently recruiting patients. In AKI, a phase I study has demonstrated the safety of hMSCs infusion in patients undergoing cardiac surgery with high risk to develop AKI. A phase II study is still active. The results of these studies will determine the real feasibility of MSC therapy in critically ill patients.

  17. Leaf-sequencing for intensity-modulated arc therapy using graph algorithms

    SciTech Connect

    Luan Shuang; Wang Chao; Cao Daliang; Chen, Danny Z.; Shepard, David M.; Yu, Cedric X.

    2008-01-15

    Intensity-modulated arc therapy (IMAT) is a rotational IMRT technique. It uses a set of overlapping or nonoverlapping arcs to create a prescribed dose distribution. Despite its numerous advantages, IMAT has not gained widespread clinical applications. This is mainly due to the lack of an effective IMAT leaf-sequencing algorithm that can convert the optimized intensity patterns for all beam directions into IMAT treatment arcs. To address this problem, we have developed an IMAT leaf-sequencing algorithm and software using graph algorithms in computer science. The input to our leaf-sequencing software includes (1) a set of (continuous) intensity patterns optimized by a treatment planning system at a sequence of equally spaced beam angles (typically 10 deg. apart), (2) a maximum leaf motion constraint, and (3) the number of desired arcs, k. The output is a set of treatment arcs that best approximates the set of optimized intensity patterns at all beam angles with guaranteed smooth delivery without violating the maximum leaf motion constraint. The new algorithm consists of the following key steps. First, the optimized intensity patterns are segmented into intensity profiles that are aligned with individual MLC leaf pairs. Then each intensity profile is segmented into k MLC leaf openings using a k-link shortest path algorithm. The leaf openings for all beam angles are subsequently connected together to form 1D IMAT arcs under the maximum leaf motion constraint using a shortest path algorithm. Finally, the 1D IMAT arcs are combined to form IMAT treatment arcs of MLC apertures. The performance of the implemented leaf-sequencing software has been tested for four treatment sites (prostate, breast, head and neck, and lung). In all cases, our leaf-sequencing algorithm produces efficient and highly conformal IMAT plans that rival their counterpart, the tomotherapy plans, and significantly improve the IMRT plans. Algorithm execution times ranging from a few seconds to 2 min are

  18. Application of Jean Piaget's theory of human development for nursing children in an adult intensive therapy unit.

    PubMed

    Green, A

    1991-12-01

    Piaget (1964) believed that interaction with the environment has a large part to play in human development. Matthew (1986) states that in an ideal world critically ill children should be cared for by staff trained in paediatrics, within designated paediatric intensive therapy units. Unfortunately, there are only 28 paediatric intensive therapy units in Great Britain (CMA Medical Data, 1987), consequently each year a third of children requiring intensive care are admitted to adult intensive therapy units (ITU). A knowledge and understanding of developmental psychology can therefore be beneficial to nurses in assessing which stage of development a child has reached, in order to plan the correct level of stimulation, and hence facilitate progress rather than regression in the accomplishment of developmental tasks. The psychological and social processes involved in Jean Piaget's (1896-1980) theory of human development are discussed with regard to nursing children requiring intubation and ventilation in an adult ITU.

  19. History of Pu'er Tea and comparative study for the effect of its various extracts on lipid-lowering diet.

    PubMed

    Qiong, Sun; Xishuang, Yan

    2014-07-01

    Pu'er Tea is a kind of traditional historical famous tea which gains its name for native government jurisdiction in Pu'er (now Xishuangbanna in Yunnan, Pu'er city etc), and takes Pu'er (now Ninger county of Pu'er city) city as its collecting and distributing center .It is famous all over the world because of its good benefits for reducing blood lipid, slimming weight, antibacterial, aid digestion, detoxification and other functions, it is even known as the health care beverage with "the fine quality goods for preserving people's health", "a health drink demanded everyday". Although there are a lot of current study literature about the effect of Pu'er Tea on lipid-lowering and reducing weight, but there is rarely contrast study about the effect of lipid-lowering diet with its various extracts. Therefore, this article uses the acetone, water, chloroform, ethyl acetate and n-butanol to continuously extract Pu'er Tea, then freeze and dry them into four major separate components which include the chloroform layer, ethyl acetate layer, butanol layer and the remaining water layer. Take advantage of different components for filling and feeding the ICR mice which are treated with the processing of obesity molding, then compare the extract of Pu'er Tea with the weight-loss drug L-carnitine which is popular all over the market, explore the slimming effect of each component in Pu'er Tea on the cells of ICR fat mice. The results show that the total water extract of Pu'er Tea, ethyl acetate extract, residual water extract all have obvious effect on reducing body weight and body fat of experimental mice, it also has significant lowering effect on blood lipid and liver lipid in mice, that could significantly inhibit the accumulation of lipid in fat cells and hypertrophy of fat cells, reveal that the Pu'er Tea has good function of lipid-lowering and reducing weight. At the same time, the comprehensive effect of lipid-lowering and reducing weight through Pu 'er Tea is superior to

  20. Clinical response of advanced cancer patients to cellular immunotherapy and intensity-modulated radiation therapy

    PubMed Central

    Hasumi, Kenichiro; Aoki, Yukimasa; Wantanabe, Ryuko; Mann, Dean L

    2013-01-01

    Patients afflicted with advanced cancers were treated with the intratumoral injection of autologous immature dendritic cells (iDCs) followed by activated T-cell infusion and intensity-modulated radiation therapy (IMRT). A second round of iDCs and activated T cells was then administered to patients after the last radiation cycle. This complete regimen was repeated for new and recurring lesions after 6 weeks of follow-up. One year post therapy, outcome analyses were performed to evaluate treatment efficacy. Patients were grouped according to both the number and size of tumors and clinical parameters at treatment initiation, including recurrent disease after standard cancer therapy, Stage IV disease, and no prior therapy. Irrespective of prior treatment status, 23/37 patients with ≤ 5 neoplastic lesions that were ≤ 3 cm in diameter achieved complete responses (CRs), and 5/37 exhibited partial responses (PRs). Among 130 individuals harboring larger and more numerous lesions, CRs were observed in 7/74 patients that had received prior SCT and in 2/56 previously untreated patients. Some patients manifested immune responses including an increase in CD8+CD56+ lymphocytes among circulating mononuclear cells in the course of treatment. To prospectively explore the therapeutic use of these cells, CD8+ cells were isolated from patients that had been treated with cellular immunotherapy and IMRT, expanded in vitro, and injected into recurrent metastatic sites in 13 individuals who underwent the same immunoradiotherapeutic regimens but failed to respond. CRs were achieved in 34 of 58 of such recurrent lesions while PRs in 17 of 58. These data support the expanded use of immunoradiotherapy in advanced cancer patients exhibiting progressive disease. PMID:24349874

  1. Hypofractionated Intensity-Modulated Arc Therapy for Lymph Node Metastasized Prostate Cancer

    SciTech Connect

    Fonteyne, Valerie; De Gersem, Werner; De Neve, Wilfried; Jacobs, Filip; Lumen, Nicolaas; Vandecasteele, Katrien; Villeirs, Geert; De Meerleer, Gert

    2009-11-15

    Purpose: To determine the planning results and acute toxicity after hypofractionated intensity-modulated arc radiotherapy and androgen deprivation for lymph node metastasized (Stage N1) prostate cancer. Methods and Materials: A total of 31 patients with Stage T1-T4N1M0 prostate cancer were treated with intensity-modulated arc radiotherapy and 3 years of androgen deprivation as primary treatment. The clinical target volume (CTV{sub p}) was the prostate and seminal vesicles. Elective lymph node areas ({sub e}) were delineated and expanded by 2 mm to create the CTV{sub e}. The planning target volumes (PTV{sub p} and PTV{sub e}) were created using a three-dimensional expansion of the CTV{sub p} and CTV{sub e}, respectively, of 7 mm. A median dose of 69.3 Gy and 50 Gy was prescribed to the PTV{sub p} and PTV{sub e} respectively, to be delivered in 25 fractions. Upper and lower gastrointestinal toxicity was scored using the Radiation Therapy Oncology Group toxicity and radiotherapy-induced lower intestinal toxicity scoring system. Genitourinary toxicity was scored using a combined Radiation Therapy Oncology Group, LENT-SOMA (late effects normal tissue-subjective, objective, management, analytic), and Common Toxicity Criteria toxicity scoring system. Results: The median follow-up time was 3 months. The mean prescription dose to the CTV{sub p} and PTV{sub p} was 70.4 Gy and 68.6 Gy, respectively. The minimal dose to the CTV{sub e} and PTV{sub e} was 49.0 Gy and 47.0 Gy, respectively. No acute Grade 2 or greater gastrointestinal toxicity occurred. Fourteen patients developed acute Grade 2 lower gastrointestinal toxicity. Acute Grade 3 and 2 genitourinary toxicity developed in 2 and 14 patients, respectively. Conclusion: The results of our study have shown that hypofractionated intensity-modulated arc radiotherapy as primary therapy for N1 prostate cancer is feasible with low toxicity.

  2. Cost-Effectiveness Analysis of Intensity Modulated Radiation Therapy Versus 3-Dimensional Conformal Radiation Therapy for Anal Cancer

    SciTech Connect

    Hodges, Joseph C.; Beg, Muhammad S.; Das, Prajnan; Meyer, Jeffrey

    2014-07-15

    Purpose: To compare the cost-effectiveness of intensity modulated radiation therapy (IMRT) and 3-dimensional conformal radiation therapy (3D-CRT) for anal cancer and determine disease, patient, and treatment parameters that influence the result. Methods and Materials: A Markov decision model was designed with the various disease states for the base case of a 65-year-old patient with anal cancer treated with either IMRT or 3D-CRT and concurrent chemotherapy. Health states accounting for rates of local failure, colostomy failure, treatment breaks, patient prognosis, acute and late toxicities, and the utility of toxicities were informed by existing literature and analyzed with deterministic and probabilistic sensitivity analysis. Results: In the base case, mean costs and quality-adjusted life expectancy in years (QALY) for IMRT and 3D-CRT were $32,291 (4.81) and $28,444 (4.78), respectively, resulting in an incremental cost-effectiveness ratio of $128,233/QALY for IMRT compared with 3D-CRT. Probabilistic sensitivity analysis found that IMRT was cost-effective in 22%, 47%, and 65% of iterations at willingness-to-pay thresholds of $50,000, $100,000, and $150,000 per QALY, respectively. Conclusions: In our base model, IMRT was a cost-ineffective strategy despite the reduced acute treatment toxicities and their associated costs of management. The model outcome was sensitive to variations in local and colostomy failure rates, as well as patient-reported utilities relating to acute toxicities.

  3. Quality of Intensity Modulated Radiation Therapy Treatment Plans Using a {sup 60}Co Magnetic Resonance Image Guidance Radiation Therapy System

    SciTech Connect

    Wooten, H. Omar Green, Olga; Yang, Min; DeWees, Todd; Kashani, Rojano; Olsen, Jeff; Michalski, Jeff; Yang, Deshan; Tanderup, Kari; Hu, Yanle; Li, H. Harold; Mutic, Sasa

    2015-07-15

    Purpose: This work describes a commercial treatment planning system, its technical features, and its capabilities for creating {sup 60}Co intensity modulated radiation therapy (IMRT) treatment plans for a magnetic resonance image guidance radiation therapy (MR-IGRT) system. Methods and Materials: The ViewRay treatment planning system (Oakwood Village, OH) was used to create {sup 60}Co IMRT treatment plans for 33 cancer patients with disease in the abdominal, pelvic, thorax, and head and neck regions using physician-specified patient-specific target coverage and organ at risk (OAR) objectives. Backup plans using a third-party linear accelerator (linac)-based planning system were also created. Plans were evaluated by attending physicians and approved for treatment. The {sup 60}Co and linac plans were compared by evaluating conformity numbers (CN) with 100% and 95% of prescription reference doses and heterogeneity indices (HI) for planning target volumes (PTVs) and maximum, mean, and dose-volume histogram (DVH) values for OARs. Results: All {sup 60}Co IMRT plans achieved PTV coverage and OAR sparing that were similar to linac plans. PTV conformity for {sup 60}Co was within <1% and 3% of linac plans for 100% and 95% prescription reference isodoses, respectively, and heterogeneity was on average 4% greater. Comparisons of OAR mean dose showed generally better sparing with linac plans in the low-dose range <20 Gy, but comparable sparing for organs with mean doses >20 Gy. The mean doses for all {sup 60}Co plan OARs were within clinical tolerances. Conclusions: A commercial {sup 60}Co MR-IGRT device can produce highly conformal IMRT treatment plans similar in quality to linac IMRT for a variety of disease sites. Additional work is in progress to evaluate the clinical benefit of other novel features of this MR-IGRT system.

  4. Bridging the gap between IMRT and VMAT: Dense angularly sampled and sparse intensity modulated radiation therapy

    SciTech Connect

    Li, Ruijiang; Xing, Lei

    2011-09-15

    Purpose: To propose an alternative radiation therapy (RT) planning and delivery scheme with optimal angular beam sampling and intrabeam modulation for improved dose distribution while maintaining high delivery efficiency. Methods: In the proposed approach, coined as dense angularly sampled and sparse intensity modulated RT (DASSIM-RT), a large number of beam angles are used to increase the angular sampling, leading to potentially more conformal dose distributions as compared to conventional IMRT. At the same time, intensity modulation of the incident beams is simplified to eliminate the dispensable segments, compensating the increase in delivery time caused by the increased number of beams and facilitating the plan delivery. In a sense, the proposed approach shifts and transforms, in an optimal fashion, some of the beam segments in conventional IMRT to the added beams. For newly available digital accelerators, the DASSIM-RT delivery can be made very efficient by concatenating the beams so that they can be delivered sequentially without operator's intervention. Different from VMAT, the level of intensity modulation in DASSIS-RT is field specific and optimized to meet the need of each beam direction. Three clinical cases (a head and neck (HN) case, a pancreas case, and a lung case) are used to evaluate the proposed RT scheme. DASSIM-RT, VMAT, and conventional IMRT plans are compared quantitatively in terms of the conformality index (CI) and delivery efficiency. Results: Plan quality improves generally with the number and intensity modulation of the incident beams. For a fixed number of beams or fixed level of intensity modulation, the improvement saturates after the intensity modulation or number of beams reaches to a certain level. An interplay between the two variables is observed and the saturation point depends on the values of both variables. For all the cases studied here, the CI of DASSIM-RT with 15 beams and 5 intensity levels (0.90, 0.79, and 0.84 for the HN

  5. Balancing control and simplicity: A variable aggregation method in intensity modulated radiation therapy planning*

    PubMed Central

    Süss, Philipp; Küfer, Karl-Heinz

    2008-01-01

    It is commonly believed that not all degrees of freedom are needed to produce good solutions for the treatment planning problem in intensity modulated radiation therapy (IMRT). However, typical methods to exploit this fact either increase the complexity of the optimization problem or are heuristic in nature. In this work we introduce a technique based on adaptively refining variable clusters to successively attain better treatment plans. The approach creates approximate solutions based on smaller models that may come arbitrarily close to the optimal solution. Although the method is illustrated using a specific treatment planning model, the components constituting the variable clustering and the adaptive refinement are independent of the particular optimization problem. PMID:19255600

  6. Matching Intensity-Modulated Radiation Therapy to an Anterior Low Neck Field

    SciTech Connect

    Amdur, Robert J. Liu, Chihray; Li, Jonathan; Mendenhall, William; Hinerman, Russell

    2007-10-01

    When using intensity-modulated radiation therapy (IMRT) to treat head and neck cancer with the primary site above the level of the larynx, there are two basic options for the low neck lymphatics: to treat the entire neck with IMRT, or to match the IMRT plan to a conventional anterior 'low neck' field. In view of the potential advantages of using a conventional low neck field, it is important to look for ways to minimize or manage the problems of matching IMRT to a conventional radiotherapy field. Treating the low neck with a single anterior field and the standard larynx block decreases the dose to the larynx and often results in a superior IMRT plan at the primary site. The purpose of this article is to review the most applicable studies and to discuss our experience with implementing a technique that involves moving the position of the superior border of the low neck field several times during a single treatment fraction.

  7. Simple tool for prediction of parotid gland sparing in intensity-modulated radiation therapy

    SciTech Connect

    Gensheimer, Michael F.; Hummel-Kramer, Sharon M.; Cain, David; Quang, Tony S.

    2015-10-01

    Sparing one or both parotid glands is a key goal when planning head and neck cancer radiation treatment. If the planning target volume (PTV) overlaps one or both parotid glands substantially, it may not be possible to achieve adequate gland sparing. This finding results in physicians revising their PTV contours after an intensity-modulated radiation therapy (IMRT) plan has been run and reduces workflow efficiency. We devised a simple formula for predicting mean parotid gland dose from the overlap of the parotid gland and isotropically expanded PTV contours. We tested the tool using 44 patients from 2 institutions and found agreement between predicted and actual parotid gland doses (mean absolute error = 5.3 Gy). This simple method could increase treatment planning efficiency by improving the chance that the first plan presented to the physician will have optimal parotid gland sparing.

  8. Intensity-modulated arc therapy to improve radiation dose delivery in the treatment of abdominal neuroblastoma.

    PubMed

    Gains, Jennifer E; Stacey, Christopher; Rosenberg, Ivan; Mandeville, Henry C; Chang, Yen-Ch'ing; D'Souza, Derek; Moroz, Veronica; Wheatley, Keith; Gaze, Mark N

    2013-03-01

    The standard European radiotherapy technique for children with neuroblastoma is a conventional parallel opposed pair. This frequently results in compromise on planning target volume coverage to stay within normal tissue tolerances. This study investigates the use of an intensity-modulated arc therapy (IMAT) technique to improve dose distribution and allow better protocol compliance. Among 20 previously treated patients, ten had received the full prescribed dose with conventional planning (protocol compliant) and ten had a compromise on planning target volume coverage (protocol noncompliant). All patients were replanned with IMAT. Dosimetric parameters of the conventional radiotherapy and IMAT were compared. The dose received by 98% of the planning target volume, homogeneity and conformity indices were all improved with IMAT (p < 0.001). IMAT would have enabled delivery of the full protocol dose in eight out of ten protocol-noncompliant patients. IMAT may improve outcomes through improved protocol compliance and better dose distributions.

  9. A comparison of three optimization algorithms for intensity modulated radiation therapy.

    PubMed

    Pflugfelder, Daniel; Wilkens, Jan J; Nill, Simeon; Oelfke, Uwe

    2008-01-01

    In intensity modulated treatment techniques, the modulation of each treatment field is obtained using an optimization algorithm. Multiple optimization algorithms have been proposed in the literature, e.g. steepest descent, conjugate gradient, quasi-Newton methods to name a few. The standard optimization algorithm in our in-house inverse planning tool KonRad is a quasi-Newton algorithm. Although this algorithm yields good results, it also has some drawbacks. Thus we implemented an improved optimization algorithm based on the limited-memory Broyden-Fletcher-Goldfarb-Shanno (L-BFGS) routine. In this paper the improved optimization algorithm is described. To compare the two algorithms, several treatment plans are optimized using both algorithms. This included photon (IMRT) as well as proton (IMPT) intensity modulated therapy treatment plans. To present the results in a larger context the widely used conjugate gradient algorithm was also included into this comparison. On average, the improved optimization algorithm was six times faster to reach the same objective function value. However, it resulted not only in an acceleration of the optimization. Due to the faster convergence, the improved optimization algorithm usually terminates the optimization process at a lower objective function value. The average of the observed improvement in the objective function value was 37%. This improvement is clearly visible in the corresponding dose-volume-histograms. The benefit of the improved optimization algorithm is particularly pronounced in proton therapy plans. The conjugate gradient algorithm ranked in between the other two algorithms with an average speedup factor of two and an average improvement of the objective function value of 30%.

  10. Intensity Modulated Radiation Therapy for Primary Soft Tissue Sarcoma of the Extremity: Preliminary Results

    SciTech Connect

    Alektiar, Kaled M. . E-mail: alektiak@mskcc.org; Hong, Linda; Brennan, Murray F.; Della-Biancia, Cesar; Singer, Samuel

    2007-06-01

    Purpose: To report preliminary results on using intensity modulated radiation therapy (IMRT) as an adjuvant treatment in primary soft tissue sarcoma (STS) of the extremity. Methods and Materials: Between February 2002 and March 2005, 31 adult patients with primary STS of the extremity were treated with surgery and adjuvant IMRT. Tumor size was >10 cm in 74% of patients and grade was high in 77%. Preoperative IMRT was given to 7 patients (50 Gy) and postoperative IMRT (median dose, 63 Gy) was given to 24 patients. Complete gross resection including periosteal stripping or bone resection was required in 10, and neurolysis or nerve resection in 20. The margins were positive or within 1 mm in 17. Complications from surgery and radiation therapy (RT) were assessed using the Common Terminology Criteria for Adverse Events grading system. Results: Median follow-up time was 23 months. Grade 1 RT dermatitis developed in 71% of patients, Grade 2 in 16%, and Grade 3 in 10%. Infectious wound complications developed in 13% and noninfectious complications in 10%. Two patients (6.4%) developed fractures. Grade 1 neuropathy developed in 28% of patients and Grade 2 in 5%. The rates of Grade 1 and 2 joint stiffness were each 19%. Grade 1 edema was observed in 19% of patients and Grade 2 in 13%. The 2-year local control, distant control, and overall survival were 95%, 65%, and 81%, respectively. Conclusion: Intensity modulated RT appears to provide excellent local control in a difficult group of high-risk patients. The morbidity profile is also favorable, but longer follow-up is needed to confirm the results from this study.

  11. Intensity-modulated radiation therapy, protons, and the risk of second cancers

    SciTech Connect

    Hall, Eric J. . E-mail: ejh1@columbia.edu

    2006-05-01

    Intensity-modulated radiation therapy (IMRT) allows dose to be concentrated in the tumor volume while sparing normal tissues. However, the downside to IMRT is the potential to increase the number of radiation-induced second cancers. The reasons for this potential are more monitor units and, therefore, a larger total-body dose because of leakage radiation and, because IMRT involves more fields, a bigger volume of normal tissue is exposed to lower radiation doses. Intensity-modulated radiation therapy may double the incidence of solid cancers in long-term survivors. This outcome may be acceptable in older patients if balanced by an improvement in local tumor control and reduced acute toxicity. On the other hand, the incidence of second cancers is much higher in children, so that doubling it may not be acceptable. IMRT represents a special case for children for three reasons. First, children are more sensitive to radiation-induced cancer than are adults. Second, radiation scattered from the treatment volume is more important in the small body of the child. Third, the question of genetic susceptibility arises because many childhood cancers involve a germline mutation. The levels of leakage radiation in current Linacs are not inevitable. Leakage can be reduced but at substantial cost. An alternative strategy is to replace X-rays with protons. However, this change is only an advantage if the proton machine employs a pencil scanning beam. Many proton facilities use passive modulation to produce a field of sufficient size, but the use of a scattering foil produces neutrons, which results in an effective dose to the patient higher than that characteristic of IMRT. The benefit of protons is only achieved if a scanning beam is used in which the doses are 10 times lower than with IMRT.

  12. Robust Intensity Modulated Proton Therapy (IMPT) Increases Estimated Clinical Benefit in Head and Neck Cancer Patients

    PubMed Central

    van Dijk, Lisanne V.; Steenbakkers, Roel J. H. M.; ten Haken, Bennie; van der Laan, Hans Paul; van ‘t Veld, Aart A.; Langendijk, Johannes A.; Korevaar, Erik W.

    2016-01-01

    Purpose To compare the clinical benefit of robust optimized Intensity Modulated Proton Therapy (minimax IMPT) with current photon Intensity Modulated Radiation Therapy (IMRT) and PTV-based IMPT for head and neck cancer (HNC) patients. The clinical benefit is quantified in terms of both Normal Tissue Complication Probability (NTCP) and target coverage in the case of setup and range errors. Methods and Materials For 10 HNC patients, PTV-based IMRT (7 fields), minimax and PTV-based IMPT (2, 3, 4, 5 and 7 fields) plans were tested on robustness. Robust optimized plans differed from PTV-based plans in that they target the CTV and penalize possible error scenarios, instead of using the static isotropic CTV-PTV margin. Perturbed dose distributions of all plans were acquired by simulating in total 8060 setup (±3.5 mm) and range error (±3%) combinations. NTCP models for xerostomia and dysphagia were used to predict the clinical benefit of IMPT versus IMRT. Results The robustness criterion was met in the IMRT and minimax IMPT plans in all error scenarios, but this was only the case in 1 of 40 PTV-based IMPT plans. Seven (out of 10) patients had relatively large NTCP reductions in minimax IMPT plans compared to IMRT. For these patients, xerostomia and dysphagia NTCP values were reduced by 17.0% (95% CI; 13.0–21.1) and 8.1% (95% CI; 4.9–11.2) on average with minimax IMPT. Increasing the number of fields did not contribute to plan robustness, but improved organ sparing. Conclusions The estimated clinical benefit in terms of NTCP of robust optimized (minimax) IMPT is greater than that of IMRT and PTV-based IMPT in HNC patients. Furthermore, the target coverage of minimax IMPT plans in the presence of errors was comparable to IMRT plans. PMID:27030987

  13. Multifield Optimization Intensity Modulated Proton Therapy for Head and Neck Tumors: A Translation to Practice

    SciTech Connect

    Frank, Steven J.; Cox, James D.; Gillin, Michael; Mohan, Radhe; Garden, Adam S.; Rosenthal, David I.; Gunn, G. Brandon; Weber, Randal S.; Kies, Merrill S.; Lewin, Jan S.; Munsell, Mark F.; Palmer, Matthew B.; Sahoo, Narayan; Zhang, Xiaodong; Liu, Wei; Zhu, X. Ronald

    2014-07-15

    Background: We report the first clinical experience and toxicity of multifield optimization (MFO) intensity modulated proton therapy (IMPT) for patients with head and neck tumors. Methods and Materials: Fifteen consecutive patients with head and neck cancer underwent MFO-IMPT with active scanning beam proton therapy. Patients with squamous cell carcinoma (SCC) had comprehensive treatment extending from the base of the skull to the clavicle. The doses for chemoradiation therapy and radiation therapy alone were 70 Gy and 66 Gy, respectively. The robustness of each treatment plan was also analyzed to evaluate sensitivity to uncertainties associated with variations in patient setup and the effect of uncertainties with proton beam range in patients. Proton beam energies during treatment ranged from 72.5 to 221.8 MeV. Spot sizes varied depending on the beam energy and depth of the target, and the scanning nozzle delivered the spot scanning treatment “spot by spot” and “layer by layer.” Results: Ten patients presented with SCC and 5 with adenoid cystic carcinoma. All 15 patients were able to complete treatment with MFO-IMPT, with no need for treatment breaks and no hospitalizations. There were no treatment-related deaths, and with a median follow-up time of 28 months (range, 20-35 months), the overall clinical complete response rate was 93.3% (95% confidence interval, 68.1%-99.8%). Xerostomia occurred in all 15 patients as follows: grade 1 in 10 patients, grade 2 in 4 patients, and grade 3 in 1 patient. Mucositis within the planning target volumes was seen during the treatment of all patients: grade 1 in 1 patient, grade 2 in 8 patients, and grade 3 in 6 patients. No patient experienced grade 2 or higher anterior oral mucositis. Conclusions: To our knowledge, this is the first clinical report of MFO-IMPT for head and neck tumors. Early clinical outcomes are encouraging and warrant further investigation of proton therapy in prospective clinical trials.

  14. High-Intensity Focused Ultrasound: Current Status for Image-Guided Therapy

    PubMed Central

    Copelan, Alexander; Hartman, Jason; Chehab, Monzer; Venkatesan, Aradhana M.

    2015-01-01

    Image-guided high-intensity focused ultrasound (HIFU) is an innovative therapeutic technology, permitting extracorporeal or endocavitary delivery of targeted thermal ablation while minimizing injury to the surrounding structures. While ultrasound-guided HIFU was the original image-guided system, MR-guided HIFU has many inherent advantages, including superior depiction of anatomic detail and superb real-time thermometry during thermoablation sessions, and it has recently demonstrated promising results in the treatment of both benign and malignant tumors. HIFU has been employed in the management of prostate cancer, hepatocellular carcinoma, uterine leiomyomas, and breast tumors, and has been associated with success in limited studies for palliative pain management in pancreatic cancer and bone tumors. Nonthermal HIFU bioeffects, including immune system modulation and targeted drug/gene therapy, are currently being explored in the preclinical realm, with an emphasis on leveraging these therapeutic effects in the care of the oncology patient. Although still in its early stages, the wide spectrum of therapeutic capabilities of HIFU offers great potential in the field of image-guided oncologic therapy. PMID:26622104

  15. Patient and Family Perceptions of Physical Therapy in the Medical Intensive Care Unit

    PubMed Central

    Sottile, Peter D; Nordon-Craft, Amy; Malone, Daniel; Schenkman, Margaret; Moss, Marc

    2015-01-01

    Purpose Patient and family member perceptions of physical therapy (PT) in the intensive care unit and the factors that influence their degree of satisfaction have not been described. Methods A panel of experts developed a questionnaire that assessed patient and family perceptions of PT. Critically ill patients and their family members were asked to complete the survey. Patient and family member scores were compared and stratified by age, gender, and mechanical ventilation for greater than 14 days compared to 14 days or less. Results A total of 55 patients and 49 family members completed the survey. Patients and family members reported that PT was necessary and beneficial to recovery, despite associating PT with difficulty, exertion, and discomfort. Patient perceptions were similar regardless of age or gender. Family members underestimated a patient's enjoyment of PT (p=0.03). For individuals who required prolonged mechanical ventilation (>14 days), patients reported that PT was more difficult (p=0.03), less enjoyable (p=0.049), and family members reported PT as causing greater discomfort (p=0.005). Additionally, family members of patients who required prolonged mechanical ventilation felt that PT was less beneficial (p=0.01). Conclusions Physical therapy is perceived as necessary and beneficial to recovery by critically ill patients and family members. PMID:26038155

  16. Efficacy and tolerability of a combined lipid-lowering nutraceutical on cholesterolemia, hs-CRP level and endothelial function in moderately hypercholesterolemic subjects.

    PubMed

    Cicero, A F; Colletti, A; Rosticci, M; Grandi, E; Borghi, C

    2016-01-01

    Our aim was to test, by a double-blind, placebo-controlled randomized clinical trial, whether a short-term treatment with a combined lipid-lowering nutraceutical could improve endothelial function in a cohort of moderately hypercholesterolemic subjects. Thus, 80 healthy, moderately hypercholesterolemic subjects were consecutively enrolled and, after 4 weeks of stabilization diet, they were randomized to either the tested lipid-lowering nutraceutical or placebo for 8 weeks. At the beginning and end of treatment a complete lipid pattern, safety parameters, hs-CRP and endothelial function were measured. When compared to placebo, during nutraceutical treatment patients experienced a more favorable percentage change in total cholesterol (TC vs baseline: -17.9%; TC vs placebo: -5.6%), LDL-cholesterol (LDL-C vs baseline: -23.3%; LDL-C vs placebo: -2.8%), hs-CRP (hs-CRP vs baseline: -2.4%; hs-CRP vs placebo: -1.5%), and endothelial function (pulse volume displacement vs baseline: +17%; pulse volume displacement vs placebo treatment: -3.3%). No significant difference was observed in respect to effects on triglycerides, HDL-cholesterol and safety parameters. On the basis of our data, the tested lipid-lowering nutraceutical seems to significantly improve endothelial function in moderately hypercholesterolemic subjects. These results have to be confirmed on larger patient samples and over longer periods.

  17. High remission and low relapse with prolonged intensive DMARD therapy in rheumatoid arthritis (PRINT)

    PubMed Central

    Li, Ru; Zhao, Jin-Xia; Su, Yin; He, Jing; Chen, Li-Na; Gu, Fei; Zhao, Cheng; Deng, Xue-Rong; Zhou, Wei; Hao, Yan-Jie; Xue, Yu; Liu, Hua-Xiang; Zhao, Yi; Zou, Qing-Hua; Liu, Xiang-Yuan; Zhu, Ping; Sun, Ling-Yun; Zhang, Zhuo-Li; Zou, He-Jian; Li, Xing-Fu; Liu, Yi; Fang, Yong-Fei; Keystone, Edward; McInnes, Iain B.; Li, Zhan-Guo

    2016-01-01

    Abstract Objectives: To determine whether prolonged intensive disease-modifying antirheumatic drug (DMARD) treatment (PRINT) leads to high remission and low relapse rates in patients with severe rheumatoid arthritis (RA). Methods: In this multicenter, randomized and parallel treatment trial, 346 patients with active RA (disease activity score (28 joints) [DAS28] (erythrocyte sedimentation rate [ESR]) > 5.1) were enrolled from 9 centers. In phase 1, patients received intensive treatment with methotrexate, leflunomide, and hydroxychloroquine, up to 36 weeks, until remission (DAS28 ≤ 2.6) or a low disease activity (2.6 < DAS28 ≤ 3.2) was achieved. In phase 2, patients achieving remission or low disease activity were followed up with randomization to 1 of 2 step-down protocols: leflunomide plus hydroxychloroquine combination or leflunomide monotherapy. The primary endpoints were good European League Against Rheumatism (EULAR) response (DAS28 (ESR) < 3.2 and a decrease of DAS28 by at least 1.2) during the intensive treatment and the disease state retention rate during step-down maintenance treatment. Predictors of a good EULAR response in the intensive treatment period and disease flare in the maintenance period were sought. Results: A good EULAR response was achieved in 18.7%, 36.9%, and 54.1% of patients at 12, 24, and 36 weeks, respectively. By 36 weeks, 75.4% of patients achieved good and moderate EULAR responses. Compared with those achieving low disease activity and a high health assessment questionnaire (HAQ > 0.5), patients achieving remission (DAS28 ≤ 2.6) and low HAQ (≤ 0.5) had a significantly higher retention rate when tapering the DMARDs treatment (P = 0.046 and P = 0.01, respectively). There was no advantage on tapering to combination rather than monotherapy. Conclusions: Remission was achieved in a proportion of patients with RA receiving prolonged intensive DMARD therapy. Low disease activity at the start of disease taper leads to less subsequent

  18. The effect of air fluidised bed therapy on hypermetabolism in intensive care unit patients.

    PubMed

    Blackwood, B; McLeod, H N; Lavery, G G; Hayes, E E; Rowlands, B J; Clarke, R S

    1996-08-01

    Major trauma is associated with a hypermetabolic (increased resting energy expenditure) and hypercatabolic (negative nitrogen balance) response. Studies have suggested that nursing injured patients at higher temperatures reduces the metabolic response (Ryan & Clague 1990). In this study the energy expenditure and urinary nitrogen excretion of major trauma patients was examined when nursing them on an air-fluidised bed at 32 degrees C using a crossover study design. Patients were randomised into two groups. Group A patients (n = 8) remained on a standard intensive care unit bed at an environmental temperature of 22 degrees C while Group B patients (n = 6) were placed on an air-fluidised bed operating at 32 degrees C. On days 4 and 5 after injury, energy expenditure and urinary nitrogen excretion were measured. On day 6, Group A patients transferred to an air-fluidised bed and Group B patients to a standard bed. On days 7 and 8, energy expenditure and urinary nitrogen excretion were again measured. Within group comparisons of energy expenditure and urinary nitrogen excretion were made for days 3 and 4 (period 1) and days 7 and 8 (period 2). In both groups, mean energy expenditure was significantly increased in the second period irrespective of whether air-fluidised bed therapy preceded or followed a period on a standard bed. We concluded that nursing intensive care patients on an air-fluidised bed at 32 degrees C did not influence energy expenditure or urinary nitrogen.

  19. ["The vein is missed": meanings of intravenous therapy practice in Neonatal Intensive Care Unit].

    PubMed

    Rodrigues, Elisa da Conceição; Cunha, Sueli Rezende; Gomes, Romeu

    2012-04-01

    Intravenous Therapy (IVT) is an important item among the necessary technologies for the survival of high-risk new-born babies. However, it is also a source of pain, stress and risk of serious complications. This article aims to assess the meanings of IVT as ascribed by care teams and to discuss the reflection of such meanings on the attention to new-born babies. The article, with a theoretical referential in Cultural Anthropology, presents an ethnographic case study carried out in a Neonatal Intensive Care Unit of municipal administration in Rio de Janeiro. Subjects were nine nurses, four doctors, and three nurse assistants. Data collection was carried out with a semi-structured interview and participative observation. The qualitative analysis was performed using the method of interpretation of the senses. Meanings, interweaved with the cultural network, showed that IVT practice is often reduced to peripheral puncture techniques, bringing on a series of complications for high risk new-born babies and intense emotional waste for the professional team and the family. Re-signification of IVT practice will only be possible with a critical analysis of the cultural patterns it is now based on.

  20. Low-intensity laser therapy to treat dentin hypersensitivity: comparative clinical study using different light doses

    NASA Astrophysics Data System (ADS)

    Lizarelli, Rosane F. Z.; Mazzetto, Marcello O.; Bagnato, Vanderlei S.

    2001-04-01

    Dentin hypersensitivity is the most common patient's complain related to pain. In fact, this is a challenge to treat specially if conventional techniques are used. The possibility to treat pain through a low intensity laser gives us an opportunity to solve this important clinical problem without promote a discomfort to patient. The main point here is not if this kind of treatment is anti- inflammatory to pulp and/or biostimulatory to production of irregular secondary dentin. The most important point here is to understand how much energy is necessary to reach conditions where to tooth become insensible to external stimulus. Our double-blinded study compared a group without laser (Placebo) with five other groups where different doses at 660 nm low intensity laser were employed. The final conclusion is that for 660 nm laser therapy, the doses from 0.13 to 2.0 J/cm2 were more efficiency than the others. The follow up care in this study was of 45 days.

  1. Intensity-Modulated Radiation Therapy With Concurrent Chemotherapy as Preoperative Treatment for Localized Gastric Adenocarcinoma

    SciTech Connect

    Chakravarty, Twisha; Crane, Christopher H.; Ajani, Jaffer A.; Mansfield, Paul F.; Briere, Tina M.; Beddar, A. Sam; Mok, Henry; Reed, Valerie K.; Krishnan, Sunil; Delclos, Marc E.; Das, Prajnan

    2012-06-01

    Purpose: The goal of this study was to evaluate dosimetric parameters, acute toxicity, pathologic response, and local control in patients treated with preoperative intensity-modulated radiation therapy (IMRT) and concurrent chemotherapy for localized gastric adenocarcinoma. Methods: Between November 2007 and April 2010, 25 patients with localized gastric adenocarcinoma were treated with induction chemotherapy, followed by preoperative IMRT and concurrent chemotherapy and, finally, surgical resection. The median radiation therapy dose was 45 Gy. Concurrent chemotherapy was 5-fluorouracil and oxaliplatin in 18 patients, capecitabine in 3, and other regimens in 4. Subsequently, resection was performed with total gastrectomy in 13 patients, subtotal gastrectomy in 7, and other surgeries in 5. Results: Target coverage, expressed as the ratio of the minimum dose received by 99% of the planning target volume to the prescribed dose, was a median of 0.97 (range, 0.92-1.01). The median V{sub 30} (percentage of volume receiving at least 30 Gy) for the liver was 26%; the median V{sub 20} (percentage of volume receiving at least 20 Gy) for the right and left kidneys was 14% and 24%, respectively; and the median V{sub 40} (percentage of volume receiving at least 40 Gy) for the heart was 18%. Grade 3 acute toxicity developed in 14 patients (56%), including dehydration in 10, nausea in 8, and anorexia in 5. Grade 4 acute toxicity did not develop in any patient. There were no significant differences in the rates of acute toxicity, hospitalization, or feeding tube use in comparison to those in a group of 50 patients treated with preoperative three-dimensional conformal radiation therapy with concurrent chemotherapy. R0 resection was obtained in 20 patients (80%), and pathologic complete response occurred in 5 (20%). Conclusions: Preoperative IMRT for gastric adenocarcinoma was well tolerated, accomplished excellent target coverage and normal structure sparing, and led to appropriate

  2. Acute Esophagus Toxicity in Lung Cancer Patients After Intensity Modulated Radiation Therapy and Concurrent Chemotherapy

    SciTech Connect

    Kwint, Margriet; Uyterlinde, Wilma; Nijkamp, Jasper; Chen, Chun; Bois, Josien de; Sonke, Jan-Jakob; Heuvel, Michel van den; Knegjens, Joost; Herk, Marcel van; Belderbos, Jose

    2012-10-01

    Purpose: The purpose of this study was to investigate the dose-effect relation between acute esophageal toxicity (AET) and the dose-volume parameters of the esophagus after intensity modulated radiation therapy (IMRT) and concurrent chemotherapy for patients with non-small cell lung cancer (NSCLC). Patients and Methods: One hundred thirty-nine patients with inoperable NSCLC treated with IMRT and concurrent chemotherapy were prospectively analyzed. The fractionation scheme was 66 Gy in 24 fractions. All patients received concurrently a daily dose of cisplatin (6 mg/m Superscript-Two ). Maximum AET was scored according to Common Toxicity Criteria 3.0. Dose-volume parameters V5 to V70, D{sub mean} and D{sub max} of the esophagus were calculated. A logistic regression analysis was performed to analyze the dose-effect relation between these parameters and grade {>=}2 and grade {>=}3 AET. The outcome was compared with the clinically used esophagus V35 prediction model for grade {>=}2 after radical 3-dimensional conformal radiation therapy (3DCRT) treatment. Results: In our patient group, 9% did not experience AET, and 31% experienced grade 1 AET, 38% grade 2 AET, and 22% grade 3 AET. The incidence of grade 2 and grade 3 AET was not different from that in patients treated with CCRT using 3DCRT. The V50 turned out to be the most significant dosimetric predictor for grade {>=}3 AET (P=.012). The derived V50 model was shown to predict grade {>=}2 AET significantly better than the clinical V35 model (P<.001). Conclusions: For NSCLC patients treated with IMRT and concurrent chemotherapy, the V50 was identified as most accurate predictor of grade {>=}3 AET. There was no difference in the incidence of grade {>=}2 AET between 3DCRT and IMRT in patients treated with concurrent chemoradiation therapy.

  3. Clinical Impact of Sample Interference on Intensive Insulin Therapy in Severely Burned Patients: A Pilot Study

    PubMed Central

    Tran, Nam K.; Godwin, Zachary R.; Bockhold, Jennifer C.; Passerini, Anthony G.; Cheng, Julian; Ingemason, Morgan

    2013-01-01

    Objective Severely burned patients benefit from intensive insulin therapy (IIT) for tight glycemic control (TGC). We evaluated the clinical impact of automatic correction of hematocrit and ascorbic acid interference for bedside glucose monitoring performance in critically ill burn patients. Methods The performance of two point-of-care glucose monitoring systems (GMS): (a) GMS1, an autocorrecting device, and (b) GMS2, a non-correcting device were compared. Sixty remnant arterial blood samples were collected in a prospective observational study to evaluate hematocrit and ascorbic acid effects on GMS1 vs. GMS2 accuracy paired against a plasma glucose reference. Next we enrolled 12 patients in a pilot randomized controlled trial (RCT). Patients were randomized 1:1 to receive IIT targeting a TGC interval of 111–151 mg/dL and guided by either GMS1 or GMS2. GMS bias, mean insulin rate, and glycemic variability were calculated. Results In the prospective study, GMS1 results were similar to plasma glucose results (mean bias: −0.75[4.0] mg/dL, n=60, P=0.214). GMS2 results significantly differed from paired plasma glucose results (mean bias: −5.66[18.7] mg/dL, n=60, P=0.048). Ascorbic acid therapy elicited significant GMS2 performance bias (29.2[27.2], P<0.001). RCT results reported lower mean bias (P<0.001), glycemic variability (P<0.05), mean insulin rate (P<0.001), and frequency of hypoglycemia (P<0.001) in the GMS1 group than the GMS2 group. Conclusions Anemia and high dose ascorbic acid therapy negatively impact GMS accuracy and TGC in burn patients. Automatic correction of confounding factors improves glycemic control. Further studies are warranted to determine outcomes associated with accurate glucose monitoring during IIT. PMID:23884048

  4. Incorporation of gantry angle correction for 3D dose prediction in intensity-modulated radiation therapy

    PubMed Central

    Sumida, Iori; Yamaguchi, Hajime; Kizaki, Hisao; Aboshi, Keiko; Tsujii, Mari; Yamada, Yuji; Yagi, Masashi; Ogawa, Kazuhiko

    2015-01-01

    Pretreatment dose verification with beam-by-beam analysis for intensity-modulated radiation therapy (IMRT) is commonly performed with a gantry angle of 0° using a 2D diode detector array. Any changes in multileaf collimator (MLC) position between the actual treatment gantry angle and 0° may result in deviations from the planned dose. We evaluated the effects of MLC positioning errors between the actual treatment gantry angles and nominal gantry angles. A gantry angle correction (GAC) factor was generated by performing a non-gap test at various gantry angles using an electronic portal imaging device (EPID). To convert pixel intensity to dose at the MLC abutment positions, a non-gap test was performed using an EPID and a film at 0° gantry angle. We then assessed the correlations between pixel intensities and doses. Beam-by-beam analyses for 15 prostate IMRT cases as patient-specific quality assurance were performed with a 2D diode detector array at 0° gantry angle to determine the relative dose error for each beam. The resulting relative dose error with or without GAC was added back to the original dose grid for each beam. We compared the predicted dose distributions with or without GAC for film measurements to validate GAC effects. A gamma pass rate with a tolerance of 2%/2 mm was used to evaluate these dose distributions. The gamma pass rate with GAC was higher than that without GAC (P = 0.01). The predicted dose distribution improved with GAC, although the dosimetric effect to a patient was minimal. PMID:25742866

  5. Incorporation of gantry angle correction for 3D dose prediction in intensity-modulated radiation therapy.

    PubMed

    Sumida, Iori; Yamaguchi, Hajime; Kizaki, Hisao; Aboshi, Keiko; Tsujii, Mari; Yamada, Yuji; Yagi, Masashi; Ogawa, Kazuhiko

    2015-05-01

    Pretreatment dose verification with beam-by-beam analysis for intensity-modulated radiation therapy (IMRT) is commonly performed with a gantry angle of 0° using a 2D diode detector array. Any changes in multileaf collimator (MLC) position between the actual treatment gantry angle and 0° may result in deviations from the planned dose. We evaluated the effects of MLC positioning errors between the actual treatment gantry angles and nominal gantry angles. A gantry angle correction (GAC) factor was generated by performing a non-gap test at various gantry angles using an electronic portal imaging device (EPID). To convert pixel intensity to dose at the MLC abutment positions, a non-gap test was performed using an EPID and a film at 0° gantry angle. We then assessed the correlations between pixel intensities and doses. Beam-by-beam analyses for 15 prostate IMRT cases as patient-specific quality assurance were performed with a 2D diode detector array at 0° gantry angle to determine the relative dose error for each beam. The resulting relative dose error with or without GAC was added back to the original dose grid for each beam. We compared the predicted dose distributions with or without GAC for film measurements to validate GAC effects. A gamma pass rate with a tolerance of 2%/2 mm was used to evaluate these dose distributions. The gamma pass rate with GAC was higher than that without GAC (P = 0.01). The predicted dose distribution improved with GAC, although the dosimetric effect to a patient was minimal.

  6. Fatal pneumonitis associated with intensity-modulated radiation therapy for mesothelioma

    SciTech Connect

    Allen, Aaron M. . E-mail: aallen@lroc.harvard.edu; Czerminska, Maria; Jaenne, Pasi A.; Sugarbaker, David J.; Bueno, Raphael; Harris, Jay R.; Court, Laurence; Baldini, Elizabeth H.

    2006-07-01

    Purpose: To describe the initial experience at Dana-Farber Cancer Institute/Brigham and Women's Hospital with intensity-modulated radiation therapy (IMRT) as adjuvant therapy after extrapleural pneumonectomy (EPP) and adjuvant chemotherapy. Methods and Materials: The medical records of patients treated with IMRT after EPP and adjuvant chemotherapy were retrospectively reviewed. IMRT was given to a dose of 54 Gy to the clinical target volume in 1.8 Gy daily fractions. Treatment was delivered with a dynamic multileaf collimator using a sliding window technique. Eleven of 13 patients received heated intraoperative cisplatin chemotherapy (225 mg/m{sup 2}). Two patients received neoadjuvant intravenous cisplatin/pemetrexed, and 10 patients received adjuvant cisplatin/pemetrexed chemotherapy after EPP but before radiation therapy. All patients received at least 2 cycles of intravenous chemotherapy. The contralateral lung was limited to a V20 (volume of lung receiving 20 Gy or more) of 20% and a mean lung dose (MLD) of 15 Gy. All patients underwent fluorodeoxyglucose positron emission tomography (FDG-PET) for staging, and any FDG-avid areas in the hemithorax were given a simultaneous boost of radiotherapy to 60 Gy. Statistical comparisons were done using two-sided t test. Results: Thirteen patients were treated with IMRT from December 2004 to September 2005. Six patients developed fatal pneumonitis after treatment. The median time from completion of IMRT to the onset of radiation pneumonitis was 30 days (range 5-57 days). Thirty percent of patients (4 of 13) developed acute Grade 3 nausea and vomiting. One patient developed acute Grade 3 thrombocytopenia. The median V20, MLD, and V5 (volume of lung receiving 5 Gy or more) for the patients who developed pneumonitis was 17.6% (range, 15.3-22.3%), 15.2 Gy (range, 13.3-17 Gy), and 98.6% (range, 81-100%), respectively, as compared with 10.9% (range, 5.5-24.7%) (p = 0.08), 12.9 Gy (range, 8.7-16.9 Gy) (p = 0.07), and 90% (range

  7. Understanding the continuous renal replacement therapy circuit for acute renal failure support: a quality issue in the intensive care unit.

    PubMed

    Boyle, Martin; Baldwin, Ian

    2010-01-01

    Delivery of renal replacement therapy is now a core competency of intensive care nursing. The safe and effective delivery of this form of therapy is a quality issue for intensive care, requiring an understanding of the principles underlying therapy and the functioning of machines used. Continuous hemofiltration, first described in 1977, used a system where blood flowed from arterial to venous cannulas through a small-volume, low-resistance, and high-flux filter. Monitoring of these early systems was limited, and without a machine interface, less nursing expertise was required. Current continuous renal replacement therapy machines offer user-friendly interfaces, cassette-style circuits, and comprehensive circuit diagnostics and monitoring. Although these machines conceal complexity behind a user-friendly interface, it remains important that nurses have sufficient knowledge for their use and the ability to compare and contrast circuit setups and functions for optimal and efficient treatment.

  8. Optimization and quality assurance of an image-guided radiation therapy system for intensity-modulated radiation therapy radiotherapy.

    PubMed

    Tsai, Jen-San; Micaily, Bizhan; Miyamoto, Curtis

    2012-01-01

    To develop a quality assurance (QA) of XVI cone beam system (XVIcbs) for its optimal imaging-guided radiotherapy (IGRT) implementation, and to construe prostate tumor margin required for intensity-modulated radiation therapy (IMRT) if IGRT is unavailable. XVIcbs spatial accuracy was explored with a humanoid phantom; isodose conformity to lesion target with a rice phantom housing a soap as target; image resolution with a diagnostic phantom; and exposure validation with a Radcal ion chamber. To optimize XVIcbs, rotation flexmap on coincidency between gantry rotational axis and that of XVI cone beam scan was investigated. Theoretic correlation to image quality of XVIcbs rotational axis stability was elaborately studied. Comprehensive QA of IGRT using XVIcbs has initially been explored and then implemented on our general IMRT treatments, and on special IMRT radiotherapies such as head and neck (H and N), stereotactic radiation therapy (SRT), stereotactic radiosurgery (SRS), and stereotactic body radiotherapy (SBRT). Fifteen examples of prostate setup accounted for 350 IGRT cone beam system were analyzed. IGRT accuracy results were in agreement ± 1 mm. Flexmap 0.25 mm met the manufacturer's specification. Films confirmed isodose coincidence with target (soap) via XVIcbs, otherwise not. Superficial doses were measured from 7.2-2.5 cGy for anatomic diameters 15-33 cm, respectively. Image quality was susceptible to rotational stability or patient movement. IGRT using XVIcbs on general IMRT treatments such as prostate, SRT, SRS, and SBRT for setup accuracy were verified; and subsequently coordinate shifts corrections were recorded. The 350 prostate IGRT coordinate shifts modeled to Gaussian distributions show central peaks deviated off the isocenter by 0.6 ± 3.0 mm, 0.5 ± 4.5 mm in the X(RL)- and Z(SI)-coordinates, respectively; and 2.0 ± 3.0 mm in the Y(AP)-coordinate as a result of belly and bladder capacity variations. Sixty-eight percent of confidence was within

  9. Optimization and quality assurance of an image-guided radiation therapy system for intensity-modulated radiation therapy radiotherapy

    SciTech Connect

    Tsai, Jen-San; Micaily, Bizhan; Miyamoto, Curtis

    2012-10-01

    To develop a quality assurance (QA) of XVI cone beam system (XVIcbs) for its optimal imaging-guided radiotherapy (IGRT) implementation, and to construe prostate tumor margin required for intensity-modulated radiation therapy (IMRT) if IGRT is unavailable. XVIcbs spatial accuracy was explored with a humanoid phantom; isodose conformity to lesion target with a rice phantom housing a soap as target; image resolution with a diagnostic phantom; and exposure validation with a Radcal ion chamber. To optimize XVIcbs, rotation flexmap on coincidency between gantry rotational axis and that of XVI cone beam scan was investigated. Theoretic correlation to image quality of XVIcbs rotational axis stability was elaborately studied. Comprehensive QA of IGRT using XVIcbs has initially been explored and then implemented on our general IMRT treatments, and on special IMRT radiotherapies such as head and neck (H and N), stereotactic radiation therapy (SRT), stereotactic radiosurgery (SRS), and stereotactic body radiotherapy (SBRT). Fifteen examples of prostate setup accounted for 350 IGRT cone beam system were analyzed. IGRT accuracy results were in agreement {+-} 1 mm. Flexmap 0.25 mm met the manufacturer's specification. Films confirmed isodose coincidence with target (soap) via XVIcbs, otherwise not. Superficial doses were measured from 7.2-2.5 cGy for anatomic diameters 15-33 cm, respectively. Image quality was susceptible to rotational stability or patient movement. IGRT using XVIcbs on general IMRT treatments such as prostate, SRT, SRS, and SBRT for setup accuracy were verified; and subsequently coordinate shifts corrections were recorded. The 350 prostate IGRT coordinate shifts modeled to Gaussian distributions show central peaks deviated off the isocenter by 0.6 {+-} 3.0 mm, 0.5 {+-} 4.5 mm in the X(RL)- and Z(SI)-coordinates, respectively; and 2.0 {+-} 3.0 mm in the Y(AP)-coordinate as a result of belly and bladder capacity variations. Sixty-eight percent of confidence was

  10. Disease Control After Reduced Volume Conformal and Intensity Modulated Radiation Therapy for Childhood Craniopharyngioma

    SciTech Connect

    Merchant, Thomas E.; Kun, Larry E.; Hua, Chia-Ho; Wu, Shengjie; Xiong, Xiaoping; Sanford, Robert A.; Boop, Frederick A.

    2013-03-15

    Purpose: To estimate the rate of disease control after conformal radiation therapy using reduced clinical target volume (CTV) margins and to determine factors that predict for tumor progression. Methods and Materials: Eighty-eight children (median age, 8.5 years; range, 3.2-17.6 years) received conformal or intensity modulated radiation therapy between 1998 and 2009. The study group included those prospectively treated from 1998 to 2003, using a 10-mm CTV, defined as the margin surrounding the solid and cystic tumor targeted to receive the prescription dose of 54 Gy. The CTV margin was subsequently reduced after 2003, yielding 2 groups of patients: those treated with a CTV margin greater than 5 mm (n=26) and those treated with a CTV margin less than or equal to 5 mm (n=62). Disease progression was estimated on the basis of additional variables including sex, race, extent of resection, tumor interventions, target volume margins, and frequency of weekly surveillance magnetic resonance (MR) imaging during radiation therapy. Median follow-up was 5 years. Results: There was no difference between progression-free survival rates based on CTV margins (>5 mm vs ≤5 mm) at 5 years (88.1% ± 6.3% vs 96.2% ± 4.4% [P=.6386]). There were no differences based on planning target volume (PTV) margins (or combined CTV plus PTV margins). The PTV was systematically reduced from 5 to 3 mm during the time period of the study. Factors predictive of superior progression-free survival included Caucasian race (P=.0175), no requirement for cerebrospinal fluid shunting (P=.0066), and number of surveillance imaging studies during treatment (P=.0216). Patients whose treatment protocol included a higher number of weekly surveillance MR imaging evaluations had a lower rate of tumor progression. Conclusions: These results suggest that targeted volume reductions for radiation therapy using smaller margins are feasible and safe but require careful monitoring. We are currently investigating

  11. Whole Abdominopelvic Intensity-Modulated Radiation Therapy for Desmoplastic Small Round Cell Tumor After Surgery

    SciTech Connect

    Pinnix, Chelsea C.; Fontanilla, Hiral P.; Hayes-Jordan, Andrea; Subbiah, Vivek; Bilton, Stephen D.; Chang, Eric L.; Grosshans, David R.; McAleer, Mary F.; Sulman, Eric P.; Woo, Shiao Y.; Anderson, Peter; Green, Holly L.; Mahajan, Anita

    2012-05-01

    Purpose: Desmoplastic small round cell tumor (DSCRT) is an uncommon pediatric tumor with a poor prognosis. Aggressive multimodality therapy is the current treatment approach; however. treatment toxicity is of concern. We report our results with whole abdominopelvic intensity-modulated radiation therapy (WAP-IMRT) as a component of multimodality therapy for DSCRT at a single institution. Materials/Methods: Medical records of all patients with DSCRT who received WAP-IMRT as part of definitive treatment at MD Anderson (2006-2010) were identified and reviewed. Results: Eight patients with DSRCT received WAP-IMRT with a median follow-up of 15.2 months. All patients received multiple courses of chemotherapy followed by surgical debulking of intra-abdominal disease; seven also had intraoperative hyperthermic cisplatin. WAP-IMRT was delivered to a total dose of 30 Gy postoperatively; four patients received a simultaneous boost (6-10 Gy) to sites of gross residual disease. Seven patients received concurrent chemotherapy during WAP-IMRT. No Radiation Therapy Oncology Group Grade 4 nausea, vomiting, or diarrhea occurred during RT. Red-cell transfusions were given to two patients to maintain hemoglobin levels >10 g/dL. Grade 4 cytopenia requiring growth factor support occurred in only one patient; no other significant cytopenias were noted. WAP-IMRT resulted in 25% lower radiation doses to the lumbosacral vertebral bodies and pelvic bones than conventional RT plans. The median time to local or distant failure after WAP-IMRT was 8.73 months in seven patients. One patient who had completed RT 20 months before the last follow-up remains alive without evidence of disease. Five patients (63%) experienced treatment failure in the abdomen. Distant failure occurred in three patients (37.5%). Conclusions: WAP-IMRT with concurrent radiosensitizing chemotherapy was well tolerated after aggressive surgery for DSCRT. Enhanced bone sparing with IMRT probably accounts for the low hematologic

  12. Computer-assisted selection of coplanar beam orientations in intensity-modulated radiation therapy*

    NASA Astrophysics Data System (ADS)

    Pugachev, A.; Xing, L.

    2001-09-01

    In intensity-modulated radiation therapy (IMRT), the incident beam orientations are often determined by a trial and error search. The conventional beam's-eye view (BEV) tool becomes less helpful in IMRT because it is frequently required that beams go through organs at risk (OARs) in order to achieve a compromise between the dosimetric objectives of the planning target volume (PTV) and the OARs. In this paper, we report a beam's-eye view dosimetrics (BEVD) technique to assist in the selection of beam orientations in IMRT. In our method, each beam portal is divided into a grid of beamlets. A score function is introduced to measure the `goodness' of each beamlet at a given gantry angle. The score is determined by the maximum PTV dose deliverable by the beamlet without exceeding the tolerance doses of the OARs and normal tissue located in the path of the beamlet. The overall score of the gantry angle is given by a sum of the scores of all beamlets. For a given patient, the score function is evaluated for each possible beam orientation. The directions with the highest scores are then selected as the candidates for beam placement. This procedure is similar to the BEV approach used in conventional radiation therapy, except that the evaluation by a human is replaced by a score function to take into account the intensity modulation. This technique allows one to select beam orientations without the excessive computing overhead of computer optimization of beam orientation. It also provides useful insight into the problem of selection of beam orientation and is especially valuable for complicated cases where the PTV is surrounded by several sensitive structures and where it is difficult to select a set of `good' beam orientations. Several two-dimensional (2D) model cases were used to test the proposed technique. The plans obtained using the BEVD-selected beam orientations were compared with the plans obtained using equiangular spaced beams. For all the model cases investigated

  13. Expert Consensus Contouring Guidelines for Intensity Modulated Radiation Therapy in Esophageal and Gastroesophageal Junction Cancer

    SciTech Connect

    Wu, Abraham J.; Bosch, Walter R.; Chang, Daniel T.; Hong, Theodore S.; Jabbour, Salma K.; Kleinberg, Lawrence R.; Mamon, Harvey J.; Thomas, Charles R.; Goodman, Karyn A.

    2015-07-15

    Purpose/Objective(s): Current guidelines for esophageal cancer contouring are derived from traditional 2-dimensional fields based on bony landmarks, and they do not provide sufficient anatomic detail to ensure consistent contouring for more conformal radiation therapy techniques such as intensity modulated radiation therapy (IMRT). Therefore, we convened an expert panel with the specific aim to derive contouring guidelines and generate an atlas for the clinical target volume (CTV) in esophageal or gastroesophageal junction (GEJ) cancer. Methods and Materials: Eight expert academically based gastrointestinal radiation oncologists participated. Three sample cases were chosen: a GEJ cancer, a distal esophageal cancer, and a mid-upper esophageal cancer. Uniform computed tomographic (CT) simulation datasets and accompanying diagnostic positron emission tomographic/CT images were distributed to each expert, and the expert was instructed to generate gross tumor volume (GTV) and CTV contours for each case. All contours were aggregated and subjected to quantitative analysis to assess the degree of concordance between experts and to generate draft consensus contours. The panel then refined these contours to generate the contouring atlas. Results: The κ statistics indicated substantial agreement between panelists for each of the 3 test cases. A consensus CTV atlas was generated for the 3 test cases, each representing common anatomic presentations of esophageal cancer. The panel agreed on guidelines and principles to facilitate the generalizability of the atlas to individual cases. Conclusions: This expert panel successfully reached agreement on contouring guidelines for esophageal and GEJ IMRT and generated a reference CTV atlas. This atlas will serve as a reference for IMRT contours for clinical practice and prospective trial design. Subsequent patterns of failure analyses of clinical datasets using these guidelines may require modification in the future.

  14. Intensity-Modulated Radiation Therapy for Anal Malignancies: A Preliminary Toxicity and Disease Outcomes Analysis

    SciTech Connect

    Pepek, Joseph M.; Willett, Christopher G.; Wu, Q. Jackie; Yoo, Sua; Clough, Robert W.; Czito, Brian G.

    2010-12-01

    Purpose: Intensity-modulated radiation therapy (IMRT) has the potential to reduce toxicities associated with chemoradiotherapy in the treatment of anal cancer. This study reports the results of using IMRT in the treatment of anal cancer. Methods and Materials: Records of patients with anal malignancies treated with IMRT at Duke University were reviewed. Acute toxicity was graded using the NCI CTCAEv3.0 scale. Overall survival (OS), metastasis-free survival (MFS), local-regional control (LRC) and colostomy-free survival (CFS) were calculated using the Kaplan-Meier method. Results: Forty-seven patients with anal malignancy (89% canal, 11% perianal skin) were treated with IMRT between August 2006 and September 2008. Median follow-up was 14 months (19 months for SCC patients). Median radiation dose was 54 Gy. Eight patients (18%) required treatment breaks lasting a median of 5 days (range, 2-7 days). Toxicity rates were as follows: Grade 4: leukopenia (7%), thrombocytopenia (2%); Grade 3: leukopenia (18%), diarrhea (9%), and anemia (4%); Grade 2: skin (93%), diarrhea (24%), and leukopenia (24%). The 2-year actuarial overall OS, MFS, LRC, and CFS rates were 85%, 78%, 90% and 82%, respectively. For SCC patients, the 2-year OS, MFS, LRC, and CFS rates were 100%, 100%, 95%, and 91%, respectively. Conclusions: IMRT-based chemoradiotherapy for anal cancer results in significant reductions in normal tissue dose and acute toxicities versus historic controls treated without IMRT, leading to reduced rates of toxicity-related treatment interruption. Early disease-related outcomes seem encouraging. IMRT is emerging as a standard therapy for anal cancer.

  15. Fast voxel and polygon ray-tracing algorithms in intensity modulated radiation therapy treatment planning.

    PubMed

    Fox, Christopher; Romeijn, H Edwin; Dempsey, James F

    2006-05-01

    We present work on combining three algorithms to improve ray-tracing efficiency in radiation therapy dose computation. The three algorithms include: An improved point-in-polygon algorithm, incremental voxel ray tracing algorithm, and stereographic projection of beamlets for voxel truncation. The point-in-polygon and incremental voxel ray-tracing algorithms have been used in computer graphics and nuclear medicine applications while the stereographic projection algorithm was developed by our group. These algorithms demonstrate significant improvements over the current standard algorithms in peer reviewed literature, i.e., the polygon and voxel ray-tracing algorithms of Siddon for voxel classification (point-in-polygon testing) and dose computation, respectively, and radius testing for voxel truncation. The presented polygon ray-tracing technique was tested on 10 intensity modulated radiation therapy (IMRT) treatment planning cases that required the classification of between 0.58 and 2.0 million voxels on a 2.5 mm isotropic dose grid into 1-4 targets and 5-14 structures represented as extruded polygons (a.k.a. Siddon prisms). Incremental voxel ray tracing and voxel truncation employing virtual stereographic projection was tested on the same IMRT treatment planning cases where voxel dose was required for 230-2400 beamlets using a finite-size pencil-beam algorithm. Between a 100 and 360 fold cpu time improvement over Siddon's method was observed for the polygon ray-tracing algorithm to perform classification of voxels for target and structure membership. Between a 2.6 and 3.1 fold reduction in cpu time over current algorithms was found for the implementation of incremental ray tracing. Additionally, voxel truncation via stereographic projection was observed to be 11-25 times faster than the radial-testing beamlet extent approach and was further improved 1.7-2.0 fold through point-classification using the method of translation over the cross product technique.

  16. Lymphatic atlas-based target volume definition for intensity-modulated radiation therapy planning

    NASA Astrophysics Data System (ADS)

    Qatarneh, S. M.; Kiricuta, I. C.; Brahme, A.; Noz, M. E.; Ferreira, B.; Kim, W. C.; Lind, B. K.

    2007-10-01

    Despite the improvements in current imaging modalities such as CT and MRI, the detection of normal or malignant lymph nodes remains a challenge due to the large variability in lymph node characteristics and the variation in imaging quality and the limited imaging resolution. A computerized lymph node atlas could be the ideal tool for target volume definition based on the distribution of normal lymph nodes surrounding the verified malignant nodes to improve the accuracy of intensity-modulated radiation therapy planning. The standard lymph node topography in the newly constructed 3D lymph node atlas offers a detailed topographical distribution of discrete nodal locations in relation to surrounding organs at risk. In the present paper, the recently developed lymph node atlas is used for selection and delineation of target volumes in the head and neck, thorax and pelvic region. Image registration techniques were implemented to integrate the topography of the lymph node atlas into the patient's data set. By combining the knowledge-based lymph node distribution with the patient's data set, more detailed definitions of the target volumes were obtained to facilitate biologically based treatment plan optimization. The response values of the biologically optimized treatment plans were used to derive the probability of tumor control and the probability of complications in organs at risk. The treatment outcome of the lung reference plan showed a lower probability of recurrence in comparison to planning without the lymph node atlas. The lymph node atlas can improve and standardize the target volume definition by including more accurate anatomical knowledge for target volume definition and biologically optimized radiation therapy planning.

  17. SU-E-T-124: Dosimetric Comparison of HDR Brachytherapy and Intensity Modulated Proton Therapy

    SciTech Connect

    Wu, J; Wu, H; Das, I

    2014-06-01

    Purpose: Brachytherapy is known to be able to deliver more radiation dose to tumor while minimizing radiation dose to surrounding normal tissues. Proton therapy also provides superior dose distribution due to Bragg peak. Since both HDR and Intensity Modulated Proton Therapy (IMPT) are beneficial for their quick dose drop off, our goal in this study is to compare the pace of dose gradient drop-off between HDR and IMPT plans based on the same CT image data-set. In addition, normal tissues sparing were also compared among HDR, IMPT and SBRT. Methods: Five cervical cancer cases treated with EBRT + HDR boost combination with Tandem and Ovoid applicator were used for comparison purpose. Original HDR plans with prescribed dose of 5.5 Gy x 5 fractions were generated and optimized. The 100% isodose line of HDR plans was converted to a dose volume, and treated as CTV for IMPT and SBRT planning. The same HDR CT scans were also used for IMPT plan and SBRT plan for direct comparison. The philosophy of the IMPT and SBRT planning was to create the same CTV coverage as HDR plans. All three modalities treatment plans were compared to each other with a set of predetermined criteria. Results: With similar target volume coverage in cervix cancer boost treatment, HDR provides a slightly sharper dose drop-off from 100% to 50% isodose line, averagely in all directions compared to IMPT. However, IMPT demonstrated more dose gradient drop-off at the junction of the target and normal tissues by providing more normal tissue sparing and superior capability to reduce integral dose. Conclusion: IMPT is capable of providing comparable dose drop-off as HDR. IMPT can be explored as replacement for HDR brachytherapy in various applications.

  18. Kilovoltage Intrafraction Monitoring for Prostate Intensity Modulated Arc Therapy: First Clinical Results

    SciTech Connect

    Ng, Jin Aun; Booth, Jeremy T.; Poulsen, Per R.; Fledelius, Walther; Worm, Esben Schjodt; Eade, Thomas; Hegi, Fiona; Kneebone, Andrew; Kuncic, Zdenka; Keall, Paul J.

    2012-12-01

    Purpose: Most linear accelerators purchased today are equipped with a gantry-mounted kilovoltage X-ray imager which is typically used for patient imaging prior to therapy. A novel application of the X-ray system is kilovoltage intrafraction monitoring (KIM), in which the 3-dimensional (3D) tumor position is determined during treatment. In this paper, we report on the first use of KIM in a prospective clinical study of prostate cancer patients undergoing intensity modulated arc therapy (IMAT). Methods and Materials: Ten prostate cancer patients with implanted fiducial markers undergoing conventionally fractionated IMAT (RapidArc) were enrolled in an ethics-approved study of KIM. KIM involves acquiring kV images as the gantry rotates around the patient during treatment. Post-treatment, markers in these images were segmented to obtain 2D positions. From the 2D positions, a maximum likelihood estimation of a probability density function was used to obtain 3D prostate trajectories. The trajectories were analyzed to determine the motion type and the percentage of time the prostate was displaced {>=}3, 5, 7, and 10 mm. Independent verification of KIM positional accuracy was performed using kV/MV triangulation. Results: KIM was performed for 268 fractions. Various prostate trajectories were observed (ie, continuous target drift, transient excursion, stable target position, persistent excursion, high-frequency excursions, and erratic behavior). For all patients, 3D displacements of {>=}3, 5, 7, and 10 mm were observed 5.6%, 2.2%, 0.7% and 0.4% of the time, respectively. The average systematic accuracy of KIM was measured at 0.46 mm. Conclusions: KIM for prostate IMAT was successfully implemented clinically for the first time. Key advantages of this method are (1) submillimeter accuracy, (2) widespread applicability, and (3) a low barrier to clinical implementation. A disadvantage is that KIM delivers additional imaging dose to the patient.

  19. Disease-control rates following intensity-modulated radiation therapy for small primary oropharyngeal carcinoma

    SciTech Connect

    Garden, Adam S. . E-mail: agarden@mdanderson.org; Morrison, William H.; Wong, P.-F.; Tung, Sam S.; Rosenthal, David I.; Dong Lei; Mason, Brian M.S.; Perkins, George H.; Ang, K. Kian

    2007-02-01

    Background: The purpose of this study was to assess the ability of intensity-modulated radiation therapy (IMRT) to achieve favorable disease-control rates while minimizing parotid gland doses in patients treated for small primary tumors of the oropharynx. Methods and Materials: We retrospectively identified all patients who received IMRT as treatment for a small (<4 cm) primary tumor of the oropharynx between October 2000 and June 2002. Tumor characteristics, IMRT parameters, and patient outcomes were assessed. Results: Fifty-one patients met the criteria for our study. All patients had treatment to gross disease with margin (CTV1), and all but 1 had treatment to the bilateral necks. The most common treatment schedule (39 patients) was a once-daily fractionation of prescribed doses of 63-66 Gy to the CTV1 and 54 Gy to subclinical sites, delivered in 30 fractions. Twenty-one patients (40%) had gastrostomy tubes placed during therapy; in 4 patients, the tube remained in place for more than 6 months after completion of IMRT. The median follow-up was 45 months. The 2-year actuarial locoregional control, recurrence-free, and overall survival rates were 94%, 88%, and 94%, respectively. Conclusions: These preliminary data suggest that treatment with IMRT results in favorable locoregional control of small primary oropharynx tumors. IMRT did not appear to have a more favorable acute toxicity profile in this group with respect to the use of a feeding tube; however, the mean dose of radiation delivered to the parotid gland by IMRT was decreased, because 95% of patients had a mean dose of <30 Gy to at least one gland.

  20. Intensity-Modulated Radiation Therapy Significantly Improves Acute Gastrointestinal Toxicity in Pancreatic and Ampullary Cancers

    SciTech Connect

    Yovino, Susannah; Poppe, Matthew; Jabbour, Salma; David, Vera; Garofalo, Michael; Pandya, Naimesh; Alexander, Richard; Hanna, Nader; Regine, William F.

    2011-01-01

    Purpose: Among patients with upper abdominal malignancies, intensity-modulated radiation therapy (IMRT) can improve dose distributions to critical dose-limiting structures near the target. Whether these improved dose distributions are associated with decreased toxicity when compared with conventional three-dimensional treatment remains a subject of investigation. Methods and Materials: 46 patients with pancreatic/ampullary cancer were treated with concurrent chemoradiation (CRT) using inverse-planned IMRT. All patients received CRT based on 5-fluorouracil in a schema similar to Radiation Therapy Oncology Group (RTOG) 97-04. Rates of acute gastrointestinal (GI) toxicity for this series of IMRT-treated patients were compared with those from RTOG 97-04, where all patients were treated with three-dimensional conformal techniques. Chi-square analysis was used to determine if there was a statistically different incidence in acute GI toxicity between these two groups of patients. Results: The overall incidence of Grade 3-4 acute GI toxicity was low in patients receiving IMRT-based CRT. When compared with patients who had three-dimensional treatment planning (RTOG 97-04), IMRT significantly reduced the incidence of Grade 3-4 nausea and vomiting (0% vs. 11%, p = 0.024) and diarrhea (3% vs. 18%, p = 0.017). There was no significant difference in the incidence of Grade 3-4 weight loss between the two groups of patients. Conclusions: IMRT is associated with a statistically significant decrease in acute upper and lower GI toxicity among patients treated with CRT for pancreatic/ampullary cancers. Future clinical trials plan to incorporate the use of IMRT, given that it remains a subject of active investigation.

  1. Replanning During Intensity Modulated Radiation Therapy Improved Quality of Life in Patients With Nasopharyngeal Carcinoma

    SciTech Connect

    Yang Haihua; Hu Wei; Wang Wei; Chen Peifang; Ding Weijun; Luo Wei

    2013-01-01

    Purpose: Anatomic and dosimetric changes have been reported during intensity modulated radiation therapy (IMRT) in patients with nasopharyngeal carcinoma (NPC). The purpose of this study was to evaluate the effects of replanning on quality of life (QoL) and clinical outcomes during the course of IMRT for NPC patients. Methods and Materials: Between June 2007 and August 2011, 129 patients with NPC were enrolled. Forty-three patients received IMRT without replanning, while 86 patients received IMRT replanning after computed tomography (CT) images were retaken part way through therapy. Chinese versions of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 and Head and Neck Quality of Life Questionnaire 35 were completed before treatment began and at the end of treatment and at 1, 3, 6, and 12 months after the completion of treatment. Overall survival (OS) data were compared using the Kaplan-Meier method. Results: IMRT replanning had a profound impact on the QoL of NPC patients, as determined by statistically significant changes in global QoL and other QoL scales. Additionally, the clinical outcome comparison indicates that replanning during IMRT for NPC significantly improved 2-year local regional control (97.2% vs 92.4%, respectively, P=.040) but did not improve 2-year OS (89.8% vs 82.2%, respectively, P=.475). Conclusions: IMRT replanning improves QoL as well as local regional control in patients with NPC. Future research is needed to determine the criteria for replanning for NPC patients undergoing IMRT.

  2. Adoption of Intensity Modulated Radiation Therapy For Early-Stage Breast Cancer From 2004 Through 2011

    SciTech Connect

    Wang, Elyn H.; Mougalian, Sarah S.; Soulos, Pamela R.; Smith, Benjamin D.; Haffty, Bruce G.; Gross, Cary P.; Yu, James B.

    2015-02-01

    Purpose: Intensity modulated radiation therapy (IMRT) is a newer method of radiation therapy (RT) that has been increasingly adopted as an adjuvant treatment after breast-conserving surgery (BCS). IMRT may result in improved cosmesis compared to standard RT, although at greater expense. To investigate the adoption of IMRT, we examined trends and factors associated with IMRT in women under the age of 65 with early stage breast cancer. Methods and Materials: We performed a retrospective study of early stage breast cancer patients treated with BCS followed by whole-breast irradiation (WBI) who were ≤65 years old in the National Cancer Data Base from 2004 to 2011. We used logistic regression to identify factors associated with receipt of IMRT (vs standard RT). Results: We identified 11,089 women with early breast cancer (9.6%) who were treated with IMRT and 104,448 (90.4%) who were treated with standard RT, after BCS. The proportion of WBI patients receiving IMRT increased yearly from 2004 to 2009, with 5.3% of WBI patients receiving IMRT in 2004 and 11.6% receiving IMRT in 2009. Further use of IMRT declined afterward, with the proportion remaining steady at 11.0% and 10.7% in 2010 and 2011, respectively. Patients treated in nonacademic community centers were more likely to receive IMRT (odds ratio [OR], 1.36; 95% confidence interval [CI], 1.30-1.43 for nonacademic vs academic center). Compared to privately insured patients, the uninsured patients (OR, 0.81; 95% CI, 0.70-0.95) and those with Medicaid insurance (OR, 0.87; 95% CI, 0.79-0.95) were less likely to receive IMRT. Conclusions: The use of IMRT rose from 2004 to 2009 and then stabilized. Important nonclinical factors associated with IMRT use included facility type and insurance status.

  3. Low intensity laser therapy speeds wound healing in hemophilia by enhancing platelet procoagulant activity.

    PubMed

    Hoffman, Maureane; Monroe, Dougald M

    2012-01-01

    Our group has previously shown that cutaneous wound healing is delayed and histologically abnormal in a mouse model of hemophilia. Hemostasis is not only required to stop bleeding at the time of wounding, but also produces bioactive substances that promote appropriate inflammatory and proliferative responses during healing. Low intensity laser therapy (LILT) has been reported to enhance impaired wound healing in a variety of animal and human studies. The current studies were conducted to test the hypothesis that LILT can improve healing in a hemophilia B mouse model. Three daily treatments with 12 J/sq cm of 650 nm laser illumination reduced the time to closure of a 3-mm cutaneous punch biopsy wound in the hemophilic mice. All wounds were closed at 13 days in the sham-treated hemophilic mice, compared with 10 days in the LILT-treated hemophilic mice, and 9 days in wild-type mice. While LILT can speed healing by enhancing proliferation of cutaneous cells, we found that an additional mechanism likely contributes to the efficacy of LILT in the hemophilic mice. LILT enhanced the mechanical rigidity and platelet activity of clots formed from human platelet-rich plasma. Illumination of isolated platelets increased the mitochondrial membrane potential and enhanced binding of coagulation factors to the surface of activated platelets. Thus, while LILT can directly promote proliferative responses during healing, it also appears to enhance hemostasis in an animal model with impaired coagulation. These data suggest that trials of LILT as an adjunct to the usual hemostatic therapies in hemophilia are warranted.

  4. Intensity-modulated radiation therapy (IMRT) in the treatment of anal cancer: Toxicity and clinical outcome

    SciTech Connect

    Milano, Michael T.; Jani, Ashesh B.; Farrey, Karl J.; Rash, Carla C.; Heimann, Ruth; Chmura, Steven J. . E-mail: schmura@radonc.uchicago.edu

    2005-10-01

    Purpose: To assess survival, local control, and toxicity of intensity modulated radiation therapy (IMRT) in squamous cell carcinoma of the anal canal. Methods and Materials: Seventeen patients were treated with nine-field IMRT plans. Thirteen received concurrent 5-fluorouracil and mitomycin C, whereas 1 patient received 5-fluorouracil alone. Seven patients were planned with three-dimensional anteroposterior/posterior-anterior (AP/PA) fields for dosimetric comparison to IMRT. Results: Compared with AP/PA, IMRT reduced the mean and threshold doses to small bowel, bladder, and genitalia. Treatment was well tolerated, with no Grade {>=}3 acute nonhematologic toxicity. There were no treatment breaks attributable to gastrointestinal or skin toxicity. Of patients who received mitomycin C, 38% experienced Grade 4 hematologic toxicity. IMRT did not afford bone marrow sparing, possibly resulting from the clinical decision to prescribe 45 Gy to the whole pelvis in most patients, vs. the Radiation Therapy Oncology Group-recommended 30.6 Gy whole pelvic dose. Three of 17 patients, who did not achieve a complete response, proceeded to an abdominoperineal resection and colostomy. At a median follow-up of 20.3 months, there were no other local failures. Two-year overall survival, disease-free survival, and colostomy-free survival are: 91%, 65%, and 82% respectively. Conclusions: In this hypothesis-generating analysis, the acute toxicity and clinical outcome with IMRT in the treatment of anal cancer is encouraging. Compared with historical controls, local control is not compromised despite efforts to increase conformality and reduce normal structure dose.

  5. Linear Energy Transfer-Guided Optimization in Intensity Modulated Proton Therapy: Feasibility Study and Clinical Potential

    SciTech Connect

    Giantsoudi, Drosoula; Grassberger, Clemens; Craft, David; Niemierko, Andrzej; Trofimov, Alexei; Paganetti, Harald

    2013-09-01

    Purpose: To investigate the feasibility and potential clinical benefit of linear energy transfer (LET) guided plan optimization in intensity modulated proton therapy (IMPT). Methods and Materials: A multicriteria optimization (MCO) module was used to generate a series of Pareto-optimal IMPT base plans (BPs), corresponding to defined objectives, for 5 patients with head-and-neck cancer and 2 with pancreatic cancer. A Monte Carlo platform was used to calculate dose and LET distributions for each BP. A custom-designed MCO navigation module allowed the user to interpolate between BPs to produce deliverable Pareto-optimal solutions. Differences among the BPs were evaluated for each patient, based on dose–volume and LET–volume histograms and 3-dimensional distributions. An LET-based relative biological effectiveness (RBE) model was used to evaluate the potential clinical benefit when navigating the space of Pareto-optimal BPs. Results: The mean LET values for the target varied up to 30% among the BPs for the head-and-neck patients and up to 14% for the pancreatic cancer patients. Variations were more prominent in organs at risk (OARs), where mean LET values differed by a factor of up to 2 among the BPs for the same patient. An inverse relation between dose and LET distributions for the OARs was typically observed. Accounting for LET-dependent variable RBE values, a potential improvement on RBE-weighted dose of up to 40%, averaged over several structures under study, was noticed during MCO navigation. Conclusions: We present a novel strategy for optimizing proton therapy to maximize dose-averaged LET in tumor targets while simultaneously minimizing dose-averaged LET in normal tissue structures. MCO BPs show substantial LET variations, leading to potentially significant differences in RBE-weighted doses. Pareto-surface navigation, using both dose and LET distributions for guidance, provides the means for evaluating a large variety of deliverable plans and aids in

  6. Beam angle optimization for intensity-modulated radiation therapy using a guided pattern search method

    NASA Astrophysics Data System (ADS)

    Rocha, Humberto; Dias, Joana M.; Ferreira, Brígida C.; Lopes, Maria C.

    2013-05-01

    Generally, the inverse planning of radiation therapy consists mainly of the fluence optimization. The beam angle optimization (BAO) in intensity-modulated radiation therapy (IMRT) consists of selecting appropriate radiation incidence directions and may influence the quality of the IMRT plans, both to enhance better organ sparing and to improve tumor coverage. However, in clinical practice, most of the time, beam directions continue to be manually selected by the treatment planner without objective and rigorous criteria. The goal of this paper is to introduce a novel approach that uses beam’s-eye-view dose ray tracing metrics within a pattern search method framework in the optimization of the highly non-convex BAO problem. Pattern search methods are derivative-free optimization methods that require a few function evaluations to progress and converge and have the ability to better avoid local entrapment. The pattern search method framework is composed of a search step and a poll step at each iteration. The poll step performs a local search in a mesh neighborhood and ensures the convergence to a local minimizer or stationary point. The search step provides the flexibility for a global search since it allows searches away from the neighborhood of the current iterate. Beam’s-eye-view dose metrics assign a score to each radiation beam direction and can be used within the pattern search framework furnishing a priori knowledge of the problem so that directions with larger dosimetric scores are tested first. A set of clinical cases of head-and-neck tumors treated at the Portuguese Institute of Oncology of Coimbra is used to discuss the potential of this approach in the optimization of the BAO problem.

  7. Intensity-Modulated Radiation Therapy in the Salvage of Locally Recurrent Nasopharyngeal Carcinoma

    SciTech Connect

    Qiu Sufang; Lin Shaojun; Tham, Ivan W.K.; Pan Jianji; Lu Jun; Lu, Jiade J.

    2012-06-01

    Purpose: Local recurrences of nasopharyngeal carcinoma (NPC) may be salvaged by reirradiation with conventional techniques, but with significant morbidity. Intensity-modulated radiation therapy (IMRT) may improve the therapeutic ratio by reducing doses to normal tissue. The aim of this study was to address the efficacy and toxicity profile of IMRT for a cohort of patients with locally recurrent NPC. Methods and Materials: Between August 2003 and June 2009, 70 patients with radiologic or pathologically proven locally recurrent NPC were treated with IMRT. The median time to recurrence was 30 months after the completion of conventional radiation to definitive dose. Fifty-seven percent of the tumors were classified asrT3-4. The minimum planned doses were 59.4 to 60 Gy in 1.8- to 2-Gy fractions per day to the gross disease with margins, with or without chemotherapy. Results: The median dose to the recurrent tumor was 70 Gy (range, 50-77.4 Gy). Sixty-five patients received the planned radiation therapy; 5 patients received between 50 and 60 Gy because of acute side effects. With a median follow-up time of 25 months, the rates of 2-year locoregional recurrence-free survival, disease-free survival, and overall survival were 65.8%, 65.8%, and 67.4%, respectively. Moderate to severe late toxicities were noted in 25 patients (35.7%). Eleven patients (15.7%) had posterior nasal space ulceration, 17 (24.3%) experienced cranial nerve palsies, 12 (17.1%) had trismus, and 12 (17.1%) experienced deafness. Extended disease-free interval (relative risk 2.049) and advanced T classification (relative risk 3.895) at presentation were adverse prognostic factors. Conclusion: Reirradiation with IMRT provides reasonable long-term control in patients with locally recurrent NPC.

  8. Fast intensity-modulated arc therapy based on 2-step beam segmentation

    SciTech Connect

    Bratengeier, Klaus; Gainey, Mark; Sauer, Otto A.; Richter, Anne; Flentje, Michael

    2011-01-15

    Purpose: Single or few arc intensity-modulated arc therapy (IMAT) is intended to be a time saving irradiation method, potentially replacing classical intensity-modulated radiotherapy (IMRT). The aim of this work was to evaluate the quality of different IMAT methods with the potential of fast delivery, which also has the possibility of adapting to the daily shape of the target volume. Methods: A planning study was performed. Novel double and triple IMAT techniques based on the geometrical analysis of the target organ at risk geometry (2-step IMAT) were evaluated. They were compared to step and shoot IMRT reference plans generated using direct machine parameter optimization (DMPO). Volumetric arc (VMAT) plans from commercial preclinical software (SMARTARC) were used as an additional benchmark to classify the quality of the novel techniques. Four cases with concave planning target volumes (PTV) with one dominating organ at risk (OAR), viz., the PTV/OAR combination of the ESTRO Quasimodo phantom, breast/lung, spine metastasis/spinal cord, and prostate/rectum, were used for the study. The composite objective value (COV) and other parameters representing the plan quality were studied. Results: The novel 2-step IMAT techniques with geometry based segment definition were as good as or better than DMPO and were superior to the SMARTARC VMAT techniques. For the spine metastasis, the quality measured by the COV differed only by 3%, whereas the COV of the 2-step IMAT for the other three cases decreased by a factor of 1.4-2.4 with respect to the reference plans. Conclusions: Rotational techniques based on geometrical analysis of the optimization problem (2-step IMAT) provide similar or better plan quality than DMPO or the research version of SMARTARC VMAT variants. The results justify pursuing the goal of fast IMAT adaptation based on 2-step IMAT techniques.

  9. Feasibility of intensive parent-child interaction therapy (I-PCIT): Results from an open trial

    PubMed Central

    Graziano, Paulo A.; Bagner, Daniel M.; Slavec, Janine; Hungerford, Gabriela; Kent, Kristine; Babinski, Dara; Derefinko, Karen; Pasalich, Dave

    2014-01-01

    Objective The current pilot study examined the feasibility, acceptability, and initial outcome of an intensive and more condensed version of Parent-Child Interaction Therapy (90 minute sessions for 5 days/week over the course of 2 weeks). Method Using an open trial design, 11 children (M child age = 5.01 years) and their mothers completed a baseline period of 2 weeks, a treatment period of 2 weeks, and a post-treatment evaluation. A follow-up evaluation was also conducted 4 months following treatment completion. Across all assessments, mothers completed measures of child behavior and parenting stress, and observational data was collected during three 5-minute standard situations that vary in the degree of parental control (child-led play, parent-led play, & clean-up). Results All 11 families completed the intervention with extremely high attendance and reported high satisfaction. Results across both mother report and observations showed that: a) externalizing behavior problems were stable during the baseline period; b) treatment was effective in reducing externalizing behavior problems (ds = 1.67-2.50), improving parenting skills (ds = 1.93-6.04), and decreasing parenting stress (d = .91); and c) treatment gains were maintained at follow-up (ds = .53-3.50). Conclusions Overall, preliminary data suggest that a brief and intensive format of a parent-training intervention is a feasible and effective treatment for young children with externalizing behavior problems with clinical implications for improving children's behavioral impairment in a very brief period of time. PMID:26097286

  10. Basic study on pulse-intensity-domain depth-controlled photodynamic therapy for transurethral prostate cancer

    NASA Astrophysics Data System (ADS)

    Ohmori, Sayaka; Masuda, Kensuke; Yamakawa, Yuko; Arai, Tsunenori

    2006-02-01

    Photodynamic therapy (PDT) is promising modality for cancer. Prostate cancer is the most common cancer in USA. We proposed transurethral prostate cancer treatment using the pulse-intensity-domain depth-controlled PDT to preserve urethra wall. We have found that photocytotoxicity has been suppressed under high-intensity pulsed excitation with the second generation photosensitizers. We aim to apply this effect to form intact portion on the surface of the irradiated field. Irradiation condition dependence of photocytotoxicity of rat prostate cancer cell line R3327-AT-1 was investigated with two clinical photosensitizers, Porfimer sodium and Talaporfin sodium. A pulsed laser was irradiated with the power energy density ranging from 1.25 to 10 mJ/cm2. Near-infrared luminescence from singlet oxygen in the solution of those two photosensitizers was measured transiently. We performed PDT against a rat subcutaneous prostate tumor mode with Talaporfin sodium (2mg/kg) injected intravenously 1 h prior to the irradiation. The laser was irradiated with the power energy density 2.5 or 10 mW/cm2, with the total fluence of 50 J/cm2. Photocytotoxicity in vitro and the singlet oxygen generation were both suppressed with the 10mJ/cm2 irradiation with Talaporfin sodium, while these with Porfimer sodium were kept relatively constant. The surface of the irradiated field of 1mm in thickness remained intact, while the tumor damaged layer of 1.3 mm in thickness was obtained in the case of 10mJ/cm2 irradiation. We think Talaporfin sodium has high sensitivity to the pulse energy density, which might be useful to realize urethra preserved PDT for prostate cancer.

  11. MAGIC-type polymer gel for three-dimensional dosimetry: intensity-modulated radiation therapy verification.

    PubMed

    Gustavsson, Helen; Karlsson, Anna; Bäck, Sven A J; Olsson, Lars E; Haraldsson, Pia; Engström, Per; Nyström, Håkan

    2003-06-01

    A new type of polymer gel dosimeter, which responds well to absorbed dose even when manufactured in the presence of normal levels of oxygen, was recently described by Fong et al. [Phys. Med. Biol. 46, 3105-3113 (2001)] and referred to by the acronym MAGIC. The aim of this study was to investigate the feasibility of using this new type of gel for intensity-modulated radiation therapy (IMRT) verification. Gel manufacturing was carried out in room atmosphere under normal levels of oxygen. IMRT inverse treatment planning was performed using the Helios software. The gel was irradiated using a linear accelerator equipped with a dynamic multileaf collimator, and intensity modulation was achieved using sliding window technique. The response to absorbed dose was evaluated using magnetic resonance imaging. Measured and calculated dose distributions were compared with regard to in-plane isodoses and dose volume histograms. In addition, the spatial and dosimetric accuracy was evaluated using the gamma formalism. Good agreement between calculated and measured data was obtained. In the isocenter plane, the 70% and 90% isodoses acquired using the different methods are mostly within 2 mm, with up to 3 mm disagreement at isolated points. For the planning target volume (PTV), the calculated mean relative dose was 96.8 +/- 2.5% (1 SD) and the measured relative mean dose was 98.6 +/- 2.2%. Corresponding data for an organ at risk was 34.4 +/- 0.9% and 32.7 +/- 0.7%, respectively. The gamma criterion (3 mm spatial/3% dose deviation) was fulfilled for 94% of the pixels in the target region. Discrepancies were found in hot spots the upper and lower parts of the PTV, where the measured dose was up to 11% higher than calculated. This was attributed to sub optimal scatter kernels used in the treatment planning system dose calculations. Our results indicate great potential for IMRT verification using MAGIC-type polymer gel.

  12. Preliminary evidence of genetic determinants of adiponectin response to fenofibrate in the Genetics of Lipid Lowering Drugs and Diet Network

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Adiponectin is an adipose-secreted protein that has been linked to changes in insulin sensitivity, high-density lipoprotein cholesterol levels, and inflammatory patterns. Although fenofibrate therapy can raise adiponectin levels, treatment response is heterogeneous and heritable, suggesting a role f...

  13. Quantification of beam complexity in intensity-modulated radiation therapy treatment plans

    SciTech Connect

    Du, Weiliang Cho, Sang Hyun; Zhang, Xiaodong; Kudchadker, Rajat J.; Hoffman, Karen E.

    2014-02-15

    Purpose: Excessive complexity in intensity-modulated radiation therapy (IMRT) plans increases the dose uncertainty, prolongs the treatment time, and increases the susceptibility to changes in patient or target geometry. To date, the tools for quantitative assessment of IMRT beam complexity are still lacking. In this study, The authors have sought to develop metrics to characterize different aspects of beam complexity and investigate the beam complexity for IMRT plans of different disease sites. Methods: The authors evaluated the beam complexity scores for 65 step-and-shoot IMRT plans from three sites (prostate, head and neck, and spine) and 26 volumetric-modulated arc therapy (VMAT) plans for the prostate. On the basis of the beam apertures and monitor unit weights of all segments, the authors calculated the mean aperture area, extent of aperture shape irregularity, and degree of beam modulation for each beam. Then the beam complexity values were averaged to obtain the complexity metrics of the IMRT plans. The authors studied the correlation between the beam complexity metrics and the quality assurance (QA) results. Finally, the effects of treatment planning parameters on beam complexity were studied. Results: The beam complexity scores were not uniform among the prostate IMRT beams from different gantry angles. The lateral beams had larger monitor units and smaller shape irregularity, while the anterior-posterior beams had larger modulation values. On average, the prostate IMRT plans had the smallest aperture irregularity, beam modulation, and normalized monitor units; the head and neck IMRT plans had large beam irregularity and beam modulation; and the spine stereotactic radiation therapy plans often had small beam apertures, which may have been associated with the relatively large discrepancies between planned and QA measured doses. There were weak correlations between the beam complexity scores and the measured dose errors. The prostate VMAT beams showed

  14. Inverse planning for functional image-guided intensity-modulated radiation therapy

    NASA Astrophysics Data System (ADS)

    Xing, Lei; Cotrutz, Cristian; Hunjan, Sandeep; Boyer, Arthur L.; Adalsteinsson, Elfar; Spielman, Daniel

    2002-10-01

    Radiation therapy is an image-guided process whose success critically depends on the imaging modality used for treatment planning and the level of integration of the available imaging information. In this work, we establish a dose optimization framework for incorporating metabolic information from functional imaging modalities into the intensity-modulated radiation therapy (IMRT) inverse planning process and to demonstrate the technical feasibility of planning deliberately non-uniform dose distributions in accordance with functional imaging data. For this purpose, a metabolic map from functional images is discretized into a number of abnormality levels (ALs) and then fused with CT images. To escalate dose to the metabolically abnormal regions, we assume, for a given spatial point, a linear relation between the AL and the prescribed dose. But the formalism developed here is independent of the assumption and any other relation between AL and prescription is applicable. For a given AL and prescription relation, it is only necessary to prescribe the dose to the lowest AL in the target and the desired doses to other regions with higher AL values are scaled accordingly. To accomplish differential sparing of a sensitive structure when its functional importance (FI) distribution is known, we individualize the tolerance doses of the voxels within the structure according to their FI levels. An iterative inverse planning algorithm in voxel domain is used to optimize the system with inhomogeneous dose prescription. To model intra-structural trade-off, a mechanism is introduced through the use of voxel-dependent weighting factors, in addition to the conventional structure specific weighting factors which model the inter-structural trade-off. The system is used to plan a phantom case with a few hypothetical functional distributions and a brain tumour treatment with incorporation of magnetic resonance spectroscopic imaging data. The results indicated that it is technically

  15. Bile Acid Malabsorption After Pelvic and Prostate Intensity Modulated Radiation Therapy: An Uncommon but Treatable Condition

    SciTech Connect

    Harris, Victoria; Benton, Barbara; Sohaib, Aslam; Dearnaley, David; Andreyev, H. Jervoise N.

    2012-12-01

    Purpose: Intensity modulated radiation therapy (IMRT) is a significant therapeutic advance in prostate cancer, allowing increased tumor dose delivery and increased sparing of normal tissues. IMRT planning uses strict dose constraints to nearby organs to limit toxicity. Bile acid malabsorption (BAM) is a treatable disorder of the terminal ileum (TI) that presents with symptoms similar to radiation therapy toxicity. It has not been described in patients receiving RT for prostate cancer in the contemporary era. We describe new-onset BAM in men after IMRT for prostate cancer. Methods and Materials: Diagnosis of new-onset BAM was established after typical symptoms developed, selenium-75 homocholic acid taurine (SeHCAT) scanning showed 7-day retention of <15%, and patients' symptoms unequivocally responded to a bile acid sequestrant. The TI was identified on the original radiation therapy plan, and the radiation dose delivered was calculated and compared with accepted dose-volume constraints. Results: Five of 423 men treated in a prospective series of high-dose prostate and pelvic IMRT were identified with new onset BAM (median age, 65 years old). All reported having normal bowel habits before RT. The volume of TI ranged from 26-141 cc. The radiation dose received by the TI varied between 11.4 Gy and 62.1 Gy (uncorrected). Three of 5 patients had TI treated in excess of 45 Gy (equivalent dose calculated in 2-Gy fractions, using an {alpha}/{beta} ratio of 3) with volumes ranging from 1.6 cc-49.0 cc. One patient had mild BAM (SeHCAT retention, 10%-15%), 2 had moderate BAM (SeHCAT retention, 5%-10%), and 2 had severe BAM (SeHCAT retention, <5%). The 3 patients whose TI received {>=}45 Gy developed moderate to severe BAM, whereas those whose TI received <45 Gy had only mild to moderate BAM. Conclusions: Radiation delivered to the TI during IMRT may cause BAM. Identification of the TI from unenhanced RT planning computed tomography scans is difficult and may impede accurate

  16. Affect Intensity and Phasic REM Sleep in Depressed Men before and after Treatment with Cognitive-Behavioral Therapy.

    ERIC Educational Resources Information Center

    Nofzinger, Eric A.; And Others

    1994-01-01

    Explored relationship between daytime affect and REM (rapid eye movement) sleep in 45 depressed men before and after treatment with cognitive-behavioral therapy and in control group of 43 healthy subjects. For depressed subjects only, intensity of daytime affect correlated significantly and positively with phasic REM sleep measures at pre- and…

  17. Risk of Secondary Malignant Neoplasms From Proton Therapy and Intensity-Modulated X-Ray Therapy for Early-Stage Prostate Cancer

    SciTech Connect

    Fontenot, Jonas D.; Lee, Andrew K.; Newhauser, Wayne D.

    2009-06-01

    Purpose: To assess the risk of a secondary malignant neoplasm (SMN) from proton therapy relative to intensity-modulated radiation therapy (IMRT) using X-rays, taking into account contributions from both primary and secondary sources of radiation, for prostate cancer. Methods and Materials: A proton therapy plan and a 6-MV IMRT plan were constructed for 3 patients with early-stage adenocarcinoma of the prostate. Doses from the primary fields delivered to organs at risk of developing an SMN were determined from treatment plans. Secondary doses from the proton therapy and IMRT were determined from Monte Carlo simulations and available measured data, respectively. The risk of an SMN was estimated from primary and secondary doses on an organ-by-organ basis by use of risk models from the Committee on the Biological Effects of Ionizing Radiation. Results: Proton therapy reduced the risk of an SMN by 26% to 39% compared with IMRT. The risk of an SMN for both modalities was greatest in the in-field organs. However, the risks from the in-field organs were considerably lower with the proton therapy plan than with the IMRT plan. This reduction was attributed to the substantial sparing of the rectum and bladder from exposure to the therapeutic beam by the proton therapy plan. Conclusions: When considering exposure to primary and secondary radiation, proton therapy can reduce the risk of an SMN in prostate patients compared with contemporary IMRT.

  18. Acne treatment by methyl aminolevulinate photodynamic therapy with red light vs. intense pulsed light.

    PubMed

    Hong, Jong Soo; Jung, Jae Yoon; Yoon, Ji Young; Suh, Dae Hun

    2013-05-01

    Various methods of photodynamic therapy (PDT) for acne have been introduced. However, comparative studies among them are still needed. We performed this study to compare the effect of methyl aminolevulinate (MAL) PDT for acne between red light and intense pulsed light (IPL). Twenty patients were enrolled in this eight-week, prospective, split-face study. We applied MAL cream over the whole face with a three-hour incubation time. Then patients were irradiated with 22 J/cm(2) of red light on one-half of the face and 8-10 J/cm(2) of IPL on the other half during each treatment session. We performed three treatment sessions at two-week intervals and followed-up patients until four weeks after the last session. Inflammatory and non-inflammatory acne lesions were reduced significantly on both sides. The red light side showed a better response than the IPL side after the first treatment. Serious adverse effects after treatment were not observed. MAL-PDT with red light and IPL are both an effective and safe modality in acne treatment. Red light showed a faster response time than IPL. After multiple sessions, both light sources demonstrated satisfactory results. We suggest that reducing the total dose of red light is desirable when performing MAL-PDT in Asian patients with acne compared with Caucasians.

  19. Intelligence-guided beam angle optimization in treatment planning of intensity-modulated radiation therapy.

    PubMed

    Yan, Hui; Dai, Jian-Rong

    2016-10-01

    An intelligence guided approach based on fuzzy inference system (FIS) was proposed to automate beam angle optimization in treatment planning of intensity-modulated radiation therapy (IMRT). The model of FIS is built on inference rules in describing the relationship between dose quality of IMRT plan and irradiated region of anatomical structure. Dose quality of IMRT plan is quantified by the difference between calculated and constraint doses of the anatomical structures in an IMRT plan. Irradiated region of anatomical structure is characterized by the metric, covered region of interest, which is the region of an anatomical structure under radiation field while beam's eye-view is conform to target volume. Initially, an IMRT plan is created with a single beam. The dose difference is calculated for the input of FIS and the output of FIS is obtained with processing of fuzzy inference. Later, a set of candidate beams is generated for replacing the current beam. This process continues until no candidate beams is found. Then the next beam is added to the IMRT plan and optimized in the same way as the previous beam. The new beam keeps adding to the IMRT plan until the allowed beam number is reached. Two spinal cases were investigated in this study. The preliminary results show that dose quality of IMRT plans achieved by this approach is better than those achieved by the default approach with equally spaced beam setting. It is effective to find the optimal beam combination of IMRT plan with the intelligence-guided approach.

  20. Intensity-modulated radiation therapy for malignancies of the nasal cavity and paranasal sinuses

    SciTech Connect

    Daly, Megan E.; Chen, Allen M. . E-mail: allenmchen@yahoo.com; Bucci, M. Kara; El-Sayed, Ivan; Xia Ping; Kaplan, Michael J.; Eisele, David W.

    2007-01-01

    Purpose: To report the clinical outcome of patients treated with intensity-modulated radiation therapy (IMRT) for malignancies of the nasal cavity and paranasal sinuses. Methods and Materials: Between 1998 and 2004, 36 patients with malignancies of the sinonasal region were treated with IMRT. Thirty-two patients (89%) were treated in the postoperative setting after gross total resection. Treatment plans were designed to provide a dose of 70 Gy to 95% or more of the gross tumor volume (GTV) and 60 Gy to 95% or more of the clinical tumor volume (CTV) while sparing neighboring critical structures including the optic chiasm, optic nerves, eyes, and brainstem. The primary sites were: 13 ethmoid sinus, 10 maxillary sinus, 7 nasal cavity, and 6 other. Histology was: 12 squamous cell, 7 esthesioneuroblastoma, 5 adenoid cystic, 5 undifferentiated, 5 adenocarcinoma, and 2 other. Median follow-up was 51 months among surviving patients (range, 9-82 months). Results: The 2-year and 5-year estimates of local control were 62% and 58%, respectively. One patient developed isolated distant metastasis, and none developed isolated regional failure. The 5-year rates of disease-free and overall survival were 55% and 45%, respectively. The incidence of ocular toxicity was minimal with no patients reporting decreased vision. Late complications included xerophthalmia (1 patient), lacrimal stenosis (1 patient), and cataract (1 patient). Conclusion: Although IMRT for malignancies of the sinonasal region does not appear to lead to significant improvements in disease control, the low incidence of complications is encouraging.

  1. Dosimetric comparison of tools for intensity modulated radiation therapy with gamma analysis: a phantom study

    NASA Astrophysics Data System (ADS)

    Akbas, Ugur; Okutan, Murat; Demir, Bayram; Koksal, Canan

    2015-07-01

    Dosimetry of the Intensity Modulated Radiation Therapy (IMRT) is very important because of the complex dose distributions. Diode arrays are the most common and practical measurement tools for clinical usage for IMRT. Phantom selection is critical for QA process. IMRT treatment plans are recalculated for the phantom irradiation in QA. Phantoms are made in different geometrical shapes to measure the doses of different types of irradiation techniques. Comparison of measured and calculated dose distributions for IMRT can be made by using gamma analysis. In this study, 10 head-and-neck IMRT QA plans were created with Varian Eclipse 8.9 treatment planning system. Water equivalent RW3-slab phantoms, Octavius-2 phantom and PTW Seven29 2D-array were used for QA measurements. Gantry, collimator and couch positions set to 00 and QA plans were delivered to RW3 and Octavius phantoms. Then the positions set to original angles and QA plans irradiated again. Measured and calculated fluence maps were evaluated with gamma analysis for different DD and DTA criteria. The effect of different set-up conditions for RW3 and Octavius phantoms in QA plan delivery evaluated by gamma analysis. Results of gamma analysis show that using RW3-slab phantoms with setting parameters to 00 is more appropriate for IMRT QA.

  2. Physical therapy-driven quality improvement to promote early mobility in the intensive care unit.

    PubMed

    Harris, Christy L; Shahid, Shafi

    2014-07-01

    Growing evidence shows that early mobilization of patients in the intensive care unit (ICU) is a safe and cost-effective strategy to improve patient outcomes. However, in ICUs where early mobilization has not been practiced, its adoption requires culture change by the multidisciplinary team, including physical therapists, nurses, respiratory therapists, and physicians. We describe a physical therapist-led program to introduce such changes in a medical-surgical and a cardiovascular ICU. Interdisciplinary and multidisciplinary meetings and education sessions informed critical care team members about early mobilization and encouraged knowledge sharing for safety and effectiveness. A lead physical therapist was appointed to advocate for early mobility and developed solutions to overcome the identified barriers. After the initiation of this program, the number of ICU patients receiving physical therapy evaluations increased from 364 in 2011-2012 to 542 in 2012-2013. In this article, we describe our experience from 21 patients who underwent early mobilization. A physical therapist-led initiative can help establish an ICU culture that supports early mobilization, but the change is slow and requires interdisciplinary collaboration to identify and overcome barriers.

  3. A fast optimization algorithm for multicriteria intensity modulated proton therapy planning

    SciTech Connect

    Chen Wei; Craft, David; Madden, Thomas M.; Zhang, Kewu; Kooy, Hanne M.; Herman, Gabor T.

    2010-09-15

    Purpose: To describe a fast projection algorithm for optimizing intensity modulated proton therapy (IMPT) plans and to describe and demonstrate the use of this algorithm in multicriteria IMPT planning. Methods: The authors develop a projection-based solver for a class of convex optimization problems and apply it to IMPT treatment planning. The speed of the solver permits its use in multicriteria optimization, where several optimizations are performed which span the space of possible treatment plans. The authors describe a plan database generation procedure which is customized to the requirements of the solver. The optimality precision of the solver can be specified by the user. Results: The authors apply the algorithm to three clinical cases: A pancreas case, an esophagus case, and a tumor along the rib cage case. Detailed analysis of the pancreas case shows that the algorithm is orders of magnitude faster than industry-standard general purpose algorithms (MOSEK's interior point optimizer, primal simplex optimizer, and dual simplex optimizer). Additionally, the projection solver has almost no memory overhead. Conclusions: The speed and guaranteed accuracy of the algorithm make it suitable for use in multicriteria treatment planning, which requires the computation of several diverse treatment plans. Additionally, given the low memory overhead of the algorithm, the method can be extended to include multiple geometric instances and proton range possibilities, for robust optimization.

  4. Meningioma Causing Visual Impairment: Outcomes and Toxicity After Intensity Modulated Radiation Therapy

    SciTech Connect

    Maclean, Jillian; Fersht, Naomi; Bremner, Fion; Stacey, Chris; Sivabalasingham, Suganya; Short, Susan

    2013-03-15

    Purpose: To evaluate ophthalmologic outcomes and toxicity of intensity modulated radiation therapy (IMRT) in patients with meningiomas causing visual deficits. Methods and Materials: A prospective observational study with formal ophthalmologic and clinical assessment of 30 consecutive cases of meningioma affecting vision treated with IMRT from 2007 to 2011. Prescriptions were 50.4 Gy to mean target dose in 28 daily fractions. The median follow-up time was 28 months. Twenty-six meningiomas affected the anterior visual pathway (including 3 optic nerve sheath meningiomas); 4 were posterior to the chiasm. Results: Vision improved objectively in 12 patients (40%). Improvements were in visual field (5/16 patients), color vision (4/9 patients), acuity (1/15 patients), extraocular movements (3/11 patients), ptosis (1/5 patients), and proptosis (2/6 patients). No predictors of clinical response were found. Two patients had minor reductions in tumor dimensions on magnetic resonance imaging, 1 patient had radiological progression, and the other patients were stable. One patient experienced grade 2 keratitis, 1 patient had a minor visual field loss, and 5 patients had grade 1 dry eye. Conclusion: IMRT is an effective method for treating meningiomas causing ophthalmologic deficits, and toxicity is minimal. Thorough ophthalmologic assessment is important because clinical responses often occur in the absence of radiological change.

  5. On Linear Infeasibility Arising in Intensity-Modulated Radiation Therapy Inverse Planning.

    PubMed

    Censor, Yair; Ben-Israel, Adi; Xiao, Ying; Galvin, James M

    2008-03-01

    Intensity-modulated radiation therapy (IMRT) gives rise to systems of linear inequalities, representing the effects of radiation on the irradiated body. These systems are often infeasible, in which case one settles for an approximate solution, such as an {α, β}-relaxation, meaning that no more than α percent of the inequalities are violated by no more than β percent. For real-world IMRT problems, there is a feasible {α, β}-relaxation for sufficiently large α, β > 0, however large values of these parameters may be unacceptable medically.The {α, β}-relaxation problem is combinatorial, and for given values of the parameters can be solved exactly by Mixed Integer Programming (MIP), but this may be impractical because of problem size, and the need for repeated solutions as the treatment progresses.As a practical alternative to the MIP approach we present a heuristic non-combinatorial method for finding an approximate relaxation. The method solves a Linear Program (LP) for each pair of values of the parameters {α, β} and progresses through successively increasing values until an acceptable solution is found, or is determined non-existent. The method is fast and reliable, since it consists of solving a sequence of LP's.

  6. A novel linear programming approach to fluence map optimization for intensity modulated radiation therapy treatment planning.

    PubMed

    Romeijn, H Edwin; Ahuja, Ravindra K; Dempsey, James F; Kumar, Arvind; Li, Jonathan G

    2003-11-07

    We present a novel linear programming (LP) based approach for efficiently solving the intensity modulated radiation therapy (IMRT) fluence-map optimization (FMO) problem to global optimality. Our model overcomes the apparent limitations of a linear-programming approach by approximating any convex objective function by a piecewise linear convex function. This approach allows us to retain the flexibility offered by general convex objective functions, while allowing us to formulate the FMO problem as a LP problem. In addition, a novel type of partial-volume constraint that bounds the tail averages of the differential dose-volume histograms of structures is imposed while retaining linearity as an alternative approach to improve dose homogeneity in the target volumes, and to attempt to spare as many critical structures as possible. The goal of this work is to develop a very rapid global optimization approach that finds high quality dose distributions. Implementation of this model has demonstrated excellent results. We found globally optimal solutions for eight 7-beam head-and-neck cases in less than 3 min of computational time on a single processor personal computer without the use of partial-volume constraints. Adding such constraints increased the running times by a factor of 2-3, but improved the sparing of critical structures. All cases demonstrated excellent target coverage (> 95%), target homogeneity (< 10% overdosing and < 7% underdosing) and organ sparing using at least one of the two models.

  7. Combining segment generation with direct step-and-shoot optimization in intensity-modulated radiation therapy

    SciTech Connect

    Carlsson, Fredrik

    2008-09-15

    A method for generating a sequence of intensity-modulated radiation therapy step-and-shoot plans with increasing number of segments is presented. The objectives are to generate high-quality plans with few, large and regular segments, and to make the planning process more intuitive. The proposed method combines segment generation with direct step-and-shoot optimization, where leaf positions and segment weights are optimized simultaneously. The segment generation is based on a column generation approach. The method is evaluated on a test suite consisting of five head-and-neck cases and five prostate cases, planned for delivery with an Elekta SLi accelerator. The adjustment of segment shapes by direct step-and-shoot optimization improves the plan quality compared to using fixed segment shapes. The improvement in plan quality when adding segments is larger for plans with few segments. Eventually, adding more segments contributes very little to the plan quality, but increases the plan complexity. Thus, the method provides a tool for controlling the number of segments and, indirectly, the delivery time. This can support the planner in finding a sound trade-off between plan quality and treatment complexity.

  8. Low Intensity Laser Therapy (LILT) Versus Transcutaneous Electrical Nerve Stimulation On Microcirculation In Diabetic Neuropathy

    NASA Astrophysics Data System (ADS)

    Battecha, Kadria H.; Atya, Azza M.

    2011-09-01

    Reduced microcirculation is a morbid element of neuropathy and one of the most common complications of uncontrolled diabetes. Many physical modalities have gained a considerable attention for enhancing cutaneous microcirculation in diabetic patients and prevent its serious complications. Accordingly, the present study was conducted to compare between the effect of low intensity laser therapy (LILT) and transcutaneous electrical nerve stimulation (TENS) on microcirculation in diabetic neuropathy. Thirty diabetic polyneuropathic patients ranged in age from 45-60 years participated in this study. They were randomly divided into two groups of equal number; patients in group (A) received LILT on plantar surface of foot with a dose of 3 J/cm2 and wavelength (904 nm), while those in group (B) received TENS on lower leg for 30 minutes with frequency (2 HZ). Treatment was conducted 3 times/week for 6 weeks. The cutaneous microcirculation was evaluated by Laser Doppler flowmetry at the baseline and at the end of treatment. Results revealed that group (A) showed statistically significant increase in the cutaneous microcirculation compared with group (B). So, it was concluded that LILT has to be more efficient than TENS in increasing cutaneous microcirculation in patients with diabetic neuropathy.

  9. The Accuracy of Inhomogeneity Corrections in Intensity Modulated Radiation Therapy Planning in Philips Pinnacle System

    SciTech Connect

    Alaei, Parham; Higgins, Patrick D.

    2011-10-01

    The degree of accuracy of inhomogeneity corrections in a treatment planning system is dependent on the algorithm used by the system. The choice of field size, however, could have an effect on the calculation accuracy as well. There have been several evaluation studies on the accuracy of inhomogeneity corrections used by different algorithms. Most of these studies, however, focus on evaluating the dose in phantom using simplified geometry and open/static fields. This work focuses on evaluating the degree of dose accuracy in calculations involving intensity-modulated radiation therapy (IMRT) fields incident on a phantom containing both lung- and bone-equivalent heterogeneities using 6 and 10 MV beams. IMRT treatment plans were generated using the Philips Pinnacle treatment planning system and delivered to a phantom containing 55 thermoluminescent dosimeter (TLD) locations within the lung and bone and near the lung and bone interfaces with solid water. The TLD readings were compared with the dose predicted by the planning system. We find satisfactory agreement between planned and delivered doses, with an overall absolute average difference between measurement and calculation of 1.2% for the 6 MV and 3.1% for the 10 MV beam with larger variations observed near the interfaces and in areas of high-dose gradient. The results presented here demonstrate that the convolution algorithm used in the Pinnacle treatment planning system produces accurate results in IMRT plans calculated and delivered to inhomogeneous media, even in regions that potentially lack electronic equilibrium.

  10. Rational use of intensity-modulated radiation therapy: the importance of clinical outcome.

    PubMed

    De Neve, Wilfried; De Gersem, Werner; Madani, Indira

    2012-01-01

    During the last 2 decades, intensity-modulated radiation therapy (IMRT) became a standard technique despite its drawbacks of volume delineation, planning, robustness of delivery, challenging quality assurance, and cost as compared with non-IMRT. The theoretic advantages of IMRT dose distributions are generally accepted, but the clinical advantages remain debatable because of the lack of clinical assessment of the effort that is required to overshadow the disadvantages. Rational IMRT use requires a positive advantage/drawback balance. Only 5 randomized clinical trials (RCTs), 3 in the breast and 2 in the head and neck, which compare IMRT with non-IMRT (2-dimensional technique in four fifths of the trials), have been published (as of March 2011), and all had toxicity as the primary endpoint. More than 50 clinical trials compared results of IMRT-treated patients with a non-IMRT group, mostly historical controls. RCTs systematically showed a lower toxicity in IMRT-treated patients, and the non-RCTs confirmed these findings. Toxicity reduction, counterbalancing the drawbacks of IMRT, was convincing for breast and head and neck IMRT. For other tumor sites, the arguments favoring IMRT are weaker because of the inability to control bias outside the randomized setting. For anticancer efficacy endpoints, like survival, disease-specific survival, or locoregional control, the balance between advantages and drawbacks is fraught with uncertainties because of the absence of robust clinical data.

  11. High Intensity Focused Ultrasound for Cancer Therapy--harnessing its non-linearity

    SciTech Connect

    Haar, Gail ter

    2008-06-24

    In medicine in general, and for cancer treatments in particular, there is a drive to find effective non-invasive therapies. High Intensity Focused Ultrasound (HIFU) represents one such technique. In principle, it is simple--a high energy ultrasound beam is brought to a tight focus within a target which may lie several centimetres below the skin surface (for example, in a tumour of the liver), and is used to destroy a selected tissue volume. The main mechanism for cell killing in a HIFU beam is heat. Ultrasound energy absorption is frequency dependent, the higher frequencies being absorbed most strongly. Significant thermal advantage may therefore be gained from non-linear propagation, which generates higher harmonics, in tissue. Acoustic cavitation and thermal exsolution of gas (boiling) also contribute to tissue damage. This activity leads to the local mechanical disruption of cells. In addition, the non-linear oscillation of these bubbles leads to enhanced energy deposition. The acoustic emissions from such bubbles are characteristic of their behaviour and may be correlated to some extent with the appearance of the disruption produced. The more widespread clinical acceptance of HIFU is awaiting faster, and more efficient, energy delivery and treatment monitoring. A better understanding of the nonlinear aspects of HIFU propagation in tissue is thus important if this technique is to benefit more patients.

  12. Validation of a track repeating algorithm for intensity modulated proton therapy: clinical cases study

    NASA Astrophysics Data System (ADS)

    Yepes, Pablo P.; Eley, John G.; Liu, Amy; Mirkovic, Dragan; Randeniya, Sharmalee; Titt, Uwe; Mohan, Radhe

    2016-04-01

    Monte Carlo (MC) methods are acknowledged as the most accurate technique to calculate dose distributions. However, due its lengthy calculation times, they are difficult to utilize in the clinic or for large retrospective studies. Track-repeating algorithms, based on MC-generated particle track data in water, accelerate dose calculations substantially, while essentially preserving the accuracy of MC. In this study, we present the validation of an efficient dose calculation algorithm for intensity modulated proton therapy, the fast dose calculator (FDC), based on a track-repeating technique. We validated the FDC algorithm for 23 patients, which included 7 brain, 6 head-and-neck, 5 lung, 1 spine, 1 pelvis and 3 prostate cases. For validation, we compared FDC-generated dose distributions with those from a full-fledged Monte Carlo based on GEANT4 (G4). We compared dose-volume-histograms, 3D-gamma-indices and analyzed a series of dosimetric indices. More than 99% of the voxels in the voxelized phantoms describing the patients have a gamma-index smaller than unity for the 2%/2 mm criteria. In addition the difference relative to the prescribed dose between the dosimetric indices calculated with FDC and G4 is less than 1%. FDC reduces the calculation times from 5 ms per proton to around 5 μs.

  13. SU-E-P-18: Intensity-Modulated Radiation Therapy for Cervical Esophageal Squamous Cell Carcinoma

    SciTech Connect

    Bai, W; Qiao, X; Zhou, Z; Song, Y; Zhang, R; Zhen, C

    2015-06-15

    Purpose: To retrospectively analyze the outcomes and prognostic factors of cervical esophageal squamous cell carcinoma (SCC) treated with intensity modulated radiation therapy (IMRT). Methods: Thirty-seven patients with cervical esophageal SCC treated with IMRT were analyzed retrospectively. They received 54–66 Gy in 27–32 fractions. Nineteen patients received concurrent (n=12) or sequential (n=7) platinum-based two drugs chemoradiotherapy. Overall survival (OS), local control rates (LCR) and prognostic factors were evaluated. Acute toxicities and patterns of first failures were observed. Results: The median follow-up was 46 months for alive patients. The l-, 3-, 4- and 5-year OS of the all patients were 83.8%, 59.1%, 47.5% and 32.6% respectively. The median survival time was 46 months. The l-, 3-,4- and 5-year LCR were 82.9%, 63.0%, 54.5% and 54.5%, respectively. Univariate and Multivariate analysis all showed that size of GTV was an independent prognostic factor (p=0.033, p=0.039). There were no patients with Grade 3 acute radiation esophagitis and Grade 2–4 acute pneumonitis. The local failure accounted for 70.0% of all treatment-related failures. Conclusion: IMRT is safe and effective in the treatment of cervical esophageal squamous cell carcinoma. Size of GTV is an independent prognostic factor. Local failure still remains the main reason of treatment failures. The authors declare no conflicts of interest in preparing this article.

  14. Validation of a track repeating algorithm for intensity modulated proton therapy: clinical cases study.

    PubMed

    Yepes, Pablo P; Eley, John G; Liu, Amy; Mirkovic, Dragan; Randeniya, Sharmalee; Titt, Uwe; Mohan, Radhe

    2016-04-07

    Monte Carlo (MC) methods are acknowledged as the most accurate technique to calculate dose distributions. However, due its lengthy calculation times, they are difficult to utilize in the clinic or for large retrospective studies. Track-repeating algorithms, based on MC-generated particle track data in water, accelerate dose calculations substantially, while essentially preserving the accuracy of MC. In this study, we present the validation of an efficient dose calculation algorithm for intensity modulated proton therapy, the fast dose calculator (FDC), based on a track-repeating technique. We validated the FDC algorithm for 23 patients, which included 7 brain, 6 head-and-neck, 5 lung, 1 spine, 1 pelvis and 3 prostate cases. For validation, we compared FDC-generated dose distributions with those from a full-fledged Monte Carlo based on GEANT4 (G4). We compared dose-volume-histograms, 3D-gamma-indices and analyzed a series of dosimetric indices. More than 99% of the voxels in the voxelized phantoms describing the patients have a gamma-index smaller than unity for the 2%/2 mm criteria. In addition the difference relative to the prescribed dose between the dosimetric indices calculated with FDC and G4 is less than 1%. FDC reduces the calculation times from 5 ms per proton to around 5 μs.

  15. Compact multileaf collimator for conformal and intensity modulated fast neutron therapy: Electromechanical design and validation

    SciTech Connect

    Farr, J. B.; Maughan, R. L.; Yudelev, M.; Blosser, E.; Brandon, J.; Horste, T.; Forman, J. D.

    2006-09-15

    The electromechanical properties of a 120-leaf, high-resolution, computer-controlled, fast neutron multileaf collimator (MLC) are presented. The MLC replaces an aging, manually operated multirod collimator. The MLC leaves project 5 mm in the isocentric plane perpendicular to the beam axis. A taper is included on the leaves matching beam divergence along one axis. The 5-mm leaf projection width is chosen to give high-resolution conformality across the entire field. The maximum field size provided is 30x30 cm{sup 2}. To reduce the interleaf transmission a 0.254-mm blocking step is included. End-leaf steps totaling 0.762 mm are also provided allowing opposing leaves to close off within the primary radiation beam. The neutron MLC also includes individual 45 deg. and 60 deg. automated universal tungsten wedges. The automated high-resolution neutron collimation provides an increase in patient throughput capacity, enables a new modality, intensity modulated neutron therapy, and limits occupational radiation exposure by providing remote operation from a shielded console area.

  16. Brain Plasticity following Intensive Bimanual Therapy in Children with Hemiparesis: Preliminary Evidence

    PubMed Central

    Weinstein, Maya; Myers, Vicki; Green, Dido; Schertz, Mitchell; Shiran, Shelly I.; Geva, Ronny; Artzi, Moran; Gordon, Andrew M.; Fattal-Valevski, Aviva; Ben Bashat, Dafna

    2015-01-01

    Neuroplasticity studies examining children with hemiparesis (CH) have focused predominantly on unilateral interventions. CH also have bimanual coordination impairments with bimanual interventions showing benefits. We explored neuroplasticity following hand-arm bimanual intensive therapy (HABIT) of 60 hours in twelve CH (6 females, mean age 11 ± 3.6 y). Serial behavioral evaluations and MR imaging including diffusion tensor (DTI) and functional (fMRI) imaging were performed before, immediately after, and at 6-week follow-up. Manual skills were assessed repeatedly with the Assisting Hand Assessment, Children's Hand Experience Questionnaire, and Jebsen-Taylor Test of Hand Function. Beta values, indicating the level of activation, and lateralization index (LI), indicating the pattern of brain activation, were computed from fMRI. White matter integrity of major fibers was assessed using DTI. 11/12 children showed improvement after intervention in at least one measure, with 8/12 improving on two or more tests. Changes were retained in 6/8 children at follow-up. Beta activation in the affected hemisphere increased at follow-up, and LI increased both after intervention and at follow-up. Correlations between LI and motor function emerged after intervention. Increased white matter integrity was detected in the corpus callosum and corticospinal tract after intervention in about half of the participants. Results provide first evidence for neuroplasticity changes following bimanual intervention in CH. PMID:26640717

  17. Peers, Regulators, and Professions: The Influence of Organizations in Intensive Insulin Therapy Adoption

    PubMed Central

    Campion, Thomas R.; Gadd, Cynthia S.

    2011-01-01

    Following the landmark Leuven study in 2001, health care organizations implemented intensive insulin therapy (IIT) as the standard of care for critically ill patients. However, a recent meta-analysis showed no mortality benefit and an increased safety risk for patients treated with IIT. IIT affects labor and capital decisions related to nurses, physicians, pharmacists, managers, laboratory personnel, and informatics staff. The expenditure of labor and capital to provide IIT without corresponding outcome improvements suggests the adoption of IIT produces inefficiency in hospitals. In sociology and organizational studies, the tendency for organizations to become more similar without necessarily becoming more efficient is called institutional isomorphism. Institutional isomorphism examines the pressure organizations encounter from peers, regulators, and professions through mimetic, coercive, and normative mechanisms, respectively. To enhance their prospects of survival, organizations establish and maintain legitimacy by adopting socially acceptable approaches to work endorsed by successful peer organizations, regulatory agencies, and professional societies. In this paper, the authors describe how organizational influence—through the Leuven study, the Joint Commission, and professional organizations—played a role in the widespread adoption of IIT. Divergence from institutionalized forms may explain variation in IIT studies following Leuven. Healthcare researchers, practitioners, and managers should consider organizational influence when implementing large scale clinical activities. PMID:19369854

  18. Accounting for range uncertainties in the optimization of intensity modulated proton therapy.

    PubMed

    Unkelbach, Jan; Chan, Timothy C Y; Bortfeld, Thomas

    2007-05-21

    Treatment plans optimized for intensity modulated proton therapy (IMPT) may be sensitive to range variations. The dose distribution may deteriorate substantially when the actual range of a pencil beam does not match the assumed range. We present two treatment planning concepts for IMPT which incorporate range uncertainties into the optimization. The first method is a probabilistic approach. The range of a pencil beam is assumed to be a random variable, which makes the delivered dose and the value of the objective function a random variable too. We then propose to optimize the expectation value of the objective function. The second approach is a robust formulation that applies methods developed in the field of robust linear programming. This approach optimizes the worst case dose distribution that may occur, assuming that the ranges of the pencil beams may vary within some interval. Both methods yield treatment plans that are considerably less sensitive to range variations compared to conventional treatment plans optimized without accounting for range uncertainties. In addition, both approaches--although conceptually different--yield very similar results on a qualitative level.

  19. An integral quality monitoring system for real-time verification of intensity modulated radiation therapy

    SciTech Connect

    Islam, Mohammad K.; Norrlinger, Bernhard D.; Smale, Jason R.; Heaton, Robert K.; Galbraith, Duncan; Fan, Cary; Jaffray, David A.

    2009-12-15

    Purpose: To develop an independent and on-line beam monitoring system, which can validate the accuracy of segment-by-segment energy fluence delivery for each treatment field. The system is also intended to be utilized for pretreatment dosimetric quality assurance of intensity modulated radiation therapy (IMRT), on-line image-guided adaptive radiation therapy, and volumetric modulated arc therapy. Methods: The system, referred to as the integral quality monitor (IQM), utilizes an area integrating energy fluence monitoring sensor (AIMS) positioned between the final beam shaping device [i.e., multileaf collimator (MLC)] and the patient. The prototype AIMS consists of a novel spatially sensitive large area ionization chamber with a gradient along the direction of the MLC motion. The signal from the AIMS provides a simple output for each beam segment, which is compared in real time to the expected value. The prototype ionization chamber, with a physical area of 22x22 cm{sup 2}, has been constructed out of aluminum with the electrode separations varying linearly from 2 to 20 mm. A calculation method has been developed to predict AIMS signals based on an elementwise integration technique, which takes into account various predetermined factors, including the spatial response function of the chamber, MLC characteristics, beam transmission through the secondary jaws, and field size factors. The influence of the ionization chamber on the beam has been evaluated in terms of transmission, surface dose, beam profiles, and depth dose. The sensitivity of the system was tested by introducing small deviations in leaf positions. A small set of IMRT fields for prostate and head and neck plans was used to evaluate the system. The ionization chamber and the data acquisition software systems were interfaced to two different types of linear accelerators: Elekta Synergy and Varian iX. Results: For a 10x10 cm{sup 2} field, the chamber attenuates the beam intensity by 7% and 5% for 6 and 18

  20. Acute intensive insulin therapy exacerbates diabetic blood-retinal barrier breakdown via hypoxia-inducible factor-1α and VEGF

    PubMed Central

    Poulaki, Vassiliki; Qin, Wenying; Joussen, Antonia M.; Hurlbut, Peter; Wiegand, Stanley J.; Rudge, John; Yancopoulos, George D.; Adamis, Anthony P.

    2002-01-01

    Acute intensive insulin therapy is an independent risk factor for diabetic retinopathy. Here we demonstrate that acute intensive insulin therapy markedly increases VEGF mRNA and protein levels in the retinae of diabetic rats. Retinal nuclear extracts from insulin-treated rats contain higher hypoxia-inducible factor-1α (HIF-1α) levels and demonstrate increased HIF-1α–dependent binding to hypoxia-responsive elements in the VEGF promoter. Blood-retinal barrier breakdown is markedly increased with acute intensive insulin therapy but can be reversed by treating animals with a fusion protein containing a soluble form of the VEGF receptor Flt; a control fusion protein has no such protective effect. The insulin-induced retinal HIF-1α and VEGF increases and the related blood-retinal barrier breakdown are suppressed by inhibitors of p38 mitogen-activated protein kinase (MAPK) and phosphatidylinositol (PI) 3-kinase, but not inhibitors of p42/p44 MAPK or protein kinase C. Taken together, these findings indicate that acute intensive insulin therapy produces a transient worsening of diabetic blood-retinal barrier breakdown via an HIF-1α–mediated increase in retinal VEGF expression. Insulin-induced VEGF expression requires p38 MAPK and PI 3-kinase, whereas hyperglycemia-induced VEGF expression is HIF-1α–independent and requires PKC and p42/p44 MAPK. To our knowledge, these data are the first to identify a specific mechanism for the transient worsening of diabetic retinopathy, specifically blood-retinal barrier breakdown, that follows the institution of intensive insulin therapy. PMID:11901189

  1. Availability of physical therapy assistance in neonatal intensive care units in the city of São Paulo, Brazil

    PubMed Central

    Liberali, Joyce; Davidson, Josy; dos Santos, Amelia Miyashiro Nunes

    2014-01-01

    Objective To describe the characteristics of physical therapy assistance to newborns and to provide a profile of physical therapists working in intensive care units in the city of São Paulo, Brazil. Methods This cross-sectional study was conducted in every hospital in São Paulo city that had at least one intensive care unit bed for newborns registered at the National Registry of Health Establishments in 2010. In each unit, three types of physical therapists were included: an executive who was responsible for the physical therapy service in that hospital (chief-physical therapists), a physical therapist who was responsible for the physical therapy assistance in the neonatal unit (reference-physical therapists), and a randomly selected physical therapist who was directly involved in the neonatal care (care-physical therapists). Results Among the 67 hospitals eligible for the study, 63 (94.0%) had a physical therapy service. Of those hospitals, three (4.8%) refused to participate. Thus, 60 chief-PTs, 52 reference-physical therapists, and 44 care-physical therapists were interviewed. During day shifts, night shifts, and weekends/holidays, there were no physical therapists in 1.7%, 45.0%, and 13.3% of the intensive care units, respectively. Physical therapy assistance was available for 17.8±7.2 hours/day, and each physical therapist cared for 9.4±2.6 newborns during six working hours. Most professionals had completed at least one specialization course. Conclusion Most neonatal intensive care units in the city of São Paulo had physical therapists working on the day shift. However, other shifts had incomplete staff with less than 18 hours of available physical therapy assistance per day. PMID:24770690

  2. Improving intensity-modulated radiation therapy using the anatomic beam orientation optimization algorithm

    SciTech Connect

    Potrebko, Peter S.; McCurdy, Boyd M. C.; Butler, James B.; El-Gubtan, Adel S.

    2008-05-15

    A novel, anatomic beam orientation optimization (A-BOO) algorithm is proposed to significantly improve conventional intensity-modulated radiation therapy (IMRT). The A-BOO algorithm vectorially analyses polygonal surface mesh data of contoured patient anatomy. Five optimal (5-opt) deliverable beam orientations are selected based on (1) tangential orientation bisecting the target and adjacent organ's-at-risk (OARs) to produce precipitous dose gradients between them and (2) parallel incidence with polygon features of the target volume to facilitate conformal coverage. The 5-opt plans were compared to standard five, seven, and nine equiangular-spaced beam plans (5-equi, 7-equi, 9-equi) for: (1) gastric, (2) Radiation Therapy Oncology Group (RTOG) P-0126 prostate, and (3) RTOG H-0022 oropharyngeal (stage-III, IV) cancer patients. In the gastric case, the noncoplanar 5-opt plan reduced the right kidney V 20 Gy by 32.2%, 23.2%, and 20.6% compared to plans with five, seven, and nine equiangular-spaced beams. In the prostate case, the coplanar 5-opt plan produced similar rectal sparing as the 7-equi and 9-equi plans with a reduction of the V 75, V 70, V 65, and V 60 Gy of 2.4%, 5.3%, 7.0%, and 9.5% compared to the 5-equi plan. In the stage-III and IV oropharyngeal cases, the noncoplanar 5-opt plan substantially reduced the V 30 Gy and mean dose to the contralateral parotid compared to plans with five, seven, and nine equiangular-spaced beams: (stage-III) 7.1%, 5.2%, 6.8%, and 5.1, 3.5, 3.7 Gy and (stage-IV) 10.2%, 10.2%, 9.8% and 7.0, 7.1, 7.2 Gy. The geometry-based A-BOO algorithm has been demonstrated to be robust for application to a variety of IMRT treatment sites. Beam orientations producing significant improvements in OAR sparing over conventional IMRT can be automatically produced in minutes compared to hours with existing dose-based beam orientation optimization methods.

  3. Influence of robust optimization in intensity-modulated proton therapy with different dose delivery techniques

    SciTech Connect

    Liu Wei; Li Yupeng; Li Xiaoqiang; Cao Wenhua; Zhang Xiaodong

    2012-06-15

    Purpose: The distal edge tracking (DET) technique in intensity-modulated proton therapy (IMPT) allows for high energy efficiency, fast and simple delivery, and simple inverse treatment planning; however, it is highly sensitive to uncertainties. In this study, the authors explored the application of DET in IMPT (IMPT-DET) and conducted robust optimization of IMPT-DET to see if the planning technique's sensitivity to uncertainties was reduced. They also compared conventional and robust optimization of IMPT-DET with three-dimensional IMPT (IMPT-3D) to gain understanding about how plan robustness is achieved. Methods: They compared the robustness of IMPT-DET and IMPT-3D plans to uncertainties by analyzing plans created for a typical prostate cancer case and a base of skull (BOS) cancer case (using data for patients who had undergone proton therapy at our institution). Spots with the highest and second highest energy layers were chosen so that the Bragg peak would be at the distal edge of the targets in IMPT-DET using 36 equally spaced angle beams; in IMPT-3D, 3 beams with angles chosen by a beam angle optimization algorithm were planned. Dose contributions for a number of range and setup uncertainties were calculated, and a worst-case robust optimization was performed. A robust quantification technique was used to evaluate the plans' sensitivity to uncertainties. Results: With no uncertainties considered, the DET is less robust to uncertainties than is the 3D method but offers better normal tissue protection. With robust optimization to account for range and setup uncertainties, robust optimization can improve the robustness of IMPT plans to uncertainties; however, our findings show the extent of improvement varies. Conclusions: IMPT's sensitivity to uncertainties can be improved by using robust optimization. They found two possible mechanisms that made improvements possible: (1) a localized single-field uniform dose distribution (LSFUD) mechanism, in which the

  4. SU-E-T-62: Cardiac Toxicity in Dynamic Conformal Arc Therapy, Intensity-Modulated Radiation Therapy and Volumetric Modulated Arc Therapy of Lung Cancers

    SciTech Connect

    Ming, X; Zhang, Y; Feng, Y; Zhou, L; Deng, J

    2014-06-01

    Purpose: The cardiac toxicity for lung cancer patients, each treated with dynamic conformal arc therapy (DAT), intensity-modulated radiation therapy (IMRT), or volumetric modulated arc therapy (VMAT) is investigated. Methods: 120 lung patients were selected for this study: 25 treated with DAT, 50 with IMRT and 45 with VMAT. For comparison, all plans were generated in the same treatment planning system, normalized such that the 100% isodose lines encompassed 95% of planning target volume. The plan quality was evaluated in terms of homogeneity index (HI) and 95% conformity index (%95 CI) for target dose coverage and mean dose, maximum dose, V{sub 30} Gy as well as V{sub 5} Gy for cardiac toxicity analysis. Results: When all the plans were analyzed, the VMAT plans offered the best target coverage with 95% CI = 0.992 and HI = 1.23. The DAT plans provided the best heart sparing with mean heart dose = 2.3Gy and maximum dose = 11.6Gy, as compared to 5.7 Gy and 31.1 Gy by IMRT as well as 4.6 Gy and 30.9 Gy by VMAT. The mean V30Gy and V5Gy of the heart in the DAT plans were up to 11.7% lower in comparison to the IMRT and VMAT plans. When the tumor volume was considered, the VMAT plans spared up to 70.9% more doses to the heart when the equivalent diameter of the tumor was larger than 4cm. Yet the maximum dose to the heart was reduced the most in the DAT plans with up to 139.8% less than that of the other two plans. Conclusion: Overall, the VMAT plans achieved the best target coverage among the three treatment modalities, and would spare the heart the most for the larger tumors. The DAT plans appeared advantageous in delivering the least maximum dose to the heart as compared to the IMRT and VMAT plans.

  5. Stereotactic body radiation therapy planning with duodenal sparing using volumetric-modulated arc therapy vs intensity-modulated radiation therapy in locally advanced pancreatic cancer: A dosimetric analysis

    SciTech Connect

    Kumar, Rachit; Wild, Aaron T.; Ziegler, Mark A.; Hooker, Ted K.; Dah, Samson D.; Tran, Phuoc T.; Kang, Jun; Smith, Koren; Zeng, Jing; Pawlik, Timothy M.; Tryggestad, Erik; Ford, Eric; Herman, Joseph M.

    2013-10-01

    Stereotactic body radiation therapy (SBRT) achieves excellent local control for locally advanced pancreatic cancer (LAPC), but may increase late duodenal toxicity. Volumetric-modulated arc therapy (VMAT) delivers intensity-modulated radiation therapy (IMRT) with a rotating gantry rather than multiple fixed beams. This study dosimetrically evaluates the feasibility of implementing duodenal constraints for SBRT using VMAT vs IMRT. Non–duodenal sparing (NS) and duodenal-sparing (DS) VMAT and IMRT plans delivering 25 Gy in 1 fraction were generated for 15 patients with LAPC. DS plans were constrained to duodenal D{sub max} of<30 Gy at any point. VMAT used 1 360° coplanar arc with 4° spacing between control points, whereas IMRT used 9 coplanar beams with fixed gantry positions at 40° angles. Dosimetric parameters for target volumes and organs at risk were compared for DS planning vs NS planning and VMAT vs IMRT using paired-sample Wilcoxon signed rank tests. Both DS VMAT and DS IMRT achieved significantly reduced duodenal D{sub mean}, D{sub max}, D{sub 1cc}, D{sub 4%}, and V{sub 20} {sub Gy} compared with NS plans (all p≤0.002). DS constraints compromised target coverage for IMRT as demonstrated by reduced V{sub 95%} (p = 0.01) and D{sub mean} (p = 0.02), but not for VMAT. DS constraints resulted in increased dose to right kidney, spinal cord, stomach, and liver for VMAT. Direct comparison of DS VMAT and DS IMRT revealed that VMAT was superior in sparing the left kidney (p<0.001) and the spinal cord (p<0.001), whereas IMRT was superior in sparing the stomach (p = 0.05) and the liver (p = 0.003). DS VMAT required 21% fewer monitor units (p<0.001) and delivered treatment 2.4 minutes faster (p<0.001) than DS IMRT. Implementing DS constraints during SBRT planning for LAPC can significantly reduce duodenal point or volumetric dose parameters for both VMAT and IMRT. The primary consequence of implementing DS constraints for VMAT is increased dose to other organs at

  6. Multibeam tomotherapy: A new treatment unit devised for multileaf collimation, intensity-modulated radiation therapy

    SciTech Connect

    Achterberg, Nils; Mueller, Reinhold G.

    2007-10-15

    A fully integrated system for treatment planning, application, and verification for automated multileaf collimator (MLC) based, intensity-modulated, image-guided, and adaptive radiation therapy (IMRT, IGRT and ART, respectively) is proposed. Patient comfort, which was the major development goal, will be achieved through a new unit design and short treatment times. Our device for photon beam therapy will consist of a new dual energy linac with five fixed treatment heads positioned evenly along one plane but one electron beam generator only. A minimum of moving parts increases technical reliability and reduces motion times to a minimum. Motion is allowed solely for the MLCs, the robotic patient table, and the small angle gantry rotation of {+-}36 deg. . Besides sophisticated electron beam guidance, this compact setup can be built using existing modules. The flattening-filter-free treatment heads are characterized by reduced beam-on time and contain apertures restricted in one dimension to the area of maximum primary fluence output. In the case of longer targets, this leads to a topographic intensity modulation, thanks to the combination of 'step and shoot' MLC delivery and discrete patient couch motion. Owing to the limited number of beam directions, this multislice cone beam serial tomotherapy is referred to as 'multibeam tomotherapy.' Every patient slice is irradiated by one treatment head at any given moment but for one subfield only. The electron beam is then guided to the next head ready for delivery, while the other heads are preparing their leaves for the next segment. The 'Multifocal MLC-positioning' algorithm was programmed to enable treatment planning and optimize treatment time. We developed an overlap strategy for the longitudinally adjacent fields of every beam direction, in doing so minimizing the field match problem and the effects of possible table step errors. Clinical case studies show for the same or better planning target volume coverage, better

  7. Multibeam tomotherapy: a new treatment unit devised for multileaf collimation, intensity-modulated radiation therapy.

    PubMed

    Achterberg, Nils; Müller, Reinhold G

    2007-10-01

    A fully integrated system for treatment planning, application, and verification for automated multileaf collimator (MLC) based, intensity-modulated, image-guided, and adaptive radiation therapy (IMRT, IGRT and ART, respectively) is proposed. Patient comfort, which was the major development goal, will be achieved through a new unit design and short treatment times. Our device for photon beam therapy will consist of a new dual energy linac with five fixed treatment heads positioned evenly along one plane but one electron beam generator only. A minimum of moving parts increases technical reliability and reduces motion times to a minimum. Motion is allowed solely for the MLCs, the robotic patient table, and the small angle gantry rotation of +/- 36 degrees. Besides sophisticated electron beam guidance, this compact setup can be built using existing modules. The flattening-filter-free treatment heads are characterized by reduced beam-on time and contain apertures restricted in one dimension to the area of maximum primary fluence output. In the case of longer targets, this leads to a topographic intensity modulation, thanks to the combination of "step and shoot" MLC delivery and discrete patient couch motion. Owing to the limited number of beam directions, this multislice cone beam serial tomotherapy is referred to as "multibeam tomotherapy." Every patient slice is irradiated by one treatment head at any given moment but for one subfield only. The electron beam is then guided to the next head ready for delivery, while the other heads are preparing their leaves for the next segment. The "Multifocal MLC-positioning" algorithm was programmed to enable treatment planning and optimize treatment time. We developed an overlap strategy for the longitudinally adjacent fields of every beam direction, in doing so minimizing the field match problem and the effects of possible table step errors. Clinical case studies show for the same or better planning target volume coverage, better

  8. Short-term intensive insulin therapy at diagnosis in type 2 diabetes: plan for filling the gaps.

    PubMed

    Weng, Jianping; Retnakaran, Ravi; Ariachery C, Ammini; Ji, Linong; Meneghini, Luigi; Yang, Wenying; Woo, Jeong-Taek

    2015-09-01

    Short-term intensive insulin therapy is unique amongst therapies for type 2 diabetes because it offers the potential to preserve and improve beta-cell function without additional pharmacological treatment. On the basis of clinical experience and the promising results of a series of studies in newly diagnosed patients, mostly in Asian populations, an expert workshop was convened to assess the available evidence and the potential application of short-term intensive insulin therapy should it be advocated for inclusion in clinical practice. Participants included primary care physicians and endocrinologists. We endorse the concept of short-term intensive insulin therapy as an option for some patients with type 2 diabetes at the time of diagnosis and have identified the following six areas where additional knowledge could help clarify optimal use in clinical practice: (1) generalizability to primary care, (2) target population and biomarkers, (3) follow-up treatment, (4) education of patients and providers, (5) relevance of ethnicity, and (6) health economics.

  9. Intensity-Modulated Proton Therapy Versus Helical Tomotherapy in Nasopharynx Cancer: Planning Comparison and NTCP Evaluation

    SciTech Connect

    Widesott, Lamberto Pierelli, Alessio; Fiorino, Claudio; Dell'Oca, Italo; Broggi, Sara; Cattaneo, Giovanni Mauro; Di Muzio, Nadia; Fazio, Ferruccio; Calandrino, Riccardo; Schwarz, Marco

    2008-10-01

    Purpose: To compare intensity-modulated proton therapy (IMPT) and helical tomotherapy (HT) treatment plans for nasopharynx cancer using a simultaneous integrated boost approach. Methods and Materials: The data from 6 patients who had previously been treated with HT were used. A three-beam IMPT technique was optimized in the Hyperion treatment planning system, simulating a 'beam scanning' technique. HT was planned using the tomotherapy treatment planning system. Both techniques were optimized to simultaneously deliver 66 Gy in 30 fractions to planning target volume (PTV1; GTV and enlarged nodes) and 54 Gy to PTV2 subclinical, electively treated nodes. Normal tissue complication probability calculation was performed for the parotids and larynx. Results: Very similar PTVs coverage and homogeneity of the target dose distribution for IMPT and HT were found. The conformity index was significantly lower for protons than for photons (1.19 vs. 1.42, respectively). The mean dose to the ipsilateral and contralateral parotid glands decreased by 6.4 Gy and 5.6 Gy, respectively, with IMPT. The volume of mucosa and esophagus receiving {>=}20 Gy and {>=}30 Gy with IMPT was significantly lower than with HT. The average volume of larynx receiving {>=}50 Gy was significantly lower with HT, while for thyroid, it was comparable. The volume receiving {>=}30, {>=}20, and {>=}10 Gy in total body volume decreased with IMPT by 14.5%, 19.4%, and 23.1%, respectively. The normal tissue complication probability for the parotid glands was significantly lower with IMPT for all sets of parameters; however, we also estimated an almost full recovery of the contralateral parotid with HT. The normal tissue complication probability for the larynx was not significantly different between the two irradiation techniques. Conclusion: Excellent target coverage, homogeneity within the PTVs, and sparing of the organs at risk were reached with both modalities. IMPT allows for better sparing of most organs at

  10. A critical evaluation of worst case optimization methods for robust intensity-modulated proton therapy planning

    SciTech Connect

    Fredriksson, Albin Bokrantz, Rasmus

    2014-08-15

    Purpose: To critically evaluate and compare three worst case optimization methods that have been previously employed to generate intensity-modulated proton therapy treatment plans that are robust against systematic errors. The goal of the evaluation is to identify circumstances when the methods behave differently and to describe the mechanism behind the differences when they occur. Methods: The worst case methods optimize plans to perform as well as possible under the worst case scenario that can physically occur (composite worst case), the combination of the worst case scenarios for each objective constituent considered independently (objectivewise worst case), and the combination of the worst case scenarios for each voxel considered independently (voxelwise worst case). These three methods were assessed with respect to treatment planning for prostate under systematic setup uncertainty. An equivalence with probabilistic optimization was used to identify the scenarios that determine the outcome of the optimization. Results: If the conflict between target coverage and normal tissue sparing is small and no dose-volume histogram (DVH) constraints are present, then all three methods yield robust plans. Otherwise, they all have their shortcomings: Composite worst case led to unnecessarily low plan quality in boundary scenarios that were less difficult than the worst case ones. Objectivewise worst case generally led to nonrobust plans. Voxelwise worst case led to overly conservative plans with respect to DVH constraints, which resulted in excessive dose to normal tissue, and less sharp dose fall-off than the other two methods. Conclusions: The three worst case methods have clearly different behaviors. These behaviors can be understood from which scenarios that are active in the optimization. No particular method is superior to the others under all circumstances: composite worst case is suitable if the conflicts are not very severe or there are DVH constraints whereas

  11. Intensity modulated radiation-therapy for preoperative posterior abdominal wall irradiation of retroperitoneal liposarcomas

    SciTech Connect

    Bossi, Alberto . E-mail: alberto.bossi@uz.kuleuven.ac.be; De Wever, Ivo; Van Limbergen, Erik; Vanstraelen, Bianca

    2007-01-01

    Purpose: Preoperative external-beam radiation therapy (preop RT) in the management of Retroperitoneal Liposarcomas (RPLS) typically involves the delivery of radiation to the entire tumor mass: yet this may not be necessary. The purpose of this study is to evaluate a new strategy of preop RT for RPLS in which the target volume is limited to the contact area between the tumoral mass and the posterior abdominal wall. Methods and Materials: Between June 2000 and Jan 2005, 18 patients with the diagnosis of RPLS have been treated following a pilot protocol of pre-op RT, 50 Gy in 25 fractions of 2 Gy/day. The Clinical Target Volume (CTV) has been limited to the posterior abdominal wall, region at higher risk for local relapse. A Three-Dimensional conformal (3D-CRT) and an Intensity Modulated (IMRT) plan were generated and compared; toxicity was reported following the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events v3.0. Results: All patients completed the planned treatment and the acute toxicity was tolerable: 2 patients experienced Grade 3 and 1 Grade 2 anorexia while 2 patients developed Grade 2 nausea. IMRT allows a better sparing of the ipsilateral and the contralateral kidney. All tumors were successfully resected without major complications. At a median follow-up of 27 months 2 patients developed a local relapse and 1 lung metastasis. Conclusions: Our strategy of preop RT is feasible and well tolerated: the rate of resectability is not compromised by limiting the preop CTV to the posterior abdominal wall and a better critical-structures sparing is obtained with IMRT.

  12. Joint health and functional ability in children with haemophilia who receive intensive replacement therapy.

    PubMed

    Groen, W; van der Net, J; Bos, K; Abad, A; Bergstrom, B-M; Blanchette, V S; Feldman, B M; Funk, S; Helders, P; Hilliard, P; Manco-Johnson, M; Petrini, P; Zourikian, N; Fischer, K

    2011-09-01

    Joint physical examination is an important outcome in haemophilia; however its relationship with functional ability is not well established in children with intensive replacement therapy. Boys aged 4-16 years were recruited from two European and three North American treatment centres. Joint physical structure and function was measured with the Haemophilia Joint Health Score (HJHS) while functional ability was measured with the revised Childhood Health Assessment Questionnaire (CHAQ₃₈. Two haemophilia-specific domains were created by selecting items of the CHAQ₃₈ that cover haemophilia-specific problems. Associations between CHAQ, HJHS, cumulative number of haemarthroses and age were assessed. A total of 226 subjects - mean 10.8 years old (SD 3.8) - participated; the majority (68%) had severe haemophilia. Most severe patients (91%) were on prophylactic treatment. Lifetime number of haemarthroses [median=5; interquartile range (IQR)=1-12] and total HJHS (median = 5; IQR=1-12) correlated strongly (ρ = 0.51). Total HJHS did not correlate with age and only weakly (ρ=-0.19) with functional ability scores (median=0; IQR=-0.06-0). Overall, haemarthroses were reported most frequently in the ankles. Detailed analysis of ankle joint health scores revealed moderate associations (ρ=0.3-0.5) of strength, gait and atrophy with lower extremity tasks (e.g. stair climbing). In this population, HJHS summating six joints did not perform as well as individual joint scores, however, certain elements of ankle impairment, specifically muscle strength, atrophy and gait associated significantly with functional loss in lower extremity activities. Mild abnormalities in ankle assessment by HJHS may lead to functional loss. Therefore, ankle joints may warrant special attention in the follow up of these children.

  13. A 2-D diode array and analysis software for verification of intensity modulated radiation therapy delivery.

    PubMed

    Jursinic, Paul A; Nelms, Ben E

    2003-05-01

    An analysis is made of a two-dimensional array of diodes that can be used for measuring dose generated in a plane by a radiation beam. This measuring device is the MapCHECK Model 1175 (Sun Nuclear, Melbourne, FL). This device has 445 N-type diodes in a 22 x 22 cm2 2-D array with variable spacing. The entire array of diodes is easily calibrated to allow for measurements in absolute dose. For IMRT quality assurance, each beam is measured individually with the beam central axis oriented perpendicular to the plane of diodes. Software is available to do the analytical comparison of measurements versus dose distributions calculated by a treatment planning system. Comparison criteria of percent difference and distance-to-agreement are defined by the operator. Data are presented that show the diode array has linear response when beam fluence changes by over 300-fold, which is typical of the level of modulation in intensity modulated radiation therapy, IMRT, beams. A linear dependence is also shown for a 100-fold change in monitors units delivered. Methods for how this device can be used in the clinic for quality assurance of IMRT fields are described. Measurements of typical IMRT beams that are modulated by compensators and MLCs are presented with comparisons to treatment planning system dose calculations. A time analysis is done for typical IMRT quality assurance measurements. The setup, calibration, and analysis time for the 2-D diode array are on the order of 20 min, depending on numbers of fields. This is significantly less time than required to do similar analysis with radiographic film. The 2-D diode array is ideal for per-plan quality assurance after an IMRT system is fully commissioned.

  14. Proton energy optimization and reduction for intensity-modulated proton therapy.

    PubMed

    Cao, Wenhua; Lim, Gino; Liao, Li; Li, Yupeng; Jiang, Shengpeng; Li, Xiaoqiang; Li, Heng; Suzuki, Kazumichi; Zhu, X Ronald; Gomez, Daniel; Zhang, Xiaodong

    2014-11-07

    Intensity-modulated proton therapy (IMPT) is commonly delivered via the spot-scanning technique. To 'scan' the target volume, the proton beam is controlled by varying its energy to penetrate the patient's body at different depths. Although scanning the proton beamlets or spots with the same energy can be as fast as 10-20 m s(-1), changing from one proton energy to another requires approximately two additional seconds. The total IMPT delivery time thus depends mainly on the number of proton energies used in a treatment. Current treatment planning systems typically use all proton energies that are required for the proton beam to penetrate in a range from the distal edge to the proximal edge of the target. The optimal selection of proton energies has not been well studied. In this study, we sought to determine the feasibility of optimizing and reducing the number of proton energies in IMPT planning. We proposed an iterative mixed-integer programming optimization method to select a subset of all available proton energies while satisfying dosimetric criteria. We applied our proposed method to six patient datasets: four cases of prostate cancer, one case of lung cancer, and one case of mesothelioma. The numbers of energies were reduced by 14.3%-18.9% for the prostate cancer cases, 11.0% for the lung cancer cases and 26.5% for the mesothelioma case. The results indicate that the number of proton energies used in conventionally designed IMPT plans can be reduced without degrading dosimetric performance. The IMPT delivery efficiency could be improved by energy layer optimization leading to increased throughput for a busy proton center in which a delivery system with slow energy switch is employed.

  15. Proton energy optimization and reduction for intensity-modulated proton therapy

    NASA Astrophysics Data System (ADS)

    Cao, Wenhua; Lim, Gino; Liao, Li; Li, Yupeng; Jiang, Shengpeng; Li, Xiaoqiang; Li, Heng; Suzuki, Kazumichi; Zhu, X. Ronald; Gomez, Daniel; Zhang, Xiaodong

    2014-10-01

    Intensity-modulated proton therapy (IMPT) is commonly delivered via the spot-scanning technique. To ‘scan’ the target volume, the proton beam is controlled by varying its energy to penetrate the patient’s body at different depths. Although scanning the proton beamlets or spots with the same energy can be as fast as 10-20 m s-1, changing from one proton energy to another requires approximately two additional seconds. The total IMPT delivery time thus depends mainly on the number of proton energies used in a treatment. Current treatment planning systems typically use all proton energies that are required for the proton beam to penetrate in a range from the distal edge to the proximal edge of the target. The optimal selection of proton energies has not been well studied. In this study, we sought to determine the feasibility of optimizing and reducing the number of proton energies in IMPT planning. We proposed an iterative mixed-integer programming optimization method to select a subset of all available proton energies while satisfying dosimetric criteria. We applied our proposed method to six patient datasets: four cases of prostate cancer, one case of lung cancer, and one case of mesothelioma. The numbers of energies were reduced by 14.3%-18.9% for the prostate cancer cases, 11.0% for the lung cancer cases and 26.5% for the mesothelioma case. The results indicate that the number of proton energies used in conventionally designed IMPT plans can be reduced without degrading dosimetric performance. The IMPT delivery efficiency could be improved by energy layer optimization leading to increased throughput for a busy proton center in which a delivery system with slow energy switch is employed.

  16. An Anatomically Validated Brachial Plexus Contouring Method for Intensity Modulated Radiation Therapy Planning

    SciTech Connect

    Van de Velde, Joris; Audenaert, Emmanuel; Speleers, Bruno; Vercauteren, Tom; Mulliez, Thomas; Vandemaele, Pieter; Achten, Eric; Kerckaert, Ingrid; D'Herde, Katharina; De Neve, Wilfried; Van Hoof, Tom

    2013-11-15

    Purpose: To develop contouring guidelines for the brachial plexus (BP) using anatomically validated cadaver datasets. Magnetic resonance imaging (MRI) and computed tomography (CT) were used to obtain detailed visualizations of the BP region, with the goal of achieving maximal inclusion of the actual BP in a small contoured volume while also accommodating for anatomic variations. Methods and Materials: CT and MRI were obtained for 8 cadavers positioned for intensity modulated radiation therapy. 3-dimensional reconstructions of soft tissue (from MRI) and bone (from CT) were combined to create 8 separate enhanced CT project files. Dissection of the corresponding cadavers anatomically validated the reconstructions created. Seven enhanced CT project files were then automatically fitted, separately in different regions, to obtain a single dataset of superimposed BP regions that incorporated anatomic variations. From this dataset, improved BP contouring guidelines were developed. These guidelines were then applied to the 7 original CT project files and also to 1 additional file, left out from the superimposing procedure. The percentage of BP inclusion was compared with the published guidelines. Results: The anatomic validation procedure showed a high level of conformity for the BP regions examined between the 3-dimensional reconstructions generated and the dissected counterparts. Accurate and detailed BP contouring guidelines were developed, which provided corresponding guidance for each level in a clinical dataset. An average margin of 4.7 mm around the anatomically validated BP contour is sufficient to accommodate for anatomic variations. Using the new guidelines, 100% inclusion of the BP was achieved, compared with a mean inclusion of 37.75% when published guidelines were applied. Conclusion: Improved guidelines for BP delineation were developed using combined MRI and CT imaging with validation by anatomic dissection.

  17. Electromagnetic-Guided Dynamic Multileaf Collimator Tracking Enables Motion Management for Intensity-Modulated Arc Therapy

    SciTech Connect

    Keall, Paul J.; Sawant, Amit; Cho, Byungchul; Ruan, Dan; Wu Junqing; Poulsen, Per; Petersen, Jay; Newell, Laurence J.; Cattell, Herbert; Korreman, Stine

    2011-01-01

    Purpose: Intensity-modulated arc therapy (IMAT) is attractive because of high-dose conformality and efficient delivery. However, managing intrafraction motion is challenging for IMAT. The purpose of this research was to develop and investigate electromagnetically guided dynamic multileaf collimator (DMLC) tracking as an enabling technology to treat moving targets during IMAT. Methods and Materials: A real-time three-dimensional DMLC-based target tracking system was developed and integrated with a linear accelerator. The DMLC tracking software inputs a real-time electromagnetically measured target position and the IMAT plan, and dynamically creates new leaf positions directed at the moving target. Low- and high-modulation IMAT plans were created for lung and prostate cancer cases. The IMAT plans were delivered to a three-axis motion platform programmed with measured patient motion. Dosimetric measurements were acquired by placing an ion chamber array on the moving platform. Measurements were acquired with tracking, without tracking (current clinical practice), and with the phantom in a static position (reference). Analysis of dose distribution differences from the static reference used a {gamma}-test. Results: On average, 1.6% of dose points for the lung plans and 1.2% of points for the prostate plans failed the 3-mm/3% {gamma}-test with tracking; without tracking, 34% and 14% (respectively) of points failed the {gamma}-test. The delivery time was the same with and without tracking. Conclusions: Electromagnetic-guided DMLC target tracking with IMAT has been investigated for the first time. Dose distributions to moving targets with DMLC tracking were significantly superior to those without tracking. There was no loss of treatment efficiency with DMLC tracking.

  18. Patterns of Disease Recurrence Following Treatment of Oropharyngeal Cancer With Intensity Modulated Radiation Therapy

    SciTech Connect

    Garden, Adam S.; Dong, Lei; Morrison, William H.; Stugis, Erich M.; Glisson, Bonnie S.; Schwartz, David L.; Kies, Merill S.; Ang, K. Kian; Rosenthal, David I.

    2013-03-15

    Purpose: To report mature results of a large cohort of patients diagnosed with squamous cell carcinoma of the oropharynx who were treated with intensity modulated radiation therapy (IMRT). Methods and Materials: The database of patients irradiated at The University of Texas, M.D. Anderson Cancer Center was searched for patients diagnosed with oropharyngeal cancer and treated with IMRT between 2000 and 2007. A retrospective review of outcome data was performed. Results: The cohort consisted of 776 patients. One hundred fifty-nine patients (21%) were current smokers, 279 (36%) former smokers, and 337 (43%) never smokers. T and N categories and American Joint Committee on Cancer group stages were distributed as follows: T1/x, 288 (37%); T2, 288 (37%); T3, 113 (15%); T4, 87 (11%); N0, 88(12%); N1/x, 140 (18%); N2a, 101 (13%); N2b, 269 (35%); N2c, 122 (16%); and N3, 56 (7%); stage I, 18(2%); stage II, 40(5%); stage III, 150(19%); and stage IV, 568(74%). Seventy-one patients (10%) presented with nodes in level IV. Median follow-up was 54 months. The 5-year overall survival, locoregional control, and overall recurrence-free survival rates were 84%, 90%, and 82%, respectively. Primary site recurrence developed in 7% of patients, and neck recurrence with primary site control in 3%. We could only identify 12 patients (2%) who had locoregional recurrence outside the high-dose target volumes. Poorer survival rates were observed in current smokers, patients with larger primary (T) tumors and lower neck disease. Conclusions: Patients with oropharyngeal cancer treated with IMRT have excellent disease control. Locoregional recurrence was uncommon, and most often occurred in the high dose volumes. Parotid sparing was accomplished in nearly all patients without compromising tumor coverage.

  19. Disease Control and Ototoxicity Using Intensity-Modulated Radiation Therapy Tumor-Bed Boost for Medulloblastoma

    SciTech Connect

    Polkinghorn, William R.; Dunkel, Ira J.; Souweidane, Mark M.; Khakoo, Yasmin; Lyden, David C.; Gilheeney, Stephen W.; Becher, Oren J.; Budnick, Amy S.; Wolden, Suzanne L.

    2011-11-01

    Purpose: We previously reported excellent local control for treating medulloblastoma with a limited boost to the tumor bed. In order to decrease ototoxicity, we subsequently implemented a tumor-bed boost using intensity-modulated radiation therapy (IMRT), the clinical results of which we report here. Patients and Methods: A total of 33 patients with newly diagnosed medulloblastoma, 25 with standard risk, and 8 with high risk, were treated on an IMRT tumor-bed boost following craniospinal irradiation (CSI). Six standard-risk patients were treated with an institutional protocol with 18 Gy CSI in conjunction with intrathecal iodine-131-labeled monoclonal antibody. The majority of patients received concurrent vincristine and standard adjuvant chemotherapy. Pure-tone audiograms were graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0. Results: Median age was 9 years old (range, 4-46 years old). Median follow-up was 63 months. Kaplan-Meier estimates of progression-free survival (PFS) and overall survival (OS) rates for standard-risk patients who received 23.4 or 36 Gy CSI (not including those who received 18 Gy CSI with radioimmunotherapy) were 81.4% and 88.4%, respectively, at 5 years; 5-year PFS and OS rates for high-risk patients were both 87.5%. There were no isolated posterior fossa failures outside of the boost volume. Posttreatment audiograms were available for 31 patients, of whom 6%, at a median follow-up of 19 months, had developed Grade 3 hearing loss. Conclusion: An IMRT tumor-bed boost results in excellent local control while delivering a low mean dose to the cochlea, resulting in a low rate of ototoxicity.

  20. Hypofractionated Dose-Painting Intensity Modulated Radiation Therapy With Chemotherapy for Nasopharyngeal Carcinoma: A Prospective Trial

    SciTech Connect

    Bakst, Richard L.; Lee, Nancy; Pfister, David G.; Zelefsky, Michael J.; Hunt, Margie A.; Kraus, Dennis H.; Wolden, Suzanne L.

    2011-05-01

    Purpose: To evaluate the feasibility of dose-painting intensity-modulated radiation therapy (DP-IMRT) with a hypofractionated regimen to treat nasopharyngeal carcinoma (NPC) with concomitant toxicity reduction. Methods and Materials: From October 2002 through April 2007, 25 newly diagnosed NPC patients were enrolled in a prospective trial. DP-IMRT was prescribed to deliver 70.2 Gy using 2.34-Gy fractions to the gross tumor volume for the primary and nodal sites while simultaneously delivering 54 Gy in 1.8-Gy fractions to regions at risk of microscopic disease. Patients received concurrent and adjuvant platin-based chemotherapy similar to the Intergroup 0099 trial. Results: Patient and disease characteristics are as follows: median age, 46; 44% Asian; 68% male; 76% World Health Organization III; 20% T1, 52% T2, 16% T3, 12% T4; 20% N0, 36% N1, 36% N2, 8% N3. With median follow-up of 33 months, 3-year local control was 91%, regional control was 91%, freedom from distant metastases was 91%, and overall survival was 89%. The average mean dose to each cochlea was 43 Gy. With median audiogram follow-up of 14 months, only one patient had clinically significant (Grade 3) hearing loss. Twelve percent of patients developed temporal lobe necrosis; one patient required surgical resection. Conclusions: Preliminary findings using a hypofractionated DP-IMRT regimen demonstrated that local control, freedom from distant metastases, and overall survival compared favorably with other series of IMRT and chemotherapy. The highly conformal boost to the tumor bed resulted low rates of severe ototoxicity (Grade 3-4). However, the incidence of in-field brain radiation necrosis indicates that 2.34 Gy per fraction is not safe in this setting.

  1. Automation and Intensity Modulated Radiation Therapy for Individualized High-Quality Tangent Breast Treatment Plans

    SciTech Connect

    Purdie, Thomas G.; Dinniwell, Robert E.; Fyles, Anthony; Sharpe, Michael B.

    2014-11-01

    Purpose: To demonstrate the large-scale clinical implementation and performance of an automated treatment planning methodology for tangential breast intensity modulated radiation therapy (IMRT). Methods and Materials: Automated planning was used to prospectively plan tangential breast IMRT treatment for 1661 patients between June 2009 and November 2012. The automated planning method emulates the manual steps performed by the user during treatment planning, including anatomical segmentation, beam placement, optimization, dose calculation, and plan documentation. The user specifies clinical requirements of the plan to be generated through a user interface embedded in the planning system. The automated method uses heuristic algorithms to define and simplify the technical aspects of the treatment planning process. Results: Automated planning was used in 1661 of 1708 patients receiving tangential breast IMRT during the time interval studied. Therefore, automated planning was applicable in greater than 97% of cases. The time for treatment planning using the automated process is routinely 5 to 6 minutes on standard commercially available planning hardware. We have shown a consistent reduction in plan rejections from plan reviews through the standard quality control process or weekly quality review multidisciplinary breast rounds as we have automated the planning process for tangential breast IMRT. Clinical plan acceptance increased from 97.3% using our previous semiautomated inverse method to 98.9% using the fully automated method. Conclusions: Automation has become the routine standard method for treatment planning of tangential breast IMRT at our institution and is clinically feasible on a large scale. The method has wide clinical applicability and can add tremendous efficiency, standardization, and quality to the current treatment planning process. The use of automated methods can allow centers to more rapidly adopt IMRT and enhance access to the documented

  2. Ototoxicity After Intensity-Modulated Radiation Therapy and Cisplatin-Based Chemotherapy in Children With Medulloblastoma

    SciTech Connect

    Paulino, Arnold C.; Lobo, Mark; Teh, Bin S.; Okcu, M. Fatih; South, Michael; Butler, E. Brian; Su, Jack; Chintagumpala, Murali

    2010-12-01

    Purpose: To report the incidence of Pediatric Oncology Group (POG) Grade 3 or 4 ototoxicity in a cohort of patients treated with craniospinal irradiation (CSI) followed by posterior fossa (PF) and/or tumor bed (TB) boost using intensity-modulated radiation therapy (IMRT). Methods and Materials: From 1998 to 2006, 44 patients with medulloblastoma were treated with CSI followed by IMRT to the PF and/or TB and cisplatin-based chemotherapy. Patients with standard-risk disease were treated with 18 to 23.4 Gy CSI followed by either a (1) PF boost to 36 Gy and TB boost to 54 to 55.8 Gy or (2) TB boost to 55.8 Gy. Patients with high-risk disease received 36 to 39.6 Gy CSI followed by a (1) PF boost to 54 to 55.8 Gy, (2) PF boost to 45 Gy and TB boost to 55.8 Gy, or (3) TB boost to 55.8 Gy. Median audiogram follow-up was 41 months (range, 11-92.4 months). Results: POG Grade Ototoxicity 0, 1, 2, 3. and 4 was found in 29, 32, 11, 13. and 3 ears. respectively, with POG Grade 3 or 4 accounting for 18.2% of cases. There was a statistically significant difference in mean radiation dose (D{sub mean}) cochlea according to degree of ototoxicity, with D{sub mean} cochlea increasing with severity of hearing loss (p = 0.027). Conclusions: Severe ototoxicity was seen in 18.2% of ears in children treated with IMRT boost and cisplatin-based chemotherapy. Increasing dose to the cochlea was associated with increasing severity of hearing loss.

  3. Gamma evaluation combined with isocenter optimal matching in intensity modulated radiation therapy quality assurance

    NASA Astrophysics Data System (ADS)

    Bak, Jino; Choi, Jin Hwa; Park, Suk Won; Park, Kwangwoo; Park, Sungho

    2015-12-01

    Two-dimensional (2D) dose comparisons are widely performed by using a gamma evaluation with patient-specific intensity modulated radiation therapy quality assurance (IMRT QA) or dose delivery quality assurance (DQA). In this way, a pass/fail determination is made for a particular treatment plan. When gamma evaluation results are close to the failure criterion, the pass/fail decision may change applying a small shift to the center of the 2D dose distribution. In this study, we quantitatively evaluated the meaning of such a small relative shift in a 2D dose distribution comparison. In addition, we propose the use of a small shift for a pass/fail criterion in gamma analysis, where the concept of isocenter optimal matching (IOM) is applied to IMRT QA of 20 patients. Gamma evaluations were performed to compare two dose distributions, one with and the other without IOM. In-house software was developed in C++ in order to find IOM values including both translational and rotational shifts. Upon gamma evaluation failure, further investigation was initiated using IOM. In this way, three groups were categorized: group 1 for `pass' on gamma evaluation, group 21 for `fail' on the gamma evaluation and `pass' on the gamma the evaluation with IOM, and group 22 for `fail' on the both gamma evaluations and the IOM calculation. IOM results revealed that some failures could be considered as a `pass'. In group 21, 88.98% (fail) of the averaged gamma pass rate changed to 90.45% (pass) when IOM was applied. On average, a ratio of γ ≥ 1 was reduced by 11.06% in 20 patients. We propose that gamma evaluations that do not pass with a rate of 85% to 90% may be augmented with IOM to reveal a potential pass result.

  4. Planning Hybrid Intensity Modulated Radiation Therapy for Whole-breast Irradiation

    SciTech Connect

    Farace, Paolo; Zucca, Sergio; Solla, Ignazio; Fadda, Giuseppina; Durzu, Silvia; Porru, Sergio; Meleddu, Gianfranco; Deidda, Maria Assunta; Possanzini, Marco; Orru, Sivia; Lay, Giancarlo

    2012-09-01

    Purpose: To test tangential and not-tangential hybrid intensity modulated radiation therapy (IMRT) for whole-breast irradiation. Methods and Materials: Seventy-eight (36 right-, 42 left-) breast patients were randomly selected. Hybrid IMRT was performed by direct aperture optimization. A semiautomated method for planning hybrid IMRT was implemented using Pinnacle scripts. A plan optimization volume (POV), defined as the portion of the planning target volume covered by the open beams, was used as the target objective during inverse planning. Treatment goals were to prescribe a minimum dose of 47.5 Gy to greater than 90% of the POV and to minimize the POV and/or normal tissue receiving a dose greater than 107%. When treatment goals were not achieved by using a 4-field technique (2 conventional open plus 2 IMRT tangents), a 6-field technique was applied, adding 2 non tangential (anterior-oblique) IMRT beams. Results: Using scripts, manual procedures were minimized (choice of optimal beam angle, setting monitor units for open tangentials, and POV definition). Treatment goals were achieved by using the 4-field technique in 61 of 78 (78%) patients. The 6-field technique was applied in the remaining 17 of 78 (22%) patients, allowing for significantly better achievement of goals, at the expense of an increase of low-dose ({approx}5 Gy) distribution in the contralateral tissue, heart, and lungs but with no significant increase of higher doses ({approx}20 Gy) in heart and lungs. The mean monitor unit contribution to IMRT beams was significantly greater (18.7% vs 9.9%) in the group of patients who required 6-field procedure. Conclusions: Because hybrid IMRT can be performed semiautomatically, it can be planned for a large number of patients with little impact on human or departmental resources, promoting it as the standard practice for whole-breast irradiation.

  5. Validity of bedside blood glucose measurement in critically ill patients with intensive insulin therapy

    PubMed Central

    Mahmoodpoor, Ata; Hamishehkar, Hadi; Shadvar, Kamran; Sanaie, Sarvin; Iranpour, Afshin; Fattahi, Vahid

    2016-01-01

    Background and Aims: There have been variable results on the practice of tight glycemic control, and studies have demonstrated that point-of-care (POC) glucometers have variable accuracy. Glucometers must be accurate, and many variables can affect blood glucose levels. The purpose of this study was to determine the difference between blood glucose concentrations obtained from POC glucometers and laboratory results in critically ill patients with intensive insulin therapy. Materials and Methods: This was a descriptive study which enrolled 300 critically ill patients. Four samples of arterial blood were collected and analyzed at the bedside with the POC glucometer and also in the central laboratory to obtain the blood glucose level. To define the effect of various factors on this relation, we noted the levels of hemoglobin (Hb), PaO2, body temperature, bilirubin, history of drug usage, and sepsis. Results: There were not any significant differences between blood sugar levels using laboratory and glucometer methods of measurements. There was a good and significant correlation between glucose levels between two methods (r = 0.81, P < 0.001). Among evaluated factors (body temperature, bilirubin level, blood pressure, Hb level, PaO2, sepsis, and drugs) which added one by one in model, just drugs decreased the correlation more than others (r = 0.78). Conclusions: The results of POC glucometer differ from laboratory glucose concentrations, especially in critically ill patients with unstable hemodynamic status while receiving several drugs. This may raise the concern about using POC devices for tight glycemic control in critically ill patients. These results should be interpreted with caution because of the large variation of accuracy among different glucometer devices. PMID:27994380

  6. In vitro study of cell survival following dynamic MLC intensity-modulated radiation therapy dose delivery

    SciTech Connect

    Moiseenko, Vitali; Duzenli, Cheryl; Durand, Ralph E.

    2007-04-15

    The possibility of reduced cell kill following intensity-modulated radiation therapy (IMRT) compared to conventional radiation therapy has been debated in the literature. This potential reduction in cell kill relates to prolonged treatment times typical of IMRT dose delivery and consequently increased repair of sublethal lesions. While there is some theoretical support to this reduction in cell kill published in the literature, direct experimental evidence specific to IMRT dose delivery patterns is lacking. In this study we present cell survival data for three cell lines: Chinese hamster V79 fibroblasts, human cervical carcinoma, SiHa and colon adenocarcinoma, WiDr. Cell survival was obtained for 2.1 Gy delivered as acute dose with parallel-opposed pair (POP), irradiation time 75 s, which served as a reference; regular seven-field IMRT, irradiation time 5 min; and IMRT with a break for multiple leaf collimator (MLC) re-initialization after three fields were delivered, irradiation time 10 min. An actual seven-field dynamic MLC IMRT plan for a head and neck patient was used. The IMRT plan was generated for a Varian EX or iX linear accelerator with 120 leaf Millenium MLC. Survival data were also collected for doses 1x, 2x, 3x, 4x, and 5x 2.1 Gy to establish parameters of the linear-quadratic equation describing survival following acute dose delivery. Cells were irradiated inside an acrylic cylindrical phantom specifically designed for this study. Doses from both IMRT and POP were validated using ion chamber measurements. A reproducible increase in cell survival was observed following IMRT dose delivery. This increase varied from small for V79, with a surviving fraction of 0.8326 following POP vs 0.8420 following uninterrupted IMRT, to very pronounced for SiHa, with a surviving fraction of 0.3903 following POP vs 0.5330 for uninterrupted IMRT. When compared to IMRT or IMRT with a break for MLC initialization, cell survival following acute dose delivery was

  7. Practical considerations for the dosing and adjustment of continuous renal replacement therapy in the intensive care unit.

    PubMed

    Galvagno, Samuel M; Hong, Caron M; Lissauer, Matthew E; Baker, Andrew K; Murthi, Sarah B; Herr, Daniel L; Stein, Deborah M

    2013-12-01

    Familiarity with the initiation, dosing, adjustment, and termination of continuous renal replacement therapy (CRRT) is a core skill for contemporary intensivists. Guidelines for how to administer CRRT in the intensive care unit are not well documented. The purpose of this review is to discuss the modalities, terminology, and components of CRRT, with an emphasis on the practical aspects of dosing, adjustments, and termination. Management of electrolyte and acid-base derangements commonly encountered with acute renal failure is emphasized. Knowledge regarding the practical aspects of managing CRRT in the intensive care unit is a prerequisite for achieving desired physiological end points.

  8. Impact of combined lipid lowering and blood pressure control on coronary plaque: myocardial ischemia treated by percutaneous coronary intervention and plaque regression by lipid lowering and blood pressure controlling assessed by intravascular ultrasonography (MILLION) study.

    PubMed

    Kawashiri, Masa-Aki; Sakata, Kenji; Hayashi, Kenshi; Gamou, Tadatsugu; Kanaya, Honin; Miwa, Kenji; Ueda, Kosei; Higashikata, Toshinori; Mizuno, Sumio; Michishita, Ichiro; Namura, Masanobu; Nitta, Yutaka; Katsuda, Shoji; Okeie, Kazuyasu; Hirase, Hiroaki; Tada, Hayato; Uchiyama, Katsuharu; Konno, Tetsuo; Ino, Hidekazu; Nagase, Keisuke; Yamagishi, Masakazu

    2016-10-31

    The aim of the study was to elucidate the aggressive reduction of both low-density lipoprotein cholesterol (LDL-C) and blood pressure (BP) reduced coronary atherosclerotic plaque volume compared with a standard treatment of LDL-C and BP in Japanese patients with coronary artery disease (CAD). This study is a prospective, randomized, and open-labelled with a blind-endpoint evaluation study. A total of 97 patients (81 men, mean age 62.0 ± 9.6) with CAD undergoing intravascular ultrasonography (IVUS)-guided percutaneous coronary intervention (PCI) were randomized, and 68 patients had IVUS examinations at baseline and at 18-24 months follow-up. Patients were randomly assigned to standard or aggressive strategies targeting LDL-C and a BP of 100 mg/dL and 140/90 mmHg vs. 70 mg/dL and 120/70 mmHg, respectively. The primary endpoint was the percent change in coronary plaque volume. Both standard and aggressive strategies succeeded to achieve target levels of LDL-C and BP; 74.9 ± 14.7 vs. 63.7 ± 11.9 mg/dL (NS) and 124.1 ± 9.4/75.8 ± 7.7 vs. 113.6 ± 9.6/65.8 ± 9.4 mmHg (systolic BP; NS, diastolic BP; p < 0.05), respectively. Both groups showed a significant reduction in the coronary plaque volume of -9.4 ± 10.7% and -8.7 ± 8.6% (NS) in standard and aggressive therapies, respectively. Both standard and aggressive intervention significantly regressed coronary plaque volume by the same degree, suggesting the importance of simultaneous reductions of LDL-C and BP for prevention of CAD.

  9. Simvastatin Efficiently Lowers Small LDL-IgG Immune Complex Levels: A Therapeutic Quality beyond the Lipid-Lowering Effect

    PubMed Central

    Ferstl, Ulrika; Ledinski, Gerhard; Binder, Josepha; Cvirn, Gerhard; Stojakovic, Tatjana; Trauner, Michael; Koidl, Christoph; Tafeit, Erwin; Amrein, Karin; Scharnagl, Hubert; Jürgens, Günther; Hallström, Seth

    2016-01-01

    We investigated a polyethylene glycol non-precipitable low-density lipoprotein (LDL) subfraction targeted by IgG and the influence of statin therapy on plasma levels of these small LDL-IgG-immune complexes (LDL-IgG-IC). LDL-subfractions were isolated from 6 atherosclerotic subjects and 3 healthy individuals utilizing iodixanol density gradient ultracentrifugation. Cholesterol, apoB and malondialdehyde (MDA) levels were determined in each fraction by enzymatic testing, dissociation-enhanced lanthanide fluorescence immunoassay and high-performance liquid chromatography, respectively. The levels of LDL-IgG-IC were quantified densitometrically following lipid electrophoresis, particle size distribution was assessed with dynamic light scattering and size exclusion chromatography. The influence of simvastatin (40 mg/day for three months) on small LDL-IgG-IC levels and their distribution among LDL-subfractions (salt gradient separation) were investigated in 11 patients with confirmed coronary artery disease (CAD). We demonstrate that the investigated LDL-IgG-IC are small particles present in atherosclerotic patients and healthy subjects. In vitro assembly of LDL-IgG-IC resulted in particle density shifts indicating a composition of one single molecule of IgG per LDL particle. Normalization on cholesterol levels revealed MDA values twice as high for LDL-subfractions rich in small LDL-IgG-IC if compared to dominant LDL-subfractions. Reactivity of affinity purified small LDL-IgG-IC to monoclonal antibody OB/04 indicates a high degree of modified apoB and oxidative modification. Simvastatin therapy studied in the CAD patients significantly lowered LDL levels and to an even higher extent, small LDL-IgG-IC levels without affecting their distribution. In conclusion simvastatin lowers levels of small LDL-IgG-IC more effectively than LDL-cholesterol and LDL-apoB levels in atherosclerotic patients. This antiatherogenic effect may additionally contribute to the known beneficial

  10. Dosimetric and radiobiological comparison of Forward Tangent Intensity Modulated Radiation Therapy (FT-IMRT) and Volumetric Modulated Arc Therapy (VMAT) for early stage whole breast cancer

    NASA Astrophysics Data System (ADS)

    Moshiri Sedeh, Nader

    Intensity Modulated Radiation Therapy (IMRT) is a well-known type of external beam radiation therapy. The advancement in technology has had an inevitable influence in radiation oncology as well that has led to a newer and faster dose delivery technique called Volumetric Modulated Arc Therapy (VMAT). Since the presence of the VMAT modality in clinics in the late 2000, there have been many studies in order to compare the results of the VMAT modality with the current popular modality IMRT for various tumor sites in the body such as brain, prostate, head and neck, cervix and anal carcinoma. This is the first study to compare VMAT with IMRT for breast cancer. The results show that the RapidArc technique in Eclipse version 11 does not improve all aspects of the treatment plans for the breast cases automatically and easily, but it needs to be manipulated by extra techniques to create acceptable plans thus further research is needed.

  11. The Society of Behavioral Medicine position statement on the CMS decision memo on intensive behavior therapy for obesity.

    PubMed

    Pagoto, Sherry L; Pbert, Lori; Emmons, Karen

    2012-12-01

    In 2011, the Centers for Medicare and Medicaid Services (CMS) issued a decision to cover intensive behavior therapy for obesity in the primary care setting. The Society of Behavioral Medicine (SBM) Public Policy Leadership Group reviewed the CMS decision and has issued a position statement. SBM is in support of the CMS decision to cover intensive behavior therapy for obesity but expresses significant concern that aspects of the decision will severely limit the impact of the decision. Concerns focus on the degree to which this care can be feasibly implemented in its current form given the limitations in providers who are covered and the short length of counseling visits relative to evidence-based protocols. SBM is in strong support of modifications that would include providers who have expertise in weight control (e.g., psychologists and dietitians) and to expand the treatment time to better match protocols with confirmed efficacy.

  12. Dosimetric comparison of hybrid volumetric-modulated arc therapy, volumetric-modulated arc therapy, and intensity-modulated radiation therapy for left-sided early breast cancer

    SciTech Connect

    Lin, Jia-Fu; Yeh, Dah-Cherng; Yeh, Hui-Ling; Chang, Chen-Fa; Lin, Jin-Ching

    2015-10-01

    To compare the dosimetric performance of 3 different treatment techniques: hybrid volumetric-modulated arc therapy (hybrid-VMAT), pure-VMAT, and fixed-field intensity-modulated radiation therapy (F-IMRT) for whole-breast irradiation of left-sided early breast cancer. The hybrid-VMAT treatment technique and 2 other treatment techniques—pure-VMAT and F-IMRT—were compared retrospectively in 10 patients with left-sided early breast cancer. The treatment plans of these patients were replanned using the same contours based on the original computed tomography (CT) data sets. Dosimetric parameters were calculated to evaluate plan quality. Total monitor units (MUs) and delivery time were also recorded and evaluated. The hybrid-VMAT plan generated the best results in dose coverage of the target and the dose uniformity inside the target (p < 0.0001 for conformal index [CI]; p = 0.0002 for homogeneity index [HI] of planning target volume [PTV]{sub 50.4} {sub Gy} and p < 0.0001 for HI of PTV{sub 62} {sub Gy}). Volumes of ipsilateral lung irradiated to doses of 20 Gy (V{sub 20} {sub Gy}) and 5 Gy (V{sub 5} {sub Gy}) by the hybrid-VMAT plan were significantly less than those of the F-IMRT and the pure-VMAT plans. The volume of ipsilateral lung irradiated to a dose of 5 Gy was significantly less using the hybrid-VMAT plan than that using the F-IMRT or the pure-VMAT plan. The total mean MUs for the hybrid-VMAT plan were significantly less than those for the F-IMRT or the pure-VMAT plan. The mean machine delivery time was 3.23 ± 0.29 minutes for the hybrid-VMAT plans, which is longer than that for the pure-VMAT plans but shorter than that for the F-IMRT plans. The hybrid-VMAT plan is feasible for whole-breast irradiation of left-sided early breast cancer.

  13. Continuous-time method and its discretization to inverse problem of intensity-modulated radiation therapy treatment planning

    NASA Astrophysics Data System (ADS)

    Fujimoto, Ken'ichi; Tanaka, Yoshihiro; Abou Al-Ola, Omar M.; Yoshinaga, Tetsuya

    2014-06-01

    We propose a novel approach for solving box-constrained inverse problems in intensity-modulated radiation therapy (IMRT) treatment planning based on the idea of continuous dynamical methods and split-feasibility algorithms. Our method can compute a feasible solution without the second derivative of an objective function, which is required for gradient-based optimization algorithms. We prove theoretically that a double Kullback-Leibler divergence can be used as the Lyapunov function for the IMRT planning system.

  14. Prolonged high-dose intravenous magnesium therapy for severe tetanus in the intensive care unit: a case series

    PubMed Central

    2010-01-01

    Introduction Tetanus rarely occurs in developed countries, but it can result in fatal complications including respiratory failure due to generalized muscle spasms. Magnesium infusion has been used to treat spasticity in tetanus, and its effectiveness is supported by several case reports and a recent randomized controlled trial. Case presentations Three Caucasian Greek men aged 30, 50 and 77 years old were diagnosed with tetanus and admitted to a general 12-bed intensive care unit in 2006 and 2007 for respiratory failure due to generalized spasticity. Intensive care unit treatment included antibiotics, hydration, enteral nutrition, early tracheostomy and mechanical ventilation. Intravenous magnesium therapy controlled spasticity without the need for additional muscle relaxants. Their medications were continued for up to 26 days, and adjusted as needed to control spasticity. Plasma magnesium levels, which were measured twice a day, remained in the 3 to 4.5 mmol/L range. We did not observe hemodynamic instability, arrhythmias or other complications related to magnesium therapy in these patients. All patients improved, came off mechanical ventilation, and were discharged from the intensive care unit in a stable condition. Conclusion In comparison with previous reports, our case series contributes the following meaningful additional information: intravenous magnesium therapy was used on patients already requiring mechanical ventilation and remained effective for up to 26 days (significantly longer than in previous reports) without significant toxicity in two patients. The overall outcome was good in all our patients. However, the optimal dose, optimal duration and maximum safe duration of intravenous magnesium therapy are unknown. Therefore, until more data on the safety and efficacy of magnesium therapy are available, its use should be limited to carefully selected tetanus cases. PMID:20356376

  15. Postoperative Intensity-Modulated Arc Therapy for Cervical and Endometrial Cancer: A Prospective Report on Toxicity

    SciTech Connect

    Vandecasteele, Katrien; Tummers, Philippe; Makar, Amin; Eijkeren, Marc van; Delrue, Louke; Denys, Hannelore; Lambert, Bieke; Beerens, Anne-Sophie; Van den Broecke, Rudy; Lambein, Kathleen; Fonteyne, Valerie; De Meerleer, Gert

    2012-10-01

    Purpose: To report on toxicity after postoperative intensity-modulated arc therapy (IMAT) for cervical (CC) and endometrial cancer (EC). Methods and Materials: Twenty-four CC and 41 EC patients were treated with postoperative IMAT. If indicated, para-aortic lymph node irradiation (preventive or when affected, PALN) and/or concomitant cisplatin (40 mg/m Superscript-Two , weekly) was administered. The prescribed dose for IMAT was 45 Gy (CC, 25 fractions) and 46 Gy (EC, 23 fractions), followed by a brachytherapeutic boost if possible. Radiation-related toxicity was assessed prospectively. The effect of concomitant cisplatin and PALN irradiation was evaluated. Results: Regarding acute toxicity (n = 65), Grade 3 and 2 acute gastrointestinal toxicity was observed in zero and 63% of patients (79% CC, 54% EC), respectively. Grade 3 and 2 acute genitourinary toxicity was observed in 1% and 18% of patients, respectively. Grade 2 (21%) and 3 (12%) hematologic toxicity (n = 41) occurred only in CC patients. Seventeen percent of CC patients and 2% of EC patients experienced Grade 2 fatigue and skin toxicity, respectively. Adding cisplatin led to an increase in Grade >2 nausea (57% vs. 9%; p = 0.01), Grade 2 nocturia (24% vs. 4%; p = 0.03), Grade {>=}2 hematologic toxicity (38% vs. nil, p = 0.003), Grade {>=}2 leukopenia (33% vs. nil, p = 0.009), and a strong trend toward more fatigue (14% vs. 2%; p = 0.05). Para-aortic lymph node irradiation led to an increase of Grade 2 nocturia (31% vs. 4%, p = 0.008) and a strong trend toward more Grade >2 nausea (44% vs. 18%; p = 0.052). Regarding late toxicity (n = 45), no Grade 3 or 4 late toxicity occurred. Grade 2 gastrointestinal toxicity, genitourinary toxicity, and fatigue occurred in 4%, 9%, and 1% of patients. Neither concomitant cisplatin nor PALN irradiation increased late toxicity rates. Conclusions: Postoperative IMAT for EC or CC is associated with low acute and late toxicity. Concomitant chemotherapy and PALN irradiation

  16. Larynx-sparing techniques using intensity-modulated radiation therapy for oropharyngeal cancer

    SciTech Connect

    Bar Ad, Voichita; Lin, Haibo; Hwang, Wei-Ting; Deville, Curtiland; Dutta, Pinaki R.; Tochner, Zelig; Both, Stefan

    2012-01-01

    The purpose of the current study was to explore whether the laryngeal dose can be reduced by using 2 intensity-modulated radiation therapy (IMRT) techniques: whole-neck field IMRT technique (WF-IMRT) vs. junctioned IMRT (J-IMRT). The effect on planning target volumes (PTVs) coverage and laryngeal sparing was evaluated. WF-IMRT technique consisted of a single IMRT plan, including the primary tumor and the superior and inferior neck to the level of the clavicular heads. The larynx was defined as an organ at risk extending superiorly to cover the arytenoid cartilages and inferiorly to include the cricoid cartilage. The J-IMRT technique consisted of an IMRT plan for the primary tumor and the superior neck, matched to conventional antero-posterior opposing lower neck fields at the level of the thyroid notch. A central block was used for the anterior lower neck field at the level of the larynx to restrict the dose to the larynx. Ten oropharyngeal cancer cases were analyzed. Both the primary site and bilateral regional lymphatics were included in the radiotherapy targets. The averaged V95 for the PTV57.6 was 99.2% for the WF-IMRT technique compared with 97.4% (p = 0.02) for J-IMRT. The averaged V95 for the PTV64 was 99.9% for the WF-IMRT technique compared with 98.9% (p = 0.02) for J-IMRT and the averaged V95 for the PT70 was 100.0% for WF-IMRT technique compared with 99.5% (p = 0.04) for J-IMRT. The averaged mean laryngeal dose was 18 Gy with both techniques. The averaged mean doses within the matchline volumes were 69.3 Gy for WF-MRT and 66.2 Gy for J-IMRT (p = 0.03). The WF-IMRT technique appears to offer an optimal coverage of the target volumes and a mean dose to the larynx similar with J-IMRT and should be further evaluated in clinical trials.

  17. Larynx-sparing techniques using intensity-modulated radiation therapy for oropharyngeal cancer.

    PubMed

    Bar Ad, Voichita; Lin, Haibo; Hwang, Wei-Ting; Deville, Curtiland; Dutta, Pinaki R; Tochner, Zelig; Both, Stefan

    2012-01-01

    The purpose of the current study was to explore whether the laryngeal dose can be reduced by using 2 intensity-modulated radiation therapy (IMRT) techniques: whole-neck field IMRT technique (WF-IMRT) vs. junctioned IMRT (J-IMRT). The effect on planning target volumes (PTVs) coverage and laryngeal sparing was evaluated. WF-IMRT technique consisted of a single IMRT plan, including the primary tumor and the superior and inferior neck to the level of the clavicular heads. The larynx was defined as an organ at risk extending superiorly to cover the arytenoid cartilages and inferiorly to include the cricoid cartilage. The J-IMRT technique consisted of an IMRT plan for the primary tumor and the superior neck, matched to conventional antero-posterior opposing lower neck fields at the level of the thyroid notch. A central block was used for the anterior lower neck field at the level of the larynx to restrict the dose to the larynx. Ten oropharyngeal cancer cases were analyzed. Both the primary site and bilateral regional lymphatics were included in the radiotherapy targets. The averaged V95 for the PTV57.6 was 99.2% for the WF-IMRT technique compared with 97.4% (p = 0.02) for J-IMRT. The averaged V95 for the PTV64 was 99.9% for the WF-IMRT technique compared with 98.9% (p = 0.02) for J-IMRT and the averaged V95 for the PT70 was 100.0% for WF-IMRT technique compared with 99.5% (p = 0.04) for J-IMRT. The averaged mean laryngeal dose was 18 Gy with both techniques. The averaged mean doses within the matchline volumes were 69.3 Gy for WF-MRT and 66.2 Gy for J-IMRT (p = 0.03). The WF-IMRT technique appears to offer an optimal coverage of the target volumes and a mean dose to the larynx similar with J-IMRT and should be further evaluated in clinical trials.

  18. Effectiveness of robust optimization in intensity-modulated proton therapy planning for head and neck cancers

    SciTech Connect

    Liu Wei; Li Xiaoqiang; Park, Peter C.; Ronald Zhu, X.; Mohan, Radhe; Frank, Steven J.; Li Yupeng; Dong Lei

    2013-05-15

    Purpose: Intensity-modulated proton therapy (IMPT) is highly sensitive to uncertainties in beam range and patient setup. Conventionally, these uncertainties are dealt using geometrically expanded planning target volume (PTV). In this paper, the authors evaluated a robust optimization method that deals with the uncertainties directly during the spot weight optimization to ensure clinical target volume (CTV) coverage without using PTV. The authors compared the two methods for a population of head and neck (H and N) cancer patients. Methods: Two sets of IMPT plans were generated for 14 H and N cases, one being PTV-based conventionally optimized and the other CTV-based robustly optimized. For the PTV-based conventionally optimized plans, the uncertainties are accounted for by expanding CTV to PTV via margins and delivering the prescribed dose to PTV. For the CTV-based robustly optimized plans, spot weight optimization was guided to reduce the discrepancy in doses under extreme setup and range uncertainties directly, while delivering the prescribed dose to CTV rather than PTV. For each of these plans, the authors calculated dose distributions under various uncertainty settings. The root-mean-square dose (RMSD) for each voxel was computed and the area under the RMSD-volume histogram curves (AUC) was used to relatively compare plan robustness. Data derived from the dose volume histogram in the worst-case and nominal doses were used to evaluate the plan optimality. Then the plan evaluation metrics were averaged over the 14 cases and were compared with two-sided paired t tests. Results: CTV-based robust optimization led to more robust (i.e., smaller AUCs) plans for both targets and organs. Under the worst-case scenario and the nominal scenario, CTV-based robustly optimized plans showed better target coverage (i.e., greater D{sub 95%}), improved dose homogeneity (i.e., smaller D{sub 5%}- D{sub 95%}), and lower or equivalent dose to organs at risk. Conclusions: CTV

  19. EBT GAFCHROMIC{sup TM} film dosimetry in compensator-based intensity modulated radiation therapy

    SciTech Connect

    Vaezzadeh, Seyedali; Allahverdi, Mahmoud; Nedaie, Hasan A.; Ay, Mohammadreza; Shirazi, Alireza; Yarahmadi, Mehran

    2013-07-01

    The electron benefit transfer (EBT) GAFCHROMIC films possess a number of features making them appropriate for high-quality dosimetry in intensity-modulated radiation therapy (IMRT). Compensators to deliver IMRT are known to change the beam-energy spectrum as well as to produce scattered photons and to contaminate electrons; therefore, the accuracy and validity of EBT-film dosimetry in compensator-based IMRT should be investigated. Percentage-depth doses and lateral-beam profiles were measured using EBT films in perpendicular orientation with respect to 6 and 18 MV photon beam energies for: (1) different thicknesses of cerrobend slab (open, 1.0, 2.0, 4.0, and 6.0 cm), field sizes (5×5, 10×10, and 20×20 cm{sup 2}), and measurement depths (D{sub max}, 5.0 and 10.0 cm); and (2) step-wedged compensator in a solid phantom. To verify results, same measurements were implemented using a 0.125 cm{sup 3} ionization chamber in a water phantom and also in Monte Carlo simulations using the Monte Carlo N-particle radiation transport computer code. The mean energy of photons was increased due to beam hardening in comparison with open fields at both 6 and 18 MV energies. For a 20×20 cm{sup 2} field size of a 6 MV photon beam and a 6.0 cm thick block, the surface dose decreased by about 12% and percentage-depth doses increased up to 3% at 30.0 cm depth, due to the beam-hardening effect induced by the block. In contrast, at 18 MV, the surface dose increased by about 8% and depth dose reduced by 3% at 30.0 cm depth. The penumbral widths (80% to 20%) increase with block thickness, field size, and beam energy. The EBT film results were in good agreement with the ionization chamber dose profiles and Monte Carlo N-particle radiation transport computer code simulation behind the step-wedged compensator. Also, there was a good agreement between the EBT-film and the treatment-planning results on the anthropomorphic phantom. The EBT films can be accurately used as a 2D dosimeter for dose

  20. Origin of Tumor Recurrence After Intensity Modulated Radiation Therapy for Oropharyngeal Squamous Cell Carcinoma

    SciTech Connect

    Raktoe, Sawan A.S.; Dehnad, Homan; Raaijmakers, Cornelis P.J.; Braunius, Weibel; Terhaard, Chris H.J.

    2013-01-01

    Purpose: To model locoregional recurrences of oropharyngeal squamous cell carcinomas (OSCC) treated with primary intensity modulated radiation therapy (IMRT) in order to find the origins from which recurrences grow and relate their location to original target volume borders. Methods and Materials: This was a retrospective analysis of OSCC treated with primary IMRT between January 2002 and December 2009. Locoregional recurrence volumes were delineated on diagnostic scans and coregistered rigidly with treatment planning computed tomography scans. Each recurrence was analyzed with two methods. First, overlapping volumes of a recurrence and original target were measured ('volumetric approach') and assessed as 'in-field', 'marginal', or 'out-field'. Then, the center of mass (COM) of a recurrence volume was assumed as the origin from where a recurrence expanded, the COM location was compared with original target volume borders and assessed as 'in-field', 'marginal', or 'out-field'. Results: One hundred thirty-one OSCC were assessed. For all patients alive at the end of follow-up, the mean follow-up time was 40 months (range, 12-83 months); 2 patients were lost to follow-up. The locoregional recurrence rate was 27%. Of all recurrences, 51% were local, 23% were regional, and 26% had both local and regional recurrences. Of all recurrences, 74% had imaging available for assessment. Regarding volumetric analysis of local recurrences, 15% were in-field gross tumor volume (GTV), and 65% were in-field clinical tumor volume (CTV). Using the COM approach, we found that 70% of local recurrences were in-field GTV and 90% were in-field CTV. Of the regional recurrences, 25% were volumetrically in-field GTV, and using the COM approach, we found 54% were in-field GTV. The COM of local out-field CTV recurrences were maximally 16 mm outside CTV borders, whereas for regional recurrences, this was 17 mm. Conclusions: The COM model is practical and specific for recurrence assessment. Most

  1. Investigation of geometric uncertainty introduced dosimetric variation in intensity modulated proton therapy (IMPT) and its intervention

    NASA Astrophysics Data System (ADS)

    Zhang, Miao

    The intensity modulated proton therapy (IMPT) can generate plans with reduced normal tissue toxicity and increased target dose conformity. However, geometric uncertainty associated with the treatment process could introduce large dose variations between the delivered dose distribution and the planned. There are three common types of geometric uncertainty: setup uncertainty, inter-, and intra-fractional organ motion. This thesis work will investigate setup uncertainty and inter-fractional organ motion introduced dose variation and find solutions to minimize such variations. A proton treatment planning system was developed by using Geant4 Monte Carlo toolbox as the dose calculation engine. The setup uncertainty was studied on the head and neck cancer site. Plan delivery simulation shown large dose variation occurred even with small amount of setup uncertainty. Two intervention strategies were investigated: (i) different proton pencil beam sizes, and (ii) the energy margin. By varying proton pencil beam size, we found the larger the beam size the less the dose variation, nevertheless the higher normal tissue dose. The energy margin is a planning strategy incorporating the possible motion effect into the planning stage by assigning proton pencil beams an energy value large enough to guarantee protons will travel to where they are planned. The energy margin solution was tested to be effective to minimize the dose variation in the distal edge tracking (DET) based IMPT. The inter-fractional motion was studied by looking at the daily prostate shift in the prostate cancer treatment. Delivery simulation for prostate cancer IMPT shown large dose variation would result even if the image guidance (IG) technique was used to realign the prostate back to its original location on the planning CT. A novel on-line adaptive image guided IMPT (A-IG-IMPT) technique was proposed to minimize the dose variation. By updating the energy value for individual proton pencil beam from the on

  2. Introducing an on-line adaptive procedure for prostate image guided intensity modulate proton therapy.

    PubMed

    Zhang, M; Westerly, D C; Mackie, T R

    2011-08-07

    With on-line image guidance (IG), prostate shifts relative to the bony anatomy can be corrected by realigning the patient with respect to the treatment fields. In image guided intensity modulated proton therapy (IG-IMPT), because the proton range is more sensitive to the material it travels through, the realignment may introduce large dose variations. This effect is studied in this work and an on-line adaptive procedure is proposed to restore the planned dose to the target. A 2D anthropomorphic phantom was constructed from a real prostate patient's CT image. Two-field laterally opposing spot 3D-modulation and 24-field full arc distal edge tracking (DET) plans were generated with a prescription of 70 Gy to the planning target volume. For the simulated delivery, we considered two types of procedures: the non-adaptive procedure and the on-line adaptive procedure. In the non-adaptive procedure, only patient realignment to match the prostate location in the planning CT was performed. In the on-line adaptive procedure, on top of the patient realignment, the kinetic energy for each individual proton pencil beam was re-determined from the on-line CT image acquired after the realignment and subsequently used for delivery. Dose distributions were re-calculated for individual fractions for different plans and different delivery procedures. The results show, without adaptive, that both the 3D-modulation and the DET plans experienced delivered dose degradation by having large cold or hot spots in the prostate. The DET plan had worse dose degradation than the 3D-modulation plan. The adaptive procedure effectively restored the planned dose distribution in the DET plan, with delivered prostate D(98%), D(50%) and D(2%) values less than 1% from the prescription. In the 3D-modulation plan, in certain cases the adaptive procedure was not effective to reduce the delivered dose degradation and yield similar results as the non-adaptive procedure. In conclusion, based on this 2D phantom

  3. Verification of intensity modulated radiation therapy beams using a tissue equivalent plastic scintillator dosimetry system

    NASA Astrophysics Data System (ADS)

    Petric, Martin Peter

    This thesis describes the development and implementation of a novel method for the dosimetric verification of intensity modulated radiation therapy (IMRT) fields with several advantages over current techniques. Through the use of a tissue equivalent plastic scintillator sheet viewed by a charge-coupled device (CCD) camera, this method provides a truly tissue equivalent dosimetry system capable of efficiently and accurately performing field-by-field verification of IMRT plans. This work was motivated by an initial study comparing two IMRT treatment planning systems. The clinical functionality of BrainLAB's BrainSCAN and Varian's Helios IMRT treatment planning systems were compared in terms of implementation and commissioning, dose optimization, and plan assessment. Implementation and commissioning revealed differences in the beam data required to characterize the beam prior to use with the BrainSCAN system requiring higher resolution data compared to Helios. This difference was found to impact on the ability of the systems to accurately calculate dose for highly modulated fields, with BrainSCAN being more successful than Helios. The dose optimization and plan assessment comparisons revealed that while both systems use considerably different optimization algorithms and user-control interfaces, they are both capable of producing substantially equivalent dose plans. The extensive use of dosimetric verification techniques in the IMRT treatment planning comparison study motivated the development and implementation of a novel IMRT dosimetric verification system. The system consists of a water-filled phantom with a tissue equivalent plastic scintillator sheet built into the top surface. Scintillation light is reflected by a plastic mirror within the phantom towards a viewing window where it is captured using a CCD camera. Optical photon spread is removed using a micro-louvre optical collimator and by deconvolving a glare kernel from the raw images. Characterization of this

  4. Intrafractional 3D localization using kilovoltage digital tomosynthesis for sliding-window intensity modulated radiation therapy

    PubMed Central

    Zhang, Pengpeng; Hunt, Margie; Pham, Hai; Tang, Grace; Mageras, Gig

    2016-01-01

    Purpose To implement novel imaging sequences integrated into intensity modulated radiation therapy (IMRT) and determine 3D positions for intrafractional patient motion monitoring and management. Method In one method, we converted a static gantry IMRT beam into a series of arcs in which dose index and multileaf collimator positions for all control points were unchanged, but gantry angles were modified to oscillate ±3° around the original angle. Kilovoltage (kV) projections were acquired continuously throughout delivery and reconstructed to provide a series of 6° arc digital tomosynthesis (DTS) images which served to evaluate the in-plane positions of embedded-fiducials/vertebral-body. To obtain out-of-plane positions via triangulation, a 20° gantry rotation with beam hold-off was inserted during delivery to produce a pair of 6° DTS images separated by 14°. In a second method, the gantry remained stationary, but both kV source and detector moved over a 15° longitudinal arc using pitch and translational adjustment of the robotic arms. Evaluation of localization accuracy in an anthropomorphic Rando phantom during simulated intrafractional motion used programmed couch translations from customized scripts. Purpose-built software was used to reconstruct DTS images, register them to reference template images and calculate 3D fiducial positions. Result No significant dose difference (<0.5%) was found between the original and converted IMRT beams. For a typical hypofractionated spine treatment, 200 single DTS (6° arc) and 10 paired DTS (20° arc) images were acquired for each IMRT beam, providing in-plane and out-of-plane monitoring every 1.6 and 34.5 seconds, respectively. Mean ± standard deviation error in predicted position was −0.3±0.2 mm, −0.1±0.1 mm in-plane, and 0.2±0.4 mm out-of-plane with rotational gantry, 0.8±0.1 mm, −0.7±0.3 mm in-plane and 1.1±0.1 mm out-of-plane with translational source/detector. Conclusion Acquiring 3D fiducial positions

  5. Postoperative Intensity Modulated Radiation Therapy in High Risk Prostate Cancer: A Dosimetric Comparison

    SciTech Connect

    Digesu, Cinzia; Cilla, Savino; De Gaetano, Andrea; Massaccesi, Mariangela; Macchia, Gabriella; Ippolito, Edy; Deodato, Francesco; Panunzi, Simona; Iapalucci, Chiara; Mattiucci, Gian Carlo; D'Angelo, Elisa; Padula, Gilbert D.A.; Valentini, Vincenzo; Cellini, Numa

    2011-10-01

    The aim of this study was to compare intensity-modulated radiation therapy (IMRT) with 3D conformal technique (3D-CRT), with respect to target coverage and irradiation of organs at risk for high dose postoperative radiotherapy (PORT) of the prostate fossa. 3D-CRT and IMRT treatment plans were compared with respect to dose to the rectum and bladder. The dosimetric comparison was carried out in 15 patients considering 2 different scenarios: (1) exclusive prostate fossa irradiation, and (2) pelvic node irradiation followed by a boost on the prostate fossa. In scenario (1), a 3D-CRT plan (box technique) and an IMRT plan were calculated and compared for each patient. In scenario (2), 3 treatment plans were calculated and compared for each patient: (a) 3D-CRT box technique for both pelvic (prophylactic nodal irradiation) and prostate fossa irradiation (3D-CRT only); (b) 3D-CRT box technique for pelvic irradiation followed by an IMRT boost to the prostatic fossa (hybrid 3D-CRT and IMRT); and (c) IMRT for both pelvic and prostate fossa irradiation (IMRT only). For exclusive prostate fossa irradiation, IMRT significantly reduced the dose to the rectum (lower Dmean, V50%, V75%, V90%, V100%, EUD, and NTCP) and the bladder (lower Dmean, V50%, V90%, EUD and NTCP). When prophylactic irradiation of the pelvis was also considered, plan C (IMRT only) performed better than plan B (hybrid 3D-CRT and IMRT) as respect to both rectum and bladder irradiation (reduction of Dmean, V50%, V75%, V90%, equivalent uniform dose [EUD], and normal tissue complication probability [NTCP]). Plan (b) (hybrid 3D-CRT and IMRT) performed better than plan (a) (3D-CRT only) with respect to dose to the rectum (lower Dmean, V75%, V90%, V100%, EUD, and NTCP) and the bladder (Dmean, EUD, and NTCP). Postoperative IMRT in prostate cancer significantly reduces rectum and bladder irradiation compared with 3D-CRT.

  6. Factors influencing the incidence of sinusitis in nasopharyngeal carcinoma patients after intensity-modulated radiation therapy.

    PubMed

    Su, Yan-xia; Liu, Lan-ping; Li, Lei; Li, Xu; Cao, Xiu-juan; Dong, Wei; Yang, Xin-hua; Xu, Jin; Yu, Shui; Hao, Jun-fang

    2014-12-01

    The aim of the study was to investigate the incidence of sinusitis in nasopharyngeal carcinoma (NPC) patients before and after intensity-modulated radiation therapy (IMRT) and to analyze factors associated with the incidence of sinusitis following IMRT. We retrospectively analyzed 283 NPC patients who received IMRT in our hospital from March 2009 to May 2011. The diagnostic criteria for sinusitis are based on computed tomography (CT) or magnetic resonance imaging (MRI) findings. CT or MRI scans were performed before and after IMRT to evaluate the incidence of sinusitis. Factors influencing the incidence of sinusitis were analyzed by log-rank univariate and logistic multivariate analyses. Among the 283 NPC patients, 128 (45.2 %) suffered from sinusitis before radiotherapy. The incidence rates of sinusitis in patients with T1, T2, T3, and T4 NPC before radiotherapy were 22.6, 37.5, 46.8, and 61.3 %, respectively (χ 2 = 14.548, p = 0.002). Among the 155 NPC patients without sinusitis before radiotherapy, the incidence rates of sinusitis at the end of radiotherapy and at 1, 3, 6, 9, 12, and 18 months after radiotherapy were 32.9, 43.2, 61.3, 68.4, 73.5, 69.7, and 61.3 %, respectively (χ 2 = 86.461, p < 0.001). Univariate analysis showed that T stage, invasion of the nasal cavity, nasal irrigation, and radiation dose to the nasopharynx were associated with the incidence of sinusitis in NPC patients after IMRT (p = 0.003, 0.006, 0.002, and 0.020). Multivariate analysis showed that T stage, invasion of the nasal cavity, and nasal irrigation were influential factors for the incidence of sinusitis in NPC patients after IMRT (p = 0.002, 0.002, and 0.000). There was a higher incidence of sinusitis with higher T stage among NPC patients before radiotherapy, and the incidence of sinusitis in NPC patients after IMRT was high (45.2 %). The incidence of sinusitis increased rapidly within the first 3 months after IMRT, and the number of sinusitis cases peaked at 6-9 months after

  7. Treatment of Oral Cavity Squamous Cell Carcinoma With Adjuvant or Definitive Intensity-Modulated Radiation Therapy

    SciTech Connect

    Sher, David J.; Thotakura, Vijaya; Balboni, Tracy A.; Norris, Charles M.; Haddad, Robert I.; Posner, Marshall R.; Lorch, Jochen; Goguen, Laura A.; Annino, Donald J.; Tishler, Roy B.

    2011-11-15

    Purpose: The optimal management of oral cavity squamous cell carcinoma (OCSCC) typically involves surgical resection followed by adjuvant radiotherapy or chemoradiotherapy (CRT) in the setting of adverse pathologic features. Intensity-modulated radiation therapy (IMRT) is frequently used to treat oral cavity cancers, but published IMRT outcomes specific to this disease site are sparse. We report the Dana-Farber Cancer Institute experience with IMRT-based treatment for OCSCC. Methods and Materials: Retrospective study of all patients treated at Dana-Farber Cancer Institute for OCSCC with adjuvant or definitive IMRT between August 2004 and December 2009. The American Joint Committee on Cancer disease stage criteria distribution of this cohort included 5 patients (12%) with stage I; 10 patients (24%) with stage II (n = 10, 24%),; 14 patients (33%) with stage III (n = 14, 33%),; and 13 patients (31%) with stage IV. The primary endpoint was overall survival (OS); secondary endpoints were locoregional control (LRC) and acute and chronic toxicity. Results: Forty-two patients with OCSCC were included, 30 of whom were initially treated with surgical resection. Twenty-three (77%) of 30 surgical patients treated with adjuvant IMRT also received concurrent chemotherapy, and 9 of 12 (75%) patients treated definitively without surgery were treated with CRT or induction chemotherapy and CRT. With a median follow-up of 2.1 years (interquartile range, 1.1-3.1 years) for all patients, the 2-year actuarial rates of OS and LRC following adjuvant IMRT were 85% and 91%, respectively, and the comparable results for definitive IMRT were 63% and 64% for OS and LRC, respectively. Only 1 patient developed symptomatic osteoradionecrosis, and among patients without evidence of disease, 35% experienced grade 2 to 3 late dysphagia, with only 1 patient who was continuously gastrostomy-dependent. Conclusions: In this single-institution series, postoperative IMRT was associated with promising LRC

  8. A GPU-accelerated and Monte Carlo-based intensity modulated proton therapy optimization system

    SciTech Connect

    Ma, Jiasen Beltran, Chris; Seum Wan Chan Tseung, Hok; Herman, Michael G.

    2014-12-15

    Purpose: Conventional spot scanning intensity modulated proton therapy (IMPT) treatment planning systems (TPSs) optimize proton spot weights based on analytical dose calculations. These analytical dose calculations have been shown to have severe limitations in heterogeneous materials. Monte Carlo (MC) methods do not have these limitations; however, MC-based systems have been of limited clinical use due to the large number of beam spots in IMPT and the extremely long calculation time of traditional MC techniques. In this work, the authors present a clinically applicable IMPT TPS that utilizes a very fast MC calculation. Methods: An in-house graphics processing unit (GPU)-based MC dose calculation engine was employed to generate the dose influence map for each proton spot. With the MC generated influence map, a modified least-squares optimization method was used to achieve the desired dose volume histograms (DVHs). The intrinsic CT image resolution was adopted for voxelization in simulation and optimization to preserve spatial resolution. The optimizations were computed on a multi-GPU framework to mitigate the memory limitation issues for the large dose influence maps that resulted from maintaining the intrinsic CT resolution. The effects of tail cutoff and starting condition were studied and minimized in this work. Results: For relatively large and complex three-field head and neck cases, i.e., >100 000 spots with a target volume of ∼1000 cm{sup 3} and multiple surrounding critical structures, the optimization together with the initial MC dose influence map calculation was done in a clinically viable time frame (less than 30 min) on a GPU cluster consisting of 24 Nvidia GeForce GTX Titan cards. The in-house MC TPS plans were comparable to a commercial TPS plans based on DVH comparisons. Conclusions: A MC-based treatment planning system was developed. The treatment planning can be performed in a clinically viable time frame on a hardware system costing around 45

  9. Intrafractional 3D localization using kilovoltage digital tomosynthesis for sliding-window intensity modulated radiation therapy.

    PubMed

    Zhang, Pengpeng; Hunt, Margie; Pham, Hai; Tang, Grace; Mageras, Gig

    2015-09-07

    To implement novel imaging sequences integrated into intensity modulated radiation therapy (IMRT) and determine 3D positions for intrafractional patient motion monitoring and management.In one method, we converted a static gantry IMRT beam into a series of arcs in which dose index and multileaf collimator positions for all control points were unchanged, but gantry angles were modified to oscillate ± 3° around the original angle. Kilovoltage (kV) projections were acquired continuously throughout delivery and reconstructed to provide a series of 6° arc digital tomosynthesis (DTS) images which served to evaluate the in-plane positions of embedded-fiducials/vertebral-body. To obtain out-of-plane positions via triangulation, a 20° gantry rotation with beam hold-off was inserted during delivery to produce a pair of 6° DTS images separated by 14°. In a second method, the gantry remained stationary, but both kV source and detector moved over a 15° longitudinal arc using pitch and translational adjustment of the robotic arms. Evaluation of localization accuracy in an anthropomorphic Rando phantom during simulated intrafractional motion used programmed couch translations from customized scripts. Purpose-built software was used to reconstruct DTS images, register them to reference template images and calculate 3D fiducial positions.No significant dose difference (<0.5%) was found between the original and converted IMRT beams. For a typical hypofractionated spine treatment, 200 single DTS (6° arc) and 10 paired DTS (20° arc) images were acquired for each IMRT beam, providing in-plane and out-of-plane monitoring every 1.6 and 34.5 s, respectively. Mean ± standard deviation error in predicted position was -0.3 ± 0.2 mm, -0.1 ± 0.1 mm in-plane, and 0.2 ± 0.4 mm out-of-plane with rotational gantry, 0.8 ± 0.1 mm, -0.7 ± 0.3 mm in-plane and 1.1 ± 0.1 mm out-of-plane with translational source/detector.Acquiring 3D fiducial positions from kV-DTS during fixed gantry

  10. Evaluation of a fast method of EPID-based dosimetry for intensity modulated radiation therapy

    PubMed Central

    Nelms, Benjamin E.; Rasmussen, Karl H.; Tomé, Wolfgang A.

    2010-01-01

    Electronic portal imaging devices (EPIDs) could potentially be useful for Intensity Modulated Radiation Therapy (IMRT) QA. The data density, high resolution, large active area, and efficiency of the MV EPID make it an attractive option. However, EPIDs were designed to be effective imaging devices, but not dosimeters, and as a result they do not measure dose in tissue-equivalent materials. EPIDose (Sun Nuclear, Melbourne, FL) is a tool designed for the use of EPIDs in IMRT QA that uses raw MV EPID images (no additional build-up and independent of gantry angle, but with dark and flood field corrections applied) to estimate absolute dose planes normal to the beam axis in a homogeneous media, i.e. similar to conventional IMRT QA methods. However, because of the inherent challenges of the EPID-based dosimetry, validating and commissioning such a system must be done very carefully, exploring the range of use cases and using well-proven “standards” for comparison. In this work, a multi-institutional study was performed to verify accurate EPID image to dose plane conversion over a variety of conditions. Converted EPID images were compared to 2D diode array absolute dose measurements for one hundred and eighty eight (188) fields from twenty eight (28) clinical IMRT treatment plans generated using a number of commercially available treatment planning systems (TPS) covering various treatment sites including prostate, head and neck, brain, and lung. The data included three beam energies (6, 10, and 15 MV) and both step-and-shoot and dynamic MLC fields. Out of 26,207 points of comparison over 188 fields analyzed the average overall field pass rate was 99.7% when 3mm/3% DTA criteria were used (range 94.0-100 per field). The pass rates for more stringent criteria were 97.8% for 2mm/2% DTA (range 82.0-100 per field), and 84.6% for 1mm/1% DTA (range 54.7-100 per field). Individual patient specific sites as well as different beam energies followed similar trends to the overall

  11. Including robustness in multi-criteria optimization for intensity-modulated proton therapy

    NASA Astrophysics Data System (ADS)

    Chen, Wei; Unkelbach, Jan; Trofimov, Alexei; Madden, Thomas; Kooy, Hanne; Bortfeld, Thomas; Craft, David

    2012-02-01

    We present a method to include robustness in a multi-criteria optimization (MCO) framework for intensity-modulated proton therapy (IMPT). The approach allows one to simultaneously explore the trade-off between different objectives as well as the trade-off between robustness and nominal plan quality. In MCO, a database of plans each emphasizing different treatment planning objectives, is pre-computed to approximate the Pareto surface. An IMPT treatment plan that strikes the best balance between the different objectives can be selected by navigating on the Pareto surface. In our approach, robustness is integrated into MCO by adding robustified objectives and constraints to the MCO problem. Uncertainties (or errors) of the robust problem are modeled by pre-calculated dose-influence matrices for a nominal scenario and a number of pre-defined error scenarios (shifted patient positions, proton beam undershoot and overshoot). Objectives and constraints can be defined for the nominal scenario, thus characterizing nominal plan quality. A robustified objective represents the worst objective function value that can be realized for any of the error scenarios and thus provides a measure of plan robustness. The optimization method is based on a linear projection solver and is capable of handling large problem sizes resulting from a fine dose grid resolution, many scenarios, and a large number of proton pencil beams. A base-of-skull case is used to demonstrate the robust optimization method. It is demonstrated that the robust optimization method reduces the sensitivity of the treatment plan to setup and range errors to a degree that is not achieved by a safety margin approach. A chordoma case is analyzed in more detail to demonstrate the involved trade-offs between target underdose and brainstem sparing as well as robustness and nominal plan quality. The latter illustrates the advantage of MCO in the context of robust planning. For all cases examined, the robust optimization for

  12. Particle swarm optimizer for weighting factor selection in intensity-modulated radiation therapy optimization algorithms.

    PubMed

    Yang, Jie; Zhang, Pengcheng; Zhang, Liyuan; Shu, Huazhong; Li, Baosheng; Gui, Zhiguo

    2017-01-01

    In inverse treatment planning of intensity-modulated radiation therapy (IMRT), the objective function is typically the sum of the weighted sub-scores, where the weights indicate the importance of the sub-scores. To obtain a high-quality treatment plan, the planner manually adjusts the objective weights using a trial-and-error procedure until an acceptable plan is reached. In this work, a new particle swarm optimization (PSO) method which can adjust the weighting factors automatically was investigated to overcome the requirement of manual adjustment, thereby reducing the workload of the human planner and contributing to the development of a fully automated planning process. The proposed optimization method consists of three steps. (i) First, a swarm of weighting factors (i.e., particles) is initialized randomly in the search space, where each particle corresponds to a global objective function. (ii) Then, a plan optimization solver is employed to obtain the optimal solution for each particle, and the values of the evaluation functions used to determine the particle's location and the population global location for the PSO are calculated based on these results. (iii) Next, the weighting factors are updated based on the particle's location and the population global location. Step (ii) is performed alternately with step (iii) until the termination condition is reached. In this method, the evaluation function is a combination of several key points on the dose volume histograms. Furthermore, a perturbation strategy - the crossover and mutation operator hybrid approach - is employed to enhance the population diversity, and two arguments are applied to the evaluation function to improve the flexibility of the algorithm. In this study, the proposed method was used to develop IMRT treatment plans involving five unequally spaced 6MV photon beams for 10 prostate cancer cases. The proposed optimization algorithm yielded high-quality plans for all of the cases, without human

  13. Optimal beam design on intensity-modulated radiation therapy with simultaneous integrated boost in nasopharyngeal cancer

    SciTech Connect

    Cheng, Mei-Chun; Hu, Yu-Wen; Liu, Ching-Sheng; Lee, Jeun-Shenn; Huang, Pin-I; Yen, Sang-Hue; Lee, Yuh-Lin; Hsieh, Chun-Mei; Shiau, Cheng-Ying

    2014-10-01

    This study aims to determine the optimal beam design among various combinations of field numbers and beam trajectories for intensity-modulated radiation therapy (IMRT) with simultaneous integrated boost (SIB) technique for the treatment of nasopharyngeal cancer (NPC). We used 10 fields with gantry angles of 155°, 130°, 75°, 25°, 0° L, 0° R, 335°, 285°, 230°, and 205° denoted as F10. To decrease doses in the spinal cord, the F10 technique was designed by featuring 2 pairs of split-opposed beam fields at 155° to 335° and 205° to 25°, as well as one pair of manually split beam fields at 0°. The F10 technique was compared with 4 other common field arrangements: F7E, 7 fields with 50° equally spaced gantry angles; F7, the basis of F10 with 155°, 130°, 75°, 0°, 285°, 230°, and 205°; F9E, 9 fields with 40° equally spaced gantry angles; and FP, 7 posterior fields with 180°, 150°, 120°, 90°, 270°, 240°, and 210°. For each individual case of 10 patients, the customized constraints derived after optimization with the standard F10 technique were applied to 4 other field arrangements. The 4 new optimized plans of each individual case were normalized to achieve the same coverage of planning target volume (PTV){sub 63} {sub Gy} as that of the standard F10 technique. The F10 field arrangement exhibited the best coverage in PTV{sub 70} {sub Gy} and the least mean dose in the trachea-esophagus region. Furthermore, the F10 field arrangement demonstrated the highest level of conformity in the low-dose region and the least monitor unit. The F10 field arrangement performed more outstandingly than the other field arrangements in PTV{sub 70} {sub Gy} coverage and spared the central organ. This arrangement also exhibited the highest conformity and delivery efficiency. The F10 technique is recommended as the standard beam geometry for the SIB-IMRT of NPC.

  14. A feedback constraint optimization method for intensity-modulated radiation therapy of nasopharyngeal carcinoma

    PubMed Central

    LI, YONGWU; SUN, XIAONAN; WANG, QI; ZHOU, QINXUAN; GU, BENXING; SHI, GUOZHI; JIANG, DONGLIANG

    2015-01-01

    Intensity-modulated radiation therapy (IMRT) is able to achieve good target conformance with a limited dose to organs at risk (OARs); however, IMRT increases the irradiation volume and monitor units (MUs) required. The present study aimed to evaluate the use of an IMRT plan with fewer segments and MUs, while maintaining quality in the treatment of nasopharyngeal carcinoma. In the present study, two types of IMRT plan were therefore compared: The direct machine parameter optimization (DMPO)-RT method and the feedback constraint DMPO-RT (fc_DMPO-RT) method, which utilizes compensative feedback constraint in DMPO-RT and maintains optimization. Plans for 23 patients were developed with identical dose prescriptions. Each plan involved synchronous delivery to various targets, with identical OAR constraints, by means of 7 coplanar fields. The average dose, maximum dose, dose-volume histograms of targets and the OAR, MUs of the plan, the number of segments, delivery time and accuracy were subsequently compared. The fc_DMPO-RT exhibited superior dose distribution in terms of the average, maximum and minimum doses to the gross tumor volume compared with that of DMPO-RT (t=62.7, 20.5 and 22.0, respectively; P<0.05). The fc_DMPO-RT also resulted in a smaller maximum dose to the spinal cord (t=7.3; P<0.05), as well as fewer MUs, fewer segments and decreased treatment times than that of the DMPO-RT (t=6.2, 393.4 and 244.3, respectively; P<0.05). The fc_DMPO-RT maintained plan quality with fewer segments and MUs, and the treatment time was significantly reduced, thereby resulting in reduced radiation leakage and an enhanced curative effect. Therefore, introducing feedback constraint into DMPO may result in improved IMRT planning. In nasopharyngeal carcinoma specifically, feedback constraint resulted in the improved protection of OARs in proximity of targets (such as the brainstem and parotid) due to sharp dose distribution and reduced MUs. PMID:26622793

  15. SU-F-BRD-06: Robust Dose Calculation in Intensity Modulated Proton Therapy

    SciTech Connect

    Brosch, R; Liu, W

    2015-06-15

    Purpose: Commissioning data for intensity modulated proton therapy (IMPT) must be post-processed by fits to ad-hoc functions to derive the dose calculation kernel parameters in a treatment planning system (TPS). Whether from experimental measurement or Monte Carlo simulation, the limited and noisy nature of such data makes this task very challenging. We present a method to improve the modeling of the lateral dose distribution of clinical energy proton beams in water to commission an in-house IMPT dose calculation engine. Methods: A linear sum of three Gaussian distribution functions was fitted to the lateral dose data in logarithmic scale. Starting values of fitting solutions were determined from the Generalized Highland Approximation. We exhaustively optimized the combinations of data weights with upper bounds of the fitting solutions to minimize confidence intervals of the fitting solutions while maintaining the coefficient of determination (R{sup 2}). Results: Across all energies, average confidence bounds improved 72.88% [Max: 88.28%, Min: 55.05%] for small angle coulomb scattering, 114.25% [409.13%, 66.72%,] for nuclear scattering, and 68.66% [141.09%, 33.27%] for large angle coulomb scattering, while the coefficients of determination of the fits (R{sup 2}) remained comparable. On average R {sup 2} only changed 0.18% and were very close to 1 (approx. 0.999). Wilcoxon signed rank tests comparing unweighted/unbounded fits with weighted/bounded fits averaged 0.0146 (Max: 0.177, Min: 7.05×10−{sup 7}) for small angle Coulomb, 0.0903 (0.945, 7.05×10−{sup 7}) for nuclear, and 0.254 (0.871, 1.86×10−{sup 6}) for large angle Coulomb scattering. This allows rejection of the null hypothesis for small angle Coulomb scattering at the 0.015 level and nuclear interaction at the 0.1 level. Conclusion: Optimal weights assigned to IMPT lateral dose data minimized fitting to stochastic noise in the tail region. Optimizing the upper bounds of fitting parameters improved

  16. Adverse Events of Extracorporeal Ultrasound-Guided High Intensity Focused Ultrasound Therapy

    PubMed Central

    Yu, Tinghe; Luo, Jun

    2011-01-01

    Background High-intensity focused ultrasound (HIFU) is considered to be an alternative to surgery. Extracorporeal ultrasound-guided HIFU (USgFU) has been clinically used to treat solid tumors. Preliminary trials in a small sample of a Western population suggested that this modality was safe. Most trials are performed in China thereby providing comprehensive data for understanding the safety profile. The aim of this study was to evaluate adverse events of USgFU therapy. Methods and Findings Clinical data were searched in 2 Chinese databases. Adverse events of USgFU were summarized and compared with those of magnetic resonance-guided HIFU (MRgFU; for uterine, bone or breast tumor) and transrectal ultrasound-guided HIFU (for prostate cancer or benign prostate hyperplasia). USgFU treatment was performed using 7 types of device. Side effects were evaluated in 13262 cases. There were fewer adverse events in benign lesions than in malignant lesions (11.81% vs. 21.65%, p<0.0001). Rates of adverse events greatly varied between the disease types (0–280%, p<0.0001) and between the applied HIFU devices in both malignant (10.58–44.38%, p<0.0001) and benign lesions (1.67–17.57%, p<0.0001). Chronological analysis did not demonstrate a decrease in the rate of adverse events. Based upon evaluable adverse events, incidences in USgFU were consistent with those in MRgFU or transrectal HIFU. Some side effects frequently occurred following transrectal HIFU were not reported in USgFU. Several events including intrahepatic metastasis, intraoperative high fever, and occlusions of the superior mesenteric artery should be of particular concern because they have not been previously noted. The types of adverse events suggested that they were ultrasonic lesions. Conclusion The frequency of adverse events depended on the location of the lesion and the type of HIFU device; however, side effects of USgFU were not yet understood. USgFU did not decrease the incidence of adverse events compared

  17. A Randomized, Rater-Blinded, Parallel Trial of Intensive Speech Therapy in Sub-Acute Post-Stroke Aphasia: The SP-I-R-IT Study

    ERIC Educational Resources Information Center

    Martins, Isabel Pavao; Leal, Gabriela; Fonseca, Isabel; Farrajota, Luisa; Aguiar, Marta; Fonseca, Jose; Lauterbach, Martin; Goncalves, Luis; Cary, M. Carmo; Ferreira, Joaquim J.; Ferro, Jose M.

    2013-01-01

    Background: There is conflicting evidence regarding the benefits of intensive speech and language therapy (SLT), particularly because intensity is often confounded with total SLT provided. Aims: A two-centre, randomized, rater-blinded, parallel study was conducted to compare the efficacy of 100 h of SLT in a regular (RT) versus intensive (IT)…

  18. Dosimetric Comparison of Three-Dimensional Conformal Proton Radiotherapy, Intensity-Modulated Proton Therapy, and Intensity-Modulated Radiotherapy for Treatment of Pediatric Craniopharyngiomas

    SciTech Connect

    Boehling, Nicholas S.; Grosshans, David R.; Bluett, Jaques B.; Palmer, Matthew T.; Song, Xiaofei; Amos, Richard A.; Sahoo, Narayan; Meyer, Jeffrey J.; Mahajan, Anita; Woo, Shiao Y.

    2012-02-01

    Purpose: Cranial irradiation in pediatric patients is associated with serious long-term adverse effects. We sought to determine whether both three-dimensional conformal proton radiotherapy (3D-PRT) and intensity-modulated proton therapy (IMPT) compared with intensity-modulated radiotherapy (IMRT) decrease integral dose to brain areas known to harbor neuronal stem cells, major blood vessels, and other normal brain structures for pediatric patients with craniopharyngiomas. Methods and Materials: IMRT, forward planned, passive scattering proton, and IMPT plans were generated and optimized for 10 pediatric patients. The dose was 50.4 Gy (or cobalt Gy equivalent) delivered in 28 fractions with the requirement for planning target volume (PTV) coverage of 95% or better. Integral dose data were calculated from differential dose-volume histograms. Results: The PTV target coverage was adequate for all modalities. IMRT and IMPT yielded the most conformal plans in comparison to 3D-PRT. Compared with IMRT, 3D-PRT and IMPT plans had a relative reduction of integral dose to the hippocampus (3D-PRT, 20.4; IMPT, 51.3%{sup Asterisk-Operator }), dentate gyrus (27.3, 75.0%{sup Asterisk-Operator }), and subventricular zone (4.5, 57.8%{sup Asterisk-Operator }). Vascular organs at risk also had reduced integral dose with the use of proton therapy (anterior cerebral arteries, 33.3{sup Asterisk-Operator }, 100.0%{sup Asterisk-Operator }; middle cerebral arteries, 25.9%{sup Asterisk-Operator }, 100%{sup Asterisk-Operator }; anterior communicating arteries, 30.8{sup Asterisk-Operator }, 41.7%{sup Asterisk-Operator }; and carotid arteries, 51.5{sup Asterisk-Operator }, 77.6{sup Asterisk-Operator }). Relative reduction of integral dose to the infratentorial brain (190.7{sup Asterisk-Operator }, 109.7%{sup Asterisk-Operator }), supratentorial brain without PTV (9.6, 26.8%{sup Asterisk-Operator }), brainstem (45.6, 22.4%{sup Asterisk-Operator }), and whole brain without PTV (19.4{sup Asterisk

  19. Videomicroscopic and histopathological investigation of intense pulsed light therapy for solar lentigines.

    PubMed

    Kawada, Akira; Asai, Mutsuyo; Kameyama, Hiroko; Sangen, Yoshiko; Aragane, Yoshinori; Tezuka, Tadashi; Iwakiri, Kouji

    2002-08-01

    A noncoherent, broadband, intense pulsed light source has been effective for symptoms of photoaging skin as a nonablative method. The purpose of this study was to investigate the mechanism of efficacy of intense pulsed light for solar lentigines, a symptom of photoaging skin, with videomicroscopy and histopathology. Skin lesions of patients with solar lentigines who received one treatment of intense pulsed light were examined. Sixteen of 20 patients showed tiny crusts clinically. These tiny crusts were confirmed to be micro-crust formation after epidermal injury with sequential observation using videomicroscope and histopathology. Drop-off of micro-crusts with ample melanin pigments lead to clinical improvement of skin lesions. Intense pulsed light with absorption spectrum for melanin induced injury of melanin-containing epidermal cells via photothermal effects, suggesting that intense pulsed light may be a new modality for solar lentigines.

  20. Evidence for Intensive Aphasia Therapy: Consideration of Theories From Neuroscience and Cognitive Psychology.

    PubMed

    Dignam, Jade K; Rodriguez, Amy D; Copland, David A

    2016-03-01

    Treatment intensity is a critical component to the delivery of speech-language pathology and rehabilitation services. Within aphasia rehabilitation, however, insufficient evidence currently exists to guide clinical decision making with respect to the optimal treatment intensity. This review considers perspectives from 2 key bodies of research, the neuroscience and cognitive psychology literature, with respect to the scheduling of aphasia rehabilitation services. Neuroscience research suggests that intensive training is a key element of rehabilitation and is necessary to achieve functional and neurologic changes after a stroke occurs. In contrast, the cognitive psychology literature suggests that optimal long-term learning is achieved when training is provided in a distributed or nonintensive schedule. These perspectives are evaluated and discussed with respect to the current evidence for treatment intensity in aphasia rehabilitation. In addition, directions for future research are identified, including study design, methods of defining and measuring treatment intensity, and selection of outcome measures in aphasia rehabilitation.

  1. Non-receptor-mediated actions are responsible for the lipid-lowering effects of iodothyronines in FaO rat hepatoma cells.

    PubMed

    Grasselli, Elena; Voci, Adriana; Canesi, Laura; Goglia, Fernando; Ravera, Silvia; Panfoli, Isabella; Gallo, Gabriella; Vergani, Laura

    2011-07-01

    Iodothyronines influence lipid metabolism and energy homeostasis. Previous studies demonstrated that 3,5-l-diiodothyronine (T(2)), as well as 3,3',5-L-triiodothyronine (T(3)), was able to both prevent and reverse hepatic steatosis in rats fed a high-fat diet, and this effect depends on a direct action of iodothyronines on the hepatocyte. However, the involvement of thyroid hormone receptors (TRs) in mediating the lipid-lowering effect of iodothyronines was not elucidated. In this study, we investigated the ability of T(2) and T(3) to reduce the lipid overloading using the rat hepatoma FaO cells defective for functional TRs. The absence of constitutive mRNA expression of both TRα1 and TRβ1 in FaO cells was verified by RT-qPCR. To mimic the fatty liver condition, FaO cells were treated with a fatty acid mixture and then exposed to pharmacological doses of T(2) or T(3) for 24 h. Lipid accumulation, mRNA expression of the peroxisome proliferator-activated receptors (PPAR-α, -γ, -δ) the acyl-CoA oxidase (AOX), and the stearoyl CoA desaturase (SCD1), as well as fuel-stimulated O(2) consumption in intact cells, were evaluated. Lipid accumulation was associated with an increase in triacylglycerol content, PPARγ mRNA expression, and a decrease in PPARδ and SCD1 mRNA expression. The addition of T(2) or T(3) to lipid-overloaded cells resulted in i) reduction in lipid content; ii) downregulation of PPARα, PPARγ, and AOX expression; iii) increase in PPARδ expression; and iv) stimulation of mitochondrial uncoupling. These data demonstrate, for the first time, that in the hepatocyte, the lipid-lowering actions of both T(2) and T(3) are not mediated by TRs.

  2. Lipid lowering agents use and systemic and oral inflammation in overweight or obese adult Puerto Ricans: the San Juan Overweight Adults Longitudinal Study (SOALS)

    PubMed Central

    Andriankaja, Oelisoa M.; Jiménez, James J.; Muñoz-Torres, Francisco J.; Pérez, Cynthia M.; Vergara, José L.; Joshipura, Kaumudi

    2015-01-01

    The effects of lipid-lowering agents (LLA) on reducing systemic and oral inflammation have not been evaluated. Objective To assess the association of LLA use with high-sensitivity C-reactive protein (hs-CRP) and oral inflammation. Design Cross-sectional analysis using baseline data from 1,300 overweight/obese participants aged 40–65 years, recruited for the ongoing San Juan Overweight Adults Longitudinal Study. Serum hs-CRP was measured by ELISA, gingival/periodontal inflammation was evaluated as bleeding upon probing (BOP), and LLA was self-reported. Separate logistic models were performed for systemic and oral inflammation. Results 24% participants reported history of dyslipidemia, of which, 50.3% self-reported LLA use. Sixty percent of the participants had elevated hs-CRP (>3 mg/dL) and 50% had high BOP (defined as at or above the median: 21%). After adjusting for age, gender, smoking, HDL-C, physical activity, diabetes, blood pressure medications, and percent body fat composition, LLA users had significantly lower odds of elevated hs-CRP compared to LLA non-users (OR=0.58; 95% CI: 0.39–0.85). After adjusting for age, gender, smoking status, educational level, mean plaque index, and percent body fat, LLA users had significantly lower odds of high BOP compared to LLA non-users (OR= 0.62; 95% CI: 0.42–0.91). Conclusions Lipid-lowering agents may reduce both systemic and oral inflammatory responses. PMID:26407668

  3. Lipid-lowering and anti-inflammatory effects of omega 3 ethyl esters and krill oil: a randomized, cross-over, clinical trial

    PubMed Central

    Rosticci, Martina; Morbini, Martino; Cagnati, Marcella; Grandi, Elisa; Parini, Angelo; Borghi, Claudio

    2016-01-01

    Introduction Polyunsaturated fatty acids (PUFAs) derived from different sources could have different lipid-lowering effects in humans. The main aim of our study was to compare the short-term triglyceride-lowering efficacy of krill oil and purified omega 3 ethyl ester PUFAs in mildly overweight hypertriglyceridemic subjects. Material and methods This double-blind, randomized clinical trial was carried out in 25 moderately hypertriglyceridemic subjects (TG = 150–500 mg/dl). After a 4-week run-in, participants were allocated to treatment with similar pills containing omega 3 ethyl ester PUFAs 1000 mg twice a day vs. krill oil 500 mg twice a day. After 4 weeks of treatment, participants were asked to observe a 4-week wash-out period, and they were then assigned to the alternative treatment for a further period of 4 weeks. Results Although both PUFA sources were able to improve TG plasma levels, esterified omega 3 PUFAs were more efficacious than krill oil (p < 0.05). Nonetheless, only krill oil treatment was able to significantly improve high-density lipoprotein cholesterol and apolipoprotein AI levels, compared to both baseline (p < 0.05) and end of treatment with esterified omega 3 PUFAs (p < 0.05) values. Both treatments were able to significantly reduce high-sensitivity C-reactive protein (hs-CRP) levels from the baseline (p < 0.05), but krill oil improved it more efficaciously than esterified omega 3 PUFAs (p < 0.05). Conclusions Krill oil has lipid-lowering effects comparable with those obtained through a 4-fold higher dose of purified omega 3 ethyl ester PUFAs in mildly overweight hypertriglyceridemic subjects, while more efficaciously reducing hs-CRP. PMID:27279841

  4. Evolution of Volume and Signal Intensity on Fluid-attenuated Inversion Recovery MR Images after Endovascular Stroke Therapy.

    PubMed

    Federau, Christian; Mlynash, Michael; Christensen, Soren; Zaharchuk, Greg; Cha, Brannon; Lansberg, Maarten G; Wintermark, Max; Albers, Gregory W

    2016-07-01

    Purpose To analyze both volume and signal evolution on magnetic resonance (MR) fluid-attenuated inversion recovery (FLAIR) images between the images after endovascular therapy and day 5 (which was the prespecified end point for infarct volume in the Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution [DEFUSE 2] trial) in a subset of patients enrolled in the DEFUSE 2 study. Materials and Methods This study was approved by the local ethics committee at all participating sites. Informed written consent was obtained from all patients. In this post hoc analysis of the DEFUSE 2 study, 35 patients with FLAIR images acquired both after endovascular therapy (median time after symptom onset, 12 hours) and at day 5 were identified. Patients were separated into two groups based on the degree of reperfusion achieved on time to maximum greater than 6-second perfusion imaging (≥90% vs <90%). After coregistration and signal normalization, lesion volumes and signal intensity were assessed by using FLAIR imaging for the initial lesion (ie, visible after endovascular therapy) and the recruited lesion (the additional lesion visible on day 5, but not visible after endovascular therapy). Statistical significance was assessed by using Wilcoxon signed-rank, Mann-Whitney U, and Fisher exact tests. Results All 35 patients had FLAIR lesion growth between the after-revascularization examination and day 5. Median lesion growth was significantly larger in patients with <90% reperfusion (27.85 mL) compared with ≥90% (8.12 mL; P = .003). In the initial lesion, normalized signal did not change between after endovascular therapy (median, 1.60) and day 5 (median, 1.58) in the ≥90% reperfusion group (P = .97), but increased in the <90% reperfusion group (from 1.60 to 1.73; P = .01). In the recruited lesion, median normalized signal increased significantly in both groups between after endovascular therapy and day 5 (after endovascular therapy, from 1.19 to 1.56, P

  5. A Comparison of Helical Intensity-Modulated Radiotherapy, Intensity-Modulated Radiotherapy, and 3D-Conformal Radiation Therapy for Pancreatic Cancer

    SciTech Connect

    Poppe, Matthew M.; Narra, Venkat; Yue, Ning J.; Zhou Jinghao; Nelson, Carl; Jabbour, Salma K.

    2011-01-01

    We assessed dosimetric differences in pancreatic cancer radiotherapy via helical intensity-modulated radiotherapy (HIMRT), linac-based IMRT, and 3D-conformal radiation therapy (3D-CRT) with regard to successful plan acceptance and dose to critical organs. Dosimetric analysis was performed in 16 pancreatic cases that were planned to 54 Gy; both post-pancreaticoduodenectomy (n = 8) and unresected (n = 8) cases were compared. Without volume modification, plans met constraints 75% of the time with HIMRT and IMRT and 13% with 3D-CRT. There was no statistically significantly improvement with HIMRT over conventional IMRT in reducing liver V35, stomach V45, or bowel V45. HIMRT offers improved planning target volume (PTV) dose homogeneity compared with IMRT, averaging a lower maximum dose and higher volume receiving the prescription dose (D100). HIMRT showed an increased mean dose over IMRT to bowel and liver. Both HIMRT and IMRT offer a statistically significant improvement over 3D-CRT in lowering dose to liver, stomach, and bowel. The results were similar for both unresected and resected patients. In pancreatic cancer, HIMRT offers improved dose homogeneity over conventional IMRT and several significant benefits to 3D-CRT. Factors to consider before incorporating IMRT into pancreatic cancer therapy are respiratory motion, dose inhomogeneity, and mean dose.

  6. Intensity of statin therapy and new hospitalizations for heart failure in patients with type 2 diabetes

    PubMed Central

    Kishimoto, Ichiro; Makino, Hisashi; Ohata, Yoko; Tamanaha, Tamiko; Tochiya, Mayu; Anzai, Toshihisa; Kusano, Kengo; Noguchi, Teruo; Yasuda, Satoshi; Ogawa, Hisao

    2015-01-01

    Objective To examine a relationship between statin intensity and heart failure (HF) incidence in diabetes. Research design and methods We performed a retrospective cohort study of patients with type 2 diabetes (n=600; age, 66.3 years; men, 68%). Patients were categorized into three groups by baseline statin treatments—moderate-intensity, low-intensity, or no statin—and the independent association between the statin category and HF hospitalization during follow-up was examined. Results Over the course of the median 6-year follow-up, 17.7% of the patients were hospitalized for HF. Cox regression analysis revealed a significant association between the baseline statin category and HF incidence (p=0.002), independently of age, sex, hypertension, B-type natriuretic peptide, glycated hemoglobin, estimated glomerular filtration rate, and low-density lipoprotein (LDL) cholesterol levels. The moderate-intensity statin group had a significantly lower risk for HF than the low-intensity statin group with an adjusted HR of 0.31 (95% CI 0.13 to 0.65, p=0.0014). Interestingly, among patients with prevalent coronary artery diseases (CAD) and with baseline LDL controlled to less than 100 mg/dL, the frequency of HF was still significantly lower in the moderate-intensity group than in the low-intensity group or the no statin group. The effect of baseline statin category on HF was independent of incident CAD events during follow-up. Conclusions In type 2 diabetes, moderate-intensity statins, in comparison to low-intensity or no statin, were associated with lower HF incidence independently of LDL levels or of CAD events. PMID:26566447

  7. Comparison of intensity modulated radiotherapy (IMRT) with intensity modulated particle therapy (IMPT) using fixed beams or an ion gantry for the treatment of patients with skull base meningiomas

    PubMed Central

    2012-01-01

    Background To examine the potential improvement in treatment planning for patients with skull base meningioma using IMRT compared to carbon ion or proton beams with and without a gantry. Methods Five patients originally treated with photon IMRT were selected for the study. Ion beams were chosen using a horizontal beam or an ion gantry. Intensity controlled raster scanning and the intensity modulated particle therapy mode were used for plan optimization. The evaluation included analysis of dose-volume histograms of the target volumes and organs at risk. Results In comparison with carbon and proton beams only with horizontal beams, carbon ion treatment plans could spare the OARs more and concentrated on the target volumes more than proton and photon IMRT treatment plans. Using only a horizontal fixed beam, satisfactory plans could be achieved for skull base tumors. Conclusion The results of the case studies showed that using IMPT has the potential to overcome the lack of a gantry for skull base tumors. Carbon ion plans offered slightly better dose distributions than proton plans, but the differences were not clinically significant with established dose prescription concepts. PMID:22439607

  8. Clinical efficiency of applying low-intensity laser therapy in treating dyscirculatory encephalopathy

    NASA Astrophysics Data System (ADS)

    Putilina, M. V.; Kozlov, V. I.; Vakhtin, V. I.

    2001-04-01

    An investigation was made of applying laser therapy combined with drug preparations in treating 300 patients affected by dyscirculatory encephalopathy. Neurological and neuropsychological examinations together with electroencephalography, rheoencephalography, computerized tomography, and magnetic resonance imaging were used to assess the patients' states prior to and after the treatment. It was found that the combined application of laser therapy and drug preparations produced a more pronounced therapeutic effect as compared with that produced by the separate application of laser therapy and drug preparations. The results obtained allowed us to conclude that the 0.89 micrometers laser infrared radiation increased patients' susceptibility to drugs. Moreover, the combined laser therapy improved the cerebral bloodflow and activated the metabolic and plastic functions of neurons. This decreased or eliminated late complications provoked by the cerebral blood circulation insufficiency.

  9. A novel conformity index for intensity modulated radiation therapy plan evaluation

    SciTech Connect

    Cheung, Fion W. K.; Law, Maria Y. Y.

    2012-09-15

    Purpose: Intensity modulated radiation therapy (IMRT) has gained popularity in the treatment of cancers. Manual evaluation of IMRT plans for head-and-neck cancers has been especially challenging necessitating efficient and objective assessment tools. In this work, the authors address this issue by developing a personalized conformity index (CI) for comparison of IMRT plans for head-and-neck cancers and evaluating its plan quality discerning power in comparison with other widely used CIs. Methods: A two-dimensional CI with dose and distance incorporated (CI{sub DD}) was developed using the MATLAB program language, to quantify the planning target volume (PTV) coverage. Valuable information contained in the digital imaging and communication in medicine (DICOM) RT objects were harvested for computation of each of the CI{sub DD} components. Apart from the dose penalty factor, a distance-based exponential function was employed by varying the penalty weight associated with the location of cold spots within the PTV. With the goal of deriving a customized penalty factor, the distances between individual pixel and its nearest PTV boundary was found. Using the exponential function, the impact of distance penalty was substantially larger for cold spots closer to the PTV centroid but petered out quickly wherever they were situated in the vicinity of PTV border. In order to evaluate the CI{sub DD} scoring system, three CT image data sets of nasopharyngeal carcinoma (NPC) patients were collected. Ten IMRT plans with degrading qualities were generated from each dataset and were ranked based on CI{sub DD} and other existing indices. The coefficient of variance was calculated for each dataset to compare the degree of variation. Results: The CI{sub DD} scoring system that considered spatial importance of each voxel within the PTV was successfully developed. The results demonstrated that the CI{sub DD} including four discrete factors could provide accurate rankings of plan quality by

  10. The impact of daily setup variations on head-and-neck intensity-modulated radiation therapy

    SciTech Connect

    Hong, Theodore S.; Tome, Wolfgang A.; Chappell, Richard J.; Chinnaiyan, Prakash; Mehta, Minesh P.; Harari, Paul M. . E-mail: harari@humonc.wisc.edu

    2005-03-01

    Purpose: Intensity-modulated radiation therapy (IMRT) in the treatment of head-and-neck (H and N) cancer provides the opportunity to diminish normal tissue toxicity profiles and thereby enhance patient quality of life. However, highly conformal treatment techniques commonly establish steep dose gradients between tumor and avoidance structures. Daily setup variations can therefore significantly compromise the ultimate precision of idealized H and N IMRT delivery. This study provides a detailed analysis regarding the potential impact of daily setup variations on the overall integrity of H and N IMRT. Methods and materials: A series of 10 patients with advanced H and N cancer were prospectively enrolled in a clinical trial to examine daily H and N radiation setup accuracy. These patients were treated with conventional shrinking field design using three-dimensional treatment planning techniques (not IMRT). Immobilization and alignment were performed using modern H and N practice techniques including conventional thermoplastic masking, baseplate fixation to the treatment couch, three-point laser alignment, and weekly portal film evaluation. After traditional laser alignment, setup accuracy was assessed daily for each patient by measuring 3 Cartesian and 3 angular deviations from the specified isocenter using a high-precision, optically guided patient localization system, which affords submillimeter setup accuracy. These positional errors were then applied to a distinct series of 10 H and N IMRT plans for detailed analysis regarding the impact of daily setup variation (without optical guidance) on the ultimate integrity of IMRT plans over a 30-day treatment course. Dose-volume histogram (DVH), equivalent uniform dose (EUD), mean total dose (mTd), and maximal total dose (MTD) for normal structures were analyzed for IMRT plans with and without incorporation of daily setup variation. Results: Using conventional H and N masking and laser alignment for daily positioning, the

  11. The efficacy of low-level 940 nm laser therapy with different energy intensities on bone healing.

    PubMed

    Atasoy, Kerem Turgut; Korkmaz, Yavuz Tolga; Odaci, Ersan; Hanci, Hatice

    2017-01-05

    The aim of this study was to evaluate the efficacy of low-level 940 nm laser therapy with energy intensities of 5, 10 and 20 J/cm2 on bone healing in an animal model. A total of 48 female adult Wistar rats underwent surgery to create bone defects in the right tibias. Low-level laser therapy (LLLT) was applied immediately after surgery and on post-operative days 2, 4, 6, 8, 10 and 12 in three study groups with energy intensities of 5 J/cm2, 10 J/cm2 and 20 J/cm2 using a 940 nm Gallium-Aluminium-Arsenide (Ga-Al-As) laser, while one control group underwent only the tibia defect surgery. All animals were sacrificed 4 or 8 weeks post-surgery. Fibroblasts, osteoblasts, osteocytes, osteoclasts and newly formed vessels were evaluated by a histological examination. No significant change was observed in the number of osteocytes, osteoblasts, osteoclasts and newly formed vessels at either time period across all laser groups. Although LLLT with the 10 J/cm2 energy density increased fibroblast activity at the 4th week in comparison with the 5 and 20 J/cm2 groups, no significant change was observed between the laser groups and the control group. These results indicate that low-level 940 nm laser with different energy intensities may not have marked effects on the bone healing process in both phases of bone formation.

  12. Pilot study comparing multi-family therapy to single family therapy for adults with anorexia nervosa in an intensive eating disorder program.

    PubMed

    Dimitropoulos, Gina; Farquhar, Jamie C; Freeman, Victoria Emily; Colton, Patricia Anne; Olmsted, Marion Patricia

    2015-07-01

    Multi-family therapy (MFT) has yet to be evaluated in families of adults with anorexia nervosa (AN). The study aims were: (i) assess the feasibility of MFT for AN; and, (ii) assess whether MFT is associated with improved outcomes for families compared with single-family therapy (SFT). Adult patients with AN consecutively referred to an eating disorder treatment program were assigned (non-randomly) to receive eight sessions of SFT or MFT. Assessment occurred pre-therapy, immediately post-therapy, and at 3-month follow-up. A total of 37 female patients (13 SFT, 24 MFT) and 45 family members (16 SFT, 29 MFT) completed treatment. There were significant time effects for patients' BMI, eating disorder-related psychopathology and multiple family outcome measures. There were no differences between MFT and SFT on family outcome measures at end of treatment and 3 months post treatment. MFT is a feasible intervention that can be used in adult intensive treatment for those with AN.

  13. Lipid Lowering Agents Aeromedical Concerns

    DTIC Science & Technology

    2001-06-01

    Hyperlipidemia is one of the major risk factors for prevent coronary heart disease . In particular, LDL coronary heart disease , a disease which, after a long...gastro- LDL- cholesterol . Thus the liver is the primary site intestinal side effects. Because of the difficulty of action of statins . Administration of...suspicious for myopathy. the most potent drugs available for reducing plasma concentration of LDL cholesterol . Statins reduce In common with other HMG-CoA

  14. Assessing client self-narrative change in emotion-focused therapy of depression: an intensive single case analysis.

    PubMed

    Angus, Lynne E; Kagan, Fern

    2013-12-01

    Personality researchers use the term self-narrative to refer to the development of an overall life story that places life events in a temporal sequence and organizes them in accordance to overarching themes. In turn, it is often the case that clients seek out psychotherapy when they can no longer make sense of their life experiences, as a coherent story. Angus and Greenberg (L. Angus and L. Greenberg, 2011, Working with narrative in emotion-focused therapy: Changing stories, healing lives. Washington, DC: American Psychological Association Press) view the articulation and consolidation of an emotionally integrated self-narrative account as an important part of the therapeutic change process that is essential for sustained change in emotion-focused therapy of depression. The purpose of the present study was to investigate client experiences of change, and self-narrative reconstruction, in the context of one good outcome emotion-focused therapy dyad drawn from the York II Depression Study. Using the Narrative Assessment Interview (NAI) method, client view of self and experiences of change were assessed at three points in time--after session one, at therapy termination, and at 6 months follow-up. Findings emerging from an intensive narrative theme analyses of the NAI transcripts--and 1 key therapy session identified by the client--are reported and evidence for the contributions of narrative and emotion processes to self-narrative change in emotion-focused therapy of depression are discussed. Finally, the implications of assessing clients' experiences of self-narrative change for psychotherapy research and practice are addressed.

  15. A model-aided segmentation in urethra identification based on an atlas human autopsy image for intensity modulated radiation therapy.

    PubMed

    Song, Yan; Muller, Boris; Burman, Chandra; Mychalczak, Borys; Song, Yulin

    2007-01-01

    In order to protect urethra in radiation therapy of prostate cancer, the urethra must be identified and localized as an organ at risk (OAR) for the inverse treatment planning in intensity modulated radiation therapy (IMRT). Because the prostatic urethra and its surrounding prostate tissue have similar physical characteristics, such as linear attenuation coefficient and density, it is difficult to distinct the OAR from the target in CT images. To localize the urethra without using contrast agent or additional imaging modalities other than planning CT images, a different approach was developed using a standard atlas of human anatomy image. This paper reports an investigation, in which an adult urethra was modeled based on a human anatomic image. An elastic model was build to account for a uniform tissue deformation of the prostate. This model was then applied to patients to localize their urethras and preliminary results are presented.

  16. Full Neurological Recovery after Extreme Hypoglycemia during Intensive Insulin Therapy: A Case Report

    PubMed Central

    Piot, Veerle M.; Verrijcken, Anton; Vanhoof, Marc; Mertens, Ilse; Soetens, Filiep

    2012-01-01

    Since 2000, there has been an ongoing debate regarding tightness of glycemic control in critically ill patients. An increased risk of hypoglycemia is observed in patients treated with an intensive insulin protocol targeting “normoglycemia,” probably accounting for a reduction of the overall benefit. Hypoglycemia is associated with neurological side effects and is found to be an independent predictor of mortality in most trials; however, long-term sequelae are rare if glucose is administered early. We describe a case of prolonged, extreme hypoglycemia in a critically ill patient treated according to an intensive insulin protocol who recovered without any neurological deficit at discharge. PMID:22920826

  17. A comprehensive dosimetric study of pancreatic cancer treatment using three-dimensional conformal radiation therapy (3DCRT), intensity-modulated radiation therapy (IMRT), volumetric-modulated radiation therapy (VMAT), and passive-scattering and modulated-scanning proton therapy (PT)

    SciTech Connect

    Ding, Xuanfeng; Dionisi, Francesco; Tang, Shikui; Ingram, Mark; Hung, Chun-Yu; Prionas, Evangelos; Lichtenwalner, Phil; Butterwick, Ian; Zhai, Huifang; Yin, Lingshu; Lin, Haibo; Kassaee, Alireza; Avery, Stephen

    2014-07-01

    With traditional photon therapy to treat large postoperative pancreatic target volume, it often leads to poor tolerance of the therapy delivered and may contribute to interrupted treatment course. This study was performed to evaluate the potential advantage of using passive-scattering (PS) and modulated-scanning (MS) proton therapy (PT) to reduce normal tissue exposure in postoperative pancreatic cancer treatment. A total of 11 patients with postoperative pancreatic cancer who had been previously treated with PS PT in University of Pennsylvania Roberts Proton Therapy Center from 2010 to 2013 were identified. The clinical target volume (CTV) includes the pancreatic tumor bed as well as the adjacent high-risk nodal areas. Internal (iCTV) was generated from 4-dimensional (4D) computed tomography (CT), taking into account target motion from breathing cycle. Three-field and 4-field 3D conformal radiation therapy (3DCRT), 5-field intensity-modulated radiation therapy, 2-arc volumetric-modulated radiation therapy, and 2-field PS and MS PT were created on the patients’ average CT. All the plans delivered 50.4 Gy to the planning target volume (PTV). Overall, 98% of PTV was covered by 95% of the prescription dose and 99% of iCTV received 98% prescription dose. The results show that all the proton plans offer significant lower doses to the left kidney (mean and V{sub 18} {sub Gy}), stomach (mean and V{sub 20} {sub Gy}), and cord (maximum dose) compared with all the photon plans, except 3-field 3DCRT in cord maximum dose. In addition, MS PT also provides lower doses to the right kidney (mean and V{sub 18} {sub Gy}), liver (mean dose), total bowel (V{sub 20} {sub Gy} and mean dose), and small bowel (V{sub 15} {sub Gy} absolute volume ratio) compared with all the photon plans and PS PT. The dosimetric advantage of PT points to the possibility of treating tumor bed and comprehensive nodal areas while providing a more tolerable treatment course that could be used for dose

  18. [Ion-exchange hemosorption in the intensive therapy of liver insufficiency in patients with obstructive jaundice].

    PubMed

    Minina, K Z; Kurapov, E P; Goncharov, V V; Leĭkin, Iu A; Tarasova, T I; Treushnikova, N Iu

    1989-01-01

    Hemosorption on thromboresistant ion-exchange resins synthetized at D. I. Mendeleev Moscow Chemical Technological Institute (MCTI) was used in combined therapy of hepatic failure. Use was made of anion-exchange resin A-I-II MCTI, catonit C-I-II MCTI, polyampholit. Stability of hemodynamic parameters, absence of blood element disturbances, effective sampling of anionic and cationic metabolites have been observed.

  19. Sensitivity of reticulocyte indices to iron therapy in an intensely training athlete.

    PubMed

    Ashenden, M J; Dobson, G P; Hahn, A G

    1998-09-01

    Iron deficiency anaemia, and its debilitating effect on performance, is an area of concern for many female athletes. Automated technologies that analyse individual reticulocytes may provide a sensitive measure of bone marrow response to iron supplementation. The reticulocyte characteristics of a female volleyball player with frank iron deficiency anaemia, and her subsequent response to oral iron therapy, are reported.

  20. Intensive Dysarthria Therapy for Older Children with Cerebral Palsy: Findings from Six Cases

    ERIC Educational Resources Information Center

    Pennington, Lindsay; Smallman, Claire; Farrier, Faith

    2006-01-01

    Children with cerebral palsy often have speech, language and communication difficulties that affect their access to social and educational activities. Speech and language therapy to improve the intelligibility of the speech of children with cerebral palsy has long been advocated, but there is a dearth of research investigating therapy…

  1. Intensive Speech and Language Therapy for Older Children with Cerebral Palsy: A Systems Approach

    ERIC Educational Resources Information Center

    Pennington, Lindsay; Miller, Nick; Robson, Sheila; Steen, Nick

    2010-01-01

    Aim: To investigate whether speech therapy using a speech systems approach to controlling breath support, phonation, and speech rate can increase the speech intelligibility of children with dysarthria and cerebral palsy (CP). Method: Sixteen children with dysarthria and CP participated in a modified time series design. Group characteristics were…

  2. Pain Intensity and Opioid Utilization in Response to CPAP Therapy in Veterans with Obstructive Sleep Apnea on Chronic Opioid Treatment

    PubMed Central

    Jaoude, Philippe; Lal, Ashima; Vermont, Leah; Porhomayon, Jahan; El-Solh, Ali A.

    2016-01-01

    Study Objectives: Sleep fragmentation has been linked to poor pain tolerance and lowered pain threshold. Little evidence exists on whether continuous positive airway pressure (CPAP) adherence in veterans with obstructive sleep apnea (OSA) who are taking opioids for non-malignant pain would ameliorate pain and reduce consumption of opioids. Methods: A retrospective case-control study was performed at a VA sleep center. Pain intensity was assessed using the Numerical Categorical Scale prior to CPAP treatment and 12-mo follow-up. Opioids intake was assessed using the morphine equivalent daily dose (MEDD). Adherence to CPAP was evaluated with the built-in meter. Results: We reviewed 113 patients with OSA (apnea-hypopnea index [AHI] 35.9 ± 29.5) using a MEDD of 61.6 mg (range 5–980 mg) and a control group of 113 veterans with OSA (AHI 33.4 ± 27.3) on no opioids treatment. CPAP adherence was significantly lower at 12 mo in opioid-treated patients compared to controls (37% versus 55%; p = 0.01). Greater pain intensity was the only independent variable associated with CPAP non-adherence at 12-mo follow-up (p = 0.03). Compared to baseline, no significant difference was observed in pain intensity or consumption of opioids in CPAP adherent patients. Conclusions: CPAP treatment did not reduce pain intensity or consumption of opioids in veterans with chronic pain who have coexisting OSA. CPAP adherence was lower in opioid-treated veterans with OSA compared to opioid-free veterans with OSA. Pain intensity was the only determinant of CPAP adherence. Future studies are needed to evaluate pain management program on adherence to CPAP. Citation: Jaoude P, Lal A, Vermont L, Porhomayon J, El-Solh AA. Pain intensity and opioid utilization in response to cpap therapy in veterans with obstructive sleep apnea on chronic opioid treatment. J Clin Sleep Med 2016;12(8):1105–1111. PMID:27250815

  3. Study finds low-intensity therapy for Burkitt lymphoma highly effective

    Cancer.gov

    Adult patients with a type of cancer known as Burkitt lymphoma had excellent long-term survival rates—upwards of 90 percent—following treatment with low-intensity chemotherapy regimens, according to a new clinical trial finding. Burkitt lymphoma is the mo

  4. [Particle load in intensive therapy. Possible solutions using a multi-lumen catheter and Intrapur filter].

    PubMed

    Schröder, F

    1990-06-01

    Patients at intensive care units need very many drugs applicated via a central venous katheter. Particles caused by incompatibility reactions or coming from disposible materials possibly can provoke severe complications such as embolism, anaphylactoid reactions or ARDS. The combined use of multilumen katheters and Intrapur filters brings a significant reduction of these particles, as shown by an infusion regime.

  5. Intensive (Daily) Behavior Therapy for School Refusal: A Multiple Baseline Case Series

    ERIC Educational Resources Information Center

    Tolin, David F.; Whiting, Sara; Maltby, Nicholas; Diefenbach, Gretchen J.; Lothstein, Mary Anne; Hardcastle, Surrey; Catalano, Amy; Gray, Krista

    2009-01-01

    The following multiple baseline case series examines school refusal behavior in 4 male adolescents. School refusal symptom presentation was ascertained utilizing a functional analysis from the School Refusal Assessment Scale (Kearney, 2002). For the majority of cases, treatment was conducted within a 15-session intensive format over a 3-week…

  6. Patterns of Care and Outcomes Associated With Intensity-Modulated Radiation Therapy Versus Conventional Radiation Therapy for Older Patients With Head-and-Neck Cancer

    SciTech Connect

    Yu, James B.; Soulos, Pamela R.; Sharma, Richa; Makarov, Danil V.; Decker, Roy H.; Smith, Benjamin D.; Desai, Rani A.; Cramer, Laura D.; Gross, Cary P.

    2012-05-01

    Purpose: Intensity-modulated radiation therapy (IMRT) requires a high degree of expertise compared with standard radiation therapy (RT). We performed a retrospective cohort study of Medicare patients treated with IMRT compared with standard RT to assess outcomes in national practice. Methods and Materials: Using the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database, we identified patients treated with radiation for cancer of the head and neck from 2002 to 2005. We used multivariate Cox models to determine whether the receipt of IMRT was associated with differences in survival. Results: We identified 1613 patients, 33.7% of whom received IMRT. IMRT was not associated with differences in survival: the 3-year overall survival was 50.5% for IMRT vs. 49.6% for standard RT (p = 0.47). The 3-year cancer-specific survival was 60.0% for IMRT vs. 58.8% (p = 0.45). Conclusion: Despite its complexity and resource intensive nature, IMRT use seems to be as safe as standard RT in national community practice, because the use of IMRT did not have an adverse impact on survival.

  7. Comparison of Postprandial Responses to a High-Fat Meal in Hypertriglyceridemic Men and Women before and after Treatment with Fenofibrate in the Genetics and Lipid Lowering Drugs and Diet Network (GOLDN) Study

    PubMed Central

    Glasser, Stephen P.; Wojczynski, Mary K.; Oberman, A. I.; Kabagambe, Edmond K.; Tsai, Michael Y.; Ordovas, Jose M.; Straka, Robert J.; Arnett, Donna K.

    2013-01-01

    Context The fenofibrate effect on the subclass size distribution of lipoproteins before and after a high-fat challenge is not well studied. Objective To characterize the baseline and post-prandial response (PPL) to a high-fat challenge following fenofibrate therapy, on changes in LDL, HDL, and VLDL particle subclasses, number, and size in 271 hypertriglyceridemic participants. Methods Participants from the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) study who conducted PPL studies both before and after three weeks of fenofibrate (160 mg/d) treatment were analyzed. Particle size distributions were determined using nuclear magnetic resonance imaging, and lipid determinations were measured at fasting (0 hr), 3.5 hours, and 6 hours after ingestion of a standardized high-fat meal. Analyses were stratified by gender. Changes in particle subclass distributions were assessed using repeated measures analysis of variance adjusted for pedigree. Results Before PPL, fenofibrate in men (adjusted for age, field center, smoking status, diabetes, and weight circumference) lowered fasting and postprandial VLDL primarily due to reductions in postprandial levels of large and medium VLDL particles (9 SE +/–0.7 to 4 +/–0.4 and 78 / –4 to 36 / –3 nmol/L both P < .0001, resp.). Fenofibrate also reduced fasting and postprandial total LDL particles, primarily a result of reduced small LDL particles (1497 = / – 37 to 1088 = / – 36 nmol/L, P < .0001). Directional changes were similar in men and women but the magnitude of change was different for some parameters. Conclusion Fenofibrate treatment resulted in a lower triglyceride excursion following a high-fat meal. This investigation provides new knowledge of the magnitude and time course of fenofibrate induced attenuation of Lipoprotein subclass size distribution following a postprandial lipid challenge. PMID:24971173

  8. Proton-beam vs intensity-modulated radiation therapy. Which is best for treating prostate cancer?

    PubMed

    Nguyen, Paul L; Trofimov, Alexei; Zietman, Anthony L

    2008-06-01

    There is a growing interest in the use of proton therapy for the treatment of many cancers. With its unique dose-distribution properties, proton therapy has the potential to improve the therapeutic ratio of prostate radiation by allowing for an increase in dose without a substantial increase in side effects. While much evidence supports this notion in the context of many oncologic sites, only limited clinical data have compared protons to photons in prostate cancer. Therefore, the increasing enthusiasm for the use of protons in prostate cancer has aroused considerable concern. Some have questioned its ability to limit morbidity, and others have questioned its value relative to the cost. In addition, theoretical concerns have been raised about a potential additional risk for secondary malignancies. In this article, we review the current status of the evidence supporting the use of protons in prostate cancer and discuss the active controversies that surround this modality.

  9. Laser-driven beam lines for delivering intensity modulated radiation therapy with particle beams

    NASA Astrophysics Data System (ADS)

    Hofmann, K. M.; Schell, S.; Wilkens, J. J.

    2013-07-01

    Laser-accelerated particles can provide a promising opportunity for radiation therapy of cancer. Potential advantages arise from combining a compact, cost-efficient treatment unit with the physical advantages in dose delivery of charged particle beams. We consider different dose delivery schemes and the required devices to design a possible treatment unit. The secondary radiation produced in several beam line elements remains a challenge to be addressed.

  10. Sensitivity of reticulocyte indices to iron therapy in an intensely training athlete

    PubMed Central

    Ashenden, M. J.; Dobson, G. P.; Hahn, A. G.

    1998-01-01

    Iron deficiency anaemia, and its debilitating effect on performance, is an area of concern for many female athletes. Automated technologies that analyse individual reticulocytes may provide a sensitive measure of bone marrow response to iron supplementation. The reticulocyte characteristics of a female volleyball player with frank iron deficiency anaemia, and her subsequent response to oral iron therapy, are reported. 




 PMID:9773180

  11. Laser-driven beam lines for delivering intensity modulated radiation therapy with particle beams

    SciTech Connect

    Hofmann, K. M.; Schell, S.; Wilkens, J. J.

    2013-07-26

    Laser-accelerated particles can provide a promising opportunity for radiation therapy of cancer. Potential advantages arise from combining a compact, cost-efficient treatment unit with the physical advantages in dose delivery of charged particle beams. We consider different dose delivery schemes and the required devices to design a possible treatment unit. The secondary radiation produced in several beam line elements remains a challenge to be addressed.

  12. Cortical thickness in children receiving intensive therapy for idiopathic apraxia of speech.

    PubMed

    Kadis, Darren S; Goshulak, Debra; Namasivayam, Aravind; Pukonen, Margit; Kroll, Robert; De Nil, Luc F; Pang, Elizabeth W; Lerch, Jason P

    2014-03-01

    Children with idiopathic apraxia experience difficulties planning the movements necessary for intelligible speech. There is increasing evidence that targeted early interventions, such as Prompts for Restructuring Oral Muscular Phonetic Targets (PROMPT), can be effective in treating these disorders. In this study, we investigate possible cortical thickness correlates of idiopathic apraxia of speech in childhood, and changes associated with participation in an 8-week block of PROMPT therapy. We found that children with idiopathic apraxia (n = 11), aged 3-6 years, had significantly thicker left supramarginal gyri than a group of typically-developing age-matched controls (n = 11), t(20) = 2.84, p ≤ 0.05. Over the course of therapy, the children with apraxia (n = 9) experienced significant thinning of the left posterior superior temporal gyrus (canonical Wernicke's area), t(8) = 2.42, p ≤ 0.05. This is the first study to demonstrate experience-dependent structural plasticity in children receiving therapy for speech sound disorders.

  13. A Phase II Study of Intensity Modulated Radiation Therapy to the Pelvis for Postoperative Patients With Endometrial Carcinoma: Radiation Therapy Oncology Group Trial 0418

    SciTech Connect

    Jhingran, Anuja; Winter, Kathryn; Portelance, Lorraine; Miller, Brigitte; Salehpour, Mohammad; Gaur, Rakesh; Souhami, Luis; Small, William; Berk, Lawrence; Gaffney, David

    2012-09-01

    Purpose: To determine the feasibility of pelvic intensity modulated radiation therapy (IMRT) for patients with endometrial cancer in a multi-institutional setting and to determine whether this treatment is associated with fewer short-term bowel adverse events than standard radiation therapy. Methods: Patients with adenocarcinoma of the endometrium treated with pelvic radiation therapy alone were eligible. Guidelines for target definition and delineation, dose prescription, and dose-volume constraints for the targets and critical normal structures were detailed in the study protocol and a web-based atlas. Results: Fifty-eight patients were accrued by 25 institutions; 43 were eligible for analysis. Forty-two patients (98%) had an acceptable IMRT plan; 1 had an unacceptable variation from the prescribed dose to the nodal planning target volume. The proportions of cases in which doses to critical normal structures exceeded protocol criteria were as follows: bladder, 67%; rectum, 76%; bowel, 17%; and femoral heads, 33%. Twelve patients (28%) developed grade {>=}2 short-term bowel adverse events. Conclusions: Pelvic IMRT for endometrial cancer is feasible across multiple institutions with use of a detailed protocol and centralized quality assurance (QA). For future trials, contouring of vaginal and nodal tissue will need continued monitoring with good QA and better definitions will be needed for organs at risk.

  14. Three-dimensional conformal intensity-modulated radiation therapy of left femur foci does not damage the sciatic nerve

    PubMed Central

    Xu, Wanlong; Zhao, Xibin; Wang, Qing; Sun, Jungang; Xu, Jiangbo; Zhou, Wenzheng; Wang, Hao; Yan, Shigui; Yuan, Hong

    2014-01-01

    During radiotherapy to kill femoral hydatid tapeworms, the sciatic nerve surrounding the focus can be easily damaged by the treatment. Thus, it is very important to evaluate the effects of radiotherapy on the surrounding nervous tissue. In the present study, we used three-dimensional, conformal, intensity-modulated radiation therapy to treat bilateral femoral hydatid disease in Meriones meridiani. The focus of the hydatid disease on the left femur was subjected to radiotherapy (40 Gy) for 14 days, and the right femur received sham irradiation. Hematoxylin-eosin staining, electron microscopy, and terminal deoxynucleotidyl transferase-dUTP nick end labeling assays on the left femurs showed that the left sciatic nerve cell structure was normal, with no obvious apoptosis after radiation. Trypan blue staining demonstrated that the overall protoscolex structure in bone parasitized with Echinococcus granulosus disappeared in the left femur of the animals after treatment. The mortality of the protoscolex was higher in the left side than in the right side. The succinate dehydrogenase activity in the protoscolex in bone parasitized with Echinococcus granulosus was lower in the left femur than in the right femur. These results suggest that three-dimensional conformal intensity-modulated radiation therapy achieves good therapeutic effects on the secondary bone in hydatid disease in Meriones meridiani without damaging the morphology or function of the sciatic nerve. PMID:25422645

  15. Bone Marrow Sparing in Intensity Modulated Proton Therapy for Cervical Cancer: Efficacy and Robustness under Range and Setup Uncertainties

    PubMed Central

    Dinges, Eric; Felderman, Nicole; McGuire, Sarah; Gross, Brandie; Bhatia, Sudershan; Mott, Sarah; Buatti, John; Wang, Dongxu

    2015-01-01

    Background and Purpose This study evaluates the potential efficacy and robustness of functional bone marrow sparing (BMS) using intensity-modulated proton therapy (IMPT) for cervical cancer, with the goal of reducing hematologic toxicity. Material and Methods IMPT plans with prescription dose of 45 Gy were generated for ten patients who have received BMS intensity-modulated x-ray therapy (IMRT). Functional bone marrow was identified by 18F-flourothymidine positron emission tomography. IMPT plans were designed to minimize the volume of functional bone marrow receiving 5–40 Gy while maintaining similar target coverage and healthy organ sparing as IMRT. IMPT robustness was analyzed with ±3% range uncertainty errors and/or ±3mm translational setup errors in all three principal dimensions. Results In the static scenario, the median dose volume reductions for functional bone marrow by IMPT were: 32% for V5GY, 47% for V10Gy, 54% for V20Gy, and 57% for V40Gy, all with p<0.01 compared to IMRT. With assumed errors, even the worst-case reductions by IMPT were: 23% for V5Gy, 37% for V10Gy, 41% for V20Gy, and 39% for V40Gy, all with p<0.01. Conclusions The potential sparing of functional bone marrow by IMPT for cervical cancer is significant and robust under realistic systematic range uncertainties and clinically relevant setup errors. PMID:25981130

  16. Association of DNA Methylation at CPT1A Locus with Metabolic Syndrome in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) Study.

    PubMed

    Das, Mithun; Sha, Jin; Hidalgo, Bertha; Aslibekyan, Stella; Do, Anh N; Zhi, Degui; Sun, Dianjianyi; Zhang, Tao; Li, Shengxu; Chen, Wei; Srinivasan, Sathanur R; Tiwari, Hemant K; Absher, Devin; Ordovas, Jose M; Berenson, Gerald S; Arnett, Donna K; Irvin, Marguerite R

    2016-01-01

    In this study, we conducted an epigenome-wide association study of metabolic syndrome (MetS) among 846 participants of European descent in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN). DNA was isolated from CD4+ T cells and methylation at ~470,000 cytosine-phosphate-guanine dinucleotide (CpG) pairs was assayed using the Illumina Infinium HumanMethylation450 BeadChip. We modeled the percentage methylation at individual CpGs as a function of MetS using linear mixed models. A Bonferroni-corrected P-value of 1.1 x 10(-7) was considered significant. Methylation at two CpG sites in CPT1A on chromosome 11 was significantly associated with MetS (P for cg00574958 = 2.6x10(-14) and P for cg17058475 = 1.2x10(-9)). Significant associations were replicated in both European and African ancestry participants of the Bogalusa Heart Study. Our findings suggest that methylation in CPT1A is a promising epigenetic marker for MetS risk which could become useful as a treatment target in the future.

  17. The anti-hyperglycemic efficacy of a lipid-lowering drug Daming capsule and the underlying signaling mechanisms in a rat model of diabetes mellitus

    PubMed Central

    Zhang, Yong; Li, Xiaoguang; Li, Jiamin; Zhang, Qingwei; Chen, Xiaohui; Liu, Xin; Zhang, Yue; Zhang, Haiying; Yang, Huan; Hu, Yingying; Wu, Xianxian; Li, Xin; Ju, Jiaming; Yang, Baofeng

    2016-01-01

    Diabetes mellitus (DM) is a metabolic disorder manifested by hyperglycemia. Daming Capsule (DMC), a combination of traditional Chinese herbs, is used clinically as a lipid-lowering drug. This study was designed to evaluate if DMC possesses an anti-hyperglycemic effect and to elucidate the underlying mechanisms. Compared to diabetic rats, the rats received DMC (200 mg/kg/d) had significantly lower blood lipid and glucose levels. DMC markedly restored the decreased secretion of GLP-1 and GIP as well as the coding gene GCG and GIP in ileum. Moreover, DMC normalized depressed GCG and GIP transcription by significantly enhancing the GSK-3β/β-catenin signaling pathway and expression of TCF7L2, a transactivator of GCG and GIP in diabetic rats. DMC possesses an anti-hyperglycemic property characterized by preservation/stimulation of GLP-1 and GIP secretion in DM rats. Here, we proposed DMC → GSK-3β/β-catenin↑ → TCF7L2↑ → GLP-1, GIP secretion↑ → blood glucose↓ as a regulatory pathway of blood glucose homeostasis. Our findings suggest DMC as a promising therapeutic drug in the clinical treatment of diabetes. PMID:27721485

  18. Comparison of Low-Dose Rosuvastatin with Atorvastatin in Lipid-Lowering Efficacy and Safety in a High-Risk Pakistani Cohort: An Open-Label Randomized Trial

    PubMed Central

    Arshad, Abdul Rehman

    2014-01-01

    Background. Treatment of hyperlipidemia is helpful in both primary and secondary prevention of coronary heart disease and stroke. Aim. To compare lipid-lowering efficacy of rosuvastatin with atorvastatin. Methodology. This open-label randomized controlled trial was carried out at 1 Mountain Medical Battalion from September 2012 to August 2013 on patients with type 2 diabetes, hypertension, myocardial infarction, or stroke, meriting treatment with a statin. Those with secondary causes of dyslipidemia were excluded. Blood samples for estimation of serum total cholesterol, triglycerides, HDL-C, and LDL-C were collected after a 12-hour fast. Patients were randomly allocated to receive either atorvastatin 10 mg HS or rosuvastatin 5 mg HS daily. Lipid levels were rechecked after six weeks. Results. Atorvastatin was used in 63 patients and rosuvastatin in 66. There was a greater absolute and percent reduction in serum LDL-C levels with rosuvastatin as compared to atorvastatin (0.96 versus 0.54 mg/dL; P = 0.011 and 24.34 versus 13.66%; P = 0.045), whereas reduction in all other fractions was equal. Myalgias were seen in 5 (7.94%) patients treated with atorvastatin and 8 (12.12%) patients treated with rosuvastatin (P: 0.432). Conclusion. Rosuvastatin produces a greater reduction in serum LDL-C levels and should therefore be preferred over atorvastatin. PMID:24800084

  19. A family-specific linkage analysis of blood lipid response to fenofibrate in the Genetics of Lipid Lowering Drug and Diet Network (GOLDN)

    PubMed Central

    Hidalgo, Bertha; Aslibekyan, Stella; Wiener, Howard W.; Irvin, Marguerite R.; Straka, Robert J.; Borecki, Ingrid B.; Tiwari, Hemant K.; Tsai, Michael Y.; Hopkins, Paul N.; Ordovas, Jose M.; Arnett, Donna K.

    2015-01-01

    Cost-effective identification of novel pharmacogenetic variants remains a pressing need in the field. Using data from the Genetics of Lipid Lowering Drugs and Diet Network, we identified genomic regions of relevance to fenofibrate response in a sample of 173 families. Our approach included a multipoint linkage scan, followed by selection of the families showing evidence of linkage. We identified a strong signal for changes in LDL-C on chromosome 7 (peak LOD score=4.76) in the full sample (n=821). The signal for LDL-C response remained even after adjusting for baseline LDL-C. Restricting analyses only to the families contributing to the linkage signal for LDL-C (N=19), we observed a peak LOD score of 5.17 for chromosome 7. Two genes under this peak (ABCB4 and CD36) were of biological interest. These results suggest that linked family analyses might be a useful approach to gene discovery in the presence of a complex (e.g. multigenic) phenotype. PMID:26203732

  20. Preliminary outcome and toxicity report of extended-field, intensity-modulated radiation therapy for gynecologic malignancies

    SciTech Connect

    Salama, Joseph K. . E-mail: jsalama@radonc.uchicago.edu; Mundt, Arno J.; Roeske, John; Mehta, Neil

    2006-07-15

    Purpose: The aim of this article is to report a preliminary analysis of our initial clinical experience with extended-field intensity-modulated radiotherapy for gynecologic malignancies. Methods and Materials: Between November 2002 and May 2005, 13 women with gynecologic malignancies were treated with extended-field radiation therapy. Of the women, 7 had endometrial cancer, 4 cervical cancer, 1 recurrent endometrial cancer, and 1 suspected cervical cancer. All women underwent computed tomography planning, with the upper vagina, parametria, and uterus (if present) contoured within the CTV. In addition, the clinical target volume contained the pelvic and presacral lymph nodes as well as the para-aortic lymph nodes. All acute toxicity was scored according to the Common Terminology Criteria for Adverse Events (CTCAE v 3.0). All late toxicity was scored using the Radiation Therapy Oncology Group late toxicity score. Results: The median follow-up was 11 months. Extended-field intensity-modulated radiation therapy (IMRT) for gynecologic malignancies was well tolerated. Two patients experienced Grade 3 or higher toxicity. Both patients were treated with concurrent cisplatin based chemotherapy. Neither patient was planned with bone marrow sparing. Eleven patients had no evidence of late toxicity. One patient with multiple previous surgeries experienced a bowel obstruction. One patient with bilateral grossly involved and unresectable common iliac nodes experienced bilateral lymphedema. Extended-field-IMRT achieved good local control with only 1 patient, who was metastatic at presentation, and 1 patient not able to complete treatment, experiencing in-field failure. Conclusions: Extended-field IMRT is safe and effective with a low incidence of acute toxicity. Longer follow-up is needed to assess chronic toxicity, although early results are promising.

  1. A pilot study of intensity modulated radiation therapy with hypofractionated stereotactic body radiation therapy (SBRT) boost in the treatment of intermediate- to high-risk prostate cancer.

    PubMed

    Oermann, Eric K; Slack, Rebecca S; Hanscom, Heather N; Lei, Sue; Suy, Simeng; Park, Hyeon U; Kim, Joy S; Sherer, Benjamin A; Collins, Brian T; Satinsky, Andrew N; Harter, K William; Batipps, Gerald P; Constantinople, Nicholas L; Dejter, Stephen W; Maxted, William C; Regan, James B; Pahira, John J; McGeagh, Kevin G; Jha, Reena C; Dawson, Nancy A; Dritschilo, Anatoly; Lynch, John H; Collins, Sean P

    2010-10-01

    Clinical data suggest that large radiation fractions are biologically superior to smaller fraction sizes in prostate cancer radiotherapy. The CyberKnife is an appealing delivery system for hypofractionated radiosurgery due to its ability to deliver highly conformal radiation and to track and adjust for prostate motion in real-time. We report our early experience using the CyberKnife to deliver a hypofractionated stereotactic body radiation therapy (SBRT) boost to patients with intermediate- to high-risk prostate cancer. Twenty-four patients were treated with hypofractionated SBRT and supplemental external radiation therapy plus or minus androgen deprivation therapy (ADT). Patients were treated with SBRT to a dose of 19.5 Gy in 3 fractions followed by intensity modulated radiation therapy (IMRT) to a dose of 50.4 Gy in 28 fractions. Quality of life data were collected with American Urological Association (AUA) symptom score and Expanded Prostate Cancer Index Composite (EPIC) questionnaires before and after treatment. PSA responses were monitored; acute urinary and rectal toxicities were assessed using Common Toxicity Criteria (CTC) v3. All 24 patients completed the planned treatment with an average follow-up of 9.3 months. For patients who did not receive ADT, the median pre-treatment PSA was 10.6 ng/ml and decreased in all patients to a median of 1.5 ng/ml by 6 months post-treatment. Acute effects associated with treatment included Grade 2 urinary and gastrointestinal toxicity but no patient experienced acute Grade 3 or greater toxicity. AUA and EPIC scores returned to baseline by six months post-treatment. Hypofractionated SBRT combined with IMRT offers radiobiological benefits of a large fraction boost for dose escalation and is a well tolerated treatment option for men with intermediate- to high-risk prostate cancer. Early results are encouraging with biochemical response and acceptable toxicity. These data provide a basis for the design of a phase II clinical

  2. The clinical potential of high energy, intensity and energy modulated electron beams optimized by simulated annealing for conformal radiation therapy

    NASA Astrophysics Data System (ADS)

    Salter, Bill Jean, Jr.

    Purpose. The advent of new, so called IVth Generation, external beam radiation therapy treatment machines (e.g. Scanditronix' MM50 Racetrack Microtron) has raised the question of how the capabilities of these new machines might be exploited to produce extremely conformal dose distributions. Such machines possess the ability to produce electron energies as high as 50 MeV and, due to their scanned beam delivery of electron treatments, to modulate intensity and even energy, within a broad field. Materials and methods. Two patients with 'challenging' tumor geometries were selected from the patient archives of the Cancer Therapy and Research Center (CTRC), in San Antonio Texas. The treatment scheme that was tested allowed for twelve, energy and intensity modulated beams, equi-spaced about the patient-only intensity was modulated for the photon treatment. The elementary beams, incident from any of the twelve allowed directions, were assumed parallel, and the elementary electron beams were modeled by elementary beam data. The optimal arrangement of elementary beam energies and/or intensities was optimized by Szu-Hartley Fast Simulated Annealing Optimization. Optimized treatment plans were determined for each patient using both the high energy, intensity and energy modulated electron (HIEME) modality, and the 6 MV photon modality. The 'quality' of rival plans were scored using three different, popular objective functions which included Root Mean Square (RMS), Maximize Dose Subject to Dose and Volume Limitations (MDVL - Morrill et. al.), and Probability of Uncomplicated Tumor Control (PUTC) methods. The scores of the two optimized treatments (i.e. HIEME and intensity modulated photons) were compared to the score of the conventional plan with which the patient was actually treated. Results. The first patient evaluated presented a deeply located target volume, partially surrounding the spinal cord. A healthy right kidney was immediately adjacent to the tumor volume, separated

  3. Spot-scanning beam proton therapy vs intensity-modulated radiation therapy for ipsilateral head and neck malignancies: A treatment planning comparison

    SciTech Connect

    Kandula, Shravan; Zhu, Xiaorong; Garden, Adam S.; Gillin, Michael; Rosenthal, David I.; Ang, Kie-Kian; Mohan, Radhe; Amin, Mayankkumar V.; Garcia, John A.; Wu, Richard; Sahoo, Narayan; Frank, Steven J.

    2013-01-01

    Radiation therapy for head and neck malignancies can have side effects that impede quality of life. Theoretically, proton therapy can reduce treatment-related morbidity by minimizing the dose to critical normal tissues. We evaluated the feasibility of spot-scanning proton therapy for head and neck malignancies and compared dosimetry between those plans and intensity-modulated radiation therapy (IMRT) plans. Plans from 5 patients who had undergone IMRT for primary tumors of the head and neck were used for planning proton therapy. Both sets of plans were prepared using computed tomography (CT) scans with the goals of achieving 100% of the prescribed dose to the clinical target volume (CTV) and 95% to the planning TV (PTV) while maximizing conformity to the PTV. Dose-volume histograms were generated and compared, as were conformity indexes (CIs) to the PTVs and mean doses to the organs at risk (OARs). Both modalities in all cases achieved 100% of the dose to the CTV and 95% to the PTV. Mean PTV CIs were comparable (0.371 IMRT, 0.374 protons, p = 0.953). Mean doses were significantly lower in the proton plans to the contralateral submandibular (638.7 cGy IMRT, 4.3 cGy protons, p = 0.002) and parotid (533.3 cGy IMRT, 48.5 cGy protons, p = 0.003) glands; oral cavity (1760.4 cGy IMRT, 458.9 cGy protons, p = 0.003); spinal cord (2112.4 cGy IMRT, 249.2 cGy protons, p = 0.002); and brainstem (1553.52 cGy IMRT, 166.2 cGy protons, p = 0.005). Proton plans also produced lower maximum doses to the spinal cord (3692.1 cGy IMRT, 2014.8 cGy protons, p = 0.034) and brainstem (3412.1 cGy IMRT, 1387.6 cGy protons, p = 0.005). Normal tissue V{sub 10}, V{sub 30}, and V{sub 50} values were also significantly lower in the proton plans. We conclude that spot-scanning proton therapy can significantly reduce the integral dose to head and neck critical structures. Prospective studies are underway to determine if this reduced dose translates to improved quality of life.

  4. Effect of postremission therapy before reduced-intensity conditioning allogeneic transplantation for acute myeloid leukemia in first complete remission.

    PubMed

    Warlick, Erica D; Paulson, Kristjan; Brazauskas, Ruta; Zhong, Xiaobo; Miller, Alan M; Camitta, Bruce M; George, Biju; Savani, Bipin N; Ustun, Celalettin; Marks, David I; Waller, Edmund K; Baron, Frédéric; Freytes, César O; Socie, Gérard; Akpek, Gorgun; Schouten, Harry C; Lazarus, Hillard M; Horwitz, Edwin M; Koreth, John; Cahn, Jean-Yves; Bornhauser, Martin; Seftel, Matthew; Cairo, Mitchell S; Laughlin, Mary J; Sabloff, Mitchell; Ringdén, Olle; Gale, Robert Peter; Kamble, Rammurti T; Vij, Ravi; Gergis, Usama; Mathews, Vikram; Saber, Wael; Chen, Yi-Bin; Liesveld, Jane L; Cutler, Corey S; Ghobadi, Armin; Uy, Geoffrey L; Eapen, Mary; Weisdorf, Daniel J; Litzow, Mark R

    2014-02-01

    The impact of pretransplant (hematopoietic cell transplantation [HCT]) cytarabine consolidation therapy on post-HCT outcomes has yet to be evaluated after reduced-intensity or nonmyeloablative conditioning. We analyzed 604 adults with acute myeloid leukemia in first complete remission (CR1) reported to the Center for International Blood and Marrow Transplant Research who received a reduced-intensity or nonmyeloablative conditioning HCT from an HLA-identical sibling, HLA-matched unrelated donor, or umbilical cord blood donor from 2000 to 2010. We compared transplant outcomes based on exposure to cytarabine postremission consolidation. Three-year survival rates were 36% (95% confidence interval [CI], 29% to 43%) in the no consolidation arm and 42% (95% CI, 37% to 47%) in the cytarabine consolidation arm (P = .16). Disease-free survival was 34% (95% CI, 27% to 41%) and 41% (95% CI, 35% to 46%; P = .15), respectively. Three-year cumulative incidences of relapse were 37% (95% CI, 30% to 44%) and 38% (95% CI, 33% to 43%), respectively (P = .80). Multivariate regression confirmed no effect of consolidation on relapse, disease-free survival, and survival. Before reduced-intensity or nonmyeloablative conditioning HCT, these data suggest pre-HCT consolidation cytarabine does not significantly alter outcomes and support prompt transition to transplant as soon as morphologic CR1 is attained. If HCT is delayed while identifying a donor, our data suggest that consolidation does not increase transplant treatment-related mortality and is reasonable if required.

  5. Low intensity ultrasound induces apoptosis via MPT channel on mitochondrial membrane: Target for regulating cancer therapy or not?

    NASA Astrophysics Data System (ADS)

    Feng, Yi; Wan, Mingxi

    2017-03-01

    To discuss how the mitochondrion is involved in low intensity ultrasound induced apoptosis, HepG2 cells were irradiated by low intensity focused ultrasound (ISPTA = 3W/cm2, 1 min) and then cultured from 3-12 h post irradiation in the study. The morphological alteration was examined by light and fluorescent microscopy respectively. Cell viability and apoptosis were examined by trypan blue staining and flow cytometry with double staining of FITC-labelled Annexin-V/PI. Key proteins responded to irradiation were screened out by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and shotgun proteomic methods with Agilent 1100 HPLC-Chip-MS technology. Representative apoptotic morphological characteristics and increased percentage of apoptotic cells were achieved. Six important proteins (4 up-regulated and 2 down-regulated) were selected and analyzed. It revealed low intensity focused ultrasound could induce apoptosis in HepG2 cells and the US-induced apoptosis was mitochondria-dependent and caspases-dependent. Moreover, mitochondrial membrane permeability transition (MPT) is related to ultrasound induced apoptosis, but VDAC may be not the main MPT channel. Understanding it could help to assist the cancer therapy by regulating the MPT as the target.

  6. Numerical simulation of high intensity focused ultrasound temperature distribution for transcranial brain therapy

    NASA Astrophysics Data System (ADS)

    Zhang, Qian; Wang, Yizhe; Zhou, Wenzheng; Zhang, Ji; Jian, Xiqi

    2017-03-01

    To provide a reference for the HIFU clinical therapeutic planning, the temperature distribution and lesion volume are analyzed by the numerical simulation. The adopted numerical simulation is based on a transcranial ultrasound therapy model, including an 8 annular-element curved phased array transducer. The acoustic pressure and temperature elevation are calculated by using the approximation of Westervelt Formula and the Pennes Heat Transfer Equation. In addition, the Time Reversal theory and eliminating hot spot technique are combined to optimize the temperature distribution. With different input powers and exposure times, the lesion volume is evaluated based on temperature threshold theory. The lesion region could be restored at the expected location by the time reversal theory. Although the lesion volume reduces after eliminating the peak temperature in the skull and more input power and exposure time is required, the injury of normal tissue around skull could be reduced during the HIFU therapy. The prediction of thermal deposition in the skull and the lesion region could provide a reference for clinical therapeutic dose.

  7. Assessments of Sequential Intensity Modulated Radiation Therapy Boost (SqIB) Treatments Using HART

    NASA Astrophysics Data System (ADS)

    Pyakuryal, Anil

    2009-05-01

    A retrospective study was pursued to evaluate the SqIB treatments performed on ten head and neck cancer patients(n=10).Average prescription doses (PDs) of 39 Gy,15Gy and 17.8Gy were delivered consecutively from larger to smaller planning target volumes(ptvs) in three different treatment plans using 6 MV X-ray photon beams from a Linear accelerator (SLA Linac, Elekta) on BID weak on-weak off schedules. These plans were statistically evaluated on basis of plan indices (PIs),dose response of targets and critical structures, and dose tolerance(DT) of various organs utilizing the DVH analysis automated software known as Histogram Analysis in Radiation Therapy-HART(S.Jang et al., 2008, Med Phys 35, p.2812). Mean SqIB PIs were found consistent with the reported values for varying radio-surgical systems.The 95.5%(n=10)of each ptvs and the gross tumor volume also received 95% (n=10)of PDs in treatments. The average volume of ten organs (N=10) affected by each PDs shrank with decreasing size of ptvs in above plans.A largest volume of Oropharynx (79%,n=10,N=10) irradiated at PD, but the largest volume of Larynx (98%, n=10, N=10) was vulnerable to DT of structure (TD50).Thus, we have demonstrated the efficiency and accuracy of HART in the assessment of Linac based plans in radiation therapy treatments of cancer.

  8. [Nutritive provision of children during intensive therapy in the early post-aggressive period].

    PubMed

    Uglitskikh, A K

    2007-01-01

    The purpose of the study conducted at the intensive care units (ICI) of a Tushino children's city hospital (CCH), Moscow, in 2000-2005, was to enhance the efficiency of treatment in children with brain injuries, severe pneumonias, or appendicitis-induced peritonitis in the early postaggression period, by optimizing their feeding. Examination of 224 patients aged 1 month to 15 years, treated at the ICI of the Tushino CCH for brain injuries, severe pneumonias, or appendicitis-induced peritonitis in 2000-2005, indicated that mixed (parenteral and enteral) feeding was more effective in children in the early postaggression period than enteral feeding. Consideration of the size of protein losses and the amount of dietary protein and energy and estimation of nitrogen balance revealed that, by increasing the amount of dietary protein and energy, lowering protein losses, and thus producing positive changes in nitrogen balance, higher blood glucose decrease rates, and in a number of anthropometric and somatometric indices, mixed (parenteral and enteral) feeding is an effective method of nutritive provision in children at an intensive care unit.

  9. High intensity focused ultrasound technology, its scope and applications in therapy and drug delivery.

    PubMed

    Phenix, Christopher Peter; Togtema, Melissa; Pichardo, Samuel; Zehbe, Ingeborg; Curiel, Laura

    2014-01-01

    Ultrasonography is a safe, inexpensive and wide-spread diagnostic tool capable of producing real-time non-invasive images without significant biological effects. However, the propagation of higher energy, intensity and frequency ultrasound waves through living tissues can induce thermal, mechanical and chemical effects useful for a variety of therapeutic applications. With the recent development of clinically approved High Intensity Focused Ultrasound (HIFU) systems, therapeutic ultrasound is now a medical reality. Indeed, HIFU has been used for the thermal ablation of pathological lesions; localized, minimally invasive ultrasound-mediated drug delivery through the transient formation of pores on cell membranes; the temporary disruption of skin and the blood brain barrier; the ultrasound induced break-down of blood clots; and the targeted release of drugs using ultrasound and temperature sensitive drug carriers. This review seeks to engage the pharmaceutical research community by providing an overview on the biological effects of ultrasound as well as highlighting important therapeutic applications, current deficiencies and future directions.

  10. Importance of Radiation Oncologist Experience Among Patients With Head-and-Neck Cancer Treated With Intensity-Modulated Radiation Therapy

    PubMed Central

    Boero, Isabel J.; Paravati, Anthony J.; Xu, Beibei; Cohen, Ezra E.W.; Mell, Loren K.; Le, Quynh-Thu

    2016-01-01

    Purpose Over the past decade, intensity-modulated radiation therapy (IMRT) has replaced conventional radiation techniques in the management of head-and-neck cancers (HNCs). We conducted this population-based study to evaluate the influence of radiation oncologist experience on outcomes in patients with HNC treated with IMRT compared with patients with HNC treated with conventional radiation therapy. Methods We identified radiation providers from Medicare claims of 6,212 Medicare beneficiaries with HNC treated between 2000 and 2009. We analyzed the impact of provider volume on all-cause mortality, HNC mortality, and toxicity end points after treatment with either conventional radiation therapy or IMRT. All analyses were performed by using either multivariable Cox proportional hazards or Fine-Gray regression models controlling for potential confounding variables. Results Among patients treated with conventional radiation, we found no significant relationship between provider volume and patient survival or any toxicity end point. Among patients receiving IMRT, those treated by higher-volume radiation oncologists had improved survival compared with those treated by low-volume providers. The risk of all-cause mortality decreased by 21% for every additional five patients treated per provider per year (hazard ratio [HR], 0.79; 95% CI, 0.67 to 0.94). Patients treated with IMRT by higher-volume providers had decreased HNC-specific mortality (subdistribution HR, 0.68; 95% CI, 0.50 to 0.91) and decreased risk of aspiration pneumonia (subdistribution HR, 0.72; 95% CI, 0.52 to 0.99). Conclusion Patients receiving IMRT for HNC had improved outcomes when treated by higher-volume providers. These findings will better inform patients and providers when making decisions about treatment, and emphasize the critical importance of high-quality radiation therapy for optimal treatment of HNC. PMID:26729432

  11. Testing the Effectiveness of Cognitive Analytic Therapy for Hypersexuality Disorder: An Intensive Time-Series Evaluation.

    PubMed

    Kellett, Stephen; Simmonds-Buckley, Mel; Totterdell, Peter

    2016-07-06

    The evidence base for treatment of hypersexuality disorder (HD) has few studies with appropriate methodological rigor. This study therefore conducted a single case experiment of cognitive analytic therapy (CAT) for HD using an A/B design with extended follow-up. Cruising, pornography usage, masturbation frequency and associated cognitions and emotions were measured daily in a 231-day time series. Following a three-week assessment baseline (A: 21 days), treatment was delivered via outpatient sessions (B: 147 days), with the follow-up period lasting 63 days. Results show that cruising and pornography usage extinguished. The total sexual outlet score no longer met caseness, and the primary nomothetic hypersexuality outcome measure met recovery criteria. Reduced pornography consumption was mediated by reduced obsessionality and greater interpersonal connectivity. The utility of the CAT model for intimacy problems shows promise. Directions for future HD outcome research are also provided.

  12. Laser-driven beam lines for delivering intensity modulated radiation therapy with particle beams

    PubMed Central

    Hofmann, Kerstin M; Schell, Stefan; Wilkens, Jan J

    2012-01-01

    Abstract Laser-accelerated particles are a promising option for radiation therapy of cancer by potentially combining a compact, cost-efficient treatment unit with the physical advantages of charged particle beams. To design such a treatment unit we consider different dose delivery schemes and analyze the necessary devices in the required particle beam line for each case. Furthermore, we point out that laser-driven treatment units may be ideal tools for motion adaptation during radiotherapy. Reasons for this are the potential of a flexible gantry and the time structure of the beam with high particle numbers in ultrashort bunches. One challenge that needs to be addressed is the secondary radiation produced in several beam line elements. (© 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) PMID:22930653

  13. Laser-driven beam lines for delivering intensity modulated radiation therapy with particle beams.

    PubMed

    Hofmann, Kerstin M; Schell, Stefan; Wilkens, Jan J

    2012-11-01

    Laser-accelerated particles are a promising option for radiation therapy of cancer by potentially combining a compact, cost-efficient treatment unit with the physical advantages of charged particle beams. To design such a treatment unit we consider different dose delivery schemes and analyze the necessary devices in the required particle beam line for each case. Furthermore, we point out that laser-driven treatment units may be ideal tools for motion adaptation during radiotherapy. Reasons for this are the potential of a flexible gantry and the time structure of the beam with high particle numbers in ultrashort bunches. One challenge that needs to be addressed is the secondary radiation produced in several beam line elements.

  14. Impact of pharmacist’s interventions on cost of drug therapy in intensive care unit

    PubMed Central

    Saokaew, Surasak; Maphanta, Sirada; Thangsomboon., Pornchanok

    2008-01-01

    Pharmacist participation in patient care team has been shown to reduce incidence of adverse drug events, and overall drug costs. However, impact of pharmacist participation in the multidisciplinary intensive care team on cost saving and cost avoidance has little been studied in Thailand. Objective: To describe the characteristics of the interventions and to determine pharmacist’s interventions led to change in cost saving and cost avoidance in intensive care unit (ICU). Methods: A Prospective, standard care-controlled study design was used to compare cost saving and cost avoidance of patients receiving care from patient care team (including a clinical pharmacist) versus standard care (no pharmacist on team). All patients admitted to the medical intensive care unit 1 and 2 during the same period were included in the study. The outcome measures were overall drug cost and length of ICU stay. Interventions made by the pharmacist in the study group were documented. The analyses of acceptance and cost saving and/or cost avoidance were also performed. Results: A total of 65 patients were admitted to either ICU 1 or 2 during the 5 week-study period. The pharmacist participated in patient care and made total of 127 interventions for the ICU-1 team. Ninety-eight percent of the interventions were accepted and implemented by physicians. The difference of overall drug cost per patient between two groups was 182.01 USD (1,076.37 USD in study group and 1,258.38 USD in control group, p=0.138). The average length of ICU stay for the intervention group and the control group was not significantly different (7.16 days vs. 6.18 days, p=0.995). The 125 accepted interventions were evaluated for cost saving and cost avoidance. Pharmacist’s interventions yielded a total of 1,971.43 USD from drug cost saving and 294.62 USD from adverse drug event cost avoidance. The net cost saved and avoided from pharmacist interventions was 2,266.05 USD. Interventions involving antibiotic use

  15. A new Monte Carlo-based treatment plan optimization approach for intensity modulated radiation therapy.

    PubMed

    Li, Yongbao; Tian, Zhen; Shi, Feng; Song, Ting; Wu, Zhaoxia; Liu, Yaqiang; Jiang, Steve; Jia, Xun

    2015-04-07

    Intensity-modulated radiation treatment (IMRT) plan optimization needs beamlet dose distributions. Pencil-beam or superposition/convolution type algorithms are typically used because of their high computational speed. However, inaccurate beamlet dose distributions may mislead the optimization process and hinder the resulting plan quality. To solve this problem, the Monte Carlo (MC) simulation method has been used to compute all beamlet doses prior to the optimization step. The conventional approach samples the same number of particles from each beamlet. Yet this is not the optimal use of MC in this problem. In fact, there are beamlets that have very small intensities after solving the plan optimization problem. For those beamlets, it may be possible to use fewer particles in dose calculations to increase efficiency. Based on this idea, we have developed a new MC-based IMRT plan optimization framework that iteratively performs MC dose calculation and plan optimization. At each dose calculation step, the particle numbers for beamlets were adjusted based on the beamlet intensities obtained through solving the plan optimization problem in the last iteration step. We modified a GPU-based MC dose engine to allow simultaneous computations of a large number of beamlet doses. To test the accuracy of our modified dose engine, we compared the dose from a broad beam and the summed beamlet doses in this beam in an inhomogeneous phantom. Agreement within 1% for the maximum difference and 0.55% for the average difference was observed. We then validated the proposed MC-based optimization schemes in one lung IMRT case. It was found that the conventional scheme required 10(6) particles from each beamlet to achieve an optimization result that was 3% difference in fluence map and 1% difference in dose from the ground truth. In contrast, the proposed scheme achieved the same level of accuracy with on average 1.2 × 10(5) particles per beamlet. Correspondingly, the computation

  16. [Quality of nursing care in intensive therapy: evaluation through operational auditing].

    PubMed

    Padilha, Elaine Fátima; Matsuda, Laura Misue

    2011-01-01

    This study aimed to evaluate the quality of nursing care of an Adult Intensive Care Unit. Data from fifty in-hospital patients, who stayed in ICU for more than three days, were collected through observation, physical examination and patients' medical-information records analysis, using an Operational Auditing Plan. Care considered of quality were those that obtained positive answer percentage ≥ 70%, as those related to Physical Safety (71%) and Equipment Use (72%). Physical Activity (28%) and Oxygenation/Ventilation (29%) reached the lowest scores. We concluded that is urgent to implement continuing education actions in the service studied, since most care items and sub-items did not present the quality needed.

  17. Clinical Application of High-intensity Focused Ultrasound in Cancer Therapy

    PubMed Central

    Hsiao, Yi-Hsuan; Kuo, Shou-Jen; Tsai, Horng-Der; Chou, Ming-Chih; Yeh, Guang-Perng

    2016-01-01

    The treatment of cancer is an important issue in both developing and developed countries. Clinical use of ultrasound in cancer is not only for the diagnosis but also for the treatment. Focused ultrasound surgery (FUS) is a noninvasive technique. By using the combination of high-intensity focused ultrasound (HIFU) and imaging method, FUS has the potential to ablate tumor lesions precisely. The main mechanisms of HIFU ablation involve mechanical and thermal effects. Recent advances in HIFU have increased its popularity. Some promising results were achieved in managing various malignancies, including pancreas, prostate, liver, kidney, breast and bone. Other applications include brain tumor ablation and disruption of the blood-brain barrier. We aim at briefly outlining the clinical utility of FUS as a noninvasive technique for a variety of types of cancer treatment. PMID:26918034

  18. Anti-Aging and Tissue Regeneration Ability of Policosanol Along with Lipid-Lowering Effect in Hyperlipidemic Zebrafish via Enhancement of High-Density Lipoprotein Functionality

    PubMed Central

    Lee, Eun-Young; Yoo, Jeong-Ah; Lim, So-Mang

    2016-01-01

    Abstract We investigated the tissue regeneration and lipid-lowering effects of policosanol (PCO) by employing a hyperlipidemic zebrafish model. A reconstituted high-density lipoprotein containing policosanol (PCO-rHDL) facilitated greater cell growth and replication with less apoptosis and reactive oxygen species (ROS) production in BV-2 microglial cell lines. From in vivo study, injection of rHDL containing apolipoprotein A-I (ApoA-I) caused 76 ± 4% (p = 0.01) greater tissue regeneration activity than the phosphate-buffered saline (PBS) control, whereas PCO-rHDL caused 94 ± 7% (p = 0.002) increased regeneration. PCO in ethanol (EtOH) showed lower cholesteryl ester transfer protein (CETP) inhibitory ability than did anacetrapib, whereas PCO-rHDL showed higher inhibitory ability than anacetrapib, suggesting a synergistic effect between PCO and rHDL. Following 9 weeks of PCO consumption, the PCO group (0.003% PCO in Tetrabit) showed the highest survivability (80%), whereas normal diet (ND) and high-cholesterol diet (HCD) control groups showed 67% and 70% survival rates, respectively. Supplementation with a HCD resulted in two-fold elevation of CETP activity along with 3- and 2.5-fold increases in serum total cholesterol (TC) and triglycerides (TGs) levels, respectively. Consumption of PCO for 9 weeks resulted in 40 ± 5% (p = 0.01 vs. HCD) and 33 ± 4% (p = 0.02 vs. HCD) reduction of TC and TGs levels, respectively. Serum high-density lipoprotein cholesterol (HDL-C) level increased up to 37 ± 2 mg/dL (p = 0.004), whereas the percentage of HDL-C/TC increased up to 20 ± 2% from 5 ± 1% compared to the HCD control. The serum glucose level was reduced to 47 ± 2% (p = 0.002) compared to the HCD control. Fatty liver change and hepatic inflammation levels were remarkably increased upon HCD consumption and were two-fold higher than that under ND. However, the PCO group showed 58 ± 5% (p = 0.001) and 50

  19. Effects of dietary fats on plasma lipids and lipoproteins: an hypothesis for the lipid-lowering effect of unsaturated fatty acids

    PubMed Central

    Spritz, Norton; Mishkel, Maurice A.

    1969-01-01

    Several aspects of the effects of dietary fat on plasma lipids and lipoproteins were investigated in 12 subjects during the long-term feeding of formulas containing 40% of their calories as either saturated or unsaturated fats. The changes in fatty acid composition of plasma lipids, shown previously to occur after prolonged feedings of a dietary fat, required 10-14 days to be complete and were synchronous with the effect of the fat on plasma lipid concentrations. The change in lipid concentration occurred in low but not in high density lipoproteins. The effects on lipid levels of the low density lipoproteins were found to occur with little or no effect on the concentration of the protein moiety of these lipoproteins; as a result, cholesterol- and phospholipid to protein ratios in low density lipoproteins fell during unsaturated fat feeding. The effects of dietary fat on plasma phospholipids were studied in detail: the relative amounts of phosphatidylcholine, phosphatidylethanolamine, sphingomyelin, and lysophosphatidylcholine were unaffected by the type of dietary fat. However, the molecular species of phosphatidylcholine were markedly affected. More than 90% of the fatty acids at the α-position were saturated during both saturated and unsaturated feedings. In contrast, during unsaturated feedings, linoleate at the β-position outnumbered oleate by approximately 4:1, whereas during saturated feedings these two types of fatty acids were present in nearly equal amounts. This paper also presents the following hypothesis for the lipid-lowering effect of unsaturated dietary fat: since unsaturated fatty acids occupy a greater area than saturated acids, they alter the spatial configuration of the lipids into which they are incorporated; as a result, fewer lipid molecules can be accommodated by the apoprotein of the low-density lipoproteins (LDL), and thus the lipid content of the lipoprotein is lowered. The experimental findings of this study, while not proving this

  20. Genetic variants modify the effect of age on APOE methylation in the Genetics of Lipid Lowering Drugs and Diet Network study

    PubMed Central

    Ma, Yiyi; Smith, Caren E; Lai, Chao-Qiang; Irvin, Marguerite R; Parnell, Laurence D; Lee, Yu-Chi; Pham, Lucia; Aslibekyan, Stella; Claas, Steven A; Tsai, Michael Y; Borecki, Ingrid B; Kabagambe, Edmond K; Berciano, Silvia; Ordovás, José M; Absher, Devin M; Arnett, Donna K

    2015-01-01

    Although apolipoprotein E (APOE) variants are associated with age-related diseases, the underlying mechanism is unknown and DNA methylation may be a potential one. With methylation data, measured by the Infinium Human Methylation 450 array, from 993 participants (age ranging from 18 to 87 years) in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) study, and from Encyclopedia of DNA Elements (ENCODE) consortium, combined with published methylation datasets, we described the methylation pattern of 13 CpG sites within APOE locus, their correlations with gene expression across cell types, and their relationships with age, plasma lipids, and sequence variants. Based on methylation levels and the genetic regions, we categorized the 13 APOE CpG sites into three groups: Group 1 showed hypermethylation (> 50%) and were located in the promoter region, Group 2 exhibited hypomethylation (< 50%) and were located in the first two exons and introns, and Group 3 showed hypermethylation (> 50%) and were located in the exon 4. APOE methylation was negatively correlated with gene expression (minimum r = −0.66, P = 0.004). APOE methylation was significantly associated with age (minimum P = 2.06E-08) and plasma total cholesterol (minimum P = 3.53E-03). Finally, APOE methylation patterns differed across APOE ε variants (minimum P = 3.51E-05) and the promoter variant rs405509 (minimum P = 0.01), which further showed a significant interaction with age (P = 0.03). These findings suggest that methylation may be a potential mechanistic explanation for APOE functions related to aging and call for further molecular mechanistic studies. PMID:25476875

  1. I4, a synthetic anti-diabetes agent, attenuates atherosclerosis through its lipid-lowering, anti-inflammatory and anti-apoptosis properties.

    PubMed

    Ma, Lingman; Qian, Lifen; Ying, Qidi; Zhang, Yan; Zhou, Changlin; Wu, Guanzhong

    2017-01-15

    Here, we investigated whether I4, which was initially developed as a hypoglycemic agent, possesses anti-atherosclerotic activity and attempted to elucidate the probable mechanism of action underlying this activity. ApoE(-/-) mice were fed a Western diet and simultaneously administered I4, glimepiride, or pioglitazone once daily for 12 weeks, and the atherosclerotic vascular lesions, lipid content, and expression levels of LOX-1, ICAM-1, VCAM-1 and Bax/Bcl-2 in mouse aortas were assessed. RAW264.7 macrophage-derived foam cells were obtained via ox-LDL stimulation to investigate the lipid-lowering, anti-atherosclerotic inflammation and anti-apoptotic effect of I4. The data indicated that I4 significantly decreased the lipid accumulation in the circulation and tissue, especially for TG and FFA levels (p < 0.05 vs model group), alleviating the arterial and liver lesions induced by lipotoxicity. Its lipid-reducing effects may due to LOX-1and CD36 expression suppression. I4, at doses of 20 mg/kg and 10 mg/kg, significantly decreased serum IL-6, IL-1β, and TNF-α production and suppressed the expression of p-ERK, p-p38, VCAM-1 and ICAM-1 protein. I4 attenuated atherosclerotic inflammation by blocking NF-κB nuclear translocation, suppressing MAPK/NF-κB signaling pathway and diminishing NF-κB-VCAM-1 promoter region binding. Additionally, I4 suppressed p-p53 and cleaved-caspase-3 expression to inhibit foam cell apoptosis induced by ox-LDL uptake. Overall, I4 exerts potent inhibitory effects on atherosclerosis onset and development.

  2. Comparison of testicular dose delivered by intensity-modulated radiation therapy (IMRT) and volumetric-modulated arc therapy (VMAT) in patients with prostate cancer

    SciTech Connect

    Martin, Jeffrey M.; Handorf, Elizabeth A.; Price, Robert A.; Cherian, George; Buyyounouski, Mark K.; Chen, David Y.; Kutikov, Alexander; Johnson, Matthew E.; Ma, Chung-Ming Charlie; Horwitz, Eric M.

    2015-10-01

    A small decrease in testosterone level has been documented after prostate irradiation, possibly owing to the incidental dose to the testes. Testicular doses from prostate external beam radiation plans with either intensity-modulated radiation therapy (IMRT) or volumetric-modulated arc therapy (VMAT) were calculated to investigate any difference. Testicles were contoured for 16 patients being treated for localized prostate cancer. For each patient, 2 plans were created: 1 with IMRT and 1 with VMAT. No specific attempt was made to reduce testicular dose. Minimum, maximum, and mean doses to the testicles were recorded for each plan. Of the 16 patients, 4 received a total dose of 7800 cGy to the prostate alone, 7 received 8000 cGy to the prostate alone, and 5 received 8000 cGy to the prostate and pelvic lymph nodes. The mean (range) of testicular dose with an IMRT plan was 54.7 cGy (21.1 to 91.9) and 59.0 cGy (25.1 to 93.4) with a VMAT plan. In 12 cases, the mean VMAT dose was higher than the mean IMRT dose, with a mean difference of 4.3 cGy (p = 0.019). There was a small but statistically significant increase in mean testicular dose delivered by VMAT compared with IMRT. Despite this, it unlikely that there is a clinically meaningful difference in testicular doses from either modality.

  3. A dosimetric comparative study: Volumetric modulated arc therapy vs intensity-modulated radiation therapy in the treatment of nasal cavity carcinomas

    SciTech Connect

    Nguyen, Kham; Cummings, David; Lanza, Vincent C.; Morris, Kathleen; Wang, Congjun; Sutton, Jordan; Garcia, John

    2013-10-01

    The purpose of this study was to evaluate the differences between volumetric modulated arc therapy (VMAT) and intensity-modulated radiation therapy (IMRT) in the treatment of nasal cavity carcinomas. The treatment of 10 patients, who had completed IMRT treatment for resected tumors of the nasal cavity, was replanned with the Philips Pinnacle{sup 3} Version 9 treatment-planning system. The IMRT plans used a 9-beam technique whereas the VMAT (known as SmartArc) plans used a 3-arc technique. Both types of plans were optimized using Philips Pinnacle{sup 3} Direct Machine Parameter Optimization algorithm. IMRT and VMAT plans' quality was compared by evaluating the maximum, minimum, and mean doses to the target volumes and organs at risk, monitor units (MUs), and the treatment delivery time. Our results indicate that VMAT is capable of greatly reducing treatment delivery time and MUs compared with IMRT. The reduction of treatment delivery time and MUs can decrease the effects of intrafractional uncertainties that can occur because of patient movement during treatment delivery. VMAT's plans further reduce doses to critical structures that are in close proximity to the target volume.

  4. Dosimetric effects of weight loss or gain during volumetric modulated arc therapy and intensity-modulated radiation therapy for prostate cancer

    SciTech Connect

    Pair, Matthew L.; Du, Weiliang; Rojas, Hector D.; Kanke, James E.; McGuire, Sean E.; Lee, Andrew K.; Kuban, Deborah A.; Kudchadker, Rajat J.

    2013-10-01

    Weight loss or gain during the course of radiation therapy for prostate cancer can alter the planned dose to the target volumes and critical organs. Typically, source-to-surface distance (SSD) measurements are documented by therapists on a weekly basis to ensure that patients' exterior surface and isocenter-to-skin surface distances remain stable. The radiation oncology team then determines whether the patient has undergone a physical change sufficient to require a new treatment plan. The effect of weight change (SSD increase or decrease) on intensity-modulated radiation therapy (IMRT) or volumetric modulated arc therapy (VMAT) dosimetry is not well known, and it is unclear when rescanning or replanning is needed. The purpose of this study was to determine the effects of weight change (SSD increase or decrease) on IMRT or VMAT dose delivery in patients with prostate cancer and to determine the SSD change threshold for replanning. Whether IMRT or VMAT provides better dose stability under weight change conditions was also determined. We generated clinical IMRT and VMAT prostate and seminal vesicle treatment plans for varying SSDs for 10 randomly selected patients with prostate cancer. The differences due to SSD change were quantified by a specific dose change for a specified volume of interest. The target mean dose, decreased or increased by 2.9% per 1-cm SSD decrease or increase in IMRT and by 3.6% in VMAT. If the SSD deviation is more than 1 cm, the radiation oncology team should determine whether to continue treatment without modifications, to adjust monitor units, or to resimulate and replan.

  5. Four-Dimensional Computed Tomography-Based Treatment Planning for Intensity-Modulated Radiation Therapy and Proton Therapy for Distal Esophageal Cancer

    SciTech Connect

    Zhang Xiaodong; Zhao Kuaile; Guerrero, Thomas M.; Mcguire, Sean E.; Yaremko, Brian; Komaki, Ritsuko; Cox, James D.; Hui Zhouguang; Li Yupeng; Newhauser, Wayne D.; Mohan, Radhe; Liao Zhongxing

    2008-09-01

    Purpose: To compare three-dimensional (3D) and four-dimensional (4D) computed tomography (CT)-based treatment plans for proton therapy or intensity-modulated radiation therapy (IMRT) for esophageal cancer in terms of doses to the lung, heart, and spinal cord and variations in target coverage and normal tissue sparing. Methods and Materials: The IMRT and proton plans for 15 patients with distal esophageal cancer were designed from the 3D average CT scans and then recalculated on 10 4D CT data sets. Dosimetric data were compared for tumor coverage and normal tissue sparing. Results: Compared with IMRT, median lung volumes exposed to 5, 10, and 20 Gy and mean lung dose were reduced by 35.6%, 20.5%, 5.8%, and 5.1 Gy for a two-beam proton plan and by 17.4%, 8.4%, 5%, and 2.9 Gy for a three-beam proton plan. The greater lung sparing in the two-beam proton plan was achieved at the expense of less conformity to the target (conformity index [CI], 1.99) and greater irradiation of the heart (heart-V40, 41.8%) compared with the IMRT plan(CI, 1.55, heart-V40, 35.7%) or the three-beam proton plan (CI, 1.46, heart-V40, 27.7%). Target coverage differed by more than 2% between the 3D and 4D plans for patients with substantial diaphragm motion in the three-beam proton and IMRT plans. The difference in spinal cord maximum dose between 3D and 4D plans could exceed 5 Gy for the proton plans partly owing to variations in stomach gas filling. Conclusions: Proton therapy provided significantly better sparing of lung than did IMRT. Diaphragm motion and stomach gas-filling must be considered in evaluating target coverage and cord doses.

  6. Prospective Randomized Phase 2 Trial of Intensity Modulated Radiation Therapy With or Without Oncolytic Adenovirus-Mediated Cytotoxic Gene Therapy in Intermediate-Risk Prostate Cancer

    SciTech Connect

    Freytag, Svend O.; Stricker, Hans; Lu, Mei; Elshaikh, Mohamed; Aref, Ibrahim; Pradhan, Deepak; Levin, Kenneth; Kim, Jae Ho; Peabody, James; Siddiqui, Farzan; Barton, Kenneth; Pegg, Jan; Zhang, Yingshu; Cheng, Jingfang; Oja-Tebbe, Nancy; Bourgeois, Renee; Gupta, Nilesh; Lane, Zhaoli; Rodriguez, Ron; DeWeese, Theodore; and others

    2014-06-01

    Purpose: To assess the safety and efficacy of combining oncolytic adenovirus-mediated cytotoxic gene therapy (OAMCGT) with intensity modulated radiation therapy (IMRT) in intermediate-risk prostate cancer. Methods and Materials: Forty-four men with intermediate-risk prostate cancer were randomly assigned to receive either OAMCGT plus IMRT (arm 1; n=21) or IMRT only (arm 2; n=23). The primary phase 2 endpoint was acute (≤90 days) toxicity. Secondary endpoints included quality of life (QOL), prostate biopsy (12-core) positivity at 2 years, freedom from biochemical/clinical failure (FFF), freedom from metastases, and survival. Results: Men in arm 1 exhibited a greater incidence of low-grade influenza-like symptoms, transaminitis, neutropenia, and thrombocytopenia than men in arm 2. There were no significant differences in gastrointestinal or genitourinary events or QOL between the 2 arms. Two-year prostate biopsies were obtained from 37 men (84%). Thirty-three percent of men in arm 1 were biopsy-positive versus 58% in arm 2, representing a 42% relative reduction in biopsy positivity in the investigational arm (P=.13). There was a 60% relative reduction in biopsy positivity in the investigational arm in men with <50% positive biopsy cores at baseline (P=.07). To date, 1 patient in each arm exhibited biochemical failure (arm 1, 4.8%; arm 2, 4.3%). No patient developed hormone-refractory or metastatic disease, and none has died from prostate cancer. Conclusions: Combining OAMCGT with IMRT does not exacerbate the most common side effects of prostate radiation therapy and suggests a clinically meaningful reduction in positive biopsy results at 2 years in men with intermediate-risk prostate cancer.

  7. SU-E-T-764: Track Repeating Algorithm for Proton Therapy Applied to Intensity Modulated Proton Therapy for Head-And-Neck Patients

    SciTech Connect

    Yepes, P; Mirkovic, D; Mohan, R

    2015-06-15

    Purpose: To determine the suitability of fast Monte Carlo techniques for dose calculation in particle therapy based on track-repeating algorithm for Intensity Modulated Proton Therapy, IMPT. The application of this technique will make possible detailed retrospective studies of large cohort of patients, which may lead to a better determination of Relative Biological Effects from the analysis of patient data. Methods: A cohort of six head-and-neck patients treated at the University of Texas MD Anderson Cancer Center with IMPT were utilized. The dose distributions were calculated with the standard Treatment Plan System, TPS, MCNPX, GEANT4 and FDC, a fast track-repeating algorithm for proton therapy for the verification and the patient plans. FDC is based on a GEANT4 database of trajectories of protons in a water. The obtained dose distributions were compared to each other utilizing the g-index criteria for 3mm-3% and 2mm-2%, for the maximum spatial and dose differences. The γ-index was calculated for voxels with a dose at least 10% of the maximum delivered dose. Dose Volume Histograms are also calculated for the various dose distributions. Results: Good agreement between GEANT4 and FDC is found with less than 1% of the voxels with a γ-index larger than 1 for 2 mm-2%. The agreement between MCNPX with FDC is within the requirements of clinical standards, even though it is slightly worse than the comparison with GEANT4.The comparison with TPS yielded larger differences, what is also to be expected because pencil beam algorithm do not always performed well in highly inhomogeneous areas like head-and-neck. Conclusion: The good agreement between a track-repeating algorithm and a full Monte Carlo for a large cohort of patients and a challenging, site like head-and-neck, opens the path to systematic and detailed studies of large cohorts, which may yield better understanding of biological effects.

  8. Two-Year and Lifetime Cost-Effectiveness of Intensity Modulated Radiation Therapy Versus 3-Dimensional Conformal Radiation Therapy for Head-and-Neck Cancer

    SciTech Connect

    Kohler, Racquel E.; Sheets, Nathan C.; Wheeler, Stephanie B.; Nutting, Chris; Hall, Emma; Chera, Bhishamjit S.

    2013-11-15

    Purpose: To assess the cost-effectiveness of intensity modulated radiation therapy (IMRT) versus 3-dimensional conformal radiation therapy (3D-CRT) in the treatment of head-and neck-cancer (HNC). Methods and Materials: We used a Markov model to simulate radiation therapy-induced xerostomia and dysphagia in a hypothetical cohort of 65-year-old HNC patients. Model input parameters were derived from PARSPORT (CRUK/03/005) patient-level trial data and quality-of-life and Medicare cost data from published literature. We calculated average incremental cost-effectiveness ratios (ICERs) from the US health care perspective as cost per quality-adjusted life-year (QALY) gained and compared our ICERs with current cost-effectiveness standards whereby treatment comparators less than $50,000 per QALY gained are considered cost-effective. Results: In the first 2 years after initial treatment, IMRT is not cost-effective compared with 3D-CRT, given an average ICER of $101,100 per QALY gained. However, over 15 years (remaining lifetime on the basis of average life expectancy of a 65-year-old), IMRT is more cost-effective at $34,523 per QALY gained. Conclusion: Although HNC patients receiving IMRT will likely experience reduced xerostomia and dysphagia symptoms, the small quality-of-life benefit associated with IMRT is not cost-effective in the short term but may be cost-effective over a patient's lifetime, assuming benefits persist over time and patients are healthy and likely to live for a sustained period. Additional data quantifying the long-term benefits of IMRT, however, are needed.

  9. A fast algorithm for solving a linear feasibility problem with application to Intensity-Modulated Radiation Therapy.

    PubMed

    Herman, Gabor T; Chen, Wei

    2008-03-01

    The goal of Intensity-Modulated Radiation Therapy (IMRT) is to deliver sufficient doses to tumors to kill them, but without causing irreparable damage to critical organs. This requirement can be formulated as a linear feasibility problem. The sequential (i.e., iteratively treating the constraints one after another in a cyclic fashion) algorithm ART3 is known to find a solution to such problems in a finite number of steps, provided that the feasible region is full dimensional. We present a faster algorithm called ART3+. The idea of ART3+ is to avoid unnecessary checks on constraints that are likely to be satisfied. The superior performance of the new algorithm is demonstrated by mathematical experiments inspired by the IMRT application.

  10. An unusual source for an outbreak of methicillin-resistant Staphylococcus aureus on an intensive therapy unit.

    PubMed

    Cotterill, S; Evans, R; Fraise, A P

    1996-03-01

    During a four-month period, six patients on an intensive therapy unit became colonized or infected with methicillin-resistant Staphylococcus aureus (MRSA). Four of these patients were colonized by the Epidemic MRSA strain 15 (EMRSA 15). The outbreak was characterized by the fact that all four of these patients were nursed in the same bed on the unit before acquisition of the organism. Investigation of the outbreak led the authors to believe that the source of the MRSA may have been the exhaust ducting of the adjacent isolation room ventilation system which allowed the organisms to enter the unit via a partially open window positioned above that particular bed. The cycle was broken once the ventilation system was repaired and the window above the bed was properly sealed.

  11. WE-G-12A-01: High Intensity Focused Ultrasound Surgery and Therapy

    SciTech Connect

    Farahani, K; O'Neill, B

    2014-06-15

    More and more emphasis is being made on alternatives to invasive surgery and the use of ionizing radiation to treat various diseases including cancer. Novel screening, diagnosis, treatment and monitoring of response to treatment are also hot areas of research and new clinical technologies. Ultrasound(US) has gained traction in all of the aforementioned areas of focus. Especially with recent advances in the use of ultrasound to noninvasively treat various diseases/organ systems. This session will focus on covering MR-guided focused ultrasound and the state of the art clinical applications, and the second speaker will survey the more cutting edge technologies e.g. Focused Ultrasound (FUS) mediated drug delivery, principles of cavitation and US guided FUS. Learning Objectives: Fundamental physics and physical limitations of US interaction with tissue and nanoparticles The alteration of tissue transport using focused ultrasound US control of nanoparticle drug carriers for targeted release The basic principles of MRI-guided focused ultrasound (MRgFUS) surgery and therapy the current state of the art clinical applications of MRgFUS requirements for quality assurance and treatment planning.

  12. Low-Intensity Shock Wave Therapy and Its Application to Erectile Dysfunction

    PubMed Central

    Lei, Hongen; Liu, Jing; Li, Huixi; Wang, Lin; Xu, Yongde; Tian, Wenjie; Lin, Guiting

    2013-01-01

    Although phosphodiesterase type 5 inhibitors (PDE5Is) are a revolution in the treatment of erectile dysfunction (ED) and have been marketed since 1998, they cannot restore pathological changes in the penis. Low-energy shock wave therapy (LESWT) has been developed for treating ED, and clinical studies have shown that LESWT has the potential to affect PDE5I non-responders with ED with few adverse effects. Animal studies have shown that LESWT significantly improves penile hemodynamics and restores pathological changes in the penis of diabetic ED animal models. Although the mechanisms remain to be investigated, recent studies have reported that LESWT could partially restore corpus cavernosum fibromuscular pathological changes, endothelial dysfunction, and peripheral neuropathy. LESWT could be a novel modality for treating ED, and particularly PDE5I non-responders with organic ED, in the near future. However, further extensive evidence-based basic and clinical studies are needed. This review intends to summarize the scientific background underlying the effect of LESWT on ED. PMID:24459653

  13. TU-EF-304-07: Monte Carlo-Based Inverse Treatment Plan Optimization for Intensity Modulated Proton Therapy

    SciTech Connect

    Li, Y; Tian, Z; Jiang, S; Jia, X; Song, T; Wu, Z; Liu, Y

    2015-06-15

    Purpose: Intensity-modulated proton therapy (IMPT) is increasingly used in proton therapy. For IMPT optimization, Monte Carlo (MC) is desired for spots dose calculations because of its high accuracy, especially in cases with a high level of heterogeneity. It is also preferred in biological optimization problems due to the capability of computing quantities related to biological effects. However, MC simulation is typically too slow to be used for this purpose. Although GPU-based MC engines have become available, the achieved efficiency is still not ideal. The purpose of this work is to develop a new optimization scheme to include GPU-based MC into IMPT. Methods: A conventional approach using MC in IMPT simply calls the MC dose engine repeatedly for each spot dose calculations. However, this is not the optimal approach, because of the unnecessary computations on some spots that turned out to have very small weights after solving the optimization problem. GPU-memory writing conflict occurring at a small beam size also reduces computational efficiency. To solve these problems, we developed a new framework that iteratively performs MC dose calculations and plan optimizations. At each dose calculation step, the particles were sampled from different spots altogether with Metropolis algorithm, such that the particle number is proportional to the latest optimized spot intensity. Simultaneously transporting particles from multiple spots also mitigated the memory writing conflict problem. Results: We have validated the proposed MC-based optimization schemes in one prostate case. The total computation time of our method was ∼5–6 min on one NVIDIA GPU card, including both spot dose calculation and plan optimization, whereas a conventional method naively using the same GPU-based MC engine were ∼3 times slower. Conclusion: A fast GPU-based MC dose calculation method along with a novel optimization workflow is developed. The high efficiency makes it attractive for clinical

  14. A Phase 1 Study of Everolimus + Weekly Cisplatin + Intensity Modulated Radiation Therapy in Head-and-Neck Cancer

    SciTech Connect

    Fury, Matthew G.; Lee, Nancy Y.; Sherman, Eric; Ho, Alan L.; Rao, Shyam; Heguy, Adriana; Shen, Ronglai; Korte, Susan; Lisa, Donna; Ganly, Ian; Patel, Snehal; Wong, Richard J.; Shaha, Ashok; Shah, Jatin; Haque, Sofia; Katabi, Nora; Pfister, David G.

    2013-11-01

    Purpose: Elevated expression of eukaryotic protein synthesis initiation factor 4E (eIF4E) in histologically cancer-free margins of resected head and neck squamous cell carcinomas (HNSCCs) is mediated by mammalian target of rapamycin complex 1 (mTORC1) and has been associated with increased risk of disease recurrence. Preclinically, inhibition of mTORC1 with everolimus sensitizes cancer cells to cisplatin and radiation. Methods and Materials: This was single-institution phase 1 study to establish the maximum tolerated dose of daily everolimus given with fixed dose cisplatin (30 mg/m{sup 2} weekly × 6) and concurrent intensity modulated radiation therapy for patients with locally and/or regionally advanced head-and-neck cancer. The study had a standard 3 + 3 dose-escalation design. Results: Tumor primary sites were oral cavity (4), salivary gland (4), oropharynx (2), nasopharynx (1), scalp (1), and neck node with occult primary (1). In 4 of 4 cases in which resected HNSCC surgical pathology specimens were available for immunohistochemistry, elevated expression of eIF4E was observed in the cancer-free margins. The most common grade ≥3 treatment-related adverse event was lymphopenia (92%), and dose-limiting toxicities (DLTs) were mucositis (n=2) and failure to thrive (n=1). With a median follow up of 19.4 months, 2 patients have experienced recurrent disease. The maximum tolerated dose was everolimus 5 mg/day. Conclusions: Head-and-neck cancer patients tolerated everolimus at therapeutic doses (5 mg/day) given with weekly cisplatin and intensity modulated radiation therapy. The regimen merits further evaluation, especially among patients who are status post resection of HNSCCs that harbor mTORC1-mediated activation of eIF4E in histologically negative surgical margins.

  15. Intensity modulated radiation therapy versus three-dimensional conformal radiation therapy for the treatment of high grade glioma: a dosimetric comparison.

    PubMed

    MacDonald, Shannon M; Ahmad, Salahuddin; Kachris, Stefanos; Vogds, Betty J; DeRouen, Melissa; Gittleman, Alicia E; DeWyngaert, Keith; Vlachaki, Maria T

    2007-04-19

    The present study compared the dosimetry of intensity-modulated radiation therapy (IMRT) and three-dimensional conformal radiation therapy (3D-CRT) techniques in patients treated for high-grade glioma. A total of 20 patients underwent computed tomography treatment planning in conjunction with magnetic resonance imaging fusion. Prescription dose and normal-tissue constraints were identical for the 3D-CRT and IMRT plans. The prescribed dose was 59.4 Gy delivered at 1.8 Gy per fraction using 4-10 MV photons. Normal-tissue dose constraints were 50-54 Gy for the optic chiasm and nerves, and 55-60 Gy for the brainstem. The IMRT plan yielded superior target coverage as compared with the 3D-CRT plan. Specifically, minimum and mean planning target volume cone down doses were 54.52 Gy and 61.74 Gy for IMRT and 50.56 Gy and 60.06 Gy for 3D-CRT (p < or = 0.01). The IMRT plan reduced the percent volume of brainstem receiving a dose greater than 45 Gy by 31% (p = 0.004) and the percent volume of brain receiving a dose greater than 18 Gy, 24 Gy, and 45 Gy by 10% (p = 0.059), 14% (p = 0.015), and 40% (p < or = 0.0001) respectively. With IMRT, the percent volume of optic chiasm receiving more than 45 Gy was also reduced by 30.40% (p = 0.047). As compared with 3D-CRT, IMRT significantly increased the tumor control probability (p < or = 0.005) and lowered the normal-tissue complication probability for brain and brainstem (p < 0.033). Intensity-modulated radiation therapy improved target coverage and reduced radiation dose to the brain, brainstem, and optic chiasm. With the availability of new cancer imaging tools and more effective systemic agents, IMRT may be used to intensify tumor doses while minimizing toxicity, therefore potentially improving outcomes in patients with high-grade glioma.

  16. Escalated median dose for pituitary macroadenomas using intensity-modulated radiation therapy

    SciTech Connect

    Robinson, D.; Murray, B.; Underwood, L.; Halls, S.; Roa, W

    2004-03-31

    Three-dimensional conformal radiotherapy (3D CRT) has become an established treatment for pituitary macroadenomas. This study is an investigation into the possible dosimetric advantages of intensity-modulated radiotherapy for such critically located tumors. Three consecutive patients with pituitary macroadenoma previously treated with 3D CRT were replanned with inverse-planned IMRT using Helax-TMS (V.6.0, Helax AB, Uppsala, Sweden. Fusion of computed tomography (CT) with postoperative magnetic resonance imaging (MRI) was performed within the planning system to define the gross tumor volume (GTV), planning target volume (PTV), and normal structures including the optic chiasm. Dose-volume histograms (DVHs) for the 3D CRT plans were then compared with those of the corresponding prospective IMRT plans. Both techniques maintained critical structure doses below tolerance levels while maintaining a minimum dose of 45 Gy to 100% of the PTV. While IMRT plans deliver consistently more heterogeneous dose distributions to the PTV, the median PTV dose is elevated in the IMRT plans compared with the 3D CRT plans. For critically located tumors like these pituitary macroadenomas, IMRT allows escalation of the median dose to the tumor without an accompanying loss in critical structure sparing or creating unacceptable cold spots within the PTV.

  17. Low-intensity pulsed ultrasound therapy: a potential strategy to stimulate tendon-bone junction healing.

    PubMed

    Ying, Zhi-min; Lin, Tiao; Yan, Shi-gui

    2012-12-01

    Incorporation of a tendon graft within the bone tunnel represents a challenging clinical problem. Successful anterior cruciate ligament (ACL) reconstruction requires solid healing of the tendon graft in the bone tunnel. Enhancement of graft healing to bone is important to facilitate early aggressive rehabilitation and a rapid return to pre-injury activity levels. No convenient, effective or inexpensive procedures exist to enhance tendon-bone (T-B) healing after surgery. Low-intensity pulsed ultrasound (LIPUS) improves local blood perfusion and angiogenesis, stimulates cartilage maturation, enhances differentiation and proliferation of osteoblasts, and motivates osteogenic differentiation of mesenchymal stem cells (MSCs), and therefore, appears to be a potential non-invasive tool for T-B healing in early stage of rehabilitation of ACL reconstruction. It is conceivable that LIPUS could be used to stimulate T-B tunnel healing in the home, with the aim of accelerating rehabilitation and an earlier return to normal activities in the near future. The purpose of this review is to demonstrate how LIPUS stimulates T-B healing at the cellular and molecular levels, describe studies in animal models, and provide a future direction for research.

  18. Low-intensity pulsed ultrasound therapy: a potential strategy to stimulate tendon-bone junction healing*

    PubMed Central

    Ying, Zhi-min; Lin, Tiao; Yan, Shi-gui

    2012-01-01

    Incorporation of a tendon graft within the bone tunnel represents a challenging clinical problem. Successful anterior cruciate ligament (ACL) reconstruction requires solid healing of the tendon graft in the bone tunnel. Enhancement of graft healing to bone is important to facilitate early aggressive rehabilitation and a rapid return to pre-injury activity levels. No convenient, effective or inexpensive procedures exist to enhance tendon-bone (T-B) healing after surgery. Low-intensity pulsed ultrasound (LIPUS) improves local blood perfusion and angiogenesis, stimulates cartilage maturation, enhances differentiation and proliferation of osteoblasts, and motivates osteogenic differentiation of mesenchymal stem cells (MSCs), and therefore, appears to be a potential non-invasive tool for T-B healing in early stage of rehabilitation of ACL reconstruction. It is conceivable that LIPUS could be used to stimulate T-B tunnel healing in the home, with the aim of accelerating rehabilitation and an earlier return to normal activities in the near future. The purpose of this review is to demonstrate how LIPUS stimulates T-B healing at the cellular and molecular levels, describe studies in animal models, and provide a future direction for research. PMID:23225850

  19. [Effects of an intensive therapy program for behaviorally disordered mentally handicapped patients on staff personnel in residential care].

    PubMed

    Elbing, U; Rohmann, U H

    1994-03-01

    This study evaluates the effects of an intensive therapy program designed for mentally handicapped persons with severely disturbed or autistic behavior on their staff personal which had an active role in the program. The staff members rated their professional competence, quality of interaction with the client, team culture and work satisfaction before and after being engaged in the program, with additional ratings of their personal aims at the beginning of the program. Three sets of data were obtained with the program being conducted three times in a row. The testings of the related as well as the independent samples show differentiated program effects. The main effect is an increase of the professional competence and quality of interaction, especially by the qualified staff members. Trainees put emphasis on the development of their personal relationship with the client. The results are discussed in terms of the impact of learning processes specific to the roles of the staff members and motivational factors on learning and therapy outcome, along with institutional conditions influencing successful learning. Thus the program facilitates the professional and interpersonal learning process of staff members in a specific way with success as well as with limitations.

  20. Evaluation of engraftment and immunological tolerance after reduced intensity conditioning in a rhesus hematopoietic stem cell gene therapy model.

    PubMed

    Uchida, N; Weitzel, R P; Evans, M E; Green, R; Bonifacino, A C; Krouse, A E; Metzger, M E; Hsieh, M M; Donahue, R E; Tisdale, J F

    2014-02-01

    Reduced intensity conditioning (RIC) is desirable for hematopoietic stem cell (HSC) targeted gene therapy; however, RIC may be insufficient for efficient engraftment and inducing immunological tolerance to transgenes. We previously established long-term gene marking in our rhesus macaque autologous HSC transplantation model following 10 Gy total body irradiation (TBI). In this study, we evaluated RIC transplantation with 4 Gy TBI in two rhesus macaques that received equal parts of CD34(+) cells transduced with green fluorescent protein (GFP)-expressing lentiviral vector and empty vector not expressing transgenes. In both animals, equivalently low gene marking between GFP and empty vectors was observed 6 months post-transplantation, even with efficient transduction of CD34(+) cells in vitro. Autologous lymphocyte infusion with GFP marking resulted in an increase of gene marking in lymphocytes in a control animal with GFP tolerance, but not in the two RIC-transplanted animals. In vitro assays revealed strong cellular and humoral immune responses to GFP protein in the two RIC-transplanted animals, but this was not observed in controls. In summary, 4 Gy TBI is insufficient to permit engraftment of genetically modified HSCs and induce immunological tolerance to transgenes. Our findings should help in the design of conditioning regimens in gene therapy trials.

  1. Restoring one's language edifice: A case study of long-term effects of intensive aphasia therapy employing cognitive modifiability strategies.

    PubMed

    Anaki, David; Goldenberg, Rosalind; Devisheim, Haim; Rosenfelder, Diana; Falik, Lou; Harif, Idit

    2016-06-23

    NG is an architect who suffered a left occipital-parietal hemorrhage cerebral vascular accident (CVA) in 2000, resulting in aphasia of Wernicke and conduction types. He was characterized with fluent paraphasic speech, decreased repetition, and impaired object naming. Comprehension was relatively preserved but reading and writing were severely compromised, as well as his auditory working memory. Despite a grim prognosis he underwent intensive aphasia therapy, lasting from 2001 to 2010, at the Center for Cognitive Rehabilitation of the Brain Injured at the Feuerstein Institute. The tailored-made interventions, applied in NG's therapy, were based upon the implementation of the principles of the Structural Mediated Learning Experience (MLE) and the Feuerstein Instrumental Enrichment (FIE) Program, to optimize his rehabilitation. As a result NG improved in most of his impaired linguistic capacities, attested by the results of neuropsychological and linguistic assessments performed throughout the years. More importantly, he was able to manage again his daily functions at a high level, and to resume his occupational role as an architect, a role which he holds to this day.

  2. Comparison of intensity-modulated radiotherapy with three-dimensional conformal radiation therapy planning for glioblastoma multiforme

    SciTech Connect

    Chan, Maria F.; Schupak, Karen; Burman, Chandra; Chui, C.-S.; Ling, C. Clifton

    2003-12-31

    This study was designed to assess the feasibility and potential benefit of using intensity-modulated radiotherapy (IMRT) planning for patients newly diagnosed with glioblastoma multiforme (GBM). Five consecutive patients with confirmed histopathologically GBM were entered into the study. These patients were planned and treated with 3-dimensional conformal radiation therapy (3DCRT) using our standard plan of 3 noncoplanar wedged fields. They were then replanned with the IMRT method that included a simultaneous boost to the gross tumor volume (GTV). The dose distributions and dose-volume histograms (DHVs) for the planning treatment volume (PTV), GTV, and the relevant critical structures, as obtained with 3DCRT and IMRT, respectively, were compared. In both the 3DCRT and IMRT plans, 59.4 Gy was delivered to the GTV plus a margin of 2.5 cm, with doses to critical structures below the tolerance threshold. However, with the simultaneous boost in IMRT, a higher tumor dose of {approx}70 Gy could be delivered to the GTV, while still maintaining the uninvolved brain at dose levels of the 3DCRT technique. In addition, our experience indicated that IMRT planning is less labor intensive and time consuming than 3DCRT planning. Our study shows that IMRT planning is feasible and efficient for radiotherapy of GBM. In particular, IMRT can deliver a simultaneous boost to the GTV while better sparing the normal brain and other critical structures.

  3. Limited Advantages of Intensity-Modulated Radiotherapy Over 3D Conformal Radiation Therapy in the Adjuvant Management of Gastric Cancer

    SciTech Connect

    Alani, Shlomo; Soyfer, Viacheslav; Strauss, Natan; Schifter, Dan; Corn, Benjamin W.

    2009-06-01

    Purpose: Although chemoradiotherapy was considered the standard adjuvant treatment for gastric cancer, a recent Phase III trial (Medical Research Council Adjuvant Gastric Infusional Chemotherapy [MAGIC]) did not include radiotherapy in the randomization scheme because it was considered expendable. Given radiotherapy's potential, efforts needed to be made to optimize its use for treating gastric cancer. We assessed whether intensity-modulated radiotherapy (IMRT) could improve upon our published results in patients treated with three-dimensional (3D) conformal therapy. Methods and Materials: Fourteen patients with adenocarcinoma of the stomach were treated with adjuvant chemoradiotherapy using a noncoplanar four-field arrangement. Subsequently, a nine-field IMRT plan was designed using a CMS Xio IMRT version 4.3.3 module. Two IMRT beam arrangements were evaluated: beam arrangement 1 consisted of gantry angles of 0 deg., 53 deg., 107 deg., 158 deg., 204 deg., 255 deg., and 306 deg.. Beam arrangement 2 consisted of gantry angles of 30 deg., 90 deg., 315 deg., and 345 deg.; a gantry angle of 320 deg./couch, 30 deg.; and a gantry angle of 35{sup o}/couch, 312{sup o}. Both the target volume coverage and the dose deposition in adjacent critical organs were assessed in the plans. Dose-volume histograms were generated for the clinical target volume, kidneys, spine, and liver. Results: Comparison of the clinical target volumes revealed satisfactory coverage by the 95% isodose envelope using either IMRT or 3D conformal therapy. However, IMRT was only marginally better than 3D conformal therapy at protecting the spine and kidneys from radiation. Conclusions: IMRT confers only a marginal benefit in the adjuvant treatment of gastric cancer and should be used only in the small subset of patients with risk factors for kidney disease or those with a preexisting nephropathy.

  4. Breast Intensity-Modulated Radiation Therapy Reduces Time Spent With Acute Dermatitis for Women of All Breast Sizes During Radiation

    SciTech Connect

    Freedman, Gary M. Li Tianyu; Nicolaou, Nicos; Chen Yan; Ma, Charlie C.-M.; Anderson, Penny R.

    2009-07-01

    Purpose: To study the time spent with radiation-induced dermatitis during a course of radiation therapy for breast cancer in women treated with conventional or intensity-modulated radiation therapy (IMRT). Methods and Materials: The study population consisted of 804 consecutive women with early-stage breast cancer treated with breast-conserving surgery and radiation from 2001 to 2006. All patients were treated with whole-breast radiation followed by a boost to the tumor bed. Whole-breast radiation consisted of conventional wedged photon tangents (n = 405) earlier in the study period and mostly of photon IMRT (n = 399) in later years. All patients had acute dermatitis graded each week of treatment. Results: The breakdown of the cases of maximum acute dermatitis by grade was as follows: 3%, Grade 0; 34%, Grade 1; 61%, Grade 2; and 2%, Grade 3. The breakdown of cases of maximum toxicity by technique was as follows: 48%, Grade 0/1, and 52%, Grade 2/3, for IMRT; and 25%, Grade 0/1, and 75%, Grade 2/3, for conventional radiation therapy (p < 0.0001). The IMRT patients spent 82% of weeks during treatment with Grade 0/1 dermatitis and 18% with Grade 2/3 dermatitis, compared with 29% and 71% of patients, respectively, treated with conventional radiation (p < 0.0001). Furthermore, the time spent with Grade 2/3 toxicity was decreased in IMRT patients with small (p = 0.0015), medium (p < 0.0001), and large (p < 0.0001) breasts. Conclusions: Breast IMRT is associated with a significant decrease both in the time spent during treatment with Grade 2/3 dermatitis and in the maximum severity of dermatitis compared with that associated with conventional radiation, regardless of breast size.

  5. A Study of the Influence of Low Intensity Laser Therapy on Painful Temporomandibular Disorder Patients

    PubMed Central

    Sattayut, S.; Bradley, P.

    2012-01-01

    A double-blind clinical trial was conducted on 30 female Temporomandibular Disorders (TMD) patients who had pain as a chief complaint. The patients were randomly allocated into three groups based on Low Intensity Laser (LILT) regimes namely 820 nm Gallium Aluminium Arsenide (GaAlAs) laser at energy densities of 21.4J/cm2, 107 J/cm2 and placebo laser. Each patient had three LILT treatments in a week. The pressure pain threshold (PPT) of trigger points in masticatory muscles, unassisted maximum mouth opening without pain (MOSP) and symptom severity index (SSI) were recorded as baseline data and monitored after every treatment. Jaw kinesiology, electromyography (EMG) and pain rating index from McGill pain questionnaire were also recorded as baseline and final results. The analysis of covariance and further analysis showed that the higher energy density laser group had significant increases in PPT and EMG amplitude recorded from voluntary clenching (cEMG) compared with the placebo group at P values 0.0001 and 0.022 respectively. A significantly greater number of patients recovered from myofascial pain and TMJ arthralgia as assessed clinically in the higher energy group compared with the placebo (P value = 0.02 and 0.006 respectively). There was no statistically significant difference in the other parameters of assessment among the groups at a P value 0.05. At a period of 2 to 4 weeks review after LILT, there was an average 52% reduction of pain as assessed by SSI. PMID:24511188

  6. Radiation efficacy and biological risk from whole-breast irradiation via intensity modulated radiation therapy (IMRT)

    NASA Astrophysics Data System (ADS)

    Desantis, David M.

    Radiotherapy is an established modality for women with breast cancer. During the delivery of external beam radiation to the breast, leakage, scattered x-rays from the patient and the linear accelerator also expose healthy tissues and organs outside of the breast, thereby increasing the patient's whole-body dose, which then increases the chance of developing a secondary, radiation-induced cancer. Generally, there are three IntensityModulated Radiotherapy (IMRT) delivery techniques from a conventional linear accelerator; forward planned (FMLC), inverse planned 'sliding window' (DMLC), and inverse planned 'step-and-shoot' (SMLC). The goal of this study was to determine which of these three techniques delivers an optimal dose to the breast with the least chance of causing a fatal, secondary, radiation-induced cancer. A conventional, non-IMRT, 'Wedge' plan also was compared. Computerized Tomography (CT) data sets for both a large and small sized patient were used in this study. With Varian's Eclipse AAA algorithm, the organ doses specified in the revised ICRP 60 publication were used to calculate the whole-body dose. Also, an anthropomorphic phantom was irradiated with thermoluminescent dosimeters (TLD) at each organ site for measured doses. The risk coefficient from the Biological Effects of Ionizing Radiation (BEIR) VII report of 4.69 x 10-2 deaths per Gy was used to convert whole-body dose to risk of a fatal, secondary, radiation-induced cancer. The FMLC IMRT delivered superior tumor coverage over the 3D conventional plan and the inverse DMLC or SMLC treatment plans delivered clinically equivalent tumor coverage. However, the FMLC plan had the least likelihood of inadvertently causing a fatal, secondary, radiation-induced cancer compared to the inverse DMLC, SMLC, and Wedge plans.

  7. Dosimetric effects of endorectal balloons on intensity-modulated radiation therapy plans for prostate cancer

    NASA Astrophysics Data System (ADS)

    Kim, Jae-Sung; Chung, Jin-Beom; Kim, In-Ah; Eom, Keun-Yong

    2013-10-01

    We used an endorectal balloon (ERB) for prostate immobilization during intensity-modulated radiotherapy (IMRT) for prostate cancer treatment. To investigate the dosimetric effects of ERB-filling materials, we changed the ERB Hounsfield unit (HU) from 0 to 1000 HU in 200-HU intervals to simulate the various ERB fillings; 0 HU simulated a water-filled ERB, and 1000 HU simulated the densest material-filled ERB. Dosimetric data (coverage, homogeneity, conformity, maximal dose, and typical volume dose) for the tumor and the organs at risk (OARs) were evaluated in prostate IMRT treatment plans with 6-MV and 15-MV beams. The tumor coverage appeared to differ by approximately 1%, except for the clinical target volume (CTV) V100% and the planning target volume (PTV) V100%. The largest difference for the various ERB fillings was observed in the PTV V100%. In spite of increasing HU, the prostate IMRT plans at both energies had relatively low dosimetric effects on the PTV and the CTV. However, the maximal and the typical volume doses (D25%, D30%, and D50%) to the rectal wall and the bladder increased with increasing HU. For an air-filled ERB, the maximal doses to the rectal wall and the monitor units were lower than the corresponding values for the water-filled and the densest material-filled ERBs. An air-filled ERB spared the rectal wall because of its dosimetric effect. Thus, we conclude that the use of an air-filled ERB provides a dosimetric benefit to the rectal wall without a loss of target coverage and is an effective option for prostate IMRT treatment.

  8. Severe alcohol withdrawal syndrome: Evolution of care and impact of adjunctive therapy on course and complications of 171 intensive care unit patients.

    PubMed

    Puscas, Mircea; Hasoon, Mohammed; Eechevarria, Carlos; Cooper, Tracy; Tamura, Leslie; Chebbo, Ahmad; W Carlson, Richard

    2016-01-01

    This single site retrospective observational study assessed the evolution of sedation therapy for severe alcohol withdrawal syndrome in the intensive care unit. Patient records for 2 intervals were reviewed: Interval 1, which included 87 intensive care unit patients admitted January 2005 through September 2007, for whom benzodiazedpine monotherapy was utilized; and Interval 2, January 2010 through December 2010, for whom 54 of 84 (64.3%) intensive care unit patients, including all those intubated, received adjunctive agents, including dexmedetomidine or propofol. Clinical management was similar for both intervals, as well as prevalence of alcohol withdrawal syndrome versus total adult hospital admissions and comorbid conditions. Overall, respiratory failure (53 versus 39%), seizures (36 versus 18%), and pneumonia (51 versus 38%) were less frequent during Interval 2 (all p < .05), with lower benzodiazedpine basal dose requirements for those given adjunctive therapy. However, if instances of pneumonia or respiratory failure related to seizures prior to intensive care unit admission are excluded, the prevalence of these complications was similar (p = ns) for Interval 1 and Interval 2. Intensive care unit and hospital length of stay were not altered by adjunctive therapy, which was typically employed for more severely affected patients. High intensity sedation with adjunctive drugs led to few cardiovascular adverse events and may have facilitated management, but did not alter intensive care unit course of severe alcohol withdrawal syndrome.

  9. SU-E-J-274: Responses of Medulloblastoma Cells to Radiation Dosimetric Parameters in Intensity-Modulated Radiation Therapy

    SciTech Connect

    Park, J; Park, J; Rogalla, S; Contag, C; Woo, D; Lee, D; Park, H; Suh, T

    2015-06-15

    Purpose: To evaluate radiation responses of the medulloblastoma cell line Daoy in intensity-modulated radiation therapy (IMRT), quantitative variations to variable radiation dosimetic parameters were tracked by bioluminescent images (BLIs). Methods: The luciferase and green fluorescent protein positive Daoy cells were cultured on dishes. The medulloblastoma cells irradiated to different dose rate, interval of fractionated doses, field margin and misalignment, and dose uniformity in IMRT were monitored using bioluminescent images. The cultured cells were placed into a dedicated acrylic phantom to deliver intensity-modulated fluences and calculate accurate predicted dose distribution. The radiation with dose rate from 0.5 Gy/min to 15 Gy/min was irradiated by adjusting monitor unit per minute and source-to-surface distances. The intervals of fractionated dose delivery were changed considering the repair time of double strand breaks (DSB) revealed by straining of gamma-H2AX.The effect of non-uniform doses on the cells were visualized by registering dose distributions and BLIs. The viability according to dosimetric parameters was correlated with bioluminescent intensities for cross-check of radiation responses. Results: The DSB and cell responses due to the first fractionated dose delivery significantly affected final tumor control rather than other parameters. The missing tumor volumes due to the smaller field margin than the tumor periphery or field misalignment caused relapse of cell responses on BLIs. The dose rate and gradient had effect on initial responses but could not bring out the distinguishable killing effect on cancer cells. Conclusion: Visualized and quantified bioluminescent images were useful to correlate the dose distributions with spatial radiation effects on cells. This would derive the effective combination of dose delivery parameters and fractionation. Radiation responses in particular IMRT configuration could be reflected to image based-dose re-optimization.

  10. Effects of Respiratory Motion on Passively Scattered Proton Therapy Versus Intensity Modulated Photon Therapy for Stage III Lung Cancer: Are Proton Plans More Sensitive to Breathing Motion?

    SciTech Connect

    Matney, Jason; Park, Peter C.; Bluett, Jaques; Chen, Yi Pei; Liu, Wei; Court, Laurence E.; Liao, Zhongxing; Li, Heng; Mohan, Radhe

    2013-11-01

    Purpose: To quantify and compare the effects of respiratory motion on paired passively scattered proton therapy (PSPT) and intensity modulated photon therapy (IMRT) plans; and to establish the relationship between the magnitude of tumor motion and the respiratory-induced dose difference for both modalities. Methods and Materials: In a randomized clinical trial comparing PSPT and IMRT, radiation therapy plans have been designed according to common planning protocols. Four-dimensional (4D) dose was computed for PSPT and IMRT plans for a patient cohort with respiratory motion ranging from 3 to 17 mm. Image registration and dose accumulation were performed using grayscale-based deformable image registration algorithms. The dose–volume histogram (DVH) differences (4D-3D [3D = 3-dimensional]) were compared for PSPT and IMRT. Changes in 4D-3D dose were correlated to the magnitude of tumor respiratory motion. Results: The average 4D-3D dose to 95% of the internal target volume was close to zero, with 19 of 20 patients within 1% of prescribed dose for both modalities. The mean 4D-3D between the 2 modalities was not statistically significant (P<.05) for all dose–volume histogram indices (mean ± SD) except the lung V5 (PSPT: +1.1% ± 0.9%; IMRT: +0.4% ± 1.2%) and maximum cord dose (PSPT: +1.5 ± 2.9 Gy; IMRT: 0.0 ± 0.2 Gy). Changes in 4D-3D dose were correlated to tumor motion for only 2 indices: dose to 95% planning target volume, and heterogeneity index. Conclusions: With our current margin formalisms, target coverage was maintained in the presence of respiratory motion up to 17 mm for both PSPT and IMRT. Only 2 of 11 4D-3D indices (lung V5 and spinal cord maximum) were statistically distinguishable between PSPT and IMRT, contrary to the notion that proton therapy will be more susceptible to respiratory motion. Because of the lack of strong correlations with 4D-3D dose differences in PSPT and IMRT, the extent of tumor motion was not an adequate predictor of potential

  11. Four-Week Course of Radiation for Breast Cancer Using Hypofractionated Intensity Modulated Radiation Therapy With an Incorporated Boost

    SciTech Connect

    Freedman, Gary M. . E-mail: Gary.Freedman@FCCC.edu; Anderson, Penny R.; Goldstein, Lori J.; Ma Changming; Li Jinsheng; Swaby, Ramona F.; Litwin, Samuel; Watkins-Bruner, Deborah; Sigurdson, Elin R.; Morrow, Monica

    2007-06-01

    Purpose: Standard radiation for early breast cancer requires daily treatment for 6 to 7 weeks. This is an inconvenience to many women, and for some a barrier for breast conservation. We present the acute toxicity of a 4-week course of hypofractionated radiation. Methods and Materials: A total of 75 patients completed radiation on a Phase II trial approved by the hospital institutional review board. Eligibility criteria were broad to include any patient normally eligible for standard radiation: age {>=}18 years, invasive or in situ cancer, American Joint Committee on Cancer Stage 0 to II, breast-conserving surgery, and any systemic therapy not given concurrently. The median age was 52 years (range, 31-81 years). Of the patients, 15% had ductal carcinoma in situ, 67% T1, and 19% T2; 71% were N0, 17% N1, and 12% NX. Chemotherapy was given before radiation in 44%. Using photon intensity-modulated radiation therapy and incorporated electron beam boost, the whole breast received 45 Gy and the lumpectomy bed 56 Gy in 20 treatments over 4 weeks. Results: The maximum acute skin toxicity by the end of treatment was Grade 0 in 9 patients (12%), Grade 1 in 49 (65%) and Grade 2 in 17 (23%). There was no Grade 3 or higher skin toxicity. After radiation, all Grade 2 toxicity had resolved by 6 weeks. Hematologic toxicity was Grade 0 in most patients except for Grade 1 neutropenia in 2 patients, and Grade 1 anemia in 11 patients. There were no significant differences in baseline vs. 6-week posttreatment patient-reported or physician-reported cosmetic scores. Conclusions: This 4-week course of postoperative radiation using intensity-modulated radiation therapy is feasible and is associated with acceptable acute skin toxicity and quality of life. Long-term follow-up data are needed. This radiation schedule may represent an alternative both to longer 6-week to 7-week standard whole-breast radiation and more radically shortened 1-week, partial-breast treatment schedules.

  12. The hypoalgesic effects of low-intensity infrared laser therapy: a study on 555 cases

    NASA Astrophysics Data System (ADS)

    Tam, Giuseppe

    2004-09-01

    Objective: Low energy lasers are widely used to treat a variety of musculoskeletal conditions. The aim of this clinical study is to determine the action of the IR diode laser 904 nm pulsed on pain reduction therapy. Summary Background Data: With respect to pain, has been shown the Low power density laser increases the endorphin synthesis in the dorsal posterior horn of the spinal cord stopping the production of bradykinin and serotonin. Besides laser causes local vasodilatation of the capillaries and an improved circulation of drainage liquids in interstitial space causing an analgesic effect. Additionally, laser interferes in the cytochines (TNF-α, interleukin-1 and interleukin-6) that drive inflammation in the arthritis and are secreted from CD4 e T cells. Methods: Treatment was carried out on 555 cases and 525 patients (322 women and 203 men) in the period between 1987 and 2002. The patients, whose age ranged from 25 to 70, with a mean age of 45 years, were suffering from rheumatic, degenerative and traumatic pathologies. The majority of the patients had been seen by orthopaedists and rheumatologists and had undergone x-ray, ultrasound scanning, Tac, RM examination. All patients had received drug-based treatment and/or physiotherapy with poor results. Two thirds were experiencing acute symptomatic pain, while the others presented a chronic pathology with recurrent crises. We used a pulsed IR diode laser, GaAs 904 nm, maximum power 60 W, frequency impulse 1300 Hz, pulsed duration 200 nanoseconds; peak power per pulse 27W; maximal energy density: 9J/cm2; total number of Joules per treatment session: 10-75J/cm2, chronic 12-90J/cm2. Average number of applications: 12; maximum number of applications: 20. Results: In the evaluation of the results the following parameters have been considered: disappearance of spontaneous and induced pain (Likert scale, Rolland Morris disability scale, dynamometer). The pathologies treated were osteoarthritis in general, epicondylitis

  13. Serodiagnostic markers for the prediction of the outcome of intensive phase tuberculosis therapy.

    PubMed

    Baumann, Ralf; Kaempfer, Susanne; Chegou, Novel N; Nene, Nonhlanhla F; Veenstra, Hanne; Spallek, Ralf; Bolliger, Chris T; Lukey, Pauline T; van Helden, Paul D; Singh, Mahavir; Walzl, Gerhard

    2013-03-01

    Treatment failure and relapse may affect many tuberculosis (TB) patients who undergo standard anti-TB therapy. Several independent studies suggested unsuccessful sputum culture conversion at month 2 of treatment (slow response) as risk factor for treatment failure and relapse. However, earlier than month 2 identification of patients with a high risk for poor treatment outcome would offer significant clinical trial and individual patient care benefits. The sensitivity and specificity of serological IgG and IgA responses against four recombinant mycobacterial antigens (ABC transporter PstS3, secreted l-alanine dehydrogenase, culture filtrate protein Tpx and 6 kDa early secretory antigenic target esxa (ESAT-6)) were evaluated separately in a blinded fashion in 21 smear-positive pulmonary TB patient sera taken at diagnosis before commencement of directly observed anti-TB treatment short course comprising 13 slow responder and eight fast responder subjects. We observed a general pattern of higher antibody levels in sera of slow responders. Most pronounced were high levels of anti-alanine dehydrogenase IgG, anti-Tpx IgG, anti-ESAT-6 IgG and anti-ESAT-6 IgA antibodies at diagnosis being associated with slow response with 100% specificity each and 46.2, 53.8, 53.8 or 53.8% sensitivity, respectively, when compared to fast response (P = 0.020, 0.021, 0.040 and 0.011, respectively). Discriminant analysis showed that the combined use of anti-Tpx IgG and anti-ESAT-6 IgA antibody titers before treatment predicted slow responders with 90.5% accuracy. These preliminary results suggest that combinations of serodiagnostic markers measured prior to initiation of treatment may be suitable for the prediction of early treatment response. This approach holds promise and requires further evaluation for its utility in the prediction of treatment failure and relapse, the evaluation of new TB therapeutics, as well as in the care of individual patients.

  14. [Evaluation of an intensive therapy program for treatment of severe behavioral disorders in mentally handicapped patients with autistic or psychotic behavior].

    PubMed

    Elbing, U; Rohmann, U H

    1993-09-01

    The development of severely disturbed and socially accepted behavior in mentally handicapped persons with autistic or psychotic symptoms is documented before, during and after an intensive therapy program conducted in a residential institution for mentally handicapped persons. Seven single case studies were made as long term observation with a duration between 18 and 33 weeks, mostly with a multiple baseline design. One or two follow ups with at least four weeks length were conducted in six out of seven cases up to four years after the end of the intensive therapy. The main results show (1) the decrease of disturbed behavior and the increase of socially accepted behavior during the therapy program, and (2) the significant reduction of the disturbed behavior patterns taking place during the baseline phase before the beginning of the therapy in all cases but one. The results are discussed under the aspects of a possible explanation for the findings and their impact on the discussion about psychotherapy research.

  15. A novel software and conceptual design of the hardware platform for intensity modulated radiation therapy

    SciTech Connect

    Nguyen, Dan; Ruan, Dan; O’Connor, Daniel; Woods, Kaley; Low, Daniel A.; Sheng, Ke; Boucher, Salime

    2016-02-15

    Purpose: To deliver high quality intensity modulated radiotherapy (IMRT) using a novel generalized sparse orthogonal collimators (SOCs), the authors introduce a novel direct aperture optimization (DAO) approach based on discrete rectangular representation. Methods: A total of seven patients—two glioblastoma multiforme, three head & neck (including one with three prescription doses), and two lung—were included. 20 noncoplanar beams were selected using a column generation and pricing optimization method. The SOC is a generalized conventional orthogonal collimators with N leaves in each collimator bank, where N = 1, 2, or 4. SOC degenerates to conventional jaws when N = 1. For SOC-based IMRT, rectangular aperture optimization (RAO) was performed to optimize the fluence maps using rectangular representation, producing fluence maps that can be directly converted into a set of deliverable rectangular apertures. In order to optimize the dose distribution and minimize the number of apertures used, the overall objective was formulated to incorporate an L2 penalty reflecting the difference between the prescription and the projected doses, and an L1 sparsity regularization term to encourage a low number of nonzero rectangular basis coefficients. The optimization problem was solved using the Chambolle–Pock algorithm, a first-order primal–dual algorithm. Performance of RAO was compared to conventional two-step IMRT optimization including fluence map optimization and direct stratification for multileaf collimator (MLC) segmentation (DMS) using the same number of segments. For the RAO plans, segment travel time for SOC delivery was evaluated for the N = 1, N = 2, and N = 4 SOC designs to characterize the improvement in delivery efficiency as a function of N. Results: Comparable PTV dose homogeneity and coverage were observed between the RAO and the DMS plans. The RAO plans were slightly superior to the DMS plans in sparing critical structures. On average, the maximum and

  16. A novel software and conceptual design of the hardware platform for intensity modulated radiation therapy

    PubMed Central

    Nguyen, Dan; Ruan, Dan; O’Connor, Daniel; Woods, Kaley; Low, Daniel A.; Boucher, Salime; Sheng, Ke

    2016-01-01

    Purpose: To deliver high quality intensity modulated radiotherapy (IMRT) using a novel generalized sparse orthogonal collimators (SOCs), the authors introduce a novel direct aperture optimization (DAO) approach based on discrete rectangular representation. Methods: A total of seven patients—two glioblastoma multiforme, three head & neck (including one with three prescription doses), and two lung—were included. 20 noncoplanar beams were selected using a column generation and pricing optimization method. The SOC is a generalized conventional orthogonal collimators with N leaves in each collimator bank, where N = 1, 2, or 4. SOC degenerates to conventional jaws when N = 1. For SOC-based IMRT, rectangular aperture optimization (RAO) was performed to optimize the fluence maps using rectangular representation, producing fluence maps that can be directly converted into a set of deliverable rectangular apertures. In order to optimize the dose distribution and minimize the number of apertures used, the overall objective was formulated to incorporate an L2 penalty reflecting the difference between the prescription and the projected doses, and an L1 sparsity regularization term to encourage a low number of nonzero rectangular basis coefficients. The optimization problem was solved using the Chambolle–Pock algorithm, a first-order primal–dual algorithm. Performance of RAO was compared to conventional two-step IMRT optimization including fluence map optimization and direct stratification for multileaf collimator (MLC) segmentation (DMS) using the same number of segments. For the RAO plans, segment travel time for SOC delivery was evaluated for the N = 1, N = 2, and N = 4 SOC designs to characterize the improvement in delivery efficiency as a function of N. Results: Comparable PTV dose homogeneity and coverage were observed between the RAO and the DMS plans. The RAO plans were slightly superior to the DMS plans in sparing critical structures. On average, the maximum and

  17. Should Antihypertensive Treatment Recommendations Differ in Patients With and Without Coronary Heart Disease? (From the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial [ALLHAT])

    PubMed Central

    Alderman, Michael H.; Davis, Barry R.; Piller, Linda B.; Ford, Charles E.; Baraniuk, M. Sarah; Pressel, Sara L.; Assadi, Mahshid A.; Einhorn, Paula T.; Haywood, L. Julian; Ilamathi, Ekambaram; Oparil, Suzanne; Retta, Tamrat M.

    2015-01-01

    Thiazide-type diuretics have been recommended for initial treatment of hypertension in most patients, but should this recommendation differ for patients with and without coronary heart disease (CHD)? The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) was a randomized, double-blind hypertension treatment trial in 42,418 participants with high risk of combined cardiovascular disease (CVD) (25% with pre-existing CHD). This post-hoc analysis compares long-term major clinical outcomes in those assigned amlodipine (n=9048) or lisinopril (n=9054) with those assigned chlorthalidone (n=15,255), stratified by CHD status. After 4–8 years, randomized treatment was discontinued. Total follow-up (active treatment + passive surveillance using national databases for deaths and hospitalizations) was 8–13 years. For most CVD outcomes, ESRD, and total mortality, there were no differences across randomized treatment arms regardless of baseline CHD status. In-trial rates of CVD were significantly higher for lisinopril compared with chlorthalidone, and rates of heart failure were significantly higher for amlodipine compared with chlorthalidone in those with and without CHD (overall HRs: 1.10, p<0.001 and 1.38, p<0.001, respectively). During extended follow-up, significant outcomes according to CHD status interactions (p=0.012) were noted in amlodipine versus chlorthalidone comparison for CVD and CHD mortality, HR=0.88, p=0.04 and 0.84, p=0.04, respectively, in those with CHD at baseline and 1.06, p=0.15 and 1.08, p=0.17 in those without. The results of the overall increased stroke mortality in lisinopril compared to chlorthalidone (HR=1.2; p=0.03) and hospitalized heart failure in amlodipine compared to chlorthalidone (HR=1.12; p=0.01) during extended follow-up did not differ by baseline CHD status. In conclusion, these results provide no reason to alter our previous recommendation to include a properly dosed diuretic (such as chlorthalidone 12

  18. Should Antihypertensive Treatment Recommendations Differ in Patients With and Without Coronary Heart Disease? (from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial [ALLHAT]).

    PubMed

    Alderman, Michael H; Davis, Barry R; Piller, Linda B; Ford, Charles E; Baraniuk, M Sarah; Pressel, Sara L; Assadi, Mahshid A; Einhorn, Paula T; Haywood, L Julian; Ilamathi, Ekambaram; Oparil, Suzanne; Retta, Tamrat M

    2016-01-01

    Thiazide-type diuretics have been recommended for initial treatment of hypertension in most patients, but should this recommendation differ for patients with and without coronary heart disease (CHD)? The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) was a randomized, double-blind hypertension treatment trial in 42,418 participants with high risk of combined cardiovascular disease (CVD) (25% with preexisting CHD). This post hoc analysis compares long-term major clinical outcomes in those assigned amlodipine (n = 9048) or lisinopril (n = 9,054) with those assigned chlorthalidone (n = 15,255), stratified by CHD status. After 4 to 8 years, randomized treatment was discontinued. Total follow-up (active treatment + passive surveillance using national databases for deaths and hospitalizations) was 8 to 13 years. For most CVD outcomes, end-stage renal disease, and total mortality, there were no differences across randomized treatment arms regardless of baseline CHD status. In-trial rates of CVD were significantly higher for lisinopril compared with chlorthalidone, and rates of heart failure were significantly higher for amlodipine compared with chlorthalidone in those with and without CHD (overall hazard ratios [HRs] 1.10, p <0.001, and 1.38, p <0.001, respectively). During extended follow-up, significant outcomes according to CHD status interactions (p = 0.012) were noted in amlodipine versus chlorthalidone comparison for CVD and CHD mortality (HR 0.88, p = 0.04, and 0.84, p = 0.04, respectively) in those with CHD at baseline (HR 1.06, p = 0.15, and 1.08, p = 0.17) and in those without. The results of the overall increased stroke mortality in lisinopril compared with chlorthalidone (HR 1.2; p = 0.03) and hospitalized heart failure in amlodipine compared with chlorthalidone (HR 1.12; p = 0.01) during extended follow-up did not differ by baseline CHD status. In conclusion, these results provide no reason to alter our previous

  19. Clinical significance of incident hypokalemia and hyperkalemia in treated hypertensive patients in the antihypertensive and lipid-lowering treatment to prevent heart attack trial.

    PubMed

    Alderman, Michael H; Piller, Linda B; Ford, Charles E; Probstfield, Jeffrey L; Oparil, Suzanne; Cushman, William C; Einhorn, Paula T; Franklin, Stanley S; Papademetriou, Vasilios; Ong, Stephen T; Eckfeldt, John H; Furberg, Curt D; Calhoun, David A; Davis, Barry R

    2012-05-01

    Concerns exist that diuretic-induced changes in serum potassium may have adverse effects in hypertensive patients. The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial, a large practice-based clinical trial, made it possible to examine consequences of observed changes in potassium during care in conventional practice settings. Normokalemic participants randomized to chlorthalidone (C) versus amlodipine or lisinopril as a first-step drug were stratified by year-1 potassium. Postyear-1 outcomes among hypokalemics (potassium, <3.5 mmol/L) and hyperkalemics (potassium, >5.4 mmol/L) were compared with normokalemics (potassium, 3.5-5.4 mmol/L). Year-1 hypokalemia incidence was 6.8%; incidence in C (12.9%) differed from amlodipine (2.1%; P<0.001) and lisinopril (1.0%; P<0.01). Hyperkalemia incidence (2.0%) was greater in lisinopril (3.6%) than in C (1.2%; P<0.01) or amlodipine (1.9%; P<0.01). Coronary heart disease occurred in 8.1% with hypokalemia, 8.0% with normokalemia, and 11.1% with hyperkalemia. Overall, mortality was higher in hypokalemics than in normokalemics (Cox hazard ratio, 1.21 [95% CI, 1.02-1.44]) with statistically significant (interaction, P<0.01) disparity in hazard ratios for the 3 treatment arms (hazard ratios, C=1.21, amlodipine=1.60, lisinopril=3.82). Hyperkalemia was associated with increased risk of combined cardiovascular disease (hazard ratio, 1.58 [95% CI, 1.15-2.18]) without significant treatment interactions. In conventional practice settings, the uncommon appearance of hyperkalemia was associated with increased cardiovascular disease risk. Hypokalemia was associated with increased mortality; however, the statistically significant heterogeneity in hazard ratios across treatment groups strongly suggests that the observed increase in mortality is unrelated to the specific effects of C. Thus, for most patients, concerns about potassium levels should not influence the clinician's decision about initiating hypertension

  20. GENOME-WIDE ASSOCIATION STUDY OF TRIGLYCERIDE RESPONSE TO A HIGH-FAT MEAL AMONG PARTICIPANTS OF THE NHLBI GENETICS OF LIPID LOWERING DRUGS AND DIET NETWORK (GOLDN)