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Sample records for intensive insulin therapy

  1. 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...

  2. Intensive insulin therapy to maintain normoglycemia after cardiac surgery.

    PubMed

    Van den Berghe, G

    2011-01-01

    Drugs used in the perioperative period could have an effect on survival as recently pointed out by an international consensus conference on the reduction in mortality in cardiac anesthesia and intensive care. Insulin infusion to achieve a strict glycemic control is the best example of how an ancillary (i.e. non-surgical) drug/technique/strategy might influence survival rates in patients undergoing cardiac surgery. The author of this "expert opinion" presents her insights into the use of insulin in this setting and suggest that based on available evidence based medicine, insulin infusion, titrated to "normoglycemia" is a complex intervention, that not only requires the simple administration of a "drug", the hormone insulin, but also needs tools and skills to accurately measure and control blood glucose to achieve normoglycemia while avoiding hypoglycemia and large glucose fluctuations. PMID:23439402

  3. Effects of changes in basal/total daily insulin ratio in type 2 diabetes patients on intensive insulin therapy including insulin glargine (JUN-LAN Study 6).

    PubMed

    Tamaki, Motoyuki; Shimizu, Tomoaki; Kanazawa, Akio; Fujitani, Yoshio; Watada, Hirotaka; Kawamori, Ryuzo; Hirose, Takahisa

    2008-08-01

    Intensive insulin therapy composed of bolus and basal insulin has been believed as the most powerful recipe for glycemic control of both type 1 and type 2 diabetes. In this study, we investigated the effects of changes in basal/total daily insulin ratio (B/TD ratio) in type 2 diabetes patients on intensive insulin therapy including insulin glargine. The B/TD ratio used in our Japanese patients was about 0.35, and the ratio was increased up to about 0.46+/-0.12 without change of total insulin daily dose. After 24-week-treatment, mean glycated albumin of the patients whose B/TD ratio was increased was significantly lower than those of the patients whose B/TD ratio was not changed. Our results suggest that adequate supplementation of basal insulin may be important for maximum effect of bolus insulin even in Japanese who have serious defect in postprandial rapid insulin secretion.

  4. Effect of patient-selected intensive insulin therapy on quality of life.

    PubMed

    Chantelau, E; Schiffers, T; Schütze, J; Hansen, B

    1997-02-01

    The purpose of the study was to assess quality of life in patients with IDDM in relation to the type of insulin therapy. Two patient cohorts were studied. In cohort A, 77 patients deliberately intensified their traditional insulin injection therapy from up to two daily injections with syringe to multiple daily injections with insulin-pen; in cohort B, 55 patients changed from intensive therapy with pen to insulin pump-treatment (CSII). The therapeutic regimens were changed during a 5-day in-patient treatment and teaching course. The DCCT questionnaire was applied before and up to 6 months after changing of therapy. Treatment satisfaction increased after intensification of insulin therapy in both groups, mainly due to greater flexibility with leisure-time activities, and with the diet. Pump-users reported reduced problems with hypoglycemia (P < 0.02). HbA1c indicating acceptable metabolic control already before the study, remained unchanged. Therapy-associated inconvenience, mainly in association with lifestyle, improved in IDDM patients deliberately intensifying their insulin therapy by pens or pumps (CSII). Pump-treatment, rather than pen-therapy, conferred particular protection from hypoglycaemia.

  5. The future is now: software-guided intensive insulin therapy in the critically ill.

    PubMed

    Rattan, Rishi; Nasraway, Stanley A

    2013-03-01

    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.

  6. 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

  7. Effects of intensive insulin therapy upon pancreatic β cell function in patients newly diagnosed with type II diabetes

    PubMed Central

    Wang, Defeng; Sun, Li; Song, Guangyao; Chen, Shuchun

    2015-01-01

    Objective: This study was designed to evaluate the clinical efficacy of intensive insulin therapy for patients newly diagnosed with type 2 diabetes. Methods: A total of 219 patients newly diagnosed with type 2 diabetes were randomly assigned into insulin group (n = 55), gliclazide group (n = 52), metformin group (n = 55) and pioglitazone group (n = 57). On the basis of diet and physical interventions, patients in the insulin group received intensive insulin therapy. Those in other three groups were given oral intake of medication. All treatment schemes endured for 12 weeks. A variety of indexes including fasting blood-glucose (FPG), FPG at 2 h after diet (FPG 2 h), hemoglobin A1 c (HbAlc), area under the curve (AUC) for insulin (insulin AUC) after glucose load, C-peptide AUC after glucose load (C-peptide AUC), changes in insulin secretion index (Homa-β) and insulin resistance index( Homa-IR) were accurately measured and statistically among different groups. Results: The insulin AUC at 0-30 min, C-peptide AUC at 0-30 min and Homa-β in the insulin group were equally significantly higher compared with those levels in the other three groups. In addition, the level of Homa-IR in the insulin, metformin and pioglitazone groups were all significantly reduced compared with the values prior to respective treatment (all P < 0.05). Conclusion: Compared with oral administration of hypoglycemic drugs, intensive insulin therapy is able to better improve pancreatic β cell function and insulin resistance for newly-diagnosed type 2 diabetes patients. PMID:25785143

  8. Intensive Insulin Therapy in Critically Ill Hospitalized Patients: Making It Safe and Effective

    PubMed Central

    Klonoff, David C

    2011-01-01

    Intensive insulin therapy (IIT) for hyperglycemia in critically ill patients has become a standard practice. Target levels for glycemia have fluctuated since 2000, as evidence initially indicated that tight glycemic control to so-called normoglycemia (80–110 mg/dl) leads to the lowest morbidity and mortality without hypoglycemic complications. Subsequent studies have demonstrated minimal clinical benefit combined with greater hypoglycemic morbidity and mortality with tight glycemic control in this population. The consensus glycemic targets were then liberalized to the mid 100s (mg/dl). Handheld POC blood glucose (BG) monitors have migrated from the outpatient setting to the hospital environment because they save time and money for managing critically ill patients who require IIT. These devices are less accurate than hospital-grade POC blood analyzers or central laboratory analyzers. Three questions must be answered to understand the role of IIT for defined populations of critically ill patients: (1) How safe is IIT, with various glycemic targets, from the risk of hypoglycemia? (2) How tightly must BG be controlled for this approach to be effective? (3) What role does the accuracy of BG measurements play in affecting the safety of this method? For each state of impaired glucose regulation seen in the hospital, such as hyperglycemia, hypoglycemia, or glucose variability, the benefits, risks, and goals of treatment, including IIT, might differ. With improved accuracy of BG monitors, IIT might be rendered even more intensive than at present, because patients will be less likely to receive inadvertent overdosages of insulin. Greater doses of insulin, but with dosing based on more accurate glucose levels, might result in less hypoglycemia, less hyperglycemia, and less glycemic variability. PMID:21722591

  9. [Psychological aspects of remission induced by intensive insulin therapy in type I diabetes. A retrospective study of 44 patients].

    PubMed

    Ziegler, O; Kolopp, M; Kahn, J P; Floquet, B; Goudot, C; Beyel, P; Drouin, P; Debry, G

    1991-01-01

    The psychological consequences of induced remission of type 1 diabetes, have not yet been investigated thoroughly. We studied the psychological status of 44 patients (16 women, 28 men), age 21 years +/- 8 months (mean +/- SD), whose remission lasted 12 +/- 9 months. Patients' psychological reactions were analyzed retrospectively, using a 20 items standardized questionnaire, investigating 3 successive periods: 1) initial intensive insulin therapy; 2) remission; 3) permanent insulin therapy. 8% of the subjects only considered the remission phase useless, whereas 49% expressed a positive appraisal. Hope was predominant feeling, 25% of the patients believing in a completed recovery of diabetes. Perceived therapeutic constraints were, in decreasing order: regimen, way of life's regularity, self monitoring of blood glucose. When starting permanent insulin therapy, opposite answers were given: 49% negative feelings, 33% positive feelings and 18% ambivalent feelings. During this period, insulin injections represented the major therapeutic constraint, followed by self monitoring of blood glucose. To summarize, induced remission does not appear to be psychologically harmful and is considered useful by a large majority of patients. Effective psychological support has to be offered to help those patients to cope with their irrational hopes of healing and to dampen their deception at the end of the remission period. PMID:1752345

  10. Insulin therapy and exercise.

    PubMed

    Kourtoglou, Georgios I

    2011-08-01

    Medical nutrition therapy and physical exercise are the cornerstones of the diabetes management. Patients with type 1 DM always need exogenous insulin administration, recently available in the form of insulin analogs. In type 2 DM, characterized by increased insulin resistance and progressive decline of the beta-cell function, various antidiabetic medications are used. Most of the subjects with type 2 DM will finally need insulin. The main site of insulin action is the skeletal muscle, while the liver is the main site of glucose storage in the form of glycogen. With the modern diabetes therapies it is possible to rapidly reach and maintain normoglycemia in both types of DM but with the cost of higher incidence of hypoglycemia, especially related to exercise. Regular physical exercise causes a lot of beneficial effects in healthy as well as diabetic subjects of all age groups. In type 1 DM physical exercise is a fundamental element for both physical and mental development. In type 2 DM it has a main role in diabetes control. The increased hepatic glucose production and the increased muscular glucose uptake during exercise are closely interrelated in all exercise intensities. In diabetes mellitus there is a disturbed energy substrate use during exercise leading to either hypo- or hyperglycemia. The influence of low or moderate intensity aerobic exercise on diabetes control has been well studied. The inappropriately high insulinemia combined with the low glucose levels can lead to severe hypoglycemia if proper measures are not taken. Prolonged exercise can also predispose to decreased glucose counter regulation. It is better for the type 1 diabetic subject to postpone the exercise session in very high (>300 mg/dl) or very low (<70 mg/dl) BG levels. Every insulin treated subject is recommended to be checked for any existing diabetic complication before the start of every exercise program. Glucose measurement with glucose meters or sometimes with Continuous Glucose

  11. Featured Article: Oxidative stress status and liver tissue defenses in diabetic rats during intensive subcutaneous insulin therapy

    PubMed Central

    Dal, Stéphanie; Jeandidier, Nathalie; Seyfritz, Elodie; Bietiger, William; Péronet, Claude; Moreau, François; Pinget, Michel; Maillard, Elisa

    2015-01-01

    Long-term insulin delivery can reduce blood glucose variability in diabetic patients. In this study, its impact on oxidative stress status, inflammation, and liver injury was investigated. Diabetes was induced in Wistar rats with a single dose of streptozotocin (100 mg/kg). Untreated rats and rats administered Insuplant® (2 UI/200 g/day) through a subcutaneous osmotic pump for one or four weeks were compared with non-diabetic controls. Body weight, fructosamine level, total cholesterol, Insulin Growth Factor-1 (IGF-1) level, lipid peroxidation, and total antioxidant capacity were measured. Hepatic injury was determined through the measurement of glycogen content, reactive oxygen species (ROS) production, and macrophage infiltration. Liver oxidative stress status was evaluated through the measurement of superoxide dismutase (SOD), catalase (CAT), and nicotinamide adenine dinucleotide phosphate-oxidase (NADPH oxidase) expression, and p38 mitogen-activated protein kinase (p38MAPK) activation. Induction of diabetes led to increased plasma oxidative stress and inflammation. Moreover, ROS production and macrophage infiltration increased in addition to SOD, CAT, and NADPH oxidase expression. Intensive insulin therapy improved metabolic control in diabetic animals as seen by a restoration of hepatic glycogen, plasma IGF-1 levels, and a decrease in plasma oxidative stress. However, insulin treatment did not result in a decrease in acute inflammation in diabetic rats as seen by continued ROS production and macrophage infiltration in the liver, and a decrease of p38MAPK activation. These results suggest that the onset of diabetes induces liver oxidative stress and inflammation, and that subcutaneous insulin administration cannot completely reverse these changes. Targeting oxidative stress and/or inflammation in diabetic patients could be an interesting strategy to improve therapeutic options. PMID:26385497

  12. Featured Article: Oxidative stress status and liver tissue defenses in diabetic rats during intensive subcutaneous insulin therapy.

    PubMed

    Dal, Stéphanie; Jeandidier, Nathalie; Seyfritz, Elodie; Bietiger, William; Péronet, Claude; Moreau, François; Pinget, Michel; Maillard, Elisa; Sigrist, Séverine

    2016-01-01

    Long-term insulin delivery can reduce blood glucose variability in diabetic patients. In this study, its impact on oxidative stress status, inflammation, and liver injury was investigated. Diabetes was induced in Wistar rats with a single dose of streptozotocin (100 mg/kg). Untreated rats and rats administered Insuplant® (2 UI/200 g/day) through a subcutaneous osmotic pump for one or four weeks were compared with non-diabetic controls. Body weight, fructosamine level, total cholesterol, Insulin Growth Factor-1 (IGF-1) level, lipid peroxidation, and total antioxidant capacity were measured. Hepatic injury was determined through the measurement of glycogen content, reactive oxygen species (ROS) production, and macrophage infiltration. Liver oxidative stress status was evaluated through the measurement of superoxide dismutase (SOD), catalase (CAT), and nicotinamide adenine dinucleotide phosphate-oxidase (NADPH oxidase) expression, and p38 mitogen-activated protein kinase (p38MAPK) activation. Induction of diabetes led to increased plasma oxidative stress and inflammation. Moreover, ROS production and macrophage infiltration increased in addition to SOD, CAT, and NADPH oxidase expression. Intensive insulin therapy improved metabolic control in diabetic animals as seen by a restoration of hepatic glycogen, plasma IGF-1 levels, and a decrease in plasma oxidative stress. However, insulin treatment did not result in a decrease in acute inflammation in diabetic rats as seen by continued ROS production and macrophage infiltration in the liver, and a decrease of p38MAPK activation. These results suggest that the onset of diabetes induces liver oxidative stress and inflammation, and that subcutaneous insulin administration cannot completely reverse these changes. Targeting oxidative stress and/or inflammation in diabetic patients could be an interesting strategy to improve therapeutic options.

  13. Continuous subcutaneous insulin infusion versus intensive conventional insulin therapy in type I and type II diabetic pregnancy.

    PubMed

    Carta, Q; Meriggi, E; Trossarelli, G F; Catella, G; Dal Molin, V; Menato, G; Gagliardi, L; Massobrio, M; Vitelli, A

    1986-06-01

    Two groups of pregnant diabetic women, fifteen with type I and fourteen with type II diabetes, were randomly assigned either to CSII or to ICT and the subgroups compared with respect to glycaemic control, insulin requirement and perinatal out-come. Ten non-diabetic pregnant women served as controls for the variations in the metabolic parameters considered (24-hour mean blood glucose and glycosylated hemoglobin). Strict glycaemic control was achieved and maintained by both regimens before week 13 in all patients with type I and in 57.1% of patients with type II diabetes. The mean insulin requirements in the type I group increased up to week 34-36 and then stabilized to term in patients receiving CSII and rose progressively to term in those receiving ICT. In the type II group insulin requirements rose up to week 36 in patients receiving CSII and up to week 32 in those receiving ICT, stabilizing thereafter on both regimens. No significant differences in mean insulin requirement at the different stages of gestation were found between the patients receiving CSII and those receiving ICT of either group. Perinatal outcome was satisfactory in both groups, although control of foetal growth was better with ICT than with CSII. CSII is a practical, safe and effective method of maintaining maternal normoglycemia in pregnancy but for the present we cannot consider it superior to ICT in the treatment of pregnant diabetic women.

  14. [Insulin therapy of diabetes].

    PubMed

    Lechleitner, Monika; Roden, Michael; Weitgasser, Raimund; Ludvik, Bernhard; Fasching, Peter; Hoppichler, Friedrich; Kautzky-Willer, Alexandra; Schernthaner, Guntram; Prager, Rudolf; Wascher, Thomas C

    2016-04-01

    Hyperglycemia contributes to morbidity and mortality in patients with diabetes. Thus, reaching treatment targets with regard to control of glycemia is a central goal in the therapy of diabetic patients. The present article represents the recommendations of the Austrian Diabetes Association for the practical use of insulin according to current scientific evidence and clinical studies. PMID:27052221

  15. [Inhaled insulin, new perspective for insulin therapy].

    PubMed

    Radermecker, R P; Sélam, J L

    2005-01-01

    Since the discovery of insulin and its use in diabetes care, patients, physicians and nurses dream of another way of insulin administration than the subcutaneous injections actually used. Different types of insulin administration have been evaluated and, particularly, that using the pulmonary route. The use of this alternative method to deliver insulin may result in improved patient compliance, facilitate intensified therapies and avoid the delay of initiating insulin administration because patient's reluctance. The different insulin pulmonary delivering devices actually studied will be presented. Preliminary data comparing this way of administration and the subcutaneous injection of human regular insulin are good, but sufficient data comparing inhaled insulin with the new short-acting insulin analogues are not yet available. Among various difficulties of the pulmonary insulin delivery, the finding of an effective promoter, capable of increasing the bioavailability of insulin, is a crucial issue. The cost of such insulin administration might also be a problem. Finally, careful studies concerning the safety of this kind of administration, particularly potential long-term pulmonary toxicity, are mandatory. Nevertheless, inhaled insulin is an attractive topic in which most important pharmaceutical companies are currently involved.

  16. Insulin pump therapy in pregnancy.

    PubMed

    Kesavadev, Jothydev

    2016-09-01

    Control of blood glucose during pregnancy is difficult because of wide variations, ongoing hormonal changes and mood swings. The need for multiple injections, pain at the injection site, regular monitoring and skillful handling of the syringes/pen further makes insulin therapy inconvenient. Insulin pump is gaining popularity in pregnancy because it mimics the insulin delivery of a healthy human pancreas. Multiple guidelines have also recommended the use of insulin pump in pregnancy to maintain the glycaemic control. The pump can release small doses of insulin continuously (basal), or a bolus dose close to mealtime to control the spike in blood glucose after a meal and the newer devices can shut down insulin delivery before the occurrence of hypoglycaemia. Pump insulin of choice is rapid acting analogue insulin. This review underscores the role of insulin pump in pregnancy, their usage, advantages and disadvantages in the light of existing literature and clinic experience. PMID:27582150

  17. Adherence to Insulin Therapy.

    PubMed

    Sarbacker, G Blair; Urteaga, Elizabeth M

    2016-08-01

    IN BRIEF Six million people with diabetes use insulin either alone or in combination with an oral medication. Many barriers exist that lead to poor adherence with insulin. However, there is an underwhelming amount of data on interventions to address these barriers and improve insulin adherence. Until pharmacological advancements create easier, more acceptable insulin regimens, it is imperative to involve patients in shared decision-making. PMID:27574371

  18. Insulin therapy in pregnancy.

    PubMed

    Kalra, Sanjay; Jawad, Fatema

    2016-09-01

    Insulin is the mainstay of pharmacotherapy in pregnancy complicated by diabetes. This review covers the various insulin regimes and preparations, explaining how to use them, and decide appropriate doses in pregnancy. It approaches insulin treatment from a patient - centred, as well as physician and obstetrician friendly viewpoint, providing pragmatic guidance for management of diabetes in pregnancy. PMID:27582152

  19. Predictors of sustained drug-free diabetes remission over 48 weeks following short-term intensive insulin therapy in early type 2 diabetes

    PubMed Central

    Kramer, Caroline K; Zinman, Bernard; Choi, Haysook; Retnakaran, Ravi

    2016-01-01

    Objective In early type 2 diabetes (T2DM), short-term intensive insulin therapy (IIT) for 2–4 weeks can decrease insulin resistance, reduce glucagonemia, improve β-cell function, and even induce a remission of diabetes that can last up to 1 year in some patients. However, little is known about the predictors of such a sustained remission. Methods We evaluated data from the placebo arm of a double-blind randomized controlled trial in which patients with early T2DM (≤7 years duration) underwent 4 weeks of IIT (basal detemir, bolus aspart), followed by placebo therapy for 48 weeks (n=25). Participants underwent an oral glucose tolerance test every 12 weeks, enabling serial assessment of insulin sensitivity, α-cell response, and β-cell function. Diabetes remission was defined as A1c<6.5% on no medication for T2DM. Results At 48 weeks post-IIT, 56% of the participants remained in remission. Comparison of remitters to non-remitters revealed no differences in waist, body mass index, insulin sensitivity (Matsuda index), or glucagon profile, either at baseline or over 48 weeks. Compared to non-remitters, the remission group had lower baseline A1c (p=0.006) and better baseline β-cell function (Insulin Secretion-Sensitivity Index-2) (p=0.01) that was then sustained across 48 weeks post-IIT (p=0.006). On logistic regression analyses, however, shorter duration of diabetes supplanted baseline A1c (p=0.24) and β-cell function (p=0.19) as an independent predictor of remission (p=0.04). In particular, diabetes duration <2 years predicted persistence of remission (p=0.006). Conclusions The key determinant of the likelihood of inducing sustained drug-free diabetes remission with short-term IIT is early intervention, particularly within the first 2 years after diagnosis. Trial registration number ClinicalTrials.Gov NCT01270789; Post-results. PMID:27547422

  20. Insulin therapies: Current and future trends at dawn

    PubMed Central

    Yaturu, Subhashini

    2013-01-01

    Insulin is a key player in the control of hyperglycemia for type 1 diabetes patients and selective individuals in patients of type 2 diabetes. Insulin delivery systems that are currently available for the administration of insulin include insulin syringes, insulin infusion pumps, jet injectors and pens. The traditional and most predictable method for the administration of insulin is by subcutaneous injections. The major drawback of current forms of insulin therapy is their invasive nature. To decrease the suffering, the use of supersonic injectors, infusion pumps, sharp needles and pens has been adopted. Such invasive and intensive techniques have spurred the search for alternative, more acceptable methods for administering insulin. Several non-invasive approaches for insulin delivery are being pursued. The newer methods explored include the artificial pancreas with closed-loop system, transdermal insulin, and buccal, oral and pulmonary routes. This review focuses on the new concepts that are being explored for use in future. PMID:23493823

  1. Misadventures in insulin therapy: are you at risk?

    PubMed Central

    Grissinger, Matthew; Lease, Michael

    2003-01-01

    About dollar 1 out of every dollar 7 spent on health care is related to diabetes mellitus, a leading cause of blindness and kidney failure and a strong risk factor for heart disease. Prevalence of the disease has increased by a third among adults in general in the last decade, but intensive therapy has been shown to delay the onset and slow the progression of diabetes-related complications. While insulin therapy remains key in the management of type 1 diabetes, many patients with type 2, or insulin-resistant, diabetes encounter insulin administration errors that compromise the quality of insulin delivery. Insulin errors are a major, but modifiable, barrier to dosing accuracy and optimal diabetes control for many patients. Future trends to combat the problem include increased use of insulin inhalers and smaller doses of rapid- or short-acting insulin to supplement longer-acting injections. PMID:12653373

  2. Misadventures in insulin therapy: are you at risk?

    PubMed

    Grissinger, Matthew; Lease, Michael

    2003-02-01

    About dollar 1 out of every dollar 7 spent on health care is related to diabetes mellitus, a leading cause of blindness and kidney failure and a strong risk factor for heart disease. Prevalence of the disease has increased by a third among adults in general in the last decade, but intensive therapy has been shown to delay the onset and slow the progression of diabetes-related complications. While insulin therapy remains key in the management of type 1 diabetes, many patients with type 2, or insulin-resistant, diabetes encounter insulin administration errors that compromise the quality of insulin delivery. Insulin errors are a major, but modifiable, barrier to dosing accuracy and optimal diabetes control for many patients. Future trends to combat the problem include increased use of insulin inhalers and smaller doses of rapid- or short-acting insulin to supplement longer-acting injections. PMID:12653373

  3. Insulin therapy in children and adolescents with type 1 diabetes.

    PubMed

    Malik, Faisal S; Taplin, Craig E

    2014-04-01

    Treatment of type 1 diabetes mellitus (T1DM) requires lifelong administration of exogenous insulin. The primary goal of treatment of T1DM in children and adolescents is to maintain near-normoglycemia through intensive insulin therapy, avoid acute complications, and prevent long-term microvascular and macrovascular complications, while facilitating as close to a normal life as possible. Effective insulin therapy must, therefore, be provided on the basis of the needs, preferences, and resources of the individual and the family for optimal management of T1DM. To achieve target glycemic control, the best therapeutic option for patients with T1DM is basal-bolus therapy either with multiple daily injections (MDI) or continuous subcutaneous insulin infusion (CSII). Many formulations of insulin are available to help simulate endogenous insulin secretion as closely as possible in an effort to eliminate the symptoms and complications of hyperglycemia, while minimizing the risk of hypoglycemia secondary to therapy. When using MDI, basal insulin requirements are given as an injection of long- or intermediate-acting insulin analogs, while meal-related glucose excursions are controlled with bolus injections of rapid-acting insulin analogs. Alternatively, CSII can be used, which provides a 24-h preselected but adjustable basal rate of rapid-acting insulin, along with patient-activated mealtime bolus doses, eliminating the need for periodic injections. Both MDI treatment and CSII therapy must be supported by comprehensive education that is appropriate for the individual needs of the patient and family before and after initiation. Current therapies still do not match the endogenous insulin profile of pancreatic β-cells, and all still pose risks of suboptimal control, hypoglycemia, and ketosis in children and adolescents. The safety and success of a prescribed insulin regimen is, therefore, dependent on self-monitoring of blood glucose and/or a continuous glucose monitoring system

  4. Intensity modulated proton therapy.

    PubMed

    Kooy, H M; Grassberger, C

    2015-07-01

    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 highest level of

  5. 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

  6. [Intensified insulin therapy and insulin micro-pumps during pregnancy].

    PubMed

    Galuppi, V

    1994-06-01

    Before conception and during pregnancy in diabetic patients, every possible effort should be made in order to obtain a good, if not perfect, metabolic control and to warrant maternal and fetal health. Multiple daily injections are required to achieve a very strict glucose regulation in pregnant patients with insulin-dependent diabetes mellitus. The most usual intensive insulin administration patterns require 3 premeal doses of short-acting insulin and 1 (at bedtime) or 2 (one in the morning and one at bedtime) injections of intermediate or slow-acting insulin. As an alternative choice, insulin pumps allow a continuous subcutaneous infusion with short-acting insulin according to a basal rate which cover the insulin need during the night and between meals. Premeal and presnack surges of insulin are administrated by the patient herself. Home glucose monitoring must be used to adjust insulin doses. Target glucose levels every diabetic pregnant woman should try to achieve are lower than in non-pregnant women: fasting glycaemia should be below 100 mg/dl, 1 hour post-prandial value below 140 mg/dl and 2 hour post-prandial level below 120 mg/dl. The stricter the control and treatment goals are, the more frequently hypoglycaemia may occur. Hypoglycaemia may be harmful especially for patients with severe diabetic complications and may affect the fetus. Therefore, every pregnant diabetic woman should receive individualized treatment and glycaemic goals according to her clinical features, her compliance and her social and cultural background.

  7. Short acting insulin analogues in intensive care unit patients

    PubMed Central

    Bilotta, Federico; Guerra, Carolina; Badenes, Rafael; Lolli, Simona; Rosa, Giovanni

    2014-01-01

    Blood glucose control in intensive care unit (ICU) patients, addressed to actively maintain blood glucose concentration within defined thresholds, is based on two major therapeutic interventions: to supply an adequate calories load and, when necessary, to continuously infuse insulin titrated to patients needs: intensive insulin therapy (IIT). Short acting insulin analogues (SAIA) have been synthesized to improve the chronic treatment of patients with diabetes but, because of the pharmacokinetic characteristics that include shorter on-set and off-set, they can be effectively used also in ICU patients and have the potential to be associated with a more limited risk of inducing episodes of iatrogenic hypoglycemia. Medical therapies carry an intrinsic risk for collateral effects; this can be more harmful in patients with unstable clinical conditions like ICU patients. To minimize these risks, the use of short acting drugs in ICU patients have gained a progressively larger room in ICU and now pharmaceutical companies and researchers design drugs dedicated to this subset of medical practice. In this article we report the rationale of using short acting drugs in ICU patients (i.e., sedation and treatment of arterial hypertension) and we also describe SAIA and their therapeutic use in ICU with the potential to minimize iatrogenic hypoglycemia related to IIT. The pharmacodynamic and pharmachokinetic characteristics of SAIA will be also discussed. PMID:24936244

  8. [Perspectives in the treatment of type 2 diabetes. Role of insulin therapy?].

    PubMed

    Bringer, J; Renard, E; Galtier Dereure, F; Jaffiol, C

    1994-01-01

    Independently of its initial mechanism, Type 2 diabetes associates in various degrees disorders in insulin sensibility and secretion. The dissociated insulin resistance among tissues explains the predictable imperfection of insulin therapy in this disease due to frequent weight increase and the potential risks of insulin on atherogenesis raised on the basis of experimental studies. All diabetic subjects are not equally insulin resistant and do not have the same insulin secretory capacity evaluated in practice by means of the response of insulin or C peptide plasma levels to various secreting agents. Intensity and duration of hyperglycaemia, muscular mass, physical activity and way of life, age, weight and fat patterning, the presence of complications, acceptance, education feasibility and compliance are essential in selecting towards insulin therapy. Meanwhile, as the results of the prospective studies in progress become available, it seems that insulin should be restricted to the smallest useful dosage possible and that weight change should be carefully checked within the weeks following initiation of insulin. The future of insulin therapy in Type 2 diabetes requires (1) better selection of patients showing a demonstrated beneficial effect of insulin, (2) the association of insulin with new molecules capable of reducing its dosage and preventing its deleterious effects, (3) a change in the mode of insulin administration, with an appropriate balance between comfort and efficacy, (4) change in the insulin structure towards analogues or compounds related to insulin but with less perverted effects.

  9. [Estimation of different models of insulin therapy in noninsulin-dependent diabetes mellitus].

    PubMed

    Trznadel-Morawska, I; Małecki, M; Sieradzki, J

    1997-01-01

    The aim of the study was to find out which model of insulin therapy in patients with noninsulin-dependent diabetes mellitus with secondary inefficacy of sulphonylurea is most effective for glycemia normalization, inhibition of late complications, prevention of atherosclerosis and better quality of life. In 27 patients aged 40-70 years with a history of diabetes over 3 years, BMI < 30, treated with maximal doses of Euclamine we applied 4 therapeutic models: 1) intensive insulin therapy (M1), 2) two injections of three insulins (M2), 3) Euclamin 20 mg + intermediate insulin (M3), 4) Euclamine 20 mg + intermediate insulin (M4). The study lasted 3 months whereas education was carried out within the first two weeks. The following parameters were evaluated: beta cell reserve (glibenclamide test), peptide C level, HbA1C concentration, glycemia profile, lipids, creatinine level. Foci of infection were eradicated. It was found out that: 1) all models of insulin therapy, produced near normoglycemia, 2) the model of intensive insulin therapy does not generate hyperinsulinism in face of body weight loss and improved lipid profile, 3) the model of intensive insulin therapy shows long-term efficacy in the absence of effects when assessing fasting glycemia state (HbA1C, Schilchtkrull's index, lipid indices), 4) the model combining Euclamine with intermediate insulin is on intermediate step leading to another form of insulin therapy. PMID:9380804

  10. [Insulin therapy in type 2 diabetes].

    PubMed

    Dores, Jorge

    2013-04-01

    Type 2 diabetes is a growing prevalent disease, usually symptomless, with devastating chronic complications for the individual, family and society. Its progressive nature leads to the dose escalating and the association of different drugs which will rapidly become insufficient to achieve the glycemic goals established individually. Insulin is the most effective drug to control diabetes but there is frequently a silent contract to resist to its implementation between the healthcare team and people with type 2 diabetes. This publication aims to share information about this therapeutic option, eliminating old myths and giving an understandable teaching about all the process of insulin therapy centered on the person with type 2 diabetes. Sharing knowledge with different groups of healthcare professionals regarding the glycemic goals and how to reach them with distinct kinds of available insulins, will allow the release by multiprofessional teams of a homogeneous and non contradictory information to the people with type 2 diabetes. Moreover, a good engagement between physicians and nurse educators in the same team is the cornerstone to the initiation and intensification of insulin therapy. The decision of starting insulin therapy is not the end of the process. The progressive nature of the disease compels to empower the patient to adjust its dose of insulin according to the self monitoring blood glucose data and to realize that the decision of a single therapeutic scheme is not definitive, being adapted upon the clinical condition of the person along the diabetes evolution.

  11. A practical guide to basal and prandial insulin therapy.

    PubMed

    Holman, R R; Turner, R C

    1985-01-01

    Separating basal and meal-related insulin requirements allows a systematic approach to subcutaneous insulin therapy. Simple guidelines for both the doctor and patient can cater for the spectrum of severity of diabetes. A non-insulin-dependent diabetic who, despite dieting, continues to have moderate fasting hyperglycaemia (6-10 mmol/l) may need only a basal insulin supplement, whereas a totally insulin-dependent diabetic usually needs similar amounts of basal and meal-related insulin. The likely insulin requirements of individual diabetics can be predicted, including the increased amounts required by obese patients. The algorithms have been developed using ultralente to provide the basal insulin requirement, but the principles and doses probably apply to other similarly long-acting insulins or an insulin pump. The insulin doses can be easily altered for varying lifestyles, including night work, religious fasts or long distance aeroplane travel, and for temporary disturbances such as operations or intercurrent infections.

  12. Microdialysis based monitoring of subcutaneous interstitial and venous blood glucose in Type 1 diabetic subjects by mid-infrared spectrometry for intensive insulin therapy

    NASA Astrophysics Data System (ADS)

    Heise, H. Michael; Kondepati, Venkata Radhakrishna; Damm, Uwe; Licht, Michael; Feichtner, Franz; Mader, Julia Katharina; Ellmerer, Martin

    2008-02-01

    Implementing strict glycemic control can reduce the risk of serious complications in both diabetic and critically ill patients. For this purpose, many different blood glucose monitoring techniques and insulin infusion strategies have been tested towards the realization of an artificial pancreas under closed loop control. In contrast to competing subcutaneously implanted electrochemical biosensors, microdialysis based systems for sampling body fluids from either the interstitial adipose tissue compartment or from venous blood have been developed, which allow an ex-vivo glucose monitoring by mid-infrared spectrometry. For the first option, a commercially available, subcutaneously inserted CMA 60 microdialysis catheter has been used routinely. The vascular body interface includes a double-lumen venous catheter in combination with whole blood dilution using a heparin solution. The diluted whole blood is transported to a flow-through dialysis cell, where the harvesting of analytes across the microdialysis membrane takes place at high recovery rates. The dialysate is continuously transported to the IR-sensor. Ex-vivo measurements were conducted on type-1 diabetic subjects lasting up to 28 hours. Experiments have shown excellent agreement between the sensor readout and the reference blood glucose concentration values. The simultaneous assessment of dialysis recovery rates renders a reliable quantification of whole blood concentrations of glucose and metabolites (urea, lactate etc) after taking blood dilution into account. Our results from transmission spectrometry indicate, that the developed bed-side device enables reliable long-term glucose monitoring with reagent- and calibration-free operation.

  13. Insulin Therapy for the Management of Hyperglycemia in Hospitalized Patients

    PubMed Central

    McDonnell, Marie E.; Umpierrez, Guillermo E.

    2013-01-01

    It has long been established that hyperglycemia with or without a prior diagnosis of diabetes increases both mortality and disease-specific morbidity in hospitalized patients1–4 and that goal-directed insulin therapy can improve outcomes.5–9 During the past decade, since the widespread institutional adoption of intensified insulin protocols after the publication of a landmark trial,5,10 the pendulum in the inpatient diabetes literature has swung away from achieving intensive glucose control and toward more moderate and individualized glycemic targets.11,12 This change in clinical practice is the result of several factors, including challenges faced by hospitals to coordinate glycemic control across all levels of care,13,14 publication of negative prospective trials,15,16 revised recommendations from professional organizations,17,18 and increasing evidence on the deleterious effect of hypoglycemia.19–22 This article reviews the pathophysiology of hyperglycemia during illness, the mechanisms for increased complications and mortality due to hyperglycemia and hypoglycemia, beneficial mechanistic effects of insulin therapy and provides updated recommendations for the inpatient management of diabetes in the critical care setting and in the general medicine and surgical settings.23,24 PMID:22575413

  14. Intensifying Insulin Therapy in Type 2 Diabetes: Choices & Challenges.

    PubMed

    Kumar, Ajay; Kesavadev, Jothydev; Sethi, Bipin; Jain, Sunil M; Guruprasad, C S; Shah, Siddharth N

    2015-05-01

    Insulin therapy remains the cornerstone of effective diabetes management. Timely intensification of insulin therapy reduces the progression of diabetes and the development of diabetes-related complications. Given that overall hyperglycaemia is a relative contribution of both fasting and postprandial hyperglycaemia, use of basal insulin alone may not achieve optimal glucose control due to its inability to cover postprandial glucose excursions. Intensifying therapy with addition of bolus insulin or switching to premixed insulin is a viable option in patients failing on basal alone therapy. Although the benefits of early insulin treatment are well established, a considerable delay in intensifying insulin therapy in patients with sub-optimal glycaemic control is still observed. Most of the patients and physicians are reluctant to intensify therapy due to the fear of hypoglycaemia, regimen complexity, and increased burden of multiple daily injections. In this context, there is a need for a flexible, alternative intensification option taking into account individual patient considerations to achieve or maintain individual glycaemic targets. An ideal insulin regimen should mimic physiological insulin release while providing optimal glycaemic control with low risk of hypoglycaemia, weight gain and fewer daily injections. The current paper reviews the challenges of insulin intensification in patients with type 2 diabetes mellitus poorly controlled on current treatment regimens. PMID:26548029

  15. [Insulin pump therapy in children, adolescents and adults].

    PubMed

    Stadler, Marietta; Zlamal-Fortunat, Sandra; Schütz-Fuhrmann, Ingrid; Rami-Merhar, Birgit; Fröhlich-Reiterer, Elke; Hofer, Sabine; Mader, Julia; Resl, Michael; Kautzky-Willer, Alexandra; Weitgasser, Raimund; Prager, Rudolf; Bischof, Martin

    2016-04-01

    This position statement is based on the current evidence available on the safety and benefits of continuous subcutaneous insulin pump therapy (CSII) in diabetes with an emphasis on the effects of CSII on glycemic control, hypoglycaemia rates, occurrence of ketoacidosis, quality of life and the use of insulin pump therapy in pregnancy. The current article represents the recommendations of the Austrian Diabetes Association for the clinical praxis of insulin pump treatment in children, adolescents and adults. PMID:27052245

  16. Intraperitoneal insulin therapy for a patient with type 1 diabetes with insulin injection site inflammation

    PubMed Central

    Lee, Siang Ing; Narendran, Parth

    2014-01-01

    A 36-year-old man with type 1 diabetes developed skin inflammation at the site of subcutaneous insulin injection after 10 years of basal bolus subcutaneous insulin therapy. This inflammation led to poor insulin absorption, poorly controlled blood glucose and subsequently to ketoacidosis. The problem persisted despite a trial of continuous subcutaneous insulin infusion. The patient went on to be treated with continuous intraperitoneal insulin infusion. Three months after the procedure, he was achieving good glucose control and was able to resume his normal life, with the only complication being an episode of cellulitis surrounding the port site. PMID:25188930

  17. Continuous insulin therapy versus multiple insulin injections in the management of type 1 diabetes: a longitutinal study

    PubMed Central

    Ribeiro, Maria Estela Bellini; Liberatore, Raphael Del Roio; Custodio, Rodrigo; Martinelli, Carlos Eduardo

    2016-01-01

    Abstract Objective: To compare multiple doses of insulin and continuous insulin infusion therapy as treatment for type 1 diabetes mellitus. Methods: 40 patients with type 1 diabetes mellitus (21 female) with ages between 10 and 20 years (mean=14.2) and mean duration of diabetes of 7 years used multiple doses of insulin for at least 6 months and after that, continuous insulin infusion therapy for at least 6 months. Each one of the patients has used multiple doses of insulin and continuous insulin infusion therapy. For analysis of HbA1c, mean glycated hemoglobin levels (mHbA1c) were obtained during each treatment period (multiple doses of insulin and continuous insulin infusion therapy period). Results: Although mHbA1c levels were lower during continuous insulin infusion therapy the difference was not statistically significant. During multiple doses of insulin, 14.2% had mHbA1c values below 7.5% vs. 35.71% while on continuous insulin infusion therapy; demonstrating better glycemic control with the use of continuous insulin infusion therapy. During multiple doses of insulin, 15–40 patients have severe hypoglycemic events versus 5–40 continuous insulin infusion therapy. No episodes of ketoacidosis events were recorded. Conclusions: This is the first study with this design comparing multiple doses of insulin and continuous insulin infusion therapy in Brazil showing no significant difference in HbA1c; hypoglycemic events were less frequent during continuous insulin infusion therapy than during multiple doses of insulin and the percentage of patients who achieved a HbA1c less than 7.5% was greater during continuous insulin infusion therapy than multiple doses of insulin therapy. PMID:26826879

  18. Determinants of intensive insulin therapeutic regimens in patients with type 1 diabetes: data from a nationwide multicenter survey in Brazil

    PubMed Central

    2014-01-01

    Background To evaluate the determinants of intensive insulin regimens (ITs) in patients with type 1 diabetes (T1D). Methods This multicenter study was conducted between December 2008 and December 2010 in 28 public clinics in 20 Brazilian cities. Data were obtained from 3,591 patients (56.0% female, 57.1% Caucasian). Insulin regimens were classified as follows: group 1, conventional therapy (CT) (intermediate human insulin, one to two injections daily); group 2 (three or more insulin injections of intermediate plus regular human insulin); group 3 (three or more insulin injections of intermediate human insulin plus short-acting insulin analogues); group 4, basal-bolus (one or two insulin injections of long-acting plus short-acting insulin analogues or regular insulin); and group 5, basal-bolus with continuous subcutaneous insulin infusion (CSII). Groups 2 to 5 were considered IT groups. Results We obtained complete data from 2,961 patients. Combined intermediate plus regular human insulin was the most used therapeutic regimen. CSII was used by 37 (1.2%) patients and IT by 2,669 (90.2%) patients. More patients on IT performed self-monitoring of blood glucose and were treated at the tertiary care level compared to CT patients (p < 0.001). The majority of patients from all groups had HbA1c levels above the target. Overweight or obesity was not associated with insulin regimen. Logistic regression analysis showed that economic status, age, ethnicity, and level of care were associated with IT (p < 0.001). Conclusions Given the prevalence of intensive treatment for T1D in Brazil, more effective therapeutic strategies are needed for long term-health benefits. PMID:24920963

  19. Local insulin therapy affects fracture healing in a rat model.

    PubMed

    Park, Andrew G; Paglia, David N; Al-Zube, Loay; Hreha, Jeremy; Vaidya, Swaroopa; Breitbart, Eric; Benevenia, Joseph; O'Connor, J Patrick; Lin, Sheldon S

    2013-05-01

    A significant number of lower extremity fractures result in mal-union necessitating effective treatments to restore ambulation. Prior research in diabetic animal fracture models demonstrated improved healing following local insulin application to the fracture site and indicated that local insulin therapy can aid bone regeneration, at least within an insulin-dependent diabetic animal model. This study tested whether local insulin therapy could accelerate femur fracture repair in normal, non-diabetic rats. High (20 units) and low (10 units) doses of insulin were delivered in a calcium sulfate carrier which provided sustained release of the exogenous insulin for 7 days after fracture. Histomorphometry, radiographic scoring, and torsional mechanical testing were used to measure fracture healing. The fracture calluses from rats treated with high-dose insulin had significantly more cartilage than untreated rats after 7 and 14 days of healing. After 4 weeks of healing, femurs from rats treated with low-dose insulin had significantly higher radiographic scores and mechanical strength (p < 0.05), compared to the no treatment control groups. The results of this study suggest that locally delivered insulin is a potential therapeutic agent for treating bone fractures. Further studies are necessary, such as large animal proof of concepts, prior to the clinical use of insulin for bone fracture treatment.

  20. [Cardiovascular effects of insulin therapy: from pharmacology to clinical trials].

    PubMed

    Mannucci, Edoardo

    2016-03-01

    Insulin has direct effects on vascular walls which, depending on experimental models, can be either predominantly antiatherogenic or proatherogenic. In observational studies, insulin therapy is usually associated with an increase in the incidence of major cardiovascular events. However, this result is probably determined by the effect of confounders. In clinical trials performed in the acute phase of coronary syndromes, the benefits observed with insulin therapy are probably due to the improvement of glycemic control, rather than to direct effects of insulin on the cardiovascular system. In long-term trials for primary or secondary prevention such as UKPDS and ORIGIN insulin has no relevant effects on major cardiovascular events beyond those determined by the improvement of metabolic control. On the other hand, severe hypoglycemia, which is a possible side effect of insulin therapy, is associated with a worse prognosis of cardiovascular disease. The availability of new long-acting insulin analogs, which reduce the incidence of hypoglycemia for similar levels of glycemic control, makes insulin therapy easier and potentially safer for the cardiovascular system.

  1. Insulin gene therapy for type 1 diabetes mellitus.

    PubMed

    Handorf, Andrew M; Sollinger, Hans W; Alam, Tausif

    2015-04-01

    Type 1 diabetes mellitus is an autoimmune disease resulting from the destruction of pancreatic β cells. Current treatments for patients with type 1 diabetes mellitus include daily insulin injections or whole pancreas transplant, each of which are associated with profound drawbacks. Insulin gene therapy, which has shown great efficacy in correcting hyperglycemia in animal models, holds great promise as an alternative strategy to treat type 1 diabetes mellitus in humans. Insulin gene therapy refers to the targeted expression of insulin in non-β cells, with hepatocytes emerging as the primary therapeutic target. In this review, we present an overview of the current state of insulin gene therapy to treat type 1 diabetes mellitus, including the need for an alternative therapy, important features dictating the success of the therapy, and current obstacles preventing the translation of this treatment option to a clinical setting. In so doing, we hope to shed light on insulin gene therapy as a viable option to treat type 1 diabetes mellitus.

  2. Diabetes therapy trials with inhaled insulin.

    PubMed

    Fineberg, Samuel Edwin

    2006-07-01

    Administration of insulin by inhalation was first attempted > 50 years ago. At that time, little was known concerning effective delivery systems and insulin formulations. The recent development of pulmonary delivery systems for the administration of insulin is driven by the reluctance of patients and their providers to initiate insulin earlier in the course of Type 2 diabetes, the desire to reduce the number of daily insulin injections for both Type 1 and 2 patients, and the recent emphasis on intensified glycaemic control including postprandial glycaemic control. The deep lung is a unique mucosal tissue having a surface area of > 100 m2 and is readily accessible both to the external environment and to drug delivery, provided that appropriate conditions are met. There have been four mid- to late-phase pulmonary insulin programmes using modern inhalation devices that will be reported in this paper. The programmes differ in the choice of delivery systems, the formulations of insulin and reported bioavailability, pharmacokinetic and glucodynamic profiles and adverse events. However, all systems successfully deliver insulin to the deep lung and biological effectiveness compares favourably with injected subcutaneous insulins.

  3. Engineering Synthetically Modified Insulin for Glucose-Responsive Diabetes Therapy

    PubMed Central

    Webber, Matthew J.; Anderson, Daniel G.; Langer, Robert

    2016-01-01

    Summary Though a suite of different insulin variants have been used clinically to provide greater control over pharmacokinetics, no clinically used insulin can tune its potency and/or bioavailability in a glucose-dependent manner. In order to improve therapy for diabetic patients, a vision has been the development of autonomous closed-loop approaches. Toward this goal, insulin has been synthetically modified with glucose-sensing groups or groups that can compete with free glucose for binding to glucose-binding proteins and evaluated in pre-clinical models. Specifically, it was demonstrated that site-specific modification of insulin with phenylboronic acid can result in glucose-responsive activity, leading to faster recovery in diabetic mice following a glucose challenge but with less observed hypoglycemia in healthy mice. This strategy, along with several others being pursued, holds promise to improve the fidelity in glycemic control with routine insulin therapy. PMID:27570535

  4. Management of progressive type 2 diabetes: role of insulin therapy

    PubMed Central

    Chemitiganti, Ramachandra Rahul V; Spellman, Craig W

    2009-01-01

    Insulin is an effective treatment for achieving tight glycemic control and improving clinical outcomes in patients with diabetes. While insulin therapy is required from the onset of diagnosis in type 1 disease, its role in type 2 diabetes requires consideration as to when to initiate and advance therapy. In this article, we review a case study that unfolds over 5 years and discuss the therapeutic decision points, initiation and advancement of insulin regimens, and analyze new data regarding the advantages and disadvantages of tight management of glucose levels. PMID:19573240

  5. The Role of Comfort and Discomfort in Insulin Therapy

    PubMed Central

    2012-01-01

    Abstract Despite the recognized importance of optimal insulin therapy, patient adherence to insulin therapy is an ongoing clinical care challenge. Insulin omission continues to be frequent and underestimated and has been correlated with poorer glycemic control and increased rates of diabetes-related complications. Insulin users consistently indentify multiple factors that contribute to insulin injection-related anxiety and to non-adherence. Injection-related discomfort continues to bear a significant contribution. Over the last decade, with advances in needle manufacturing technology, shorter and narrower needles have been associated with progressively improving patient self-rating of injection discomfort. Consequently, patient surveys of insulin users show discomfort to rank in the bottom third of significant contributors by prevalence. However, healthcare providers (HCP) and family member care providers continue to demonstrate a high level of anticipated and perceived pain for the patient. HCP anxiety and pain anticipation are each associated with patient anxiety and may therefore play a significant contributing role in patient non-adherence. PMID:22537418

  6. Non-insulin pharmacological therapy in pregnancy.

    PubMed

    Bajaj, Sarita

    2016-09-01

    During pregnancy, when glycaemic levels remain uncontrolled, despite lifestyle modification, pharmacotherapy is advised, usually insulin which has been the gold standard for treatment. Recent studies however suggest that certain oral anti diabetic agents (OADs) may be safe and acceptable alternatives. There may be potential advantages for the use of metformin over insulin in GDM with respect to maternal weight gain and neonatal outcomes. However, as metformin crosses the placenta, its use during pregnancy raises concerns regarding potential adverse effects on the mother and foetus. Glibenclamide, a second generation sulfonylurea, more effective in glycaemic control in women with GDM has a lower treatment failure rate than metformin but there is lack of long term follow up data. Even though generally well tolerated, some studies report higher rates of preeclampsia, macrosomia, neonatal jaundice, neonatal hypoglycaemia and longer stay in neonatal care unit. PMID:27582151

  7. The fluctuation of blood glucose, insulin and glucagon concentrations before and after insulin therapy in type 1 diabetes

    NASA Astrophysics Data System (ADS)

    Arif, Idam; Nasir, Zulfa

    2015-09-01

    A dynamical-systems model of plasma glucose, insulin and glucagon concentrations has been developed to investigate the effects of insulin therapy on blood glucose, insulin and glucagon regulations in type 1 diabetic patients. Simulation results show that the normal regulation of blood glucose concentration depends on insulin and glucagon concentrations. On type 1 diabetic case, the role of insulin on regulating blood glucose is not optimal because of the destruction of β cells in pancreas. These β cells destructions cause hyperglycemic episode affecting the whole body metabolism. To get over this, type 1 diabetic patients need insulin therapy to control the blood glucose level. This research has been done by using rapid acting insulin (lispro), long-acting insulin (glargine) and the combination between them to know the effects of insulin therapy on blood glucose, insulin and glucagon concentrations. Simulation results show that these different types of insulin have different effects on blood glucose concentration. Insulin therapy using lispro shows better blood glucose control after consumption of meals. Glargin gives better blood glucose control between meals and during sleep. Combination between lispro and glargine shows better glycemic control for whole day blood glucose level.

  8. Insulin infusion therapy in critically ill patients.

    PubMed

    Boutin, Jean-Marie; Gauthier, Lyne

    2014-04-01

    While dysglycemia (hyperglycemia, hypoglycemia and glucose variability) is clearly associated with increased mortality in critically ill patients, target range of blood glucose control remains controversial. Standardized insulin infusion protocols constitute the basis of treatment of these patients. The choice of protocol and its implementation is a great challenge. In this article, we review the published data to help define the essential elements that compose a good protocol and apply the right conditions to make it safe and effective. PMID:24690510

  9. Myostatin inhibition therapy for insulin-deficient type 1 diabetes.

    PubMed

    Coleman, Samantha K; Rebalka, Irena A; D'Souza, Donna M; Deodhare, Namita; Desjardins, Eric M; Hawke, Thomas J

    2016-01-01

    While Type 1 Diabetes Mellitus (T1DM) is characterized by hypoinsulinemia and hyperglycemia, persons with T1DM also develop insulin resistance. Recent studies have demonstrated that insulin resistance in T1DM is a primary mediator of the micro and macrovascular complications that invariably develop in this chronic disease. Myostatin acts to attenuate muscle growth and has been demonstrated to be elevated in streptozotocin-induced diabetic models. We hypothesized that a reduction in mRNA expression of myostatin within a genetic T1DM mouse model would improve skeletal muscle health, resulting in a larger, more insulin sensitive muscle mass. To that end, Akita diabetic mice were crossed with Myostatin(Ln/Ln) mice to ultimately generate a novel mouse line. Our data support the hypothesis that decreased skeletal muscle expression of myostatin mRNA prevented the loss of muscle mass observed in T1DM. Furthermore, reductions in myostatin mRNA increased Glut1 and Glut4 protein expression and glucose uptake in response to an insulin tolerance test (ITT). These positive changes lead to significant reductions in resting blood glucose levels as well as pronounced reductions in associated diabetic symptoms, even in the absence of exogenous insulin. Taken together, this study provides a foundation for considering myostatin inhibition as an adjuvant therapy in T1DM as a means to improve insulin sensitivity and blood glucose management. PMID:27581061

  10. Myostatin inhibition therapy for insulin-deficient type 1 diabetes

    PubMed Central

    Coleman, Samantha K.; Rebalka, Irena A.; D’Souza, Donna M.; Deodhare, Namita; Desjardins, Eric M.; Hawke, Thomas J.

    2016-01-01

    While Type 1 Diabetes Mellitus (T1DM) is characterized by hypoinsulinemia and hyperglycemia, persons with T1DM also develop insulin resistance. Recent studies have demonstrated that insulin resistance in T1DM is a primary mediator of the micro and macrovascular complications that invariably develop in this chronic disease. Myostatin acts to attenuate muscle growth and has been demonstrated to be elevated in streptozotocin-induced diabetic models. We hypothesized that a reduction in mRNA expression of myostatin within a genetic T1DM mouse model would improve skeletal muscle health, resulting in a larger, more insulin sensitive muscle mass. To that end, Akita diabetic mice were crossed with MyostatinLn/Ln mice to ultimately generate a novel mouse line. Our data support the hypothesis that decreased skeletal muscle expression of myostatin mRNA prevented the loss of muscle mass observed in T1DM. Furthermore, reductions in myostatin mRNA increased Glut1 and Glut4 protein expression and glucose uptake in response to an insulin tolerance test (ITT). These positive changes lead to significant reductions in resting blood glucose levels as well as pronounced reductions in associated diabetic symptoms, even in the absence of exogenous insulin. Taken together, this study provides a foundation for considering myostatin inhibition as an adjuvant therapy in T1DM as a means to improve insulin sensitivity and blood glucose management. PMID:27581061

  11. Problems of intensive therapy in childhood cancer

    SciTech Connect

    Skelton, J.; Pizzo, P.A.

    1986-07-15

    Tremendous progress has been made in the treatment of childhood cancers. Certain hematologic malignancies have an impressive cure rate with the current intensive antineoplastic treatment regimens. There is optimism that the treatment of children who have advanced stage solid tumors with intensive, multimodality therapy may improve their chances for long-term survival. These treatment programs, though potentially curative, are highly toxic, with severe myelosuppression and damage to other organ systems. An awareness of these potential toxicities, an understanding of how to prevent or minimize certain problems, and the ability to treat those complications which do arise are all essential to the successful management of childhood cancer. 206 references.

  12. [Organ replacement therapy - renal replacement therapy in intensive care medicine].

    PubMed

    Kraus, Daniel; Wanner, Christoph

    2016-09-01

    Critically ill patients who are treated in an intensive care unit are at increased risk of developing acute renal failure. Every episode of renal failure decreases life expectancy. However, acute renal failure is no longer an immediate cause of death because renal function can be substituted medically and mechanically, by the use of renal replacement therapy. Hemodialysis and hemofiltration are the 2 fundamental modalities of renal replacement therapy and may be performed intermittently or continuously. The decision for one particular therapy has to be made for each patient individually. Peritoneal dialysis is an alternative treatment for acute renal failure, but is not available for immediate use in most centers. Contrast media and rhabdomyolysis are 2 common causes of toxic renal failure in the intensive care unit. However, they cannot be prevented by hemodialysis. PMID:27631449

  13. Nanoparticle based insulin delivery system: the next generation efficient therapy for Type 1 diabetes.

    PubMed

    Sharma, Garima; Sharma, Ashish Ranjan; Nam, Ju-Suk; Doss, George Priya C; Lee, Sang-Soo; Chakraborty, Chiranjib

    2015-01-01

    Diabetic cases have increased rapidly in recent years throughout the world. Currently, for type-1 diabetes mellitus (T1DM), multiple daily insulin (MDI) injections is the most popular treatment throughout the world. At this juncture, researchers are trying to develop different insulin delivery systems, especially through oral and pulmonary route using nanocarrier based delivery system. This next generation efficient therapy for T1DM may help to improve the quality of life of diabetic patients who routinely employ insulin by the subcutaneous route. In this paper, we have depicted various next generation nanocarrier based insulin delivery systems such as chitosan-insulin nanoparticles, PLGA-insulin nanoparticles, dextran-insulin nanoparticles, polyalkylcyanoacrylated-insulin nanoparticles and solid lipid-insulin nanoparticles. Modulation of these insulin nanocarriers may lead to successful oral or pulmonary insulin nanoformulations in future clinical settings. Therefore, applications and limitations of these nanoparticles in delivering insulin to the targeted site have been thoroughly discussed. PMID:26498972

  14. Exercise Intensity Modulates Glucose-Stimulated Insulin Secretion when Adjusted for Adipose, Liver and Skeletal Muscle Insulin Resistance

    PubMed Central

    Malin, Steven K.; Rynders, Corey A.; Weltman, Judy Y.; Barrett, Eugene J.; Weltman, Arthur

    2016-01-01

    Little is known about the effects of exercise intensity on compensatory changes in glucose-stimulated insulin secretion (GSIS) when adjusted for adipose, liver and skeletal muscle insulin resistance (IR). Fifteen participants (8F, Age: 49.9±3.6yr; BMI: 31.0±1.5kg/m2; VO2peak: 23.2±1.2mg/kg/min) with prediabetes (ADA criteria, 75g OGTT and/or HbA1c) underwent a time-course matched Control, and isocaloric (200kcal) exercise at moderate (MIE; at lactate threshold (LT)), and high-intensity (HIE; 75% of difference between LT and VO2peak). A 75g OGTT was conducted 1 hour post-exercise/Control, and plasma glucose, insulin, C-peptide and free fatty acids were determined for calculations of skeletal muscle (1/Oral Minimal Model; SMIR), hepatic (HOMAIR), and adipose (ADIPOSEIR) IR. Insulin secretion rates were determined by deconvolution modeling for GSIS, and disposition index (DI; GSIS/IR; DISMIR, DIHOMAIR, DIADIPOSEIR) calculations. Compared to Control, exercise lowered SMIR independent of intensity (P<0.05), with HIE raising HOMAIR and ADIPOSEIR compared with Control (P<0.05). GSIS was not reduced following exercise, but DIHOMAIR and DIADIPOSEIR were lowered more following HIE compared with Control (P<0.05). However, DISMIR increased in an intensity based manner relative to Control (P<0.05), which corresponded with lower post-prandial blood glucose levels. Taken together, pancreatic insulin secretion adjusts in an exercise intensity dependent manner to match the level of insulin resistance in skeletal muscle, liver and adipose tissue. Further work is warranted to understand the mechanism by which exercise influences the cross-talk between tissues that regulate blood glucose in people with prediabetes. PMID:27111219

  15. Effects of Prior Intensive Insulin Therapy and Risk Factors on Visual Quality-of-Life in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) Cohort

    PubMed Central

    Gubitosi-Klug, Rose A.; Sun, Wanjie; Cleary, Patricia A.; Braffett, Barbara H.; Aiello, Lloyd Paul; Das, Arup; Tamborlane, William; Klein, Ronald

    2016-01-01

    glycemic control in DCCT (explained treatment effect: 100%). Those with VA worse than 20/100 reported the lowest VQOL score. Conclusions and Relevance In the DCCT/EDIC cohort, VQOL remains high in both treatment groups. Intensive diabetes therapy modestly improved VQOL 30 years after the start of the DCCT. VA had the greatest impact on VQOL from among all risk factors. PMID:26584339

  16. Interaction between plastic catheter tubings and regular insulin preparations used for continuous subcutaneous insulin-infusion therapy.

    PubMed

    Chantelau, E; Lange, G; Gasthaus, M; Boxberger, M; Berger, M

    1987-01-01

    In search of possible interactions between plastic tubings used for insulin-pump treatment and commercial regular insulin preparations, various catheter sets made from polyvinyl chloride (PVC), polyethylene (PE), and nylon plastics were perfused at 30 degrees C in a laboratory setting for up to 72 h. The perfused insulin solutions were analyzed by high-performance liquid chromatography and atomic absorption spectroscopy. Although no plasticizer, e.g., dioctyl phthalate, or nickel or chromium ions were found in the perfusates, substantial interactions between the plastics and the insulin solutions were detected, extraction of bacteriostatic additives from the insulin solutions in particular. The PVC retained up to 88% of the bacteriostatics from the insulin preparations, whereas PE tubings retained only 10-15%. Whether the loss of preservatives during perfusion through PVC catheters predisposes to cutaneous infections during insulin-pump therapy remains to be shown.

  17. 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

  18. Antimicrobial therapy in neonatal intensive care unit.

    PubMed

    Tzialla, Chryssoula; Borghesi, Alessandro; Serra, Gregorio; Stronati, Mauro; Corsello, Giovanni

    2015-01-01

    Severe infections represent the main cause of neonatal mortality accounting for more than one million neonatal deaths worldwide every year. Antibiotics are the most commonly prescribed medications in neonatal intensive care units (NICUs) and in industrialized countries about 1% of neonates are exposed to antibiotic therapy. Sepsis has often nonspecific signs and symptoms and empiric antimicrobial therapy is promptly initiated in high risk of sepsis or symptomatic infants. However continued use of empiric broad-spectrum antibiotic treatment in the setting of negative cultures especially in preterm infants may not be harmless.The benefits of antibiotic therapy when indicated are clearly enormous, but the continued use of antibiotics without any microbiological justification is dangerous and only leads to adverse events. The purpose of this review is to highlight the inappropriate use of antibiotics in the NICUs, to exam the impact of antibiotic treatment in preterm infants with negative cultures and to summarize existing knowledge regarding the appropriate choice of antimicrobial agents and optimal duration of therapy in neonates with suspected or culture-proven sepsis in order to prevent serious consequences. PMID:25887621

  19. Management of insulin pump therapy in children with type 1 diabetes.

    PubMed

    Abdullah, Nadeem; Pesterfield, Claire; Elleri, Daniela; Dunger, David B

    2014-12-01

    Insulin pump therapy is a current treatment option for children and adolescents with type 1 diabetes. Insulin pumps can provide a greater flexibility in insulin administration and meal planning, as compared with multiple insulin injections, and they may be particularly suitable for the paediatric age group. Many young people with diabetes have integrated insulin pumps into their daily practice. The use of insulin pumps can also be supplemented by the information retrieved from continuous glucose monitoring in the sensor-augmented pump therapy, which may improve glycaemic control. In this review, we describe the principles of pump therapy and summarise features of commercially available insulin pumps, with focus on practical management and the advantages and disadvantages of this technology.

  20. Single-energy intensity modulated proton therapy

    NASA Astrophysics Data System (ADS)

    Farace, Paolo; Righetto, Roberto; Cianchetti, Marco

    2015-09-01

    In this note, an intensity modulated proton therapy (IMPT) technique, based on the use of high single-energy (SE-IMPT) pencil beams, is described. The method uses only the highest system energy (226 MeV) and only lateral penumbra to produce dose gradient, as in photon therapy. In the study, after a preliminary analysis of the width of proton pencil beam penumbras at different depths, SE-IMPT was compared with conventional IMPT in a phantom containing titanium inserts and in a patient, affected by a spinal chordoma with fixation rods. It was shown that SE-IMPT has the potential to produce a sharp dose gradient and that it is not affected by the uncertainties produced by metal implants crossed by the proton beams. Moreover, in the chordoma patient, target coverage and organ at risk sparing of the SE-IMPT plan resulted comparable to that of the less reliable conventional IMPT technique. Robustness analysis confirmed that SE-IMPT was not affected by range errors, which can drastically affect the IMPT plan. When accepting a low-dose spread as in modern photon techniques, SE-IMPT could be an option for the treatment of lesions (e.g. cervical bone tumours) where steep dose gradient could improve curability, and where range uncertainty, due for example to the presence of metal implants, hampers conventional IMPT.

  1. Single-energy intensity modulated proton therapy.

    PubMed

    Farace, Paolo; Righetto, Roberto; Cianchetti, Marco

    2015-10-01

    In this note, an intensity modulated proton therapy (IMPT) technique, based on the use of high single-energy (SE-IMPT) pencil beams, is described.The method uses only the highest system energy (226 MeV) and only lateral penumbra to produce dose gradient, as in photon therapy. In the study, after a preliminary analysis of the width of proton pencil beam penumbras at different depths, SE-IMPT was compared with conventional IMPT in a phantom containing titanium inserts and in a patient, affected by a spinal chordoma with fixation rods.It was shown that SE-IMPT has the potential to produce a sharp dose gradient and that it is not affected by the uncertainties produced by metal implants crossed by the proton beams. Moreover, in the chordoma patient, target coverage and organ at risk sparing of the SE-IMPT plan resulted comparable to that of the less reliable conventional IMPT technique. Robustness analysis confirmed that SE-IMPT was not affected by range errors, which can drastically affect the IMPT plan.When accepting a low-dose spread as in modern photon techniques, SE-IMPT could be an option for the treatment of lesions (e.g. cervical bone tumours) where steep dose gradient could improve curability, and where range uncertainty, due for example to the presence of metal implants, hampers conventional IMPT. PMID:26352616

  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. 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…

  4. Obviating much of the need for insulin therapy in type 2 diabetes mellitus: A re-assessment of insulin therapy's safety profile.

    PubMed

    Schwartz, Stanley S; Jellinger, Paul S; Herman, Mary E

    2016-08-01

    Current processes of care for diabetes mellitus (DM) were shaped during the era when insulin therapy was considered inexorable to the management of advanced stage type 2 (T2DM), though this no longer appears to be categorically true. There are also dashed hopes that insulin therapy can prevent or stall diabetes. While exogenous insulin remains a life-sparing tool for fully insulin-dependent DM, insulin therapy-induced hyperinsulinemia now appears to contribute to serious safety issues beyond hypoglycemia and weight gain. Iatrogenic and compensatory hyperinsulinemia are metabolic disruptors of β-cells, liver, muscle, kidney, brain, heart and vasculature, inflammation, and lipid homeostasis, among other systems. This may compromise β-cells, exacerbate insulin resistance (IR), and increase risk of cardiovascular (CV) disease. Striking associations between exogenous insulin and risks of CV events, cancer, and all-cause mortality in clinical trial and real-world cohorts caution that insulin may pose more harm than previously evidenced. At our disposal are numerous alternate tools that, alone or in combination, efficaciously manage hyperglycemia and glucolipotoxicity, and do so without inducing hypoglycemia, weight gain, or hyperinsulinemia. Moreover, these new tools support true precision therapy, as modern day drug classes can be aligned with the various mediating pathways of hyperglycemia at work in any given patient. Some also appear to promote β-cell survival, with intriguing data being presented for newer agents, such as incretins. As such, we encourage preferential use of non-insulin antidiabetic agents to injected insulin for the management of non-insulin-dependent patients with T2DM, including in advanced stage T2DM. The goal of this article is to augment existing literature to 1) correct misconceptions on the rationale and necessity for insulin therapy in T2DM, 2) discuss emerging negative safety data with insulin therapy, and, 3) offer a practical means to

  5. Obviating much of the need for insulin therapy in type 2 diabetes mellitus: A re-assessment of insulin therapy's safety profile.

    PubMed

    Schwartz, Stanley S; Jellinger, Paul S; Herman, Mary E

    2016-08-01

    Current processes of care for diabetes mellitus (DM) were shaped during the era when insulin therapy was considered inexorable to the management of advanced stage type 2 (T2DM), though this no longer appears to be categorically true. There are also dashed hopes that insulin therapy can prevent or stall diabetes. While exogenous insulin remains a life-sparing tool for fully insulin-dependent DM, insulin therapy-induced hyperinsulinemia now appears to contribute to serious safety issues beyond hypoglycemia and weight gain. Iatrogenic and compensatory hyperinsulinemia are metabolic disruptors of β-cells, liver, muscle, kidney, brain, heart and vasculature, inflammation, and lipid homeostasis, among other systems. This may compromise β-cells, exacerbate insulin resistance (IR), and increase risk of cardiovascular (CV) disease. Striking associations between exogenous insulin and risks of CV events, cancer, and all-cause mortality in clinical trial and real-world cohorts caution that insulin may pose more harm than previously evidenced. At our disposal are numerous alternate tools that, alone or in combination, efficaciously manage hyperglycemia and glucolipotoxicity, and do so without inducing hypoglycemia, weight gain, or hyperinsulinemia. Moreover, these new tools support true precision therapy, as modern day drug classes can be aligned with the various mediating pathways of hyperglycemia at work in any given patient. Some also appear to promote β-cell survival, with intriguing data being presented for newer agents, such as incretins. As such, we encourage preferential use of non-insulin antidiabetic agents to injected insulin for the management of non-insulin-dependent patients with T2DM, including in advanced stage T2DM. The goal of this article is to augment existing literature to 1) correct misconceptions on the rationale and necessity for insulin therapy in T2DM, 2) discuss emerging negative safety data with insulin therapy, and, 3) offer a practical means to

  6. Redecision Family Therapy: Its Use with Intensive Multiple Family Groups.

    ERIC Educational Resources Information Center

    Kadis, Leslie B.; McClendon, Ruth Ann

    1981-01-01

    Describes intensive multiple family group therapy which combines the advantages of group therapy with those of time-limited, goal-oriented approaches. Using the Redecision Family Therapy model further refines the technique by integrating the seemingly disparate methods of intra- psychic and systemic therapy. (Author)

  7. Diabetes Patients' Experiences With the Implementation of Insulin Therapy and Their Perceptions of Computer-Assisted Self-Management Systems for Insulin Therapy

    PubMed Central

    Gude, Wouter T; Holleman, Frits; Hoekstra, Joost BL; Peek, Niels

    2014-01-01

    Background Computer-assisted decision support is an emerging modality to assist patients with type 2 diabetes mellitus (T2DM) in insulin self-titration (ie, self-adjusting insulin dose according to daily blood glucose levels). Computer-assisted insulin self-titration systems mainly focus on helping patients overcome barriers related to the cognitive components of insulin titration. Yet other (eg, psychological or physical) barriers could still impede effective use of such systems. Objective Our primary aim was to identify experiences with and barriers to self-monitoring of blood glucose, insulin injection, and insulin titration among patients with T2DM. Our research team developed a computer-assisted insulin self-titration system, called PANDIT. The secondary aim of this study was to evaluate patients’ perceptions of computer-assisted insulin self-titration. We included patients who used PANDIT in a 4-week pilot study as well as patients who had never used such a system. Methods In-depth, semi-structured interviews were conducted individually with patients on insulin therapy who were randomly recruited from a university hospital and surrounding general practices in the Netherlands. The interviews were transcribed verbatim and analyzed qualitatively. To classify the textual remarks, we created a codebook during the analysis, in a bottom-up and iterative fashion. To support examination of the final coded data, we used three theories from the field of health psychology and the integrated model of user satisfaction and technology acceptance by Wixom and Todd. Results When starting insulin therapy, some patients feared a lifelong commitment to insulin therapy and disease progression. Also, many barriers arose when implementing insulin therapy (eg, some patients were embarrassed to inject insulin in public). Furthermore, patients had difficulties increasing the insulin dose because they fear hypoglycemia, they associate higher insulin doses with disease progression

  8. 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.

  9. Effects of Exercise Intensity on Postprandial Improvement in Glucose Disposal and Insulin Sensitivity in Prediabetic Adults

    PubMed Central

    Rynders, Corey A.; Weltman, Judy Y.; Jiang, Boyi; Breton, Marc; Patrie, James; Barrett, Eugene J.

    2014-01-01

    Background: A single bout of exercise improves postprandial glycemia and insulin sensitivity in prediabetic patients; however, the impact of exercise intensity is not well understood. The present study compared the effects of acute isocaloric moderate (MIE) and high-intensity (HIE) exercise on glucose disposal and insulin sensitivity in prediabetic adults. Methods: Subjects (n = 18; age 49 ± 14 y; fasting glucose 105 ± 11 mg/dL; 2 h glucose 170 ± 32 mg/dL) completed a peak O2 consumption/lactate threshold (LT) protocol plus three randomly assigned conditions: 1) control, 1 hour of seated rest, 2) MIE (at LT), and 3) HIE (75% of difference between LT and peak O2 consumption). One hour after exercise, subjects received an oral glucose tolerance test (OGTT). Plasma glucose, insulin, and C-peptide concentrations were sampled at 5- to 10-minute intervals at baseline, during exercise, after exercise, and for 3 hours after glucose ingestion. Total, early-phase, and late-phase area under the glucose and insulin response curves were compared between conditions. Indices of insulin sensitivity (SI) were derived from OGTT data using the oral minimal model. Results: Compared with control, SI improved by 51% (P = .02) and 85% (P < .001) on the MIE and HIE days, respectively. No differences in SI were observed between the exercise conditions (P = .62). Improvements in SI corresponded to significant reductions in the glucose, insulin, and C-peptide area under the curve values during the late phase of the OGTT after HIE (P < .05), with only a trend for reductions after MIE. Conclusion: These results suggest that in prediabetic adults, acute exercise has an immediate and intensity-dependent effect on improving postprandial glycemia and insulin sensitivity. PMID:24243632

  10. Effect of exercise intensity and volume on persistence of insulin sensitivity during training cessation.

    PubMed

    Bajpeyi, Sudip; Tanner, Charles J; Slentz, Cris A; Duscha, Brian D; McCartney, Jennifer S; Hickner, Robert C; Kraus, William E; Houmard, Joseph A

    2009-04-01

    The purpose of this study was to determine whether exercise prescriptions differing in volume or intensity also differ in their ability to retain insulin sensitivity during an ensuing period of training cessation. Sedentary, overweight/obese subjects were assigned to one of three 8-mo exercise programs: 1) low volume/moderate intensity [equivalent of approximately 12 miles/wk, 1,200 kcal/wk at 40-55% peak O(2) consumption (Vo(2peak)), 200 min exercise/wk], 2) low volume/vigorous intensity ( approximately 12 miles/wk, 1,200 kcal/wk at 65-80% Vo(2peak), 125 min/wk), and 3) high volume/vigorous intensity ( approximately 20 miles/wk, 2,000 kcal/wk at 65-80% Vo(2peak), 200 min/wk). Insulin sensitivity (intravenous glucose tolerance test, S(I)) was measured when subjects were sedentary and at 16-24 h and 15 days after the final training bout. S(I) increased with training compared with the sedentary condition (P < or = 0.05) at 16-24 h with all of the exercise prescriptions. S(I) decreased to sedentary, pretraining values after 15 days of training cessation in the low-volume/vigorous-intensity group. In contrast, at 15 days S(I) was significantly elevated compared with sedentary (P < or = 0.05) in the prescriptions utilizing 200 min/wk (low volume/moderate intensity, high volume/vigorous intensity). In the high-volume/vigorous-intensity group, indexes of muscle mitochondrial density followed a pattern paralleling insulin action by being elevated at 15 days compared with pretraining; this trend was not evident in the low-volume/moderate-intensity group. These findings suggest that in overweight/obese subjects a relatively chronic persistence of enhanced insulin action may be obtained with endurance-oriented exercise training; this persistence, however, is dependent on the characteristics of the exercise training performed.

  11. Intensity-modulated radiation therapy: dynamic MLC (DMLC) therapy, multisegment therapy and tomotherapy. An example of QA in DMLC therapy.

    PubMed

    Webb, S

    1998-10-01

    Intensity-modulated radiation therapy will make a quantum leap in tumor control. It is the new radiation therapy for the new millennium. The major methods to achieve IMRT are: 1. dynamic multileaf collimator (DMLC) therapy, 2. multisegment therapy, and 3. tomotherapy. The principles of these 3 techniques are briefly reviewed. Each technique presents unique QA issues which are outlined. As an example this paper will present the results of a recent new study of an important QA concern in DMLC therapy.

  12. High intensity interval training improves liver and adipose tissue insulin sensitivity

    PubMed Central

    Marcinko, Katarina; Sikkema, Sarah R.; Samaan, M. Constantine; Kemp, Bruce E.; Fullerton, Morgan D.; Steinberg, Gregory R.

    2015-01-01

    Objective Endurance exercise training reduces insulin resistance, adipose tissue inflammation and non-alcoholic fatty liver disease (NAFLD), an effect often associated with modest weight loss. Recent studies have indicated that high-intensity interval training (HIIT) lowers blood glucose in individuals with type 2 diabetes independently of weight loss; however, the organs affected and mechanisms mediating the glucose lowering effects are not known. Intense exercise increases phosphorylation and inhibition of acetyl-CoA carboxylase (ACC) by AMP-activated protein kinase (AMPK) in muscle, adipose tissue and liver. AMPK and ACC are key enzymes regulating fatty acid metabolism, liver fat content, adipose tissue inflammation and insulin sensitivity but the importance of this pathway in regulating insulin sensitivity with HIIT is unknown. Methods In the current study, the effects of 6 weeks of HIIT were examined using obese mice with serine–alanine knock-in mutations on the AMPK phosphorylation sites of ACC1 and ACC2 (AccDKI) or wild-type (WT) controls. Results HIIT lowered blood glucose and increased exercise capacity, food intake, basal activity levels, carbohydrate oxidation and liver and adipose tissue insulin sensitivity in HFD-fed WT and AccDKI mice. These changes occurred independently of weight loss or reductions in adiposity, inflammation and liver lipid content. Conclusions These data indicate that HIIT lowers blood glucose levels by improving adipose and liver insulin sensitivity independently of changes in adiposity, adipose tissue inflammation, liver lipid content or AMPK phosphorylation of ACC. PMID:26909307

  13. Intranasal Insulin Therapy for Cognitive Impairment and Neurodegeneration: Current State of the Art

    PubMed Central

    de la Monte, Suzanne M.

    2015-01-01

    Introduction Growing evidence supports the concept that insulin resistance plays an important role in the pathogenesis of cognitive impairment and neurodegeneration, including in Alzheimer's disease (AD). The metabolic hypothesis has led to the development and utilization of insulin- and insulin agonist-based treatments. Therapeutic challenges faced include the ability to provide effective treatments that do not require repeated injections and also minimize potentially hazardous off-target effects. Areas covered This review covers the role of intra-nasal insulin therapy for cognitive impairment and neurodegeneration, particularly Alzheimer's disease. The literature reviewed focuses on data published within the past 5 years as this field is evolving rapidly. The author provides evidence that brain insulin resistance is an important and early abnormality in Alzheimer's disease, and that increasing brain supply and utilization of insulin improves cognition and memory. Emphasis was placed on discussing outcomes of clinical trials and interpreting discordant results to clarify the benefits and limitations of intranasal insulin therapy. Expert Opinion Intranasal insulin therapy can efficiently and directly target the brain to support energy metabolism, myelin maintenance, cell survival, and neuronal plasticity, which begin to fail in the early stages of neurodegeneration. Efforts must continue toward increasing the safety, efficacy, and specificity of intranasal insulin therapy. PMID:24215447

  14. Intensity-Modulated Radiation Therapy (IMRT)

    MedlinePlus

    ... modulating—or controlling—the intensity of the radiation beam in multiple small volumes. IMRT also allows higher ... of multiple intensity-modulated fields coming from different beam directions produce a custom tailored radiation dose that ...

  15. Patients' with type 2 diabetes willingness to pay for insulin therapy and clinical outcomes

    PubMed Central

    Feher, Michael D; Brazier, John; Schaper, Nicolaas; Vega-Hernandez, Gabriela; Bøgelund, Mette

    2016-01-01

    Objectives This study assessed patient preferences, using willingness to pay as a method to measure different treatment characteristics or attributes associated with injectable insulin therapy in patients with type 2 diabetes. Research design and methods Adults with type 2 diabetes in 12 countries, diagnosed >6 months prior and receiving insulin for >3 months, were recruited through a representative online panel. Data were collected via online questionnaire and analyzed using a standard choice model for discrete choice experiment. Results A total of 3758 patients from North America (n=646), South America (n=1537), and Europe (n=1575) completed the study. Mean glycated hemoglobin (HbA1c) levels in North America, South America, and Europe were 63 mmol/mol (7.9%), 75 mmol/mol (9.0%), and 64 mmol/mol (8.0%), respectively. In the three regions, monthly willingness to pay was US$116, US$74, and US$92, respectively, for a 1%-point decrease in HbA1c; US$99, US$80, and US$104 for one less major hypoglycemic event per year; and US$64, US$37 and US$60 for a 3 kg weight decrease. To avoid preinjection preparation of insulin, the respective values were US$47, US$18, and US$37, and US$25, US$25, and US$24 for one less injection per day. Among respondents on basal-only insulin who had previously tried a more intensive regimen, reasons for switching back included difficulty in handling multiple injections and risk of hypoglycemic events. Conclusions Reducing HbA1c, frequency of major hypoglycemic events and weight decrease were the highest valued outcomes in each region. The administrative burden of injections was also considered important. PMID:27158518

  16. Intensive lifestyle intervention including high-intensity interval training program improves insulin resistance and fasting plasma glucose in obese patients☆

    PubMed Central

    Marquis-Gravel, Guillaume; Hayami, Douglas; Juneau, Martin; Nigam, Anil; Guilbeault, Valérie; Latour, Élise; Gayda, Mathieu

    2015-01-01

    Objectives To analyze the effects of a long-term intensive lifestyle intervention including high-intensity interval training (HIIT) and Mediterranean diet (MedD) counseling on glycemic control parameters, insulin resistance and β-cell function in obese subjects. Methods The glycemic control parameters (fasting plasma glucose, glycated hemoglobin), insulin resistance, and β-cell function of 72 obese subjects (54 women; mean age = 53 ± 9 years) were assessed at baseline and upon completion of a 9-month intensive lifestyle intervention program conducted at the cardiovascular prevention and rehabilitation center of the Montreal Heart Institute, from 2009 to 2012. The program included 2–3 weekly supervised exercise training sessions (HIIT and resistance exercise), combined to MedD counseling. Results Fasting plasma glucose (FPG) (mmol/L) (before: 5.5 ± 0.9; after: 5.2 ± 0.6; P < 0.0001), fasting insulin (pmol/L) (before: 98 ± 57; after: 82 ± 43; P = 0.003), and insulin resistance, as assessed by the HOMA-IR score (before: 3.6 ± 2.5; after: 2.8 ± 1.6; P = 0.0008) significantly improved, but not HbA1c (%) (before: 5.72 ± 0.55; after: 5.69 ± 0.39; P = 0.448), nor β-cell function (HOMA-β, %) (before: 149 ± 78; after: 144 ± 75; P = 0.58). Conclusion Following a 9-month intensive lifestyle intervention combining HIIT and MedD counseling, obese subjects experienced significant improvements of FPG and insulin resistance. This is the first study to expose the effects of a long-term program combining HIIT and MedD on glycemic control parameters among obese subjects. PMID:26844086

  17. Exercise at anaerobic threshold intensity and insulin secretion by isolated pancreatic islets of rats

    PubMed Central

    de Oliveira, Camila Aparecida Machado; Paiva, Mauricio Ferreira; Mota, Clécia Alencar Soares; Ribeiro, Carla; de Almeida Leme, José Alexandre Curiacos; Luciano, Eliete

    2010-01-01

    To evaluate the effect of acute exercise and exercise training at the anaerobic threshold (AT) intensity on aerobic conditioning and insulin secretion by pancreatic islets, adult male Wistar rats were submitted to the lactate minimum test (LMT) for AT determination. Half of the animals were submitted to swimming exercise training (trained), 1 h/day, 5 days/week during 8 weeks, with an overload equivalent to the AT. The other half was kept sedentary. At the end of the experimental period, the rats were submitted to an oral glucose tolerance test and to another LMT. Then, the animals were sacrificed at rest or immediately after 20 minutes of swimming exercise at the AT intensity for pancreatic islets isolation. At the end of the experiment mean workload (% bw) at AT was higher and blood lactate concentration (mmol/L) was lower in the trained than in the control group. Rats trained at the AT intensity showed no alteration in the areas under blood glucose and insulin during OGTT test. Islet insulin content of trained rats was higher than in the sedentary rats while islet glucose uptake did not differ among the groups. The static insulin secretion in response to the high glucose concentration (16.7 mM) of the sedentary group at rest was lower than the sedentary group submitted to the acute exercise and the inverse was observed in relation to the trained groups. Physical training at the AT intensity improved the aerobic condition and altered insulin secretory pattern by pancreatic islets. PMID:21099318

  18. 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

  19. Combination therapy with GLP-1 receptor agonists and basal insulin: a systematic review of the literature

    PubMed Central

    Balena, R; Hensley, I E; Miller, S; Barnett, A H

    2013-01-01

    Treatment algorithms for type 2 diabetes call for intensification of therapy over time as the disease progresses and glycaemic control worsens. If diet, exercise and oral antihyperglycaemic medications (OAMs) fail to maintain glycaemic control then basal insulin is added and ultimately prandial insulin may be required. However, such an intensification strategy carries risk of increased hypoglycaemia and weight gain, both of which are associated with worse long-term outcomes. An alternative strategy is to intensify therapy by the addition of a short-acting glucagon-like peptide-1 receptor agonist (GLP-1 RA) rather than prandial insulin. Short-acting GLP-1 RAs such as exenatide twice daily are particularly effective at reducing postprandial glucose while basal insulin has a greater effect on fasting glucose, providing a physiological rationale for this complementary approach. This review analyzes the latest randomized controlled clinical trials of insulin/GLP-1 RA combination therapy and examines results from ‘real-world’ use of the combinations as reported through observational and clinical practice studies. The most common finding across all types of studies was that combination therapy improved glycaemic control without weight gain or an increased risk of hypoglycaemia. Many studies reported weight loss and a reduction in insulin use when a GLP-1 RA was added to existing insulin therapy. Overall, the relative degree of benefit to glycaemic control and weight was influenced by the insulin titration employed in conjunction with the GLP-1 RA. The greatest glycaemic benefits were observed in studies with structured titration of insulin to glycaemic targets while the greatest weight benefits were observed in studies with a protocol-specified focus on insulin sparing. The adverse event profile of GLP-1 RAs in the reviewed trials was similar to that reported with GLP-1 RAs as monotherapy or in combination with OAMs with gastrointestinal events being the most commonly

  20. [Diet therapy in non-insulin dependent diabetes mellitus (NIDDM)].

    PubMed

    Cavallo-Perin, P; Bodoni, P; Marena, S

    1997-12-01

    The main approach in NIDDM therapy is diet. Most patients present insulin resistance characterized by overweight, VLDL increase, minimal increase of LDL, decrease of HDL cholesterol, and hypertension. The overall goals of nutrition therapy are the maintenance of near normal glucose levels, and the achievement of optimal serum lipid levels with adequate calories for maintaining or attaining a reasonable body weight. In presence of obesity and hypertension even a slightly weight loss could achieve an improvement in metabolic control and in hypertension with a better life expectance. General-ly carbohydrate intake would represent the 50-60% of total caloric amount (with preference to those with low glycemic index), and lipids no more than 35% (less than 10% of these 10-15% from monounsaturated fats with less than 300 mg/day of cholesterol). If elevated very low density lipoproteins level is the primary problem, a beneficial approach is 10% of total caloric intake from saturated fats, 10% from polyunsaturated, and 15-20% from monounsaturated fats with less than 200 mg/day of cholesterol and 40% of carbohydrates. A large amount of fructose (20% of calories) may increase LDL levels but sweeteners as saccarine or aspartame are approved and determine a better diet compliance. Daily consumpion of 20-35 g of dietary fibres from food sources is recommended for metabolic control. Protein intake would be of about 10% of total caloric amount especially in presence of diabetic nepropathy. Alcohol would not exceed 30 g/day for men and 20 g/day for women keeping in mild that alcohol may worsen metabolic control, diet compliance, and may be dangerous itself. For people with hypertension a decrease of dietary sodium intake is recommended. Nutritional recommendations are developed to meet treatment goals and desired outcomes. Monitoring metabolic parameters, blood pressure, and body weight is very important to ensure successful outcomes.

  1. Insulin

    MedlinePlus

    ... pump is connected to your body by a flexible tube that has a tip that sticks under your skin. A cartridge of insulin is put in the pump. The insulin flows through the tube into your body. The pump controls how much insulin goes into your body. The ...

  2. [Pathogenesis of diabetic microangiopathy. Fluoroangioretinal observations during monocomponent insulin therapy].

    PubMed

    Anselmetti, G; Antoniotti, V; Barbero, P L; Castellazzi, R; Gamba, S; Bruni, B

    1978-01-01

    Current theories on the pathogenesis of diabetic microangiopathy and their effective therapeutical implications are reviewed. The possible role of insulin antibody production in insulin-treated diabetics concerning development and progression of retinopathy is particularly discussed. Thus the opportunity of a monocomponent (MC) insulin treatment in all newly diagnosed insulin-dependent diabetics is considered. The authors have carried out fluorescein angiography in two groups of subjects with JOD comparable for age, sex, diabetes duration (5-7 years), insulin requirement, metabolic control, absence of diabetic heredity as well as of clinical (ophtalmoscopic) signs of microangiopathy (retinopathy). The first group had been treated from the beginning with MC porcine insulin (Monotard) only; the second one with conventional Lente only. Early fluoroangiographic signs of retinopathy ("pre-retinopathy") as increased capillary filling, ischaemic areas, alterations in capillary permeability, microangioaneurysms, "primary exudation" had to be detected. In 2 out of 10 cases in the first group one isolated sign was found; one or more signs were found in the second group. In the first group the insulin antibody titer (IB) was under or nearly above the detection limit; in the second group insulin antibody titer was significantly positive. These preliminary findings suggest a larger prospective study. PMID:756200

  3. 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…

  4. Comparison of Combined Tofogliflozin and Glargine, Tofogliflozin Added to Insulin, and Insulin Dose-Increase Therapy in Uncontrolled Type 2 Diabetes

    PubMed Central

    Suzuki, Katsunori; Mitsuma, Yurie; Sato, Takaaki; Anraku, Takumi; Hatta, Mariko

    2016-01-01

    Background Some patients with type 2 diabetes mellitus (T2DM) on insulin have poor glycemic control and require add-on therapy to reach target glucose values. Increased insulin doses or the addition of an oral antidiabetic drug (OAD) may improve glycemic control, but many patients fail to achieve target values. The aim of this study was to compare the treatment efficacy and safety of three different therapies in such patients. Methods T2DM outpatients with poor glycemic control (HbA1c ≥ 7.0%) despite insulin therapy (including patients on OADs other than a sodium-glucose cotransporter 2 (SGLT2) inhibitor) were included. The patients had a body mass index (BMI) of ≥ 22 kg/m2 and an estimated glomerular filtration rate (eGFR) of ≥ 45 mL/min/1.73 m2, did not have depletion of endogenous insulin, and had stable glucose levels for 3 months before study entry on insulin therapy. Treatment was continued for 24 weeks with insulin dose-increase therapy, tofogliflozin add-on therapy, or a combination of insulin glargine + tofogliflozin. The primary endpoints were HbA1c, weight, and total insulin dose. Secondary endpoints included fasting plasma glucose (FPG), blood pressure, lipid profiles, and incidence of adverse events. Results At baseline, the participants’ median age was 59.0 years, mean BMI was 28.7 kg/m2, mean eGFR was 89.2 mL/min/1.73 m2, mean HbA1c was 8.7%, and mean FPG was 174.1 mg/dL. The mean duration of insulin therapy was approximately 7 years. The mean daily insulin dose was approximately 40 U in the three groups. Overall, 85% received other background OADs in addition to insulin. Over the 24-week period, HbA1c in the insulin group decreased slightly initially and then plateaued; daily total insulin dose and weight increased, and blood pressure increased slightly. In the insulin + tofogliflozin group and the glargine + tofogliflozin group, HbA1c decreased greatly initially, and this continued over the 24-week period, with HbA1c decreases of -1.0% and

  5. [Overprotectiveness as a coping reaction in intensive physical therapy].

    PubMed

    Sarimski, K; Hoffmann, I W

    1993-06-01

    25 mothers of children with cerebral palsy who were doing daily intensive physical therapy (Vojta) completed questionnaires concerning their child's temperament, parental attitudes and how they coped with everyday problems. Their responses were compared to those given by mothers who were not under the stress of conducting therapy. The results revealed compensatory coping processes: Mothers doing therapy try to compensate for their child's stress by being overprotective in ambiguous everyday situations. PMID:8342332

  6. Intense Pulsed Light Therapy for Skin Rejuvenation.

    PubMed

    DiBernardo, Barry E; Pozner, Jason N

    2016-07-01

    Intense pulsed light (IPL), also known as pulsed light and broad band light, is a nonlaser light source used to treat a variety of vascular and pigmented lesions, photo damage, active acne, and unwanted hair. Current IPL systems are much improved from older-generation devices with better calibration, integrated cooling, and improved tuning. These devices are extremely popular because of their versatility and are often the first devices recommended and purchased in many offices. PMID:27363767

  7. Continuous subcutaneous IGF-1 therapy via insulin pump in a patient with Donohue syndrome

    PubMed Central

    Weber, David R.; Stanescu, Diana E.; Semple, Robert; Holland, Cheryl; Magge, Sheela N.

    2015-01-01

    Donohue syndrome (DS) is a severe form of congenital insulin resistance due to mutation(s) in the insulin receptor (INSR) gene. Given the similarities between insulin and insulin-like growth factor 1 (IGF-1) receptors, recombinant human IGF-1 (rhIGF-1) has been used to treat severe insulin resistance due to INSR mutation(s). Traditional subcutaneous therapy may be limited by the shortened IGF-1 half-life in these patients. We report the case of a female with molecularly confirmed DS treated with continuous rhIGF-1 therapy via an insulin pump. With treatment, the patient’s hemoglobin A1c decreased from 9.8% to 8.8%, and her weight increased by 0.8 kg. Development of an ovarian tumor complicated her course, but it was unclear whether this was related to rhIGF-1 therapy. Limited treatment options exist for patients with DS. The use of continuous rhIGF-1 via an insulin pump may be a viable option, although further experience is needed to establish safety and efficacy. PMID:25153212

  8. 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

  9. Insulin resistance and response to antiviral therapy in chronic hepatitis C: mechanisms and management.

    PubMed

    del Campo, José A; López, Reyes Aparcero; Romero-Gómez, Manuel

    2010-01-01

    Insulin resistance has been found to be an independent factor predicting sustained response to peginterferon plus ribavirin in patients with chronic hepatitis C. Insulin resistance seems to be involved in decreased sensitivity to interferon and could block interferon intracellular signaling. Insulin resistance promotes steatosis and fibrosis progression, induces pro-inflammatory cytokine secretion and increases adipose tissue, decreasing interferon availability. Moreover, suppressor of cytokines 3 and protein tyrosine-phosphatase seems to be able to block interferon and insulin signaling, building a feed-forward loop. Insulin resistance can be treated with exercise, diet or through the use of drugs that improve insulin sensitivity, like biguanides or glitazones. A recent controlled, randomized, double-blind clinical trial (TRIC-1) examined the effect of adding metformin to standard therapy in the treatment of hepatitis C. This study demonstrated that women infected with hepatitis C virus genotype 1 and HOMA >2 treated with metformin showed a greater drop in viral load during the first 12 weeks and a doubled sustained viral response in comparison with females receiving placebo. Pioglitazone has been used in previous nonresponders and naïve patients with disappointing results in two pilot trials. The mechanisms by which the virus promotes insulin resistance seems to be genotype-dependent and could explain, at least in part, the discrepancies between insulin sensitizers. Insulin resistance is a new target in the challenging management of chronic hepatitis C. PMID:20460925

  10. [Intensive therapy after solid organ transplantation].

    PubMed

    Lichtenstern, C; Müller, M; Schmidt, J; Mayer, K; Weigand, M A

    2010-12-01

    Transplantation medicine is an interdisciplinary task and the priority objective is a fast recovery to patient independence. After kidney transplantation the crucial aims are monitoring of transplant perfusion, maintainance of an adequate volume status and avoidance of nephrotoxic medications. Transplantation for patients with advanced chronic liver failure has become more common since the implementation of the model of end stage liver disease (MELD) allocation system which is associated with more complicated proceedings. The essentials of critical care after liver transplantation are monitoring of transplant function, diagnosis of perfusion or biliary tract problems, specific substitution of coagulation factors and hemodynamic optimation due to avoidance of hepatic congestion. Many patients listed for heart transplantation need preoperative intensive care due to impaired heart function. Postoperatively a specific cardiac support with pulmonary arterial dilatators and inotropics is usually necessary. Lung transplantation aims at an improvement of patient quality of life. Postoperative critical care should provide a limitation of the pulmonary arterial pressure, avoidance of volume overload and rapid weaning from the respirator.

  11. Does insulin therapy for type 1 diabetes mellitus protect against Alzheimer's disease?

    PubMed

    Rdzak, Grzegorz M; Abdelghany, Osama

    2014-12-01

    Alzheimer's disease is the most common cause of dementia in the United States. A better understanding of the disease's underlying pathways may provide novel treatment and/or prevention strategies for this progressive chronic neurodegenerative disorder. In recent years, there has been a growing interest in the possible links between insulin and Alzheimer's disease. Insulin-induced hypoglycemia causes adaptive changes in the brain, including an improved ability to use alternative fuels. Insulin has been shown to facilitate reduction of intracellular amyloid plaque and downregulation of amyloid-β-derived diffusible ligand-binding sites. Insulin also promotes tau hypophosphorylation, which stabilizes microtubules and promotes tubulin polymerization. Excess exogenous insulin may also play a role in overcoming the decreased utilization and transport of glucose in patients with Alzheimer's disease. Intranasal insulin therapy may have beneficial effects on cognition and function in patients with Alzheimer's disease, as well as having only minor adverse effects, and this route of administration been the focus in clinical trials. These data support the mechanistic pathways that might link excess exogenous insulin administered to patients with type 1 diabetes mellitus to possible protection from Alzheimer's disease and provide a rationale for using insulin to prevent the disease in high-risk patients.

  12. High-dose insulin therapy in beta-blocker and calcium channel-blocker poisoning.

    PubMed

    Engebretsen, Kristin M; Kaczmarek, Kathleen M; Morgan, Jenifer; Holger, Joel S

    2011-04-01

    INTRODUCTION. High-dose insulin therapy, along with glucose supplementation, has emerged as an effective treatment for severe beta-blocker and calcium channel-blocker poisoning. We review the experimental data and clinical experience that suggests high-dose insulin is superior to conventional therapies for these poisonings. PRESENTATION AND GENERAL MANAGEMENT. Hypotension, bradycardia, decreased systemic vascular resistance (SVR), and cardiogenic shock are characteristic features of beta-blocker and calcium-channel blocker poisoning. Initial treatment is primarily supportive and includes saline fluid resuscitation which is essential to correct vasodilation and low cardiac filling pressures. Conventional therapies such as atropine, glucagon and calcium often fail to improve hemodynamic status in severely poisoned patients. Catecholamines can increase blood pressure and heart rate, but they also increase SVR which may result in decreases in cardiac output and perfusion of vascular beds. The increased myocardial oxygen demand that results from catecholamines and vasopressors may be deleterious in the setting of hypotension and decreased coronary perfusion. METHODS. The Medline, Embase, Toxnet, and Google Scholar databases were searched for the years 1975-2010 using the terms: high-dose insulin, hyperinsulinemia-euglycemia, beta-blocker, calcium-channel blocker, toxicology, poisoning, antidote, toxin-induced cardiovascular shock, and overdose. In addition, a manual search of the Abstracts of the North American Congress of Clinical Toxicology and the Congress of the European Association of Poisons Centres and Clinical Toxicologists published in Clinical Toxicology for the years 1996-2010 was undertaken. These searches identified 485 articles of which 72 were considered relevant. MECHANISMS OF HIGH-DOSE INSULIN BENEFIT. There are three main mechanisms of benefit: increased inotropy, increased intracellular glucose transport, and vascular dilatation. EFFICACY OF HIGH

  13. Impact of patient attitudes and beliefs to insulin therapy upon initiation, and their attitudinal changes after initiation: the DAWN Japan study.

    PubMed

    Odawara, Masato; Ishii, Hitoshi; Tajima, Naoko; Iwamoto, Yasuhiko

    2016-01-01

    Objective As a part of the Diabetes Attitudes, Wishes and Needs (DAWN) Japan study, a multi-center, questionnaire-based survey conducted between 2004 and 2005, this analysis aimed to (1) explore patients' attitudes and beliefs contributing to their decision to start insulin therapy, and (2) assess the changes in their attitudes and beliefs after actual initiation. Methods Insulin-naive patients with type 2 diabetes who were recommended to start insulin therapy (n = 149) were invited to answer a 21-item questionnaire consisting of five clusters assessing their attitudes and beliefs toward insulin therapy. The questionnaire was administered twice: first upon insulin recommendation, and then 1 month after insulin initiation for those who started and 4 months after for those who did not. Results Of 130 patients included in the analysis, 74 patients (56.9%) started insulin therapy. 'Negative image of injections' and 'Positive image toward insulin therapy' were significantly associated with patient decision to start insulin therapy (odds ratios [95% CI]: 0.49 [0.32-0.76] and 2.58 [1.51-4.42], respectively). After insulin initiation, 'Negative image of injections', 'Positive image toward insulin therapy', 'Feelings of guilt regarding diabetes self-management', and 'Negative image toward insulin therapy' decreased significantly (P < 0.001 for all). 'Social/interpersonal effects' did not change after insulin initiation. Conclusions This study demonstrated that patients who started insulin therapy were less likely to have negative images of injections and more likely to have positive images toward insulin therapy. Starting insulin therapy did not deteriorate the patient's overall impression of therapy. The key limitation is the relatively small sample size (n = 130). The results suggest that education about the benefits of insulin therapy may help patients who are not ready to initiate insulin overcome their barrier to early insulin initiation and practical

  14. Novel therapy for insulin-dependent diabetes mellitus: infusion of in vitro-generated insulin-secreting cells.

    PubMed

    Dave, S D; Vanikar, A V; Trivedi, H L; Thakkar, U G; Gopal, S C; Chandra, T

    2015-02-01

    Insulin-dependent diabetes mellitus (IDDM) is a metabolic disease usually resulting from autoimmune-mediated β-cell destruction requiring lifetime exogenous insulin replacement. Mesenchymal stem cells (MSC) hold promising therapy. We present our experience of treating IDDM with co-infusion of in vitro autologous adipose tissue-derived MSC-differentiated insulin-secreting cells (ISC) with hematopoietic stem cells (HSC). This was an Institutional Review Board approved prospective non-randomized open-labeled clinical trial after informed consent from ten patients. ISC were differentiated from autologous adipose tissue-derived MSC and were infused with bone marrow-derived HSC in portal, thymic circulation by mini-laparotomy and in subcutaneous circulation. Patients were monitored for blood sugar levels, serum C-peptide levels, glycosylated hemoglobin (Hb1Ac) and glutamic acid decarboxylase (GAD) antibodies. Insulin administration was made on sliding scale with an objective of maintaining FBS < 150 mg/dL and PPBS around 200 mg/dL. Mean 3.34 mL cell inoculums with 5.25 × 10(4) cells/μL were infused. No untoward effects were observed. Over a mean follow-up of 31.71 months, mean serum C-peptide of 0.22 ng/mL before infusion had sustained rise of 0.92 ng/mL with decreased exogenous insulin requirement from 63.9 international units (IU)/day to 38.6 IU/day. Improvement in mean Hb1Ac was observed from 10.99 to 6.72%. Mean GAD antibodies were positive in all patients with mean of 331.10 IU/mL, which decreased to mean of 123 IU/mL. Co-infusion of autologous ISC with HSC represents a viable novel therapeutic option for IDDM.

  15. Intensive statin therapy for Indians: Part-I. Benefits.

    PubMed

    Enas, Enas A; Pazhoor, Hancy Chennikkara; Kuruvila, Arun; Vijayaraghavan, Krishnaswami

    2011-01-01

    The underlying disorder in the vast majority of cases of cardiovascular disease (CVD) is atherosclerosis, for which low-density lipoprotein cholesterol (LDL-C) is recognized as the first and foremost risk factor. HMG-CoA reductase inhibitors, popularly called statins, are highly effective and remarkably safe in reducing LDL-C and non-HDL-C levels. Evidence from clinical trials have demonstrated that statin therapy can reduce the risk of myocardial infarction (MI), stroke, death, and the need for coronary artery revascularization procedures (CARPs) by 25-50%, depending on the magnitude of LDL-C lowering achieved. Benefits are seen in men and women, young and old, and in people with and without diabetes or prior diagnosis of CVD. Clinical trials comparing standard statin therapy to intensive statin therapy have clearly demonstrated greater benefits in CVD risk reduction (including halting the progression and even reversing coronary atherosclerosis) without any corresponding increase in risk. Numerous outcome trials of intensive statin therapy using atorvastatin 80 mg/d have demonstrated the safety and the benefits of lowering LDL-C to very low levels. This led the USNCEP Guideline Committee to standardize 40 mg/dL as the optimum LDL-C level, above which the CVD risk begins to rise. Recent studies have shown intensive statin therapy can also lower CVD events even in low-risk individuals with LDL-C <110 mg/dL. Because of the heightened risk of CVD in Asian Indians, the LDL-C target is set at 30 mg/dL lower than that recommended by NCEP. Accordingly, the LDL-C goal is < 70 mg/dL for Indians who have CVD, diabetes, metabolic syndrome, or chronic kidney disease. Intensive statin therapy is often required in these populations as well as others who require a > or = 50% reduction in LDL-C. Broader acceptance of this lower LDL-C targets and its implementation could reduce the CVD burden in the Indian population by 50% in the next 25 years. Clinical trial data support an

  16. Use of insulin degludec, a new basal insulin with an ultra-long duration of action, in basal-bolus therapy in type 1 and type 2 diabetes.

    PubMed

    Kerlan, Véronique; Gouet, Didier; Marre, Michel; Renard, Éric

    2013-12-01

    Insulin degludec is a new basal insulin analogue with an ultra-long duration of action that provides a flat and stable action profile with a duration of action greater than 42 hours. Two clinical trials comparing insulin degludec and insulin glargine in basal-bolus therapy have recently been published. Both were 52-week, multicentre, randomised (3:1), treat-to-target trials in patients already using insulin. In both type 1 (n=629) and type 2 diabetes (n=1006), insulin degludec was non-inferior to insulin glargine with respect to reduction in HbA1c at 52 weeks. There were also no significant differences between treatment groups with respect to fasting plasma glucose. At similar levels of glycaemic control, however, insulin degludec was associated with lower rates of hypoglycaemia than insulin glargine. In type 1 diabetes, overall confirmed hypoglycaemia (plasma glucose concentration<3.1 mmol/L or severe episodes requiring assistance) was similar in the two treatment groups, but nocturnal confirmed hypoglycaemia (occurring from 00h01 to 05h59) was 25% lower with insulin degludec (P=0.021). In type 2 diabetes, overall confirmed hypoglycaemia was 18% lower (P=0.0359) and nocturnal confirmed hypoglycaemia was 25% lower (P=0.0399) with insulin degludec. Reductions in hypoglycaemia could reduce physicians' and patients' fears and encourage them to titrate insulin more aggressively, and to adhere more closely to treatment, with consequent better glycaemic control. The results of these trials suggest that insulin degludec has a place in the French clinical setting in basal-bolus therapy in type 1 and type 2 diabetes.

  17. Glucose-Responsive Implantable Polymeric Microdevices for "Smart" Insulin Therapy of Diabetes

    NASA Astrophysics Data System (ADS)

    Chu, Michael Kok Loon

    Diabetes mellitus is a chronic illness manifested by improper blood glucose management, affecting over 350 million worldwide. As a result, all type 1 patients and roughly 20% of type 2 patients require exogenous insulin therapy to survive. Typically, daily multiple injections are taken to maintain normal glucose levels in response glucose spikes from meals. However, patient compliance and dosing accuracy can fluctuate with variation in meals, exercise, glucose metabolism or stress, leading to poor clinical outcomes. A 'smart', closed-loop insulin delivery system providing on-demand release kinetics responding to circulating glucose levels would be a boon for diabetes patients, replacing constant self monitoring and insulin. This thesis focuses on the development of a novel, 'smart' insulin microdevice that can provide on-demand insulin release in response to blood glucose levels. In the early stage, the feasibility of integrating a composite membrane with pH-responsive nanoparticles embedded in ethylcellulose membrane to provide pH-responsive in vitro release was examined and confirmed using a model drug, vitamin B12. In the second microdevice, glucose oxidase for generating pH signals from glucose oxidation, catalase and manganese dioxide nanoparticles, as peroxide scavengers, were used in a bioinorganic, albumin-based membrane cross-linked with a polydimethylsiloxane (PDMS) grid-microdevice system. This prototype device demonstrated insulin release in response to glucose levels in vitro and regulating plasma glucose in type 1 diabetic rats when implanted intraperitoneally. Advancement allowing for subcutaneous implantation and improved biocompatibility was achieved with surface modification of PDMS microdevices grafted with activated 20 kDa polyethylene glycol (PEG) chains, dramatically reducing immune response and local inflammation. When implanted subcutaneously in diabetic rats, glucose-responsive insulin delivery microdevices showed short and long

  18. 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. PMID:27612885

  19. Factors in Gestational Diabetes Mellitus Predicting the Needs for Insulin Therapy.

    PubMed

    Zhang, Ya; Shao, Jiashen; Li, Feifei; Xu, Xianming

    2016-01-01

    Objective. To identify factors predicting the need for insulin therapy in pregnancies complicated by gestational diabetes mellitus (GDM). Methods. A total of 1352 patients with GDM diagnosed by the 75-g/2-h oral glucose tolerance test (OGTT) were enrolled in this study. Univariate and multivariate analysis were performed; receiver operating characteristics (ROC) were also drawn. Results. There was a significant difference in factors such as maternal age, pregestational BMI, first visit SBP, first visit DBP, FBG of first visit, FBG at time of OGTT, 75-g OGTT glucose value (fasting, after 1 h and 2 h), and serum HbA1c level at diagnosis between patients with insulin therapy and patients with medical nutrition therapy (MNT) alone. Multivariate analysis showed that higher FBG at time of OGTT, first 75 g OGTT 2 h plasma glucose, and HbA1c concentration at diagnosis lead to more likely need of insulin therapy. Conclusion. The probability of insulin therapy can be estimated in pregnant women with GDM based on fasting and 2 h glucose values during OGTT and HbA1c value at diagnosis of GDM. PMID:27478440

  20. Factors in Gestational Diabetes Mellitus Predicting the Needs for Insulin Therapy

    PubMed Central

    Zhang, Ya; Shao, Jiashen; Li, Feifei

    2016-01-01

    Objective. To identify factors predicting the need for insulin therapy in pregnancies complicated by gestational diabetes mellitus (GDM). Methods. A total of 1352 patients with GDM diagnosed by the 75-g/2-h oral glucose tolerance test (OGTT) were enrolled in this study. Univariate and multivariate analysis were performed; receiver operating characteristics (ROC) were also drawn. Results. There was a significant difference in factors such as maternal age, pregestational BMI, first visit SBP, first visit DBP, FBG of first visit, FBG at time of OGTT, 75-g OGTT glucose value (fasting, after 1 h and 2 h), and serum HbA1c level at diagnosis between patients with insulin therapy and patients with medical nutrition therapy (MNT) alone. Multivariate analysis showed that higher FBG at time of OGTT, first 75 g OGTT 2 h plasma glucose, and HbA1c concentration at diagnosis lead to more likely need of insulin therapy. Conclusion. The probability of insulin therapy can be estimated in pregnant women with GDM based on fasting and 2 h glucose values during OGTT and HbA1c value at diagnosis of GDM. PMID:27478440

  1. Long-term interdisciplinary therapy reduces endotoxin level and insulin resistance in obese adolescents

    PubMed Central

    2012-01-01

    Aim The purpose of the present study was to assess the dietary fat intake, glucose, insulin, Homeostasis model assessment for insulin resistance HOMA-IR, and endotoxin levels and correlate them with adipokine serum concentrations in obese adolescents who had been admitted to long-term interdisciplinary weight-loss therapy. Design The present study was a longitudinal clinical intervention of interdisciplinary therapy. Adolescents (n = 18, aged 15–19 y) with a body mass index > 95th percentile were admitted and evaluated at baseline and again after 1 year of interdisciplinary therapy. We collected blood samples, and IL-6, adiponectin, and endotoxin concentrations were measured by ELISA. Food intake was measured using 3-day diet records. In addition, we assessed glucose and insulin levels as well as the homeostasis model assessment for insulin resistance (HOMA-IR). Results The most important finding from the present investigation was that the long-term interdisciplinary lifestyle therapy decreased dietary fat intake and endotoxin levels and improved HOMA-IR. We observed positive correlations between dietary fat intake and endotoxin levels, insulin levels, and the HOMA-IR. In addition, endotoxin levels showed positive correlations with IL-6 levels, insulin levels and the HOMA-IR. Interestingly, we observed a negative correlation between serum adiponectin and both dietary fat intake and endotoxin levels. Conclusions The present results indicate an association between dietary fat intake and endotoxin level, which was highly correlated with a decreased pro-inflammatory state and an improvement in HOMA-IR. In addition, this benefits effect may be associated with an increased adiponectin level, which suggests that the interdisciplinary therapy was effective in improving inflammatory pathways. PMID:22989045

  2. Gene Therapy for Diabetes Mellitus in Rats by Hepatic Expression of Insulin

    NASA Astrophysics Data System (ADS)

    Kolodka, Tadeusz M.; Finegold, Milton; Moss, Larry; Woo, Savio L. C.

    1995-04-01

    Type 1 diabetes mellitus is caused by severe insulin deficiency secondary to the autoimmune destruction of pancreatic β cells. Patients need to be controlled by periodic insulin injections to prevent the development of ketoacidosis, which can be fatal. Sustained, low-level expression of the rat insulin 1 gene from the liver of severely diabetic rats was achieved by in vivo administration of a recombinant retroviral vector. Ketoacidosis was prevented and the treated animals exhibited normoglycemia during a 24-hr fast, with no evidence of hypoglycemia. Histopathological examination of the liver in the treated animals showed no apparent abnormalities. Thus, the liver is an excellent target organ for ectopic expression of the insulin gene as a potential treatment modality for type 1 diabetes mellitus by gene therapy.

  3. Long-term insulin glargine therapy in type 2 diabetes mellitus: a focus on cardiovascular outcomes.

    PubMed

    Joseph, Joshua J; Donner, Thomas W

    2015-01-01

    Cardiovascular disease is the leading cause of mortality in type 2 diabetes mellitus. Hyperinsulinemia is associated with increased cardiovascular risk, but the effects of exogenous insulin on cardiovascular disease progression have been less well studied. Insulin has been shown to have both cardioprotective and atherosclerosis-promoting effects in laboratory animal studies. Long-term clinical trials using insulin to attain improved diabetes control in younger type 1 and type 2 diabetes patients have shown improved cardiovascular outcomes. Shorter trials of intensive diabetes control with high insulin use in higher risk patients with type 2 diabetes have shown either no cardiovascular benefit or increased all cause and cardiovascular mortality. Glargine insulin is a basal insulin analog widely used to treat patients with type 1 and type 2 diabetes. This review focuses on the effects of glargine on cardiovascular outcomes. Glargine lowers triglycerides, leads to a modest weight gain, causes less hypoglycemia when compared with intermediate-acting insulin, and has a neutral effect on blood pressure. The Outcome Reduction With Initial Glargine Intervention (ORIGIN trial), a 6.2 year dedicated cardiovascular outcomes trial of glargine demonstrated no increased cardiovascular risk.

  4. Combination therapy of dyslipidemia in non-insulin-dependent diabetes mellitus and the metabolic syndrome.

    PubMed

    Rembold, Christopher M

    2004-10-01

    Non-insulin-dependent diabetes mellitus (NIDDM) and the metabolic syndrome separately and additively increase the risk for atherosclerotic cardiovascular disease. Considering the high cardiovascular risk associated with NIDDM and the metabolic syndrome, aggressive therapy of dyslipidemia with tailored combination therapy should be considered given informed consent and discussion of risks. In addition to statins, niacin, and fibrates, therapies shown to decrease the risk for atherosclerotic cardiovascular disease include omega-3 fatty acids, diet, exercise, and optimal blood pressure control with thiazides and blockers of the renin-angiotensin system. These therapies should also be considered to reduce the high cardiovascular risk associated with NIDDM and the metabolic syndrome.

  5. Combination therapies in the management of type 2 diabetes: the use of insulin degludec/liraglutide

    PubMed Central

    Minze, Molly G; Chastain, Lisa M

    2016-01-01

    The global burden of type 2 diabetes is estimated to currently affect over 350 million people worldwide and is anticipated to continue increasing over the next 20 years. Current treatment guidelines recommend the choice of pharmacotherapy based upon patient-specific parameters, with combination therapy for patients with a hemoglobin A1c level ≥9%. A new combination therapy of insulin degludec + liraglutide provides a long-acting basal insulin with a glucagon-like peptide agonist. In clinical trials, this combination product has reduced hemoglobin A1c and fasting plasma glucose more than the individual agents alone. Further advantages observed with this combination include weight loss and decrease in hypoglycemia compared to basal insulin alone. PMID:27099505

  6. Low intensity exercise prevents disturbances in rat cardiac insulin signaling and endothelial nitric oxide synthase induced by high fructose diet.

    PubMed

    Stanišić, Jelena; Korićanac, Goran; Ćulafić, Tijana; Romić, Snježana; Stojiljković, Mojca; Kostić, Milan; Pantelić, Marija; Tepavčević, Snežana

    2016-01-15

    Increase in fructose consumption together with decrease in physical activity contributes to the development of metabolic syndrome and consequently cardiovascular diseases. The current study examined the preventive role of exercise on defects in cardiac insulin signaling and function of endothelial nitric oxide synthase (eNOS) in fructose fed rats. Male Wistar rats were divided into control, sedentary fructose (received 10% fructose for 9 weeks) and exercise fructose (additionally exposed to low intensity exercise) groups. Concentration of triglycerides, glucose, insulin and visceral adipose tissue weight were determined to estimate metabolic syndrome development. Expression and/or phosphorylation of cardiac insulin receptor (IR), insulin receptor substrate 1 (IRS1), tyrosine-specific protein phosphatase 1B (PTP1B), Akt, extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) and eNOS were evaluated. Fructose overload increased visceral adipose tissue, insulin concentration and homeostasis model assessment index. Exercise managed to decrease visceral adiposity and insulin level and to increase insulin sensitivity. Fructose diet increased level of cardiac PTP1B and pIRS1 (Ser307), while levels of IR and ERK1/2, as well as pIRS1 (Tyr 632), pAkt (Ser473, Thr308) and pERK1/2 were decreased. These disturbances were accompanied by reduced phosphorylation of eNOS at Ser1177. Exercise managed to prevent most of the disturbances in insulin signaling caused by fructose diet (except phosphorylation of IRS1 at Tyr 632 and phosphorylation and protein expression of ERK1/2) and consequently restored function of eNOS. Low intensity exercise could be considered as efficient treatment of cardiac insulin resistance induced by fructose diet.

  7. Insulin

    NASA Technical Reports Server (NTRS)

    2004-01-01

    The manipulation of organic materials--cells, tissues, and even living organisms--offers many exciting possibilities for the future from organic computers to improved aquaculture. Commercial researchers are using the microgravity environment to produce large near perfect protein crystals Research on insulin has yielded crystals that far surpass the quality of insulin crystals grown on the ground. Using these crystals industry partners are working to develop new and improved treatments for diabetes. Other researchers are exploring the possibility of producing antibiotics using plant cell cultures which could lead to both orbital production and the improvement of ground-based antibiotic production.

  8. Psychological barriers to optimal insulin therapy: more concerns in adolescent females than males

    PubMed Central

    Wisting, Line; Bang, Lasse; Skrivarhaug, Torild; Dahl-Jørgensen, Knut; Rø, Øyvind

    2016-01-01

    Objective The aim of this study is to investigate psychological barriers (illness perceptions, insulin beliefs, and coping strategies) to optimal insulin therapy among adolescents with type 1 diabetes (T1D), with a specific focus on gender differences and mode of treatment (insulin pump vs pen). Methods A total of 105 males and females (12–20 years) participated in this study. The Brief Illness Perception Questionnaire, the Beliefs about Medicines Questionnaire, and the Adolescent Coping Orientation for Problem Experiences were completed. Additionally, diabetes clinical data were collected by the Norwegian Childhood Diabetes Registry. Results Females had significantly more negative illness perceptions than males on all dimensions (p<0.05), with moderate-to-large effect sizes. Regarding insulin beliefs, females scored significantly higher than males on insulin concern (p<0.001), indicating more concerns about insulin. There were no significant gender differences on perceptions of insulin necessity. Finally, females scored significantly higher on the coping strategies being social and solving family problems (p<0.01), indicating more positive coping among females than males for these subscales. In terms of treatment mode, the only statistically significant difference in the psychological aspects was for the illness perception treatment control, with patients using insulin pen reporting more negative perceptions on this dimension than patients using insulin pump. Conclusions Addressing psychological aspects may be a clinically important supplement to standard somatic T1D care. The consistent finding of gender differences across the psychological measures implies that a tailored treatment approach for males and females with T1D may be warranted. PMID:27403325

  9. Beneficial effects of combined resveratrol and metformin therapy in treating diet-induced insulin resistance.

    PubMed

    Frendo-Cumbo, Scott; MacPherson, Rebecca E K; Wright, David C

    2016-08-01

    The polyphenol compound resveratrol (RSV) has attracted attention due to its reputed beneficial effects on insulin sensitivity. Our lab has previously identified protective effects of RSV against the development of type 2 diabetes in rats. These effects occurred in a manner similar to thiazolidinedione's (TZDs), a class of insulin sensitizing drugs. TZDs are commonly prescribed in combination with metformin (MET) and thus we sought to examine the combined effects of RSV and MET in treating insulin resistance. Male C57BL6 mice were fed a low- (LFD; 10% Kcal from fat) or high-fat diet (HFD; 60% Kcal from fat) for 9 weeks to induce glucose and insulin intolerance. HFD mice were then assigned to control (HFD), MET (231.28 ± 12.24 mg/kg/day), RSV (93.68 ± 3.51 mg/kg/day), or combined (COM; MET 232.01 ± 17.12 mg/kg/day and RSV 92.77 ± 6.92 mg/kg/day) treatment groups. Changes in glucose and insulin tolerance and tissue-specific insulin signaling were measured 4 weeks post-treatment. RSV or MET alone did not have beneficial effects on glucose tolerance, although MET significantly improved insulin tolerance compared to HFD Glucose and insulin tolerance were significantly improved in COM compared to HFD and this was mirrored by enhanced insulin-stimulated AKT phosphorylation in triceps muscle and inguinal subcutaneous adipose tissue in COM compared to HFD mice. Improvements with COM treatment were not explained by differences in body weight, adiposity, or markers of adipose tissue inflammation. In summary, this study provides evidence of beneficial effects of combined RSV and MET therapy in treating impairments in glucose homeostasis. PMID:27482073

  10. Intensive insulin treatment increases donor site wound protein synthesis in burn patients

    PubMed Central

    Tuvdendorj, Demidmaa; Zhang, Xiao-Jun; Chinkes, David L.; Aarsland, Asle; Kulp, Gabriela A.; Jeschke, Marc G.; Herndon, David N.

    2013-01-01

    Background In the treatment of burns, patients’ own skin is the preferred material to cover burn wounds, resulting in the need to create a donor site wound. Enhancement of healing of the donor site wound would be beneficial in burn patients. Insulin, an anabolic agent, is routinely used to treat hyperglycemia after injury. We investigated whether intensive insulin treatment (INS) increases fractional synthesis rate (FSR) of the donor site wound protein and decreases the length of hospitalization normalized for total body surface area burned (LOS/TBSA). Methods FSR of the donor site wound protein was measured in pediatric patients randomized to control (CNT) (n = 13) and INS (n = 10) treatments. Depending on the postoperative day when the tracer study was done studies were divided into “Early” (days < 5) and “Late” (days >=5) periods. Results FSR of the donor site wound protein was greater in the INS group at the “Early” period of wound healing (CNT vs. INS, 8.2±3.8 vs. 13.1±6.9 %/day, p: < 0.05); but not at the “Late” (CNT vs. INS, 19.7±4.6 vs. 16.6±4.0 %/day, p > 0.05). Despite these differences LOS/TBSA was not decreased in the INS group. Correlation analyses demonstrated that independently of the treatment regimen FSR positively correlated (p < 0.05) with time post creation of the donor site and negatively correlated (p < 0.05) with LOS/TBSA. Conclusions Insulin treatment increased FSR of the donor site wound protein in the early period of wound healing; FSR correlated with LOS/TBSA independently of the treatment regimen. PMID:21236451

  11. Acute and chronic effects of glyceryl trinitrate therapy on insulin and glucose regulation in humans.

    PubMed

    Jedrzkiewicz, Sean; Parker, John D

    2013-05-01

    This study examined the effect of acute and sustained transdermal glyceryl trinitrate (GTN) therapy on insulin and glucose regulation. Totally, 12 males (18-30 years) underwent a glucose tolerance test at baseline (visit 1), 90 minutes after acute transdermal GTN 0.6 mg/h (visit 2), following 7 days of continuous GTN (visit 3), and 2 to 3 days after stopping GTN (visit 4). At each visit, plasma glucose and insulin concentrations were measured before and 30, 60, 90, and 120 minutes after a 75-g oral glucose load. Indices of glucose metabolism that were examined included the insulin sensitivity index, the homeostasis model assessment of insulin resistance (HOMA-IR), and the insulinogenic index. The acute administration of GTN had no effect on glucose and insulin responses (visit 2). However, after 7 days of GTN exposure (visit 3) there was an increase in the mean glucose concentration measured after the oral glucose load. On visit 1, the mean glucose concentration (± standard deviation) following the 75 g oral glucose challenge was 5.7 ± 0.5 µmol/L. On visit 3, after 7 days of transdermal GTN therapy, the mean glucose concentration after the oral glucose was significantly higher; 6.2 ± 0.5 µmol/L (P < .015; 95% confidence intervals 0.25-0.77). There was also an increase in the HOMA-IR index; on visit 1, the median HOMA-IR (interquartile range) was 5.2 (3.9) versus 6.9 (6.8) on visit 3 (P < .015). Other indices of glucose metabolism did not change. These observations document that GTN therapy modifies glucose metabolism causing evidence of increased insulin resistance during sustained therapy in normal humans.

  12. The Experiences of School Nurses Caring for Students Receiving Continuous Subcutaneous Insulin Infusion Therapy

    ERIC Educational Resources Information Center

    Darby, Wendy

    2006-01-01

    Diabetes mellitus is the most common metabolic disorder in childhood. Today, children with diabetes are receiving new technologically advanced treatment options, such as continuous subcutaneous insulin infusion (CSII) therapy. School nurses are the primary health caregivers of children with diabetes during school hours. Therefore, it is important…

  13. Exercise and improved insulin sensitivity in older women: evidence of the enduring benefits of higher intensity training.

    PubMed

    DiPietro, Loretta; Dziura, James; Yeckel, Catherine W; Neufer, P Darrell

    2006-01-01

    Few studies have compared the relative benefits of moderate- vs. higher intensity exercise training on improving insulin sensitivity in older people while holding exercise volume constant. Healthy older (73 +/- 10 yr) women (N = 25) who were inactive, but not obese, were randomized into one of three training programs (9-mo duration): 1) high-intensity [80% peak aerobic capacity (V(O2)peak); T(H)] aerobic training; 2) moderate-intensity (65% V(O2)peak; T(M)) aerobic training; or 3) low-intensity (stretching) placebo control (50% V(O2)peak); C(TB)). Importantly, exercise volume (300 kcal/session) was held constant for subjects in both the T(H) and the T(M) groups. V(O2)peak was determined by using a graded exercise challenge on a treadmill. Total body fat and lean mass were determined with dual-energy X-ray absorptiometry. The rate of insulin-stimulated glucose utilization as well as the suppression of lipolysis were determined approximately 72 h after the final exercise bout by using a two-step euglycemic-hyperinsulinemic clamp. We observed improved glucose utilization at the higher insulin dose with training, but these improvements were statistically significant only in the T(H) (21%; P = 0.02) compared with the T(M) (16%; P = 0.17) and C(TB) (8%; P = 0.37) groups and were observed without changes in either body composition or V(O2)peak. Likewise in the T(H) group, we detected a significant improvement in insulin-stimulated suppression (%) of adipose tissue lipolysis at the low-insulin dose (38-55%, P < 0.05). Our findings suggest that long-term higher intensity exercise training provides more enduring benefits to insulin action compared with moderate- or low-intensity exercise, likely due to greater transient effects.

  14. 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.

  15. Integrated insulin pump therapy with continuous glucose monitoring for improved adherence: technology update.

    PubMed

    Tumminia, Andrea; Sciacca, Laura; Frittitta, Lucia; Squatrito, Sebastiano; Vigneri, Riccardo; Le Moli, Rosario; Tomaselli, Letizia

    2015-01-01

    Insulin pump therapy combined with real-time continuous glucose monitoring, known as sensor-augmented pump (SAP) therapy, has been shown to improve metabolic control and to reduce the rate of hypoglycemia in adults with type 1 diabetes compared to multiple daily injections or standard continuous subcutaneous insulin infusion. Glycemic variability is also reduced in patients on SAP therapy. This approach allows patients to monitor their glucose levels being informed of glycemic concentration and trend. Trained diabetic patients, therefore, can appropriately modify insulin infusion and/or carbohydrate intake in order to prevent hypo- or hyperglycemia. For these reasons, SAP therapy is now considered the gold standard for type 1 diabetes treatment. To be clinically effective, however, devices and techniques using advanced technology should not only have the potential to theoretically ameliorate metabolic control, but also be well accepted by patients in terms of satisfaction and health-related quality of life, because these factors will improve treatment adherence and consequently overall outcome. SAP therapy is generally well tolerated by patients; however, many clinical trials have identified significant noncompliance in the use of this device, most notably in the pediatric and adolescent populations. In this review we aim to analyze the main reasons for good or poor adherence to SAP therapy and to provide useful tips in order to fully benefit from this kind of novel therapeutic approach. PMID:26379428

  16. Integrated insulin pump therapy with continuous glucose monitoring for improved adherence: technology update

    PubMed Central

    Tumminia, Andrea; Sciacca, Laura; Frittitta, Lucia; Squatrito, Sebastiano; Vigneri, Riccardo; Le Moli, Rosario; Tomaselli, Letizia

    2015-01-01

    Insulin pump therapy combined with real-time continuous glucose monitoring, known as sensor-augmented pump (SAP) therapy, has been shown to improve metabolic control and to reduce the rate of hypoglycemia in adults with type 1 diabetes compared to multiple daily injections or standard continuous subcutaneous insulin infusion. Glycemic variability is also reduced in patients on SAP therapy. This approach allows patients to monitor their glucose levels being informed of glycemic concentration and trend. Trained diabetic patients, therefore, can appropriately modify insulin infusion and/or carbohydrate intake in order to prevent hypo- or hyperglycemia. For these reasons, SAP therapy is now considered the gold standard for type 1 diabetes treatment. To be clinically effective, however, devices and techniques using advanced technology should not only have the potential to theoretically ameliorate metabolic control, but also be well accepted by patients in terms of satisfaction and health-related quality of life, because these factors will improve treatment adherence and consequently overall outcome. SAP therapy is generally well tolerated by patients; however, many clinical trials have identified significant noncompliance in the use of this device, most notably in the pediatric and adolescent populations. In this review we aim to analyze the main reasons for good or poor adherence to SAP therapy and to provide useful tips in order to fully benefit from this kind of novel therapeutic approach. PMID:26379428

  17. How intensive does anomia therapy for people with aphasia need to be?

    PubMed

    Sage, Karen; Snell, Claerwen; Lambon Ralph, Matthew A

    2011-01-01

    The intensity of aphasia therapy has been a key clinical question. The aim of this case-series study was to compare the outcome of intensive and non-intensive therapy in the relearning of words for people with aphasia. Eight participants took part in a study comparing the intensity of delivery of the therapy. Participants received two courses of the same therapy (each lasting 10 sessions) delivered either intensively or non-intensively. Therapy consisted of confrontation naming with progressive phonemic and orthographic cues. Post-therapy assessments were carried out immediately after the study and one month later. Performance was also monitored during each therapy session. Immediately post-therapy, both types of therapy had improved naming accuracy considerably and there was no significant difference between the two interventions. One month later, seven out of eight participants showed a small yet significant difference in naming accuracy, favouring non-intensive over intense therapy. There were no differences in the learning patterns during the therapy sessions between the intensive and non-intensive therapies. For the majority of people with aphasia post-stroke, both intense and non-intense therapy for anomia leads to improved naming performance. Retention at one-month post therapy is relatively superior after non-intensive therapy.

  18. High-Intensity Focused Ultrasound Therapy: an Overview for Radiologists

    PubMed Central

    Kim, Young-sun; Choi, Min Joo; Lim, Hyo Keun; Choi, Dongil

    2008-01-01

    High-intensity focused ultrasound therapy is a novel, emerging, therapeutic modality that uses ultrasound waves, propagated through tissue media, as carriers of energy. This completely non-invasive technology has great potential for tumor ablation as well as hemostasis, thrombolysis and targeted drug/gene delivery. However, the application of this technology still has many drawbacks. It is expected that current obstacles to implementation will be resolved in the near future. In this review, we provide an overview of high-intensity focused ultrasound therapy from the basic physics to recent clinical studies with an interventional radiologist's perspective for the purpose of improving the general understanding of this cutting-edge technology as well as speculating on future developments. PMID:18682666

  19. Analysis of the add-on effect of α-glucosidase inhibitor, acarbose in insulin therapy: A pilot study

    PubMed Central

    Li, Feng-Fei; Fu, Li-Yuan; Xu, Xiao-Hua; Su, Xiao-Fei; Wu, Jin-Dan; Ye, Lei; Ma, Jian-Hua

    2016-01-01

    The aim of the present study was to evaluate the add-on effect of acarbose therapy in oxidative stress, and the lipid and inflammatory profiles of patients with type 2 diabetes mellitus (T2DM) treated with insulin. This was an open and unblended study. Patients (n=134) with T2DM (haemoglobin A1c range, 9.0–12.0%) were recruited. After continuous subcutaneous insulin infusion for 7 days for initial rapid correction of hyperglycaemia, a premixed insulin titration period (duration, 4–6 days) subsequently followed. Patients were then randomized (1:1) into two groups as follows: An acarbose plus pre-mixed 30/70 insulin group or a pre-mixed 30/70 insulin only group; each group received treatment for 2 weeks. Plasma high-sensitivity C-reactive protein (Hs-CRP), 8-iso-prostaglandin F2α (8-iso PGF2α), tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-6 levels were measured before and after therapy. Patients that received acarbose plus insulin demonstrated greater reduction in 8-iso PGF2α, Hs-CRP, TNF-α, IL-1β and IL-6 levels when compared with the insulin only patients. Thus, acarbose add-on insulin therapy was identified to be associated with greater improvements in oxidative stress and inflammation in patients with T2DM when compared with those that received insulin only therapy.

  20. Improving the efficacy of type 1 diabetes therapy by transplantation of immunoisolated insulin-producing cells.

    PubMed

    Ngoc, Phan Kim; Phuc, Pham Van; Nhung, Truong Hai; Thuy, Duong Thanh; Nguyet, Nguyen Thi Minh

    2011-06-01

    Type 1 diabetes occurs when pancreatic islet β-cells are damaged and are thus unable to secrete insulin. Pancreas- or islet-grafting therapy offers highly efficient treatment but is limited by inadequate donor islets or pancreases for transplantation. Stem-cell therapy holds tremendous potential and promises to enhance treatment efficiency by overcoming the limitations of traditional therapies. In this study, we evaluated the efficiency of preclinical diabetic treatment. Diabetes was induced in mice by injections of streptozotocin. Mesenchymal stem cells (MSCs) were derived from mouse bone marrow or human umbilical cord blood and subsequently differentiated into insulin-producing cells. These insulin-producing cells were encapsulated in an alginate membrane to form capsules. Finally, these capsules were grafted into diabetic mice by intraperitoneal injection. Treatment efficiency was evaluated by monitoring body weight and blood glucose levels. Immune reactions after transplantation were monitored by counting total white blood cells. Allografting or xenografting of encapsulated insulin-producing cells (IPCs) reduced blood glucose levels and increased body weight following transplantation. Encapsulation with alginate conferred immune isolation and prevented graft rejection. These results provide further evidence supporting the use of allogeneic or xenogeneic MSCs obtained from bone marrow or umbilical cord blood for treating type 1 diabetes. PMID:21567289

  1. Weight in adolescents with type 1 diabetes mellitus during continuous subcutaneous insulin infusion (CSII) therapy.

    PubMed

    Raile, K; Noelle, V; Landgraf, R; Schwarz, H P

    2002-05-01

    Continuous subcutaneous insulin infusion (CSII) has become increasingly popular as a form of intensified insulin therapy in adolescents with type 1 diabetes mellitus (DM). One reported drawback was increased weight gain in adolescents after initiation of insulin pump therapy. In a prospective, longitudinal, non-randomized and case controlled study, we followed 12 adolescents (mean age 13.6 yr, 8 males, 4 females) from 6 months before the start of CSII to 12 months on CSII. These 12 adolescents with DM on CSII were matched for age, gender, HbA1c, duration of DM, and body mass index (BMI) with 12 adolescents who continued on multiple injection therapy (MIT). In addition, six of the 12 adolescents on CSII intended to control their weight by means of the insulin pump. These six vs six adolescents within the CSII group were further analyzed for weight development and eating habits. Clinical indications for CSII were dawn phenomenon, night-time hypoglycemia and patient request for more flexibility in DM management. All patients had been in satisfactory metabolic control on MIT. After 12 months of CSII, the daily insulin requirement remained significantly lower than 18 months before (0.79 +/- 0.11 vs 1.02 +/- 27 U/kg/d, p = 0.034) and number of daily meals was lower (4.1 +/- 0.9 vs 6.5 +/- 0.7, p = 0.006). Mean initial HbA1c was 7.4% in the MIT and CSII patients, and remained comparable between these two groups. BMI was not different between the CSII and MIT group over the entire study period. However, those adolescents on CSII who intended to control their weight by means of the insulin pump were able to achieve relative weight loss during the,first 6 months on CSII. Two patients of the CSII group had one severe hypoglycemic episode with loss of consciousness. In conclusion, CSII does not lead to weight gain by itself, but allows sufficient weight control without a negative effect on metabolic control. The general threat of weight gain in patients who switch to insulin

  2. Effects of intensive dietary treatment on insulin-stimulated skeletal muscle glycogen synthase activation and insulin secretion in newly presenting type 2 diabetic patients.

    PubMed

    Johnson, A B; Argyraki, M; Thow, J C; Broughton, D; Jones, I R; Taylor, R

    1990-06-01

    Ten newly presenting, untreated, Europid Type 2 diabetic patients were studied before and after 8 weeks treatment with intensive diet alone. Nine normal control subjects were also studied. The degree of activation of skeletal muscle glycogen synthase (GS) was used as an intracellular marker of insulin action, prior to and during a 240-min insulin infusion (100 mU kg-1 h-1). Fasting blood glucose decreased from 12.1 +/- 0.9 (+/- SE) to 9.2 +/- 0.8 mmol l-1 (p less than 0.01), but there was no change in fasting insulin concentrations, 9.9 +/- 2.3 vs 9.3 +/- 2.1 mU l-1. Fractional GS activity did not increase in the Type 2 diabetic patients during the insulin infusion either at presentation (change -1.5 +/- 1.9%) or after treatment (change +0.9 +/- 1.8%), and was markedly decreased compared with the control subjects (change +14.5 +/- 2.8%, both p less than 0.001). Glucose requirement during the clamp was decreased in the Type 2 diabetic patients at presentation (2.2 +/- 0.7 vs 7.3 +/- 0.6 mg kg-1 min-1, p less than 0.001), and despite improvement following dietary treatment to 3.3 +/- 0.6 mg kg-1 min-1 (p less than 0.01) remained lower than in the control subjects (p less than 0.001). Fasting plasma non-esterified fatty acid (NEFA) concentrations were elevated at presentation (p less than 0.05), and failed to suppress normally during the insulin infusion. After treatment fasting NEFA concentrations decreased (p less than 0.05) and suppressed normally (p less than 0.05). Insulin secretion was assessed following an intravenous bolus of glucose (0.5 g kg-1) at euglycaemia before and after treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

  3. Redesigning an intensive insulin service for patients with type 1 diabetes: a patient consultation exercise

    PubMed Central

    Ozcan, Seyda; Rogers, Helen; Choudhary, Pratik; Amiel, Stephanie A; Cox, Alison; Forbes, Angus

    2013-01-01

    Context Providing effective support for patients in using insulin effectively is essential for good diabetes care. For that support to be effective it must reflect and attend to the needs of patients. Purpose To explore the perspectives of adult type 1 diabetes patients on their current diabetes care in order to generate ideas for creating a new patient centered intensive insulin clinic. Methods A multi-method approach was used, comprising: an observational exercise of current clinical care; three focus groups (n = 17); and a survey of service users (n = 419) to test the ideas generated from the observational exercise and focus groups (rating 1 to 5 in terms of importance). The ideas generated by the multi-method approach were organized thematically and mapped onto the Chronic Care Model (CCM). Results The themes and preferences for service redesign in relation to CCM components were: health care organization, there was an interest in having enhanced systems for sharing clinical information; self-management support, patients would like more flexible and easy to access resources and more help with diabetes technology and psychosocial support; delivery system design and clinical information systems, the need for greater integration of care and better use of clinic time; productive relationships, participants would like more continuity; access to health professionals, patient involvement and care planning. The findings from the patient survey indicate high preferences for most of the areas for service enhancement identified in the focus groups and observational exercise. Clinical feedback and professional continuity (median = 5, interquartile range = 1) were the most highly rated. Conclusion The patient consultation process had generated important ideas on how the clinical team and service can improve the care provided. Key areas for service development were: a stronger emphasis of collaborative care planning; improved patient choice in the use of health technology

  4. 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.

  5. The Efficacy of Vildagliptin Concomitant With Insulin Therapy in Type 2 Diabetic Subjects

    PubMed Central

    Ito, Daisuke; Inoue, Kazuyuki; Kaneko, Kimie; Yanagisawa, Morifumi; Sumita, Takashi; Ikegami, Yuichi; Awata, Takuya; Ishida, Hitoshi; Katayama, Shigehiro; Inukai, Kouichi

    2015-01-01

    Background In Japan, dipeptidyl peptidase 4 (DPP4) inhibitors have become standard therapeutic agents for type 2 diabetes, and numbers of patients receiving insulin therapy combined with DPP4 inhibitors, which is a highly effective regimen, are increasing. Methods In this study, we evaluated the efficacy of vildagliptin administered at the dose of 100 mg twice daily in 57 patients with type 2 diabetes already receiving insulin treatment. Results The 36 patients who simply received add-on vildagliptin showed a 0.6% decrease in HbA1c levels, despite a marked insulin dose reduction, mainly bolus insulin, of approximately 8.3 units. In addition, body mass index exhibited a significant negative correlation with the efficacy of vildagliptin, i.e., ΔHbA1c. On the other hand, the 21 patients switched from 50 mg of sitagliptin to vildagliptin showed HbA1c decreases approaching 0.7%. Conclusion Taking into consideration that twice-daily oral vildagliptin has already been reported to be advantageous in reducing postprandial hyperglycemia, this drug was suggested to be more effective in reducing HbA1c than sitagliptin under conditions in which it is used as a supplement to basal insulin, as in this study. PMID:25780477

  6. Personalized intensification of insulin therapy in type 2 diabetes - does a basal-bolus regimen suit all patients?

    PubMed

    Giugliano, D; Sieradzki, J; Stefanski, A; Gentilella, R

    2016-08-01

    Many patients with type 2 diabetes mellitus (T2DM) require insulin therapy. If basal insulin fails to achieve glycemic control, insulin intensification is one possible treatment intensification strategy. We summarized clinical data from randomized clinical trials designed to compare the efficacy and safety of basal-bolus and premixed insulin intensification regimens. We defined a between-group difference of ≥0.3% in end-of-study glycated hemoglobin (HbA1c) as clinically meaningful. A PubMed database search supplemented by author-identified papers yielded 15 trials which met selection criteria: randomized design, patients with T2DM receiving basal-bolus (bolus injection ≤3 times/day) vs. premixed (≤3 injections/day) insulin regimens, primary/major endpoint(s) HbA1c- and/or hypoglycemia-related, and trial duration ≥12 weeks. Glycemic control improved with both basal-bolus and premixed insulin regimens with - in most cases - acceptable levels of weight gain and hypoglycemia. A clinically meaningful difference between regimens in glycemic control was recorded in only four comparisons, all of which favored basal-bolus therapy. The incidence of hypoglycemia was significantly different between regimens in only three comparisons, one of which favored premixed insulin and two basal-bolus therapy. Of the four trials that reported a significant difference between regimens in bodyweight change, two favored basal-bolus therapy and two favored premixed insulin. Thus, on a population level, neither basal-bolus therapy nor premixed insulin showed a consistent advantage in terms of glycemic control, hypoglycemic risk, or bodyweight gain. It is therefore recommended that clinicians should adopt an individualized approach to insulin intensification - taking into account the benefits and risks of each treatment approach and the attitude and preferences of each patient - in the knowledge that both basal-bolus and premixed regimens may be successful.

  7. Combined therapy of insulin-producing cells and haematopoietic stem cells offers better diabetic control than only haematopoietic stem cells' infusion for patients with insulin-dependent diabetes.

    PubMed

    Dave, Shruti D; Trivedi, Hargovind L; Gopal, Saroj C; Chandra, Tulika

    2014-09-08

    Insulin-dependent diabetes mellitus (IDDM) is a chronic condition characterised by impaired blood sugar metabolism and autoimmunity. We report two children: a 5-year-old girl on exogenous insulin therapy of 30 IU/day and a 9-year-old boy on short-acting insulin 30 IU/day, long-acting insulin 70 IU/day, with IDDM since 4 and 7 years, respectively. We infused in vitro-generated donor bone marrow (BM)-derived haematopoietic stem cells (HSC) in patient 1 and insulin-secreting cells trans-differentiated from autologous adipose tissue-derived mesenchymal stem cells along with BM-HSC in patient 2 under non-myeloablative conditioning. Patient 1 improved during the initial 6 months, but then again lost metabolic control with increased blood sugar levels and insulin requirement of 32 IU/day; we lost her to follow-up after 18 months. Patient 2, over follow-up of 24.87 months, has stable blood sugar levels with glycosylated haemoglobin of 6.4% and present insulin requirement of 15 IU/day.

  8. Combined therapy of insulin-producing cells and haematopoietic stem cells offers better diabetic control than only haematopoietic stem cells’ infusion for patients with insulin-dependent diabetes

    PubMed Central

    Dave, Shruti D; Trivedi, Hargovind L; Gopal, Saroj C; Chandra, Tulika

    2014-01-01

    Insulin-dependent diabetes mellitus (IDDM) is a chronic condition characterised by impaired blood sugar metabolism and autoimmunity. We report two children: a 5-year-old girl on exogenous insulin therapy of 30 IU/day and a 9-year-old boy on short-acting insulin 30 IU/day, long-acting insulin 70 IU/day, with IDDM since 4 and 7 years, respectively. We infused in vitro-generated donor bone marrow (BM)-derived haematopoietic stem cells (HSC) in patient 1 and insulin-secreting cells trans-differentiated from autologous adipose tissue-derived mesenchymal stem cells along with BM-HSC in patient 2 under non-myeloablative conditioning. Patient 1 improved during the initial 6 months, but then again lost metabolic control with increased blood sugar levels and insulin requirement of 32 IU/day; we lost her to follow-up after 18 months. Patient 2, over follow-up of 24.87 months, has stable blood sugar levels with glycosylated haemoglobin of 6.4% and present insulin requirement of 15 IU/day. PMID:25199184

  9. 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

  10. Calculation of the intake of three intense sweeteners in young insulin-dependent diabetics.

    PubMed

    Garnier-Sagne, I; Leblanc, J C; Verger, P

    2001-07-01

    In 1994, European Directive 94/35/CE authorised the use as food additives of five intense sweeteners for which Acceptable Daily Intakes (ADI) were established. The same directive stipulated that member states should organise a monitoring system to determine the consumption of these substances. Diabetic children are normally considered to constitute a group with a high consumption of sweeteners (European Commission, 1998. Report on Methodology for the Monitoring of Food Additives Intake across the European Union. Report of the Scientific Cooperation, Task 4.2 SCOOP/INT/REPORT/2. European Commission Directorate General III, Brussels.). A stepwise approach to the food additive intake in the general population had shown that three of the five authorised intense sweeteners (aspartame, saccharin and acesulfame K) are used at particularly high levels in sugar-free foods and are also very commonly utilised as table-top sweeteners. This paper presents the results of a food intake survey conducted in a group of French, insulin-dependent children in 1997, aimed at estimating the Theoretical Maximum Daily Intake (TMDI) for these three sweeteners and comparing this with the relevant ADI values. A 5-day diary questionnaire was used to estimate the intake of sugar-free, artificially sweetened foods and table-top sweeteners. When assessing the intake of each additive, all sugar-free products were assumed to be sweetened using a single sweetener at its maximum authorised level. This study was performed in five age groups, and based on the mean and 97.5th percentile of the distribution of consumption, demonstrated that it was unlikely that total exposure could rise above the ADI.

  11. 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.

  12. Intensity-Modulated Arc Therapy for Pediatric Posterior Fossa Tumors

    SciTech Connect

    Beltran, Chris; Gray, Jonathan; Merchant, Thomas E.

    2012-02-01

    Purpose: To compare intensity-modulated arc therapy (IMAT) to noncoplanar intensity-modulated radiation therapy (IMRT) in the treatment of pediatric posterior fossa tumors. Methods and Materials: Nine pediatric patients with posterior fossa tumors, mean age 9 years (range, 6-15 years), treated using IMRT were chosen for this comparative planning study because of their tumor location. Each patient's treatment was replanned to receive 54 Gy to the planning target volume (PTV) using five different methods: eight-field noncoplanar IMRT, single coplanar IMAT, double coplanar IMAT, single noncoplanar IMAT, and double noncoplanar IMAT. For each method, the dose to 95% of the PTV was held constant, and the doses to surrounding critical structures were minimized. The different plans were compared based on conformity, total linear accelerator dose monitor units, and dose to surrounding normal tissues, including the entire body, whole brain, temporal lobes, brainstem, and cochleae. Results: The doses to the target and critical structures for the various IMAT methods were not statistically different in comparison with the noncoplanar IMRT plan, with the following exceptions: the cochlear doses were higher and whole brain dose was lower for coplanar IMAT plans; the cochleae and temporal lobe doses were lower and conformity increased for noncoplanar IMAT plans. The advantage of the noncoplanar IMAT plan was enhanced by doubling the treatment arc. Conclusion: Noncoplanar IMAT results in superior treatment plans when compared to noncoplanar IMRT for the treatment of posterior fossa tumors. IMAT should be considered alongside IMRT when treatment of this site is indicated.

  13. 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

  14. 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.

  15. Combination therapy with DPP-4 inhibitors and insulin in patients with type 2 diabetes mellitus: what is the evidence?

    PubMed

    Charbonnel, Bernard; Schweizer, Anja; Dejager, Sylvie

    2013-04-01

    As type 2 diabetes mellitus (T2DM) progresses, most patients will require insulin replacement therapy. Whether oral antidiabetic drug (OAD) therapy should be retained when initiating insulin is still debated. While the rationale to keep metformin with insulin is strong (mostly as an insulin-sparing agent to limit weight gain), the evidence is less clear for other OADs. In particular, the question now comes up what the expected benefit could be of combining the newer agents, such as the dipeptidyl peptidase-4 (DPP-4) inhibitors with insulin. Additionally, when metformin is no longer a treatment option, as in the case of patients with severe renal impairment, insulin is often used as monotherapy, with little evidence of benefit in maintaining other OADs. In this specific situation, it is also of interest to evaluate the potential benefit of combined treatment with a DPP-4 inhibitor and insulin. Among the classic limitations of insulin therapy in patients with T2DM, hypoglycemia remains a major barrier to glycemic control, along with weight gain exacerbation. The oral DPP-4 inhibitors improve glycemic control by increasing the sensitivity of the islet cells to glucose, and thus are not associated with an increased risk for hypoglycemia and are weight neutral. In addition to the expected benefits associated with limiting insulin dose and regimen complexity, the specific advantages the DPP-4 inhibitor drug class on hypoglycemia and weight gain could justify combining DPP-4 inhibitors with insulin; additionally, a DPP-4 inhibitor may be of special value to decrease glycemic excursions that are not properly addressed by basal insulin therapy and metformin use, even after optimizing titration of the basal insulin. However, given the common original perception that treatment with DPP-4 inhibitors may be less beneficial with increasing disease progression because of the loss of β-cell function, the potential relevance of these agents in the setting of advanced T2DM treated

  16. Intensity modulating and other radiation therapy devices for dose painting.

    PubMed

    Galvin, James M; De Neve, Wilfried

    2007-03-10

    The introduction of intensity-modulated radiation therapy (IMRT) in the early 1990s created the possibility of generating dramatically improved dose distributions that could be tailored to fit a complex geometric arrangement of targets that push against or even surround healthy critical structures. IMRT is a new treatment paradigm that goes beyond the capabilities of the earlier technology called three-dimensional radiation therapy (3DCRT). IMRT took the older approach of using fields that conformed to the silhouette of the target to deliver a relatively homogeneous intensity of radiation and separated the conformal fields into many subfields so that intensity could be varied to better control the final dose distribution. This technique makes it possible to generate radiation dose clouds that have indentations in their surface. Initially, this technology was mainly used to avoid and thus control the dose delivered to critical structures so that they are not seriously damaged in the process of irradiating nearby targets to an appropriately high dose. Avoidance of critical structures allowed homogeneous dose escalation that led to improved local control for small tumors. However, the normal tissue component of large tumors often prohibits homogeneous dose escalation. A newer concept of dose-painting IMRT is aimed at exploiting inhomogeneous dose distributions adapted to tumor heterogeneity. Tumor regions of increased radiation resistance receive escalated dose levels, whereas radiation-sensitive regions receive conventional or even de-escalated dose levels. Dose painting relies on biologic imaging such as positron emission tomography, functional magnetic resonance imaging, and magnetic resonance spectroscopy. This review will describe the competing techologies for dose painting with an emphasis on their commonalities.

  17. Intrasound therapy in tendon healing: is intensity a factor?

    PubMed Central

    Aiyegbusi, AI; Duru, FIO; Akinbo, SR; Noronha, CC; Okanlawon, AO

    2010-01-01

    Objective This study investigated the effects of low- and high-intensity intrasound therapy (LITR and HITR, respectively) given once daily and twice daily on the morphology and oxidative stress in healing tendon tissue following an acute injury. Methods Eighty-five male rats, randomized into six groups were further subdivided into groups A, B, and C, except for Group 1 which was subdivided into A and B only. Groups 2–6 underwent an induced crush injury. The six groups were allocated to: serve as controls (Group 1), receive no treatment (Group 2), HITR twice daily (Group 3), HITR once daily (Group 4), LITR twice daily (Group 5), and LITR once daily (Group 6). Intrasound therapy (ITR) was commenced 24 hours postinjury and was given once daily or twice daily over the first 14 days postinjury. The animals in subgroups A and B were sacrificed on day 15 postinjury, and those in subgroup C were sacrificed on day 31 postinjury. The tendons were excised, and processed for histology and malondialdehyde (MDA) assay. Results There was no significant difference in the tenocyte population between the HITR- and LITR-treated groups. However, twice-daily treatment in either the low- or high-intensity mode resulted in significant tenocyte proliferation compared with the once-daily treated groups, and also had the highest percentage of tenoblasts compared with the population of tenocytes in the proliferative phase of healing. All treatment protocols marginally lowered the MDA level. Conclusion The role of IRT in tendon healing is influenced more by the frequency of treatment rather than the intensity of the delivered dosage.

  18. Development of a support skill scale in insulin therapy: a nationwide study in Japan.

    PubMed

    Nishigaki, Masakazu; Shimizu, Yasuko; Kuroda, Kumiko; Mori, Kozue; Ohara, Yuko; Seto, Natsuko; Yoneda, Akiko; Miyatake, Yoko; Kazuma, Keiko; Masaki, Harue

    2012-11-01

    The aim of this cross-sectional, nationwide study in Japan was to develop a support skill scale for insulin therapy (IT-SSS) and to evaluate its validity and reliability. The sample consisted of 1604 nurses at 123 hospitals throughout the country. The factor validity, known-group validity, convergent validity, discriminant validity and internal consistency of IT-SSS were assessed. IT-SSS consisted of 26 minimum and 25 standard support skills. They included 4 subscales for minimum skills: management strategy for hypoglycemia, education about insulin injection technique, individual assessment and support about insulin rejection, and collaboration with medical professionals and patient/family. Three subscales for standard skills: apprehensions concerning the will and emotion of the patient, management for blood glucose control, and coordination in insulin management. Cronbach's alpha coefficient was between 0.75 and 0.90, suggesting strong internal consistency. Multitrait analysis showed that convergent validity was complete, and discriminant validity was found to be almost complete in both minimum and standard skill scales (scaling success rates of 97.6% and 98.7% across all subgroups, respectively). Known group analysis clearly showed that specialist nurses have significantly higher skills than general nurses. These findings indicate that IT-SSS has a reasonable factor validity, convergent validity, discriminant validity, known group validity, and internal consistency.

  19. Short-term insulin therapy in adolescents with type 2 diabetes mellitus.

    PubMed

    Sellers, E A C; Dean, H J

    2004-11-01

    The optimum pharmacological treatment of type 2 diabetes mellitus (DM2) in youth for those who fail to achieve adequate glycemic control (HbA1c <7%) with lifestyle intervention is unknown. The aim of this pilot study was to observe the effect of short-term insulin therapy (<16 weeks duration) on glycemic control in youth with DM2. A pre-mix 30/70 insulin was given twice daily to 18 youth aged 10-18 years with DM2 for 8.7+/-4.3 weeks with a starting dose of 0.5 U/kg/day. HbA1c, body mass index (BMI) and episodes of hypoglycemia were monitored during the treatment period and for a 12-month period after insulin was stopped. Mean HbA1c decreased from 12.81% to 7.59% (95% CI 6.54, 8.64). This improvement persisted for 12 months without any further drug therapy. There was no significant change in mean BMI and there were no episodes of moderate or severe hypoglycemia. Decreasing beta-cell glucose toxicity with rapid improvement of blood glucose may play an important role in treatment of DM2 in adolescents. Early success in achieving target blood glucose levels is an important aspect of adolescent DM2 care.

  20. Clinical Implementation of Intensity Modulated Proton Therapy for Thoracic Malignancies

    SciTech Connect

    Chang, Joe Y.; Li, Heng; Zhu, X. Ronald; Liao, Zhongxing; Zhao, Lina; Liu, Amy; Li, Yupeng; Sahoo, Narayan; Poenisch, Falk; Gomez, Daniel R.; Wu, Richard; Gillin, Michael; Zhang, Xiaodong

    2014-11-15

    Purpose: Intensity modulated proton therapy (IMPT) can improve dose conformality and better spare normal tissue over passive scattering techniques, but range uncertainties complicate its use, particularly for moving targets. We report our early experience with IMPT for thoracic malignancies in terms of motion analysis and management, plan optimization and robustness, and quality assurance. Methods and Materials: Thirty-four consecutive patients with lung/mediastinal cancers received IMPT to a median 66 Gy(relative biological equivalence [RBE]). All patients were able to undergo definitive radiation therapy. IMPT was used when the treating physician judged that IMPT conferred a dosimetric advantage; all patients had minimal tumor motion (<5 mm) and underwent individualized tumor-motion dose-uncertainty analysis and 4-dimensional (4D) computed tomographic (CT)-based treatment simulation and motion analysis. Plan robustness was optimized by using a worst-case scenario method. All patients had 4D CT repeated simulation during treatment. Results: IMPT produced lower mean lung dose (MLD), lung V{sub 5} and V{sub 20}, heart V{sub 40}, and esophageal V{sub 60} than did IMRT (P<.05) and lower MLD, lung V{sub 20}, and esophageal V{sub 60} than did passive scattering proton therapy (PSPT) (P<.05). D{sub 5} to the gross tumor volume and clinical target volume was higher with IMPT than with intensity modulated radiation therapy or PSPT (P<.05). All cases were analyzed for beam-angle-specific motion, water-equivalent thickness, and robustness. Beam angles were chosen to minimize the effect of respiratory motion and avoid previously treated regions, and the maximum deviation from the nominal dose-volume histogram values was kept at <5% for the target dose and met the normal tissue constraints under a worst-case scenario. Patient-specific quality assurance measurements showed that a median 99% (range, 95% to 100%) of the pixels met the 3% dose/3 mm distance criteria for the

  1. Intensity modulated arc therapy (IMAT) with centrally blocked rotational fields.

    PubMed

    Cotrutz, C; Kappas, C; Webb, S

    2000-08-01

    A new technique for intensity-modulated beam (IMB) delivery that combines the features of intensity modulated arc therapy (IMAT) with the use of 'classical blocks' is proposed. The role of the blocks is to realize the high-gradient modulation of the intensity profile corresponding to the region to be protected within the body contour, while the MLC leaves or the secondary collimator defines the rest of the field and delivers intensity-modulated multiple rotational segments. The centrally blocked radiation fields are applied sequentially, in several rotations. Each rotation of the gantry is responsible for delivering one segment of the optimal intensity profile. The new IMAT technique is applied for a treatment geometry represented by an annular target volume centrally located within a circular body contour. The annulus encompasses a circular critical structure, which is to be protected. The beam opening and corresponding weight of each segment are determined in two ways. The first method applies a linear optimization algorithm to precalculated centrally blocked radial dose profiles. These radial profiles are calculated for a set of beam openings, ranging from the largest field that covers the whole planning target volume (PTV) to the smallest, which is 1 cm larger than the width of the central block. The optimization is subjected to dose homogeneity constraints imposed on a linear combination of these profiles and finally delivers the dimensions and weights of the rotational beams to be used in combination. The second method decomposes into several subfields the fluence profile of a rotational beam known to deliver a constant dose level to PTV. This fluence profile is determined by using the analytical method proposed by Brahme for the case of the annular PTV and the concentric organ at risk (OAR). The proper segmentation of this intensity profile provides the field sizes and corresponding weights of the subfields to be used in combination. Both methods show that

  2. 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.

  3. Development and evaluation of a virtual intensive therapy unit - VITU.

    PubMed

    Theodoropoulos, A; Kneebone, R; Dornan, B; Leonard, R; Bello, F

    2007-01-01

    Complex and safety critical healthcare environments like the Intensive Therapy Unit demand highly skilled professionals efficiently interacting with their technologically advanced surroundings and with each other. The ITU environment is daunting to newcomers and contains considerable potential for harm by inexpert treatment. In spite of this, current training is largely workplace based and depends upon observation and supervised practice with real patients. We propose the development of a distributed collaborative environment that recreates key elements of critical care. Centred on a 'virtual bedspace', team members will care for the patient in a way that accurately reflects actual practice and therefore minimises any learning gap. Graded exposure to increasing levels of complexity will ensure that collaborative learning takes place alongside each participant's clinical experience and complements it appropriately.

  4. Intensity-modulated radiation therapy: supportive data for prostate cancer.

    PubMed

    Cahlon, Oren; Hunt, Margie; Zelefsky, Michael J

    2008-01-01

    Since its introduction into clinical use in the mid-1990s, intensity-modulated radiation therapy (IMRT) has emerged as the most effective and widely used form of external-beam radiotherapy for localized prostate cancer. Multiple studies have confirmed the importance of delivering sufficiently high doses to the prostate to achieve cure. The dosimetric superiority of IMRT over conventional techniques to produce conformal dose distributions that allow for organ sparing has been shown. A growing number of reports have confirmed that IMRT is the safest way to deliver high doses of external-beam irradiation to the prostate and the regional lymph nodes. Advances in imaging and onboard verification systems continue to advance the capabilities of IMRT and have potential implications with regards to further dose escalation and hypofractionated regimens. The clinical data in support of IMRT and the associated technical aspects of IMRT treatment planning and implementation are highlighted in this review.

  5. 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.

  6. Safe and Efficacious Use of Automated Bolus Advisors in Individuals Treated With Multiple Daily Insulin Injection (MDI) Therapy

    PubMed Central

    Parkin, Christopher G.; Barnard, Katharine; Hinnen, Deborah A.

    2015-01-01

    Numerous studies have shown that use of integrated automated bolus advisors (BAs) provides significant benefits to individuals using insulin pump devices, including improved glycemic control and greater treatment satisfaction. Within the past few years, BA devices have been developed specifically for individuals treated with multiple daily insulin injection (MDI) therapy; however, many clinicians who treat these individuals may be unfamiliar with insulin pump therapy and, thus, BA use. Findings from the Automated Bolus Advisor Control and Usability Study (ABACUS) revealed that BA use can be efficacious and clinically meaningful in MDI therapy, and that most patients are willing and able to use this technology appropriately when adequate clinical support is provided. The purpose of this article is to review key learnings from ABACUS and provide practical advice for initiating BA use and monitoring therapy. PMID:25795641

  7. Sodium-glucose co-transporter-2 inhibitors as add-on therapy to insulin: rationale and evidences.

    PubMed

    Singh, Awadhesh Kumar; Singh, Ritu

    2016-01-01

    Sodium-glucose co-transporter-2 inhibitors (SGLT-2I) are recently approved class of anti-hyperglycaemic agents for the treatment of type 2 diabetes mellitus (T2DM). SGLT-2I inhibits renal glucose reabsorption, thereby ensuing urinary glucose excretion in a dose-dependent manner. This caloric loss and osmotic diuresis, secondary to increased urinary glucose excretion, has a unique potential to counter insulin induced weight gain and fluid retention, with little potential of hypoglycemic exacerbation. Also, as these agents act independently of insulin secretion or action, they are effective even in long-standing diabetes with depleted β-cell reserve. Improvement in insulin sensitivity, as observed with SGLT-2I can also facilitate insulin action. Furthermore, significant reduction in total daily insulin dosage and reduction of body weight as observed during combination therapy renders SGLT-2I, a near-ideal partner to insulin. This review aims to evaluate the safety and efficacy of currently used SGLT-2I as an add-on to insulin therapy in the treatment of T2DM.

  8. Historical Data Enhances Safety Supervision System Performance in T1DM Insulin Therapy Risk Management★

    PubMed Central

    Hughes-Karvetski, Colleen; Patek, Stephen D.; Breton, Marc D.; Kovatchev, Boris P.

    2012-01-01

    Safety measures to prevent or mitigate hypoglycemia are an important component of open loop, closed loop, and advisory mode insulin therapy control settings in type 1 diabetes. In recent work, we introduce a method for the automatic, gradual attenuation of the insulin pump delivery rate when a risk of hypoglycemia is detected, a method that we refer to as brakes. In the methods presented here, we demonstrate the use of historical glucose measurement data to inform and enhance the ability of the brakes to prevent hypoglycemia in real-time. The updated brakes are based on a patient-specific, time-varying model that reflects the typical trajectory of glycemic fluctuations throughout the day. Historical heightened risk of hypoglycemia throughout the day prompts an increase in the aggressiveness of insulin attenuation as compared to the original brakes that are based on real-time data alone. Through the use of available real-time data supplemented with historical glucose information to assess hypoglycemic risk, we are able to better anticipate and prevent hypoglycemia. PMID:22342221

  9. Approaching Oxygen-Guided Intensity-Modulated Radiation Therapy.

    PubMed

    Epel, Boris; Redler, Gage; Pelizzari, Charles; Tormyshev, Victor M; Halpern, Howard J

    2016-01-01

    The outcome of cancer radiation treatment is strongly correlated with tumor oxygenation. The aim of this study is to use oxygen tension distributions in tumors obtained using Electron Paramagnetic Resonance (EPR) imaging to devise better tumor radiation treatment. The proposed radiation plan is delivered in two steps. In the first step, a uniform 50% tumor control dose (TCD50) is delivered to the whole tumor. For the second step an additional dose boost is delivered to radioresistant, hypoxic tumor regions. FSa fibrosarcomas grown in the gastrocnemius of the legs of C3H mice were used. Oxygen tension images were obtained using a 250 MHz pulse imager and injectable partially deuterated trityl OX63 (OX71) spin probe. Radiation was delivered with a novel animal intensity modulated radiation therapy (IMRT) XRAD225Cx microCT/radiation therapy delivery system. In a simplified scheme for boost dose delivery, the boost area is approximated by a sphere, whose radius and position are determined using an EPR O2 image. The sphere that irradiates the largest fraction of hypoxic voxels in the tumor was chosen using an algorithm based on Receiver Operator Characteristic (ROC) analysis. We used the fraction of irradiated hypoxic volume as the true positive determinant and the fraction of irradiated normoxic volume as the false positive determinant in the terms of that analysis. The most efficient treatment is the one that demonstrates the shortest distance from the ROC curve to the upper left corner of the ROC plot. The boost dose corresponds to the difference between TCD90 and TCD50 values. For the control experiment an identical radiation dose to the normoxic tumor area is delivered.

  10. Ultrasound-based guidance of intensity-modulated radiation therapy.

    PubMed

    Fung, Albert Y C; Ayyangar, Komanduri M; Djajaputra, David; Nehru, Ramasamy M; Enke, Charles A

    2006-01-01

    In ultrasound-guided intensity-modulated radiation therapy (IMRT) of prostate cancer, ultrasound imaging ascertains the anatomical position of patients during x-ray therapy delivery. The ultrasound transducers are made of piezoelectric ceramics. The same crystal is used for both ultrasound production and reception. Three-dimensional (3D) ultrasound devices capture and correlate series of 2-dimensional (2D) B-mode images. The transducers are often arranged in a convex array for focusing. Lower frequency reaches greater depth, but results in low resolution. For clear image, some gel is usually applied between the probe and the skin contact surface. For prostate positioning, axial and sagittal scans are performed, and the volume contours from computed tomography (CT) planning are superimposed on the ultrasound images obtained before radiation delivery at the linear accelerator. The planning volumes are then overlaid on the ultrasound images and adjusted until they match. The computer automatically deduces the offset necessary to move the patient so that the treatment area is in the correct location. The couch is translated as needed. The currently available commercial equipment can attain a positional accuracy of 1-2 mm. Commercial manufacturer designs differ in the detection of probe coordinates relative to the isocenter. Some use a position-sensing robotic arm, while others have infrared light-emitting diodes or pattern-recognition software with charge-couple-device cameras. Commissioning includes testing of image quality and positional accuracy. Ultrasound is mainly used in prostate positioning. Data for 7825 daily fractions of 234 prostate patients indicated average 3D inter-fractional displacement of about 7.8 mm. There was no perceivable trend of shift over time. Scatter plots showed slight prevalence toward superior-posterior directions. Uncertainties of ultrasound guidance included tissue inhomogeneities, speckle noise, probe pressure, and inter

  11. Ultrasound-based guidance of intensity-modulated radiation therapy

    SciTech Connect

    Fung, Albert Y.C. . E-mail: afung@unmc.edu; Ayyangar, Komanduri M.; Djajaputra, David; Nehru, Ramasamy M.; Enke, Charles A.

    2006-04-01

    In ultrasound-guided intensity-modulated radiation therapy (IMRT) of prostate cancer, ultrasound imaging ascertains the anatomical position of patients during x-ray therapy delivery. The ultrasound transducers are made of piezoelectric ceramics. The same crystal is used for both ultrasound production and reception. Three-dimensional (3D) ultrasound devices capture and correlate series of 2-dimensional (2D) B-mode images. The transducers are often arranged in a convex array for focusing. Lower frequency reaches greater depth, but results in low resolution. For clear image, some gel is usually applied between the probe and the skin contact surface. For prostate positioning, axial and sagittal scans are performed, and the volume contours from computed tomography (CT) planning are superimposed on the ultrasound images obtained before radiation delivery at the linear accelerator. The planning volumes are then overlaid on the ultrasound images and adjusted until they match. The computer automatically deduces the offset necessary to move the patient so that the treatment area is in the correct location. The couch is translated as needed. The currently available commercial equipment can attain a positional accuracy of 1-2 mm. Commercial manufacturer designs differ in the detection of probe coordinates relative to the isocenter. Some use a position-sensing robotic arm, while others have infrared light-emitting diodes or pattern-recognition software with charge-couple-device cameras. Commissioning includes testing of image quality and positional accuracy. Ultrasound is mainly used in prostate positioning. Data for 7825 daily fractions of 234 prostate patients indicated average 3D inter-fractional displacement of about 7.8 mm. There was no perceivable trend of shift over time. Scatter plots showed slight prevalence toward superior-posterior directions. Uncertainties of ultrasound guidance included tissue inhomogeneities, speckle noise, probe pressure, and inter

  12. 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.

  13. 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.

  14. Patterns and Predictors of Intensive Statin Therapy among Patients with Diabetes Mellitus after Acute Myocardial Infarction

    PubMed Central

    Abdallah, Mouin S.; Kosiborod, Mikhail; Tang, Fengming; Karrowni, Wassef Y.; Maddox, Thomas M.; McGuire, Darren K.; Spertus, John A.; Arnold, Suzanne V.

    2014-01-01

    Intensive statin therapy is a central component of secondary prevention after acute myocardial infarction (AMI), particularly among high-risk patients, such as those with diabetes mellitus (DM). However, the frequency and predictors of intensive statin therapy use after AMI among patients with DM have not been described. We examined patterns of intensive statin therapy use (defined as a statin with expected LDL-C lowering of >50%) at discharge among AMI patients with known DM enrolled in a 24-site US registry. Predictors of intensive statin therapy use were evaluated using multivariable hierarchical Poisson regression models. Among 1300 patients with DM after AMI, 22% were prescribed intensive statin therapy at hospital discharge. In multivariable models, ST-elevation AMI (RR 1.48, 95% CI 1.29–1.70), insurance for medications (RR 1.28, 95% CI 1.00–1.63) and higher LDL-C levels (RR 1.05 per 1 mg/dL, 95% CI 1.02–1.07) were independent predictors of intensive statin therapy whereas higher GRACE scores were associated with lower rates of intensive statin therapy (RR 0.94 per 10 points; 95% CI 0.91–0.98). In conclusion, only 1 in 5 patients with DM were prescribed intensive statin therapy at discharge after an AMI. Predictors of intensive statin therapy use suggest important opportunities to improve quality of care in this patient population. PMID:24560324

  15. From the Cover: Cell-replacement therapy for diabetes: Generating functional insulin-producing tissue from adult human liver cells

    NASA Astrophysics Data System (ADS)

    Sapir, Tamar; Shternhall, Keren; Meivar-Levy, Irit; Blumenfeld, Tamar; Cohen, Hamutal; Skutelsky, Ehud; Eventov-Friedman, Smadar; Barshack, Iris; Goldberg, Iris; Pri-Chen, Sarah; Ben-Dor, Lya; Polak-Charcon, Sylvie; Karasik, Avraham; Shimon, Ilan; Mor, Eytan; Ferber, Sarah

    2005-05-01

    Shortage in tissue availability from cadaver donors and the need for life-long immunosuppression severely restrict the large-scale application of cell-replacement therapy for diabetic patients. This study suggests the potential use of adult human liver as alternate tissue for autologous beta-cell-replacement therapy. By using pancreatic and duodenal homeobox gene 1 (PDX-1) and soluble factors, we induced a comprehensive developmental shift of adult human liver cells into functional insulin-producing cells. PDX-1-treated human liver cells express insulin, store it in defined granules, and secrete the hormone in a glucose-regulated manner. When transplanted under the renal capsule of diabetic, immunodeficient mice, the cells ameliorated hyperglycemia for prolonged periods of time. Inducing developmental redirection of adult liver offers the potential of a cell-replacement therapy for diabetics by allowing the patient to be the donor of his own insulin-producing tissue. pancreas | transdifferentiation

  16. 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.

  17. Intensity-modulated radiation therapy for head and neck carcinoma.

    PubMed

    Grégoire, Vincent; De Neve, Wilfried; Eisbruch, Avraham; Lee, Nancy; Van den Weyngaert, Danielle; Van Gestel, Dirk

    2007-05-01

    Intensity-modulated radiation therapy (IMRT) for head and neck tumors refers to a new approach that aims at increasing the radiation dose gradient between the target tissues and the surrounding normal tissues at risk, thus offering the prospect of increasing the locoregional control probability while decreasing the complication rate. As a prerequisite, IMRT requires a proper selection and delineation of target volumes. For the latter, recent data indicate the potential of functional imaging to complement anatomic imaging modalities. Nonrandomized clinical series in paranasal sinuses and pharyngolaryngeal carcinoma have shown that IMRT was able to achieve a very high rate of locoregional control with less morbidity, such as dry-eye syndrome, xerostomia, and swallowing dysfunction. The promising results of IMRT are likely to be achieved when many treatment conditions are met, for example, optimal selection and delineation of the target volumes and organs at risk, appropriate physical quality control of the irradiation, and accurate patient setup with the use of onboard imaging. Because of the complexity of the various tasks, it is thus likely that these conditions will only be met in institutions having large patient throughput and experience with IMRT. Therefore, patient referral to those institutions is recommended.

  18. Effect of Rosiglitazone and Insulin Combination Therapy on Inflammation Parameters and Adipocytokine Levels in Patients with Type 1 DM

    PubMed Central

    Guclu, Metin; Oz Gul, Ozen; Cander, Soner; Unal, Oguzkaan; Ozkaya, Guven; Sarandol, Emre; Ersoy, Canan

    2015-01-01

    Aim. To investigate the efficacy of combined therapy of insulin and rosiglitazone on metabolic and inflammatory parameters, insulin sensitivity, and adipocytokine levels in patients with type 1 diabetes mellitus (type 1 DM). Material and Methods. A total of 61 adults with type 1 DM were randomly and prospectively assigned in open-label fashion to take insulin and rosiglitazone 4 mg/day (n = 30) or insulin alone (n = 31) for a period of 18 weeks while undergoing insulin therapy without acute metabolic complications. Results. Combination therapy did not significantly improve metabolic and inflammatory parameters, insulin sensitivity, and adiponectin levels. While leptin and resistin levels decreased in both groups (group 1: resistin 6.96 ± 3.06 to 4.99 ± 2.64, P = 0.006; leptin 25.8 ± 17.6 to 20.1 ± 12.55, P = 0.006; group 2: resistin 7.16 ± 2.30 to 5.57 ± 2.48, P = 0.031; leptin 16.72 ± 16.1 to 14.0 ± 13.4, P = 0.007) Hgb and fibrinogen levels decreased only in group 1 (Hgb 13.72 ± 1.98 to 13.16 ± 1.98, P = 0.015, and fibrinogen 4.00 ± 1.08 to 3.46 ± 0.90, P = 0.002). Patients in both groups showed weight gain and the incidence of hypoglycemia was not lower. Discussion. The diverse favorable effects of TZDs were not fully experienced in patients with type 1 DM. These results are suggesting that insulin sensitizing and anti-inflammatory characteristics of TZDs were likely to be more pronounced in patients who were not totally devoid of endogenous insulin secretion. PMID:26273677

  19. Sustainability of lifestyle changes following an intensive lifestyle intervention in insulin resistant adults: Follow-up at 2-years.

    PubMed

    Dale, Kelly S; Mann, Jim I; McAuley, Kirsten A; Williams, Sheila M; Farmer, Victoria L

    2009-01-01

    The objective of this study was to determine whether overweight insulin resistant individuals who lost weight and improved cardiovascular risk factors during a 4-month lifestyle intervention could sustain these lifestyle changes in the long-term. Seventy-nine insulin resistant adults were randomised to a control group or either a modest or intensive lifestyle intervention group for 4-months. Thereafter the two intervention groups were combined and all participants were followed-up at 8, 12 and 24 months. Anthropometry, blood pressure, fasting glucose, lipids, insulin and aerobic fitness were measured and dietary intake was assessed. An interview was conducted to determine factors which participants perceived facilitated or hindered maintenance of healthy lifestyle habits. Seventy-two (91.1%), sixty-nine (87.3%) and sixty-two (78.5%) participants were retained at 8, 12 and 24-month respectively. At 4-months the adjusted difference in weight between the modest and control groups was -3.4 kg (95% CI -5.4, -1.3) p=0.002 and intensive and control groups was -4.7 kg (-6.9, -2.4) p=0.0001 respectively. At 2-years there were no significant differences for weight when the initial 3 groups were compared or when the combined intervention group was compared with the control group. At 2-years, 64% of participants reported that more frequent follow-up would have helped them to maintain healthy lifestyle habits. Even intensive counselling for 4-months with 4-monthly and then yearly monitoring were not enough for maintaining lifestyle changes sufficient to sustain weight loss. More frequent monitoring for an indefinite period was perceived by two-thirds of participants as necessary for them to maintain their initial lifestyle changes.

  20. Prospective randomised study of intensive insulin treatment on long term survival after acute myocardial infarction in patients with diabetes mellitus. DIGAMI (Diabetes Mellitus, Insulin Glucose Infusion in Acute Myocardial Infarction) Study Group.

    PubMed Central

    Malmberg, K.

    1997-01-01

    OBJECTIVES: To test the hypothesis that intensive metabolic treatment with insulin-glucose infusion followed by multidose insulin treatment in patients with diabetes mellitus and acute myocardial infarction improves the prognosis. DESIGN: Patients with diabetes mellitus and acute myocardial infarction were randomly allocated standard treatment plus insulin-glucose infusion for at least 24 hours followed by multidose insulin treatment or standard treatment (controls). SUBJECTS: 620 patients were recruited, of whom 306 received intensive insulin treatment and 314 served as controls. MAIN OUTCOME MEASURE: Long term all cause mortality. RESULTS: The mean (range) follow up was 3.4 (1.6-5.6) years. There were 102 (33%) deaths in the treatment group compared with 138 (44%) deaths in the control group (relative risk (95% confidence interval) 0.72 (0.55 to 0.92); P = 0.011). The effect was most pronounced among the predefined group that included 272 patients without previous insulin treatment and at a low cardiovascular risk (0.49 (0.30 to 0.80); P = 0.004). CONCLUSION: Insulin-glucose infusion followed by intensive subcutaneous insulin in diabetic patients with acute myocardial infarction improves long term survival, and the effect seen at one year continues for at least 3.5 years, with an absolute reduction in mortality of 11%. This means that one life was saved for nine treated patients. The effect was most apparent in patients who had not previously received insulin treatment and who were at a low cardiovascular risk. PMID:9169397

  1. Non-insulin antidiabetic therapy in cardiac patients: current problems and future prospects.

    PubMed

    Fisman, Enrique Z; Motro, Michael; Tenenbaum, Alexander

    2008-01-01

    ) these hazards are not mere 'side effects' but are deeply rooted in the drugs' mechanisms of action; (3) current data indicate that combined glibenclamide/metformin therapy seems to present a special risk and should be avoided in the long-term management of type 2 diabetics with proven CAD, and (4) Non-Insulin Antidiabetic Therapy in Diabetic Cardiac Patients 155 customized antihyperglycemic pharmacological approaches should be investigated for the optimal treatment of diabetic patients with heart disease. New possibilities are represented by incretin mimetic compounds, dipeptidyl peptidase (DPP)-4 inhibitors, inhaled insulin and eventually oral insulin. PMID:18230961

  2. Insulin resistance, hyperglycemia, glucosuria, and galactosuria in intensively milk-fed calves: dependency on age and effects of high lactose intake.

    PubMed

    Hugi, D; Bruckmaier, R M; Blum, J W

    1997-02-01

    Calves intensively fed milk replacers frequently develop postprandial insulin resistance, characterized by excessively elevated plasma insulin concentrations, hyperglycemia, and glucosuria. To test the hypothesis that insulin secretion and insulin-dependent dependent glucose metabolism are modified by age and carbohydrate intake, 20 male calves (Simmental x Red Holstein) were fed a milk replacer containing 290 and 423 g lactose/kg DM from 60-70 to 190-200 kg BW. Responses of insulin and glucose to milk replacer intake and orally administered glucose and pre- and postprandial glucose responses to i.v. infused glucose and i.v. injected insulin were tested at 75-105 and 160-200 kg BW. Urine was collected during 24h to determine glucose, galactose, dopamine, noradrenaline, and creatinine excretion. Insulin resistance, hyperinsulinemia, hyperglycemia, glucosuria, and galactosuria developed with increasing age and occurred primarily postprandially. High lactose intake enhanced postprandial hyperglycemia but did not significantly increase glucosuria, galactosuria, and hyperinsulinemia. Based on urinary excretion of dopamine and noradrenaline there was a marked age-dependent increase in the activity of the sympathetic nervous system, which was not modified by lactose intake. high feeding intensity and lactose intake, excessive hyperinsulinemia per se and enhanced activity of the sympathetic nervous system possibly contributed to the development of insulin resistance. Glucose-dependent insulinotropic polypeptide, growth hormone and cortisol concentrations, and iron intake were low and comparable in both groups and therefore were etiologically not involved in the development of insulin resistance. Increasing circulating concentrations of insulin-like growth factor I during growth may have in part allowed high growth rates in the presence of insulin resistance.

  3. 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

  4. Controlled study on the use of hand-held insulin dosage computers enabling conversion to and optimizing of meal-related insulin therapy regimens.

    PubMed

    Schrezenmeir, J; Achterberg, H; Bergeler, J; Küstner, E; Stümer, W; Hutten, H; Beyer, J

    1985-01-01

    We developed a program for a pocket computer (Sharp PC-1500) enabling conversion to and optimizing of meal-related insulin injection regimens. The dosage of regular insulin injected at meal times by a penshaped device (Novo Pen) was calculated in dependence of the carbohydrate content of the ingested meal, daytime, difference of actual and target blood glucose, 4 daily glucose levels of the last 2 or 4 days and physical activity. Long-acting insulin was proposed in dependence of morning blood levels of the preceding days. The response to elevated levels was additionally determined by night values. All quantifications were based on equivalent factors reflecting relations between insulin need and blood glucose changes and carbohydrate intake, respectively. This permits a so-called "quantified adaptation", where all these factors are individually defined and steadily actualized by the computer according to the data processed during adaptation. In a controlled cross-over study 12 type 1 diabetics were treated with conventional therapy (CT = 2-3 injections daily) and computer-assisted meal-related insulin therapy (CAMIT = 3-4 injections daily), each for a 6 weeks period. Although the number of meals was reduced from 6-7 to 3-5 and carbohydrate intake was allowed to vary from day to day, parameters of metabolic control were significantly improved by CAMIT compared to CT: mean blood glucose decreased from 9.10 +/- 2.96 to 6.22 +/- 0.65 mmol/l with CAMIT and only from 8.86 +/- 1.83 to 6.91 +/- 0.90 mmol/l with CT (p less than 0.05) and HbA1 from 10.2 +/- 1.5 to 8.6 +/- 0.8% with CAMIT and only from 9.8 +/- 1.3 to 9.1 +/- 1.0% with CT.(ABSTRACT TRUNCATED AT 250 WORDS)

  5. Survey of resident education in intensity-modulated radiation therapy.

    PubMed

    Malik, Renuka; Oh, Julia L; Roeske, John C; Mundt, Arno J

    2005-06-01

    Intensity-modulated radiation therapy (IMRT) has been gaining increasing popularity among practicing physicians in the U.S., but the extent to which radiation oncology residents are taught the principles of this technology and are trained to use IMRT remains unknown. In this paper, we assessed the current level of resident education in IMRT in the United States. Chief residents at all 77 accredited radiation oncology programs were sent a 13-question survey addressing formal didactics and hands-on experience in IMRT. The survey assessed the frequency, subject, and format of IMRT didactics. Questions also addressed the number of IMRT patients and anatomical sites treated, resident involvement in the IMRT process, and the intent of IMRT use. Finally, residents were asked for their opinions on their IMRT education. Sixty-one surveys (79%) were completed. Overall, forty-three respondents (71%) reported receiving formal IMRT didactics, with nearly one-third reporting extensive didactics (> or = 3 lectures/seminars et cetera per year). The most common didactic formats were lectures (95%) and journal clubs (63%), most commonly supervised by physicists (98%). Involvement by physicians and radiobiologists were reported by 63% and 7% of respondents, respectively. Overall, 87% of respondents had hands-on IMRT training, with nearly one-half having treated > 25 patients. The most common sites treated were head and neck (94%) and prostate (81%). Involvement in all aspects of the IMRT process was common, particularly target and tissue delineation (98%) and plan evaluation (93%). Most respondents (79%) with hands-on experience reported receiving formal didactics. However, nearly one-third received no or only minimal formal didactics. The percentage of respondents desiring increased IMRT didactics and hands-on experience were 70% and 47%, respectively. Our results suggest that the great majority of radiation oncology residents in the United States are currently exposed to didactics

  6. 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.

  7. The effects of high-intensity interval training on glucose regulation and insulin resistance: a meta-analysis.

    PubMed

    Jelleyman, C; Yates, T; O'Donovan, G; Gray, L J; King, J A; Khunti, K; Davies, M J

    2015-11-01

    The aim of this meta-analysis was to quantify the effects of high-intensity interval training (HIIT) on markers of glucose regulation and insulin resistance compared with control conditions (CON) or continuous training (CT). Databases were searched for HIIT interventions based upon the inclusion criteria: training ≥2 weeks, adult participants and outcome measurements that included insulin resistance, fasting glucose, HbA1c or fasting insulin. Dual interventions and participants with type 1 diabetes were excluded. Fifty studies were included. There was a reduction in insulin resistance following HIIT compared with both CON and CT (HIIT vs. CON: standardized mean difference [SMD] = -0.49, confidence intervals [CIs] -0.87 to -0.12, P = 0.009; CT: SMD = -0.35, -0.68 to -0.02, P = 0.036). Compared with CON, HbA1c decreased by 0.19% (-0.36 to -0.03, P = 0.021) and body weight decreased by 1.3 kg (-1.9 to -0.7, P < 0.001). There were no statistically significant differences between groups in other outcomes overall. However, participants at risk of or with type 2 diabetes experienced reductions in fasting glucose (-0.92 mmol L(-1), -1.22 to -0.62, P < 0.001) compared with CON. HIIT appears effective at improving metabolic health, particularly in those at risk of or with type 2 diabetes. Larger randomized controlled trials of longer duration than those included in this meta-analysis are required to confirm these results.

  8. Association of Hyperglycemia, Glucocorticoids, and Insulin Use with Morbidity and Mortality in the Pediatric Intensive Care Unit

    PubMed Central

    Wintergerst, Kupper A; Foster, Michael B; Sullivan, Janice E; Woods, Charles R

    2012-01-01

    Background Studies of pediatric intensive care unit (PICU) patients have shown a significant association of morbidity and mortality with hyperglycemia. We retrospectively evaluated the degree of hyperglycemia as well as its correlation with glucocorticoid and insulin use and assessed its association with hospital length of stay (LOS) and mortality. This study preceded the initiation of a standard glycemic control protocol. Methods We examined medical records at Kosair Children's Hospital for all PICU admissions from 2008 of patients without diabetes mellitus. Critical illness hyperglycemia (CIH) was defined by having three or more peak glucose values greater than thresholds of 110, 140, 180, and 200 mg/dl. These patients were evaluated for glucocorticoid, insulin use, and outcome measures. Results We evaluated the eligible 1173 admissions, where 10.5% of these patients reached the highest threshold (200 mg/dl) of CIH. Glucocorticoids were used in 43% of these patients, with dexamethasone being the most common (58%). There was a significant correlation between glucocorticoids and higher peak glucose values, where 81% of the patients who were above the 200 mg/dl cutoff level were treated with glucocorticoids. Only 36.8% in that group were also treated with insulin. Patients at the 200 mg/dl cutoff had the highest median PICU and total hospital length of stays (4 and 10 days, respectfully). Mortality was associated with increasing glucose levels, reaching 18.7% among patients above the 200 mg/dl cutoff. Conclusion Hyperglycemia was prevalent in the PICU and was associated with increased morbidity, as characterized by increased LOS and increased mortality. Glucocorticoid use was prevalent among patients exhibiting hyperglycemia. Insulin use was uncommon. PMID:22401317

  9. The effects of high-intensity interval training on glucose regulation and insulin resistance: a meta-analysis.

    PubMed

    Jelleyman, C; Yates, T; O'Donovan, G; Gray, L J; King, J A; Khunti, K; Davies, M J

    2015-11-01

    The aim of this meta-analysis was to quantify the effects of high-intensity interval training (HIIT) on markers of glucose regulation and insulin resistance compared with control conditions (CON) or continuous training (CT). Databases were searched for HIIT interventions based upon the inclusion criteria: training ≥2 weeks, adult participants and outcome measurements that included insulin resistance, fasting glucose, HbA1c or fasting insulin. Dual interventions and participants with type 1 diabetes were excluded. Fifty studies were included. There was a reduction in insulin resistance following HIIT compared with both CON and CT (HIIT vs. CON: standardized mean difference [SMD] = -0.49, confidence intervals [CIs] -0.87 to -0.12, P = 0.009; CT: SMD = -0.35, -0.68 to -0.02, P = 0.036). Compared with CON, HbA1c decreased by 0.19% (-0.36 to -0.03, P = 0.021) and body weight decreased by 1.3 kg (-1.9 to -0.7, P < 0.001). There were no statistically significant differences between groups in other outcomes overall. However, participants at risk of or with type 2 diabetes experienced reductions in fasting glucose (-0.92 mmol L(-1), -1.22 to -0.62, P < 0.001) compared with CON. HIIT appears effective at improving metabolic health, particularly in those at risk of or with type 2 diabetes. Larger randomized controlled trials of longer duration than those included in this meta-analysis are required to confirm these results. PMID:26481101

  10. [Basal C peptide levels in response to intravenous tolbutamide in the detection of incorrect insulin therapy (or prolonged misuse)].

    PubMed

    Wemeau, J L; Fourlinnie, J C; Beuscart, R; Vaast, D; Romon, M; Vie, M C; Fossati, P

    1983-03-01

    Fifty nine insulin dependant diabetics were hospitalised for a trial withdrawal of insulin: 17 patients rapidly showed signs of lack of insulin, 18 did not develop cetoacidosis but could not be stabilised on diet and oral hypoglycemic agents, 24 were stabilised without insulin. A statistical study (multifactorial analysis of correlations, plotting of ROC graphs) validated the classification of these diabetics into 3 groups. It also showed that in patients with hypoglycemia, the values of C-protein, and after intravenous injection of tolbutamide, were good predictive factors for insulin-dependance: all patients with basal C-protein less than 1,9 ng/ml could not be stabilised without insulin; when the basal C-protein greater than or equal to 1,9 ng/ml and the amplitude of response at the 5th min was greater than or equal to 0,4 ng/ml, the diabetes could be stabilised by diet and oral hypoglycemic agents in 90 p. 100 of cases. This institutes an easy, reliable and economic method of detecting abusive insulin therapy.

  11. 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…

  12. [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. PMID:27614497

  13. Remission in models of type 1 diabetes by gene therapy using a single-chain insulin analogue

    NASA Astrophysics Data System (ADS)

    Lee, Hyun Chul; Kim, Su-Jin; Kim, Kyung-Sup; Shin, Hang-Cheol; Yoon, Ji-Won

    2000-11-01

    A cure for diabetes has long been sought using several different approaches, including islet transplantation, regeneration of β cells and insulin gene therapy. However, permanent remission of type 1 diabetes has not yet been satisfactorily achieved. The development of type 1 diabetes results from the almost total destruction of insulin-producing pancreatic β cells by autoimmune responses specific to β cells. Standard insulin therapy may not maintain blood glucose concentrations within the relatively narrow range that occurs in the presence of normal pancreatic β cells. We used a recombinant adeno-associated virus (rAAV) that expresses a single-chain insulin analogue (SIA), which possesses biologically active insulin activity without enzymatic conversion, under the control of hepatocyte-specific L-type pyruvate kinase (LPK) promoter, which regulates SIA expression in response to blood glucose levels. Here we show that SIA produced from the gene construct rAAV-LPK-SIA caused remission of diabetes in streptozotocin-induced diabetic rats and autoimmune diabetic mice for a prolonged time without any apparent side effects. This new SIA gene therapy may have potential therapeutic value for the cure of autoimmune diabetes in humans.

  14. Insulin oedema.

    PubMed Central

    Evans, D. J.; Pritchard-Jones, K.; Trotman-Dickenson, B.

    1986-01-01

    A 35 year old markedly underweight woman presented with uncontrolled diabetes. Following insulin therapy she developed gross fluid retention with extensive peripheral oedema, bilateral pleural effusions and weight gain of 18.8 kg in 22 days, accompanied by a fall in plasma albumin. She responded well to treatment with diuretics and salt-poor albumin, losing 10.3 kg in 6 days without recurrence of oedema. Severe insulin oedema is an uncommon complication of insulin therapy and may be due to effects of insulin on both vascular permeability and the renal tubule. Images Figure 2 PMID:3529068

  15. Engaging GPs in insulin therapy initiation: a qualitative study evaluating a support program in the Belgian context

    PubMed Central

    2014-01-01

    Background A program supporting the initiation of insulin therapy in primary care was introduced in Belgium, as part of a larger quality improvement project on diabetes care. This paper reports on a study exploring factors influencing the engagement of general practitioners (GPs) in insulin therapy initiation (research question 1) and exploring factors relevant for future program development (research question 2). Methods We have used semi-structured interviews to answer the first research question: two focus group interviews with GPs who had at least one patient in the insulin initiation program and 20 one-to-one interviews with GPs who were not regular users of the overall support program in the region. To explore factors relevant for future program development, the data from the GPs were triangulated with data obtained from individual interviews with patients (n = 10), the diabetes nurse educator (DNE) and the specialist involved in the program, and data extracted from meeting reports evaluating the insulin initiation support program. Results We found differences between GPs engaged and those not engaged in insulin initiation in attitude, subjective norm and perceived behavioural control regarding insulin initiation. In general the support program was evaluated in a positive way by users of the program. Some aspects need further consideration: job boundaries between the DNE and GPs, job boundaries between GPs and specialists, protocol adherence and limited case load. Conclusion The study shows that the transition of insulin initiation from secondary care to the primary care setting is a challenge. Although a support program addressing known barriers to insulin initiation was provided, a substantial number of GPs were reluctant to engage in this aspect of care. Important issues for future program development are: an interdisciplinary approach to job clarification, a dynamic approach to the integration of expertise in primary care and feedback on protocol

  16. Complications and fetal outcome in diabetic pregnancy. Intensified conventional versus insulin pump therapy.

    PubMed

    Burkart, W; Hanker, J P; Schneider, H P

    1988-01-01

    From 1978 to 1986 a total of 189 pregnant diabetic women gave birth at our hospital. In this randomized prospective study the influence of maternal diabetes treatment in normoglycemic patients, continuous subcutaneous insulin infusion (n = 48) versus intensified conventional treatment (n = 41), is evaluated. These two groups of patients are further compared to patients (n = 28) who underwent conventional diabetes treatment during pregnancy. It can be shown from our data that the rate of complications such as preeclampsia, intrauterine growth retardation, premature labor and premature delivery can be reduced by intensified conventional and insulin pump treatment as compared to conventionally treated patients with late onset of pregnancy care. As expected, in the groups of CSII and ICT patients no difference in the rate of pregnancy complications nor in fetal outcome could be demonstrated. Among CSII pregnancies 12/48 were complicated, in the ICT population the respective figure was 13/41 (CT: 20/28). The mean gestational age at the time of delivery ranged between 38 and 40 weeks, depending on the severity of maternal diabetes. CT patients were delivered earlier in all White classes. Fetal morbidity was nearly equal in CSII and ICT children, in CT patients it was greatly enhanced. Also the mortality (perinatal and neonatal) was considerably larger in CT patients (6/28), again, in the CSII and ICT population the mortality was nearly identical (2/48 and 3/41). We conclude, from our prospective information, that insulin pump therapy during pregnancy is indicated if intensified conventional treatment does not lead to normoglycemia.(ABSTRACT TRUNCATED AT 250 WORDS)

  17. Virtual Optimization of Nasal Insulin Therapy Predicts Immunization Frequency to Be Crucial for Diabetes Protection

    PubMed Central

    Fousteri, Georgia; Chan, Jason R.; Zheng, Yanan; Whiting, Chan; Dave, Amy; Bresson, Damien; Croft, Michael; von Herrath, Matthias

    2010-01-01

    OBJECTIVE Development of antigen-specific strategies to treat or prevent type 1 diabetes has been slow and difficult because of the lack of experimental tools and defined biomarkers that account for the underlying therapeutic mechanisms. RESEARCH DESIGN AND METHODS The type 1 diabetes PhysioLab platform, a large-scale mathematical model of disease pathogenesis in the nonobese diabetic (NOD) mouse, was used to investigate the possible mechanisms underlying the efficacy of nasal insulin B:9-23 peptide therapy. The experimental aim was to evaluate the impact of dose, frequency of administration, and age at treatment on Treg induction and optimal therapeutic outcome. RESULTS In virtual NOD mice, treatment efficacy was predicted to depend primarily on the immunization frequency and stage of the disease and to a lesser extent on the dose. Whereas low-frequency immunization protected from diabetes atrributed to Treg and interleukin (IL)-10 induction in the pancreas 1–2 weeks after treatment, high-frequency immunization failed. These predictions were confirmed with wet-lab approaches, where only low-frequency immunization started at an early disease stage in the NOD mouse resulted in significant protection from diabetes by inducing IL-10 and Treg. CONCLUSIONS Here, the advantage of applying computer modeling in optimizing the therapeutic efficacy of nasal insulin immunotherapy was confirmed. In silico modeling was able to streamline the experimental design and to identify the particular time frame at which biomarkers associated with protection in live NODs were induced. These results support the development and application of humanized platforms for the design of clinical trials (i.e., for the ongoing nasal insulin prevention studies). PMID:20864513

  18. Failure to initiate early insulin therapy – A risk factor for diabetic retinopathy in insulin users with Type 2 diabetes mellitus: Sankara Nethralaya-Diabetic Retinopathy Epidemiology and Molecular Genetics Study (SN-DREAMS, Report number 35)

    PubMed Central

    Gupta, Aditi; Delhiwala, Kushal S; Raman, Rajiv P G; Sharma, Tarun; Srinivasan, Sangeetha; Kulothungan, Vaitheeswaran

    2016-01-01

    Context: Insulin users have been reported to have a higher incidence of diabetic retinopathy (DR). Aim: The aim was to elucidate the factors associated with DR among insulin users, especially association between duration, prior to initiating insulin for Type 2 diabetes mellitus (DM) and developing DR. Materials and Methods: Retrospective cross-sectional observational study included 1414 subjects having Type 2 DM. Insulin users were defined as subjects using insulin for glycemic control, and insulin nonusers as those either not using any antidiabetic treatment or using diet control or oral medications. The duration before initiating insulin after diagnosis was calculated by subtracting the duration of insulin usage from the duration of DM. DR was clinically graded using Klein's classification. SPSS (version 9.0) was used for statistical analysis. Results: Insulin users had more incidence of DR (52.9% vs. 16.3%, P < 0.0001) and sight threatening DR (19.1% vs. 2.4%, P < 0.0001) in comparison to insulin nonusers. Among insulin users, longer duration of DM (odds ratio [OR] 1.12, 95% confidence interval [CI] 1.00–1.25, P = 0.044) and abdominal obesity (OR 1.15, 95% CI 1.02–1.29, P = 0.021) was associated with DR. The presence of DR was significantly associated with longer duration (≥5 years) prior to initiating insulin therapy, overall (38.0% vs. 62.0%, P = 0.013), and in subjects with suboptimal glycemic control (32.5% vs. 67.5%, P = 0.022). Conclusions: The presence of DR is significantly associated with longer duration of diabetes (>5 years) and sub-optimal glycemic control (glycosylated hemoglobin <7.0%). Among insulin users, abdominal obesity was found to be a significant predictor of DR; DR is associated with longer duration prior to initiating insulin therapy in Type 2 DM subjects with suboptimal glycemic control. PMID:27488152

  19. Advances in three-dimensional conformal radiation therapy physics with intensity modulation.

    PubMed

    Webb, S

    2000-09-01

    Intensity-modulated radiation therapy, a specific form of conformal radiation therapy, is currently attracting a lot of attention, and there are high expectations for this class of treatment techniques. Several new technologies are in development, but physicists are still working to improve the physical basis of radiation therapy.

  20. 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…

  1. Basal insulin analogs: from pathophysiology to therapy. What we see, know, and try to comprehend?

    PubMed

    Monnier, L; Colette, C; Owens, D

    2013-12-01

    During the past 10 years, several new basal insulin analogs have been developed. There has been for 3 years controversy on the potential increased risk for cancer with insulin glargine, which ceased with the publication of the ORIGIN trial in 2012. In insulin-treated persons with type 2 diabetes, it is usual to recommend that plasma insulin concentrations remain within a 50-200 pmol/L range in order to avoid overinsulinization, a potential causative factor for increased mitogenicity. Such concentrations are achieved when daily doses of insulin glargine or NPH insulin approximate 0.4 units/kg. However, the total plasma insulin concentrations are much greater in persons treated with insulin detemir and especially insulin degludec. These insulins derive their protracted action from the insertion of a long chain fatty acid moiety to the insulin molecule thereby increasing albumin binding. As a consequence, in persons with type 2 diabetes, stable total plasma concentrations as high as either 1600 or 6000 pmol/L are observed for insulin detemir or degludec, respectively. At present, the free to bound ratio of plasma insulin concentrations remains unknown for these two compounds. A first requirement is to understand how these insulins are eliminated or degraded and secondly to quantify the respective contributions of the free and bound fractions. Therefore, prior to early phase 2 or 3 randomized clinical trials, a better comprehension of the metabolism of all the new insulins would be invaluable. PMID:24139826

  2. Optimizing insulin pump therapy: the potential advantages of using a structured diabetes management program.

    PubMed

    Lange, Karin; Ziegler, Ralph; Neu, Andreas; Reinehr, Thomas; Daab, Iris; Walz, Marion; Maraun, Michael; Schnell, Oliver; Kulzer, Bernhard; Reichel, Andreas; Heinemann, Lutz; Parkin, Christopher G; Haak, Thomas

    2015-03-01

    Use of continuous subcutaneous insulin infusion (CSII) therapy improves glycemic control, reduces hypoglycemia and increases treatment satisfaction in individuals with diabetes. As a number of patient- and clinician-related factors can hinder the effectiveness and optimal usage of CSII therapy, new approaches are needed to address these obstacles. Ceriello and colleagues recently proposed a model of care that incorporates the collaborative use of structured SMBG into a formal approach to personalized diabetes management within all diabetes populations. We adapted this model for use in CSII-treated patients in order to enable the implementation of a workflow structure that enhances patient-physician communication and supports patients' diabetes self-management skills. We recognize that time constraints and current reimbursement policies pose significant challenges to healthcare providers integrating the Personalised Diabetes Management (PDM) process into clinical practice. We believe, however, that the time invested in modifying practice workflow and learning to apply the various steps of the PDM process will be offset by improved workflow and more effective patient consultations. This article describes how to implement PDM into clinical practice as a systematic, standardized process that can optimize CSII therapy. PMID:25597225

  3. Optimizing insulin pump therapy: the potential advantages of using a structured diabetes management program.

    PubMed

    Lange, Karin; Ziegler, Ralph; Neu, Andreas; Reinehr, Thomas; Daab, Iris; Walz, Marion; Maraun, Michael; Schnell, Oliver; Kulzer, Bernhard; Reichel, Andreas; Heinemann, Lutz; Parkin, Christopher G; Haak, Thomas

    2015-03-01

    Use of continuous subcutaneous insulin infusion (CSII) therapy improves glycemic control, reduces hypoglycemia and increases treatment satisfaction in individuals with diabetes. As a number of patient- and clinician-related factors can hinder the effectiveness and optimal usage of CSII therapy, new approaches are needed to address these obstacles. Ceriello and colleagues recently proposed a model of care that incorporates the collaborative use of structured SMBG into a formal approach to personalized diabetes management within all diabetes populations. We adapted this model for use in CSII-treated patients in order to enable the implementation of a workflow structure that enhances patient-physician communication and supports patients' diabetes self-management skills. We recognize that time constraints and current reimbursement policies pose significant challenges to healthcare providers integrating the Personalised Diabetes Management (PDM) process into clinical practice. We believe, however, that the time invested in modifying practice workflow and learning to apply the various steps of the PDM process will be offset by improved workflow and more effective patient consultations. This article describes how to implement PDM into clinical practice as a systematic, standardized process that can optimize CSII therapy.

  4. Inverse planning optimization method for intensity modulated radiation therapy.

    PubMed

    Lan, Yihua; Ren, Haozheng; Li, Cunhua; Min, Zhifang; Wan, Jinxin; Ma, Jianxin; Hung, Chih-Cheng

    2013-10-01

    In order to facilitate the leaf sequencing process in intensity modulated radiation therapy (IMRT), and design of a practical leaf sequencing algorithm, it is an important issue to smooth the planned fluence maps. The objective is to achieve both high-efficiency and high-precision dose delivering by considering characteristics of leaf sequencing process. The key factor which affects total number of monitor units for the leaf sequencing optimization process is the max flow value of the digraph which formulated from the fluence maps. Therefore, we believe that one strategy for compromising dose conformity and total number of monitor units in dose delivery is to balance the dose distribution function and the max flow value mentioned above. However, there are too many paths in the digraph, and we don't know the flow value of which path is the maximum. The maximum flow value among the horizontal paths was selected and used in the objective function of the fluence map optimization to formulate the model. The model is a traditional linear constrained quadratic optimization model which can be solved by interior point method easily. We believe that the smoothed maps from this model are more suitable for leaf sequencing optimization process than other smoothing models. A clinical head-neck case and a prostate case were tested and compared using our proposed model and the smoothing model which is based on the minimization of total variance. The optimization results with the same level of total number of monitor units (TNMU) show that the fluence maps obtained from our model have much better dose performance for the target/non-target region than the maps from total variance based on the smoothing model. This indicates that our model achieves better dose distribution when the algorithm suppresses the TNMU at the same level. Although we have just used the max flow value of the horizontal paths in the diagraph in the objective function, a good balance has been achieved between

  5. Survey of resident education in intensity-modulated radiation therapy.

    PubMed

    Malik, Renuka; Oh, Julia L; Roeske, John C; Mundt, Arno J

    2005-06-01

    Intensity-modulated radiation therapy (IMRT) has been gaining increasing popularity among practicing physicians in the U.S., but the extent to which radiation oncology residents are taught the principles of this technology and are trained to use IMRT remains unknown. In this paper, we assessed the current level of resident education in IMRT in the United States. Chief residents at all 77 accredited radiation oncology programs were sent a 13-question survey addressing formal didactics and hands-on experience in IMRT. The survey assessed the frequency, subject, and format of IMRT didactics. Questions also addressed the number of IMRT patients and anatomical sites treated, resident involvement in the IMRT process, and the intent of IMRT use. Finally, residents were asked for their opinions on their IMRT education. Sixty-one surveys (79%) were completed. Overall, forty-three respondents (71%) reported receiving formal IMRT didactics, with nearly one-third reporting extensive didactics (> or = 3 lectures/seminars et cetera per year). The most common didactic formats were lectures (95%) and journal clubs (63%), most commonly supervised by physicists (98%). Involvement by physicians and radiobiologists were reported by 63% and 7% of respondents, respectively. Overall, 87% of respondents had hands-on IMRT training, with nearly one-half having treated > 25 patients. The most common sites treated were head and neck (94%) and prostate (81%). Involvement in all aspects of the IMRT process was common, particularly target and tissue delineation (98%) and plan evaluation (93%). Most respondents (79%) with hands-on experience reported receiving formal didactics. However, nearly one-third received no or only minimal formal didactics. The percentage of respondents desiring increased IMRT didactics and hands-on experience were 70% and 47%, respectively. Our results suggest that the great majority of radiation oncology residents in the United States are currently exposed to didactics

  6. Skeletal effects of growth hormone and insulin-like growth factor-I therapy.

    PubMed

    Lindsey, Richard C; Mohan, Subburaman

    2016-09-01

    The growth hormone/insulin-like growth factor (GH/IGF) axis is critically important for the regulation of bone formation, and deficiencies in this system have been shown to contribute to the development of osteoporosis and other diseases of low bone mass. The GH/IGF axis is regulated by a complex set of hormonal and local factors which can act to regulate this system at the level of the ligands, receptors, IGF binding proteins (IGFBPs), or IGFBP proteases. A combination of in vitro studies, transgenic animal models, and clinical human investigations has provided ample evidence of the importance of the endocrine and local actions of both GH and IGF-I, the two major components of the GH/IGF axis, in skeletal growth and maintenance. GH- and IGF-based therapies provide a useful avenue of approach for the prevention and treatment of diseases such as osteoporosis.

  7. Insulin-Like Growth Factor System in Cancer: Novel Targeted Therapies

    PubMed Central

    Brahmkhatri, Varsha P.; Prasanna, Chinmayi; Atreya, Hanudatta S.

    2015-01-01

    Insulin-like growth factors (IGFs) are essential for growth and survival that suppress apoptosis and promote cell cycle progression, angiogenesis, and metastatic activities in various cancers. The IGFs actions are mediated through the IGF-1 receptor that is involved in cell transformation induced by tumour. These effects depend on the bioavailability of IGFs, which is regulated by IGF binding proteins (IGFBPs). We describe here the role of the IGF system in cancer, proposing new strategies targeting this system. We have attempted to expand the general viewpoint on IGF-1R, its inhibitors, potential limitations of IGF-1R, antibodies and tyrosine kinase inhibitors, and IGFBP actions. This review discusses the emerging view that blocking IGF via IGFBP is a better option than blocking IGF receptors. This can lead to the development of novel cancer therapies. PMID:25866791

  8. Acute High-Intensity Interval Exercise-Induced Redox Signaling Is Associated with Enhanced Insulin Sensitivity in Obese Middle-Aged Men

    PubMed Central

    Parker, Lewan; Stepto, Nigel K.; Shaw, Christopher S.; Serpiello, Fabio R.; Anderson, Mitchell; Hare, David L.; Levinger, Itamar

    2016-01-01

    Background: Obesity and aging are associated with increased oxidative stress, activation of stress and mitogen activated protein kinases (SAPK), and the development of insulin resistance and metabolic disease. In contrast, acute exercise also increases oxidative stress and SAPK signaling, yet is reported to enhance insulin sensitivity and reduce the risk of metabolic disease. This study explored this paradox by investigating the effect of a single session of high-intensity interval-exercise (HIIE) on redox status, muscle SAPK and insulin protein signaling in eleven middle-aged obese men. Methods: Participants completed a 2 h hyperinsulinaemic-euglycaemic clamp at rest, and 60 min after HIIE (4 × 4 mins at 95% HRpeak; 2 min recovery periods), separated by 1–3 weeks. Results: Irrespective of exercise-induced changes to redox status, insulin stimulation both at rest and after HIIE similarly increased plasma superoxide dismutase activity, plasma catalase activity, and skeletal muscle 4-HNE; and significantly decreased plasma TBARS and hydrogen peroxide. The SAPK signaling pathways of p38 MAPK, NF-κB p65, and JNK, and the distal insulin signaling protein AS160Ser588, were activated with insulin stimulation at rest and to a greater extent with insulin stimulation after a prior bout of HIIE. Higher insulin sensitivity after HIIE was associated with higher insulin-stimulated SOD activity, JNK, p38 MAPK and NF-κB phosphorylation (r = 0.63, r = 0.71, r = 0.72, r = 0.71; p < 0.05, respectively). Conclusion:These findings support a role for redox homeostasis and SAPK signaling in insulin-stimulated glucose uptake which may contribute to the enhancement of insulin sensitivity in obese men 3 h after HIIE.

  9. Acute High-Intensity Interval Exercise-Induced Redox Signaling Is Associated with Enhanced Insulin Sensitivity in Obese Middle-Aged Men

    PubMed Central

    Parker, Lewan; Stepto, Nigel K.; Shaw, Christopher S.; Serpiello, Fabio R.; Anderson, Mitchell; Hare, David L.; Levinger, Itamar

    2016-01-01

    Background: Obesity and aging are associated with increased oxidative stress, activation of stress and mitogen activated protein kinases (SAPK), and the development of insulin resistance and metabolic disease. In contrast, acute exercise also increases oxidative stress and SAPK signaling, yet is reported to enhance insulin sensitivity and reduce the risk of metabolic disease. This study explored this paradox by investigating the effect of a single session of high-intensity interval-exercise (HIIE) on redox status, muscle SAPK and insulin protein signaling in eleven middle-aged obese men. Methods: Participants completed a 2 h hyperinsulinaemic-euglycaemic clamp at rest, and 60 min after HIIE (4 × 4 mins at 95% HRpeak; 2 min recovery periods), separated by 1–3 weeks. Results: Irrespective of exercise-induced changes to redox status, insulin stimulation both at rest and after HIIE similarly increased plasma superoxide dismutase activity, plasma catalase activity, and skeletal muscle 4-HNE; and significantly decreased plasma TBARS and hydrogen peroxide. The SAPK signaling pathways of p38 MAPK, NF-κB p65, and JNK, and the distal insulin signaling protein AS160Ser588, were activated with insulin stimulation at rest and to a greater extent with insulin stimulation after a prior bout of HIIE. Higher insulin sensitivity after HIIE was associated with higher insulin-stimulated SOD activity, JNK, p38 MAPK and NF-κB phosphorylation (r = 0.63, r = 0.71, r = 0.72, r = 0.71; p < 0.05, respectively). Conclusion:These findings support a role for redox homeostasis and SAPK signaling in insulin-stimulated glucose uptake which may contribute to the enhancement of insulin sensitivity in obese men 3 h after HIIE. PMID:27695421

  10. 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.

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

    PubMed

    Lee, Katrina; Lenards, Nishele; Holson, Janice

    2016-01-01

    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. PMID:26235550

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

    PubMed

    Lee, Katrina; Lenards, Nishele; Holson, Janice

    2016-01-01

    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.

  13. Stereotactic Body Radiation Therapy Versus Intensity-Modulated Radiation Therapy for Prostate Cancer: Comparison of Toxicity

    PubMed Central

    Yu, James B.; Cramer, Laura D.; Herrin, Jeph; Soulos, Pamela R.; Potosky, Arnold L.; Gross, Cary P.

    2014-01-01

    Purpose Stereotactic body radiation therapy (SBRT) is a technically demanding prostate cancer treatment that may be less expensive than intensity-modulated radiation therapy (IMRT). Because SBRT may deliver a greater biologic dose of radiation than IMRT, toxicity could be increased. Studies comparing treatment cost to the Medicare program and toxicity are needed. Methods We performed a retrospective study by using a national sample of Medicare beneficiaries age ≥ 66 years who received SBRT or IMRT as primary treatment for prostate cancer from 2008 to 2011. Each SBRT patient was matched to two IMRT patients with similar follow-up (6, 12, or 24 months). We calculated the cost of radiation therapy treatment to the Medicare program and toxicity as measured by Medicare claims; we used a random effects model to compare genitourinary (GU), GI, and other toxicity between matched patients. Results The study sample consisted of 1,335 SBRT patients matched to 2,670 IMRT patients. The mean treatment cost was $13,645 for SBRT versus $21,023 for IMRT. In the 6 months after treatment initiation, 15.6% of SBRT versus 12.6% of IMRT patients experienced GU toxicity (odds ratio [OR], 1.29; 95% CI, 1.05 to 1.53; P = .009). At 24 months after treatment initiation, 43.9% of SBRT versus 36.3% of IMRT patients had GU toxicity (OR, 1.38; 95% CI, 1.12 to 1.63; P = .001). The increase in GU toxicity was due to claims indicative of urethritis, urinary incontinence, and/or obstruction. Conclusion Although SBRT was associated with lower treatment costs, there appears to be a greater rate of GU toxicity for patients undergoing SBRT compared with IMRT, and prospective correlation with randomized trials is needed. PMID:24616315

  14. High-intensity focused ultrasound therapy for prostate cancer.

    PubMed

    Uchida, Toyoaki; Nakano, Mayura; Hongo, Satoko; Shoji, Sunao; Nagata, Yohishiro; Satoh, Takefumi; Baba, Shiro; Usui, Yukio; Terachi, Toshiro

    2012-03-01

    Recent advances in high-intensity focused ultrasound, which was developed in the 1940s as a viable thermal tissue ablation approach, have increased its popularity. High-intensity focused ultrasound is currently utilized the most in Europe and Japan, but has not yet been approved by the Food and Drug Administration, USA, for this indication. The purpose of the present report is to review the scientific foundation of high-intensity focused ultrasound technology and the clinical outcomes achieved with commercially available devices. Recently published articles were reviewed to evaluate the current status of high-intensity focused ultrasound as a primary or salvage treatment option for localized prostate cancer. Improvements in the clinical outcome as a result of technical, imaging and technological advancements are described herein. A wide range of treatment options for organ-confined prostate cancer is available. However, high-intensity focused ultrasound is an attractive choice for men willing to choose less invasive options, although establishing the efficacy of high-intensity focused ultrasound requires longer follow-up periods. Technological advances, together with cultural and economic factors, have caused a dramatic shift from traditional open, radical prostatectomy to minimally invasive techniques. High-intensity focused ultrasound is likely to play a significant role in the future of oncology practice. PMID:22188161

  15. Role of insulin-like growth factor monitoring in optimizing growth hormone therapy.

    PubMed

    Wetterau, L; Cohen, P

    2000-01-01

    Much has been learned over the past two decades regarding the management of growth hormone (GH) deficiency in children and adolescents. Current GH therapy under ideal circumstances enables children to attain a final height within the normal range and close to their target height. However, such a successful outcome is not always achieved and the necessity to individualize treatment according to the specific needs of each GH-deficient child is now well recognized. Consensus does not currently exist as to how to formulate individualized treatment plans. Nonetheless, a clear role for a biochemical, as well as an auxological, monitoring approach has been established. Accurate determinations of height velocity and interval height increase (expressed as the change in height Z-score) continue to be the most important parameters in monitoring the response to treatment. The importance of routinely monitoring serum levels of insulin-like growth factor-I (IGF-I) and IGF-binding protein-3 is an emerging paradigm. Firm roles have been established for this approach in the assurance of compliance and safety (particularly to avoid long-term theoretical risks). IGF monitoring also has important potential utility as a tool to assess and optimize the response to GH therapy through dose adjustments. In years to come, we expect the development of multiple GH treatment optimization strategies, including approaches such as prediction modeling, as well as serum IGF monitoring and dose adjustments, to evolve and improve. PMID:11202212

  16. Insulin-dependent (type I) diabetes mellitus.

    PubMed Central

    Rodger, W

    1991-01-01

    Insulin-dependent (type I) diabetes mellitus is a chronic disease characterized by hyperglycemia, impaired metabolism and storage of important nutrients, evidence of autoimmunity, and long-term vascular and neurologic complications. Insulin secretory function is limited. Cell membrane binding is not primarily involved. The goal of treatment is to relieve symptoms and to achieve blood glucose levels as close to normal as possible without severe hypoglycemia. However, even with education and self-monitoring of the blood glucose level, attaining recommended target values (plasma glucose level less than 8.0 mmol/L before main meals for adults) remains difficult. Human insulin offers no advantage in glycemic control but is important in the management and prevention of immune-related clinical problems (e.g., injection-site lipoatrophy, insulin resistance and allergy) associated with the use of beef or pork insulin. Therapy with one or two injections per day of mixed short-acting or intermediate-acting insulin preparations is a compromise between convenience and the potential for achieving target plasma glucose levels. Intensive insulin therapy with multiple daily injections or continuous infusion with an insulin pump improves mean glycated hemoglobin levels; however, it increases rates of severe hypoglycemia and has not been shown to decrease the incidence of clinically significant renal, retinal or neurologic dysfunction. Future prospects include automated techniques of insulin delivery, immunosuppression to preserve endogenous insulin secretion and islet transplantation. PMID:1933705

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

    MedlinePlus

    ... Benefits of Intensive Therapy for Type 1 Diabetes: Study Reports Near-Normal Glucose Levels Lead to Large ... the latest results from a landmark government-sponsored study, reported at a special symposium held at the ...

  18. [Quality of life and hypoglycemia burden in patients with type 2 diabetes mellitus on basal-bolus insulin therapy].

    PubMed

    Ionova, T I; Odin, V I; Nikitina, T P; Kurbatova, K A

    2014-01-01

    This paper presents the results of the observational program "Parameters of life quality, symptoms of hypoglycemia and treatment satisfaction in patients with type 2 diabetes mellitus on basal-bolus insulin therapy" (2012-2014). The analysis included 1000 patients. It showed that their quality of life was below that of the general population due to compromised physical, role physical, and role emotional functioning (p < 0.001). Hypoglycemia is a serious challenge to the treatment of patients with type 2 diabetes mellitus on basal-bolus insulin therapy. They are characterized by impaired physical, psychological, and social functioning compared with the patients without hypoglycemic episodes (p < 0.01). Patients experiencing mild hypoglycemic episodes were not significantly different from those without them. In patients experiencing severe hypoglycemic episodes the quality of life was much worse (ES = 0.22-0.51). The profile of hypoglycemic episodes differed in different forms of hypoglycemia. The spectrum of symptoms and problems related to hypoglycemia was broader in patients with severe and/or nocturnal hypoglycemia. Patients free from hypoglycemia were less afraid of it than those used to have hypoglycemic episodes (p < 0.001). The stronger the fear, the more pronounced disturbances in social functioning, vitality, psychic and general health (p = 0.0001). It is concluded that evaluation of quality of life and hypoglycemia-related symptoms in patients with type 2 diabetes mellitus on basal-bolus insulin therapy allows for comprehensive estimation of the effectiveness of therapy on an individual basis. PMID:25782322

  19. Attenuation of Ca2+ homeostasis, oxidative stress, and mitochondrial dysfunctions in diabetic rat heart: insulin therapy or aerobic exercise?

    PubMed

    da Silva, Márcia F; Natali, Antônio J; da Silva, Edson; Gomes, Gilton J; Teodoro, Bruno G; Cunha, Daise N Q; Drummond, Lucas R; Drummond, Filipe R; Moura, Anselmo G; Belfort, Felipe G; de Oliveira, Alessandro; Maldonado, Izabel R S C; Alberici, Luciane C

    2015-07-15

    We tested the effects of swimming training and insulin therapy, either alone or in combination, on the intracellular calcium ([Ca(2+)]i) homeostasis, oxidative stress, and mitochondrial functions in diabetic rat hearts. Male Wistar rats were separated into control, diabetic, or diabetic plus insulin groups. Type 1 diabetes mellitus was induced by streptozotocin (STZ). Insulin-treated groups received 1 to 4 UI of insulin daily for 8 wk. Each group was divided into sedentary or exercised rats. Trained groups were submitted to swimming (90 min/day, 5 days/wk, 8 wk). [Ca(2+)]i transient in left ventricular myocytes (LVM), oxidative stress in LV tissue, and mitochondrial functions in the heart were assessed. Diabetes reduced the amplitude and prolonged the times to peak and to half decay of the [Ca(2+)]i transient in LVM, increased NADPH oxidase-4 (Nox-4) expression, decreased superoxide dismutase (SOD), and increased carbonyl protein contents in LV tissue. In isolated mitochondria, diabetes increased Ca(2+) uptake, susceptibility to permeability transition pore (MPTP) opening, uncoupling protein-2 (UCP-2) expression, and oxygen consumption but reduced H2O2 release. Swimming training corrected the time course of the [Ca(2+)]i transient, UCP-2 expression, and mitochondrial Ca(2+) uptake. Insulin replacement further normalized [Ca(2+)]i transient amplitude, Nox-4 expression, and carbonyl content. Alongside these benefits, the combination of both therapies restored the LV tissue SOD and mitochondrial O2 consumption, H2O2 release, and MPTP opening. In conclusion, the combination of swimming training with insulin replacement was more effective in attenuating intracellular Ca(2+) disruptions, oxidative stress, and mitochondrial dysfunctions in STZ-induced diabetic rat hearts. PMID:25997948

  20. Disordered Eating Behaviors in Youth with Type 1 Diabetes: Prospective Pilot Assessment Following Initiation of Insulin Pump Therapy

    PubMed Central

    Markowitz, Jessica T.; Alleyn, Cielo A.; Phillips, Roxanne; Muir, Andrew; Young-Hyman, Deborah

    2013-01-01

    Abstract Background There is risk for disordered eating behaviors in type 1 diabetes, especially related to insulin manipulation. Implementation of insulin pump therapy may encourage either normalization of eating behaviors or a greater focus on food intake due to renewed emphasis on carbohydrate counting. There is need for prospective studies to assess disordered eating behaviors upon implementation of pump therapy using diabetes-specific measurement tools. Subjects and Methods In a multicenter pilot study, 43 youth with type 1 diabetes, 10–17 years old, were assessed prior to pump initiation and after 1 and 6 months of pump therapy. Youth completed the Diabetes-specific Eating Problems Survey-Revised (DEPS-R), a validated measure of risk for both diabetes-specific and general disordered eating behaviors. Results Youth (45% female), 13.3 years old with diabetes for 2.1 years, had a mean hemoglobin A1c of 8.3±1.3% (68±14.5 mmol/mol) at baseline. DEPS-R scores decreased over time (P=0.01). Overall rate of high risk for eating disorders was low. Overweight/obese youth endorsed more disordered eating behaviors than normal-weight participants. DEPS-R scores were correlated with z-score for body mass index at all three time points and with hemoglobin A1c after 1 and 6 months. Hemoglobin A1c did not change significantly over the 6 months and was higher in overweight/obese compared with normal-weight participants. Conclusions Initiation of insulin pump therapy was associated with diminished endorsement of disordered eating behaviors in youth with type 1 diabetes. Longer follow-up studies are needed to assess the impact of insulin pump therapy on glycemic control, weight status, and disordered eating behaviors in this vulnerable population. PMID:23550556

  1. [Extracorporeal therapy of patients with liver disease in the intensive care unit].

    PubMed

    Fuhrmann, V; Horvatits, T; Drolz, A; Rutter, K

    2014-05-01

    Acute and acute-on-chronic liver failure are often associated with development of organ failure. Its occurrence is associated with high morbidity and mortality. Extracorporeal replacement therapies are frequently necessary in these patient populations. Replacement therapies can be divided into renal replacement therapies and liver support therapies. These therapies consist of artificial liver support systems (i.e., MARS(®) system, Prometheus(®)), which are able to remove water-soluble and albumin-bound toxins, and of bioartifical liver support systems. This manuscript provides a review of current practice in the extracorporeal support of patients with liver diseases in the intensive care unit. PMID:24770889

  2. 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…

  3. 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…

  4. 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

  5. A double-blind randomized study comparing the effects of continuing or not continuing rosiglitazone + metformin therapy when starting insulin therapy in people with Type 2 diabetes1

    PubMed Central

    Home, P D; Bailey, C J; Donaldson, J; Chen, H; Stewart, M W

    2007-01-01

    Aims To compare the efficacy and safety of either continuing or discontinuing rosiglitazone + metformin fixed-dose combination when starting insulin therapy in people with Type 2 diabetes inadequately controlled on oral therapy. Methods In this 24-week double-blind study, 324 individuals with Type 2 diabetes inadequately controlled on maximum dose rosiglitazone + metformin therapy were randomly assigned to twice-daily premix insulin therapy (target pre-breakfast and pre-evening meal glucose ≤ 6.5 mmol/l) in addition to either rosiglitazone + metformin (8/2000 mg) or placebo. Results Insulin dose at week 24 was significantly lower with rosiglitazone + metformin (33.5 ± 1.5 U/day, mean ± se) compared with placebo [59.0 ± 3.0 U/day; model-adjusted difference −26.6 (95% CI −37.7, −15,5) U/day, P < 0.001]. Despite this, there was greater improvement in glycaemic control [HbA1c rosiglitazone + metformin vs. placebo 6.8 ± 0.1 vs. 7.5 ± 0.1%; difference −0.7 (−0.8, −0.5)%, P < 0.001] and more individuals achieved glycaemic targets (HbA1c < 7.0% 70 vs. 34%, P < 0.001). The proportion of individuals reporting at least one hypoglycaemic event during the last 12 weeks of treatment was similar in the two groups (rosiglitazone + metformin vs. placebo 25 vs. 27%). People receiving rosiglitazone + metformin in addition to insulin reported greater treatment satisfaction than those receiving insulin alone. Both treatment regimens were well tolerated but more participants had oedema [12 (7%) vs. 4 (3%)] and there was more weight gain [3.7 vs. 2.6 kg; difference 1.1 (0.2, 2.1) kg, P = 0.02] with rosiglitazone + metformin. Conclusions Addition of insulin to rosiglitazone + metformin enabled more people to reach glycaemic targets with less insulin, and was generally well tolerated. PMID:17403121

  6. 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.

  7. Shifts in metabolic parameters surrounding glucose homoeostasis resulting from tricyclic antidepressant therapy: implications of insulin resistance?

    PubMed

    Chadwick, W; Wilson, G; van de Venter, M; Oelofsen, W; Roux, S

    2007-01-01

    This study displayed the physiological effects the tricyclic antidepressants amitriptyline or trimipramine have on glucose homoeostasis in male Wistar rats. An insulin secreting cell line (INS-1) was also used to determine effects tricyclic antidepressants have on insulin secretion and insulin displacement. Thirty rats each received a 1 mg kg-1 dose of amitriptyline or trimipramine for a period of 14 weeks; another 14 rats served as the control group. Blood glucose, serum insulin and muscle and liver glycogen levels were determined. Kidney, liver and muscle insulin degradation was measured and compared with insulin degrading enzyme concentrations in the latter two tissues. INS-1 cells were used to determine the effect 1 microM amitriptyline has on insulin secretion. Displacement studies for [3H]glibenclamide by amitriptyline or trimipramine were undertaken on INS-1 cells. A significant increase in blood glucose (P<0.01) was found for both test groups after 6 and 14 weeks of receiving the medication, which may be related to a significant decrease in liver and muscle glycogen levels (P<0.001). Serum insulin levels remained unchanged, although a significant increase in insulin degradation was observed in the muscle, liver and kidney, which may be related to a significant increase in insulin degrading enzyme (P<0.001) that was found. A significant increase in insulin secretion was observed for the INS-1 cells treated with amitriptyline, although no significant displacement for the [3H]glibenclamide was evident for amitriptyline or trimipramine. The significant alterations in glucose homoeostasis observed, as well as the significant changes associated with insulin secretion and degradation associated with amitriptyline or trimipramine treatment, imply that prolonged use of these medicines may lead to insulin resistance and full blown diabetes. PMID:17227626

  8. Umbilical Cord Derived Mesenchymal Stem Cells Useful in Insulin Production - Another Opportunity in Cell Therapy

    PubMed Central

    Sarang, Shabari; Viswanathan, Chandra

    2016-01-01

    Background and Objectives Type 1 Diabetes Mellitus (T1DM) is an autoimmune disorder resulting out of T cell mediated destruction of pancreatic beta cells. Immunomodulatory properties of mesenchymal stem cells may help to regenerate beta cells and/or prevent further destruction of remnant, unaffected beta cells in diabetes. We have assessed the ability of umbilical cord derived MSCs (UCMSCs) to differentiate into functional islet cells in vitro. Methods and Results We have isolated UCMSCs and allowed sequential exposure of various inducing agents and growth factors. We characterized these cells for confirmation of the presence of islet cell markers and their functionality. The spindle shaped undifferentiated UCMSCs, change their morphology to become triangular in shape. These cells then come together to form the islet like structures which then grow in size and mature over time. These cells express pancreatic and duodenal homeobox −1 (PDX-1), neurogenin 3 (Ngn-3), glucose transporter 2 (Glut 2) and other pancreatic cell markers like glucagon, somatostatin and pancreatic polypeptide and lose expression of MSC markers like CD73 and CD105. They were functionally active as demonstrated by release of physiological insulin and C-peptide in response to elevated glucose concentrations. Conclusions Pancreatic islet like cells with desired functionality can thus be obtained in reasonable numbers from undifferentiated UCMSCs invitro. This could help in establishing a “very definitive source” of islet like cells for cell therapy. UCMSCs could thus be a game changer in treatment of diabetes. PMID:27426087

  9. Insulin-like Growth Factor: Current Concepts and New Developments in Cancer Therapy

    PubMed Central

    King, Erin R.; Wong, Kwong-Kwok

    2013-01-01

    The insulin-like growth factor (IGF) family and the IGF-1 receptor (IGF-1R) play an important role in cancer. This intricate and complex signaling pathway provides many opportunities for therapeutic intervention, and several novel therapeutics aimed at the IGF-1R, particularly monoclonal antibodies and small molecule tyrosine kinase inhibitors, are under clinical investigation. This article provides a patent overview of the IGF signaling pathway and its complexity, addresses the justification for the use of IGF-1R-targeted therapy, and reviews the results of in vivo and in vitro novel therapeutics. Over the past year, the completion of several phase I, II, and III trials have provided interesting new information about the clinical activity of these novel compounds, particularly CP-751,871, IMC-A12, R1507, AMG-479, AVE-1642, MK-0646, XL-228, OSI-906, and BMS-754807. We review the important preliminary results from clinical trials with these compounds and conclude with a discussion about future therapeutic efforts. PMID:21875414

  10. The Insulin/IGF System in Colorectal Cancer Development and Resistance to Therapy.

    PubMed

    Vigneri, Paolo Giovanni; Tirrò, Elena; Pennisi, Maria Stella; Massimino, Michele; Stella, Stefania; Romano, Chiara; Manzella, Livia

    2015-01-01

    The insulin/insulin-like growth factor (IGF) system is a major determinant in the pathogenesis and progression of colorectal cancer (CRC). Indeed, several components of this signaling network, including insulin, IGF-1, IGF-2, the IGF-binding proteins, the insulin receptor (IR), the IGF-1 receptor (IGF-1R), and IR substrate proteins 1 and 2 contribute to the transformation of normal colon epithelial cells. Moreover, the insulin/IGF system is also implicated in the development of resistance to both chemotherapeutic drugs and epidermal growth factor receptor targeted agents. The identification of hybrid receptors comprising both the IR and IGF-1R adds further complexity to this signaling network. Thus, a comprehensive understanding of the biological functions performed by each component of the insulin/IGF system is required to design successful drugs for the treatment of CRC patients. PMID:26528439

  11. The Insulin/IGF System in Colorectal Cancer Development and Resistance to Therapy

    PubMed Central

    Vigneri, Paolo Giovanni; Tirrò, Elena; Pennisi, Maria Stella; Massimino, Michele; Stella, Stefania; Romano, Chiara; Manzella, Livia

    2015-01-01

    The insulin/insulin-like growth factor (IGF) system is a major determinant in the pathogenesis and progression of colorectal cancer (CRC). Indeed, several components of this signaling network, including insulin, IGF-1, IGF-2, the IGF-binding proteins, the insulin receptor (IR), the IGF-1 receptor (IGF-1R), and IR substrate proteins 1 and 2 contribute to the transformation of normal colon epithelial cells. Moreover, the insulin/IGF system is also implicated in the development of resistance to both chemotherapeutic drugs and epidermal growth factor receptor targeted agents. The identification of hybrid receptors comprising both the IR and IGF-1R adds further complexity to this signaling network. Thus, a comprehensive understanding of the biological functions performed by each component of the insulin/IGF system is required to design successful drugs for the treatment of CRC patients. PMID:26528439

  12. Effects of different intensities of physical exercise on insulin sensitivity and protein kinase B/Akt activity in skeletal muscle of obese mice

    PubMed Central

    Marinho, Rodolfo; de Moura, Leandro Pereira; Rodrigues, Bárbara de Almeida; Pauli, Luciana Santos Souza; da Silva, Adelino Sanchez Ramos; Ropelle, Eloize Cristina Chiarreotto; de Souza, Claudio Teodoro; Cintra, Dennys Esper Corrêa; Ropelle, Eduardo Rochete; Pauli, José Rodrigo

    2014-01-01

    ABSTRACT Objective: To investigate the effects of different intensities of acute exercise on insulin sensitivity and protein kinase B/Akt activity in skeletal muscle of obese mice. Methods: Swiss mice were randomly divided into four groups, and fed either a standard diet (control group) or high fat diet (obese sedentary group and obese exercise group 1 and 2) for 12 weeks. Two different exercise protocols were used: swimming for 1 hour with or without an overload of 5% body weight. The insulin tolerance test was performed to estimate whole-body sensitivity. Western blot technique was used to determine protein levels of protein kinase B/Akt and phosphorylation by protein Kinase B/Akt in mice skeletal muscle. Results: A single bout of exercise inhibited the high fat diet-induced insulin resistance. There was increase in phosphorylation by protein kinase B/Akt serine, improve in insulin signaling and reduce of fasting glucose in mice that swam for 1 hour without overload and mice that swan for 1 hour with overload of 5%. However, no significant differences were seen between exercised groups. Conclusion: Regardless of intensity, aerobic exercise was able to improve insulin sensitivity and phosphorylation by protein kinase B/Ak, and proved to be a good form of treatment and prevention of type 2 diabetes. PMID:24728251

  13. 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.

  14. 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.

  15. 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.

  16. Consensus evidence-based guidelines for use of insulin pump therapy in the management of diabetes as per Indian clinical practice.

    PubMed

    Kesavadev, Jothydev; Jain, Sunil M; Muruganathan, A; Das, Ashok Kumar

    2014-07-01

    The use of insulin pump in diabetes is likely to increase with recent advances in technology. Although the evidence for the superiority of pumps over multiple daily injections (MDI) is inconsistent, data from accumulating uncontrolled studies indicate greater reductions in glycated haemoglobin in patients switching to continuous subcutaneous insulin infusion (CSII) from MDI therapy. Due to the variability in insulin requirements and sensitivity to CSII pumps, hyperglycaemia in these patients is managed by endocrinologists using individualised therapy. A panel of experts reviewed the existing guidelines and framed recommendations specific to the clinical practice in Indian conditions for use of CSII pumps in the management of hyperglycaemia. Selection of right patient with basic education, motivation and learning skills are essential for successful implementation of CSII therapy with sophisticated programmes. Rapid acting insulin analogues with better pharmacokinetic and pharmacodynamic profile, physical and chemical stability and compatibility with most commercially available insulin pumps are preferred over regular insulin to achieve safe and stable glycaemic control. Further, educating pump users on proper use of CSII pumps, insulin dose adjustments, and handling of accessories are recommended in the current consensus guidelines. Practice of self-monitoring of blood glucose and glycated haemoglobin levels are essential to adjust insulin dosage for the management of diabetes. Use of CSII pumps in special patient populations should be carefully assessed and initiated by endocrinologist. The proposed guidelines can form a basis for use of CSII pumps in the management of hyperglycaemia in the Indian scenario. PMID:25668935

  17. Ezetimibe combined with standard diet and exercise therapy improves insulin resistance and atherosclerotic markers in patients with metabolic syndrome

    PubMed Central

    Ohbu-Murayama, Kyoko; Adachi, Hisashi; Hirai, Yuji; Enomoto, Mika; Fukami, Ako; Obuchi, Aya; Yoshimura, Ayako; Nakamura, Sachiko; Nohara, Yume; Nakao, Erika; Umeki, Yoko; Fukumoto, Yoshihiro

    2015-01-01

    Aims/Introduction Ezetimibe lowers serum lipid levels by inhibiting intestinal absorption of dietary and biliary cholesterol. However, the effect of ezetimibe on insulin resistance remains unclear. The aim of the present study was to examine this issue in patients with metabolic syndrome in local-dwelling Japanese, who were not being treated with lipid-lowering drugs. Materials and Methods In 2009, 1,943 participants received a health examination in the Tanushimaru Study, a Japanese cohort of the Seven Countries Study, of whom 490 participants had metabolic syndrome. Among them, 61 participants (41 men and 20 women) were examined in the present study. They were treated with 10 mg of ezetimibe once a day for 24 weeks, combined with standard diet and exercise therapy. Results Bodyweight (P < 0.001), body mass index (P < 0.001), systolic blood pressure (P = 0.003), diastolic blood pressure (P < 0.001), triglycerides (P = 0.002), non-high-density lipoprotein cholesterol (P = 0.001), low-density lipoprotein cholesterol (P < 0.001) and homeostasis model assessment of insulin resistance (P = 0.011) significantly decreased after the observational period. There were no statistically significant differences in the effects of ezetimibe between men and women. Univariate analysis showed that the reduction of homeostasis model assessment of insulin resistance was not associated with the improvement of other metabolic components. Conclusions Ezetimibe combined with standard diet and exercise therapy improves not only bodyweight and atherogenic lipid profiles, but also insulin resistance, blood pressure and anthropometric factors in metabolic syndrome in local-dwelling Japanese. Interestingly, the improvement of insulin resistance had no correlation with other metabolic components. PMID:25969718

  18. High-intensity interval training without weight loss improves exercise but not basal or insulin-induced metabolism in overweight/obese African American women.

    PubMed

    Arad, Avigdor D; DiMenna, Fred J; Thomas, Naketa; Tamis-Holland, Jacqueline; Weil, Richard; Geliebter, Allan; Albu, Jeanine B

    2015-08-15

    The purpose of this randomized controlled clinical trial was to determine the effect of a 14-week high-intensity interval training (HIIT) intervention with weight stability on metabolic flexibility, insulin sensitivity, and cardiorespiratory fitness in sedentary, premenopausal, nondiabetic, overweight/obese African American women. Twenty-eight subjects were allocated to one of two groups: HIIT, which performed three sessions per week of four high-intensity cycling intervals, or a control group (CON), which maintained their normal level of physical activity. Diet was controlled for all subjects to ensure weight stability. Pre- and postintervention (pre/post), subjects completed an incremental cycling test to limit of tolerance and, following a 10-day high-fat controlled feeding period, a euglycemic-hyperinsulinemic clamp to determine insulin sensitivity and substrate oxidation. Nine members of HIIT (age, 29 ± 4 yr; body mass, 90.1 ± 13.8 kg) and eleven members of CON (age, 30 ± 7 yr; body mass, 85.5 ± 10.7 kg) completed the study. HIIT experienced an increased limit of tolerance (post, 1,124 ± 202 s; pre, 987 ± 146 s; P < 0.05), gas exchange threshold (post, 1.29 ± 0.34 liters/min; pre, 0.97 ± 0.23 liters/min; P < 0.05), and fat oxidation at the same absolute submaximal work rate compared with CON (P < 0.05 for group-by-time interaction in all cases). However, changes in peak oxygen consumption (V̇o2peak), insulin sensitivity, free fatty acid suppression during insulin stimulation, and metabolic flexibility were not different in HIIT compared with CON. High-intensity interval training with weight stability increased exercise fat oxidation and tolerance in subjects at risk for diabetic progression, but did not improve insulin sensitivity or fat oxidation in the postabsorptive or insulin-stimulated state.

  19. High-intensity interval training without weight loss improves exercise but not basal or insulin-induced metabolism in overweight/obese African American women.

    PubMed

    Arad, Avigdor D; DiMenna, Fred J; Thomas, Naketa; Tamis-Holland, Jacqueline; Weil, Richard; Geliebter, Allan; Albu, Jeanine B

    2015-08-15

    The purpose of this randomized controlled clinical trial was to determine the effect of a 14-week high-intensity interval training (HIIT) intervention with weight stability on metabolic flexibility, insulin sensitivity, and cardiorespiratory fitness in sedentary, premenopausal, nondiabetic, overweight/obese African American women. Twenty-eight subjects were allocated to one of two groups: HIIT, which performed three sessions per week of four high-intensity cycling intervals, or a control group (CON), which maintained their normal level of physical activity. Diet was controlled for all subjects to ensure weight stability. Pre- and postintervention (pre/post), subjects completed an incremental cycling test to limit of tolerance and, following a 10-day high-fat controlled feeding period, a euglycemic-hyperinsulinemic clamp to determine insulin sensitivity and substrate oxidation. Nine members of HIIT (age, 29 ± 4 yr; body mass, 90.1 ± 13.8 kg) and eleven members of CON (age, 30 ± 7 yr; body mass, 85.5 ± 10.7 kg) completed the study. HIIT experienced an increased limit of tolerance (post, 1,124 ± 202 s; pre, 987 ± 146 s; P < 0.05), gas exchange threshold (post, 1.29 ± 0.34 liters/min; pre, 0.97 ± 0.23 liters/min; P < 0.05), and fat oxidation at the same absolute submaximal work rate compared with CON (P < 0.05 for group-by-time interaction in all cases). However, changes in peak oxygen consumption (V̇o2peak), insulin sensitivity, free fatty acid suppression during insulin stimulation, and metabolic flexibility were not different in HIIT compared with CON. High-intensity interval training with weight stability increased exercise fat oxidation and tolerance in subjects at risk for diabetic progression, but did not improve insulin sensitivity or fat oxidation in the postabsorptive or insulin-stimulated state. PMID:26112241

  20. Lifestyle modification interventions differing in intensity and dietary stringency improve insulin resistance through changes in lipoprotein profiles

    PubMed Central

    Costantino, N. S.; Blackburn, H. L.; Engler, R. J. M.; Kashani, M.; Vernalis, M. N.

    2016-01-01

    Summary Objective Metabolic dysfunction characterized by insulin resistance (IR) is an important risk factor for type‐2 diabetes and coronary artery disease (CAD). The aim of this study was to determine if clinical lifestyle interventions differing in scope and intensity improve IR, defined by the lipoprotein IR (LPIR) score, in individuals differing in the severity of metabolic dysfunction. Methods Subjects with diagnosed type‐2 diabetes, CAD or significant risk factors participated in one of two clinical lifestyle modification interventions: (i) intensive non‐randomized programme with a strict vegetarian diet (n = 90 participants, 90 matched controls) or (ii) moderate randomized trial following a Mediterranean‐style diet (n = 89 subjects, 58 controls). On‐treatment and intention‐to‐treat analyses assessed changes over 1 year in LPIR, lipoprotein profiles and metabolic risk factors in intervention participants and controls in both programmes. Results In the on‐treatment analysis, both interventions led to weight loss: [−8.9% (95% CI, −10.3 to −7.4), intensive programme; −2.8% (95% CI, −3.8 to −1.9), moderate programme; adjusted P < 0.001] and a decrease in the LPIR score [−13.3% (95% CI, −18.2 to −8.3), intensive; −8.8% (95% CI, −12.9 to −4.7), moderate; adjusted P < 0.01] compared with respective controls. Of the six lipoprotein parameters comprising LPIR, only large very‐low‐density lipoprotein particle concentrations decreased significantly in participants compared with controls in both programmes [−26.3% (95% CI, −43.0 to −9.6), intensive; −14.2% (95% CI, −27.4 to −1.0), moderate; P < 0.05]. Intention‐to‐treat analysis confirmed and strengthened the primary results. Conclusion A stringent lifestyle modification intervention with a vegetarian diet and a moderate lifestyle modification intervention following a Mediterranean diet were both effective for improving IR defined by the

  1. Lifestyle modification interventions differing in intensity and dietary stringency improve insulin resistance through changes in lipoprotein profiles

    PubMed Central

    Costantino, N. S.; Blackburn, H. L.; Engler, R. J. M.; Kashani, M.; Vernalis, M. N.

    2016-01-01

    Summary Objective Metabolic dysfunction characterized by insulin resistance (IR) is an important risk factor for type‐2 diabetes and coronary artery disease (CAD). The aim of this study was to determine if clinical lifestyle interventions differing in scope and intensity improve IR, defined by the lipoprotein IR (LPIR) score, in individuals differing in the severity of metabolic dysfunction. Methods Subjects with diagnosed type‐2 diabetes, CAD or significant risk factors participated in one of two clinical lifestyle modification interventions: (i) intensive non‐randomized programme with a strict vegetarian diet (n = 90 participants, 90 matched controls) or (ii) moderate randomized trial following a Mediterranean‐style diet (n = 89 subjects, 58 controls). On‐treatment and intention‐to‐treat analyses assessed changes over 1 year in LPIR, lipoprotein profiles and metabolic risk factors in intervention participants and controls in both programmes. Results In the on‐treatment analysis, both interventions led to weight loss: [−8.9% (95% CI, −10.3 to −7.4), intensive programme; −2.8% (95% CI, −3.8 to −1.9), moderate programme; adjusted P < 0.001] and a decrease in the LPIR score [−13.3% (95% CI, −18.2 to −8.3), intensive; −8.8% (95% CI, −12.9 to −4.7), moderate; adjusted P < 0.01] compared with respective controls. Of the six lipoprotein parameters comprising LPIR, only large very‐low‐density lipoprotein particle concentrations decreased significantly in participants compared with controls in both programmes [−26.3% (95% CI, −43.0 to −9.6), intensive; −14.2% (95% CI, −27.4 to −1.0), moderate; P < 0.05]. Intention‐to‐treat analysis confirmed and strengthened the primary results. Conclusion A stringent lifestyle modification intervention with a vegetarian diet and a moderate lifestyle modification intervention following a Mediterranean diet were both effective for improving IR defined by the

  2. [Modern drug therapy in cardiovascular intensive care medicine].

    PubMed

    Lemm, H; Dietz, S; Janusch, M; Buerke, M

    2015-06-01

    Vasoactive drugs and inotropes are important in the hemodynamic management of patients with cardiogenic shock despite modest volume administration. Currently, the concept of cardiac relief is pursued in the treatment of acute heart failure. In this article we present the use of different drugs in the intensive care unit for acute heart failure and cardiogenic shock. In acute heart failure catecholamines are only used during the transition from heart failure to cardiogenic shock. Here, the therapeutic concept of ventricular unloading is more sought after. This can be achieved by the use of diuretics, nitrates, levosimendan (inodilatator), or in the future serelaxin. The hemodynamic management in cardiogenic shock occurs after moderate volume administration with dobutamine to increase inotropy. If no adequate perfusion pressures are achieved, norepinephrine can be administered as a vasopressor. If there is still no sufficient increase in cardiac output, the inodilatator levosimendan can be used. Levosimendan instead of phosphodiesterase inhibitors in this case is preferable. The maxim of hemodynamic management in cardiogenic shock is the transient use of inotropes and vasopressors in the lowest dose possible and only for as long as necessary. This means that one should continuously check whether the dose can be reduced. There are no mortality data demonstrating the utility of hemodynamic monitoring based on objective criteria—but it makes sense to use inotropes and vasopressors sparingly.

  3. The effects and mechanisms of insulin on systemic inflammatory response and immune cells in severe trauma, burn injury, and sepsis.

    PubMed

    Deng, Hu-Ping; Chai, Jia-Ke

    2009-10-01

    Insulin resistance, hyperglycemia, inflammatory disorders and immune dysfunction cause high morbidity and mortality in patients with severe trauma, burn injuries, or sepsis. Many studies have shown that intensive insulin therapy can combat insulin resistance, decrease blood glucose levels, and induce anabolic processes, thus, decreasing morbidity and mortality. Moreover, in recent years, it has been proven that insulin can attenuate systemic inflammatory responses and modulate the proliferation, apoptosis, differentiation and immune functions of certain immune cells, especially monocytes/macrophages, neutrophils, and T cells associated with severe trauma, burn injury, or sepsis. This effect of insulin may expand our understanding of intensive insulin therapy in critically ill patients. This review attempts to summarize studies on the modulatory effects and mechanisms of insulin therapy on systemic inflammation and immune cells in severe trauma, burn injury and sepsis, and further propose some questions for future studies.

  4. Effect of glycerol on sustained insulin release from PVA hydrogels and its application in diabetes therapy

    PubMed Central

    Cai, Yunpeng; Che, Junyi; Yuan, Minglu; Shi, Xiaohong; Chen, Wei; Yuan, Wei-En

    2016-01-01

    The present study aimed to investigate the effects of glycerol on the physical properties and release of an insulin-loaded polyvinyl alcohol (PVA) hydrogel film. The insulin-loaded hydrogel composite film was produced using the freeze-thawing method, after which the in vitro swelling ratio, transmittance and insulin release, and the in vivo pharmacodynamics, of hydrogels containing various volumes of glycerol were investigated. The results demonstrated that the addition of glycerol reduced the swelling ratio and increased the softness of the PVA hydrogel film. An analysis of insulin release in vitro and of the hypoglycemic effects in rats demonstrated that the PVA hydrogel film had a sustained release of insulin and long-acting effect over 10 days. The results of the present study suggested that, as a hydrophilic plasticizer, glycerol was able to enhance the release of insulin in the early stage of release profile by enhancing the formation of water channels, although the total swelling ratio was decreased. Therefore, the insulin-loaded glycerol/PVA hydrogel film may be a promising sustained-release preparation for the treatment of diabetes. PMID:27698690

  5. Effect of glycerol on sustained insulin release from PVA hydrogels and its application in diabetes therapy

    PubMed Central

    Cai, Yunpeng; Che, Junyi; Yuan, Minglu; Shi, Xiaohong; Chen, Wei; Yuan, Wei-En

    2016-01-01

    The present study aimed to investigate the effects of glycerol on the physical properties and release of an insulin-loaded polyvinyl alcohol (PVA) hydrogel film. The insulin-loaded hydrogel composite film was produced using the freeze-thawing method, after which the in vitro swelling ratio, transmittance and insulin release, and the in vivo pharmacodynamics, of hydrogels containing various volumes of glycerol were investigated. The results demonstrated that the addition of glycerol reduced the swelling ratio and increased the softness of the PVA hydrogel film. An analysis of insulin release in vitro and of the hypoglycemic effects in rats demonstrated that the PVA hydrogel film had a sustained release of insulin and long-acting effect over 10 days. The results of the present study suggested that, as a hydrophilic plasticizer, glycerol was able to enhance the release of insulin in the early stage of release profile by enhancing the formation of water channels, although the total swelling ratio was decreased. Therefore, the insulin-loaded glycerol/PVA hydrogel film may be a promising sustained-release preparation for the treatment of diabetes.

  6. Analysis of alternatives for insulinizing patients to achieve glycemic control and avoid accompanying risks of hypoglycemia

    PubMed Central

    GAO, JIALIN; XIONG, QIANYIN; MIAO, JUN; ZHANG, YAO; XIA, LIBING; LU, MEIQIN; ZHANG, BINHUA; CHEN, YUEPING; ZHANG, ANSU; YU, CUI; WANG, LI-ZHUO

    2015-01-01

    The aims of the present study were to explore the efficacy of glycemic control and the risks of hypoglycemia with different methods of insulin therapy, and to provide reference data for the clinical treatment of diabetes. In this retrospective study, hospitalized patients diagnosed with type 2 diabetes between March and December 2014, in the Department of Endocrinology in the First Affiliated Hospital of Wannan Medical College, were divided into three groups, including an intensive insulin analogue therapy group, a premixed insulin analogue treatment group and a premixed human insulin therapy group. The efficacy of glycemic control and the incidence of hypoglycemia were determined in each of the insulin treatment groups. Compared with the other treatment groups, the intensive insulin analogue therapy group was associated with superior blood glucose control, shorter time to reach standard insulin regimen, shorter hospitalization time, fewer fluctuations in blood glucose levels and lower insulin dosage on discharge from hospital. However, this treatment was also associated with a high risk of hypoglycemia. In conclusion, when combined with the effective prevention of hypoglycemia and appropriate nursing care (especially in hospital care), intensive insulin analogue therapy may provide the greatest benefit to patients. PMID:26137223

  7. Initiating or Switching to Biphasic Insulin Aspart 30/70 Therapy in Subjects with Type 2 Diabetes Mellitus. An Observational Study

    PubMed Central

    Breum, Leif; Almdal, Thomas; Eiken, Pia; Lund, Per; Christiansen, Erik; on behalf of the Danish BIAsp Study Group

    2008-01-01

    OBJECTIVE: To investigate tolerability and glycemic control over 26 weeks in patients with type 2 diabetes (T2D) who initiated insulin with, or switched to, biphasic insulin aspart 30/70 (BIAsp 30) in routine clinical care. METHODS: This was a non-randomized, non-interventional, open-label, observational study involving patients under the care of approximately 150 insulin-prescribing physicians in Denmark. All patients enrolled were prescribed BIAsp 30 in routine care. Starting dose, dose titration and injection frequency were determined individually by each physician. Information on serious adverse drug reactions (SADR), glycemic parameters and hypoglycemic events were obtained from patients’ notes, patients’ diaries and recall, and transferred to case report forms by physicians at baseline (during 4 weeks prior to BIAsp 30 therapy) and after 12 and 26 weeks of treatment. RESULTS: 421 subjects were recruited and 392 provided safety data. The age (mean ± SD) was 62.0 ± 11.4 years, body mass index (BMI) 30.4 ± 6.4 kg/m2, duration of diabetes 9.1 ± 8.1 years and HbA1c (%) 9.4 ± 1.7. 199 subjects were prior insulin users and 193 were insulin-naïve patients. Four patients reported a SADR (3 hypoglycemia, 1 severe hypoglycemia). HbA1c was significantly reduced after 26 weeks of BIAsp 30 therapy: prior insulin users -1.2%, insulin-naïve patients -2.2% (both p < 0.001). 28% and 41% of patients, respectively, reached target HbA1c < 7%. Overall the hypoglycemia rate was lower for insulin-naïve patients than for prior insulin users: 5.0 vs. 6.6 episodes/patient-year (p < 0.05). CONCLUSION: Initiating insulin with, or switching insulin to, BIAsp 30 in routine care was safe and effective in patients with T2D. PMID:19099087

  8. High Prevalence of Dyslipidemia and Insulin Resistance in HIV-Infected Pre-Pubertal African Children on Antiretroviral Therapy

    PubMed Central

    Innes, Steve; Abdullah, Kameelah L.; Haubrich, Richard; Cotton, Mark F.; Browne, Sara H.

    2015-01-01

    BACKGROUND Data describing the true extent of antiretroviral therapy (ART)-induced dyslipidemia and insulin resistance in perinatally-infected children on ART in Africa is sparse. METHODS Fasting total cholesterol, LDL, HDL, triglycerides, insulin and glucose were performed on the first 100, of 190 pediatric ART clinic attendees. Diet assessment was performed by a trained dietician. Lipoatrophy was formally graded by consensus between two expert HIV pediatricians. Durations of previous ART exposures, clinical stage, pre-ART viral load, nadir and current CD4 were recorded. Dual energy X-ray Absorptiometry (DEXA) was performed on a subset of 42 patients selected semi-randomly. RESULTS Prevalences of insulin resistance, abnormal total cholesterol, LDL, HDL and triglyceride were 10%, 13%, 12%, 13 % and 9% respectively. Overall, 40% had at least one lipid abnormality or insulin resistance. Adjusted mean LDL cholesterol increased by 0.24mmol/L for each additional year of cumulative lopinavir/r exposure (p=0.03) after correcting for age, gender, body mass index, previous stavudine exposure, age at ART initiation, dietary fat and refined carbohydrate, while adjusted mean LDL cholesterol was 0.9mmol/L higher in children exposed to efavirenz within the previous six months (p=0.02). Adjusting for age, gender and ethnicity, DEXA revealed that greater trunk fat and lower peripheral subcutaneous fat were associated with elevated triglycerides but not with total cholesterol, LDL, HDL or HOMA. Similarly, the presence of visually obvious lipoatrophy was associated with elevated triglycerides but not with total cholesterol, LDL, HDL, HOMA or lactate. CONCLUSIONS Prevalences of insulin resistance and dyslipidemia were high. Cumulative lopinovir is an independent risk factor for dyslipidemia, with efavirenz exposure having only transitory effect. PMID:26421804

  9. Race, socioeconomic status, and treatment center are associated with insulin pump therapy in youth in the first year following diagnosis of type 1 diabetes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Increasing numbers of children and adolescents with type 1 diabetes (T1D) have been placed on insulin pump therapy. Nevertheless, data are limited regarding patterns of pump use during the first year of treatment and the clinical and socioeconomic factors associated with early use of pump therapy. T...

  10. Iodine-131-metaiodobenzylguanidine therapy with reduced-intensity allogeneic stem cell transplantation in recurrent neuroblastoma.

    PubMed

    Takahashi, Hiroka; Manabe, Atsushi; Aoyama, Chiaki; Kamiya, Takahiro; Kato, Itaru; Takusagawa, Ayako; Ogawa, Chitose; Ozawa, Miwa; Hosoya, Ryota; Yokoyama, Kunihiko

    2008-03-01

    Neuroblastoma is the most common extracranial solid tumor of childhood, and iodine-131-metaiodobenzylguanidine (MIBG) therapy is a new approach for grade IV neuroblastoma. We describe the case history of a 3-year-old girl with recurrent neuroblastoma who received MIBG therapy with reduced-intensity allogeneic stem cell transplantation (RIST) because of an extensive bone marrow involvement. The post-transplant course was uneventful and complete chimerism was obtained. Neither acute nor chronic graft-versus-host disease (GVHD) was observed. The patient remained in remission for 3 months after RIST until the second relapse. MIBG therapy combined with RIST warrants further trials.

  11. Comparison of high-intensity laser therapy and ultrasound treatment in the patients with lumbar discopathy.

    PubMed

    Boyraz, Ismail; Yildiz, Ahmet; Koc, Bunyamin; Sarman, Hakan

    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

  12. Comparison of high-intensity laser therapy and ultrasound treatment in the patients with lumbar discopathy.

    PubMed

    Boyraz, Ismail; Yildiz, Ahmet; Koc, Bunyamin; Sarman, Hakan

    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.

  13. 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

  14. 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…

  15. 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…

  16. Variability of Basal Rate Profiles in Insulin Pump Therapy and Association with Complications in Type 1 Diabetes Mellitus

    PubMed Central

    Laimer, Markus; Melmer, Andreas; Mader, Julia K.; Schütz-Fuhrmann, Ingrid; Engels, Heide-Rose; Götz, Gabriele; Pfeifer, Martin; Hermann, Julia M.; Stettler, Christoph; Holl, Reinhard W.

    2016-01-01

    Background Traditionally, basal rate profiles in continuous subcutaneous insulin infusion therapy are individually adapted to cover expected insulin requirements. However, whether this approach is indeed superior to a more constant BR profile has not been assessed so far. This study analysed the associations between variability of BR profiles and acute and chronic complications in adult type 1 diabetes mellitus. Materials and Methods BR profiles of 3118 female and 2427 male patients from the “Diabetes-Patienten-Verlaufsdokumentation” registry from Germany and Austria were analysed. Acute and chronic complications were recorded 6 months prior and after the most recently documented basal rate. The “variability index” was calculated as variation of basal rate intervals in percent and describes the excursions of the basal rate intervals from the median basal rate. Results The variability Index correlated positively with severe hypoglycemia (r = .06; p<0.001), hypoglycemic coma (r = .05; p = 0.002), and microalbuminuria (r = 0.05; p = 0.006). In addition, a higher variability index was associated with higher frequency of diabetic ketoacidosis (r = .04; p = 0.029) in male adult patients. Logistic regression analysis adjusted for age, gender, duration of disease and total basal insulin confirmed significant correlations of the variability index with severe hypoglycemia (β = 0.013; p<0.001) and diabetic ketoacidosis (β = 0.012; p = 0.017). Conclusions Basal rate profiles with higher variability are associated with an increased frequency of acute complications in adults with type 1 diabetes. PMID:26938444

  17. Targeting triglyceride/fatty acid cycling in β-cells as a therapy for augmenting glucose-stimulated insulin secretion.

    PubMed

    Cantley, James; Biden, Trevor J

    2010-01-01

    Insulin secretion from pancreatic β-cells is triggered by signals arising from the metabolism of glucose and acting through separate initiation and amplification pathways. Despite decades of investigation, crucial details of this mechanism remain poorly understood, especially those relating to the amplifying pathway(s). Advances in this area are vital if we are to understand why insulin secretion fails in type 2 diabetes and to develop strategies to overcome this failure. Indeed, targeting the amplifying pathway(s) would constitute an attractive therapy for augmenting insulin secretion because it would closely link secretory responsiveness to the prevailing glycaemia. It is therefore noteworthy that the possibility of augmenting the amplification pathway(s) has recently been highlighted by studies investigating a metabolic cycle that links the breakdown of triacylglycerol (TAG), release of fatty acid (FA), and subsequent re-incorporation of that FA into TAG. This work reinvigorates and extends the long-standing idea that partitioning of endogenous lipid metabolism towards esterification products promotes the amplification phase of the secretory response. These conceptual advances, and their possible therapeutic application, will be discussed in the following article.

  18. Sotagliflozin, a Dual SGLT1 and SGLT2 Inhibitor, as Adjunct Therapy to Insulin in Type 1 Diabetes

    PubMed Central

    Zambrowicz, Brian P.; Rosenstock, Julio; Lapuerta, Pablo; Bode, Bruce W.; Garg, Satish K.; Buse, John B.; Banks, Phillip; Heptulla, Rubina; Rendell, Marc; Cefalu, William T.

    2015-01-01

    OBJECTIVE To assess the safety and efficacy of dual sodium–glucose cotransporter (SGLT) 1 and SGLT2 inhibition with sotagliflozin as adjunct therapy to insulin in type 1 diabetes. RESEARCH DESIGN AND METHODS We treated 33 patients with sotagliflozin, an oral dual SGLT1 and SGLT2 inhibitor, or placebo in a randomized, double-blind trial assessing safety, insulin dose, glycemic control, and other metabolic parameters over 29 days of treatment. RESULTS In the sotagliflozin-treated group, the percent reduction from baseline in the primary end point of bolus insulin dose was 32.1% (P = 0.007), accompanied by lower mean daily glucose measured by continuous glucose monitoring (CGM) of 148.8 mg/dL (8.3 mmol/L) (P = 0.010) and a reduction of 0.55% (5.9 mmol/mol) (P = 0.002) in HbA1c compared with the placebo group that showed 6.4% reduction in bolus insulin dose, a mean daily glucose of 170.3 mg/dL (9.5 mmol/L), and a decrease of 0.06% (0.65 mmol/mol) in HbA1c. The percentage of time in target glucose range 70–180 mg/dL (3.9–10.0 mmol/L) increased from baseline with sotagliflozin compared with placebo, to 68.2% vs. 54.0% (P = 0.003), while the percentage of time in hyperglycemic range >180 mg/dL (10.0 mmol/L) decreased from baseline, to 25.0% vs. 40.2% (P = 0.002), for sotagliflozin and placebo, respectively. Body weight decreased (1.7 kg) with sotagliflozin compared with a 0.5 kg gain (P = 0.005) in the placebo group. CONCLUSIONS As adjunct to insulin, dual SGLT1 and SGLT2 inhibition with sotagliflozin improved glycemic control and the CGM profile with bolus insulin dose reduction, weight loss, and no increased hypoglycemia in type 1 diabetes. PMID:26049551

  19. Intensity-Modulated Radiation Therapy, Proton Therapy, or Conformal Radiation Therapy and Morbidity and Disease Control in Localized Prostate Cancer

    PubMed Central

    Sheets, Nathan C.; Goldin, Gregg H.; Meyer, Anne-Marie; Wu, Yang; Chang, YunKyung; Stürmer, Til; Holmes, Jordan A.; Reeve, Bryce B.; Godley, Paul A.; Carpenter, William R.; Chen, Ronald C.

    2013-01-01

    Context There has been rapid adoption of newer radiation treatments such as intensitymodulated radiation therapy (IMRT) and proton therapy despite greater cost and limited demonstrated benefit compared with previous technologies. Objective To determine the comparative morbidity and disease control of IMRT, proton therapy, and conformal radiation therapy for primary prostate cancer treatment. Design, Setting, and Patients Population-based study using Surveillance, Epidemiology, and End Results–Medicare-linked data from 2000 through 2009 for patients with nonmetastatic prostate cancer. Main Outcome Measures Rates of gastrointestinal and urinary morbidity, erectile dysfunction, hip fractures, and additional cancer therapy. Results Use of IMRT vs conformal radiation therapy increased from 0.15% in 2000 to 95.9% in 2008. In propensity score–adjusted analyses (N=12 976), men who received IMRT vs conformal radiation therapy were less likely to receive a diagnosis of gastrointestinal morbidities (absolute risk, 13.4 vs 14.7 per 100 person-years; relative risk [RR], 0.91; 95% CI, 0.86–0.96) and hip fractures (absolute risk, 0.8 vs 1.0 per 100 person-years; RR, 0.78; 95% CI, 0.65–0.93) but more likely to receive a diagnosis of erectile dysfunction (absolute risk, 5.9 vs 5.3 per 100 person-years; RR, 1.12; 95% CI, 1.03–1.20). Intensitymodulated radiation therapy patients were less likely to receive additional cancer therapy (absolute risk, 2.5 vs 3.1 per 100 person-years; RR, 0.81; 95% CI, 0.73–0.89). In a propensity score–matched comparison between IMRT and proton therapy (n=1368), IMRT patients had a lower rate of gastrointestinal morbidity (absolute risk, 12.2 vs 17.8 per 100 person-years; RR, 0.66; 95% CI, 0.55–0.79). There were no significant differences in rates of other morbidities or additional therapies between IMRT and proton therapy. Conclusions Among patients with nonmetastatic prostate cancer, the use of IMRT compared with conformal radiation

  20. Efficacy and safety of the glucagon-like peptide-1 receptor agonist liraglutide added to insulin therapy in poorly regulated patients with type 1 diabetes—a protocol for a randomised, double-blind, placebo-controlled study: The Lira-1 study

    PubMed Central

    Dejgaard, Thomas Fremming; Knop, Filip Krag; Tarnow, Lise; Frandsen, Christian Seerup; Hansen, Tanja Stenbæk; Almdal, Thomas; Holst, Jens Juul; Madsbad, Sten; Andersen, Henrik Ullits

    2015-01-01

    Introduction Intensive insulin therapy is recommended for the treatment of type 1 diabetes (T1D). Hypoglycaemia and weight gain are the common side effects of insulin treatment and may reduce compliance. In patients with insulin-treated type 2 diabetes, the addition of glucagon-like peptide-1 receptor agonist (GLP-1RA) therapy has proven effective in reducing weight gain and insulin dose. The present publication describes a protocol for a study evaluating the efficacy and safety of adding a GLP-1RA to insulin treatment in overweight patients with T1D in a randomised, double-blinded, controlled design. Methods and analysis In total, 100 patients with type 1 diabetes, poor glycaemic control (glycated haemoglobin (HbA1c) >8%) and overweight (body mass index >25 kg/m2) will be randomised to either liraglutide 1.8 mg once daily or placebo as an add-on to intensive insulin therapy in this investigator initiated, double-blinded, placebo-controlled parallel study. The primary end point is glycaemic control as measured by changes in HbA1c. Secondary end points include changes in the insulin dose, hypoglyacemic events, body weight, lean body mass, fat mass, food preferences and adverse events. Glycaemic excursions, postprandial glucagon levels and gastric emptying rate during a standardised liquid meal test will also be studied. Ethics and dissemination The study is approved by the Danish Medicines Authority, the Regional Scientific-Ethical Committee of the Capital Region of Denmark and the Data Protection Agency. The study will be carried out under the surveillance and guidance of the good clinical practice (GCP) unit at Copenhagen University Hospital Bispebjerg in accordance with the ICH-GCP guidelines and the Helsinki Declaration. Trial registration number NCT01612468. PMID:25838513

  1. 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.

  2. Effects of Insulin Therapy on Myocardial Lipid Content and Cardiac Geometry in Patients with Type-2 Diabetes Mellitus

    PubMed Central

    Jankovic, Drazenka; Winhofer, Yvonne; Promintzer-Schifferl, Miriam; Wohlschläger-Krenn, Evelyne; Anderwald, Christian Heinz; Wolf, Peter; Scherer, Thomas; Reiter, Gert; Trattnig, Siegfried; Luger, Anton; Krebs, Michael; Krssak, Martin

    2012-01-01

    Aims/Hypothesis Recent evidence suggests a link between myocardial steatosis and diabetic cardiomyopathy. Insulin, as a lipogenic and growth-promoting hormone, might stimulate intramyocardial lipid (MYCL) deposition and hypertrophy. Therefore, the aim of the present study was to investigate the short-term effects of insulin therapy (IT) on myocardial lipid content and morphology in patients with T2DM. Methods Eighteen patients with T2DM were recruited (age 56±2 years; HbA1c: 10.5±0.4%). In 10 patients with insufficient glucose control under oral medication IT was initiated due to secondary failure of oral glucose lowering therapy (IT-group), while 8 individuals did not require additional insulin substitution (OT-group). In order to assess MYCL and intrahepatic lipid (IHLC) content as well as cardiac geometry and function magnetic resonance spectroscopy (MRS) and imaging (MRI) examinations were performed at baseline (IT and OT) and 10 days after initiation of IT. Follow up measurements took place 181±49 days after IT. Results Interestingly, basal MYCLs were 50% lower in IT- compared to OT-group (0.41±0.12 vs. 0.80±0.11% of water signal; p = 0.034). After 10 days of IT, an acute 80%-rise in MYCL (p = 0.008) was observed, while IHLC did not change. Likewise, myocardial mass (+13%; p = 0.004), wall thickness in end-diastole (+13%; p = 0.030) and concentricity, an index of cardiac remodeling, increased (+28%; p = 0.026). In the long-term MYCL returned to baseline, while IHCL significantly decreased (−31%; p = 0.000). No acute changes in systolic left ventricular function were observed. Conclusions/Interpretation The initiation of IT in patients with T2DM was followed by an acute rise in MYCL concentration and myocardial mass. PMID:23226508

  3. Effects of low-intensity laser therapy over mini-implants success rate in pigs.

    PubMed

    Garcez, Aguinaldo S; Suzuki, Selly Sayuri; Martinez, Elisabeth Ferreira; Iemini, Mylene Garcez; Suzuki, Hideo

    2015-02-01

    The success rate of miniscrews when used as temporary orthodontic anchorage is relatively high, but some factors could affect its clinical success such as inflammation around the miniscrew. Low-intensity laser therapy has been widely used for biostimulation of tissue and wound healing specially for its anti-inflammatory effects. The purpose of this study was to evaluate the effect of low-intensity laser therapy over the miniscrew success rate. Five Landrace's pigs received 50 miniscrews on the buccal side of the mandible and on the palate of the maxilla. All the miniscrews were immediately loaded with 250 gf. The laser group were irradiated with a 780-nm diode laser with 70 mWs for 1 min (dose = 34 J/cm(2)); the contralateral side was used as the control group. The miniscrews were photographed and analyzed clinically every week to determine their stability and presence of local inflammation. After 3 weeks, histological analysis and fluorescent microscopy were performed to compare the laser and the control side. Clinical results showed a success rate of 60% for the control group and 80% for the laser-treated group. The histological analysis and fluorescent microscopy demonstrated that the laser group had less inflammatory cells than the control group and the bone neoformation around the miniscrew was more intense. Low-intensity laser therapy increased the success rate of orthodontic miniscrews, probably due to anti-inflammatory effect and bone stimulation. PMID:23929562

  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

    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.

  5. 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

  6. Initiating therapy or switching to biphasic insulin aspart improves glycaemic control in type 2 diabetes: an Indian experience from the A1chieve study.

    PubMed

    Kumar, A; Sharma, S K; Rajput, R; Unnikrishnan, A G

    2013-01-01

    Biphasic insulin aspart 30 (BIAsp 30) has been used in patients for almost a decade; There is a wealth of knowledge from clinical trials to document its efficacy and safety and suggest that BIAsp 30 is an option for initiation and intensification of insulin therapy in patients with type 2 diabetes mellitus (T2DM). The A1chieve was a non-interventional study that explored the safety and effectiveness of initiating or switching to insulin analogues in routine clinical practice in more than 60,000 patients from 28 different countries. In this manuscript, we discuss the findings from the subgroup of the Indian cohort who were treated with BIAsp 30. In a cohort of 15287 who were on BIAsp 30, 12645 (83%) were insulin naive and 2642 (17%) had been on insulin therapy earlier. Glycaemic parameters were high at baseline. Mean (SD) HbA1c was 9.2% (1.3) in the these and was comparable in the insulin naive and insulin experienced groups. After 24 weeks of therapy with BIAsp 30, there were reductions in HbA1c in both the insulin naive group, [-1.8 (1.3)] and insulin experienced group [-1.6 (1.3)]. Fasting plasma glucose (FPG) and postprandial plasma glucose (PPG) levels were also reduced significantly from baseline [-3.4 (2.7) and -4.8 (3.8) mmol/L, respectively, p < 0.05). Overall, hypoglycaemia decreased from 1.33 events/patient years at baseline to 0.19 events/patient years at 24 weeks. There was also an increase in quality of life score as evaluated by EQ-5D questionnaire. Initiating insulin therapy with or switching to BIAsp 30 in patients with poor glycaemic control leads to an improvement in glycaemic profile with no major hypoglycaemia or clinically significant weight gain. Therapy with BIAsp 30 also improves the quality of life in patients with type 2 diabetes.

  7. Insulin resistance, role of metformin and other noninsulin therapies in pediatric type 1 diabetes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Type 1 diabetes mellitus (T1DM) in youth is a challenging chronic medical condition. Its management should address not only the glycemic control but also insulin resistance and cardiovascular disease risk factors which are increasingly recognized to be present in youth with TID. Current knowledge on...

  8. Cellular therapies based on stem cells and their insulin-producing surrogates: a 2015 reality check.

    PubMed

    Giannoukakis, Nick; Trucco, Massimo

    2015-05-01

    Stem cell technology has recently gained a substantial amount of interest as one method to create a potentially limitless supply of transplantable insulin-producing cells to treat, and possibly cure diabetes mellitus. In this review, we summarize the state-of-the art of stem cell technology and list the potential sources of stem cells that have been shown to be useful as insulin-expressing surrogates. We also discuss the milestones that have been reached and those that remain to be addressed to generate bona fide beta cell-similar, insulin-producing surrogates. The caveats, limitations, and realistic expectations are also considered for current and future technology. In spite of the tremendous technical advances realized in the past decade, especially in the field of reprogramming adult somatic cells to become stem cells, the state-of-the art still relies on lengthy and cumbersome in vitro culture methods that yield cell populations that are not particularly glucose-responsive when transplanted into diabetic hosts. Despite the current impediments toward clinical translation, including the potential for immune rejection, the availability of technology to generate patient-specific reprogrammable stem cells has, and will be critical for, important insights into the genetics, epigenetics, biology, and physiology of insulin-producing cells in normal and pathologic states. This knowledge could accelerate the time to reach the desired breakthrough for safe and efficacious beta cell surrogates.

  9. Insulin-degrading enzyme inhibition, a novel therapy for type 2 diabetes?

    PubMed

    Costes, Safia; Butler, Peter C

    2014-08-01

    The insulin-degrading enzyme (IDE) has been identified as a type 2 diabetes and Alzheimer's disease susceptibility gene, though its physiological function remains unclear. Maianti et al. (2014) now propose that an IDE inhibitor may be a promising therapeutic strategy for type 2 diabetes.

  10. Diamel Therapy in Polycystic Ovary Syndrome Reduces Hyperinsulinaemia, Insulin Resistance, and Hyperandrogenaemia

    PubMed Central

    Hernández-Yero, Arturo; Santana Pérez, Felipe; Ovies Carballo, Gisel; Cabrera-Rode, Eduardo

    2012-01-01

    For to determine the effect of Diamel on the insulin resistance, insulin sensitivity, and sexual hormones results in women with polycystic ovary syndrome (PCOS). A study was carried out on 37 patients with this disorder. A triple-blind clinical trial was designed in which the Diamel food supplement was compared with a placebo. The women with reproductive ages were randomly distributed in two groups, with 18 and 19 women respectively, and they took Diamel or placebo and were followed up during 6 months with clinical and biochemical evaluation. A significant decrease in the HOMA-IR from the initial value at six months was observed in the group with Diamel. The insulin sensitivity improved considerably in this group. The rate of menstrual recovery was higher in the group with Diamel, and two patients from this group obtained pregnancy. The hormone levels shows a significant decrease in testosterone at 3 months in the group with Diamel compared with the control group. The LH also decreases in the same group when comparing the start with 6 months.We concluded that the Diamel decreases insulin resistance and improves sensitivity to this hormone in women with PCOS, with improvement in the levels of LH and testosterone. PMID:22778733

  11. Is thiazolidinediones use a factor in delaying the need for insulin therapy in type 2 patients with diabetes? A population-based cohort study

    PubMed Central

    Carney, Greg A; Bassett, Ken; Wright, James M; Dormuth, Colin R

    2012-01-01

    Objective To understand the independent role of thiazolidinediones (TZDs) in delaying progression to parenteral insulin therapy. Design Population-based retrospective cohort study. Setting British Columbia, Canada. Participants A total of 18 867 type 2 diabetes patients (mean age 58.9) treated with metformin as first-line therapy who then switched or added a TZD or sulphonylurea as a second-line treatment between 1 January 1998 and 31 March 2008. Outcome measures Multivariable Poisson regression models were used to estimate the effect of using TZD compared to sulphonylureas on time to the initiation of insulin treatment (third-line). Results The adjusted rate difference in women aged <60 showed 2.22 fewer insulin initiation events per 100 person-years (PYs) in the TZD group versus the sulphonylurea group (95% CI −3.46 to −0.99). Men in the same age group had 1.50 fewer insulin initiation events per 100 PYs in the TZD group versus the sulphonylurea group (95% CI −2.44 to −0.56). The average time in days to initiation on insulin in the sulphonylurea, rosiglitazone and pioglitazone group was 343, 252 and 339, respectively. The cumulative hazard for starting insulin for sulphonylurea patients at 12, 24, 36 and 48 months was approximately three times higher compared to TZD patients. Conclusions Second-line TZD therapy compared to second-line sulphonylurea therapy was associated with a lower incidence of insulin initiation as third-line treatment in patients with type 2 diabetes, with a mean delay of 90 days. This duration of delay must be weighed against the absence of a proven reduction in morbidity or mortality with TZDs and their known serious cardiovascular harm. PMID:23148347

  12. Effect of low level laser therapy and high intensity laser therapy on endothelial cell proliferation in vitro: preliminary communication

    NASA Astrophysics Data System (ADS)

    Lukowicz, Malgorzata; Szymanska, Justyna; Goralczyk, Krzysztof; Zajac, Andrzej; Rość, Danuta

    2013-01-01

    Background: The main purpose of this study was to analyze the influence of power intensity and wavelength of Low Level Laser Therapy (LLLT) and HILT (High Intensity Laser Therapy) on endothelial cell proliferation. Material and methods: The tests were done on human umbilical vein endothelial cells (HUVEC). Cultures were exposed to laser irradiation of 660 nm and 670 nm at different dosages, power output was 10 - 40 mW as well as 820 nm with power 100 mW and 808 nm with power 1500 mW. Energy density was from 0.28 to 11,43 J/cm2. Cell proliferation of a control and tested culture was evaluated with a colorimetric device to detect live cells. The tests were repeated 8 times. Results: We observed good effects of LLLT on live isolated ECs and no effects in experiments on previous deep-frozen cultures. Also HILT stimulated the proliferation of HUVEC. Conclusion: Endothelial cells play a key role in vascular homeostasis in humans. We observed the stimulatory effect of LLLT and HILT on proliferation of HUVEC. Many factors influence the proliferation of EC, so is it necessary to continue the experiment with different doses, intensity and cell concentration.

  13. Safety and efficacy of insulin glargine 300 u/mL compared with other basal insulin therapies in patients with type 2 diabetes mellitus: a network meta-analysis

    PubMed Central

    Freemantle, Nick; Chou, Engels; Frois, Christian; Zhuo, Daisy; Lehmacher, Walter; Vlajnic, Aleksandra; Wang, Hongwei; Chung, Hsing-wen; Zhang, Quanwu; Wu, Eric; Gerrits, Charles

    2016-01-01

    Objective To compare the efficacy and safety of a concentrated formulation of insulin glargine (Gla-300) with other basal insulin therapies in patients with type 2 diabetes mellitus (T2DM). Design This was a network meta-analysis (NMA) of randomised clinical trials of basal insulin therapy in T2DM identified via a systematic literature review of Cochrane library databases, MEDLINE and MEDLINE In-Process, EMBASE and PsycINFO. Outcome measures Changes in HbA1c (%) and body weight, and rates of nocturnal and documented symptomatic hypoglycaemia were assessed. Results 41 studies were included; 25 studies comprised the main analysis population: patients on basal insulin-supported oral therapy (BOT). Change in glycated haemoglobin (HbA1c) was comparable between Gla-300 and detemir (difference: −0.08; 95% credible interval (CrI): −0.40 to 0.24), neutral protamine Hagedorn (NPH; 0.01; −0.28 to 0.32), degludec (−0.12; −0.42 to 0.20) and premixed insulin (0.26; −0.04 to 0.58). Change in body weight was comparable between Gla-300 and detemir (0.69; −0.31 to 1.71), NPH (−0.76; −1.75 to 0.21) and degludec (−0.63; −1.63 to 0.35), but significantly lower compared with premixed insulin (−1.83; −2.85 to −0.75). Gla-300 was associated with a significantly lower nocturnal hypoglycaemia rate versus NPH (risk ratio: 0.18; 95% CrI: 0.05 to 0.55) and premixed insulin (0.36; 0.14 to 0.94); no significant differences were noted in Gla-300 versus detemir (0.52; 0.19 to 1.36) and degludec (0.66; 0.28 to 1.50). Differences in documented symptomatic hypoglycaemia rates of Gla-300 versus detemir (0.63; 0.19to 2.00), NPH (0.66; 0.27 to 1.49) and degludec (0.55; 0.23 to 1.34) were not significant. Extensive sensitivity analyses supported the robustness of these findings. Conclusions NMA comparisons are useful in the absence of direct randomised controlled data. This NMA suggests that Gla-300 is also associated with a significantly lower risk of nocturnal hypoglycaemia

  14. Concentrated insulins: the new basal insulins

    PubMed Central

    Lamos, Elizabeth M; Younk, Lisa M; Davis, Stephen N

    2016-01-01

    Introduction Insulin therapy plays a critical role in the treatment of type 1 and type 2 diabetes mellitus. However, there is still a need to find basal insulins with 24-hour coverage and reduced risk of hypoglycemia. Additionally, with increasing obesity and insulin resistance, the ability to provide clinically necessary high doses of insulin at low volume is also needed. Areas covered This review highlights the published reports of the pharmacokinetic (PK) and glucodynamic properties of concentrated insulins: Humulin-R U500, insulin degludec U200, and insulin glargine U300, describes the clinical efficacy, risk of hypoglycemic, and metabolic changes observed, and finally, discusses observations about the complexity of introducing a new generation of concentrated insulins to the therapeutic market. Conclusion Humulin-R U500 has a similar onset but longer duration of action compared with U100 regular insulin. Insulin glargine U300 has differential PK/pharmacodynamic effects when compared with insulin glargine U100. In noninferiority studies, glycemic control with degludec U200 and glargine U300 is similar to insulin glargine U100 and nocturnal hypoglycemia is reduced. Concentrated formulations appear to behave as separate molecular entities when compared with earlier U100 insulin analog compounds. In the review of available published data, newer concentrated basal insulins may offer an advantage in terms of reduced intraindividual variability as well as reducing the injection burden in individuals requiring high-dose and large volume insulin therapy. Understanding the PK and pharmacodynamic properties of this new generation of insulins is critical to safe dosing, dispensing, and administration. PMID:27022271

  15. Clinical utility of insulin and insulin analogs

    PubMed Central

    Sanlioglu, Ahter D.; Altunbas, Hasan Ali; Balci, Mustafa Kemal; Griffith, Thomas S.; Sanlioglu, Salih

    2013-01-01

    Diabetes is a pandemic disease characterized by autoimmune, genetic and metabolic abnormalities. While insulin deficiency manifested as hyperglycemia is a common sequel of both Type-1 and Type-2 diabetes (T1DM and T2DM), it does not result from a single genetic defect—rather insulin deficiency results from the functional loss of pancreatic β cells due to multifactorial mechanisms. Since pancreatic β cells of patients with T1DM are destroyed by autoimmune reaction, these patients require daily insulin injections. Insulin resistance followed by β cell dysfunction and β cell loss is the characteristics of T2DM. Therefore, most patients with T2DM will require insulin treatment due to eventual loss of insulin secretion. Despite the evidence of early insulin treatment lowering macrovascular (coronary artery disease, peripheral arterial disease and stroke) and microvascular (diabetic nephropathy, neuropathy and retinopathy) complications of T2DM, controversy exists among physicians on how to initiate and intensify insulin therapy. The slow acting nature of regular human insulin makes its use ineffective in counteracting postprandial hyperglycemia. Instead, recombinant insulin analogs have been generated with a variable degree of specificity and action. Due to the metabolic variability among individuals, optimum blood glucose management is a formidable task to accomplish despite the presence of novel insulin analogs. In this article, we present a recent update on insulin analog structure and function with an overview of the evidence on the various insulin regimens clinically used to treat diabetes. PMID:23584214

  16. Insulin pumps.

    PubMed

    Pickup, J

    2010-02-01

    Insulin pump therapy is now more than 30 years old, and is an established part of the routine care of selected people with type 1 diabetes. Nevertheless, there are still significant areas of concern, particularly how pumps compare with modern injection therapy, whether the increasingly sophisticated pump technologies like onboard calculators and facility for computer download offer any real benefit, and whether we have a consensus on the clinical indications. The following papers offer some insight into these and other current questions.

  17. 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

  18. High-flow oxygen therapy and other inhaled therapies in intensive care units.

    PubMed

    Levy, Sean D; Alladina, Jehan W; Hibbert, Kathryn A; Harris, R Scott; Bajwa, Ednan K; Hess, Dean R

    2016-04-30

    In this Series paper, we review the current evidence for the use of high-flow oxygen therapy, inhaled gases, and aerosols in the care of critically ill patients. The available evidence supports the use of high-flow nasal cannulae for selected patients with acute hypoxaemic respiratory failure. Heliox might prevent intubation or improve gas flow in mechanically ventilated patients with severe asthma. Additionally, it might improve the delivery of aerosolised bronchodilators in obstructive lung disease in general. Inhaled nitric oxide might improve outcomes in a subset of patients with postoperative pulmonary hypertension who had cardiac surgery; however, it has not been shown to provide long-term benefit in patients with acute respiratory distress syndrome (ARDS). Inhaled prostacyclins, similar to inhaled nitric oxide, are not recommended for routine use in patients with ARDS, but can be used to improve oxygenation in patients who are not adequately stabilised with traditional therapies. Aerosolised bronchodilators are useful in mechanically ventilated patients with asthma and chronic obstructive pulmonary disease, but are not recommended for those with ARDS. Use of aerosolised antibiotics for ventilator-associated pneumonia and ventilator-associated tracheobronchitis shows promise, but the delivered dose can be highly variable if proper attention is not paid to the delivery method.

  19. High-flow oxygen therapy and other inhaled therapies in intensive care units.

    PubMed

    Levy, Sean D; Alladina, Jehan W; Hibbert, Kathryn A; Harris, R Scott; Bajwa, Ednan K; Hess, Dean R

    2016-04-30

    In this Series paper, we review the current evidence for the use of high-flow oxygen therapy, inhaled gases, and aerosols in the care of critically ill patients. The available evidence supports the use of high-flow nasal cannulae for selected patients with acute hypoxaemic respiratory failure. Heliox might prevent intubation or improve gas flow in mechanically ventilated patients with severe asthma. Additionally, it might improve the delivery of aerosolised bronchodilators in obstructive lung disease in general. Inhaled nitric oxide might improve outcomes in a subset of patients with postoperative pulmonary hypertension who had cardiac surgery; however, it has not been shown to provide long-term benefit in patients with acute respiratory distress syndrome (ARDS). Inhaled prostacyclins, similar to inhaled nitric oxide, are not recommended for routine use in patients with ARDS, but can be used to improve oxygenation in patients who are not adequately stabilised with traditional therapies. Aerosolised bronchodilators are useful in mechanically ventilated patients with asthma and chronic obstructive pulmonary disease, but are not recommended for those with ARDS. Use of aerosolised antibiotics for ventilator-associated pneumonia and ventilator-associated tracheobronchitis shows promise, but the delivered dose can be highly variable if proper attention is not paid to the delivery method. PMID:27203510

  20. Management of insulin therapy in urban diabetes patients is facilitated by use of an intelligent dosing system.

    PubMed

    Cook, Curtiss B; Mann, Linda J; King, Esther C; New, Katina M; Vaughn, Pamela S; Dames, Faye D; Dunbar, Virginia G; Caudle, Jane M; Tsui, Circe; George, Christopher D; McMichael, John P

    2004-06-01

    The Intelligent Dosing System (IDS, Dimensional Dosing Systems, Inc., Wexford, PA) is a software suite that incorporates patient-specific, dose-response data in a mathematical model, and then calculates the new dose of agent needed to achieve the next desired therapeutic goal. We evaluated use of the IDS for titrating insulin therapy. The IDS was placed on handheld platforms and provided to practitioners to use in adjusting total daily insulin dose. Fasting glucose, random glucose, and hemoglobin A1c were used as markers against which insulin could be adjusted. Values of markers expected at the next follow-up visit, as predicted by the model, were compared with levels actually observed. For 264 patients, 334 paired visits were analyzed. Average age was 54 years, diabetes' duration was 10 years, and body mass index was 33.2 kg/m(2); 57% were female, 88% were African American, and 92% had type 2 diabetes. The correlation between IDS suggested and actual prescribed total daily dose was high (r = 0.99), suggesting good acceptability of the IDS by practitioners. Significant decreases in fasting glucose, random glucose, and hemoglobin A1c levels were seen (all P < 0.0001). No significant difference between average expected and observed follow-up fasting glucose values was found (145 vs. 149 mg/dL, P = 0.42), and correlation was high (r = 0.79). Mean observed random glucose value at follow-up was comparable to the IDS predicted level (167 vs. 168 mg/dL, P = 0.97), and correlation was high (r = 0.73). Observed follow-up hemoglobin A1c was higher than the value expected (7.9% vs. 7.4%, P < 0.0055), but correlation was good (r = 0.70). These analyses suggest the IDS is a useful adjunct for decisions regarding insulin therapy even when using a variety of markers of glucose control, and can be used by practitioners to assist in attainment of glycemic goals.

  1. Insulin Therapy does not Interfere with Venous Endothelial Function Evaluation in Patients with Type 2 Diabetes Mellitus

    PubMed Central

    da Silva, Antônio Marcos Vargas; de Moraes Penno, Luciana; Bertoluci, Marcello Casaccia; Irigoyen, Maria Cláudia; Schaan, Beatriz D'Agord

    2010-01-01

    INTRODUCTION: Endothelium-dependent dilation is improved in insulin-treated diabetic patients, but this effect is probably due to improved glycemic control. The objective of the present study was to compare endothelium-dependent dilation in patients with well-controlled type 2 diabetes who are or are not using insulin as part of their therapy. METHODS: We studied 27 patients with type 2 diabetes (11 women, 60.3 years ± 6 years, with HbA1c < 7% and no nephropathy), including 16 patients treated with anti-diabetic agents (No-Ins, 8 women) and 11 patients treated with insulin alone or in combination with anti-diabetic agents (Ins, 3 women). Endothelial function was evaluated by the dorsal hand vein technique, which measures changes in vein diameter in response to phenylephrine, acetylcholine (endothelium-dependent vasodilation) and sodium nitroprusside (endothelium-independent vasodilation). RESULTS: Age, systolic blood pressure (No-Ins: 129.4 mmHg ± 11.8 mmHg, Ins: 134.8 mmHg ± 12.0 mmHg; P =  0.257), HbA1c, lipids and urinary albumin excretion rate [No-Ins: 9 mg/24 h (0-14.1 mg/24 h) vs. Ins: 10.6 mg/24 h (7.5-14.4 mg/24 h), P = 0.398] were similar between groups. There was no difference between endothelium-dependent vasodilation of the No-Ins group (59.3% ± 26.5%) vs. the Ins group (54.0% ± 16.3%; P = 0.526). Endothelium-independent vasodilation was also similar between the No-Ins (113.7% ± 35.3%) and Ins groups (111.9% ± 28.5%; P = 0.888). CONCLUSIONS: Subcutaneous insulin therapy does not interfere with venous endothelial function in type 2 diabetes when glycemic and blood pressure control are stable. PMID:21243287

  2. The radiation techniques of tomotherapy & intensity-modulated radiation therapy applied to lung cancer

    PubMed Central

    Zhu, Zhengfei

    2015-01-01

    Radiotherapy (RT) plays an important role in the management of lung cancer. Development of radiation techniques is a possible way to improve the effect of RT by reducing toxicities through better sparing the surrounding normal tissues. This article will review the application of two forms of intensity-modulated radiation therapy (IMRT), fixed-field IMRT and helical tomotherapy (HT) in lung cancer, including dosimetric and clinical studies. The advantages and potential disadvantages of these two techniques are also discussed. PMID:26207214

  3. 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. PMID:24932151

  4. Insulin-like growth factor receptor type I as a target for cancer therapy.

    PubMed

    Corvaia, Nathalie; Beck, Alain; Caussanel, Véronique; Goetsch, Liliane

    2013-01-01

    After more than 20 years of extensive work, insulin-like growth factor receptor 1 (IGF-IR) is still an attractive target for drug development. Due to its close homology to insulin receptor, IGF-IR is of interest for antibody design while antibody great specificity allows to discriminate between the two receptors. Major efforts from a large number of pharmaceutical companies are invested to evaluate the efficacy of such molecules in human without so far an obvious success. Discovery of biomarkers associated with efficacy and patient selection is one of the main challenges that we will have to deal with in order to target the appropriate patient population that will most benefit anti-IGF-IR monoclonal antibody (Mab) and combined treatments. This review will provide an overview of the current knowledge on IGF-IR axis for development of novel therapeutics in Oncology.

  5. Insulin therapy for the treatment of type 1 diabetes during pregnancy

    PubMed Central

    Kinsley, Brendan T.

    2014-01-01

    Pregnancies affected by type 1 diabetes (T1D) carry a major risk for poor fetal, neonatal and maternal outcomes. Achieving normoglycemia while minimizing the risk of hypoglycemia is a major goal in the management of T1D as this can greatly reduce the risk of complications. However, maintaining optimal glucose levels is challenging because insulin requirements are not uniform throughout the course of the pregnancy. Over the past decade, there has been significant improvement in the methods for glucose monitoring and insulin administration, accompanied by an increase in the number of treatment options available to pregnant patients with T1D. Through study of the scientific literature and accumulated evidence, we review advances in the management of T1D in pregnancy and offer advice on how to achieve optimal care for the patient. PMID:24224883

  6. Cardiac arrest: a late complication of glucose-insulin-potassium (GIK) therapy.

    PubMed

    Simes, D

    2001-06-01

    Rebound hyperkalaemia 4 hours after discontinuation of a glucose-insulin-potassium infusion inhibited an already compromised conduction system leading to ventricular standstill in a 41 year old man after re-do aortic valve surgery. Resuscitation was successful and allowed him to return from Australia to his home on Christmas Island. Glucose-insulin-potassium (GIK) infusions to reduce myocardial hypo-/re-perfusion injury after myocardial infarction, during coronary artery surgery and cardiopulmonary bypass are becoming more popular. There may also be a role for GIK in the treatment of refractory dysrhythmias and for myocardial protection in the brain-dead patient. However, these infusions are not without hazard and this report of rebound hyperkalaemia and cardiac arrest is unlikely to remain isolated.

  7. Hepatitis C virus induced insulin resistance impairs response to anti viral therapy

    PubMed Central

    El-Zayadi, Abdel-Rahman; Anis, Mahmoud

    2012-01-01

    Hepatitis C virus (HCV) infection is an important risk factor for insulin resistance (IR). The latter is the pathogenic foundation underlying metabolic syndrome, steatosis and cirrhosis, and possibly hepatocellular carcinoma (HCC). The interplay between genetic and environmental risk factors ultimately leads to the development of IR. Obesity is considered a major risk factor, with dysregulation of levels of secreted adipokines from distended adipose tissue playing a major role in IR. HCV-induced IR may be due to the HCV core protein inducing proteasomal degradation of insulin receptor substrates 1 and 2, blocking intracellular insulin signaling. The latter is mediated by increased levels of both tumour necrosis factor-α (TNF-α) and suppressor of cytokine signaling 3 (SOC-3). IR, through different mechanisms, plays a role in the development of steatosis and its progression to steatohepatitis, cirrhosis and even HCC. In addition, IR has a role in impairing TNF signaling cascade, which in turn blocks STAT-1 translocation and interferon stimulated genes production avoiding the antiviral effect of interferon. PMID:22294824

  8. 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

  9. 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.

  10. Reported Benefits of Insulin Therapy for Better Glycemic Control in Type 2 Diabetic Patients—Is This Applicable in Saudi Patients?

    PubMed Central

    AlSaggaf, Wafaa; Asiri, Mohammed; Ajlan, Balgees; Afif, Alaa Bin; Khalil, Roaa; Salman, Anas Bin; Alghamdi, Ahmed; Bashawieh, Osama; Alamoudi, Atheer; Aljahdali, Abeer; Aljahdali, Nouf; Patwa, Hussam; Bakhaidar, Mohammed; Bahijri, Suhad M.; Ahmed, Maimoona; Al-Shali, Khalid; Bokhari, Samia; Alhozali, Amani; Borai, Anwar; Ajabnoor, Ghada; Tuomilehto, Jaakko

    2016-01-01

    AIM To compare the effect of different treatment regimens (oral hypoglycemic agents [OHGs], insulin therapy, and combination of both) on glycemic control and other cardiometabolic risk factors in type 2 diabetes mellitus (T2DM) patients in Saudi. SUBJECTS AND METHODS Patients with T2DM, but no serious diabetic complications, were randomly recruited from the diabetes clinics at two large hospitals in Jeddah, Saudi Arabia, during June 2013 to July 2014. Only those without change in treatment modality for the last 18 months were included. Blood pressure and anthropometric measurements were measured. Treatment plan was recorded from the patients’ files. Fasting blood sample was obtained to measure glucose, HbA1c, and lipid profile. RESULTS A total of 197 patients were recruited; 41.1% were men and 58.9% were women. The mean (±SD) age was 58.5 ± 10.5 years. Most patients (60.7%) were on OHGs, 11.5% on insulin therapy, and 27.7% were using a combination of insulin and OHGs. The mean HbA1c was lower in patients using OHGs only, compared with means in those using insulin, or combined therapy in patients with disease duration of ≤10 years (P = 0.001) and also in those with a longer duration of the disease (P < 0.001). A lower mean diastolic and systolic blood pressure was found among patients on insulin alone (P < 0.01). No significant differences were found in lipid profiles among the groups. CONCLUSION Insulin therapy, without adequate diabetes education, fails to control hyperglycemia adequately in Saudi T2DM patients. There is a challenge to find out reasons for poor control and the ways as to how to improve glycemic control in T2DM. PMID:27330334

  11. Comparative evaluation of the therapeutic effect of metformin monotherapy with metformin and acupuncture combined therapy on weight loss and insulin sensitivity in diabetic patients

    PubMed Central

    Firouzjaei, A; Li, G-C; Wang, N; Liu, W-X; Zhu, B-M

    2016-01-01

    Objective: Obesity induces insulin resistance (IR), the key etiologic defect of type 2 diabetes mellitus (T2DM). Therefore, an incidence of obesity-induced diabetes is expected to decrease if obesity is controlled. Although Metformin is currently one of the main treatment options for T2DM in obese patients, resulting in an average of 5% weight loss, adequate weight control in all patients cannot be achieved with Metformin alone. Thus, additional therapies with a weight loss effect, such as acupuncture, may improve the effectiveness of Metformin. Subjective: We designed this randomized clinical trial (RCT) to compare the effects of Metformin monotherapy with that of Metformin and acupuncture combined therapy on weight loss and insulin sensitivity among overweight/obese T2DM patients, to understand whether acupuncture plus Metformin is a better approach than Metformin only on treating diabetes. To understand whether acupuncture can be an insulin sensitizer and, if so, its therapeutic mechanism. Results: Our results show that Metformin and acupuncture combined therapy significantly improves body weight, body mass index (BMI), fasting blood sugar (FBS), fasting insulin (FINS), homeostasis model assessment (HOMA) index, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), leptin, adiponectin, glucagon-like peptide-1 (GLP-1), resistin, serotonin, free fatty acids (FFAs), triglyceride (TG), low-density lipoprotein cholesterol (LDLc), high-density lipoprotein cholesterol (HDLc) and ceramides. Conclusions: Consequently, Metformin and acupuncture combined therapy is more effective than Metformin only, proving that acupuncture is an insulin sensitizer and is able to improve insulin sensitivity possibly by reducing body weight and inflammation, while improving lipid metabolism and adipokines. As a result, electro-acupuncture (EA) might be useful in controlling the ongoing epidemics in obesity and T2DM. PMID:27136447

  12. [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.

  13. Feasibility of a unified approach to intensity-modulated radiation therapy and volume-modulated arc therapy optimization and delivery

    SciTech Connect

    Hoover, Douglas A. Chen, Jeff Z.; MacFarlane, Michael; Wong, Eugene; Battista, Jerry J.

    2015-02-15

    Purpose: To study the feasibility of unified intensity-modulated arc therapy (UIMAT) which combines intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT) optimization and delivery to produce superior radiation treatment plans, both in terms of dose distribution and efficiency of beam delivery when compared with either VMAT or IMRT alone. Methods: An inverse planning algorithm for UIMAT was prototyped within the PINNACLE treatment planning system (Philips Healthcare). The IMRT and VMAT deliveries are unified within the same arc, with IMRT being delivered at specific gantry angles within the arc. Optimized gantry angles for the IMRT and VMAT phases are assigned automatically by the inverse optimization algorithm. Optimization of the IMRT and VMAT phases is done simultaneously using a direct aperture optimization algorithm. Five treatment plans each for prostate, head and neck, and lung were generated using a unified optimization technique and compared with clinical IMRT or VMAT plans. Delivery verification was performed with an ArcCheck phantom (Sun Nuclear) on a Varian TrueBeam linear accelerator (Varian Medical Systems). Results: In this prototype implementation, the UIMAT plans offered the same target dose coverage while reducing mean doses to organs at risk by 8.4% for head-and-neck cases, 5.7% for lung cases, and 3.5% for prostate cases, compared with the VMAT or IMRT plans. In addition, UIMAT can be delivered with similar efficiency as VMAT. Conclusions: In this proof-of-concept work, a novel radiation therapy optimization and delivery technique that interlaces VMAT or IMRT delivery within the same arc has been demonstrated. Initial results show that unified VMAT/IMRT has the potential to be superior to either standard IMRT or VMAT.

  14. 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

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

    PubMed

    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

  16. 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.

  17. Modeling secondary cancer risk following paediatric radiotherapy: a comparison of intensity modulated proton therapy and photon therapy

    NASA Astrophysics Data System (ADS)

    Shin, Naomi

    Proton radiotherapy is known to reduce the radiation dose delivered to normal healthy tissue compared to photon techniques. The increase in normal tissue sparing could result in fewer acute and late effects from radiation therapy. In this work proton therapy plans were created for patients previously treated using photon therapy. Intensity modulated proton therapy (IMPT) plans were planned using inverse planning in VarianRTM's Eclipse(TM) treatment planning system with a scanning proton beam model to the same relative biological effectiveness (RBE)-weighted prescription dose as the photon plan. Proton and photon plans were compared for target dose conformity and homogeneity, body volumes receiving 2 Gy and 5 Gy, integral dose, dose to normal tissues and second cancer risk. Secondary cancer risk was determined using two methods. The relative risk of secondary cancer was found using the method described by Nguyen et al. 1 by applying a linear relationship between integral dose and relative risk of secondary cancer. The second approach used Schneider et al. 's organ equivalent dose concept to describe the dose in the body and then calculate the excess absolute risk and cumulative risk for solid cancers in the body. IMPT and photon plans had similar target conformity and homogeneity. However IMPT plans had reduced integral dose and volumes of the body receiving low dose. Overall the risk of radiation induced secondary cancer was lower for IMPT plans compared to the corresponding photon plans with a reduction of ~36% using the integral dose model and ˜50% using the organ equivalent dose model. *Please refer to dissertation for footnotes.

  18. Brief intensive CBT for pediatric OCD with E-therapy maintenance.

    PubMed

    Farrell, Lara J; Oar, Ella L; Waters, Allison M; McConnell, Harry; Tiralongo, Evelin; Garbharran, Vinay; Ollendick, Thomas

    2016-08-01

    Cognitive behaviour therapy (CBT), incorporating exposure and response prevention (ERP), has received strong empirical support for the treatment of paediatric OCD, and moreover, is considered the first line treatment of choice (Geller & March, 2012). However, despite the availability of effective treatments for this chronic and debilitating disorder, only a small proportion of youth receive these evidence-based approaches. The present study aimed to examine the effectiveness of an intensive ERP-based treatment for youth OCD, using a multiple baseline controlled design. Children and youth (N=10; aged 11-16 years) with a primary diagnosis of OCD were randomly assigned to a 1- or 2-week baseline monitoring condition followed by the intervention. The efficacy of the intensive treatment, involving 1 session psychoeducation, 2-sessions ERP plus e-therapy maintenance was examined across parent- child- and clinician-rated measures at post-treatment and 6-month follow-up. Overall, there were significant reductions across time on almost all measures (except self-report anxiety), and moreover, the majority of the sample (80%) were considered reliably improved, and meeting clinically significant change. At post-treatment, 60% were in remission of symptoms, and at 6-month follow-up this increased to 70%. These findings provide strong support for intensive, time-limited approaches to ERP-based CBT for children and youth with OCD.

  19. Short-Term, Low-Dose GH Therapy Improves Insulin Sensitivity Without Modifying Cortisol Metabolism and Ectopic Fat Accumulation in Adults With GH Deficiency

    PubMed Central

    Roberts, Charles T.; Frystyk, Jan; Rooney, William D.; Pollaro, James R.; Klopfenstein, Bethany J.; Purnell, Jonathan Q.

    2014-01-01

    Context: Low-dose GH (LGH) therapy has been reported to improve insulin sensitivity in GH-deficient adults; however, the mechanism is unclear. Hypothesis: Effects of LGH therapy on insulin sensitivity are mediated through changes in cortisol metabolism and ectopic fat accumulation. Design and Setting: This was a double-blind, placebo-controlled, parallel, 3-month study. Participants and Intervention: Seventeen GH-deficient adults were randomized to receive either daily LGH or placebo injections. Fasting blood samples were collected at baseline, and months 1 and 3, whereas hyperinsulinemic-euglycemic clamps, magnetic resonance spectroscopy scans, 24-hour cortisol production rates (CPRs), and sc abdominal fat biopsies were performed at baseline and month 3. Main Outcome Measures: Clamp glucose infusion rate, intramyocellular, extramyocellular, and intrahepatic lipid content, 24-hour CPRs, adipocyte size, and adipocyte 11β-hydroxysteroid dehydrogenase activity in adults with GH deficiency were evaluated. Results: At month 1, LGH did not alter fasting levels of glucose, insulin, C-peptide, free fatty acid, adiponectin, total IGF-1, IGF-1 bioactivity, IGF-2, IGF binding protein (IGFBP)-2, or IGF-1 to IGFBP-3 molar ratio. At month 3, LGH increased clamp glucose infusion rates (P < .01) and IGF-1 to IGFBP-3 molar ratio (P < .05), but fasting glucose, insulin, C-peptide, free fatty acid, adiponectin, IGF-1 bioactivity, IGF-2, IGFBP-2, 24-hour CPRs, adipocyte size, adipocyte 11β-hydroxysteroid dehydrogenase activity, intrahepatic lipid, extramyocellular, or intramyocellular were unchanged. In the placebo group, all within-group parameters from months 1 and 3 compared with baseline were unchanged. Conclusions: Short-term LGH therapy improves insulin sensitivity without inducing basal lipolysis and had no effect on cortisol metabolism and ectopic fat accumulation in GH-deficient adults. This may reflect an LGH-induced increase in IGF-1 to IGFBP-3 molar ratio exerting

  20. High-intensity focused ultrasound (HIFU) array system for image-guided ablative therapy (IGAT)

    NASA Astrophysics Data System (ADS)

    Kaczkowski, Peter J.; Keilman, George W.; Cunitz, Bryan W.; Martin, Roy W.; Vaezy, Shahram; Crum, Lawrence A.

    2003-06-01

    Recent interest in using High Intensity Focused Ultrasound (HIFU) for surgical applications such as hemostasis and tissue necrosis has stimulated the development of image-guided systems for non-invasive HIFU therapy. Seeking an all-ultrasound therapeutic modality, we have developed a clinical HIFU system comprising an integrated applicator that permits precisely registered HIFU therapy delivery and high quality ultrasound imaging using two separate arrays, a multi-channel signal generator and RF amplifier system, and a software program that provides the clinician with a graphical overlay of the ultrasound image and therapeutic protocol controls. Electronic phasing of a 32 element 2 MHz HIFU annular array allows adjusting the focus within the range of about 4 to 12 cm from the face. A central opening in the HIFU transducer permits mounting a commercial medical imaging scanhead (ATL P7-4) that is held in place within a special housing. This mechanical fixture ensures precise coaxial registration between the HIFU transducer and the image plane of the imaging probe. Recent enhancements include development of an acoustic lens using numerical simulations for use with a 5-element array. Our image-guided therapy system is very flexible and enables exploration of a variety of new HIFU therapy delivery and monitoring approaches in the search for safe, effective, and efficient treatment protocols.

  1. High-intensity focused ultrasound: principles, therapy guidance, simulations and applications.

    PubMed

    Jenne, Jürgen W; Preusser, Tobias; Günther, Matthias

    2012-12-01

    In the past two decades, high-intensity focused ultrasound (HIFU) in combination with diagnostic ultrasound (USgFUS) or magnetic resonance imaging (MRgFUS) opened new ways of therapeutic access to a multitude of pathologic conditions. The therapeutic potential of HIFU lies in the fact that it enables the localized deposition of high-energy doses deep within the human body without harming the surrounding tissue. The addition of diagnostic ultrasound or in particular MRI with HIFU allows for planning, control and direct monitoring of the treatment process. The clinical and preclinical applications of HIFU range from the thermal treatment of benign and malign lesions, targeted drug delivery, to the treatment of thrombi (sonothrombolysis). Especially the therapy of prostate cancer under US-guidance and the ablation of benign uterine fibroids under MRI monitoring are now therapy options available to a larger number of patients. The main challenges for an abdominal application of HIFU are posed by partial or full occlusion of the target site by bones or air filled structures (e.g. colon), as well as organ motion. In non-trivial cases, the implementation of computer based modeling, simulation and optimization is desirable. This article describes the principles of HIFU, ultrasound and MRI therapy guidance, therapy planning and simulation, and gives an overview of the current and potential future applications.

  2. FusionArc optimization: A hybrid volumetric modulated arc therapy (VMAT) and intensity modulated radiation therapy (IMRT) planning strategy

    SciTech Connect

    Matuszak, Martha M.; McShan, Daniel L.; Ten Haken, Randall K.; Steers, Jennifer M.; Long, Troy; Edwin Romeijn, H.; Fraass, Benedick A.

    2013-07-15

    Purpose: To introduce a hybrid volumetric modulated arc therapy/intensity modulated radiation therapy (VMAT/IMRT) optimization strategy called FusionArc that combines the delivery efficiency of single-arc VMAT with the potentially desirable intensity modulation possible with IMRT.Methods: A beamlet-based inverse planning system was enhanced to combine the advantages of VMAT and IMRT into one comprehensive technique. In the hybrid strategy, baseline single-arc VMAT plans are optimized and then the current cost function gradients with respect to the beamlets are used to define a metric for predicting which beam angles would benefit from further intensity modulation. Beams with the highest metric values (called the gradient factor) are converted from VMAT apertures to IMRT fluence, and the optimization proceeds with the mixed variable set until convergence or until additional beams are selected for conversion. One phantom and two clinical cases were used to validate the gradient factor and characterize the FusionArc strategy. Comparisons were made between standard IMRT, single-arc VMAT, and FusionArc plans with one to five IMRT/hybrid beams.Results: The gradient factor was found to be highly predictive of the VMAT angles that would benefit plan quality the most from beam modulation. Over the three cases studied, a FusionArc plan with three converted beams achieved superior dosimetric quality with reductions in final cost ranging from 26.4% to 48.1% compared to single-arc VMAT. Additionally, the three beam FusionArc plans required 22.4%-43.7% fewer MU/Gy than a seven beam IMRT plan. While the FusionArc plans with five converted beams offer larger reductions in final cost-32.9%-55.2% compared to single-arc VMAT-the decrease in MU/Gy compared to IMRT was noticeably smaller at 12.2%-18.5%, when compared to IMRT.Conclusions: A hybrid VMAT/IMRT strategy was implemented to find a high quality compromise between gantry-angle and intensity-based degrees of freedom. This

  3. FusionArc optimization: A hybrid volumetric modulated arc therapy (VMAT) and intensity modulated radiation therapy (IMRT) planning strategy

    PubMed Central

    Matuszak, Martha M.; Steers, Jennifer M.; Long, Troy; McShan, Daniel L.; Fraass, Benedick A.; Edwin Romeijn, H.; Ten Haken, Randall K.

    2013-01-01

    Purpose: To introduce a hybrid volumetric modulated arc therapy/intensity modulated radiation therapy (VMAT/IMRT) optimization strategy called FusionArc that combines the delivery efficiency of single-arc VMAT with the potentially desirable intensity modulation possible with IMRT. Methods: A beamlet-based inverse planning system was enhanced to combine the advantages of VMAT and IMRT into one comprehensive technique. In the hybrid strategy, baseline single-arc VMAT plans are optimized and then the current cost function gradients with respect to the beamlets are used to define a metric for predicting which beam angles would benefit from further intensity modulation. Beams with the highest metric values (called the gradient factor) are converted from VMAT apertures to IMRT fluence, and the optimization proceeds with the mixed variable set until convergence or until additional beams are selected for conversion. One phantom and two clinical cases were used to validate the gradient factor and characterize the FusionArc strategy. Comparisons were made between standard IMRT, single-arc VMAT, and FusionArc plans with one to five IMRT/hybrid beams. Results: The gradient factor was found to be highly predictive of the VMAT angles that would benefit plan quality the most from beam modulation. Over the three cases studied, a FusionArc plan with three converted beams achieved superior dosimetric quality with reductions in final cost ranging from 26.4% to 48.1% compared to single-arc VMAT. Additionally, the three beam FusionArc plans required 22.4%–43.7% fewer MU/Gy than a seven beam IMRT plan. While the FusionArc plans with five converted beams offer larger reductions in final cost—32.9%–55.2% compared to single-arc VMAT—the decrease in MU/Gy compared to IMRT was noticeably smaller at 12.2%–18.5%, when compared to IMRT. Conclusions: A hybrid VMAT/IMRT strategy was implemented to find a high quality compromise between gantry-angle and intensity-based degrees of freedom

  4. A computational implementation and comparison of several intensity modulated proton therapy treatment planning algorithms

    SciTech Connect

    Li, Haisen S.; Romeijn, H. Edwin; Fox, Christopher; Palta, Jatinder R.; Dempsey, James F.

    2008-03-15

    The authors present a comparative study of intensity modulated proton therapy (IMPT) treatment planning employing algorithms of three-dimensional (3D) modulation, and 2.5-dimensional (2.5D) modulation, and intensity modulated distal edge tracking (DET) [A. Lomax, Phys. Med. Biol. 44, 185-205 (1999)] applied to the treatment of head-and-neck cancer radiotherapy. These three approaches were also compared with 6 MV photon intensity modulated radiation therapy (IMRT). All algorithms were implemented in the University of Florida Optimized Radiation Therapy system using a finite sized pencil beam dose model and a convex fluence map optimization model. The 3D IMPT and the DET algorithms showed considerable advantages over the photon IMRT in terms of dose conformity and sparing of organs at risk when the beam number was not constrained. The 2.5D algorithm did not show an advantage over the photon IMRT except in the dose reduction to the distant healthy tissues, which is inherent in proton beam delivery. The influences of proton beam number and pencil beam size on the IMPT plan quality were also studied. Out of 24 cases studied, three cases could be adequately planned with one beam and 12 cases could be adequately planned with two beams, but the dose uniformity was often marginally acceptable. Adding one or two more beams in each case dramatically improved the dose uniformity. The finite pencil beam size had more influence on the plan quality of the 2.5D and DET algorithms than that of the 3D IMPT. To obtain a satisfactory plan quality, a 0.5 cm pencil beam size was required for the 3D IMPT and a 0.3 cm size was required for the 2.5D and the DET algorithms. Delivery of the IMPT plans produced in this study would require a proton beam spot scanning technique that has yet to be developed clinically.

  5. 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

  6. Synthetic single crystal diamond dosimeters for Intensity Modulated Radiation Therapy applications

    NASA Astrophysics Data System (ADS)

    Almaviva, S.; Ciancaglioni, I.; Consorti, R.; De Notaristefani, F.; Manfredotti, C.; Marinelli, Marco; Milani, E.; Petrucci, A.; Prestopino, G.; Verona, C.; Verona-Rinati, G.

    2009-09-01

    A synthetic single crystal diamond Schottky diode, in a p-type/intrinsic/metal structure, deposited by Chemical Vapour Deposition (CVD) and operating in photovoltaic regime, with no external bias voltage applied, was tested as a dosimeter for Intensity Modulated Radiation Therapy (IMRT) applications. The device response was compared with dose measurements from two commercial ionization chambers and a 2D diode array in an IMRT prostate cancer treatment plan. The obtained results indicate that CVD synthetic single crystal diamond-based dosimeters can successfully be used for highly conformed radiotherapy and IMRT dosimetry, due to their small size and high sensitivity per unit volume.

  7. Intensive cognitive-behaviour group therapy for diagnostically heterogeneous groups of patients with psychiatric disorder.

    PubMed

    Manning, J J; Hooke, G R; Tannenbaum, D A; Blythe, T H; Clarke, T M

    1994-12-01

    This uncontrolled study evaluates the efficacy of a combined treatment of medications (for the majority of patients) and a closed group, intensive (two-week) cognitive-behaviour therapy programme for heterogeneous groups of psychiatric patients. Five hundred and thirty-one patients at a private psychiatric clinic were included in the study. Self-report measures of depression, anxiety, self-esteem and "locus of control" were administered before and after treatment and at intervals up to one year later. Statistically and clinically significant improvements were found in all measures and these improvements were maintained up to one year. The results provide support for the efficacy of the treatment.

  8. Successful nonsurgical management of post-orthodontic gingival enlargement with intensive cause-related periodontal therapy.

    PubMed

    Kwon, TaeHyun; Kim, David M; Levin, Liran

    2015-03-01

    Successful nonsurgical management of severe postorthodontic gingival enlargement and erythema in a 24-year-old male is presented. The patient received an intensive cause-related periodontal therapy, consisting of oral hygiene instruction, scaling and root planing, and weekly recall visits. At week five, complete resolution of the lesions was achieved. By targeting the primary etiologic factor, i.e., plaque, periodontal health was restored without needing surgical intervention. Reducing the bacterial load will give the biologic natural healing capacity of the body the opportunity to stabilize the periodontal condition and, thus, should be considered as the first line of intervention before a surgical approach is taken. PMID:25928969

  9. Intensive therapy induces contralateral white matter changes in chronic stroke patients with Broca's aphasia.

    PubMed

    Wan, Catherine Y; Zheng, Xin; Marchina, Sarah; Norton, Andrea; Schlaug, Gottfried

    2014-09-01

    Using a pre-post design, eleven chronic stroke patients with large left hemisphere lesions and nonfluent aphasia underwent diffusion tensor imaging and language testing before and after receiving 15 weeks of an intensive intonation-based speech therapy. This treated patient group was compared to an untreated patient group (n=9) scanned twice over a similar time period. Our results showed that the treated group, but not the untreated group, had reductions in fractional anisotropy in the white matter underlying the right inferior frontal gyrus (IFG, pars opercularis and pars triangularis), the right posterior superior temporal gyrus, and the right posterior cingulum. Furthermore, we found that greater improvements in speech production were associated with greater reductions in FA in the right IFG (pars opercularis). Thus, our findings showed that an intensive rehabilitation program for patients with nonfluent aphasia led to structural changes in the right hemisphere, which correlated with improvements in speech production. PMID:25041868

  10. 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.

  11. Targeting the insulin-like growth factor network in cancer therapy.

    PubMed

    Heidegger, Isabel; Pircher, Andreas; Klocker, Helmut; Massoner, Petra

    2011-04-15

    During the last decades, changes in the insulin-like growth factor (IGF) signaling have been related to the pathogenesis of cancer. Therefore, IGFs became highly attractive therapeutic cancer targets. Several drugs including monoclonal antibodies (mAB), small molecule tyrosine kinase inhibitors (RTKIs), anti-sense oligonucleotids (ASOs) and IGF-binding proteins (IGFBPs) targeting the IGF axis were developed. With over 60 ongoing clinical trials, the IGF1 receptor (IGF1R) is currently one of the most studied molecular targets in the field of oncology. In this review, we provide an overview on the IGF axis, its signaling pathways and its significance in neoplasia. We critically review the preclinical and clinical studies investigating the role of IGF1R as a cancer target and discuss preliminary results and possible limitations.

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

    PubMed Central

    Sale, Charlotte; Moloney, Phillip; Mathlum, Maitham

    2013-01-01

    Introduction 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. Methods 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. Results 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. Conclusion 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. PMID:26229623

  13. 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.

  14. Effects of insulin therapy on porosity, non-enzymatic glycation and mechanical competence in the bone of rats with type 2 diabetes mellitus.

    PubMed

    Campbell, G M; Tiwari, S; Picke, A-K; Hofbauer, C; Rauner, M; Morlock, M M; Hofbauer, L C; Glüer, C-C

    2016-10-01

    Type 2 diabetes mellitus increases skeletal fragility; however, the contributing mechanisms and optimal treatment strategies remain unclear. We studied the effects of diabetes and insulin therapy on non-enzymatic glycation (NEG), cortical porosity (Ct.Po) and biomechanics of the bone tissue in Zucker Diabetic Fatty (ZDF) rats. Eleven-week old ZDF diabetic and non-diabetic rats were given insulin to achieve glycaemic control or vehicle seven days per week over twelve weeks (insulin dose adapted individually 0.5 international units (IU) at week 1 to 13.0IU at week 12). The right femora were excised, micro-CT scanned, and tested in 3-point bending to measure biomechanics. NEG of the midshaft was determined from bulk fluorescence. Diabetes led to increased NEG (+50.1%, p=0.001) and Ct.Po (+22.9%, p=0.004), as well as to reduced mechanical competence (max. stress: -14.2%, p=0.041, toughness: -29.7%, p=0.016) in the bone tissue. NEG and Ct.Po both correlated positively to serum glucose (NEG: R(2)=0.41, p<0.001, Ct.Po: R(2)=0.34, p=0.003) and HbA1c (NEG: R(2)=0.42, p<0.001, Ct.Po: R(2)=0.28, p=0.008) levels, while NEG correlated negatively with bone biomechanics (elastic modulus: R(2)=0.21, p=0.023, yield stress: R(2)=0.17, p=0.047). Twelve weeks of insulin therapy had no significant effect on NEG or Ct.Po, and was unable to improve the mechanical competence of the bone tissue. A reduction of mechanical competence was observed in the bone tissue of the diabetic rats, which was explained in part by increased collagen NEG. Twelve weeks of insulin therapy did not alter NEG, Ct.Po or bone biomechanics. However, significant correlations between NEG and serum glucose and HbA1c were observed, both of which were reduced with insulin therapy. This suggests that a longer duration of insulin therapy may be required to reduce the NEG of the bone collagen and restore the mechanical competence of diabetic bone.

  15. 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.

  16. 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…

  17. Human Cortical Neural Stem Cells Expressing Insulin-Like Growth Factor-I: A Novel Cellular Therapy for Alzheimer's Disease.

    PubMed

    McGinley, Lisa M; Sims, Erika; Lunn, J Simon; Kashlan, Osama N; Chen, Kevin S; Bruno, Elizabeth S; Pacut, Crystal M; Hazel, Tom; Johe, Karl; Sakowski, Stacey A; Feldman, Eva L

    2016-03-01

    Alzheimer's disease (AD) is the most prevalent age-related neurodegenerative disorder and a leading cause of dementia. Current treatment fails to modify underlying disease pathologies and very little progress has been made to develop effective drug treatments. Cellular therapies impact disease by multiple mechanisms, providing increased efficacy compared with traditional single-target approaches. In amyotrophic lateral sclerosis, we have shown that transplanted spinal neural stem cells (NSCs) integrate into the spinal cord, form synapses with the host, improve inflammation, and reduce disease-associated pathologies. Our current goal is to develop a similar "best in class" cellular therapy for AD. Here, we characterize a novel human cortex-derived NSC line modified to express insulin-like growth factor-I (IGF-I), HK532-IGF-I. Because IGF-I promotes neurogenesis and synaptogenesis in vivo, this enhanced NSC line offers additional environmental enrichment, enhanced neuroprotection, and a multifaceted approach to treating complex AD pathologies. We show that autocrine IGF-I production does not impact the cell secretome or normal cellular functions, including proliferation, migration, or maintenance of progenitor status. However, HK532-IGF-I cells preferentially differentiate into gamma-aminobutyric acid-ergic neurons, a subtype dysregulated in AD; produce increased vascular endothelial growth factor levels; and display an increased neuroprotective capacity in vitro. We also demonstrate that HK532-IGF-I cells survive peri-hippocampal transplantation in a murine AD model and exhibit long-term persistence in targeted brain areas. In conclusion, we believe that harnessing the benefits of cellular and IGF-I therapies together will provide the optimal therapeutic benefit to patients, and our findings support further preclinical development of HK532-IGF-I cells into a disease-modifying intervention for AD.

  18. 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

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

    PubMed

    Shehata, Mohamed; Fayez, George; Nassar, Ahmed

    2015-12-01

    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

  20. TOR-centric view on insulin resistance and diabetic complications: perspective for endocrinologists and gerontologists

    PubMed Central

    Blagosklonny, M V

    2013-01-01

    This article is addressed to endocrinologists treating patients with diabetic complications as well as to basic scientists studying an elusive link between diseases and aging. It answers some challenging questions. What is the link between insulin resistance (IR), cellular aging and diseases? Why complications such as retinopathy may paradoxically precede the onset of type II diabetes. Why intensive insulin therapy may initially worsen retinopathy. How nutrient- and insulin-sensing mammalian target of rapamycin (mTOR) pathway can drive insulin resistance and diabetic complications. And how rapamycin, at rational doses and schedules, may prevent IR, retinopathy, nephropathy and beta-cell failure, without causing side effects. PMID:24336084

  1. [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. PMID:27092677

  2. Backscatter monitoring of high intensity focused ultrasound therapy using a parametric treatment model

    NASA Astrophysics Data System (ADS)

    Speyer, Gavriel; Kaczkowski, Peter; Brayman, Andrew; Crum, Lawrence

    2010-03-01

    Accurate monitoring of high intensity focused ultrasound (HIFU) surgery is critical to ensuring proper treatment. Pulse-echo diagnostic ultrasound (DU) is a recognized modality for identifying temperature differentials using speckle tracking between two DU radio frequency (RF) frames [2], [4]. This observation has motivated non-parametric temperature estimation, which associates temperature changes directly with the displacement estimates. We present an estimation paradigm termed displacement mode analysis (DMA), which uses physical modeling to associate particular patterns of observed displacement, called displacement modes, with corresponding modes of variation in the administered therapy. This correspondence allows DMA to estimate therapy directly using a linear combination of displacement modes, imbuing these displacement estimates into the reference using interpolation, and by aligning with the treatment frame, providing a therapy estimate with the heating modes. Since DMA is maximum likelihood estimation (MLE), the accuracy of its estimates can be assessed a priori, providing error bounds for estimates of applied heating, temperature, and thermal dose. Predicted performance is verified using both simulation and experiment for a point exposure of 4.2 Watts of electrical power in alginate, a tissue mimicking phantom.

  3. 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.

  4. Moving toward the ideal insulin for insulin pumps.

    PubMed

    Cengiz, Eda; Bode, Bruce; Van Name, Michelle; Tamborlane, William V

    2016-01-01

    Advances in insulin formulations have been important for diabetes management and achieving optimal glycemic control. Rapid-acting insulin analogs provide a faster time-action profile than regular insulin and are approved for use in pumps. However, the need remains for therapy to deliver a more physiologic insulin profile. New insulin formulations and delivery methods are in development, with the aim of accelerating insulin absorption to accomplish ultra-fast-acting insulin time-action profiles. Furthermore, the integration of continuous glucose monitoring with insulin pump therapy enables on-going adjustment of insulin delivery to optimize glycemic control throughout the day and night. These technological and pharmacological advances are likely to facilitate the development of closed-loop pump systems (i.e., artificial pancreas), and improve glycemic control and quality of life for patients with diabetes. PMID:26560137

  5. Differential Impact of Acute High-Intensity Exercise on Circulating Endothelial Microparticles and Insulin Resistance between Overweight/Obese Males and Females

    PubMed Central

    Durrer, Cody; Robinson, Emily; Wan, Zhongxiao; Martinez, Nic; Hummel, Michelle L.; Jenkins, Nathan T.; Kilpatrick, Marcus W.; Little, Jonathan P.

    2015-01-01

    Background An acute bout of exercise can improve endothelial function and insulin sensitivity when measured on the day following exercise. Our aim was to compare acute high-intensity continuous exercise (HICE) to high-intensity interval exercise (HIIE) on circulating endothelial microparticles (EMPs) and insulin sensitivity in overweight/obese men and women. Methods Inactive males (BMI = 30 ± 3, 25 ± 6 yr, n = 6) and females (BMI = 28 ± 2, 21 ± 3 yr, n = 7) participated in three experimental trials in a randomized counterbalanced crossover design: 1) No exercise control (Control); 2) HICE (20 min cycling @ just above ventilatory threshold); 3) HIIE (10 X 1-min @ ∼90% peak aerobic power). Exercise conditions were matched for external work and diet was controlled post-exercise. Fasting blood samples were obtained ∼18 hr after each condition. CD62E+ and CD31+/CD42b- EMPs were assessed by flow cytometry and insulin resistance (IR) was estimated by homeostasis model assessment (HOMA-IR). Results There was a significant sex X exercise interaction for CD62E+ EMPs, CD31+/CD42b- EMPs, and HOMA-IR (all P<0.05). In males, both HICE and HIIE reduced EMPs compared to Control (P≤0.05). In females, HICE increased CD62E+ EMPs (P<0.05 vs. Control) whereas CD31+/CD42b- EMPs were unaltered by either exercise type. There was a significant increase in HOMA-IR in males but a decrease in females following HIIE compared to Control (P<0.05). Conclusions Overweight/obese males and females appear to respond differently to acute bouts of high-intensity exercise. A single session of HICE and HIIE reduced circulating EMPs measured on the morning following exercise in males but in females CD62E+ EMPs were increased following HICE. Next day HOMA-IR paradoxically increased in males but was reduced in females following HIIE. Future research is needed to investigate mechanisms responsible for potential differential responses between males and females. PMID:25710559

  6. Insulin and Insulin Resistance

    PubMed Central

    2005-01-01

    As obesity and diabetes reach epidemic proportions in the developed world, the role of insulin resistance and its consequences are gaining prominence. Understanding the role of insulin in wide-ranging physiological processes and the influences on its synthesis and secretion, alongside its actions from the molecular to the whole body level, has significant implications for much chronic disease seen in Westernised populations today. This review provides an overview of insulin, its history, structure, synthesis, secretion, actions and interactions followed by a discussion of insulin resistance and its associated clinical manifestations. Specific areas of focus include the actions of insulin and manifestations of insulin resistance in specific organs and tissues, physiological, environmental and pharmacological influences on insulin action and insulin resistance as well as clinical syndromes associated with insulin resistance. Clinical and functional measures of insulin resistance are also covered. Despite our incomplete understanding of the complex biological mechanisms of insulin action and insulin resistance, we need to consider the dramatic social changes of the past century with respect to physical activity, diet, work, socialisation and sleep patterns. Rapid globalisation, urbanisation and industrialisation have spawned epidemics of obesity, diabetes and their attendant co-morbidities, as physical inactivity and dietary imbalance unmask latent predisposing genetic traits. PMID:16278749

  7. High-intensity statin therapy and regression of coronary atherosclerosis in patients with diabetes mellitus.

    PubMed

    Athyros, Vasilios G; Katsiki, Niki; Karagiannis, Asterios; Mikhailidis, Dimitri P

    2015-01-01

    Recommended low-density lipoprotein cholesterol (LDL-C) levels for patients with documented cardiovascular disease (CVD) are <100mg/dL (2.6mmol/l) with further reduction to <70mg/dL (1.8mmol/l) for higher-risk patients. High-intensity statin treatment may halt the progression as well as stabilize and induce regression of coronary atheromatous plaques while lowering CVD event rates. Diabetes mellitus (DM) is a major negative determinant of coronary artery plaque regression during statin therapy. However, regression of coronary atherosclerosis in DM patients is feasible to the same degree as in those without DM when very low LDL-C values (<70mg/dL; 1.8mmol/l) are achieved with high intensity statin treatment. The recent 2013 American College of Cardiology/American Heart Association (ACC/AHA) Guidelines on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults suggest to abandon specific LDL-C treatment targets. This strategy may deprive high risk patients, such as those with DM, from very high intensity statin treatment or drug combinations aiming to achieve very low LDL-C levels in order to reduce clinical events.

  8. Transient elevation of liver transaminase after starting insulin therapy for diabetic ketosis or ketoacidosis in newly diagnosed type 1 diabetes mellitus.

    PubMed

    Takaike, Hiroko; Uchigata, Yasuko; Iwasaki, Naoko; Iwamoto, Yasuhiko

    2004-04-01

    A mild increase of AST and/or ALT is sometimes observed among patients with diabetic ketosis or diabetic ketoacidosis (DKA) after initial insulin treatment, and the exact mechanism is still undefined. Therefore, we compared the clinical background between patients with and without transient elevation of liver transaminase (TELT) at the onset of type 1 diabetes mellitus with diabetic ketosis or DKA. Among 50 patients, 13 patients showed TELT. The TELT group was characterized by higher plasma glucose (P<0.05), higher HbA1c (P<0.05), and higher triglyceride (P<0.01) before insulin therapy than those without TELT. The TELT group needed significantly more insulin (P<0.05) for the treatment. In echo-histogram analysis of three patients with TELT, the increase of liver-kidney contrast after insulin treatment suggested fat deposition to the liver. The fat deposition to the liver might be one of the causes of the mild increase of AST and/or ALT after initial treatment of insulin in diabetic ketosis or DKA.

  9. 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.

  10. 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. PMID:1765639

  11. Modeling and Predicting Tissue Movement and Deformation for High Intensity Focused Ultrasound Therapy

    PubMed Central

    Liao, Xiangyun; Yuan, Zhiyong; Lai, Qianfeng; Guo, Jiaxiang; Zheng, Qi; Yu, Sijiao; Tong, Qianqian; Si, Weixin; Sun, Mingui

    2015-01-01

    Purpose In ultrasound-guided High Intensity Focused Ultrasound (HIFU) therapy, the target tissue (such as a tumor) often moves and/or deforms in response to an external force. This problem creates difficulties in treating patients and can lead to the destruction of normal tissue. In order to solve this problem, we present a novel method to model and predict the movement and deformation of the target tissue during ultrasound-guided HIFU therapy. Methods Our method computationally predicts the position of the target tissue under external force. This prediction allows appropriate adjustments in the focal region during the application of HIFU so that the treatment head is kept aligned with the diseased tissue through the course of therapy. To accomplish this goal, we utilize the cow tissue as the experimental target tissue to collect spatial sequences of ultrasound images using the HIFU equipment. A Geodesic Localized Chan-Vese (GLCV) model is developed to segment the target tissue images. A 3D target tissue model is built based on the segmented results. A versatile particle framework is constructed based on Smoothed Particle Hydrodynamics (SPH) to model the movement and deformation of the target tissue. Further, an iterative parameter estimation algorithm is utilized to determine the essential parameters of the versatile particle framework. Finally, the versatile particle framework with the determined parameters is used to estimate the movement and deformation of the target tissue. Results To validate our method, we compare the predicted contours with the ground truth contours. We found that the lowest, highest and average Dice Similarity Coefficient (DSC) values between predicted and ground truth contours were, respectively, 0.9615, 0.9770 and 0.9697. Conclusion Our experimental result indicates that the proposed method can effectively predict the dynamic contours of the moving and deforming tissue during ultrasound-guided HIFU therapy. PMID:25993644

  12. 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.

  13. Cardiac Exposure in the Dynamic Conformal Arc Therapy, Intensity-Modulated Radiotherapy and Volumetric Modulated Arc Therapy of Lung Cancer

    PubMed Central

    Ming, Xin; Feng, Yuanming; Liu, Huan; Zhang, Ying; Zhou, Li; Deng, Jun

    2015-01-01

    Purpose To retrospectively evaluate the cardiac exposure in three cohorts of lung cancer patients treated with dynamic conformal arc therapy (DCAT), intensity-modulated radiotherapy (IMRT), or volumetric modulated arc therapy (VMAT) at our institution in the past seven years. Methods and Materials A total of 140 lung cancer patients were included in this institutional review board approved study: 25 treated with DCAT, 70 with IMRT and 45 with VMAT. All plans were generated in a same commercial treatment planning system and have been clinically accepted and delivered. The dose distribution to the heart and the effects of tumor laterality, the irradiated heart volume and the beam-to-heart distance on the cardiac exposure were investigated. Results The mean dose to the heart among all 140 plans was 4.5 Gy. Specifically, the heart received on average 2.3, 5.2 and 4.6 Gy in the DCAT, IMRT and VMAT plans, respectively. The mean heart doses for the left and right lung tumors were 4.1 and 4.8 Gy, respectively. No patients died with evidence of cardiac disease. Three patients (2%) with preexisting cardiac condition developed cardiac disease after treatment. Furthermore, the cardiac exposure was found to increase linearly with the irradiated heart volume while decreasing exponentially with the beam-to-heart distance. Conclusions Compared to old technologies for lung cancer treatment, modern radiotherapy treatment modalities demonstrated better heart sparing. But the heart dose in lung cancer radiotherapy is still higher than that in the radiotherapy of breast cancer and Hodgkin’s disease where cardiac complications have been extensively studied. With strong correlations of mean heart dose with beam-to-heart distance and irradiated heart volume, cautions should be exercised to avoid long-term cardiac toxicity in the lung cancer patients undergoing radiotherapy. PMID:26630566

  14. 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.

  15. Insulin-derived amyloidosis

    PubMed Central

    Gupta, Yashdeep; Singla, Gaurav; Singla, Rajiv

    2015-01-01

    Amyloidosis is the term for diseases caused by the extracellular deposition of insoluble polymeric protein fibrils in tissues and organs. Insulin-derived amyloidosis is a rare, yet significant complication of insulin therapy. Insulin-derived amyloidosis at injection site can cause poor glycemic control and increased insulin dose requirements because of the impairment in insulin absorption, which reverse on change of injection site and/or excision of the mass. This entity should be considered and assessed by histopathology and immunohistochemistry, in patients with firm/hard local site reactions, which do not regress after cessation of insulin injection at the affected site. Search strategy: PubMed was searched with terms “insulin amyloidosis”. Full text of articles available in English was reviewed. Relevant cross references were also reviewed. Last search was made on October 15, 2014. PMID:25593849

  16. 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.

  17. Metformin versus placebo in combination with insulin analogues in patients with type 2 diabetes mellitus—the randomised, blinded Copenhagen Insulin and Metformin Therapy (CIMT) trial

    PubMed Central

    Lundby-Christensen, Louise; Tarnow, Lise; Boesgaard, Trine W; S Lund, Søren; Wiinberg, Niels; Perrild, Hans; Krarup, Thure; Snorgaard, Ole; Gade-Rasmussen, Birthe; Thorsteinsson, Birger; Røder, Michael; Mathiesen, Elisabeth R; Jensen, Tonny; Vestergaard, Henrik; Hedetoft, Christoffer; Breum, Leif; Duun, Elsebeth; Sneppen, Simone B; Pedersen, Oluf; Hemmingsen, Bianca; Carstensen, Bendix; Madsbad, Sten; Gluud, Christian; Wetterslev, Jørn; Vaag, Allan; Almdal, Thomas P

    2016-01-01

    Objective To assess the effect of metformin versus placebo both in combination with insulin analogue treatment on changes in carotid intima-media thickness (IMT) in patients with type 2 diabetes. Design and setting Investigator-initiated, randomised, placebo-controlled trial with a 2×3 factorial design conducted at eight hospitals in Denmark. Participants and interventions 412 participants with type 2 diabetes (glycated haemoglobin (HbA1c) ≥7.5% (≥58 mmol/mol); body mass index >25 kg/m2) were in addition to open-labelled insulin treatment randomly assigned 1:1 to 18 months blinded metformin (1 g twice daily) versus placebo, aiming at an HbA1c ≤7.0% (≤53 mmol/mol). Outcomes The primary outcome was change in the mean carotid IMT (a marker of subclinical cardiovascular disease). HbA1c, insulin dose, weight and hypoglycaemic and serious adverse events were other prespecified outcomes. Results Change in the mean carotid IMT did not differ significantly between the groups (between-group difference 0.012 mm (95% CI −0.003 to 0.026), p=0.11). HbA1c was more reduced in the metformin group (between-group difference −0.42% (95% CI −0.62% to −0.23%), p<0.001)), despite the significantly lower insulin dose at end of trial in the metformin group (1.04 IU/kg (95% CI 0.94 to 1.15)) compared with placebo (1.36 IU/kg (95% CI 1.23 to 1.51), p<0.001). The metformin group gained less weight (between-group difference −2.6 kg (95% CI −3.3 to −1.8), p<0.001). The groups did not differ with regard to number of patients with severe or non-severe hypoglycaemic or other serious adverse events, but the metformin group had more non-severe hypoglycaemic episodes (4347 vs 3161, p<0.001). Conclusions Metformin in combination with insulin did not reduce carotid IMT despite larger reduction in HbA1c, less weight gain, and smaller insulin dose compared with placebo plus insulin. However, the trial only reached 46% of the planned sample size and lack of power

  18. Novel all-extremity high-intensity interval training improves aerobic fitness, cardiac function and insulin resistance in healthy older adults.

    PubMed

    Hwang, Chueh-Lung; Yoo, Jeung-Ki; Kim, Han-Kyul; Hwang, Moon-Hyon; Handberg, Eileen M; Petersen, John W; Christou, Demetra D

    2016-09-01

    Aging is associated with decreased aerobic fitness and cardiac remodeling leading to increased risk for cardiovascular disease. High-intensity interval training (HIIT) on the treadmill has been reported to be more effective in ameliorating these risk factors compared with moderate-intensity continuous training (MICT) in patients with cardiometabolic disease. In older adults, however, weight-bearing activities are frequently limited due to musculoskeletal and balance problems. The purpose of this study was to examine the feasibility and safety of non-weight-bearing all-extremity HIIT in older adults. In addition, we tested the hypothesis that all-extremity HIIT will be more effective in improving aerobic fitness, cardiac function, and metabolic risk factors compared with all-extremity MICT. Fifty-one healthy sedentary older adults (age: 65±1years) were randomized to HIIT (n=17), MICT (n=18) or non-exercise control (CONT; n=16). HIIT (4×4min 90% of peak heart rate; HRpeak) and isocaloric MICT (70% of HRpeak) were performed on a non-weight-bearing all-extremity ergometer, 4×/week for 8weeks under supervision. All-extremity HIIT was feasible in older adults and resulted in no adverse events. Aerobic fitness (peak oxygen consumption; VO2peak) and ejection fraction (echocardiography) improved by 11% (P<0.0001) and 4% (P=0.001), respectively in HIIT, while no changes were observed in MICT and CONT (P≥0.1). Greater improvements in ejection fraction were associated with greater improvements in VO2peak (r=0.57; P<0.0001). Insulin resistance (homeostatic model assessment) decreased only in HIIT by 26% (P=0.016). Diastolic function, body composition, glucose and lipids were unaffected (P≥0.1). In conclusion, all-extremity HIIT is feasible and safe in older adults. HIIT, but not MICT, improved aerobic fitness, ejection fraction, and insulin resistance. PMID:27346646

  19. Novel all-extremity high-intensity interval training improves aerobic fitness, cardiac function and insulin resistance in healthy older adults.

    PubMed

    Hwang, Chueh-Lung; Yoo, Jeung-Ki; Kim, Han-Kyul; Hwang, Moon-Hyon; Handberg, Eileen M; Petersen, John W; Christou, Demetra D

    2016-09-01

    Aging is associated with decreased aerobic fitness and cardiac remodeling leading to increased risk for cardiovascular disease. High-intensity interval training (HIIT) on the treadmill has been reported to be more effective in ameliorating these risk factors compared with moderate-intensity continuous training (MICT) in patients with cardiometabolic disease. In older adults, however, weight-bearing activities are frequently limited due to musculoskeletal and balance problems. The purpose of this study was to examine the feasibility and safety of non-weight-bearing all-extremity HIIT in older adults. In addition, we tested the hypothesis that all-extremity HIIT will be more effective in improving aerobic fitness, cardiac function, and metabolic risk factors compared with all-extremity MICT. Fifty-one healthy sedentary older adults (age: 65±1years) were randomized to HIIT (n=17), MICT (n=18) or non-exercise control (CONT; n=16). HIIT (4×4min 90% of peak heart rate; HRpeak) and isocaloric MICT (70% of HRpeak) were performed on a non-weight-bearing all-extremity ergometer, 4×/week for 8weeks under supervision. All-extremity HIIT was feasible in older adults and resulted in no adverse events. Aerobic fitness (peak oxygen consumption; VO2peak) and ejection fraction (echocardiography) improved by 11% (P<0.0001) and 4% (P=0.001), respectively in HIIT, while no changes were observed in MICT and CONT (P≥0.1). Greater improvements in ejection fraction were associated with greater improvements in VO2peak (r=0.57; P<0.0001). Insulin resistance (homeostatic model assessment) decreased only in HIIT by 26% (P=0.016). Diastolic function, body composition, glucose and lipids were unaffected (P≥0.1). In conclusion, all-extremity HIIT is feasible and safe in older adults. HIIT, but not MICT, improved aerobic fitness, ejection fraction, and insulin resistance.

  20. Bilateral cataracts and insulin oedema in a child with type 1 diabetes mellitus.

    PubMed

    Goturu, Aruna; Jain, Neemisha; Lewis, Ivor

    2013-02-01

    We describe a teenage type 1 diabetic girl with painless pedal oedema and bilateral cataracts. She developed oedema after commencement of intensive insulin therapy and achievement of excellent glycaemic control. In addition, she was also found to have bilateral subcapsular cataracts. The oedema subsided spontaneously and she underwent surgical treatment for the cataracts. Insulin oedema is a rare complication of insulin therapy. To our knowledge, co-occurrence of these two complications in a young diabetic patient has not been described before in the English language medical literature.

  1. Insulin Pump Therapy Is Associated with Lower Rates of Retinopathy and Peripheral Nerve Abnormality

    PubMed Central

    Zabeen, Bedowra; Craig, Maria E.; Virk, Sohaib A.; Pryke, Alison; Chan, Albert K. F.; Cho, Yoon Hi; Benitez-Aguirre, Paul Z.; Hing, Stephen; Donaghue, Kim C.

    2016-01-01

    Objective To compare rates of microvascular complications in adolescents with type 1 diabetes treated with continuous subcutaneous insulin infusion (CSII) versus multiple daily injections (MDI). Research Design and Methods Prospective cohort of 989 patients (aged 12–20 years; diabetes duration >5 years) treated with CSII or MDI for >12 months. Microvascular complications were assessed from 2000–14: early retinopathy (seven-field fundal photography), peripheral nerve function (thermal and vibration threshold testing), autonomic nerve abnormality (heart rate variability analysis of electrocardiogram recordings) and albuminuria (albumin creatinine ratio/timed overnight albumin excretion). Generalized estimating equations (GEE) were used to examine the relationship between treatment and complications rates, adjusting for socio-economic status (SES) and known risk factors including HbA1c and diabetes duration. Results Comparing CSII with MDI: HbA1C was 8.6% [70mmol/mol] vs. 8.7% [72 mmol/mol]) (p = 0.7), retinopathy 17% vs. 22% (p = 0.06); microalbuminuria 1% vs. 4% (p = 0.07), peripheral nerve abnormality 27% vs. 33% (p = 0.108) and autonomic nerve abnormality 24% vs. 28% (p = 0.401). In multivariable GEE, CSII use was associated with lower rates of retinopathy (OR 0.66, 95% CI 0.45–0.95, p = 0.029) and peripheral nerve abnormality (OR 0.63, 95% CI 0.42–0.95, p = 0.026), but not albuminuria (OR 0.46, 95% CI 0.10–2.17, p = 0.33). SES was not associated with any of the complication outcomes. Conclusions In adolescents, CSII use is associated with lower rates of retinopathy and peripheral nerve abnormality, suggesting an apparent benefit of CSII over MDI independent of glycemic control or SES. PMID:27050468

  2. 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

  3. Comparison of three dimensional conformal radiation therapy, intensity modulated radiation therapy and volumetric modulated arc therapy for low radiation exposure of normal tissue in patients with prostate cancer.

    PubMed

    Cakir, Aydin; Akgun, Zuleyha; Fayda, Merdan; Agaoglu, Fulya

    2015-01-01

    Radiotherapy has an important role in the treatment of prostate cancer. Three-dimensional conformal radiation therapy (3D-CRT), intensity modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT) techniques are all applied for this purpose. However, the risk of secondary radiation-induced bladder cancer is significantly elevated in irradiated patients compared surgery-only or watchful waiting groups. There are also reports of risk of secondary cancer with low doses to normal tissues. This study was designed to compare received volumes of low doses among 3D-CRT, IMRT and VMAT techniques for prostate patients. Ten prostate cancer patients were selected retrospectively for this planning study. Treatment plans were generated using 3D-CRT, IMRT and VMAT techniques. Conformity index (CI), homogenity index (HI), receiving 5 Gy of the volume (V5%), receiving 2 Gy of the volume (V2%), receiving 1 Gy of the volume (V1%) and monitor units (MUs) were compared. This study confirms that VMAT has slightly better CI while thev olume of low doses was higher. VMAT had lower MUs than IMRT. 3D-CRT had the lowest MU, CI and HI. If target coverage and normal tissue sparing are comparable between different treatment techniques, the risk of second malignancy should be a important factor in the selection of treatment.

  4. Impact of baseline lipoprotein and C-reactive protein levels on coronary atheroma regression following high-intensity statin therapy.

    PubMed

    Puri, Rishi; Nissen, Steven E; Shao, Mingyuan; Uno, Kiyoko; Kataoka, Yu; Kapadia, Samir R; Tuzcu, E Murat; Nicholls, Stephen J

    2014-11-15

    Guidelines now recommend high-intensity statin therapy in all patients with proven atherosclerotic disease. Yet the impact of baseline lipoprotein and C-reactive protein (CRP) levels on measures of disease regression to this therapy are unknown. The aim of this study was to test the hypothesis that high-intensity statin therapy causes equivalent degrees of coronary atheroma regression irrespective of baseline lipoprotein and CRP levels. In 8 prospective randomized trials using serial coronary intravascular ultrasound, 1,881 patients who maintained or switched to 18- to 24 months of high-intensity statin therapy (rosuvastatin 40 mg or atorvastatin 80 mg) were stratified according to baseline lipoprotein and CRP levels. Changes in coronary percentage atheroma volume (PAV) and total atheroma volume (TAV) were evaluated. High-intensity statin therapy produced significant reductions from baseline in low-density lipoprotein cholesterol by 38.4%, non-high-density lipoprotein (HDL) cholesterol by 33.6%, triglycerides by 13.1%, and CRP by 33.3%, while increasing HDL cholesterol by 11.7% (p <0.001 for all). This was associated with regression of PAV by 0.7% and of TAV by 8.2 mm(3) (p <0.001 for both). No significant differences of changes in PAV and TAV were observed across baseline quintiles of low-density lipoprotein cholesterol, HDL cholesterol, non-HDL cholesterol, triglycerides, or CRP. Moreover, across all measured lipoproteins and CRP, most patients demonstrated plaque regression (defined as any change from baseline in PAV or TAV <0). In conclusion, high-intensity statin therapy attenuated the natural progression of coronary atherosclerosis in all strata of patients with coronary artery disease irrespective of baseline lipoprotein or CRP levels. These findings provide support for the latest United States guideline recommendations for the broad use of high-intensity statin therapy in all patients with atherosclerosis, regardless of baseline lipid status.

  5. Improved highly accurate localized motion imaging for monitoring high-intensity focused ultrasound therapy

    NASA Astrophysics Data System (ADS)

    Qu, Xiaolei; Azuma, Takashi; Sugiyama, Ryusuke; Kanazawa, Kengo; Seki, Mika; Sasaki, Akira; Takeuchi, Hideki; Fujiwara, Keisuke; Itani, Kazunori; Tamano, Satoshi; Takagi, Shu; Sakuma, Ichiro; Matsumoto, Yoichiro

    2016-07-01

    Visualizing an area subjected to high-intensity focused ultrasound (HIFU) therapy is necessary for controlling the amount of HIFU exposure. One of the promising monitoring methods is localized motion imaging (LMI), which estimates coagulation length by detecting the change in stiffness. In this study, we improved the accuracy of our previous LMI by dynamic cross-correlation window (DCCW) and maximum vibration amount (MVA) methods. The DCCW method was used to increase the accuracy of estimating vibration amplitude, and the MVA method was employed to increase signal-noise ratio of the decrease ratio at the coagulated area. The qualitative comparison of results indicated that the two proposed methods could suppress the effect of noise. Regarding the results of the quantitative comparison, coagulation length was estimated with higher accuracy by the improved LMI method, and the root-mean-square error (RMSE) was reduced from 2.51 to 1.69 mm.

  6. 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.

  7. Contributions of Therapist Characteristics and Stability to Intensive In-home Therapy Youth Outcomes

    PubMed Central

    Greeson, Johanna K. P.; Guo, Shenyang; Barth, Richard P.; Hurley, Sarah; Sisson, Jocelyn

    2014-01-01

    Objective This study examines the influence of therapist and youth characteristics on post-discharge outcomes from intensive in-home therapy. Method Data for 1,416 youth and 412 therapists were obtained from a behavioral health services provider. The Huber–White method was used to account for nested data; ordered logistic regression was employed to assess outcomes. Results Therapist gender and employment stability were significantly associated with youth outcomes. The likelihood of an undesirable outcome was significantly less for cases with female therapists. Conclusion Findings underscore the need for additional study concerning the impact of therapist characteristics and stability on youth outcomes, and to improve the understanding of the relationship between the two. Future studies in these areas would advance social work practice in family-based treatment programs. PMID:24944505

  8. Plasma catecholamine concentration during sedation in ventilated patients requiring intensive therapy.

    PubMed

    Kong, K L; Willatts, S M; Prys-Roberts, C; Harvey, J T; Gorman, S

    1990-01-01

    The effects of isoflurane and midazolam sedation on the catecholamine responses of ventilated patients were studied over a 24-h period. Sixty ventilated patients admitted to our intensive therapy unit were allocated randomly to receive either isoflurane or midazolam sedation. Arterial blood samples for plasma catecholamine concentrations were taken at baseline, 6 h after starting sedation and at the end of the study period. Patients sedated with isoflurane showed a progressive reduction in both adrenaline and noradrenaline concentrations during the period of sedation which reached statistical significance for adrenaline at 6 h (p less than 0.02) and at the end of the study (p less than 0.001). Patients sedated with midazolam showed no significant changes of adrenaline or noradrenaline concentrations. Overall, a more satisfactory degree of sedation was achieved with isoflurane.

  9. Improved highly accurate localized motion imaging for monitoring high-intensity focused ultrasound therapy

    NASA Astrophysics Data System (ADS)

    Qu, Xiaolei; Azuma, Takashi; Sugiyama, Ryusuke; Kanazawa, Kengo; Seki, Mika; Sasaki, Akira; Takeuchi, Hideki; Fujiwara, Keisuke; Itani, Kazunori; Tamano, Satoshi; Takagi, Shu; Sakuma, Ichiro; Matsumoto, Yoichiro

    2016-07-01

    Visualizing an area subjected to high-intensity focused ultrasound (HIFU) therapy is necessary for controlling the amount of HIFU exposure. One of the promising monitoring methods is localized motion imaging (LMI), which estimates coagulation length by detecting the change in stiffness. In this study, we improved the accuracy of our previous LMI by dynamic cross-correlation window (DCCW) and maximum vibration amount (MVA) methods. The DCCW method was used to increase the accuracy of estimating vibration amplitude, and the MVA method was employed to increase signal–noise ratio of the decrease ratio at the coagulated area. The qualitative comparison of results indicated that the two proposed methods could suppress the effect of noise. Regarding the results of the quantitative comparison, coagulation length was estimated with higher accuracy by the improved LMI method, and the root-mean-square error (RMSE) was reduced from 2.51 to 1.69 mm.

  10. 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.

  11. [Positioning therapy and early mobilization in intensive care units : Findings from the current 2015 guidelines].

    PubMed

    Hermes, C; Nydahl, P; Henzler, D; Bein, T

    2016-09-01

    The 2007 guidelines "Positioning for prophylaxis and therapy of pulmonary disorders" were completely revised in 2015 on behalf of the German Society of Anaesthesiology and Intensive Care Medicine. With regard to practical and scientific relevance, early mobilization of patients in critical care has been included in the guidelines for the first time. Furthermore, the recommendations for prone positioning have been updated, based on current evidence in medicine and nursing. In addition, recommendations regarding unsuitable positions that may actually harm patients were made. As such, the flat supine position should only be used in cases of urgent medical or nursing needs. This underlines the importance of a moderately elevated head of bed position (20(o)-45(o)) in mechanically ventilated patients.

  12. A Combined Therapy with Myo-Inositol and D-Chiro-Inositol Improves Endocrine Parameters and Insulin Resistance in PCOS Young Overweight Women.

    PubMed

    Benelli, Elena; Del Ghianda, Scilla; Di Cosmo, Caterina; Tonacchera, Massimo

    2016-01-01

    Introduction. We evaluated the effects of a therapy that combines myo-inositol (MI) and D-chiro-inositol (DCI) in young overweight women affected by polycystic ovary syndrome (PCOS), characterized by oligo- or anovulation and hyperandrogenism, correlated to insulin resistance. Methods. We enrolled 46 patients affected by PCOS and, randomly, we assigned them to two groups, A and B, treated, respectively, with the association of MI plus DCI, in a 40 : 1 ratio, or with placebo (folic acid) for six months. Thus, we analyzed pretreatment and posttreatment FSH, LH, 17-beta-Estradiol, Sex Hormone Binding Globulin, androstenedione, free testosterone, dehydroepiandrosterone sulphate, HOMA index, and fasting glucose and insulin. Results. We recorded a statistically significant reduction of LH, free testosterone, fasting insulin, and HOMA index only in the group treated with the combined therapy of MI plus DCI; in the same patients, we observed a statistically significant increase of 17-beta-Estradiol levels. Conclusions. The combined therapy of MI plus DCI is effective in improving endocrine and metabolic parameters in young obese PCOS affected women. PMID:27493664

  13. A Combined Therapy with Myo-Inositol and D-Chiro-Inositol Improves Endocrine Parameters and Insulin Resistance in PCOS Young Overweight Women

    PubMed Central

    Benelli, Elena; Del Ghianda, Scilla

    2016-01-01

    Introduction. We evaluated the effects of a therapy that combines myo-inositol (MI) and D-chiro-inositol (DCI) in young overweight women affected by polycystic ovary syndrome (PCOS), characterized by oligo- or anovulation and hyperandrogenism, correlated to insulin resistance. Methods. We enrolled 46 patients affected by PCOS and, randomly, we assigned them to two groups, A and B, treated, respectively, with the association of MI plus DCI, in a 40 : 1 ratio, or with placebo (folic acid) for six months. Thus, we analyzed pretreatment and posttreatment FSH, LH, 17-beta-Estradiol, Sex Hormone Binding Globulin, androstenedione, free testosterone, dehydroepiandrosterone sulphate, HOMA index, and fasting glucose and insulin. Results. We recorded a statistically significant reduction of LH, free testosterone, fasting insulin, and HOMA index only in the group treated with the combined therapy of MI plus DCI; in the same patients, we observed a statistically significant increase of 17-beta-Estradiol levels. Conclusions. The combined therapy of MI plus DCI is effective in improving endocrine and metabolic parameters in young obese PCOS affected women. PMID:27493664

  14. The effect of massage therapy on occupational stress of Intensive Care Unit nurses

    PubMed Central

    Nazari, Fateme; Mirzamohamadi, Mojtaba; Yousefi, Hojatollah

    2015-01-01

    Background: One of the main causes of stress in the lives of people is their jobs. Occupational stress is causing a wide range of significant issues in health and community services. Nursing is the most stressful profession in the health services. Massage therapy is one way of coping with stress. This study was conducted to determine the effect of massage therapy on stress in nurses. Materials and Methods: This study was a clinical trial on 66 male and female nurses working in intensive care units (dialysis, ICU, and CCU) of Isfahan University of Medical Sciences, Iran, in 2013. Participants were selected according to the aims and inclusion criteria of the study. Then, they were randomly divided into experimental and control groups. The Occupational Stress Inventory (OSI) (Osipow and Spokane, 1987) was completed by participants of the two groups before, immediately after, and 2 weeks after the intervention. General Swedish massage was performed on participants of the experimental group for 25 min in each session, twice a week for 4 weeks. Data were analyzed by descriptive and inferential statistics [Chi-square, t-test, and repeated measures analysis of variance (ANOVA)] using SPSS software. Results: Results showed that the difference in overall mean occupation stress scores between experimental and control groups 2 weeks after the intervention was significant (P < 0.001). Conclusions: According to the results, it is recommended that massage, as a valuable noninvasive method, be used for nurses in intensive care units to reduce their stress, promote mental health, and prevent the decrease in quality of nursing work life. PMID:26257809

  15. 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.

  16. Spherical cluster analysis for beam angle optimization in intensity-modulated radiation therapy treatment planning

    NASA Astrophysics Data System (ADS)

    Bangert, Mark; Oelfke, Uwe

    2010-10-01

    An intuitive heuristic to establish beam configurations for intensity-modulated radiation therapy is introduced as an extension of beam ensemble selection strategies applying scalar scoring functions. It is validated by treatment plan comparisons for three intra-cranial, pancreas, and prostate cases each. Based on a patient specific matrix listing the radiological quality of candidate beam directions individually for every target voxel, a set of locally ideal beam angles is generated. The spherical distribution of locally ideal beam angles is characteristic for every treatment site and patient: ideal beam angles typically cluster around distinct orientations. We interpret the cluster centroids, which are identified with a spherical K-means algorithm, as irradiation angles of an intensity-modulated radiation therapy treatment plan. The fluence profiles are subsequently optimized during a conventional inverse planning process. The average computation time for the pre-optimization of a beam ensemble is six minutes on a state-of-the-art work station. The treatment planning study demonstrates the potential benefit of the proposed beam angle optimization strategy. For the three prostate cases under investigation, the standard treatment plans applying nine coplanar equi-spaced beams and treatment plans applying an optimized non-coplanar nine-beam ensemble yield clinically comparable dose distributions. For symmetric patient geometries, the dose distribution formed by nine equi-spaced coplanar beams cannot be improved significantly. For the three pancreas and intra-cranial cases under investigation, the optimized non-coplanar beam ensembles enable better sparing of organs at risk while guaranteeing equivalent target coverage. Beam angle optimization by spherical cluster analysis shows the biggest impact for target volumes located asymmetrically within the patient and close to organs at risk.

  17. 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.

  18. 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%.

  19. 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.

  20. GLP1-RA Add-on Therapy in Patients with Type 2 Diabetes Currently on a Bolus Containing Insulin Regimen.

    PubMed

    Davies, Marie L; Pham, David Q; Drab, Scott R

    2016-08-01

    Adding glucagon-like peptide-1 receptor agonists (GLP-1 RAs) to basal insulin regimens has become a guideline-recommended treatment option for uncontrolled type 2 diabetes. However, limited data exist to support the use of GLP-1 RAs with insulin regimens, including bolus insulin in patients with type 2 diabetes. The primary objectives of this review were to identify if the combination of a GLP-1 RA and an insulin regimen containing bolus insulin resulted in improvements in HbA1c , weight loss, reduction in insulin doses, and to evaluate the side effect profile of this combination in terms of nausea and hypoglycemia risk. Eight studies using exenatide twice/day, liraglutide, and dulaglutide were reviewed ranging in average duration of follow-up from 3 to 15 months. Seven studies showed that addition of a GLP-1 RA was associated with significant HbA1c reductions ranging from 0.4% to 1.64% from baseline to follow-up. Patients in all eight studies had significant weight loss in the GLP-1 RA arm from baseline to follow-up ranging from 0.87 to 10.2 kg. In all the studies, total daily bolus insulin doses decreased 25-67% from baseline to follow-up. In some studies, a portion of patients were able to discontinue bolus insulin all together after initiation of a GLP-1 RA. In addition, in two randomized trials included in the review, the GLP-1 RA arm showed significant improvement in HbA1c and weight compared with the control group who received basal/bolus regimens. Nausea was identified in 7-42% of participants using GLP-1 RAs with insulin. Data support the use of GLP-1 RAs added to insulin regimens already containing bolus insulin for glycemic control, weight loss, and reduction or discontinuation of bolus insulin. PMID:27340935

  1. Evaluating the Effect of U-500 Insulin Therapy on Glycemic Control in Veterans With Type 2 Diabetes

    PubMed Central

    Nawarskas, Ann D.; Resch, Nina D.; Vigil, Justina M.

    2015-01-01

    IN BRIEF This article describes a single-center, retrospective chart review to determine the glycemic effect of converting from U-100 to U-500 regular insulin in veterans with type 2 diabetes and the effect of this change, if any, on the frequency of provider contacts. Results showed that U-500 insulin improved glycemic control without significantly increasing the risk of hypoglycemia or total daily insulin dose, even when follow-up contacts with providers were not structured or frequent. PMID:25653468

  2. 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

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

    PubMed

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

    2015-12-01

    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

  4. 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

  5. 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.

  6. The intensity feedback system at Heidelberg Ion-Beam Therapy Centre

    NASA Astrophysics Data System (ADS)

    Schoemers, Christian; Feldmeier, Eike; Naumann, Jakob; Panse, Ralf; Peters, Andreas; Haberer, Thomas

    2015-09-01

    At Heidelberg Ion-Beam Therapy Centre (HIT), more than 2500 tumour patients have been treated with charged particle beams since 2009 using the raster scanning method. The tumour is irradiated slice-by-slice, each slice corresponding to a different beam energy. For the particle dose of each raster point the pre-irradiation by more distal slices has to be considered. This leads to highly inhomogeneous dose distributions within one iso-energy slice. The particles are extracted from the synchrotron via transverse RF knock-out. A pure feed forward control cannot take into account fluence inhomogeneities or deal with intensity fluctuations. So far, fluctuations have been counteracted by a reduced scanning velocity. We now added a feedback loop to the extraction system. The dose monitoring ionisation chambers in front of the patient have been coupled to the extraction device in the synchrotron. Characterization and implementation of the intensity feedback system into the HIT facility is described here. By its implementation the treatment time has been reduced by 10% in average.

  7. 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.

  8. Direct-aperture optimization applied to selection of beam orientations in intensity-modulated radiation therapy

    NASA Astrophysics Data System (ADS)

    Bedford, J. L.; Webb, S.

    2007-01-01

    Direct-aperture optimization (DAO) was applied to iterative beam-orientation selection in intensity-modulated radiation therapy (IMRT), so as to ensure a realistic segmental treatment plan at each iteration. Nested optimization engines dealt separately with gantry angles, couch angles, collimator angles, segment shapes, segment weights and wedge angles. Each optimization engine performed a random search with successively narrowing step sizes. For optimization of segment shapes, the filtered backprojection (FBP) method was first used to determine desired fluence, the fluence map was segmented, and then constrained direct-aperture optimization was used thereafter. Segment shapes were fully optimized when a beam angle was perturbed, and minimally re-optimized otherwise. The algorithm was compared with a previously reported method using FBP alone at each orientation iteration. An example case consisting of a cylindrical phantom with a hemi-annular planning target volume (PTV) showed that for three-field plans, the method performed better than when using FBP alone, but for five or more fields, neither method provided much benefit over equally spaced beams. For a prostate case, improved bladder sparing was achieved through the use of the new algorithm. A plan for partial scalp treatment showed slightly improved PTV coverage and lower irradiated volume of brain with the new method compared to FBP alone. It is concluded that, although the method is computationally intensive and not suitable for searching large unconstrained regions of beam space, it can be used effectively in conjunction with prior class solutions to provide individually optimized IMRT treatment plans.

  9. 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

  10. Oral Insulin Reloaded

    PubMed Central

    Heinemann, Lutz; Plum-Mörschel, Leona

    2014-01-01

    Optimal coverage of insulin needs is the paramount aim of insulin replacement therapy in patients with diabetes mellitus. To apply insulin without breaking the skin barrier by a needle and/or to allow a more physiological provision of insulin are the main reasons triggering the continuous search for alternative routes of insulin administration. Despite numerous attempts over the past 9 decades to develop an insulin pill, no insulin for oral dosing is commercially available. By way of a structured approach, we aim to provide a systematic update on the most recent developments toward an orally available insulin formulation with a clear focus on data from clinical-experimental and clinical studies. Thirteen companies that claim to be working on oral insulin formulations were identified. However, only 6 of these companies published new clinical trial results within the past 5 years. Interestingly, these clinical data reports make up a mere 4% of the considerably high total number of publications on the development of oral insulin formulations within this time period. While this picture clearly reflects the rising research interest in orally bioavailable insulin formulations, it also highlights the fact that the lion’s share of research efforts is still allocated to the preclinical stages. PMID:24876606

  11. The rationale for intensity-modulated proton therapy in geometrically challenging cases

    NASA Astrophysics Data System (ADS)

    Safai, S.; Trofimov, A.; Adams, J. A.; Engelsman, M.; Bortfeld, T.

    2013-09-01

    Intensity-modulated proton therapy (IMPT) delivered with beam scanning is currently available at a limited number of proton centers. However, a simplified form of IMPT, the technique of field ‘patching’, has long been a standard practice in proton therapy centers. In field patching, different parts of the target volume are treated from different directions, i.e., a part of the tumor gets either full dose from a radiation field, or almost no dose. Thus, patching represents a form of binary intensity modulation. This study explores the limitations of the standard binary field patching technique, and evaluates possible dosimetric advantages of continuous dose modulations in IMPT. Specifics of the beam delivery technology, i.e., pencil beam scanning versus passive scattering and modulation, are not investigated. We have identified two geometries of target volumes and organs at risk (OAR) in which the use of field patching is severely challenged. We focused our investigations on two patient cases that exhibit these geometries: a paraspinal tumor case and a skull-base case. For those cases we performed treatment planning comparisons of three-dimensional conformal proton therapy (3DCPT) with field patching versus IMPT, using commercial and in-house software, respectively. We also analyzed the robustness of the resulting plans with respect to systematic setup errors of ±1 mm and range errors of ±2.5 mm. IMPT is able to better spare OAR while providing superior dose coverage for the challenging cases identified above. Both 3DCPT and IMPT are sensitive to setup errors and range uncertainties, with IMPT showing the largest effect. Nevertheless, when delivery uncertainties are taken into account IMPT plans remain superior regarding target coverage and OAR sparing. On the other hand, some clinical goals, such as the maximum dose to OAR, are more likely to be unmet with IMPT under large range errors. IMPT can potentially improve target coverage and OAR sparing in

  12. 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

  13. Beam orientation optimization for intensity-modulated radiation therapy using mixed integer programming.

    PubMed

    Yang, Ruijie; Dai, Jianrong; Yang, Yong; Hu, Yimin

    2006-08-01

    The purpose of this study is to extend an algorithm proposed for beam orientation optimization in classical conformal radiotherapy to intensity-modulated radiation therapy (IMRT) and to evaluate the algorithm's performance in IMRT scenarios. In addition, the effect of the candidate pool of beam orientations, in terms of beam orientation resolution and starting orientation, on the optimized beam configuration, plan quality and optimization time is also explored. The algorithm is based on the technique of mixed integer linear programming in which binary and positive float variables are employed to represent candidates for beam orientation and beamlet weights in beam intensity maps. Both beam orientations and beam intensity maps are simultaneously optimized in the algorithm with a deterministic method. Several different clinical cases were used to test the algorithm and the results show that both target coverage and critical structures sparing were significantly improved for the plans with optimized beam orientations compared to those with equi-spaced beam orientations. The calculation time was less than an hour for the cases with 36 binary variables on a PC with a Pentium IV 2.66 GHz processor. It is also found that decreasing beam orientation resolution to 10 degrees greatly reduced the size of the candidate pool of beam orientations without significant influence on the optimized beam configuration and plan quality, while selecting different starting orientations had large influence. Our study demonstrates that the algorithm can be applied to IMRT scenarios, and better beam orientation configurations can be obtained using this algorithm. Furthermore, the optimization efficiency can be greatly increased through proper selection of beam orientation resolution and starting beam orientation while guaranteeing the optimized beam configurations and plan quality.

  14. 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

  15. The effect of sulphonylurea therapy on skeletal muscle glycogen synthase activity and insulin secretion in newly presenting type 2 (non-insulin-dependent) diabetic patients.

    PubMed

    Johnson, A B; Argyraki, M; Thow, J C; Jones, I R; Broughton, D; Miller, M; Taylor, R

    1991-04-01

    Ten newly presenting, Type 2 (non-insulin-dependent), Caucasian diabetic patients were studied before and after 8 weeks treatment with the sulphonylurea gliclazide, and in parallel 13 similar patients were studied before and after 8 weeks treatment with diet alone. Eight non-diabetic subjects were also studied. Insulin action was assessed by measuring activation of skeletal muscle glycogen synthase (GS) prior to and during a 4-h hyperinsulinaemic euglycaemic clamp (100 mU kg-1 h-1). Fasting plasma glucose (+/- SE) and glycosylated haemoglobin decreased to a greater extent in the gliclazide treated patients (fall of 6.2 +/- 0.7 vs 2.1 +/- 0.5 mmol l-1, p less than 0.005 and 4.7 +/- 0.5 vs 2.1 +/- 0.5%, p less than 0.005). This was accompanied by an increase in fasting serum insulin concentrations in the gliclazide treated patients (7.0 +/- 1.3 to 10.1 +/- 1.1 mU l-1, p less than 0.005), but no change in the diet treated patients. Fractional GS activity did not increase during the clamp at presentation in either treatment group (change +2.9 +/- 1.8 and -1.5 +/- 1.9%, respectively) whereas it increased markedly in the control subjects (+16.4 +/- 3.4%, both p less than 0.001). After 8-week treatment there was a significant increase in GS activity during the clamp in the patients receiving gliclazide (+6.9 +/- 2.7%, p less than 0.05), but no change in GS activity in the patients on diet alone (+0.5 +/- 1.4%). The difference in post-treatment muscle insulin action was significant (p less than 0.05). There was no correlation between the degree of improvement in metabolic control and the improvement in response of GS to insulin in the gliclazide treated patients (r = -0.06), suggesting a possible direct drug effect on skeletal muscle. Glucose requirement during the clamp at presentation was markedly lower in both treatment groups than in the non-diabetic subjects (gliclazide 2.1 +/- 0.3, diet 2.0 +/- 0.6 vs 7.8 +/- 0.4 mg kg-1 min-1, both p less than 0.001), and despite a

  16. 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

  17. 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

  18. Accuracy of Real-time Couch Tracking During 3-dimensional Conformal Radiation Therapy, Intensity Modulated Radiation Therapy, and Volumetric Modulated Arc Therapy for Prostate Cancer

    SciTech Connect

    Wilbert, Juergen; Baier, Kurt; Hermann, Christian; Flentje, Michael; Guckenberger, Matthias

    2013-01-01

    Purpose: To evaluate the accuracy of real-time couch tracking for prostate cancer. Methods and Materials: Intrafractional motion trajectories of 15 prostate cancer patients were the basis for this phantom study; prostate motion had been monitored with the Calypso System. An industrial robot moved a phantom along these trajectories, motion was detected via an infrared camera system, and the robotic HexaPOD couch was used for real-time counter-steering. Residual phantom motion during real-time tracking was measured with the infrared camera system. Film dosimetry was performed during delivery of 3-dimensional conformal radiation therapy (3D-CRT), step-and-shoot intensity modulated radiation therapy (IMRT), and volumetric modulated arc therapy (VMAT). Results: Motion of the prostate was largest in the anterior-posterior direction, with systematic ( N-Ary-Summation ) and random ({sigma}) errors of 2.3 mm and 2.9 mm, respectively; the prostate was outside a threshold of 5 mm (3D vector) for 25.0%{+-}19.8% of treatment time. Real-time tracking reduced prostate motion to N-Ary-Summation =0.01 mm and {sigma} = 0.55 mm in the anterior-posterior direction; the prostate remained within a 1-mm and 5-mm threshold for 93.9%{+-}4.6% and 99.7%{+-}0.4% of the time, respectively. Without real-time tracking, pass rates based on a {gamma} index of 2%/2 mm in film dosimetry ranged between 66% and 72% for 3D-CRT, IMRT, and VMAT, on average. Real-time tracking increased pass rates to minimum 98% on average for 3D-CRT, IMRT, and VMAT. Conclusions: Real-time couch tracking resulted in submillimeter accuracy for prostate cancer, which transferred into high dosimetric accuracy independently of whether 3D-CRT, IMRT, or VMAT was used.

  19. Yoga: As an adjunct therapy to trim down the Ayurvedic drug requirement in non insulin-dependent diabetes mellitus

    PubMed Central

    Sharma, Rohit; Amin, Hetal; Prajapati, P.K.

    2014-01-01

    Introduction: In spite of a large number of drugs showing anti-hyperglycemic activities, none of them have been successful in complete management of diabetes mellitus (DM). Yoga and Ayurveda are the two schools of thought in India, which have a history of curing diseases since thousands of years. Yogic techniques and Ayurvedic herbs have proven their anti-diabetic potential without inducing untoward effects. The present study combines Ayurvedic medication with Yoga techniques as a new approach toward healing DM. Aims and Objectives: To assess the effect of Yoga therapy in the management of non insulin-dependent DM (NIDDM) and to decrease the oral drug dose requirement of guḍūcī ghana Tablet. Materials and Methods: Thirty known NIDDM patients of both genders, who were on guḍūcī ghana (solidified aqueous extract of Tinospora cordifolia (Willd.) Miers.) tablets from past 2 months as Ayurvedic remedy for DM were selected. Along with guḍūcī ghana administration, the subjects were instructed to follow Yogic procedures including Āsanas, prāṇāyāma, and śuddhi kriyās. The study was conducted for 8 weeks, wherein fasting blood sugar (FBS) and postprandial blood sugar (PPBS) levels along with relief in sign and symptoms were assessed at every 2 weeks intervals, and according to relief in sign and symptoms, tapering of drug dosage was carried out. The obtained data were analyzed statistically by applying paired t-test. Results and Conclusion: The results obtained were promising as the relief in diabetic symptomatology was highly significant in terms of P value. 80.83% reduction in dose of guḍūcī ghana tablets and 7.85% and 8.78% fall in FBS and PPBS levels, respectively, after the complete course of treatment. The obtained P value showed highly significant results. PMID:25593403

  20. Potentiating the efficacy of molecular targeted therapy for hepatocellular carcinoma by inhibiting the insulin-like growth factor pathway.

    PubMed

    Ou, Da-Liang; Lee, Bin-Shyun; Chang, Ya-Chi; Lin, Liang-In; Liou, Jun-Yang; Hsu, Chiun; Cheng, Ann-Lii

    2013-01-01

    Insulin-like growth factor (IGF) signaling pathway is an important regulatory mechanism of tumorigenesis and drug resistance in many cancers. The present study explored the potential synergistic effects between IGF receptor (IGFR) inhibition and other molecular targeted agents (MTA) in HCC cells. HCC cell lines (Hep3B, PLC5, and SK-Hep1) and HUVECs were tested. The MTA tested included sorafenib, sunitinib, and the IGFR kinase inhibitor NVP-AEW541. The potential synergistic antitumor effects were tested by median dose effect analysis and apoptosis assay in vitro and by xenograft models in vivo. The activity and functional significance of pertinent signaling pathways and expression of apoptosis-related proteins were measured by RNA interference and Western blotting. We found that IGF can activate IGFR and downstream AKT signaling activities in all the HCC cells tested, but the growth-stimulating effect of IGF was most prominent in Hep3B cells. NVP-AEW541 can abrogate IGF-induced activation of IGFR and AKT signaling in HCC cells. IGF can increase the resistance of HCC cells to sunitinib. The apoptosis-inducing effects of sunitinib, but not sorafenib, were enhanced when IGFR signaling activity was inhibited by NVP-AEW541 or IGFR knockdown. Chk2 kinase activation was found contributory to the synergistic anti-tumor effects between sunitinib and IGFR inhibition. Our data indicate that the apoptosis-potentiating effects of IGFR inhibition for HCC may be drug-specific. Combination therapy of IGFR inhibitors with other MTA may improve the therapeutic efficacy in HCC.

  1. 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.

  2. Utility of Smart Arc CDR for intensity-modulated radiation therapy for prostate cancer.

    PubMed

    Hatanaka, Shogo; Tamaki, Seiichi; Endo, Haruna; Mizuno, Norifumi; Nakamura, Naoki

    2014-07-01

    Volumetric-modulated arc therapy (VMAT) is a widespread intensity-modulated radiation therapy (IMRT) method, however, VMAT requires adaptation of the radiation treatment planning system (RTPS) and linear accelerator (linac); these upgrades are quite expensive. The Smart Arc of Pinnacle(3) (Philips), which is the software used in VMAT calculations, can select constant dose rate (CDR) mode. This approach has a low initial cost because the linac upgrade is not required. The objective of this study was to clarify the utility of CDR mode for prostate IMRT. Pinnacle(3) and Clinac 21EX linac (Varian, 10 MV X-rays) were used for planning. The plans were created for 28 patients using a fixed multi-field IMRT (f-IMRT), VMAT and CDR techniques. The dose distribution results were classified into three groups: optimal, suboptimal and reject. For the f-IMRT, VMAT and CDR results, 25, 26 and 21 patients were classified as 'optimal', respectively. Our results show a significant reduction in the achievement rate of 'optimal' for a CDR when the bladder volume is <100 cm(3). The total numbers of monitoring units (MUs) (average ± 1σ) were 469 ± 53, 357 ± 35 and 365 ± 33; the average optimization times were ∼50 min, 2 h and 2 h 40 min, and the irradiation times were ∼280 s, 60 s and 110 s, respectively. CDR can reduce the total MUs and irradiation time compared with f-IMRT, and CDR has a lower initial cost compared with VMAT. Thus, for institutions that do not currently perform VMAT, CDR is a useful option. Additionally, in the context of patient identification, bladder volume may be useful.

  3. Timing of high-intensity pulses for myocardial cavitation-enabled therapy

    PubMed Central

    2014-01-01

    Background High-intensity ultrasound pulses intermittently triggered from an ECG signal can interact with circulating contrast agent microbubbles to produce myocardial cavitation microlesions of potential therapeutic value. In this study, the timing of therapy pulses relative to the ECG R wave was investigated to identify the optimal time point for tissue reduction therapy with regard to both the physiological cardiac response and microlesion production. Methods Rats were anesthetized, prepared for ultrasound, placed in a heated water bath, and treated with 1.5 MHz focused ultrasound pulses targeted to the left ventricular myocardium with an 8 MHz imaging transducer. Initially, the rats were treated for 1 min at each of six different time points in the ECG while monitoring blood pressure responses to assess cardiac functional effects. Next, groups of rats were treated at three different time points: end diastole, end systole, and mid-diastole to assess the impact of timing on microlesion creation. These rats were pretreated with Evans blue injections and were allowed to recover for 1 day until hearts were harvested for scoring of injured cardiomyocytes. Results The initial results showed a wide range of cardiac premature complexes in the ECG, which corresponded with blood pressure pulses for ultrasound pulses triggered during diastole. However, the microlesion experiment did not reveal any statistically significant variations in cardiomyocyte injury. Conclusion The end of systole (R + RR/3) was identified as an optimal trigger time point which produced identifiable ECG complexes and substantial cardiomyocyte injury but minimal cardiac functional disruption during treatment. PMID:25279221

  4. 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.

  5. 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.

  6. Investigation of therapy improvement using real-time photoacoustic imaging guided high intensity focused ultrasound

    NASA Astrophysics Data System (ADS)

    Cui, Huizhong

    There are a lot of risks in cancer treatment by invasive surgery, such as bleeding, wound infection, and long recovery time, etc. Therefore, there is great need for minimally- or non-invasive treatment. High intensity focused ultrasound (HIFU) is a rapidly growing and truly non-invasive technology. It has been widely used in therapeutic applications, such as rapid tissue heating and tissue ablation. With proper imaging guidance, HIFU treatment can be performed totally noninvasively. Currently, ultrasound imaging-guided HIFU has been extensively studied. However, ultrasound imaging guidance is less precise because of the relatively low imaging contrast, sensitivity, and specificity for noninvasive detection. In this study, we employed photoacoustic imaging (PAI) technique, which has been developed a novel promising imaging technique for early cancer detection, to guide HIFU treatment. The goal of this study is to investigate the feasibility of PAI to guide, monitor in real time and enhance the HIFU therapy. In this dissertation, as the first step, the integrated PAI and HIFU system had been shown to have the feasibility to guide HIFU both ex vivo and in vivo. Then, the system was improved and developed to a real-time PAI-guided HIFU system. It is demonstrated that the sensitivity of PA detection for HIFU lesion is very high and the saturation of PA signals can be used as the indicator for tissue coagulation. During the temperature measurement using this system, laser-enhanced HIFU heating was found. Thus, we further investigated the laser enhanced technique in both HIFU heating and pulsed HIFU thrombolysis. In the HIFU therapy, laser light was employed to illuminate the sample concurrently with HIFU radiation. The resulting cavitation was detected with a passive cavitation detector. We demonstrated that concurrent light illumination during HIFU has the potential to significantly enhance HIFU by reducing cavitation threshold.

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

    SciTech Connect

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

    2006-05-15

    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.

  8. 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.

  9. 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

  10. 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.

  11. Comparative outcomes for three-dimensional conformal versus intensity-modulated radiation therapy for esophageal cancer.

    PubMed

    Freilich, J; Hoffe, S E; Almhanna, K; Dinwoodie, W; Yue, B; Fulp, W; Meredith, K L; Shridhar, R

    2015-01-01

    Emerging data suggests a benefit for using intensity modulated radiation therapy (IMRT) for the management of esophageal cancer. We retrospectively reviewed patients treated at our institution who received definitive or preoperative chemoradiation with either IMRT or 3D conformal radiation therapy (3DCRT) between October 2000 and January 2012. Kaplan Meier analysis and the Cox proportional hazard model were used to evaluate survival outcomes. We evaluated a total of 232 patients (138 IMRT, 94 3DCRT) who received a median dose of 50.4 Gy (range, 44-64.8) to gross disease. Median follow up for all patients, IMRT patients alone, and 3DCRT patients alone was 18.5 (range, 2.5-124.2), 16.5 (range, 3-59), and 25.9 months (range, 2.5-124.2), respectively. We observed no significant difference based on radiation technique (3DCRT vs. IMRT) with respect to median overall survival (OS) (median 29 vs. 32 months; P = 0.74) or median relapse free survival (median 20 vs. 25 months; P = 0.66). On multivariable analysis (MVA), surgical resection resulted in improved OS (HR 0.444; P < 0.0001). Superior OS was also associated on MVA with stage I/II disease (HR 0.523; P = 0.010) and tumor length ≤5 cm (HR 0.567; P = 0.006). IMRT was also associated on univariate analysis with a significant decrease in acute weight loss (mean 6% + 4.3% vs 9% + 7.4%, P = 0.012) and on MVA with a decrease in objective grade ≥3 toxicity, defined as any hospitalization, feeding tube, or >20% weight loss (OR 0.51; P = 0.050). Our data suggest that while IMRT-based chemoradiation for esophageal cancer does not impact survival there was significantly less toxicity. In the IMRT group there was significant decrease in weight loss and grade ≥3 toxicity compared to 3DCRT.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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

  17. Continuous renal replacement therapy: continuous blood purification in the intensive care unit.

    PubMed

    Bellomo, R; Ronco, C

    1998-05-01

    Severe acute renal failure (SARF) occurs when renal dysfunction is such that haemodialysis or haemofiltration becomes necessary to maintain homeostasis. SARF is increasingly seen in association with multiorgan failure and has become a predominantly Intensive Care Unit disorder. Because of this change in epidemiology, the treatment of SARF has evolved from being exclusively nephrologist and intermittent haemodialysis-based to being mostly intensivist and continuous haemofiltration-based, particularly in European countries with a strong ICU tradition and in Australia. Continuous renal replacement therapy (CRRT) has several advantages in critically ill patients, including greater flexibility, excellent haemodynamic tolerance, outstanding fluid balance control, excellent control of uraemia, prevention of cerebral oedema, ability to provide full and aggressive nutrition, and a possible anti-inflammatory effect. The blood purification effect of CRRT may, in fact, go beyond the simple control of uraemia. Several animal studies have now shown that CRRT attenuates the haemodynamic consequences of bacteraemia or endotoxaemia. Such studies have also shown that increasing the intensity of fluid exchange may offer further beneficial effects in the setting of sepsis. In the light of these findings, CRRT is moving into the area of adjuvant treatment of sepsis, and pilot randomized controlled trials are being conducted to test the hypothesis that CRRT, either in standard or high fluid exchange volumes, attenuates the inflammatory effects of sepsis in humans. In the future, the use of CRRT may extend beyond its initial scope into the area of adjuvant management of sepsis and continuous blood purification may become part of a complex multifaceted approach to multiorgan dysfunction.

  18. 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.

  19. 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

  20. 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

  1. 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.

  2. RISK OF SECONDARY MILIGNANT NEOPLASMS FROM PROTON THERAPY AND INTENSITY-MODULATED X-RAY THERAPY FOR EARLY-STAGE PROSTATE CANCER

    PubMed Central

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

    2014-01-01

    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. PMID:19427561

  3. Quantitative analysis of tomotherapy, linear-accelerator-based 3D conformal radiation therapy, intensity-modulated radiation therapy, and 4D conformal radiation therapy

    NASA Astrophysics Data System (ADS)

    Cho, Jae-Hwan; Lee, Hae-Kag; Dong, Kyung-Rae; Chung, Woon-Kwan; Lee, Jong-Woong; Park, Hoon-Hee

    2012-04-01

    This study quantified, evaluated and analyzed the radiation dose to which tumors and normal tissues were exposed in 3D conformal radiation therapy (CRT), intensity-modulated radiation therapy (IMRT) and tomotherapy by using a dose volume histogram (DVH) that represented the volume dose and the dose distribution of anatomical structures in the evaluation of treatment planning. Furthermore, a comparison was made for the dose to the gross tumor volume (GTV) and the planning target volume (PTV) of organ to be treated based on the change in field size for three- and four-dimensional computed tomography (3D-CT and 4D-CT) (gating based) and in the histogram with a view to proving the usefulness of 4D-CT therapy, which corresponds to respiration-gated radiation therapy. According to the study results, a comparison of 3D CRT, IMRT with a linear accelerator (LINAC), and tomotherapy demonstrated that the GTV of the cranium was higher for tomotherapy than for 3D CRT and IMRT with a LINAC by 5.2% and 4.6%, respectively. The GTV of the neck was higher for tomotherapy than for 3D CRT and IMRT with a LINAC by 6.5% and 2.0%, respectively. The GTV of the pelvis was higher for tomotherapy than for 3D CRT and IMRT with a LINAC by 8.6% and 3.7%, respectively. When the comparison was made for the 3D-CT and the 4D-CT (gating based) treatment equipment, the GTV and the PTV became smaller for 4D-CT treatment planning than for 3D-CT, which could reduce the area in which normal tissues in the surroundings are exposed to an unnecessary radiation dose. In addition, when 4D-CT treatment planning (gating based) was used, the radiation dose could be concentrated on the GTV, CTV or PTV, which meant that the treatment area exceeded that when 3D-CT's treatment planning was used. Moreover, the radiation dose on nearby normal tissues could be reduced. When 4D-CT treatment planning (gating based) was utilized, unnecessary areas that were exposed to a radiation dose could be reduced more than they could

  4. Multisystemic Therapy Improves the Patient-Provider Relationship in Families of Adolescents with Poorly Controlled Insulin Dependent Diabetes

    PubMed Central

    Carcone, April Idalski; Ellis, Deborah A.; Chen, Xinguang; Naar-King, Sylvie; Cunningham, Phillippe B.; Moltz, Kathleen

    2015-01-01

    Objective The purpose of this study was to determine if Multisystemic Therapy (MST), an intensive, home and community-based family treatment, significantly improved patient-provider relationships in families where youth had chronic poor glycemic control. Methods One hundred forty-six adolescents with type 1 or 2 diabetes in chronic poor glycemic control (HbA1c ≥ 8%) and their primary caregivers were randomly assigned to MST or a telephone support condition. Caregiver perceptions of their relationship with the diabetes multidisciplinary medical team were assessed at baseline and treatment termination with the Measure of Process of Care-20. Results At treatment termination, MST families reported significant improvement on the Coordinated and Comprehensive Care scale and marginally significant improvement on the Respectful and Supportive Care scale. Improvements on the Enabling and Partnership and Providing Specific Information scales were not significant. Conclusions Results suggest MST improves the ability of the families and the diabetes treatment providers to work together. PMID:25940767

  5. 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…

  6. 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.

  7. 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.

  8. Penile low-intensity shock wave therapy: a promising novel modality for erectile dysfunction.

    PubMed

    Abu-Ghanem, Yasmin; Kitrey, Noam D; Gruenwald, Ilan; Appel, Boaz; Vardi, Yoram

    2014-05-01

    Penile extracorporeal low-intensity shock wave therapy (LIST) to the penis has recently emerged as a novel and promising modality in the treatment of erectile dysfunction (ED). LIST has angiogenic properties and stimulates neovascularization. If applied to the corpora cavernosa, LIST can improve penile blood flow and endothelial function. In a series of clinical trials, including randomized double-blind sham-controlled studies, LIST has been shown to have a substantial effect on penile hemodynamics and erectile function in patients with vasculogenic ED. LIST is effective in patients who are responsive to phosphodiesterase 5 inhibitors (PDE5i) and can also convert PDE5i nonresponders to responders. The response to LIST wanes gradually over time, and after 2 years, about half of the patients maintain their function. Extensive research is needed to understand the effect of LIST on erectile tissue, to modify the treatment protocol to maximize its outcomes, and to identify the patients who will benefit the most from this treatment.

  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. 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.

  11. 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

    2016-04-01

    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. PMID:26961764

  12. 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.

  13. 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.

  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

    2016-04-01

    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.

  15. 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.

  16. Diabetic distal symmetric polyneuropathy: effect of low-intensity laser therapy.

    PubMed

    Khamseh, Mohammad Ebrahim; Kazemikho, Nooshafarin; Aghili, Rokhsareh; Forough, Bijan; Lajevardi, Marjan; Hashem Dabaghian, Fataneh; Goushegir, Ashrafeddin; Malek, Mojtaba

    2011-11-01

    Low-intensity laser therapy (LILT) has been considered as a treatment modality in diabetic distal symmetric polyneuropathy (DSP). The aim of this study is to determine the effectiveness of LILT on DSP. We examined 107 subjects with type 2 diabetes for detection of DSP using the Michigan Neuropathy Screening Instrument (MNSI). Seventeen subjects were eligible to be enrolled in the study. Nerve conduction studies (NCS) were performed in all eligible subjects as an objective method to confirm neuropathy. The participants received LILT three times a week for ten sessions. NCSs were reevaluated after completion of the treatment. The absolute changes in NCS parameters were considered to establish the effectiveness of the treatment. Baseline demographics were similar in all participants. The mean differences of NCV parameters were considered for comparison. At the end of the study, the subjects showed a significant increase in neural potential amplitudes (p < 0.05). This study clearly demonstrated a significant positive effect of LILT on improvement of nerve conduction velocity on diabetic distal symmetric polyneuropathy (DSP). This finding supports the therapeutic potential of LILT in DSP. PMID:21853320

  17. Organisational standards for the delivery of intensity-modulated radiation therapy in Ontario.

    PubMed

    Whitton, A; Warde, P; Sharpe, M; Oliver, T K; Bak, K; Leszczynski, K; Etheridge, S; Fleming, K; Gutierrez, E; Favell, L; Green, E

    2009-04-01

    By minimising the effect of irradiation on surrounding tissue, intensity-modulated radiation therapy (IMRT) can deliver higher, more effective doses to the targeted tumour site, minimising treatment-related morbidity and possibly improving cancer control and cure. A multidisciplinary IMRT Expert Panel was convened to develop the organisational standards for the delivery of IMRT. The systematic literature search used MEDLINE, EMBASE, the Cochrane Database, the National Guidelines Clearing House and the Health Technology Assessment Database. An environmental scan of unpublished literature used the Google search engine to review the websites of key organisations, cancer agencies/centres and vendor sites in Canada, the USA, Australia and Europe. In total, 22 relevant guidance documents were identified; 12 from the published literature and 10 from the environmental scan. Professional and organisational standards for the provision of IMRT were developed through the analysis of this evidence and the consensus opinion of the IMRT Expert Panel. The resulting standards address the following domains: planning of new IMRT programmes, practice setting requirements, tools, devices and equipment requirements; professional training requirements; role of personnel; and requirements for quality assurance and safety. Here the IMRT Expert Panel offers organisational and professional standards for the delivery of IMRT, with the intent of promoting innovation, improving access and enhancing patient care.

  18. Intensity-modulated radiation therapy for the treatment of nonanaplastic thyroid cancer

    SciTech Connect

    Rosenbluth, Benjamin D.; Serrano, Victoria B.S.; Happersett, Laura; Shaha, Ashok R.; Tuttle, R. Michael; Narayana, Ashwatha; Wolden, Suzanne L.; Rosenzweig, Kenneth E.; Chong, Lanceford M.; Lee, Nancy Y. . E-mail: leen2@mskcc.org

    2005-12-01

    Purpose: Intensity-modulated radiation therapy (IMRT) enables highly conformal treatment for thyroid cancer (TC). In this study, we review outcomes/toxicity in a series of TC patients treated with IMRT. Methods and Materials: Between July 2001 and January 2004, 20 nonanaplastic TC patients underwent IMRT. Mean age was 55. There were 3 T2 and 17 T4 patients. Sixteen patients had N1 disease. Seven patients had metastases before RT. Fifteen underwent surgery before RT. Radioactive iodine (RAI) and chemotherapy were used in 70% and 40%, respectively. Median total RT dose was 63 Gy. Results: With two local failures, 2-year local progression-free rate was 85%. There were six deaths, with a 2-year overall survival rate of 60%. For patients with M0 disease, the 2-year distant metastases-free rate was 46%. The worst acute mucositis and pharyngitis was Grade 3 (n = 7 and 3, respectively). Two patients had Grade 3 acute skin toxicity and 2 had Grade 3 acute laryngeal toxicity. No significant radiation-related late effects were reported. Conclusions: IMRT for TC is feasible and effective in appropriately selected cases. Acute toxicity is manageable with proactive clinical care. Ideal planning target volume doses have yet to be determined. Additional patients and long-term follow-up are needed to confirm these preliminary findings and to clarify late toxicities.

  19. Dosimetric evaluations of the interplay effect in respiratory-gated intensity-modulated radiation therapy

    SciTech Connect

    Chen Hungcheng; Wu, Andrew; Brandner, Edward D.; Heron, Dwight E.; Huq, M. Saiful; Yue, Ning J.; Chen Wencheng

    2009-03-15

    The interplay between a mobile target and a dynamic multileaf collimator can compromise the accuracy of intensity-modulated radiation therapy (IMRT). Our goal in this study is to investigate the dosimetric effects caused by the respiratory motion during IMRT. A moving phantom was built to simulate the typical breathing motion. Different sizes of the gating windows were selected for gated deliveries. The residual motions during the beam-on period ranged from 0.5 to 3 cm. An IMRT plan with five treatment fields from different gantry angles were delivered to the moving phantom for three irradiation conditions: Stationary condition, moving with the use of gating system, and moving without the use of gating system. When the residual motion was 3 cm, the results showed significant differences in dose distributions between the stationary condition and the moving phantom without gating beam control. The overdosed or underdosed areas enclosed about 33% of the treatment area. In contrast, the dose distribution on the moving phantom with gating window set to 0.5 cm showed no significant differences from the stationary phantom. With the appropriate setting of the gating window, the deviation of dose from the respiratory motion can be minimized. It appeals that limiting the residual motion to less than 0.5 cm is critical for the treatments of mobile structures.

  20. A pencil beam algorithm for intensity modulated proton therapy derived from Monte Carlo simulations.

    PubMed

    Soukup, Martin; Fippel, Matthias; Alber, Markus

    2005-11-01

    A pencil beam algorithm as a component of an optimization algorithm for intensity modulated proton therapy (IMPT) is presented. The pencil beam algorithm is tuned to the special accuracy requirements of IMPT, where in heterogeneous geometries both the position and distortion of the Bragg peak and the lateral scatter pose problems which are amplified by the spot weight optimization. Heterogeneity corrections are implemented by a multiple raytracing approach using fluence-weighted sub-spots. In order to derive nuclear interaction corrections, Monte Carlo simulations were performed. The contribution of long ranged products of nuclear interactions is taken into account by a fit to the Monte Carlo results. Energy-dependent stopping power ratios are also implemented. Scatter in optional beam line accessories such as range shifters or ripple filters is taken into account. The collimator can also be included, but without additional scattering. Finally, dose distributions are benchmarked against Monte Carlo simulations, showing 3%/1 mm agreement for simple heterogeneous phantoms. In the case of more complicated phantoms, principal shortcomings of pencil beam algorithms are evident. The influence of these effects on IMPT dose distributions is shown in clinical examples. PMID:16237243

  1. 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.

  2. Possible fractionated regimens for image-guided intensity-modulated radiation therapy of large arteriovenous malformations

    NASA Astrophysics Data System (ADS)

    Qi, X. Sharon; Schultz, Christopher J.; Li, X. Allen

    2007-09-01

    The aim of this study was to estimate a plausible α/β ratio for arteriovenous malformations (AVMs) based on reported clinical data, and to design possible fractionation regimens suitable for image-guided intensity-modulated radiation therapy (IG-IMRT) for large AVMs based on the newly obtained α/β ratio. The commonly used obliteration rate (OR) for AVMs with a three year angiographic follow-up from many institutes was fitted to linear-quadratic (LQ) formalism and the Poisson OR model. The determined parameters were then used to calculate possible fractionation regimens for IG-IMRT based on the concept of a biologically effective dose (BED) and an equivalent uniform dose (EUD). The radiobiological analysis yields a α/β ratio of 2.2 ± 1.6 Gy for AVMs. Three sets of possible fractionated schemes were designed to achieve equal or better biological effectiveness than the single-fraction treatments while maintaining the same probability of normal brain complications. A plausible α/β ratio was derived for AVMs and possible fractionation regimens that may be suitable for IG-IMRT for large AVM treatment are proposed. The sensitivity of parameters on the calculation was also studied. The information may be useful to design new clinical trials that use IG-IMRT for the treatment of large AVMs.

  3. 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.

  4. A nested partitions framework for beam angle optimization in intensity-modulated radiation therapy.

    PubMed

    D'Souza, Warren D; Zhang, Hao H; Nazareth, Daryl P; Shi, Leyuan; Meyer, Robert R

    2008-06-21

    Coupling beam angle optimization with dose optimization in intensity-modulated radiation therapy (IMRT) increases the size and complexity of an already large-scale combinatorial optimization problem. We have developed a novel algorithm, nested partitions (NP), that is capable of finding suitable beam angle sets by guiding the dose optimization process. NP is a metaheuristic that is flexible enough to guide the search of a heuristic or deterministic dose optimization algorithm. The NP method adaptively samples from the entire feasible region, or search space, and coordinates the sampling effort with a systematic partitioning of the feasible region at successive iterations, concentrating the search in promising subsets. We used a 'warm-start' approach by initiating NP with beam angle samples derived from an integer programming (IP) model. In this study, we describe our implementation of the NP framework with a commercial optimization algorithm. We compared the NP framework with equi-spaced beam angle selection, the IP method, greedy heuristic and random sampling heuristic methods. The results of the NP approach were evaluated using two clinical cases (head and neck and whole pelvis) involving the primary tumor and nodal volumes. Our results show that NP produces better quality solutions than the alternative considered methods. PMID:18523351

  5. A nested partitions framework for beam angle optimization in intensity-modulated radiation therapy

    NASA Astrophysics Data System (ADS)

    D'Souza, Warren D.; Zhang, Hao H.; Nazareth, Daryl P.; Shi, Leyuan; Meyer, Robert R.

    2008-06-01

    Coupling beam angle optimization with dose optimization in intensity-modulated radiation therapy (IMRT) increases the size and complexity of an already large-scale combinatorial optimization problem. We have developed a novel algorithm, nested partitions (NP), that is capable of finding suitable beam angle sets by guiding the dose optimization process. NP is a metaheuristic that is flexible enough to guide the search of a heuristic or deterministic dose optimization algorithm. The NP method adaptively samples from the entire feasible region, or search space, and coordinates the sampling effort with a systematic partitioning of the feasible region at successive iterations, concentrating the search in promising subsets. We used a 'warm-start' approach by initiating NP with beam angle samples derived from an integer programming (IP) model. In this study, we describe our implementation of the NP framework with a commercial optimization algorithm. We compared the NP framework with equi-spaced beam angle selection, the IP method, greedy heuristic and random sampling heuristic methods. The results of the NP approach were evaluated using two clinical cases (head and neck and whole pelvis) involving the primary tumor and nodal volumes. Our results show that NP produces better quality solutions than the alternative considered methods.

  6. In vivo measurements with MOSFET detectors in oropharynx and nasopharynx intensity-modulated radiation therapy

    SciTech Connect

    Marcie, Serge . E-mail: serge.marcie@cal.nice.fnclcc.fr; Charpiot, Elisabeth; Bensadoun, Rene-Jean; Ciais, Gaston; Herault, Joel; Costa, Andre; Gerard, Jean-Pierre

    2005-04-01

    Purpose: To evaluate the feasibility of in vivo measurements with metal oxide semiconductor field effect transistor (MOSFET) dosimeters for oropharynx and nasopharynx intensity-modulated radiation therapy (IMRT). Methods and Materials: During a 1-year period, in vivo measurements of the dose delivered to one or two points of the oral cavity by IMRT were obtained with MOSFET dosimeters. Measurements were obtained during each session of 48 treatment plans for 21 patients, all of whom were fitted with a custom-made mouth plate. Calculated and measured values were compared. Results: A total of 344 and 452 measurements were performed for the right and left sides, respectively, of the oral cavity. Seventy percent of the discrepancies between calculated and measured values were within {+-}5%. Uncertainties were due to interfraction patient positions, intrafraction patient movements, and interfraction MOSFET positions. Nevertheless, the discrepancies between the measured and calculated means were within {+-}5% for 92% and 95% of the right and left sides, respectively. Comparison of these discrepancies and the discrepancies between calculated values and measurements made on a phantom revealed that all differences were within {+-}5%. Conclusion: Our experience demonstrates the feasibility of in vivo measurements with MOSFET dosimeters for oropharynx and nasopharynx IMRT.

  7. Comparison of optimization algorithms in intensity-modulated radiation therapy planning

    NASA Astrophysics Data System (ADS)

    Kendrick, Rachel

    Intensity-modulated radiation therapy is used to better conform the radiation dose to the target, which includes avoiding healthy tissue. Planning programs employ optimization methods to search for the best fluence of each photon beam, and therefore to create the best treatment plan. The Computational Environment for Radiotherapy Research (CERR), a program written in MATLAB, was used to examine some commonly-used algorithms for one 5-beam plan. Algorithms include the genetic algorithm, quadratic programming, pattern search, constrained nonlinear optimization, simulated annealing, the optimization method used in Varian EclipseTM, and some hybrids of these. Quadratic programing, simulated annealing, and a quadratic/simulated annealing hybrid were also separately compared using different prescription doses. The results of each dose-volume histogram as well as the visual dose color wash were used to compare the plans. CERR's built-in quadratic programming provided the best overall plan, but avoidance of the organ-at-risk was rivaled by other programs. Hybrids of quadratic programming with some of these algorithms seems to suggest the possibility of better planning programs, as shown by the improved quadratic/simulated annealing plan when compared to the simulated annealing algorithm alone. Further experimentation will be done to improve cost functions and computational time.

  8. 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.

  9. 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. PMID:17473350

  10. 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

  11. Compact multileaf collimator for conformal and intensity modulated fast neutron therapy: electromechanical design and validation.

    PubMed

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

    2006-09-01

    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 30 x 30 cm2. 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 degrees and 60 degrees 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. PMID:17022226

  12. Racial Differences in Diffusion of Intensity-Modulated Radiation Therapy for Localized Prostate Cancer.

    PubMed

    Cobran, Ewan K; Chen, Ronald C; Overman, Robert; Meyer, Anne-Marie; Kuo, Tzy-Mey; O'Brien, Jonathon; Sturmer, Til; Sheets, Nathan C; Goldin, Gregg H; Penn, Dolly C; Godley, Paul A; Carpenter, William R

    2016-09-01

    Intensity-modulated radiation therapy (IMRT), an innovative treatment option for prostate cancer, has rapidly diffused over the past decade. To inform our understanding of racial disparities in prostate cancer treatment and outcomes, this study compared diffusion of IMRT in African American (AA) and Caucasian American (CA) prostate cancer patients during the early years of IMRT diffusion using the Surveillance, Epidemiology and End Results (SEER)-Medicare linked database. A retrospective cohort of 947 AA and 10,028 CA patients diagnosed with localized prostate cancer from 2002 through 2006, who were treated with either IMRT or non-IMRT as primary treatment within 1 year of diagnoses was constructed. Logistic regression was used to examine potential differences in diffusion of IMRT in AA and CA patients, while adjusting for socioeconomic and clinical covariates. A significantly smaller proportion of AA compared with CA patients received IMRT for localized prostate cancer (45% vs. 53%, p < .0001). Racial differences were apparent in multivariable analysis though did not achieve statistical significance, as time and factors associated with race (socioeconomic, geographic, and tumor related factors) explained the preponderance of variance in use of IMRT. Further research examining improved access to innovative cancer treatment and technologies is essential to reducing racial disparities in cancer care.

  13. 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

  14. Intensive Glycemic Control in Cardiac Surgery.

    PubMed

    Tsai, Lillian L; Jensen, Hanna A; Thourani, Vinod H

    2016-04-01

    Hyperglycemia has been found to be associated with increased morbidity and mortality in surgical patients, yet, the optimal glucose management strategy during the perioperative setting remains undetermined. While much has been published about hyperglycemia and cardiac surgery, most studies have used widely varying definitions of hyperglycemia, methods of insulin administration, and the timing of therapy. This has only allowed investigators to make general conclusions in this challenging clinical scenario. This review will introduce the basic pathophysiology of hyperglycemia in the cardiac surgery setting, describe the main clinical consequences of operative hyperglycemia, and take the reader through the published material of intensive and conservative glucose management. Overall, it seems that intensive control has modest benefits with adverse effects often outweighing these advantages. However, some studies have indicated differing results for certain patient subgroups, such as non-diabetics with acute operative hyperglycemia. Future studies should focus on distinguishing which patient populations, if any, would optimally benefit from intensive insulin therapy. PMID:26879308

  15. Choosing injectable therapy: The metabolic fulcrum.

    PubMed

    Kalra, Sanjay; Gupta, Yashdeep

    2016-07-01

    This clinical decision making hypothesis utilizes the metabolic fulcrum based approach to classify persons with diabetes into three categories: predominantly catabolic, eubolic, and predominantly [maladaptive] anabolic. This systematic arrangement helps define choice of injectable therapy in type 2 diabetes mellitus. Patients with predominant catabolism, may respond better to intensive insulin therapy. Dual action insulin, including premixed insulin and I Deg Asp (insulin degludec aspart), may be an acceptable alternative. Uncomplicated, eumetabolic patients with type 2 diabetes may use any of the various drugs available. Patients classified as having maladaptive anabolism may benefit from a GLP1RA. If this does not suffice, a GLP1RA + basal insulin combination may be effective. PMID:27427149

  16. Evaluation of a Novel Continuous Glucose Monitoring-Based Method for Mealtime Insulin Dosing—the iBolus—in Subjects with Type 1 Diabetes Using Continuous Subcutaneous Insulin Infusion Therapy: A Randomized Controlled Trial

    PubMed Central

    Ampudia-Blasco, F. Javier; Laguna, Alejandro; Revert, Ana; Vehì, Josep; Ascaso, Juan F.; Bondia, Jorge

    2012-01-01

    Abstract Objective Prandial insulin dosing is an empirical practice associated frequently with poor reproducibility in postprandial glucose response. Based on continuous glucose monitoring (CGM), a method for prandial insulin administration (iBolus) is presented and evaluated for people with type 1 diabetes using CSII therapy. Subjects and Methods An individual patient's model for a 5-h postprandial period was obtained from 6-day ambulatory CGM and used for iBolus calculation in 12 patients with type 1 diabetes. In a double-blind, crossover study each patient underwent four meal tests with 40 g or 100 g of carbohydrates (CHOs), both on two occasions. For each meal, the iBolus or the traditional bolus (tBolus) was given before mealtime (t0) in a randomized order. We measured the postprandial glycemic response as the area under the curve of plasma glucose (AUC-PG0–5h) and variability as the individual coefficient of variation (CV) of AUC-PG0–5h. The contribution of the insulin-to-CHO ratio, CHO, plasma glucose at t0 (PGt0), and insulin dose to AUC-PG0–5h and its CV was also investigated. Results AUC-PG0–5h was similar with either bolus for 40-g (iBolus vs. tBolus, 585.5±127.5 vs. 689.2±180.7 mg/dL·h) or 100-g (752.1±237.7 vs. 760.0±263.2 mg/dL·h) CHO meals. A multiple regression analysis revealed a significant model only for the tBolus, with PGt0 being the best predictor of AUC-PG0–5h explaining approximately 50% of the glycemic response. Observed variability was greater with the iBolus (CV, 16.7±15.3% vs. 10.1±12.5%) but independent of the factors studied. Conclusions A CGM-based algorithm for calculation of prandial insulin is feasible, although it does not reduce unpredictability of individual glycemic responses. Causes of variability need to be identified and analyzed for further optimization of postprandial glycemic control. PMID:23003329

  17. 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

  18. Safe and Efficacious Use of Automated Bolus Advisors in Individuals Treated With Multiple Daily Insulin Injection (MDI) Therapy: Lessons Learned From the Automated Bolus Advisor Control and Usability Study (ABACUS).

    PubMed

    Parkin, Christopher G; Barnard, Katharine; Hinnen, Deborah A

    2015-03-20

    Numerous studies have shown that use of integrated automated bolus advisors (BAs) provides significant benefits to individuals using insulin pump devices, including improved glycemic control and greater treatment satisfaction. Within the past few years, BA devices have been developed specifically for individuals treated with multiple daily insulin injection (MDI) therapy; however, many clinicians who treat these individuals may be unfamiliar with insulin pump therapy and, thus, BA use. Findings from the Automated Bolus Advisor Control and Usability Study (ABACUS) revealed that BA use can be efficacious and clinically meaningful in MDI therapy, and that most patients are willing and able to use this technology appropriately when adequate clinical support is provided. The purpose of this article is to review key learnings from ABACUS and provide practical advice for initiating BA use and monitoring therapy.

  19. 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

  20. 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.

  1. 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.

    PubMed

    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

    2013-01-01

    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 25Gy in 1 fraction were generated for 15 patients with LAPC. DS plans were constrained to duodenal Dmax of<30Gy 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 Dmean, Dmax, D1cc, D4%, and V20Gy compared with NS plans (all p≤0.002). DS constraints compromised target coverage for IMRT as demonstrated by reduced V95% (p = 0.01) and Dmean (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 risk, whereas for IMRT it is compromised target coverage

  2. 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

  3. Tumor trailing strategy for intensity-modulated radiation therapy of moving targets

    SciTech Connect

    Trofimov, Alexei; Vrancic, Christian; Chan, Timothy C. Y.; Sharp, Gregory C.; Bortfeld, Thomas

    2008-05-15

    Internal organ motion during the course of radiation therapy of cancer affects the distribution of the delivered dose and, generally, reduces its conformality to the targeted volume. Previously proposed approaches aimed at mitigating the effect of internal motion in intensity-modulated radiation therapy (IMRT) included expansion of the target margins, motion-correlated delivery (e.g., respiratory gating, tumor tracking), and adaptive treatment plan optimization employing a probabilistic description of motion. We describe and test the tumor trailing strategy, which utilizes the synergy of motion-adaptive treatment planning and delivery methods. We regard the (rigid) target motion as a superposition of a relatively fast cyclic component (e.g., respiratory) and slow aperiodic trends (e.g., the drift of exhalation baseline). In the trailing approach, these two components of motion are decoupled and dealt with separately. Real-time motion monitoring is employed to identify the 'slow' shifts, which are then corrected by applying setup adjustments. The delivery does not track the target position exactly, but trails the systematic trend due to the delay between the time a shift occurs, is reliably detected, and, subsequently, corrected. The ''fast'' cyclic motion is accounted for with a robust motion-adaptive treatment planning, which allows for variability in motion parameters (e.g., mean and extrema of the tidal volume, variable period of respiration, and expiratory duration). Motion-surrogate data from gated IMRT treatments were used to provide probability distribution data for motion-adaptive planning and to test algorithms that identified systematic trends in the character of motion. Sample IMRT fields were delivered on a clinical linear accelerator to a programmable moving phantom. Dose measurements were performed with a commercial two-dimensional ion-chamber array. The results indicate that by reducing intrafractional motion variability, the trailing strategy

  4. Assessing software upgrades, plan properties and patient geometry using intensity modulated radiation therapy (IMRT) complexity metrics

    SciTech Connect

    McGarry, Conor K.; Chinneck, Candice D.; O'Toole, Monica M.; O'Sullivan, Joe M; Prise, Kevin M.; Hounsell, Alan R.

    2011-04-15

    Purpose: The aim of this study is to compare the sensitivity of different metrics to detect differences in complexity of intensity modulated radiation therapy (IMRT) plans following upgrades, changes to planning parameters, and patient geometry. Correlations between complexity metrics are also assessed. Method: A program was developed to calculate a series of metrics used to describe the complexity of IMRT fields using monitor units (MUs) and multileaf collimator files: Modulation index (MI), modulation complexity score (MCS), and plan intensity map variation (PIMV). Each metric, including the MUs, was used to assess changes in beam complexity for six prostate patients, following upgrades in the inverse planning optimization software designed to incorporate direct aperture optimization (DAO). All beams were delivered to a 2D ionization chamber array and compared to those calculated using gamma analysis. Each complexity metric was then calculated for all beams, on a different set of six prostate IMRT patients, to assess differences between plans calculated using different minimum field sizes and different maximum segment numbers. Different geometries, including CShape, prostate, and head and neck phantoms, were also assessed using the metrics. Correlations between complexity metrics were calculated for 20 prostate IMRT patients. Results: MU, MCS, MI, and PIMV could all detect reduced complexity following an upgrade to the optimization leaf sequencer, although only MI and MCS could detect a reduction in complexity when one-step optimization (DAO) was employed rather than two-step optimization. All metrics detected a reduction in complexity when the minimum field size was increased from 1 to 4 cm and all apart from PIMV detected reduced complexity when the number of segments was significantly reduced. All metrics apart from MI showed differences in complexity depending on the treatment site. Significant correlations exist between all metrics apart from MI and PIMV for

  5. A topographic leaf-sequencing algorithm for delivering intensity modulated radiation therapy.

    PubMed

    Desai, Dharmin; Ramsey, Chester R; Breinig, Marianne; Mahan, Stephen L

    2006-08-01

    Topographic treatment is a radiation therapy delivery technique for fixed-gantry (nonrotational) treatments on a helical tomotherapy system. The intensity-modulated fields are created by moving the treatment couch relative to a fan-beam positioned at fixed gantry angles. The delivered dose distribution is controlled by moving multileaf collimator (MLC) leaves into and out of the fan beam. The purpose of this work was to develop a leaf-sequencing algorithm for creating topographic MLC sequences. Topographic delivery was modeled using the analogy of a water faucet moving over a collection of bottles. The flow rate per unit length of the water from the faucet represented the photon fluence per unit length along the width of the fan beam, the collection of bottles represented the pixels in the treatment planning fluence map, and the volume of water collected in each bottle represented the delivered fluence. The radiation fluence per unit length delivered to the target at a given position is given by the convolution of the intensity distribution per unit length over the width of the beam and the time per unit distance along the direction of travel that an MLC leaf is open. The MLC opening times for the desired dose profiles were determined using a technique based on deconvolution using a genetic algorithm. The MLC opening times were expanded in terms of a Fourier series, and a genetic algorithm was used to find the best expansion coefficients for a given dose distribution. A series of wedge shapes (15, 30, 45, and 60 deg) and "dose well" test fluence maps were created to test the algorithm's ability to generate topographic leaf sequences. The accuracy of the leaf-sequencing algorithm was measured on a helical tomotherapy system using radiographic film placed at depth in water equivalent material. The measured dose profiles were compared with the desired dose distributions. The agreement was within +/- 2% or 2 mm distance-to-agreement (DTA) in the high dose gradient

  6. A topographic leaf-sequencing algorithm for delivering intensity modulated radiation therapy

    SciTech Connect

    Desai, Dharmin; Ramsey, Chester R.; Breinig, Marianne; Mahan, Stephen L.

    2006-08-15

    Topographic treatment is a radiation therapy delivery technique for fixed-gantry (nonrotational) treatments on a helical tomotherapy system. The intensity-modulated fields are created by moving the treatment couch relative to a fan-beam positioned at fixed gantry angles. The delivered dose distribution is controlled by moving multileaf collimator (MLC) leaves into and out of the fan beam. The purpose of this work was to develop a leaf-sequencing algorithm for creating topographic MLC sequences. Topographic delivery was modeled using the analogy of a water faucet moving over a collection of bottles. The flow rate per unit length of the water from the faucet represented the photon fluence per unit length along the width of the fan beam, the collection of bottles represented the pixels in the treatment planning fluence map, and the volume of water collected in each bottle represented the delivered fluence. The radiation fluence per unit length delivered to the target at a given position is given by the convolution of the intensity distribution per unit length over the width of the beam and the time per unit distance along the direction of travel that an MLC leaf is open. The MLC opening times for the desired dose profiles were determined using a technique based on deconvolution using a genetic algorithm. The MLC opening times were expanded in terms of a Fourier series, and a genetic algorithm was used to find the best expansion coefficients for a given dose distribution. A series of wedge shapes (15, 30, 45, and 60 deg) and 'dose well' test fluence maps were created to test the algorithm's ability to generate topographic leaf sequences. The accuracy of the leaf-sequencing algorithm was measured on a helical tomotherapy system using radiographic film placed at depth in water equivalent material. The measured dose profiles were compared with the desired dose distributions. The agreement was within {+-}2% or 2 mm distance-to-agreement (DTA) in the high dose gradient

  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. 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

  9. 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.

  10. 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.

  11. Vaginal Motion and Bladder and Rectal Volumes During Pelvic Intensity-Modulated Radiation Therapy After Hysterectomy

    SciTech Connect

    Jhingran, Anuja; Salehpour, Mohammad; Sam, Marianne; Levy, Larry; Eifel, Patricia J.

    2012-01-01

    Purpose: To evaluate variations in bladder and rectal volume and the position of the vaginal vault during a 5-week course of pelvic intensity-modulated radiation therapy (IMRT) after hysterectomy. Methods and Materials: Twenty-four patients were instructed how to fill their bladders before simulation and treatment. These patients underwent computed tomography simulations with full and empty bladders and then underwent rescanning twice weekly during IMRT; patients were asked to have full bladder for treatment. Bladder and rectal volumes and the positions of vaginal fiducial markers were determined, and changes in volume and position were calculated. Results: The mean full and empty bladder volumes at simulation were 480 cc (range, 122-1,052) and 155 cc (range, 49-371), respectively. Bladder volumes varied widely during IMRT: the median difference between the maximum and minimum volumes was 247 cc (range, 96-585). Variations in rectal volume during IMRT were less pronounced. For the 16 patients with vaginal fiducial markers in place throughout IMRT, the median maximum movement of the markers during IMRT was 0.59 cm in the right-left direction (range, 0-0.9), 1.46 cm in the anterior-posterior direction (range, 0.8-2.79), and 1.2 cm in the superior-inferior direction (range, 0.6-2.1). Large variations in rectal or bladder volume frequently correlated with significant displacement of the vaginal apex. Conclusion: Although treatment with a full bladder is usually preferred because of greater sparing of small bowel, our data demonstrate that even with detailed instruction, patients are unable to maintain consistent bladder filling. Variations in organ position during IMRT can result in marked changes in the position of the target volume and the volume of small bowel exposed to high doses of radiation.

  12. 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.

  13. Automatically-generated rectal dose constraints in intensity-modulated radiation therapy for prostate cancer

    NASA Astrophysics Data System (ADS)

    Hwang, Taejin; Kim, Yong Nam; Kim, Soo Kon; Kang, Sei-Kwon; Cheong, Kwang-Ho; Park, Soah; Yoon, Jai-Woong; Han, Taejin; Kim, Haeyoung; Lee, Meyeon; Kim, Kyoung-Joo; Bae, Hoonsik; Suh, Tae-Suk

    2015-06-01

    The dose constraint during prostate intensity-modulated radiation therapy (IMRT) optimization should be patient-specific for better rectum sparing. The aims of this study are to suggest a novel method for automatically generating a patient-specific dose constraint by using an experience-based dose volume histogram (DVH) of the rectum and to evaluate the potential of such a dose constraint qualitatively. The normal tissue complication probabilities (NTCPs) of the rectum with respect to V %ratio in our study were divided into three groups, where V %ratio was defined as the percent ratio of the rectal volume overlapping the planning target volume (PTV) to the rectal volume: (1) the rectal NTCPs in the previous study (clinical data), (2) those statistically generated by using the standard normal distribution (calculated data), and (3) those generated by combining the calculated data and the clinical data (mixed data). In the calculated data, a random number whose mean value was on the fitted curve described in the clinical data and whose standard deviation was 1% was generated by using the `randn' function in the MATLAB program and was used. For each group, we validated whether the probability density function (PDF) of the rectal NTCP could be automatically generated with the density estimation method by using a Gaussian kernel. The results revealed that the rectal NTCP probability increased in proportion to V %ratio , that the predictive rectal NTCP was patient-specific, and that the starting point of IMRT optimization for the given patient might be different. The PDF of the rectal NTCP was obtained automatically for each group except that the smoothness of the probability distribution increased with increasing number of data and with increasing window width. We showed that during the prostate IMRT optimization, the patient-specific dose constraints could be automatically generated and that our method could reduce the IMRT optimization time as well as maintain the

  14. Long term effects of high intensity laser therapy in lateral epicondylitis patients.

    PubMed

    Akkurt, Ekrem; Kucuksen, Sami; Yılmaz, Halim; Parlak, Selman; Sallı, Ali; Karaca, Gülten

    2016-02-01

    The objective of this study is to investigate short- and long-term effects of high-intensity laser therapy (HILT) in lateral epicondylitis (LE) patients. Thirty patients with LE diagnosis (23 unilateral and 7 bilateral in total 37 elbows) were treated using HILT. LE patients were evaluated before, right after, and 6 months following HILT intervention post-treatment using visual analogue scale for pain (VAS) during activity and resting. Disabilities of the Arm, Shoulder, and Hand (DASH) Score and hand grip strength test (HGST) were used. The participants of the present study were also evaluated using Short-Form 36 (SF-36) before and 6 months after the treatment. Out of the 30 patients, 8 were male and 22 female with a mean age of 47.2 ± 9.7. The activity and resting VAS, DASH, and HGST scores revealed statistically significant improvement (p = 0.001) following treatment. Whereas VAS activity, DASH, and HGST scores increased after treatment until post-treatment 6 months significantly (p = 0.001), VAS resting scores remained stable (p = 0.476). A statistically significant improvement was also evident in the physical and mental components of SF-36 scores following treatment until post-treatment 6 months compared to pre-treatment scores (p = 0.001). In conclusion, the results of the present study suggest that HILT is a reliable, safe, and effective treatment option in LE patients in the short and long term considering pain, functional status, and quality of life. PMID:26714978

  15. DICOM-based computer-aided evaluation of intensity modulated radiation therapy (IMRT) treatment plans

    NASA Astrophysics Data System (ADS)

    Cheung, Fion W. K.; Law, Maria Y. Y.

    2011-03-01

    Intensity-modulated radiation therapy (IMRT) has gained popularity in the treatment of cancers because of its excellent local control with decreased normal tissue complications. Yet, computer planning for the treatment relies heavily on human inspection of resultant radiation dose distribution within the irradiated region of the body. Even for experienced planners, comparison of IMRT plans is definitely cumbersome and not error-free. To solve this problem, a computer-aided decision-support system was built for automatic evaluation of IMRT plans based on the DICOM standard. A DICOM based IMRT plan with DICOM and DICOM-RT objects including CT images, RT Structure Set, RT Dose and RT Plan were retrieved from the Treatment Planning System for programming. Utilizing the MATLAB program language, the decoding-encoding software applications were developed on the basis of the DICOM information object definitions. After tracing the clinical workflow and understanding the needs and expectations from radiation oncologists, a set of routines were written to parse key data items such as isodose curves, region of interests, dose-volume histogram from the DICOM-RT objects. Then graphical user interfaces (GUIs) were created to allow planners to query for parameters such as overdose or underdose areas. A total of 30 IMRT plans were collected in a Department of Clinical Oncology for systematic testing of the DICOM-based decision-support system. Both structural and functional tests were implemented as a major step on the road to software maturity. With promising test results, this decision-support system could represent a major breakthrough in the routine IMRT planning workflow.

  16. 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.

  17. 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.

  18. Dosimetric effects of jaw tracking in step-and-shoot intensity-modulated radiation therapy.

    PubMed

    Joy, Sarah; Starkschall, George; Kry, Stephen; Salehpour, Mohammed; White, R Allen; Lin, Steven H; Balter, Peter

    2012-03-08

    The purpose of this work was to determine the dosimetric benefit to normal tissues by tracking the multi-leaf collimator (MLC) apertures with the photon jaws in step-and-shoot intensity-modulated radiation therapy (IMRT) on the Varian 2100 platform. Radiation treatment plans for ten thoracic, three pediatric, and three head and neck cancer patients were converted to plans with the jaws tracking each segment's MLC apertures, and compared to the original plans in a commercial radiation treatment planning system (TPS). The change in normal tissue dose was evaluated in the new plan by using the parameters V5, V10, and V20 (volumes receiving 5, 10 and 20 Gy, respectively) in the cumulative dose-volume histogram for the following structures: total lung minus gross target volume, heart, esophagus, spinal cord, liver, parotids, and brainstem. To validate the accuracy of our beam model, MLC transmission was measured and compared to that predicted by the TPS. The greatest changes between the original and new plans occurred at lower dose levels. In all patients, the reduction in V20 was never more than 6.3% and was typically less than 1%; the maximum reduction in V5 was 16.7% and was typically less than 3%. The variation in normal tissue dose reduction was not predictable, and we found no clear parameters that indicated which patients would benefit most from jaw tracking. Our TPS model of MLC transmission agreed with measurements with absolute transmission differences of less than 0.1% and, thus, uncertainties in the model did not contribute significantly to the uncertainty in the dose determination. We conclude that the amount of dose reduction achieved by collimating the jaws around each MLC aperture in step-and-shoot IMRT is probably not clinically significant.

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

    PubMed Central

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

    2015-01-01

    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, 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. PMID:25295881

  20. The effect of photon energy on intensity-modulated radiation therapy (IMRT) plans for prostate cancer

    PubMed Central

    Sung, Wonmo; Park, Jong Min; Choi, Chang Heon; Ha, Sung Whan

    2012-01-01

    Purpose To evaluate the effect of common three photon energies (6-MV, 10-MV, and 15-MV) on intensity-modulated radiation therapy (IMRT) plans to treat prostate cancer patients. Materials and Methods Twenty patients with prostate cancer treated locally to 81.0 Gy were retrospectively studied. 6-MV, 10-MV, and 15-MV IMRT plans for each patient were generated using suitable planning objectives, dose constraints, and 8-field setting. The plans were analyzed in terms of dose-volume histogram for the target coverage, dose conformity, organs at risk (OAR) sparing, and normal tissue integral dose. Results Regardless of the energies chosen at the plans, the target coverage, conformity, and homogeneity of the plans were similar. However, there was a significant dose increase in rectal wall and femoral heads for 6-MV compared to those for 10-MV and 15-MV. The V20 Gy of rectal wall with 6-MV, 10-MV, and 15-MV were 95.6%, 88.4%, and 89.4% while the mean dose to femoral heads were 31.7, 25.9, and 26.3 Gy, respectively. Integral doses to the normal tissues in higher energy (10-MV and 15-MV) plans were reduced by about 7%. Overall, integral doses in mid and low dose regions in 6-MV plans were increased by up to 13%. Conclusion In this study, 10-MV prostate IMRT plans showed better OAR sparing and less integral doses than the 6-MV. The biological and clinical significance of this finding remains to be determined afterward, considering neutron dose contribution. PMID:23120741

  1. Aichi Cancer Center Initial Experience of Intensity Modulated Radiation Therapy for Nasopharyngeal Cancer Using Helical Tomotherapy

    SciTech Connect

    Kodaira, Takeshi Tomita, Natsuo; Tachibana, Hiroyuki; Nakamura, Tatsuya; Nakahara, Rie; Inokuchi, Haruo; Fuwa, Nobukazu

    2009-03-15

    Purpose: To assess the feasibility of helical tomotherapy (HT) for patients with nasopharyngeal carcinoma. Methods and Materials: From June 2006 to June 2007, 20 patients with nasopharyngeal carcinoma were treated with HT with (n = 18) or without (n = 2) systemic chemotherapy. The primary tumor and involved lymph node (PTV1) were prescribed 70 Gy and the prophylactic region 54 Gy at D95, respectively. The majority of patients received 2 Gy per fraction for PTV1 in 35 fractions. Parotid function was evaluated using quantitative scintigraphy at pretreatment, and posttreatment at 3 months and 1 year later. Results: The median patient age was 53 years, ranging from 15 to 83. Our cohort included 5, 8, 4, 2, and 1 patients with disease Stages IIB, III, IVA, IVB, and IVC, respectively. Histopathological record revealed two for World Health Organization Type I and 18 for Type 2 or 3. The median duration time for treatment preparation was 9.5 days, and all plans were thought to be acceptable regarding dose constraints of both the planning target volume and organ at risk. All patients completed their treatment procedure of intensity-modulated radiation therapy (IMRT). All patients achieved clinical remission after IMRT. The majority of patients had Grade 3 or higher toxicity of skin, mucosa, and neutropenia. At the median follow-up of 10.9 months, two patients recurred, and one patient died from cardiac disease. Parotid gland function at 1 year after completion of IMRT was significantly improved compared with that at 3 months. Conclusion: HT was clinically effective in terms of IMRT planning and utility for patients with nasopharyngeal cancer.

  2. Application of influence diagrams to prostate intensity-modulated radiation therapy plan selection

    NASA Astrophysics Data System (ADS)

    Meyer, Jürgen; Phillips, Mark H.; Cho, Paul S.; Kalet, Ira; Doctor, Jason N.

    2004-05-01

    The purpose is to incorporate clinically relevant factors such as patient-specific and dosimetric information as well as data from clinical trials in the decision-making process for the selection of prostate intensity-modulated radiation therapy (IMRT) plans. The approach is to incorporate the decision theoretic concept of an influence diagram into the solution of the multiobjective optimization inverse planning problem. A set of candidate IMRT plans was obtained by varying the importance factors for the planning target volume (PTV) and the organ-at-risk (OAR) in combination with simulated annealing to explore a large part of the solution space. The Pareto set for the PTV and OAR was analysed to demonstrate how the selection of the weighting factors influenced which part of the solution space was explored. An influence diagram based on a Bayesian network with 18 nodes was designed to model the decision process for plan selection. The model possessed nodes for clinical laboratory results, tumour grading, staging information, patient-specific information, dosimetric information, complications and survival statistics from clinical studies. A utility node was utilized for the decision-making process. The influence diagram successfully ranked the plans based on the available information. Sensitivity analyses were used to judge the reasonableness of the diagram and the results. In conclusion, influence diagrams lend themselves well to modelling the decision processes for IMRT plan selection. They provide an excellent means to incorporate the probabilistic nature of data and beliefs into one model. They also provide a means for introducing evidence-based medicine, in the form of results of clinical trials, into the decision-making process.

  3. Evaluation of Parotid Gland Function following Intensity Modulated Radiation Therapy for Head and Neck Cancer

    PubMed Central

    Lee, Seok Ho; Kim, Tae Hyun; Kim, Joo Young; Park, Sung Yong; Pyo, Hong Ryull; Shin, Kyung Hwan; Kim, Dae Yong; Kim, Joo Young

    2006-01-01

    Purpose This study was undertaken to determine the parotid gland tolerance dose levels following intensity modulated radiation therapy (IMRT) for treating patients who suffered with head and neck cancer. Materials and Methods From February 2003 through June 2004, 34 head and neck patients with 6 months of follow-up were evaluated for xerostomia after being treated by IMRT. Their median age was 59 years (range: 29~78). Xerostomia was assessed using a 4-question xerostomia questionnaire score (XQS) and a test for the salivary flow rates (unstimulated and stimulated: USFR and SSFR, respectively). The patients were also given a validated LENT SOMA scale (LSS) questionnaire. Evaluations were performed before IMRT and at 1, 3 and 6 months after IMRT. Results All 34 patients showed significant changes in the XQS, LSS and Salivary Flow rates (USFR and SSFR) after IMRT. No significant changes in the XQS or LSS were noted in 12 patients who received a total parotid mean dose of ≤3,100 cGy at 1, 3 and 6 months post-IMRT relative to the baseline values. However, for the 22 patients who received >3,100 cGy, significant increases in the XQS and LSS were observed. The USFR and SSFR from the parotid glands in 7 patients who received ≤2,750 cGy were significantly preserved at up to 6 months after IMRT. However, the USFR and SSFR in 27 patients who were treated with >2,750 cGy were significantly lower than the baseline values at all times after IMRT. Conclusion We suggest that the total parotid mean dose should be limited to ≤2,750 cGy to preserve the USFR and SSFR and so improve the subsequent quality of life. PMID:19771265

  4. 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.

  5. 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

  6. Intensity modulated radiation therapy or stereotactic fractionated radiotherapy for infratentorial ependymoma in children: a multicentric study.

    PubMed

    Weber, Damien C; Zilli, Thomas; Do, Hans Peter; Nouet, Philippe; Gumy Pause, Fabienne; Pause, Fabienne Gumy; Pica, Alessia

    2011-04-01

    This study was to evaluate the treatment dosimetry, efficacy and toxicity of intensity modulated radiation therapy (IMRT) and fractionated stereotactic radiotherapy (FSRT) in the management of infratentorial ependymoma. Between 1999 and 2007, seven children (median age, 3.1 years) with infratentorial ependymoma were planned with either IMRT (3 patients) or SFRT (4 patients), the latter after conventional posterior fossa irradiation. Two children underwent gross total resection. Median prescribed dose was 59.4 Gy (range, 55.8-60). The median follow-up for surviving patients was 4.8 years (range, 1.3-8). IMRT (median dose, 59.4 Gy) and FSRT (median dose, 55.8 Gy) achieved similar optimal target coverage. Percentages of maximum doses delivered to the cochleae (59.5 vs 85.0% Gy; P = 0.05) were significantly inferior with IMRT, when compared to FSRT planning. Percentages of maximum doses administered to the pituitary gland (38.2 vs 20.1%; P = 0.05) and optic chiasm (38.1 vs 14.1%; P = 0.001) were, however, significantly higher with IMRT, when compared to FSRT planning. No recurrences were observed at the last follow-up. The estimated 3-year progression-free survival and overall survival were 87.5 and 100%, respectively. No grade >1 acute toxicity was observed. Two patients presented late adverse events (grade 2 hypoacousia) during follow-up, without cognitive impairment. IMRT or FSRT for infratentorial ependymomas is effective and associated with a tolerable toxicity level. Both treatment techniques were able to capitalize their intrinsic conformal ability to deliver high-dose radiation. Larger series of patients treated with these two modalities will be necessary to more fully evaluate these delivery techniques.

  7. 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

  8. 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 a